JHON MURTAGH Flashcards by jalal shah

Peak age incidence 10–30 years >40 years

Clinical differentiation between type 1 and type 2 diabetes

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Age of onset
Usually young <20
Usually middle-aged >40

Clinical differentiation between type 1 and type 2 diabetes

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Onset
Rapid
Insidious/slow

Clinical differentiation between type 1 and type 2 diabetes

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___________ is also known as juvenile onset diabetes or insulin dependent diabetes mellitus
(IDDM).

Type 1

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________ is also known as maturity onset diabetes or non-insulin dependent diabetes mellitus
(NIDDM).

Type 2

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Type 1 has an autoimmune causation which is also responsible for a late-onset form known as
_______________________

late onset autoimmune diabetes in adults (LADA).

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Drug-induced diabetes (transient)

Thiazide diuretics
Oestrogen therapy (high dose—not with low-dose HRT)
Corticosteroids

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In Australians older than 25 years the prevalence of diabetes is __________, with
another 10.6% having impaired glucose tolerance

7.5%

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About 30% of those with impaired glucose tolerance will develop clinical diabetes
within ________

10 years

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Many people with type 2 diabetes are ______

asymptomatic

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___________ may be temporarily elevated during acute illness, after trauma or
surgery.

Blood glucose

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The classic symptoms of uncontrolled diabetes are:

polyuria
polydipsia
loss of weight (type 1)
tiredness and fatigue
propensity for infections, especially of the skin and genitals (vaginal thrush)

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DxT thirst + polyuria + weight loss →

The young person with type 1 diabetes

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Symptoms of complications (may be presenting feature) include:
staphylococcal skin infections
polyneuropathy: tingling or numbness in feet, pain (can be severe if present)
impotence
arterial disease: myocardial ischaemia, peripheral vascular disease

The young person with type 1 diabetes

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Examination
The physical examination should ideally follow the protocol for annual review.
Initial screening for suspected diabetes should include:
general inspection, including skin
BMI (weight/height)
waist circumference
visual acuity

diabetes

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blood pressure—lying and standing
test for peripheral neuropathy: tendon reflexes, sensation (e.g. cotton wool, 10 g
monofilament, Neurotips)
urinalysis: glucose, albumin, ketones, nitrites

diabetes

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Initial: fasting or random blood sugar, follow-up oral glucose tolerance test (OGTT) or
glycated haemoglobin (HbA1c) if indicated
Other tests according to clinical assessment (e.g. lipids, kidney function, urine albumin–
creatinine ratio (ACR), ECG)

diabetes

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Age >40 years
Family history
Overweight/obesity
Sedentary lifestyle
History of gestational diabetes, pancreatitis
Women with polycystic ovarian syndrome (PCOS)
Hypertension/ischaemic heart disease
Medication causing hyperglycaemia
Ethnic/cultural groups: Aboriginal and Torres Strait Islanders, Pacific Islanders, people from
Indian subcontinent, Chinese, Afro-Caribbeans

Risk factors for DIABETES

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People with known impaired fasting glucose/glucose tolerance (‘prediabetes’)
Age >40 years, or younger age (e.g. >30 years) with: family history (first-degree relative with
T2D), obesity (BMI >30), high-prevalence ethnic groups
Age >18 years in Aboriginal and Torres Strait Islander people
Previous gestational diabetes
People on long-term steroids or antipsychotics

Screening (type 2)

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Polycystic ovarian syndrome, especially if overweight

Previous cardiovascular event

Screening (type 2)

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The optimal frequency is every 3 years from age 40 years using AUSDRISK

Screening (type 2)

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If score ≥12, do fasting blood glucose or
HbA1c. Screen annually in very high-risk groups, including Aboriginal and Torres Strait Islander
people and those with ‘prediabetes’.5

Screening (type 2)

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If symptomatic (at least two of polydipsia, polyuria, frequent skin infections or frequent
genital thrush):
fasting venous blood glucose (VBG) ≥7.0 mmol/L
or
random VBG (at least 2 hours after last eating) ≥11.1 mmol/L
or
HbAIc >____________

6.5% (>48 mmol/mol)

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If asymptomatic:
at least two separate elevated values, either fasting, 2 or more hours postprandial, or the two
values from ____________________________

an oral glucose tolerance test (OGTT)

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If random or fasting VBG lies in an uncertain range (5.5–11.0 mmol/L) in either a symptomatic patient or a patient with risk factors (over 50 years, overweight, firstdegree relative with T2D), perform ___________________.

an OGTT

The 2-hour blood sugar on an OGTT is still the gold standard for the diagnosis of uncertain diabetes, i.e. ____________________

>11.1 mmol/L.

The OGTT should be reserved for true borderline cases and for diagnosing gestational diabetes, where a 75 mg OGTT is recommended at _____________________________

24–28 weeks’ gestation

Diabetic ulcer, allergic to penicillin, debridement done. Next?allergic to pencillin so can’t give ________________

Ticarcillin is an extended-spectrum penicillin

Elderly pt with "painful bones, renal stones, abdominal groans, and psychic moans

Hyperparathyroidism

This is the condition where the VPG is elevated above the normal range (i.e. 6.1–6.9) but does not satisfy the type 2 diagnostic criteria.

Prediabetes

This is the condition where the VPG is elevated above the normal range (i.e. 6.1–6.9) but does not satisfy the type 2 diagnostic criteria. It includes two states:

impaired fasting glucose (IFG) | impaired glucose tolerance (IGT)

A diagnosis of prediabetes is not a call to start medication, but it increases the urgency of promoting lifestyle changes such as weight reduction and ______________________.

increased physical activity

______________is unreliable in diagnosis since glycosuria occurs at different plasma glucose values in patients with different kidney thresholds.

Urinalysis

``` Venous blood glucose concentration fasting up to 6 mmol/L ```

Normal

``` Venous blood glucose concentration fasting up to 6.1–6.9 mmol/L ```

Intermediate | hyperglycaemia

``` Venous blood glucose concentration fasting up to ≥7 mmol/L ```

Diabetes

``` Venous blood glucose concentration random up to 6 mmol/L ```

Normal

``` Venous blood glucose concentration random up to ≥11.1 mmol/L ```

Diabetes

``` Oral glucose tolerance test 2-hour venous blood glucose concentration up to 7.7 mmol/L ```

Normal

``` Oral glucose tolerance test 2-hour venous blood glucose concentration up to 7.8–11 mmol/L ```

Intermediate | hyperglycaemia

``` Oral glucose tolerance test 2-hour venous blood glucose concentration up to 7.8–11 mmol/L ```

≥11.1 mmol/L | HbA1c ≥48 mmol/mol (

Gestational diabetes is the new onset of abnormal glucose tolerance during ___________.

pregnancy

Pregnancy is diabetogenic for those with a genetic predisposition

Gestational diabetes

All pregnant women should be | screened at 24–28 weeks with _________________

a 75 g oral glucose tolerance test (OGTT).

gestational diabetes is a fasting plasma glucose of | ≥5.1 mmol/L, or a post-75 g oral glucose load at 1 hour ≥10.0, or at 2 hours _____________

8.5–11.0

The incidence of diabetes rises with _________

age

On day discharge FBS OGTT at 6-12 weeks If normal then _____________

3 yearly FBS

Prevention of CAD in DM patients include control of BP, Blood sugar and LDL, AceI/Arbs in high risk and ___________________

smoking cessation

Meticulous foot care is very important in _____________

diabetic patients

IgA-TG2 (immunoglobulin A-tissue transglutaminase 2) antibody is the preferred single test for ___________ at any age. Concurrently measure total IgA level with serology testing to determine whether IgA levels are sufficient.

CD detection

Most common cause of secondary PPH

Retained products of conception

because gdm cause macrosomia and prolonged labour may result in cervical laceration and __________________

traumatic birth

This is a secondary post-partum bleeding and cannot possibly be from cervical laceration. Moreover, the presence of blood clots suggests it is ___________________

intrauterine bleeding.

because ulcer is localised and not severe. | In severe case( systemic involvement) __________________

I/v ticarcillin.

for deep and non-healing wound, do MRI to exclude osteomyelitis first, then tx with _______________

antibiotics

Says 3 mm deep ulcer is an indication for further evaluation for osteomyelitis. Here,the Q says purulent ulcer,non healing and 1 cm DEEP. So no doubt the next mx will be ______________.

MRI

rifampicin is enzyme inducer it will decrease efficacy ,rifampicin and ____________pill

contraceptive

poorly controlled sugar levels in the mother leads to hyperglycaemia in the fetus, which causes more release of Insulin, IGFs and Growth Hormone in the fetus and hence there’s more adipose deposition and ___________.

Macrosomia

The mainstay of treatment in diabetic patients with new onset proteinuria to aggressively control blood pressure, ideally below 130/80 mmHg. _________________ are therefore first-line therapy, angiotensin receptor blockers can also be used.

ACE inhibitors (D)

ischaemic/coronary heart disease cerebrovascular disease peripheral vascular disease

Macrovascular complications include:

``` death (24%) myocardial infarction (22%) stroke (33%) cardiovascular death (37%) overt nephropathy (24%) ```

An analysis of type 2 diabetes in the HOPE study12,13 showed a benefit of ramipril to reduce the risk of:

``` Kidney Nerves Infection Vessels Eyes Skin ```

Consider organs/problems affected by diabetes under the mnemonic ‘KNIVES’:

The small vessels most affected from a clinical viewpoint are the retina, nerve sheath and kidney glomerulus. In younger people it takes about 10 to 20 years after diagnosis for the problems of diabetic retinopathy, neuropathy and nephropathy to manifest.

Microvascular disease

Prevention of diabetic nephropathy is an essential goal of treatment. Early detection of the yardstick, which is microalbuminuria, is important as the process can be reversed with optimal control, particularly of _____________________

blood pressure.

The dipstick method is unreliable and the preferred | hospital method of 24-hour urine collection is considered impractical in general practice

diabetic nephropathy

Screening is done simply by a first morning urine sample to determine the albumin–creatinine ratio

diabetic nephropathy

``` ACE inhibitors (or angiotensin II receptor blockers if a cough develops) should be used for evidence of hypertension. ```

diabetic nephropathy

Retinopathy develops as a consequence of ________________disease of the retina

microvascular

Assessment of the fundus by an expert is recommended every 1–2 years, via direct ophthalmoscopy (with dilated pupils), retinal photography or, if necessary, fluorescein angiography.

Retinopathy and maculopathy

Early diagnosis of serious retinopathy is vital since the early use of laser photocoagulation may delay and prevent ________________

visual loss.

radiculopathy (diabetic lumbosacral radiculoplexopathy) sensory polyneuropathy isolated or multiple mononeuropathy isolated peripheral nerve lesions (e.g. median nerve) cranial nerve palsies (e.g. III, VI) amyotrophy

diabetic Neuropathy

autonomic neuropathy, which may lead to: erectile dysfunction postural hypotension and syncope impaired gastric emptying (gastroparesis)

diabetic Neuropathy

diarrhoea delayed or incomplete bladder emptying loss of cardiac pain → ‘silent’ ischaemia hypoglycaemic ‘unawareness’ sudden arrest, especially under anaesthetic

diabetic Neuropathy

skin: mucocutaneous candidiasis (e.g. balanitis, vulvovaginitis), staphylococcal infections (e.g. folliculitis)

poorly controlled diabetes

urinary tract: cystitis (women), pyelonephritis and perinephric abscess

poorly controlled diabetes

lungs: pneumonia (staphylococcal, streptococcal pneumonia), tuberculosis

poorly controlled diabetes

Hypoglycaemia Diabetic ketoacidosis Hyperosmolar hyperglycaemia Lactic acidosis

Diabetic metabolic complications

``` Cataracts Refractive errors of eye Sleep apnoea Depression Musculoskeletal: neuropathic joint damage (Charcot-type arthropathy), tendon rupture Foot ulcers (related to neuropathy) ```

Diabetic complications

intensive lifestyle intervention in individuals who are | overweight with impaired glucose tolerance or raised fasting blood glucose

Prevention of diabetes

reduction of ‘lifestyle’ risks—weight, smoking, low physical activity

Management of diabetes

strict glycaemic control as measured by HbA1c (target varies with circumstance, but usually ≤7%)

Management of diabetes

blood pressure control (≤140/90 mmHg, lower if tolerated)

Management of diabetes

control of blood lipid levels

Management of diabetes

four times a day (before meals and before bedtime) at first and for problems twice a day (at least once) may settle for 1–2 times a week (if good control)

Blood glucose monitoring at home | Type 1 diabetes

important for those on insulin, not routinely recommended for oral medication (monitor with HbA1c instead, in most circumstances) more useful for pregnant women, frail elderly, heavy machinery operators or symptomatic hypoglycaemia

Blood glucose monitoring at home | Type 2 diabetes

which normally comprises 4–6% of the total haemoglobin, is abnormally abundant in those with persistent hyperglycaemia, reflecting suboptimal metabolic control.

HbA1c,

__________________have a long half-life and their measure reflects the mean plasma glucose levels over the past 2–3 months and hence provides a good method of assessing overall diabetes management.

Glycohaemoglobins

__________ should be checked every 3–6 months

HbA1c

rapid-acting and short duration (ultra-short)

insulin lispro, insulin aspart

short-acting—neutral

regular, soluble

intermediate-acting

isophane (NPH) or lente

long-acting

ultralente, insulin detemir, insulin glargine

diet therapy exercise program weight loss

Type 2 diabetes | First-line treatment

Most symptoms improve within 1–4 weeks on diet and exercise

Type 2 diabetes | First-line treatment

If unsatisfactory control persists after 3–6 months, consider adding an oral hypoglycaemic agent

Type 2 diabetes | First-line treatment

The usual first-line agent is metformin, which reduces | _________________.

insulin resistance

If glycaemic targets are not achieved on monotherapy, usual practice is to add in a secretagogue, such as a sulfonylurea, which increases _____________________

insulin production

newer agents SGLT2 inhibitors (the gliflozins) and GLP-1 receptor agonists (injected) should be considered for their ___________________________

cardioprotective and renoprotective effects

``` 12 (also slowrelease daily dosage) 0.5–3 g Side effects: GIT disturbances (e.g. diarrhoea, a/n/v) ```

Metformin | a biguanide

Hypoglycaemia most common side effect

Gliclazide

Dubious mortality benefit. Caution with heart failure.

Thiazolidinediones | glitazones

Oedema, weight | gain, heart failure

Thiazolidinediones | glitazones

horners syndrome triad includes ptosis,anhidrosis,miosis .It is associated with

pancoast tumor

___________ should be painless haematuria

Bladder Ca

Precipitating factor insulin insufficient, interrupted insulin therapy, infection,infection, stress, alcohol

DkA

If no thyroid swelling but features of hyperthyroidism then __________ first then RIU scan.

TSH-R Ab

Multiple myeloma is present with fatigue lethargy and ______________

hypercalcemia

indepamide cause __________ work as diuretics

hyponatramia

indapamide causing | Hyponatremia results in ____________

confusion

Hypoglycaemia is theoretically defined as blood glucose falling below __________

4.0 mmol/L

Classic warning symptoms: sweating, tremor, palpitations, hunger, peri-oral paraesthesia

Hypoglycaemia

30 mL 50% glucose slow IV push

Treatment (reduced conscious state or unconscious)

Usually 10 mL in children. 50% glucose slow IV push

Treatment (reduced conscious state or unconscious)

This life-threatening emergency requires intensive management. It usually occurs during an illness (e.g. gastroenteritis) when insulin is omitted. It can also occur in type 2 diabetes.

Diabetic ketoacidosis24

Develops over a few days, but may occur in a few hours in ‘brittle’ diabetics

Diabetic ketoacidosis

Hyperglycaemia (often >20 mmol/L, lower or normal if on SGLT2 inhibitor)

Diabetic ketoacidosis

Preceded by polyuria, polydipsia, drowsiness

Diabetic ketoacidosis

Vomiting and abdominal pain, dehydration

Diabetic ketoacidosis

Hyperventilation—severe acidosis (acidotic breathing): ↓BP, ↑pulse, ↑resp. rate

Diabetic ketoacidosis

Ketosis (blood and urine)

Diabetic ketoacidosis

Arrange urgent hospital admission

Diabetic ketoacidosis

Early IV fluids—normal saline fast first litre, then caution

Diabetic ketoacidosis

IV insulin—slow, e.g. 10 U in first hour

Diabetic ketoacidosis

ECG—arrhythmia in electrolyte disturbances

Diabetic ketoacidosis

Diabetic ketoacidosis with __________requires fluid, sodium (eventually 3 L N saline), potassium (KCl) and insulin.

coma

People with this problem may present with an altered conscious state varying from stupor to coma and with marked dehydration

Hyperosmolar hyperglycaemia

The onset may be insidious over a period of weeks, with | fatigue, polyuria and polydipsia.

Hyperosmolar hyperglycaemia4

The key features are marked hyperglycaemia and dehydration without ketoacidosis

Hyperosmolar hyperglycaemia4

It occurs typically in uncontrolled type 2 diabetes, especially in elderly patients.

Hyperosmolar hyperglycaemia4

There may be evidence of an | underlying disorder such as pneumonia or a urinary infection

Hyperosmolar hyperglycaemia4

The essential findings are extreme | hyperglycaemia and high plasma osmolarity

Hyperosmolar hyperglycaemia4

The condition has a high mortality—even higher | than ketoacidosis.

Hyperosmolar hyperglycaemia4

IV fluids, e.g. normal to ½ normal saline, given slowly | Insulin—relatively lower doses than acidosis

Hyperosmolar hyperglycaemia4

Patients with ____________ present with marked hyperventilation ‘air hunger’ and confusion

lactic acidosis

has a high mortality rate and must be considered in the very ill person taking metformin, especially if kidney function is impaired

Lactic acidosis

Investigations reveal blood acidosis (low pH), low bicarbonate, high serum lactate, absent serum ketones and a large anion gap

Lactic acidosis

Treatment is based on removal | of the cause, rehydration and alkalinisation with IV sodium bicarbonate

Lactic acidosis

The prevalence of erectile dysfunction in men with type 2 diabetes over 40 years may be as high as __________. It may be caused by macrovascular disease, pelvic autonomic neuropathy or psychological causes.

50%

Autonomic ___________-related postural hypotension may be compounded by medication, including antihypertensives and anti-angina agents.

neuropathy

Symptoms of gastroparesis (due to autonomic neuropathy) with decreased gastric emptying include a sensation of fullness, dysphagia, reflux or recurrent nausea and vomiting, especially ________________.

after meals

Treatment options include medication with domperidone, cisapride or erythromycin

Gastroparesis

Injections of botulinum toxin type A into the pylorus via gastroscopy may facilitate gastric emptying.

Gastroparesis

In general terms, people controlled by diet alone have no restrictions for driving whereas those on ____________may obtain a conditional licence subject to annual or 2- yearly review.

insulin

Long-acting reversible contraceptives (e.g. Implanon, Mirena) or the combined oral contraceptive pill are appropriate options for birth control in women not interested in permanent sterilisation. Bear in mind the possibility of polycystic ovarian syndrome

Contraception IN DIATEICS

requires specialist evaluation and then 1- to 2-yearly review

Type 1 diabetes

For _____________screening: every 2 years to inspect retina (or use retinal photography)

ophthalmological

Many cases of type 2 diabetes remain _____________, so vigilance is important.

undiagnosed

__________is a common cause of tiredness. If elderly people with type 2 diabetes are very tired, think of _____________

Hyperglycaemia

If a person with diabetes (particularly type 1) is very drowsy and looks sick, consider first the diagnosis of ______________

ketoacidosis

__________ is vital: always examine the feet when the person comes in for review

Foot care

Treat associated hypertension with ACE inhibitors or a calcium-channel blocker (also good in combination).

DIABETES

‘Never let the sun go down on pus in a diabetic foot’—______________

admit to hospital

If a foot ulcer hasn’t healed in 6 weeks, exclude osteomyelitis. Arrange for __________ and investigate the vasculature.

an MRI

Diabetes control: _____-monthly review

hyperuricaemia due to

thiazide diuretics

___________________________, which should be used in conjunction with an educational support program, has been proved to be effective and is available as chewing gum, inhaler, oral spray, lozenges, sublingual tablets or transdermal patches (the preferred method). Ideally the nicotine should not be used longer than 3 months

Nicotine replacement therapy (NRT)

This oral agent has a similar effectiveness to NRT.

Bupropion (Zyban)

Adverse effects include insomnia and dry mouth (both common), with serious effects, such as allergic reactions and increased seizure risk.7 It is contraindicated in persons with a history of epilepsy. Recommended dose: 150 mg (o) daily for 3 days then bd for 12 weeks.

Bupropion (Zyban)

It is an effective agent but there are several adverse side effects, especially nausea with a concern about neuropsychiatric effects

Varenicline tartrate

serum _________: elevated in chronic drinkers (returns to normal with cessation of intake)

GGT

abnormal liver function tests (other than GGT)

alcohol

__________________-deficient transferrin (quite specific—dependent on an enzyme induced by alcohol)

carbohydrate

is a serious life-threatening withdrawal state. It has a high mortality rate if inadequately treated and hospitalisation is always necessary.

Alcohol withdrawal delirium (delirium tremens)

May be precipitated by intercurrent infection or trauma 1–5 days after withdrawal (usually 3–4 days) Disorientation, agitation Clouding of consciousness Marked tremor Visual hallucinations (e.g. spiders, pink elephants) Sweating, tachycardia, pyrexia Signs of dehydration

Alcohol withdrawal delirium (delirium tremens)

Hospitalisation with alcohol specialist advisory service Correct fluid and electrolyte imbalance with IV therapy Treat any systemic infection Thiamine (vitamin B1) 300 mg IM or IV daily for 3–5 days, then thiamine 300 mg (o) daily Diazepam 20 mg (o) every 2 hours (up to max. 100 mg daily)

Alcohol withdrawal delirium (delirium tremens)

Chlorpromazine is not recommended because of its potential to lower seizure threshold. Diazepam and haloperidol may worsen the symptoms of hepatic toxicity

Alcohol withdrawal delirium (delirium tremens)

Overdose is potentially fatal. The average lethal blood alcohol concentration is about 0.45–0.5%.

Alcohol overdose

``` Loss of appetite, nausea (possibly vomiting) Lacrimation/rhinorrhoea Tiredness/insomnia Muscle aches and cramps Abdominal colic Diarrhoea ```

Opioid withdrawal effects19,20

Maximum withdrawal symptoms | usually occur between 36 and 72 hours and tend to subside after 10 days

Opioid withdrawal effects19,20

Buprenorphine controlled withdrawal (short term) is used to prevent the emergence of a withdrawal syndrome

Opioid withdrawal

In Australia, most people with anaemia will have ___________ ranging from up to 5% for children to 20% for menstruating females

iron deficiency

The remainder will mainly have anaemia of ______________

chronic disorders

probably the best test to monitor iron-deficiency anaemia

The serum ferritin level, which is low in cases of iron-deficiency anaemia

DxT fatigue + palpitations + exertional dyspnoea →

anaemia

``` tiredness/fatigue muscle weakness headache and tinnitus lack of concentration faintness/dizziness dyspnoea on exertion palpitations angina on effort intermittent claudication pica—usually brittle and crunchy food ```

anaemia

inadequate diet, pregnancy, GIT loss, menorrhagia, NSAID and anticoagulant ingestion

iron deficiency

inadequate diet especially with pregnancy and alcoholism, small bowel disease

folate deficiency

``` previous gastric surgery, ileal disease or surgery, pernicious anaemia, selective diets (e.g. vegetarian, fad) ```

vitamin B12 deficiency

abrupt onset anaemia with mild jaundice

haemolysis

MCV ≤ 80 fL

microcytic

MCV >100 fL

macrocytic

MCV 80–100 fL

normocytic

Iron deficiency Thalassaemia Anaemia of chronic disease Sideroblastic anaemia

Microcytic (MCV < 80 fL)

``` Vitamin B12 deficiency Folate deficiency Myelodysplastic disorders Cytotoxic drugs Liver disease/alcoholism ```

Microcytic (MCV > 100 fL)

``` Kidney disease Anaemia of chronic disease Endocrine failure/hypothyroidism Haemolysis Aplastic anaemia ```

Normocytic (MCV 80–100 fL)

``` Microcytic anaemia Serum ferritin level low (NR: F 15–200 mcg/L: M 30–300 mcg/L) Serum iron level low Increased transferrin level Microcytic hypochromic red cells MCV ↓, MCH ↓, MCHC ↓ Reduced transferrin saturation Response to iron therapy ```

Iron-deficiency anaemia3

``` Angular cheilosis/stomatitis Glossitis Oesophageal webs Atrophic gastritis Brittle nails and koilonychias ```

Non-haematological effects of chronic iron deficiency

``` Menorrhagia Gastrointestinal bleeding (e.g. carcinoma, haemorrhoids, peptic ulcer, hiatus hernia, GORD,NSAID therapy) Frequent blood donations Malignancy Hookworm (common in tropics) ```

iron deficiency Causes1

Microcytic, hypochromic red cells Anisocytosis (variation in size), poikilocytosis (shape)—pencil-shaped rods Low serum iron level Raised iron-binding capacity Serum ferritin level low (the most useful index)

Haematological investigations:

Oral iron is continued for __________ months to replenish stores.

3 to 6

significant microcytosis quite out of proportion to the normal Hb or slight anaemia, and confirmed by finding a raised HbA2 on Hb electrophoresis.

diagnosis of heterozygous thalassaemia minor

Treatment of ______________ is transfusion to a high normal Hb with packed cells plus desferrioxamine.

thalassaemia major

Each individually, or in combination, leads to macrocytosis with or without anaemia

Alcohol and liver disease

It is usually caused by lack of intrinsic factor due to autoimmune atrophic changes and by gastrectomy

Vitamin B12 deficiency pernicious anaemia

is found in the normal diet but only in foods of animal origin and consequently very strict vegetarians may eventually develop deficiency.

Vitamin B12 (cobalamin)

``` atrophic gastritis H. pylori infection H2 receptor blockers PPI drugs other drugs, e.g. OCP, metformin chronic alcoholism HIV strict vegan diet ```

Causes of food vitamin | B12 deficiency are

The main cause is poor intake associated with old age, poverty and malnutrition, usually associated with alcoholism. It may be seen in malabsorption and regular medication with antiepileptic drugs such as phenytoin

Folic acid deficiency

Oral __________5 mg/day to replenish body stores (5–10 mg). This takes about 4 weeks but continue for 4 months.

folate

This is the most common cause of normocytic anaemia and is usually due to haematemesis and/or melaena.

Acute haemorrhage

This is often associated with anaemia due to failure of erythropoietin secretion and is unresponsive to treatment

Kidney failure

if there is a reticulocytosis, mild macrocytosis, reduced haptoglobin, increased bilirubin and urobilinogen.

Suspect haemolytic anaemia

The more common of the congenital ones are hereditary spherocytosis, sickle-cell anaemia and deficiencies of the red cell enzymes, pyruvate kinase and G-6-PD, although most cases of G-6-PD deficiency haemolyse

haemolytic anaemia

clinical features of anaemia (Hb ↓), infection (WCC ↓) or bleeding (platelets ↓).

Aplastic anaemia

Diagnosis is by bone marrow examination.

Aplastic anaemia

_______deficiency is present in up to 10–30% of children in high-risk groups

Iron

High-risk groups include those infants <6 months who are premature and/or with low birthweight; toddlers 6–36 months with a diet high in cow’s milk and low in iron-containing foods

Iron deficiency in children10

Introduce _______-containing solids early—at 4 to 5 months, e.g. cereals, vegetables, egg and meat.

iron

Encourage breastfeeding and avoid cow’s milk in the first 12 months

Iron deficiency in children

__________ anaemia is blood-loss anaemia until proved otherwise

Iron-deficiency

__________ anaemia is usually due to menorrhagia or gastrointestinal loss until proved otherwise.

Blood-loss

Serum free tri-iodothyronine (T3) measurement and serum free thyroxine (T4) can be useful in suspected ____________

T3 toxicosis

TSH receptor antibodies (TR Ab):

Graves disease

Thyroid peroxidase antibodies (TPO Ab):

Hashimoto disease

Thyroglobulin antibody (Tg Ab):

Hashimoto disease

This is the single most cost-effective investigation in the diagnosis of thyroid nodules

Fine-needle aspiration

It is the | best way to assess a nodule for malignancy

Fine-needle aspiration

The scan may help in the differential diagnosis of thyroid nodules and in causes of hyperthyroidism.

Thyroid nuclear scan and imaging

A functioning nodule is said to be less likely to be malignant than a nonfunctioning nodule (cyst, colloid nodule, haemorrhage are non-functioning; carcinoma is usually non-functioning).

Thyroid nuclear scan and imaging

A thyroid ultrasound is usually more sensitive in the detection of thyroid nodules

Thyroid ultrasound

__________goitre may be diagnosed on ultrasound while the clinical impression may be that of a solitary nodule

multinodular

_________________ may be used particularly to determine if there is significant compression in the neck from a large multinodular goitre with retrosternal extension

CT scan of the thyroid

The term __________refers to the accumulation of mucopolysaccharide in subcutaneous tissues.

myxoedema

Transient causes include subacute thyroiditis, postpartum thyroiditis and silent thyroiditis.

Hypothyroidism

Common causes of primary hypothyroidism include

radioactive iodine treatment, thyroid surgery | and Hashimoto thyroiditis

``` autoimmune disorders (e.g. autoimmune lymphocytic thyroiditis, rheumatoid arthritis, type 1 diabetes) ```

Hypothyroidism

``` cold intolerance tiredness/lethargy/somnolence physical slowing mental slowing depression huskiness of voice puffiness of face and eyes pallor loss of hair weight gain ```

Hypothyroidism

DxT tiredness + husky voice + cold intolerance →

myxoedema

``` sinus bradycardia delayed reflexes (normal muscular contraction, slow relaxation) coarse, dry and brittle hair thinning of outer third of eyebrows dry, cool skin skin pallor or yellowing obesity goitre ```

Hypothyroidism

________________, or lymphocytic thyroiditis, which is an autoimmune thyroiditis, is the commonest cause of bilateral non-thyrotoxic goitre in Australia

Hashimoto thyroiditis

bilateral goitre classically described as firm and rubbery patients may be hypothyroid or euthyroid with a possible early period of thyrotoxicosis Diagnosis is confirmed by a strongly positive antithyroid microsomal antibody (TPO Ab) titre and/or fine-needle aspiration cytology

Hashimoto thyroiditis

T4—subnormal | TSH—elevated (>10 is clear gland failure)

Laboratory diagnosis of hypothyroidism

If T4 is low and TSH is low or normal, consider pituitary dysfunction

secondary | hypothyroidism) or sick euthyroid syndrome

A raised TSH and T4 in normal range denotes

‘subclinical’ hypothyroidism

Serum cholesterol level elevated Anaemia: usually normocytic; may be macrocytic ECG: sinus bradycardia, low voltage, flat T waves

hypothyroidism

Confirm the diagnosis, provide appropriate patient education and refer the patient where appropriate.

hypothyroidism

Levothyroxine (thyroxine) 50–100 mcg daily, increasing by 25 mcg up to 100–200 mcg if required

hypothyroidism

Start with low doses (25–50 mcg daily) in >60 years and those with ischaemic heart disease and 50–100 mcg in others

hypothyroidism

Monitor TSH levels 6–8 weeks at first. As euthyroidism is achieved, monitoring may be less frequent (e.g. 2–3 months). When stable on optimum dose of T4, monitor every 2–3 years.

Thyroid medication

Rapid thyroxine replacement can precipitate myocardial infarction, especially in the elderly

Ischaemic heart disease

Continue thyroxine during pregnancy; watch for hypothyroidism (an increased dose of T4 is often required).

Pregnancy and postpartum

If euthyroid, can stop thyroxine for one week. If subthyroid, defer surgery until euthyroid.

Elective surgery

Urgent hospitalisation under specialist care is required. Intensive treatment is required, which may involve parenteral T4 or T3 as liothyronine or thyroxine by slow IV injection.

Myxoedema coma

This is a life-threatening emergency with coma, extreme hyperthermia, areflexia and respiratory depression. Precipitating factors include illness, infection, trauma and cold.

Myxoedema coma

Treatment is | supportive care, IV thyroxine or liothyronine and corticosteroids. Convert to oral T4 when stable.

Myxoedema coma

Misdiagnosing this serious condition leads to failure to thrive, retarded growth and poor school performance.

Neonatal hypothyroidism

If untreated it leads to permanent intellectual damage (cretinism).

Neonatal hypothyroidism

The clinical features of the newborn include coarse features, dry skin, supra-orbital oedema, jaundice, harsh cry, slow feeding and umbilical hernia

Neonatal hypothyroidism

It is detected by routine neonatal heel-prick blood testing

Neonatal hypothyroidism

Thyroxine replacement should be started as soon as possible

Neonatal hypothyroidism

is also relatively common and may affect up to 2% of women, who are affected four to five times more often than men

Hyperthyroidism (thyrotoxicosis)

Graves disease is the most common | cause, followed closely by nodular thyroid disease

Hyperthyroidism (thyrotoxicosis)

Autonomous functioning nodules/toxic adenoma

Hyperthyroidism (thyrotoxicosis)

Subacute thyroiditis (de Quervain thyroiditis)—viral origin

Hyperthyroidism (thyrotoxicosis)

Excessive intake of thyroid hormones—thyrotoxicosis factitia

Hyperthyroidism (thyrotoxicosis)

Heat intolerance Sweating of hands Muscle weakness Weight loss despite normal or increased appetite Emotional lability, especially anxiety, irritability Palpitations Frequent loose bowel motions

Hyperthyroidism (thyrotoxicosis)

DxT anxiety + weight loss + weakness →

thyrotoxicosis

``` agitated, restless patient warm and sweaty hands fine tremor (place paper on hands) goitre proximal myopathy hyperactive reflexes bounding peripheral pulse ± atrial fibrillation ```

Hyperthyroidism (thyrotoxicosis)

Lid retraction (small area of sclera seen above iris) Lid lag Exophthalmos Ophthalmoplegia in severe cases

Hyperthyroidism (thyrotoxicosis)

T4 (and T3) elevated TSH level suppressed Radioisotope scan Antithyroid peroxidase (TPO Ab)—often positive

Hyperthyroidism (thyrotoxicosis)

The isotope scan enables a diagnosis of Graves disease to be made when the scan shows uniform increased uptake

Hyperthyroidism (thyrotoxicosis)

Increased irregular uptake would suggest a toxic multinodular goitre, while there is poor or no uptake with de Quervain thyroiditis and thyrotoxicosis factitia

Hyperthyroidism (thyrotoxicosis)

Establish the precise cause before initiating treatment. Refer to an endocrinologist to guide treatment. Educate patients and emphasise the possibility of development of recurrent hyperthyroidism or hypothyroidism and the need for lifelong monitoring. Monitor for cardiovascular complications, osteoporosis and eye problems

Hyperthyroidism (thyrotoxicosis)

Radioactive iodine therapy (131I) Thionamide antithyroid drugs (initial doses) carbimazole 10–45 mg (o) daily starting with 10–20 mg in divided doses depending on disease activity or propylthiouracil 200–600 mg (o) daily in divided doses or methimazole

Hyperthyroidism (thyrotoxicosis)

Adjunctive drugs beta blockers (for symptoms in acute florid phase, e.g. propranolol 10–40 mg, 6 to 8 hourly); diltiazem or atenolol are alternatives lithium carbonate (rarely used when there is intolerance to thionamides) Lugol’s iodine: mainly used prior to surgery Surgery

Hyperthyroidism (thyrotoxicosis)

Younger patients with small goitres and mild case—18-month course antithyroid drugs

Treatment (Graves disease)

Large goitres or moderate-to-severe cases—antithyroid drugs until euthyroid, then surgery or

Treatment (Graves disease)

Control hyperthyroidism with antithyroid drugs, then surgery or 131I. Long-term remissions on antithyroid drugs in a toxic nodular goitre are rare.

Treatment (Graves disease)

Because there is chance of hematoma, so I think we should remove the ___________first

staples

Hypertension with hypokalemia Could be primary hyper aldosteronism or secondary hyper aldosteronism Primary is ___________ in which renin is decreased and 2’o is RTA in which renin is increased

conn’s synd

aldosterone is elevated. But doing plasma __________level will differentiate between primary hyperaldosteronism and renal artery stenosis.

renin

hyperaldosteronism, initial inx should be plasma ____________

aldosterone/renin ratio

________________ is the treatment of choice in any woman with Graves disease planning pregnancy or in the first trimester as carbimazole is associated with a rare embryopathy.

Propylthiouracil (PTU)

In the second and third trimesters, switching to ________________has been suggested due to the risk of fulminant hepatitis with PTU

carbimazole

_____________ with hypokalemic myopathy

Conn disease

Presence of High Bp and Hypokalemia

Conn's disease

Initial and best plasma free _____________then urinary VMA

metanephrin

next -24 hour urinary metanephrines | Best - plasma metanephrines

pheochromocytoma

____________goiter is most common

Multinodular

on __________If GH not suppressed: this confirmes acromegaly

OGTT

conduct pituitary MRI to determine the source of _______________ later.

excess GH

the best initial test is level of IGF-1, most accurate is glucose suppression test .

acromegaly

but it's was mentioned in class to increase the dose by 1.5 times

Pregnant woman with hypothyroidism

Wermer’s syndrome Pitiuitary tumor Parathyroid adenoma Pancreas( gastrinoma, vipnoma, insulinoma)

Men1

is the most accurate test for acromegaly, but initial inx for acromegaly is IGF-1

Oral glucose tolerance

The best would be treating by __________________ and defer her pregnancy till cure which usually takes 6 months

radio active iodine

Primary hyperparathyroidism Most common cause parathyroid adenoma Next common cause _________________

parathyroid hyperplasia

first, then USG or radioactive thyroid scan depends on the TSH level

Thyroid function test

Pt has ___________blood culture | Best is duplex Doppler

fever

history of DVT, rule out DVT first; it can also be cellulitis, but even it's cellulitis, blood culture is very limited and not routinely performed cuz ____________________

the positive rate is very low

-1.5-2.5 score

osteopenia | Ca and vit d

Hypothyroidism. Most common cause _________________

hashimoto

Most common ca is papillary but in this case as tsh is high it means it’s hypo and hushimoto is most common in hypothyroidism leading to ____________

goitre

here ACTH is releasing due to secondary cause, paraneoplastic syndrome vaiya, secreting Ectopic ACTH which is stimulating melanocyte (cause adrenal gland is fine itself) and causing _______________.

pigmentation

If zolendronic is in options that would be more gud one as __________is no more used

strontium

cant give alendronate as gerd.and not HRT and ca,vit D as already _____________

osteoporosis

Here pt has got GERD , so we can’t choose (A) Alendronate because it causes / aggravates ____________

oesophagitis

When you don’t find out the exact cause of bleeding, go for _____________

capsule endoscopy

amedex says in overt bleeding: melana, hematochezia, blood loss go for _______________

CT ANGIOGRAPHY

Occult bleeding : iron deficiency anemia and +fecal occlude blood test go for ____________

capsule

Capsule endo when __________positive

FOBt

100% sc as the cord was involved , we just wait cuz all theatres are busy ,, always cord involved means ________

first give magnesium till you find a theatre then deliver by SC ,, the next after _________is SC

magnesium

Non specific back pain caused by lifting weights. Encourage activity and analgesics. ________________ here so no imaging is warranted

No red flags

Imaging is done if there are red flags e.g ________________ or cancer etc

neurological deficits

____________for pain and encourage normal activity

Analgesics

Nsaids not given in someone with _____________

nephropathy

Allopurinol is not started in acute gout. But if the patient has an acute attack of gout while on allopurinol, we can continue the drug. But ________________ will not help with the pain or the swelling.

increasing the dose

no change of dose of allupurinol during a cute stage , we can increase the dose of allupurionol to prevent _______________ not during the attack

acute attack

Acute episode + nephropathy

Steroid

dose of allopurinol should not be changed in acute attack._____________ u can

once it settles

Acute gout- ___________contraindicated

allopurinol

Acute on top chronic gout in impaired renal | answer : ___________> D

steroid

In patients with tumors less than 1 cm located in the appendix, ____________is the treatment of choice.

appendectomy

_____________________ is indicated for tumors larger than 2 cm, lymphatic invasion, lymph node involvement

More extensive surgery

Radiculopathy with no red flag signs, so advice simple _____________and review in 1-2 wk

analgesics

Bilateral loss of pain and sensation and hx of trauma favours ________________

syringomyelia

____________common in obese young females

Pseudomotor

MS . hence _______is the investigation

MRI

Mnd there will be no ___________

numbness

``` If inr less than 4.5 __ reduce or skip next dose of warfarin # if inr more than ______ __ *stop dose of warfarin. *Check inr after 24 hrs. *Resume warfarin at reduced dose depending on results. ```

4.5

Upon commencing antidepressants, patients with bipolar disorder should be closely monitored for symptoms of mania, and if these emerge then antidepressant therapy should be ______________.

discontinued

________ infarct will have effect on upper limb and face | And it won’t cause dysphagia and dysarthria rather will cause aphasia due to broca’s and wernicke’s

Mca

excluded as dysarthria does not occur with MCA infarction ___________occurs.

Dysphasia

_____________________.as both upper and lower motor neuron lesion sign is present

amyotropic lateral sclerosis

_________but ALS diagnosis is clinical

EMG

___________________ supportive only, if hs than add acyclovir

viral meningitis

supportive for viral meningitis, if it's caused by herpes, then add ____________

aciclovir

history of infection, now presenting headache, fever, neuro focal symptoms, suspect _____________

brain abscess

________ presents with ascending bilateral weakness

GBS

Brain tumor will represent more features of raised icp over long period of time without ______________

fever

Pneumonia— _______cough sputum

fever

In ______________there is fever headache raised icp low immune

abscess

Eye opening to pain=2 Withdraws from pain=________ Incomprehensible sound=2

If patient is in ER we place a transcutaneous pacemaker, and refer to cardiology unit for ___________________________

permanent pacemaker placement.

Monte & ______ are preventors against its pathology

SCG

Depends upon age of pt if less than 5 _sodium cromiglycate | If 5 or more -______________

inhaled corticosteroids

Presbyacusis... sensorial neural deafness.. bilateral...in ______________ its unilateral

acoustic neuroma

First reduce displacement, then __________

wound debridement

bulging fontanelle is ___________for LP

contraindicated

LP is _____________in raised ICP

contraindicated

Hyperthyroidism is usually transient for 1–2 months, and follows a surge of thyroxine after a viral-type illness, then followed by hypothyroidism for 4–6 months.

Subacute thyroiditis (de Quervain thyroiditis)

Symptoms include pain | and/or tenderness over the goitre (especially on swallowing), fever, ESR elevated,

Subacute thyroiditis (de Quervain thyroiditis

Release of thyroid hormone from autoimmune destruction of thyroid

Painless postpartum thyroiditis

Treat with beta blockers for symptoms and thyroxine for | hypothyroid phase.

Painless postpartum thyroiditis

Clinical features are marked anxiety, weight loss, weakness, proximal muscle weakness, hyperpyrexia, tachycardia (>150 per minute), heart failure and arrhythmias

Thyroid crisis (thyroid storm)

It requires urgent intensive hospital management with antithyroid drugs; IV saline infusion, IV corticosteroids, anti-heart failure and antiarrhythmia therapy, especially beta blockers.

Thyroid crisis (thyroid storm)

Thyroid enlargement may be diffuse or multinodular.

Goitre

Diffuse causes include physiological, | Graves disease, thyroiditis (Hashimoto or de Quervain), iodine deficiency or it can be hereditary.

Goitre

Investigations include TFTs, needle biopsy, ultrasound and CXR.

Goitre

defined as a discrete lesion on palpation and/or ultrasonography that is distinct from the rest of the thyroid gland.

A thyroid nodule

True solitary nodule: adenoma, carcinoma (papillary or follicular)

Thyroid nodules

Ultrasound imaging Fine-needle aspiration cytology Thyroid function tests

Thyroid nodules

The main presentations are a painless nodule, a hard nodule in an enlarged gland or lymphadenopathy. Papillary carcinoma is the most common malignancy

Thyroid carcinoma8

This often involves total thyroidectomy, ablative 131I treatment, thyroxine replacement and follow-up with serum thyroglobulin measurements, 131I/thallium scanning and neck ultrasound. Fine-needle aspiration is the investigation of choice.

Thyroid carcinoma8

Fine-needle aspiration is the investigation of choice

Thyroid carcinoma

These account for 10% of intracranial tumours and are invariably benign adenomas

Pituitary tumours

They can present with hormone deficiencies, features of hypersecretory syndromes (e.g. prolactin, GH, ACTH) or by local tumour mass symptoms (e.g. headache, visual field loss, seizures, cranial nerve 3, 4, 6 palsy).

Pituitary tumours

The main causes (of many) are a pituitary adenoma (prolactinoma; micro- or macro), pituitary stalk damage, drugs—such as antipsychotics, various antidepressants, metoclopramide, cimetidine, oestrogens, opiates, marijuana—and physiological causes such as pregnancy and breastfeeding.

Hyperprolactinaemia11

Symptoms common to males and females: reduced libido, subfertility, galactorrhoea (mainly females)

Hyperprolactinaemia

Females: amenorrhoea/oligomenorrhoea Males: erectile dysfunction, reduced facial hair

Hyperprolactinaemia

Serum prolactin and macroprolactin assays

Hyperprolactinaemia

Refer for management, which may include a dopamine agonist such as cabergoline or bromocriptine, surgical resection (rarely necessary) or radiotherapy.

Hyperprolactinaemia

excessive growth of hands (increased glove size) excessive growth of tissues (e.g. nose, lips, face) excessive growth of feet (increased shoe size) increased size of jaw and tongue; kyphosis

Acromegaly

``` general: weakness, sweating, headaches sexual changes, including amenorrhoea and loss of libido disruptive snoring (sleep apnoea) ```

Acromegaly

DxT nasal problems + fitting problems (e.g. rings, shoes) + sweating →

acromegaly

Plasma growth hormone excess Elevated insulin-like growth factor 1 (IGF-1) (somatomedin)—the key test X-ray skull and hands MRI scanning pituitary

acromegaly

Consider associated impaired glucose tolerance/diabetes Obtain old photographs (if possible). Treatment options: transsphenoidal pituitary microsurgery, drugs and radiotherapy.

acromegaly

Impaired secretion of vasopressin (antidiuretic hormone) from the posterior pituitary leads to polyuria, nocturia and compensatory polydipsia, resulting in the passage of 3–20 L of dilute urine per day.

diabetes insipidus

There are several causes of ________________, the commonest being postoperative (hypothalamic-pituitary), which is usually transient only. Other causes of cranial DI include tumours, infections and infiltrations

diabetes insipidus (DI)

In nephrogenic DI the kidney tubules are | insensitive to _____________.

vasopressin

_____________________________is caused by cancer (e.g. lung, lymphomas, kidney, pancreas), pulmonary disorders, various intracranial lesions and drugs such as carbamazepine and many antipsychotic agents

The syndrome of secretion of inappropriate antidiuretic hormone (SIADH)

Management of | SIADH is essentially ______________

fluid restriction

The treatment of _____ is desmopressin, usually given twice daily intranasally

DxT weakness + polyuria + polydipsia →

diabetes insipidus

a history of postpartum haemorrhage or head injury symptoms of hypothyroidism symptoms of adrenal insufficiency symptoms suggestive of a pituitary tumour thin, wrinkled skin: ‘monkey face’ pale ‘alabaster’ skin/hairlessness

Hypopituitarism

Causes: pituitary adenoma, other parasellar tumours and inflammatory/infiltrative lesions.

Hypopituitarism

DxT (female): amenorrhoea + loss of axillary and pubic hair + breast atrophy →

hypopituitarism

DxT (male): ↓ libido + impotence + loss of body hair →

hypopituitarism

Investigate with serum pituitary hormones, imaging (MRI) and triple stimulation test.

hypopituitarism

Treatment includes HRT, surgery or radiotherapy.

hypopituitarism

Zona ___________—mineral corticoids, especially aldosterone

glomerulosa

Zona ____________—glucocorticoids

fasciculata

Zona ____________—androgens, especially DHEA

reticularis

Catecholamines—epinepherine, norepinephrine

Medulla

deficiency of cortisol and aldosterone

chronic adrenal insufficiency (Addison disease)—

cortisol excess

Cushing syndrome

Autoimmune destruction of the adrenals is the most common cause; others are infection, e.g. TB or fungal.

Addison disease

Lethargy/excessive fatigue/weakness Anorexia and nausea Diarrhoea/abdominal pain Weight loss Dizziness/funny turns, syncope: hypoglycaemia (rare); postural hypotension (common) Hyperpigmentation, especially mucous membranes of mouth and hard palate, skin creases of hands

Addison disease

remains undiagnosed, wasting leading to death may occur. Severe dehydration can be a feature.

Addison disease

DxT fatigue + a/n/v + abdominal pain (± skin discolouration)→

Addison | disease

Elevated serum potassium, low serum sodium Low plasma cortisol level (fails to respond to synthetic adrenocorticotropic hormone [ACTH]) The short synacthen stimulation test is the definitive test Consider adrenal autoantibodies and imaging? calcification of adrenals

Addison | disease

Treatment: corticosteroid replacement—hydrocortisone/fludrocortisone acetate, other options

Addison | disease

Age is important Old age cystoscopy And usg done according to protocol ua should be done prior __________

usg

An ________________ develops because of an inability to increase cortisol in response to stress, which may include intercurrent infection, surgery or trauma.

Addisonian crisis

Nausea and vomiting Acute abdominal pain Severe hypotension progressing to shock Weakness, drowsiness progressing to coma

Addisonian crisis

Establish IV line with IV fluids Hydrocortisone sodium succinate 100 mg IV initially and 50–100 mg 4–6 hourly until stable Arrange urgent hospital admission

Addisonian crisis

iatrogenic—chronic corticosteroid administration pituitary ACTH excess (Cushing disease) bilateral adrenal hyperplasia adrenal tumour (adenoma, adenocarcinoma) ectopic ACTH or (rarely) corticotrophin-releasing hormone (CRH) from non-endocrine tumours (e.g. oat cell carcinoma of lung) The clinical features are caused by the effects of excess cortisol and/or adrenal androgens

Cushing syndrome8

``` Proximal muscle wasting and weakness Central obesity, buffalo hump on neck Cushing facies: plethora, moon face, acne Weakness Hirsutism Abdominal striae Thin skin, easy bruising Hypertension Hyperglycaemia (30%) Menstrual changes (e.g. amenorrhoea) Osteoporosis Psychiatric changes ```

Cushing syndrome8

DxT plethoric moon face + thin extremities + muscle weakness →

Cushing syndrome

Cortisol excess (plasma or 24-hour urinary cortisol) Dexamethasone suppression test Late night salivary cortisol (2 measurements) Inferior petrosal sinus sampling Serum ACTH Radiological localisation: MRI for ACTH-producing pituitary tumours; CT scanning for adrenal tumours

Cushing syndrome

transsphenoidal excision of pituitary tumour. Pharmacological blockade of corticosteroid production may be necessary, ketoconazole (o) is first line.

Cushing syndrome

Most commonly due to an adrenal adenoma.

Primary hyperaldosteronism

Usually asymptomatic and hypertensive but any symptoms are features of hypokalaemia

Conn syndrome

``` weakness, headaches palpitations cramps paraesthesia polyuria and polydipsia ```

Conn syndrome

``` Aldosterone (serum and urine) ↑ Plasma renin ↓ Plasma aldosterone to renin activity ratio Na ↑, K ↓, alkalosis Imaging (MRI or CT scan) of adrenals ```

Conn syndrome

Refer for treatment including possible surgery to excise adenoma. prepare for surgery.

Conn syndrome

``` A dangerous tumour of the adrenal medulla. Clinical features are paroxysms or spells of: anxiety hypertension headache (throbbing); tremor sweating palpitations pallor/skin blanching rising sensation of tightness in upper chest and throat (angina can occur) ```

Phaeochromocytoma

DxT episodic headache + sweating + tachycardia →

phaeochromocytoma

Series of three 24-hour free catecholamines ↑ VMA | Abdominal CT or MRI scan (both highly sensitive)

phaeochromocytoma

Excise tumour, cover with alpha and beta blockers

phaeochromocytoma

condition with 21-hydroxylase deficiency being the most common of several forms.

Congenital adrenal hyperplasia (adrenogenital | syndrome)6,8

There is inadequate synthesis of cortisol and aldosterone with increased androgenisation

Congenital adrenal hyperplasia (adrenogenital | syndrome)

may present with failure to thrive or vomiting and | dehydration (SLS)

Most of those detected by abdominal imaging are benign and termed ‘incidentalomas’ but serious tumours include adrenal carcinoma, phaeochromocytoma, neuroblastoma, glucocorticoid or a mineralocorticoid secreting tumour.

Adrenal tumours

Rule: tumours >4 cm require thorough assessment as malignant tumours are large. Excision is usually advisable.

Adrenal tumours9

These are adrenal tumours ≥1 cm. Most are benign and non-functioning. An important issue is malignancy, and if this is the case, whether it is primary, secondary or functional (hormone secreting).

Incidentalomas

Investigations to consider include electrolytes, aldosterone/renin ratio, catecholamines, testosterone, DHEAs, dexamethasone suppression test, CT scan. Surgical excision should be considered under specialist guidance.

Incidentalomas

Suspect hypercalcaemia if there is weakness, tiredness, malaise, anorexia, nausea or vomiting, abdominal pain, loin pain, constipation, thirst, fever, polyuria, drowsiness, dizziness, personality changes, muscle aches and pains, visual disturbances

Hypercalcaemia

Measure urea and electrolytes (especially | calcium), creatinine, albumin.

Hypercalcaemia

Primary hyperparathyroidism, familial hypercalciuric hypercalcaemia and neoplasia, especially carcinoma of lung and breast (with metastases to bone), account for over 90% of cases.

Hypercalcaemia

Other causes include Paget disease, Williams syndrome, prolonged immobilisation, dehydration, sarcoidosis and milk-alkali syndrome.

Hypercalcaemia

Investigations include ESR, serum parathyroid hormone (N: 1.0–7 pmol/L), serum ACE levels, serum alkaline phosphatase, chest X-ray, Sestamibi scan and bone scan. Requires specialist referral.

Hypercalcaemia

DxT weakness + constipation + polyuria →

Hypercalcaemia

DxT cramps + confusion + tetany →

hypocalcaemia

is caused by an excessive secretion of parathyroid hormone and is usually due to a parathyroid adenoma.

Primary hyperparathyroidism

Classic mnemonic: bones, moans, stones, abdominal groans

Primary hyperparathyroidism

Exclusion of other causes of hypercalcaemia Serum parathyroid hormone (elevated) TC-99m Sestamibi scan to detect tumour

Primary hyperparathyroidism

Refer for possible surgical management

Primary hyperparathyroidism

Most appropriate is sputum for _________

AFB

______ is for latent TB

IGRA

next _____________ ,most appropriate sputum culture

chest x ray

dx NSTEMI with AF (which has occured as a complication of MI) ____________will help to deal with both NSTEMI and AF(due to non valvular lesion)

Antiplatelet

Inverted T wave means _______

Causes include parathyroid injury, autoimmune hyperparathyroidism, severe vitamin D deficiency and neonates of mothers with hypercalcaemia.

Hypocalcaemia

This usually presents with tetany or | more generalised neuromuscular hyperexcitability and neuropsychiatric manifestations

Hypocalcaemia

The sensory equivalents are paraesthesia in the hands, feet and around the mouth (distinguish from tetany seen in the respiratory alkalosis of hyperventilation).

Hypocalcaemia

There may be seizures and cramps. The diagnosis is by measurement of serum total calcium concentration in relation to serum albumin (s. calcium <2.10 mmol/L).

Hypocalcaemia

Two important signs are: Trousseau sign: occlusion of the brachial artery with BP cuff precipitates carpopedal spasm (wrist flexion and fingers drawn together) Chvostek sign: tapping over parotid (facial nerve) causes twitching in facial muscles

Hypocalcaemia

Treatment involves careful adjustments in dosage of calcitriol and calcium to correct hypocalcaemia and avoid hypercalcaemia and hypercalciuria (the latter may lead to kidney impairment).

Hypocalcaemia

is the most common cause of hypocalcaemia. Causes include postoperative thyroidectomy and parathyroidectomy, congenital deficiency (DiGeorge syndrome) and idiopathic (autoimmune) hypoparathyroidism.

Hypoparathyroidism

The main features are neuromuscular | hyperexcitability, tetany and neuropsychiatric manifestations.

Hypoparathyroidism

Water depletion (e.g. diabetes insipidus) Water and sodium depletion (e.g. diarrhoea) Corticosteroid excess (e.g. Cushing syndrome, Conn syndrome) Iatrogenic: excess IV hypertonic Na solutions

Hypernatraemia Na+ >145 mmol/L

Thirst, confusion, lethargy, weakness, irritability, oliguria Orthostatic hypotension Muscle twitching or cramps Signs of dehydration Severe: seizures, delirium, hyperthermia, coma

Hypernatraemia Na+ >145 mmol/L

Water retention (e.g. CCF, hypoalbuminaemia) Kidney failure to conserve salt (e.g. nephritis, diabetes mellitus, Addison disease) Gastrointestinal loss of Na+ (e.g. vomiting, diarrhoea) Drugs (e.g. diuretic excess, ACE inhibitors)

Hyponatraemia Na+ <135 mmol/L

Asymptomatic when mild Anorexia, nausea, lethargy, confusion, headache, ataxia, mental changes (e.g. in personality) Severe: convulsions, coma, death

Hyponatraemia Na+ <135 mmol/L

The first sign of ________________ (e.g. >6) may be a cardiac arrest. A medical emergency if >6.5.

hyperkalaemia

Oliguria, kidney failure Acidosis (especially metabolic) Mineralocorticoid deficiency: Addison disease, aldosterone antagonists Excessive intake of K+ (e.g. IV fluids with K) Drugs (e.g. ACE inhibitors, NSAIDs, suxamethonium) Consider artefact, e.g. haemolysed sample

Hyperkalaemia K+ >5.5 mmol/L

Malaise, muscle weakness, flaccid paralysis (rare) May be asymptomatic until cardiac toxicity May cause cardiac arrest—asystole or fibrillation ECG: peaked T waves, ↓ QT, ↑ PR interval → arrhythmias

Hyperkalaemia K+ >5.5 mmol/L

If <2.5 severe symptoms, seek urgent attention.

Hypokalaemia K+ <3.5 mmol/L

Kidney disease Gastrointestinal loss: vomiting, diarrhoea Alkalosis Mineralocorticoid excess Loss of extracellular fluid to intracellular (e.g. burns, other trauma, pyloric stenosis) Drugs (e.g. diuretics: frusemide, thiazides), purgatives, liquorice abuse Reduced intake of K+

Hypokalaemia K+ <3.5 mmol/L

Lethargy, muscle weakness and cramps, mental lethargy and confusion Severe flaccid paralysis, tetany, coma ECG: prominent U waves, depressed ST segment, T waves, arrhythmias

Hypokalaemia K+ <3.5 mmol/L

``` neck pain neck stiffness headache ‘migraine’-like headache facial pain arm pain (referred or radicular) myelopathy (sensory and motor changes in arms and legs) ipsilateral sensory changes of scalp ear pain (peri-auricular) scapular pain anterior chest pain torticollis dizziness/vertigo visual dysfunction ```

Clinical problems of cervical spinal origin

The most common pathogens are the bacteria Escherichia coli (E. coli), Staphylococcus saprophyticus, Proteus, Klebsiella and Enterococcus spp.

Urinary tract infection (UTI)

Of great concern is the | worldwide emergence of multidrug-resistant strains of E. coli.

Urinary tract infection (UTI)

The morbidity of urinary infections in both children and adults is well known but it is vital to recognise the potential for progressive kidney damage, ending in chronic kidney failure.

Urinary tract infection (UTI)

The main task in the prevention of chronic pyelonephritis is the early identification of patients with additional factors, such as reflux or obstruction, which could lead to progressive kidney damage.

Urinary tract infection (UTI)

frequency, dysuria and | loin pain.

Urinary tract infection (UTI)

Screening of asymptomatic women has shown that about 5% have bacterial UTI.

Urinary tract infection (UTI)

UTIs are largely caused by organisms from the bowel that colonise the perineum and reach the bladder via the urethra.

Urinary tract infection (UTI)

In many young women, infections are | precipitated by sexual intercourse. Ascending infection accounts for 93% of UTIs

Urinary tract infection (UTI)

Always consider any family history of urinary tract abnormalities

Urinary tract infection (UTI)

Infants less than 6 months old with a UTI have a significant risk of bacteraemia

Urinary tract infection (UTI)

Female sex Sexual intercourse Diabetes mellitus Vesicoureteral reflux (VUR) Urinary tract obstruction/malformation/stricture Pregnancy Immunosuppression Menopause Diaphragm contraception or spermicidal exposure Instrumentation Bladder polyps, carcinoma, diverticula, stones

Urinary tract infection (UTI)

Sterile pyuria

Urinary tract infection (UTI)

contamination of poorly collected urine specimens urinary infections being treated by antibiotics, i.e. inadequately treated infections genital infections (e.g. chlamydia urethritis) analgesic nephropathy staghorn calculi other kidney disorders (e.g. polycystic kidney) bladder tumours tuberculosis chemical cystitis (e.g. cytotoxic therapy) appendicitis

Sterile pyuria

This is defined as the presence of a significant growth of bacteria in the urine (concentration >108 colony forming units/L), which has not produced symptoms requiring consultation

Asymptomatic bacteriuria

pregnant women because of the risk of pyelonephritis and pregnancy complications (see CHAPTER 100 ) patients before elective urological procedures (e.g. TURP)

Asymptomatic bacteriuria

the presence of frequency, dysuria and loin pain alone or in combination, together with a significant growth of organisms on urine culture

symptomatic bacteriuria

If not pregnant —-> xray pelvis | If pregnant —>_____

usg

debridement comes first then ________

reduction

______________are teratogenic we avoid in young age

Bisphosphonate

ok that means no bisphosphonates before __________________

menupause

reproductive age group avoid ____

BSP

Always correct __________ before bispoh

vit d

First correct vit D, then _________

alendronate

Tophaceous gout ....________

prednisolone

Pt. is already on Aspirin prophylaxis and developed stroke. CEA is recommended in symptomatic stenosis of >50% and asymptomatic stenosis of __________

>70%.

In alcohol aST to alt ratio _____

2:1

temperature is 38, child’s age is 4. It could be perthes tenosynovitis or septic arthritis based on age, I chose septic arthritis coz of ___________

fever

______________ in stable Abdominal trauma

CT abdomen

fever and ryt iliac fossa pain >__________

abscess

In a case of infertility,always do ________analysis first

semen

Diagnosis here is ________if timolol and pilocarpine in option will choose that from these options

galucoma

Suspend breast feeding for 24 hour than checkin __________

bilirubin

If conjugated bilirubin is >10% of total bilirubin from the options given its ____________

Biliary atresia

If we stop warfarin or giving vit K it will take about ___days time

if emergency Sx give ffp/prothrombin concetrate (B)...if Sx can be delayed above method of stopping or reversing the action of effect of ________________

anticoagulant

apple core lesion is significant for colon ca here patient having obstructive symptoms so if no options of Prothrombin then we will go with ____

ffp

symptoms of acute abdomen, so we will do __________ASAP

intervention

if history of snake bite present and even no fangs sign present utill unless always consider snake is poisonus so reffer to _________________

tertitory hospital

yes dont give ____________untill collapse aur cardiac arrest inr more than 1.3 opthalmoplegia aur paralysis events

antivenom

___________to find out gross hematuria cause

Cystoscopy

gross haematuria in less than 55 yrs initial ________then CT scan to rule out renal CA..

gross hematuria in middle aged ,initial ure then ____to rule out rcc

investigation for ______________ should be done frst as chest pain and travel h/o are present

pul. Embolism

early syphilis-benz penicilin single dose IM, or doxycyline incase of pen allergy. should contact all sexual partners in past 3 month. ________________ at 3 months, 3 monthly

repeat serology

Asymptomatic pts with more than 70% stenosis have modest risk and should be treated ____________

conservatively

carotid endarterectomy indicated when stenosis is __________ with symptoms.

75%

Sjogren > mx is supportive complaint for this pt is dry eyes so C . ______________

artificial eye drop

_________for mild pneumonia in children

Amox

after excluding adjustment disorder- major stress or absent, autism excluded coz- _____________.

speech normal

Post operative confusion,always think about hypoxia 1st.so pulse oxymetry.__________ should be more appropriate

ABG

because warfarin should be stopped _____________ before elective surgry

4-5 days

Intrahepatic cholestasis of pregnancy-develop in late pregnancy ,no rash ,worse itching at night,____________typically develops 1-4 weeks after onset of pruritus

jaundice

Scabies must have burrows | Pruritus in 3rd trimester goes in favour of ______________

cholestasis of pregnancy

zolendronic acid is generally _____

______________( a common side effect after covid vaccine) especially in below 50 yrs and younger age groups.

myocarditis

_______________ can elevated in PE and myocarditis

Troponin

no fetal heart sounds, so to deliver the dead baby-do ___________

amniotomy

apple core appearance _________

CA colon

IV antibiotics ( for all infants below 3 months).

Urinary tract infection

Iv antibiotics then Usg

urinary tract infection (UTI) in young children

paroxetine contraindicated in ___________

pregnancy

Patient takung ACEI since long withiut any angioneurosis .... & amoxycillin since 2 days &s/s after amoxy angioneuresis appeared ...so I will blame ___________

Amoxy

Polymyalgia Rheumatica with Giantcell arteritis. | __________would be better as next step.

ESR

____________because its excercise induced asthma, Ref JM 7the edition, still check the latest 8th edition once

salbutamol

initially SABA given , if not working than we choose __________

SCG or ICS

it shuld be ______________coin like apperaence is due to hypercalcemia leads to calcification which causes coin like asralra are present due to pul htn whixh is present in all others so b

sarcidiosis

Inflammation of the bladder and/or urethra is associated with dysuria (pain or scalding with micturition) and/or urinary frequency

Acute cystitis (dysuria-frequency syndrome)

Acute bacterial infection of the kidney produces loin pain and constitutional upset, with fever, rigors, nausea and sometimes vomiting

Acute pyelonephritis1

The symptoms of acute cystitis are often also present. The differential diagnosis includes causes of the acute abdomen, such as appendicitis, cholecystitis and acute tubal or ovarian diseases. The presence of pyuria and absence of rebound tenderness are helpful in distinction.

Acute pyelonephritis1

This is cystitis occurring in the uninstrumented non-pregnant female without structural or neurological abnormalities. Acute infection is most commonly caused by E. coli and Staphylococcus saprophyticus.

Uncomplicated urinary tract infection

This is associated with anatomical or functional abnormalities (e.g. diabetes, urinary calculi) that increase the risk of serious complications or treatment failure.

Complicated urinary tract infection5

The laboratory diagnosis of ___________ depends on careful collection, examination and culture of urine

UTI

It is not mandatory for non-pregnant | women with suspected cystitis when empirical treatment may be appropriate.

The laboratory diagnosis of UTI

It is best to collect the first urine passed in the morning, when it is highly concentrated and any bacteria have been incubated in the bladder overnight

Collection of urine1

Preferably the urine should be taken to the laboratory immediately, but it can be stored for up to 24 hours at 4°C to prevent bacterial multiplication.

Collection of urine1

Clean catch midstream specimen of urine (MSU). This is best collected from a full bladder, to allow at least 100 mL of urine to be passed before collection of the MSU

Collection of urine1

Catheter specimen of urine (CSU). In women who have difficulty with collecting an uncontaminated MSU (as is commonly the case in the elderly, the infirm and the grossly obese), a short open-ended catheter can be inserted and a specimen collected after 200 mL has flushed the catheter.

Collection of urine1

Suprapubic aspirate of urine (SPA). This is an extremely reliable way to detect bacteriuria in neonates and in patients where UTI is suspected but cannot be confirmed because of low colony counts or contamination in an MSU.

Collection of urine

All children with a UTI require a urine specimen. It is diagnosed by significant growth on MSU, CSU, MCC or SPA.

Urine specimen collection in children

____________ of urinary leucocytes or nitrite are suggestive of UTI and may be an indication for empirical treatment if symptomatic

Dipstick findings

The urine is examined under a microscope to detect pyuria (more than 10 pus cells—WBCs—per high-powered field) but should be examined in a counting chamber to calculate the number of WBCs/mL of urine.

Microscopic examination

The nature and number of organisms present in the urine are the most useful indicators of UTI

Culture of the urine

Most common are enteric organisms. E. coli (especially) and Staphylococcus saprophyticus are responsible for over 90% of UTIs, with other Gram-negative organisms (Klebsiella sp. and Proteus sp.), Enterococcus sp. and Gram-positive cocci (Streptococcus faecalis and other staphylococci) also responsible.

Culture of the urine

Infections due to organisms other than E. coli (e.g. Pseudomonas sp.) are suggestive of an underlying kidney tract abnormality.

Culture of the urine

If >105 colony forming units (cfu) per mL of bacteria are present in an MSU, it is highly likely that the patient has a UTI.

Culture of the urine

On the other hand, it is most important to realise that up to 30% of women with acute bacterial cystitis have less than 105 cfu/mL in the MSU. For this reason, it is reasonable to treat women with dysuria and frequency even if they have <105 cfu/mL of organisms in an MSU

Culture of the urine

Significant levels for UTI: Microscopy: WBC >10 per mL (10 × 106/L) Culture: counts >105 cfu/mL (108/L)

Summary: MCU (microscopy and culture urine)

Keep yourself rested. Drink a lot of fluid: 2–3 cups of water at first and then 1 cup every 30 minutes. Try to empty your bladder completely each time. Use analgesics such as paracetamol for pain. Make the urine alkaline by taking sodium citrotartrate (4 g orally 6 hourly)—not if taking nitrofurantoin.

Acute uncomplicated cystitis

``` Urine dipstick Urine microscopy and culture First-line antibiotics—trimethoprim or cephalexin Alkaliniser for severe dysuria High fluid intake Check sensitivity—leave or change ABs ```

UTI: basic management

Use for 10 days in women with known urinary tract abnormality: trimethoprim 300 mg (o) daily for 3 days (first choice) or cephalexin 500 mg (o) 12 hourly for 5 days or amoxicillin + clavulanate 500/125 mg (o) 12 hourly for 5 days or nitrofurantoin 100 mg (o) 6 hourly for 5 days or norfloxacin 400 mg (o) 12 hourly for 3 days (if resistance to above agents proven and if susceptible, Caution about tendinopathy and tendon rupture.) No follow-up is required if women remain asymptomatic after treatment

Treatment (non-pregnant women)3,7

Avoid using important quinolones—norfloxacin or ciprofloxacin—as first-line agents. Cotrimoxazole is not first line because it has no advantage over trimethoprim and has more side effects. Treatment failures are usually due to a resistant organism or an underlying

Treatment (non-pregnant women)3,7

Treatment of acute cystitis (empirical): cephalexin 500 mg (o) 12 hourly for 5 days or nitrofurantoin 100 mg (o) 6 hourly for 5 days or amoxicillin + clavulanate 500/125 mg (o) 12 hourly for 5 days Repeat MCU 1--2 weeks after completion.

Pregnant women8,9 | UTI in pregnant women requires careful surveillance

Consider the cause (see risk factors above). Investigations: MCU, U&E, ultrasound. Treatment (empirical, while awaiting investigation): trimethoprim 300 mg (o) daily for 7 days or cephalexin 500 mg (o) 12 hourly for 7 days or amoxicillin + clavulanate 500/125 mg (o) 12 hourly for 7 days or nitrofurantoin 100 mg (o) 6 hourly for 7 days or norfloxacin 400mg (o) 12 hourly for 7 days Note: All males with a UTI should be investigated to exclude an underlying abnormality, e.g

Adult males7

_______________ is a treatable condition that most commonly happens in uncircumcised males.

Balanitis

____________ specificity is high in SLE

Anti-dsDNA

combination of 3rd gen cephalosporins+azithro is needed to cover resident ________________even in the absence of Chlamydia

gonorrhoea

Thiamine infusion should be given before _______________

dextrose infusion

patient under 55 highly risk for CPTA scan

V/Q

Suspected Ca. Prostate. Initial: DRE/PSA - TRUS guided biopsy. ___________indicated in fracture spine d/t mets.

MRI

___________works similar to terlipressin as vasoactive agent. Next is to scope to r/o variceal bleed

Octreotide

salt restriction - frst lifestyle modification for all ___________pts

ascites

first we do urinalysis and then creatinine and urine cytology is considered in _____________

hematuria

DRE -> UA -> sCr -> _________

US KUB

__________ to see soft tissues damage like ligaments or tendon

MRI

Patients with a level 2.5 – 4 mEq/L should have hemodialysis if they have severe symptoms such as neurologic deterioration, hemodynamic instability, acute kidney injury or ventricular arrhythmia.

lithium

Febeile convulsion -___________

no need anything

Patients presenting with acute neurological ischaemia or amaurosis initial aspirin and the best ________

surgery

bcoz risk of transmission to baby less even if symptomatic.do serology once pt is ___________

symptomatic

Urine microscopy and culture is mandatory. Mild cases can be treated with oral therapy alone for a longer duration than the recommended course for uncomplicated cystitis

Acute pyelonephritis

For empirical therapy, use amoxicillin/clavulanate (875/125 mg (o) 12 hourly) for 10–14 days or ciprofloxacin (500 mg (o) 12 hourly) for 7 days.

Acute pyelonephritis

For severe infection with suspected septicaemia, admit to hospital and treat initially with parenteral antibiotics after taking urine for microscopy and culture, and blood for culture. It is a particular problem if acquired in pregnancy.

Acute pyelonephritis

amoxicillin/ampicillin 2g IV 6 hourly plus gentamicin 4–6 mg/kg/day, single daily IV dose Follow with oral therapy for a total of 14 days. Drug levels of gentamicin require monitoring. Gentamicin can be replaced with IV cefotaxime or ceftriaxone.

Acute pyelonephritis

Consider investigation for an underlying urinary tract abnormality, especially in men and in patients that remain unwell after 72 hours of treatment

Acute pyelonephritis

Persistent (chronic) UTIs indicate that the organism is resistant to the antimicrobial agents employed or that there is an underlying abnormality such as a kidney stone or a chronically infected prostate in the male patient

Recurrent or chronic urinary tract infections

Treat an acute episode of recurrent UTI as for cystitis or pyelonephritis

Recurrent or chronic urinary tract infections

__________ in infants and very young children is often kidney in nature and may be associated with generalised symptoms such as fever, vomiting, diarrhoea and failure to thrive.

UTI

Causes of ‘smelly’ urine in children are urinary infection and/or ___________, especially with gastroenteritis

dehydration

In a girl or boy (rare presentation) with symptoms of dysuria and frequency, an underlying abnormality may be present with a reported incidence of __________________ as high as 40% and scarred kidneys (reflux nephropathy) in 27%

vesicoureteric reflux (VUR)

Thus the early detection of children with VUR and control of recurrent kidney infection could prevent the development of scars, hypertension and ____________________

chronic kidney failure

Radiological investigation of children with UTIs shows normal kidneys in approximately 66% and _____________in approximately 33%.

reflux

<1 year—ultrasound; consider ___________________ if US | abnormal

micturating cystourethrogram (MCUG)

Treat empirically in children one month or more while awaiting culture results. If less than one month, treatment with IV antibiotics is advisable.

Treatment (mild infection in children)

Treatment should be taken orally for 3–7 days: trimethoprim 4 mg/kg (max. 150 mg) bd (suspension is 50 mg/5 mL) or cephalexin 12.5 mg/kg (max. 500 mg) bd or trimethoprim/sulfamethoxazole 4/20 mg/kg (max. 160/800 mg) bd

Treatment (mild infection in children)

For empirical treatment in those ≥12 months who appear septic or are vomiting, and infants <12 months, give gentamicin IV + amoxi/ampicillin IV.

Severe infections in children

can affect women of any age, it is more prevalent in girls between 2 and 8 years. It can be confused with a UTI where there is dysuria, which is a common symptom in this type of dermatitis

Vulvovaginitis

Consider bacterial ____________in men with few urinary symptoms (frequency, urgency and dysuria), flu-like illness, fever, low backache and perineal pain

prostatitis

The prostate is exquisitely tender | on rectal examination. For mild to moderate infection, give trimethoprim

prostatitis

3-day course of trimethoprim 300 mg daily is a suitable first choice for acute uncomplicated __________in women.

cystitis

In males the prostate is the most common source of ___________UTI

recurrent

UTI is commonly associated with __________________

microscopic haematuria

The six most common causes of death from cancer in | Australia are cancer of the lung, colorectal, lymphoma, ____________, breast and pancreas

prostate

``` Lump or mass, especially neck or stomach Unusual bleeding, bruising or rash White eye Persistent nausea and vomiting Constant illness Constant tiredness and/or pallor Headache, especially early morning Continuing unexplained weight loss Recurrent or persistent fever Changes which occur suddenly and persist ```

Red flags for childhood cancer

the Philadelphia chromosome for _________________

chronic myeloid leukaemia

(elevated in trophoblastic tumours and germ cell | neoplasms of the testes and ovaries)

human chorionic gonadotrophin (HCG)

Testicular cancer (non-seminomatous) Hepatocellular carcinoma GIT cancers with and without liver metastases

AFP

Ovarian cancer (non-mucinous), breast

CA-125

CA-15-3 ___________

Breast

CA-19-9 ____________

Pancreas, colon, ovary

CEA

Colorectal cancer Pancreatic, breast, lung, small intestine, stomach, ovaries

PSA*

Prostate cancer

hCG

Choriocarcinoma Hydatidiform mole Trophoblastic diseases

DxT malaise + weight loss + cough →

lung cancer

________ cancer is one of the most common cancers in | Australia in terms of both incidence and death, accounting for at least 20% of cancer deaths

lung

___________________ include hypercalcaemia, Cushing syndrome, carcinoid syndrome, dermatomyositis, visual loss progressing to blindness from retinal degeneration, cerebellar degeneration and encephalitis.

The paraneoplastic syndromes

haematuria (60%) loin pain (40%) loin mass (palpable kidney) signs of anaemia left supraclavicular lymphadenopathy (Virchow node) varicocele (left side) hypertension symptoms of metastases (to liver, lungs, brain, bones): respiratory symptoms, neurological symptoms and signs, bone pain, pathological fracture (vertebral collapse) urinalysis—67% positive for blood

Kidney cell cancer

Diagnosis is confirmed by imaging, e.g. CT/MRI. | Refer for radical nephrectomy.

Kidney cell cancer

DxT haematuria + loin pain + palpable kidney mass →

kidney cell cancer

is responsible for 10% of all childhood malignancies.

Wilms tumour (nephroblastoma)

``` Clinical features include:4 peak incidence 2–3 years general symptoms of neoplasia palpable mass 80% abdominal pain 30% haematuria 25% ```

Wilms tumour (nephroblastoma)

Diagnosis is confirmed by urine cytology, ultrasound or CT/MRI scan.

Wilms tumour (nephroblastoma)

Early diagnosis with nephrectomy and chemotherapy leads to a very favourable prognosis (90% 5-year survival).

Wilms tumour (nephroblastoma)

DxT haematuria + abdominal mass + malaise →

Wilms tumour (nephroblastoma)

Probably the most common cancer in infancy (usually <2–3 years). 90% present under 5 years.

Neuroblastoma7

It is a tumour of the adrenal medulla (50%) and sympathetic nervous system, especially retroperitoneal neural tissue in abdomen (30%) but also in chest and neck

Neuroblastoma7

fatigue, anorexia, nausea, fever abdominal pain, abdominal swelling anaemia and weight loss May present with metastases, e.g. bone pain. Diagnosis: CT scan, skeletal survey; biopsy required

Neuroblastoma7

Treatment is based on surgical resection then chemotherapy ± localised radiotherapy. Good response to therapy especially if <18 months.

Neuroblastoma7

has the highest mortality rate of all the gynaecological cancers because the majority of patients present in the late stage of the disease.

Ovarian cancer8

It is responsible for 5% of deaths in | females.

Ovarian cancer8

It is usually asymptomatic prior to the development of metastases

Ovarian cancer8

Epithelial tumours | are the most common of malignant ovarian tumours

Ovarian cancer

They are uncommon under 40 years of age | and the average age of diagnosis is 50 years

Ovarian cancer

The most common presentation is abdominal swelling (mass and/or ascites), abdominal bloating or discomfort.

Ovarian cancer

Non-specific symptoms, which may be present for a long time before diagnosis, include abnormal uterine bleeding, urinary frequency, weight loss, abdominal discomfort, reduced capacity for food, diarrhoea, anorexia, nausea and vomiting

Ovarian cancer

Diagnosis is supported by pelvic ultrasound and serum CA-125 tumour marker

Ovarian cancer

A new test is the | OvPlex serum test, which measures five serum markers.

Ovarian cancer

DxT abdominal discomfort + anorexia + abdominal bloating/distension →

Ovarian cancer

Malignancy in this area is more likely to present with symptoms of anaemia without the patient noting obvious blood in the faeces or alteration of bowel habit

Carcinoma of caecum and ascending colon5

DxT blood in stools + abdominal discomfort + change in bowel habit →

Carcinoma of caecum and ascending colon

This is another cancer with vague symptoms, metastasising early and late presentation

Pancreatic cancer

It is mainly ductal adenocarcinoma, which, if in the head of the pancreas, presents with painless jaundice and if in the body and/or tail presents with epigastric pain radiating to the back, relieved by sitting forward

Pancreatic cancer

DxT jaundice + anorexia + abdominal discomfort/pain →

Pancreatic cancer

are caused by an acquired malignant transformation in the stem cell in the haemopoietic system.

The leukaemias

The usual age range for acute lymphatic leukaemia (ALL) is 2–10 years with a second peak at about ______________.

40 years

Symptoms of anaemia Susceptibility to infection (e.g. sore throat, mouth ulceration, chest infection) Easy bruising and bleeding (e.g. epistaxis, gingival bleeding) Bone pain (notably in children with ALL) and joint pain Symptoms due to infiltration of tissues with blast cells (e.g. gingival hypertrophy in AML)

Acute leukaemia

DxT malaise + pallor + bone pain →

ALL

DxT malaise + pallor + oral problems →

AML

``` Pallor of anaemia Petechiae, bruising Gum hypertrophy/gingivitis/stomatitis Signs of infection Variable enlargement of liver, spleen and lymph nodes Bone tenderness, especially sternum ```

Acute leukaemia

``` FBE and film: normochromic/normocytic anaemia; pancytopenia with circulatory blast cells; platelets: usually reduced Bone marrow examination PCR studies Cytogenetics ```

Acute leukaemia

Treatment: chemotherapy, immunotherapy, stem cell therapy

Acute leukaemia

As a rule, relapse of acute leukaemia means imminent death unless bone marrow transplantation is successful. The mean 5-year survival rate for childhood ALL is about 75–80%; for adult ALL 30%;

Acute leukaemia

A disorder of middle age, typically 40–60 years Insidious onset Constitutional symptoms: malaise, weight loss, fever, night sweats Symptoms of anaemia Splenomegaly (very large); abdominal discomfort Priapism Gout Markedly elevated white cell count (granulocytes) Marked left shift in myeloid series Presence of Philadelphia chr

Chronic myeloid leukaemia (CML)

A disorder of late middle age and elderly Insidious onset Constitutional symptoms: malaise, weight loss, fever, night sweats Lymphadenopathy (large rubbery nodes)—neck, axilla, groin (80%) Moderately enlarged spleen and liver (about 50%) Mild anaemia Lymphocytosis >15 × 109/L ‘Mature’ appearance of lymphocytes

Chronic lymphocytic leukaemia (CLL)

DxT fatigue + weight loss + fever/night sweats + lymphadenopathy →

CLL

which are malignant tumours of lymphoid tissue, are classified as Hodgkin lymphoma and non-Hodgkin lymphoma on the basis of histological appearance of the involved lymph tissue.

The lymphomas6

Painless (rubbery) lymphadenopathy, especially cervical nodes Constitutional symptoms (e.g. malaise, weakness, weight loss) Fever and drenching night sweats—undulant (Pel–Ebstein) fever Pruritus Alcohol-induced pain in any enlarged lymph nodes Possible enlarged spleen and liver

Hodgkin lymphoma

Diagnosis is by lymph node biopsy with histological confirmation. Other tests: FBE, CXR, CT/MRI (to stage), bone marrow biopsy, functional isotopic scanning. Staging is by using Ann Arbor nomenclature (IA to IVB). Treatment includes chemotherapy, immunotherapy and radiotherapy.

Hodgkin lymphoma

DxT malaise + fever/night sweats + pruritus →

Hodgkin lymphoma

are a heterogeneous group of cancers of lymphocytes derived from the malignant clones of B or T cells

Non-Hodgkin lymphomas

Painless lymphadenopathy—localised or widespread Constitutional symptoms possible, especially sweating Pruritus is uncommon Extra nodal sites of disease (e.g. CNS, bone, skin, GIT) Possible enlarged liver and spleen Possible nodular infiltration of skin (e.g. mycosis fungoides) Diagnosis is by lymph node biopsy. CXR and CT abdomen to stage.

non-Hodgkin | lymphoma

DxT malaise + fever/night sweats + lymphadenopathy →

non-Hodgkin | lymphoma

is a clonal malignancy of the differentiated β lymphocyte—the plasma cell.

Multiple myeloma

It | is regarded as a disease of the elderly, the mean age of presentation being 65 years

Multiple myeloma

``` he classic presenting triad in an older person is anaemia, back pain and elevated ESR, which helps to differentiate it from monoclonal gammopathy of uncertain significance (MGUS). ```

Multiple myeloma

Other investigations include serum protein electrophoresis and immunofixation, Sestamibi scan

Multiple myeloma

Bone pain (e.g. backache)—in more than 80% of patients (possible pathological fracture) Bone tenderness, e.g. femur, ribs, spine Weakness, tiredness, increased thirst Anorexia and weight loss Recurrent infections, e.g. chest infection Symptoms of anaemia Bleeding tendency Replacement of bone marrow by malignant plasma cells

Multiple myeloma

Impaired renal failure → kidney failure | Associated with amyloidosis and hypercalcaemia

Multiple myeloma

DxT weakness + unexplained back pain + susceptibility to infection →

Multiple myeloma

Diagnostic criteria comprise the presence of:7 paraprotein in serum (on electrophoresis) Bence–Jones protein in urine bony lytic lesions on skeletal survey

Multiple myeloma

Treatment is with chemotherapy including thalidomide or lenalidomide: 5-year survival rate is 50% or longer if diagnosed earlier

Multiple myeloma

primary macroglobulinaemia due to a type of malignant plasma cell abnormality.

Waldenstrom macroglobulinaemia

This uncommon but difficult-to-diagnose disorder caused by the deposition of amyloid protein is classified as primary, familial or secondary (from chronic infection, e.g. TB, inflammation, RA, some cancers, others). It may be localised or generalised. Clinical features depend on the organ targeted such as the heart (CCF), kidney (nephrotic syndrome), GIT (malabsorption), brain (dementia) and peripheral nerves (e.g. CTS). Diagnosis

Amyloidosis

Hormone secretion by carcinoid cells causes the characteristic carcinoid syndrome long before local growth or metastatic spread of the tumour is apparent (80% metastasise). Most carcinoid tumours are asymptomatic.

Carcinoid tumours and syndrome

Classic triad: skin flushing (especially face), diarrhoea (with abdominal cramps), valvular heart disease Other possible features: wheezing, telangiectasia, hypotension, cyanosis Sites of tumours: appendix/ileum, stomach, bronchi

Carcinoid tumours and syndrome

24-hour urine 5-hydroxyindoleacetic acid | Plasma chromogranin A/hepatic ultrasound

Carcinoid tumours and syndrome

Surgery or other ablation: octreotide/others

Carcinoid tumours and syndrome

This is a malignant proliferation of RBCs and also WBCs and platelets

Polycythaemia vera

``` Older person Fatigue Headache, dizziness, tinnitus Pruritus after hot bath, shower Epistaxis Facial plethora Splenomegaly Thrombosis ```

Polycythaemia vera

FBE and haematocrit Bone marrow biopsy Genetic mutations—JAK2 mutation

Polycythaemia vera

``` Testicular 98 Prostate 95 Thyroid 92 Melanoma 91 Breast (female) 91 Hodgkin lymphoma 87 Uterus 84 Bladder 77 Non-Hodgkin lymphoma 72 Colon 72 Ovary 41 Stomach 33 Liver 20 Lung 19 Pancreas ```

``` Common cancers and their 5-year survival rates (a collation of surveys) ```

Common sites of metastatic presentation are the lymph nodes, liver, lung, mediastinum and bone. Other sites include the brain, bone marrow, peritoneum, retroperitoneum, skin and the spinal cord.

Metastatic tumours

Bone. Breast, prostate, lung, Hodgkin lymphoma, kidney, thyroid, melanoma

important sites (listed below) are followed by likely primary sources

Brain. Breast, lung, colorectal, lymphoma, kidney, melanoma, prostate

These important sites (listed below) are followed by likely primary sources, with the most likely listed first.

Liver. Colon, pancreas, liver, stomach, breast, lung, melanoma

These important sites (listed below) are followed by likely primary sources, with the most likely listed first.

Lung and mediastinum. Breast, lung, colorectal, kidney, testes, cervix/uterus, Hodgkin lymphoma, melanoma

These important sites (listed below) are followed by likely primary sources, with the most likely listed first.

DxT anorexia + weight loss + jaundice (± epigastric pain) →

pancreatic | cancer

DxT fatigue + dysphagia + weight loss →

oesophageal cancer

DxT anorexia + dyspepsia + weight loss →

stomach cancer

DxT headache + a/n/v + ataxia →

medulloblastoma (children)

DxT fever + malaise (extreme) + a/n/v (± anaemia) →

neuroblastoma

DxT mental dysfunction + vomiting + (waking) headache →

cerebral | tumour (late)

DxT indrawn eye + small pupil + ptosis (± anhydrosis) →

Horner | syndrome (?lung cancer)

are well known for their adverse intra-uterine effects on the fetus.

The TORCH organisms (TORCH being an acronym for toxoplasmosis, rubella, CMV and herpes)

The mosquito-borne infections causing encephalitis and haemorrhagic fevers are mainly viral, apart from the protozoan causing malaria, and are of particular significance in ______________________

travellers | returning from endemic areas

blood: malaria, trypanosomiasis GIT: giardiasis, amoebiasis, cryptosporidium tissues: toxoplasmosis, leishmaniasis, babesiosis

The major protozoal diseases of humans are:

Most of the world’s serious _______________infections—malaria, African trypanosomiasis, leishmaniasis, amoebiasis—occur in tropical areas

protozoal

is a febrile illness caused by the human herpes virus 4 (Epstein–Barr) virus, one of the eight known herpes viruses.

Epstein–Barr mononucleosis

It is often called ‘the great imitator’ because of its multisystem involvement.

Epstein–Barr mononucleosis

It can mimic diseases such as HIV primary infection, streptococcal tonsillitis, viral hepatitis and acute lymphatic leukaemia.

Epstein–Barr mononucleosis

There are three forms: the febrile, the anginose (with | sore throat, see FIG. 18.1 ) and the glandular (with lymphadenopathy).

Epstein–Barr mononucleosis

It may occur at any age but usually between 10 and 35 years; it is commonest in the 15–25 years age group.

Epstein–Barr mononucleosis

it usually affects people in their late teenage years or early 20s. It is endemic in most countries, affecting over 95% of the adult population worldwide. Subclinical infection is common in young children. The incubation period is at least 1 month but data are insufficient to define it accurately

Epstein–Barr mononucleosis

is excreted in oropharyngeal secretions during the illness and for some months (sometimes years) after the clinical infection.

EBV

``` Slow-onset malaise 1–6 weeks Fever Myalgia Headaches, anorexia Blocked nose—mouth breathing Nasal quality to voice Sore throat (85%) Anorexia, nausea ± vomiting Rash—primary 5% Dyspepsia ```

Epstein–Barr mononucleosis

DxT malaise + sore throat + fever + lymphadenopathy →

EBM

WCC shows absolute lymphocytosis. Blood film shows atypical lymphocytes. Paul–Bunnell or Monospot test for heterophile antibody is positive (although positivity can be delayed or absent in 10% of cases; 85% positive in adults and older children). Diagnosis confirmed (if necessary) by EBV-specific antibodies, viral capsid antigen (VCA) antibodies—IgM, IgG and EB nuclear antigen (EBN-A). Consider throat culture to rule out streptococcal pharyngitis. Culture for EBV and tests for specific viral antibodies are not performed routinely

Epstein–Barr mononucleosis

Supportive measures (no specific treatment) Rest (the best treatment) during the acute stage, preferably at home and indoors NSAIDs or paracetamol to relieve discomfort Gargle soluble aspirin or 30% glucose or saline to soothe the throat Advise against alcohol, fatty foods, continued activity, especially contact sports, for 8 weeks (risk of splenic rupture) Ensure adequate hydration Corticosteroids reserved for: neurological involvement, thrombocytopenia, threatened airway obstruction (not recommended for uncomplicated cases)

Epstein–Barr mononucleosis

Intra-uterine infection may cause serious abnormalities in the fetus, including CNS involvement (microcephaly, hearing defects, motor disturbances), jaundice, hepatosplenomegaly, haemolytic anaemia and thrombocytopenia.

Cytomegalovirus infection

In healthy adults, ___________produces an illness similar to EBM with fever, malaise, arthralgia and myalgia, generalised lymphadenopathy and hepatomegaly

CMV

In the patient with normal immunity no treatment apart from supportive measures is required, as the infection is usually self-limiting.

Cytomegalovirus infection

which is caused by Toxoplasma gondii, an obligate intracellular protozoan, is a worldwide, albeit rare, infection

Toxoplasmosis

The definitive host in its life cycle is the cat (or pig or sheep) and the human is an intermediate host.

Toxoplasmosis

caused by Mycobacterium tuberculosis, still has a worldwide distribution with a very high prevalence in Asian countries where 60–80% of children below the age of 14 years are affected

Tuberculosis

This has special implication in Australia, where large numbers of Asian migrants are settling.

Tuberculosis

``` Cough Sputum: initially mucoid, later purulent Haemoptysis Dyspnoea (esp. with complications Pleuritic pain ```

Tuberculosis

``` Anorexia Fatigue Weight loss Fever (low grade) Night sweats ```

Tuberculosis

May be no respiratory signs or may be signs of fibrosis, consolidation or cavitation (amphoric breathing) Finger clubbing

Tuberculosis

``` High-risk people/situations Newborn and infants Adults over 60 years Patients with HIV/AIDS Chronic disease, e.g. diabetes Crowded or unsanitary living conditions People affected by alcohol and drugs Immigrants and refugees from endemic countries (especially Indian subcontinent, Papua New Guinea, South-East Asia, Sub Sahara and South Africa) ```

pulmonary TB

DxT malaise + cough + weight loss ± fever/night sweats + haemoptysis →

pulmonary TB

The primary infection usually involves the lungs. Transmission is by droplet infection. The focus is usually subpleural in the upper to mid zones and is almost always accompanied by lymph node involvement.

pulmonary TB

Erythema nodosum may accompany the primary infection

pulmonary TB

is the presence of infection without evidence of active disease (contained by the immune system) and inability to transmit the infection.

Latent TB infection (LTBI)

Most cases of ________in adults are due to reactivation of disease some years later

The main sites of extrapulmonary disease (in order of frequency in Australia) are the lymph nodes (the commonest, especially in young adults and children), genitourinary tract (kidney, epididymis, Fallopian tubes), pleura and pericardium, the skeletal system (arthritis and osteomyelitis with cold abscess formation), CNS (meningitis and tuberculomas), the eye (choroiditis, iridocyclitis), the skin (lupus vulgaris), the adrenal glands (Addison disease—see CHAPTER 14 ) and the GIT (ileocaecal area and peritoneum).

Extrapulmonary TB

This disorder follows diffuse dissemination of tubercle bacilli via the bloodstream, especially in those with chronic disease and immunosuppression

Miliary tuberculosis

Children living in close contact with people with smear-positive pulmonary TB are highly vulnerable to acquiring the primary infection. A possible complication is miliary TB

TB in children2

Primary disease is the more common form in young children. Reactivation is more common in adolescents.

chest X-ray; CT scan if doubtful sputum or bronchial excretion or gastric aspirates for stain (acid-fast bacilli) and culture (takes about 6–8 weeks but important); ideally requires 3 specimens over 3 days including one early morning immunochromatographic finger-prick test (new and promising) interferon gamma release assay (IGRA) QuantiFERON–TB Gold blood test NAAT/PCR test—less sensitive than culture biopsies on lesions/lymph nodes may be necessary; the hallmark is caseating granulomata fibre-optic bronchoscopy to obtain sputum may be necessary consider HIV studies

diagnosis of TB.

<5 mm—negative (note: may be negative in presence of very active pulmonary infection) 5–10 mm—typical of past BCG vaccination >5 mm—significant in immunocompromised, close contacts and HIV infection >10 mm—positive = tuberculosis infection (active or inactive) >15 mm—highly significant for ‘normal’ people

Tuberculin (Mantoux) testing and BCG vaccination

Aboriginal and Torres Strait Islander neonates in regions of high incidence neonates born to patients with leprosy or family history of leprosy children <5 years travelling for long periods to countries of high TB prevalence

BCG vaccination is recommended for:

The current antimicrobial treatment is the standard short-course therapy with four antituberculous drugs initially (rifampicin + isoniazid + pyrazinamide + ethambutol) daily for 2 months, then rifampicin + isoniazid daily for a further 4 months.

pulmonary TB

Pyridoxine 25 mg daily is recommended for adults taking isoniazid. A 3-times-weekly regimen is also an option if DOT is employed. Corticosteroids may be prescribed.

pulmonary TB

extremely common in certain Indigenous groups and is frequently acquired from sexual contacts overseas

Syphilis

It presents either as a primary lesion or through the chance finding of positive syphilis serology (reagin tests, treponemal antibody tests, PCR).

Syphilis

The primary lesion or chancre usually develops at the point of inoculation after an incubation period averaging 21 days.

Primary syphilis

The adjacent lymph nodes are discretely enlarged, firm and non-suppurating. Any anorectal ulcer or sore should be considered as syphilis until proved otherwise.

Primary syphilis

The interval between the appearance of the primary chancre and the onset of secondary manifestations varies from 6 to 12 weeks after infection

Primary syphilis

The most common feature of the secondary stage of infection is a rash, which is present in about 80% of cases. The rash is typically a symmetrical, generalised, coppery-red maculopapular eruption on the face, trunk, palms and soles and is neither itchy nor tender

Primary syphilis

Positive serology in a patient without symptoms or signs of disease is referred to as latent syphilis and is the commonest presentation of syphilis in Australia today.

Latent syphilis

Spirochaetes can be demonstrated by microscopic examination of smears from early lesions using dark field techniques and provide an immediate diagnosis in symptomatic syphilis. The direct fluorescent antibody techniques (FTAABS) can be used on this smear.

Dark field examination8

Serological tests provide indirect evidence of infection, and the diagnosis of asymptomatic syphilis relies heavily on these tests. The main types of tests are

``` reagin tests (VDRL and RPR)—not specific for syphilis but useful for screening treponemal tests (TPPA, TPI, EIA, FTAABS)—specific tests, with the latter being sensitive and widely used PCR (blood or CSF)—very sensitive ```

It is based on parenteral benzylpenicillin or procaine penicillin

syphilis

fever, | especially in patients with a history of cardiac valvular disorders.

Infective endocarditis

It is caused by microbial | infection of the cardiac valves or endocardium.

Infective endocarditis

more invasive | procedures, IV drug use and increased cardiac catheterisation

Infective endocarditis

DxT FUO + cardiac murmur + embolism →

Infective endocarditis

``` Past history of endocarditis Rheumatically abnormal valves, especially Aboriginal and Torres Strait Islander people Congenitally abnormal valves Mitral valve prolapse Calcified aortic valve Congenital cardiac defects (e.g. VSD, PDA) Prosthetic valves, shunts, conduits IV drug use Central venous catheters ```

Infective endocarditis

Streptococcus viridans (50% of cases) most susceptible to penicillin Streptococcus bovis Enterococcus faecalis

Infective endocarditis

The ‘classic tetrad’ of clinical features:9 signs of infection, signs of heart disease, signs of embolism, immunological phenomena

Infective endocarditis

Culture the blood of every patient who has a fever and a heart murmur.

Infective endocarditis

FBE and ESR: ESR ↑, anaemia and leukocytosis urine: proteinuria and microscopic haematuria blood culture: positive in about 75%8 (at least 3 sets of samples—aerobic and anaerobic culture) echocardiography—to visualise vegetations (TOE more sensitive than TTE) chest X-ray ECG

Infective endocarditis

Bactericidal antibiotics are chosen on the basis of the results of the blood culture and antibiotic sensitivities.

Infective endocarditis

treatment must be given IV for at least 2 weeks | treatment is prolonged—usually 4–6 weeks

Infective endocarditis

Benzylpenicillin + gentamicin + di(flu)cloxacillin are recommended Vancomycin needs to be considered if hospital acquired, MRSA suspected or prosthetic cardiac valve

Infective endocarditis

Consider Q fever, leptospirosis, orf, anthrax

Meat workers

______________(undulant fever, Malta fever) has diminished in prevalence since the campaign to eradicate it from cattle.

Brucellosis

DxT malaise + headache + undulant fever →

brucellosis

Brucella agglutination test (rising titre)—acute and convalescent (3–4 weeks) samples Brucella PCR testing—sensitive and rapid

brucellosis

Adults: doxycycline 100 mg (o) bd for 6 weeks + rifampicin 600 mg (o) daily for 6 weeks or gentamicin 4–6 mg/kg/day IV statim then daily for 2 weeks (monitor) Children: cotrimoxazole + rifampicin

brucellosis

_______________ is a zoonosis due to Coxiella burnetii. It is the most common abattoir-associated infection in Australia and can also occur in farmers and hunters

Q fever

It usually resolves spontaneously within 2 weeks. Rash is not a major feature but can occur if the infection persists without treatment. It is transmitted by inhaled dust, animals (wild or domestic) and unpasteurised milk.

Q fever

``` Incubation period 1–3 weeks Sudden onset fever, rigors and myalgia Dry cough (may be pneumonia in 20%)14 Petechial rash (if persisting infection) ± Abdominal pain ```

Q fever

DxT fever + headache + prostration →

Q fever

Coxiella burnetii PCR is effective

Q fever

The disease can be prevented in abattoir workers by using Q fever vaccine

Q fever

follows contamination of abraded or cut skin or mucous membranes with Page 194 Leptospira-infected urine of many animals including pigs, cattle, horses, rats and dogs.

Leptospirosis

There is a risk to dairy farmers splashed with urine during milking, especially if through open cuts or sores. Early diagnosis is important to prevent it passing into the immune phase.

Leptospirosis

DxT abrupt fever + headache + conjunctivitis →

leptospirosis

Clinical pattern especially rash of erythema migrans + serology and PCR

Lyme and lyme-like disease

spirochaete, Borrelia burgdorferi, and transmitted by Ixodes ticks, so that people living and working in the bush are susceptible

Lyme and lyme-like disease

Remove tick | A typical regimen for adults is doxycycline 100 mg bd for 21 days or amoxicillin

Lyme and lyme-like disease

Most patients are bird fanciers. Psittacosis accounts for 1–5% of hospital admissions for pneumonia.

Psittacosis (‘bird fancier’s disease’)

It is indistinguishable from other atypical | pneumonias except for history of contact with birds.

Psittacosis (‘bird fancier’s disease’)

Serology—rising antibody and PCR | Chest X-ray

Psittacosis (‘bird fancier’s disease’)

is caused by Listeria monocytogenes, a bacterium widespread in nature that can contaminate food and has been found in many fresh (e.g. fruit and vegetables) and processed foods (e.g. dairy products, especially unpasteurised milk, soft cheese, processed meats and smoked seafood).

Listeriosis

``` influenza-like illness (usually mild) food poisoning, gastroenteritis (atypical) meningitis, especially infants, elderly septicaemia (in susceptible) pneumonia (in susceptible) ```

Listeriosis

Infections from bites and scratches

cat-scratch disorder, rat bite fever

This sometimes misdiagnosed bacterial infection (Clostridium tetani) can appear from one day to several months after the injury, which may have been forgotten

Tetanus

Prodrome: fever, malaise, headache Trismus (patient cannot open mouth) Risus sardonicus (a grin-like effect from hypertonic facial muscles) Opisthotonos (arched trunk with hyperextended neck) Spasms, precipitated by minimal stimuli

Tetanus

Give tetanus antitoxin and human tetanus immunoglobin

Tetanus

(necrotising soft tissue infection) can involve skin and subcutaneous fat, fascia and muscle.

Gangrene/gas gangrene5

(clostridial myonecrosis) is caused by entry of one of several clostridia organisms, for example, Clostridium perfringens, into devitalised tissue, such as exists following severe trauma to a leg.

Gangrene/gas gangrene

Refer immediately to surgical centre for debridement Start benzylpenicillin 2.4 g IV, 4 hourly + clindamycin Hyperbaric oxygen if available

Gangrene/gas gangrene

``` Sudden onset of pain and swelling in the contaminated wound Brownish serous exudate Gas in the tissue on palpation or X-ray Prostration and systemic toxicity Circulatory failure (‘shock’) ```

Gangrene/gas gangrene

is food poisoning caused by the neurotoxin of Clostridium botulinum

Botulism5

From 12 to 36 hours after ingesting the toxin from canned, smoked or vacuum-packed food (e.g. home-canned vegetables or meat) visual problems such as diplopia suddenly appear. Suspect botulism if cranial nerve weakness with normal sensation.

Botulism

Fever, malaise Headache Minimal respiratory symptoms, non-productive cough Signs of consolidation absent Chest X-ray (diffuse infiltration) incompatible with chest signs

atypical pneumonia

DxT ‘flu’ + headache + dry cough →

atypical pneumonia

Blood tests and PCR tests are available for all the following causative organisms: Mycoplasma pneumoniae (the commonest) Adolescents and young adults: treat with doxycycline (first line) 200 mg statim then 100 mg daily for 14 days or roxithromycin 300 mg (o) daily for 14 days

atypical pneumonia

Related to cooling systems in large buildings Incubation 2–10 days Diagnostic criteria include: prodromal-like illness; a dry cough, influenza-like illness, confusion or diarrhoea; lymphopenia with marked leukocytosis; hyponatraemia; PCR test and urinary antigen assay Treatment for mild disease: azithromycin 500 mg (o) daily for 5 days or doxycycline 100 mg (o) 12 hourly for 10–14 days

Legionella pneumophila (legionnaire disease)

is inflammation of the meninges (pia and arachnoid) and the cerebrospinal fluid (CSF).

Meningitis

``` The classic triad is: headache photophobia neck stiffness Other symptoms include malaise, vomiting, fever and drowsiness ```

Meningitis

Streptococcus pneumoniae, Haemophilus influenzae (especially children), Neisseria meningitides (the big three) Listeria monocytogenes, Mycobacterium tuberculosis, Group B Streptococcus, Strep. agalactiae (common in newborn), Staphylococcus spp., Gram –ve bacilli, such as Escherichia coli, Borrelia burgdorferi, Treponema pallidum

Meningitis

Enteroviruses (Coxsackie, echovirus, poliovirus); mumps; herpes simplex HSV type 1, 2 or 6; varicella zoster virus; EBV; HIV (primary infection)

Meningitis

Cryptococcus neoformans or C. gattii | Histoplasma capsulatum

Meningitis

Lumbar puncture (see TABLE 20.1 ) CT scan Blood culture—all patients with suspected meningitis CSF microculture/PCR (PCR useful even if antibiotics given) Specific serology, e.g. HIV, EBV Note: If significant delay with these investigations, do not withhold treatment

Meningitis

is basically a childhood infection. Neonates and children aged 6–12 months are at greatest risk.

Bacterial meningitis2

Most cases begin as septicaemia, usually via the nasopharynx

Bacterial meningitis

``` Fever, pallor, vomiting ± altered conscious and mental state Lethargy Increasing irritability with drowsiness Refusal to feed, indifference to mother Neck stiffness (not always present) Cold extremities (a reliable sign) May be bulging fontanelle Kernig sign (see FIG. 20.1 ): unreliable Brudzinski sign (see FIG. 20.2 ): more reliable sign of meningeal irritation Opisthotonos ```

Bacterial meningitis

Kernig sign: pain in hamstrings with inability to straighten leg on passive knee extension with hip flexed at 90°

Bacterial meningitis

Brudzinski sign: neck flexion causes involuntary flexion of hip and knee

Bacterial meningitis

Meningeal irritation more obvious (e.g. headache, fever, vomiting, neck stiffness) Later: delirium, altered conscious state

Bacterial meningitis

First: oxygen + IV access and consult Take blood for culture (within 30 minutes of assessment)—ideally prior to hospitalisation For child give bolus of 10–20 mL/kg of N saline with added bolus up to total 60 ml/kg if signs of hypoperfusion Admit to hospital for lumbar puncture (preliminary CT scan to assess safety of LP in adults) Dexamethasone 0.15 mg/kg up to 10 mg IV (start at same time as or 15 minutes before antibiotics—controversial but shown to improve outcome)5 Ceftriaxone 2 g (child >1 month: 50 mg/kg up to 2 g) IV statim then 12 hourly for 4 days or cefotaxime 2 g (child: 50 mg/kg up to 2 g) IV

Bacterial meningitis

Treatment is extremely urgent once suspected (e.g. petechial or purpuric rash on trunk and limbs) (see FIG. 20.4 ). It should be given before reaching hospital. Empirical treatment is: benzylpenicillin 2.4 g (child: 60 mg/kg IV up to 2.4 g) statim (continue for 5 days) if IV access not possible give IM or (especially if hypersensitive to penicillin)

Bacterial meningitis

Meningococcal vaccines—B and ACWY given separately

Bacterial meningitis

This is basically a childhood infection. The most common causes are human herpes virus 6 (the cause of roseola infantum) and enteroviruses (Coxsackie and echovirus).

Viral meningitis

Most cases are benign and self-limiting, but the clinical presentation can mimic bacterial meningitis, although there are fewer obvious signs of meningeal irritation

Viral meningitis1,6

Lumbar puncture is important for diagnosis and also PCR for enterovirus. If positive, it can allow early cessation of antibiotics if commenced empirically.2 Treatment which is symptomatic includes rehydration and analgesics. Aciclovir is given for herpes meningitis. The immunocompromised require special management.

Viral meningitis1,6

Very cold hands? Think .

Viral meningitis

is inflammation of the brain parenchyma. It is mainly caused by viruses, although other organisms including some bacteria, Mycoplasma, Rickettsia and Histoplasma can cause encephalitis. Suspect it when a viral prodrome is followed by irrational behaviour, altered conscious state and possibly cranial nerve lesions.

Encephalitis

These can vary from mild to severe. Constitutional: fever (not inevitable), malaise, myalgia Meningeal features: headache, photophobia, neck stiffness Cerebral dysfunction: altered consciousness—confusion, drowsiness, personality changes, irrational behaviour, seizures, coma Focal neurological deficit

Encephalitis

A protozoal infection seen in immunocompromised patients, especially HIV. Refer for specialist advice.

Toxoplasma gondii

Lumbar puncture: CSF (usually aseptic meningitis) CSF PCR for viral studies, esp. HSV, toxoplasma CT scan—often shows cerebral oedema Gadolinium-enhanced MRI EEG—characteristic waves

Toxoplasma gondii

is a focal area of infection in the cerebrum or cerebellum.

A brain (cerebral) abscess

It presents | as a space-occupying intracerebral lesion

A brain (cerebral) abscess

Suspect in any patient with a raised intracranial | pressure.

A brain (cerebral) abscess

The infection can reach the brain by local spread or via the bloodstream; for example, endocarditis or bronchiectasis.

A brain (cerebral) abscess

There may be no clue to a focus of infection elsewhere but it can follow ear, sinus, dental, periodontal or other infection and also a skull fracture. The organisms are polymicrobial, especially microaerophilic cocci and anaerobic bacteria in the nonimmunosuppressed. In the immunosuppressed, Toxoplasma, Nocardia sp. and fungi.

A brain (cerebral) abscess

``` Raised intracranial pressure Headache Nausea and vomiting Altered conscious state Papilloedema ```

A brain (cerebral) abscess

Focal neurological signs such as hemiplegia, dysphasia, ataxia Seizures (30%) Fever (may be absent) Signs of sepsis elsewhere, e.g. teeth, endocarditis

A brain (cerebral) abscess

MRI (if available) or CT scan FBE, ESR/CRP, blood culture Note: Lumbar puncture is contraindicated. Consider endocarditis

A brain (cerebral) abscess

Management is urgent neurosurgical referral. Aspiration or biopsy is essential to guide antimicrobial treatment, which may (empirically) include metronidazole IV and a cephalosporin, e.g. ceftriaxone IV. Nocardiosis is treated with other antibiotics

A brain (cerebral) abscess

These uncommon focal infections can be extremely difficult to diagnose so an index of suspicion is required to consider such an abscess. The usual organism is Staphylococcus aureus.

Spinal subdural or epidural abscess

Back pain (increasing) ± radiculopathy Percussion tenderness over spine Evolving neurological deficit, e.g. gradual leg weakness and sensory loss ± fever (may be absent)

Spinal subdural or epidural abscess

Associated infection: furuncle, decubitus ulcer, adjacent osteomyelitis, discitis, other

Spinal subdural or epidural abscess

Back trauma with haematoma Post-subdural or epidural anaesthetic block One-third is spontaneous

Spinal subdural or epidural abscess

Blood culture | MRI scan to localise abscess and spinal cord pressure

Spinal subdural or epidural abscess

Urgent neurosurgical referral. Empirical therapy while awaiting culture results may include di/flucloxacillin IV + gentamicin IV or vancomycin IV.

Spinal subdural or epidural abscess

DxT fatigue + psychiatric symptoms + myoclonus →

CJD

Progressive dementia (starts with personality change and memory loss—eventual loss of speech) Myoclonus/muscle spasms Fatigue and somnolence Variable neurological features (e.g. ataxia, chorea)

Creutzfeldt–Jakob disease

MRI: high signal intensity in thalami CSF: positive 14-3-3 protein immunoassay EEG Brain biopsy after death (ultimate confirmation)

Creutzfeldt–Jakob disease

is a highly contagious enterovirus (picornavirus) transmitted through the faeco-oral route and is a specific spinal cord anterior horn cell enterovirus. It remains endemic in the tropics. Most infections (95%) are asymptomatic. Note: Myelitis means inflammation of the spinal cord

Poliomyelitis

Flu-like syndrome, with fever and sore throat, then ‘Pre-paralytic’ stage: nausea and vomiting, headache, stiff neck (meningeal irritation) Paralytic (0.1%): LMN lesion (flaccid paralysis)—may include spinal polio especially of lower limbs and/or bulbar polio ± respiratory failure. No sensory loss. There are 2 levels of polio: minor (recovery in a few days) and major.

Poliomyelitis

Viral studies of throat and faeces—culture and PCR Serology CSF: leucocytosis, esp. lymphocytes

Poliomyelitis

Symptomatic paralytic patients should be referred to hospital. Prevention is through vaccination

Poliomyelitis

can present at any stage of syphilis. The main syphilitic syndromes affecting the CNS are:

Neurosyphilis

Asymptomatic syphilis: present during the interval between the secondary and tertiary stages of syphilis. Meningitis including acute basal meningitis and meningovascular syphilis. The latter can present with a cerebrovascular accident. Tabes dorsalis causing meningoradiculitis with degeneration of the parenchyma of the spinal columns of the spinal cord and involvement of the pupils. Features include lightning pains, Charcot joints, ataxia and neurotrophic ulcers, Argyll Robertson pupils. General paralysis of the insane with marked personality change, dementia, dysarthria and seizures

Neurosyphilis

may include tuberculosis meningitis, tuberculoma (presenting as a cerebral abscess), spinal arachnoiditis and spinal involvement (Pott disease). Treatment with multiple antimicrobial agents is usually complex and prolonged.

Neurological TB

Worm infestations that can (rarely) cause intracerebral lesions through the formation of cysts or granulomas include cysticercosis (tapeworms, e.g. Taenia solium), Echinococcus (hydatid) and Schistosoma.

Helminthic infections

High sensitivity 95%, low specificity for SLE

Antinuclear antibody (ANA)

High sensitivity and specificity for SLE (60%): | found in rheumatoid arthritis

Anti-dsDNA

Highly specific for SLE

Smith (Sm)

Common in Sjögren syndrome and SLE | Common in Sjögren syndrome, SLE (15%)

Ro (SSA) | La (SSB)

Common in 20–30% of patients with | scleroderma

Scl-70 (antitopoisomerase)

Common in 30% of patients with polymyositis

Jo1

High sensitivity and specificity for CREST | syndrome

Anticentromere lc

High sensitivity and specificity for Wegener | granulomatosis

Antineutrophil cytoplasm | ANCA

Diagnostic in antiphospholipid syndrome

Antiphospholipids Anticardiolipin Anti-β2-GP1 antibodies

This syndrome may occur with SLE or in isolation and is responsible for recurrent arterial and/or venous thromboembolism, recurrent spontaneous abortions or thrombocytopenia in the presence of antiphospholipid antibodies but without features of SLE. Livedo reticularis, skin ulcers and neuropsychiatric disturbances have also been noted. If suspected, commence aspirin 150–300 mg (o) daily and refer to a consultant, especially during pregnancy

Antiphospholipid antibody syndrome

which is the commonest of the connective tissue disorders, is described as the ‘great pretender’.3 It is a multisystem autoimmune disorder with a wide variety of clinical features that are due to vasculitis (see FIG. 21.2 ). Arthritis is the commonest feature of SLE (90% of cases). Milder manifestations outnumber more severe forms.

Systemic lupus erythematosus

Prevalence about 1 in 1000 of population Mainly affects women in ‘high oestrogen’ period (90% of cases) Peak onset between 15 and 45 years

Systemic lupus erythematosus

Fever, malaise, tiredness common Multiple drug allergies, e.g. sulfonamides Problems with oral contraceptive pill and pregnancy Course of remission and flares

Systemic lupus erythematosus

DxT polyarthritis + fatigue + skin lesions →

Systemic lupus erythematosus

Malar (butterfly) rash Discoid rash Photosensitivity Arthritis (symmetric non-erosive arthritis in ≥2 peripheral joints) Oral ulcers (usually painless) Serositis (pleurisy or pericarditis) Kidney features (proteinuria or cellular casts) Neurological features (intractable headache, seizures or psychosis) Haematological features (haemolytic anaemia, leucopenia, lymphopenia or thrombocytopenia) Immunological features (positive anti-dsDNA, antiphospholipid antibodies, anticardiolipin or anti-Sm tests and false-positive syphilis serology) Positive antinuclear antibody (ANA) test

SLE

ESR/CRP—elevated in proportion to disease activity | ANA test—positive in 95% (perform first) (key test) but poor specificity

SLE

dsDNA antibodies—90% specific for SLE but present in only 60% (key test) ENA antibodies, especially Sm—highly specific Rheumatoid factor—positive in 50% LE cell test—inefficient and not used

SLE

For suspected SLE, the recommended approach is to perform an ANA test. If positive, then order dsDNA and ENA antibodies

SLE

Mild: NSAIDs (for arthralgia) Moderate (especially skin, joint serosa involved): low-dose antimalarials (e.g. hydroxychloroquine up to 6 mg/kg once daily) (e.g. 400 mg (o) daily for 3 months, then 200 mg daily long term)

SLE,

Rule: treat early and avoid long-term and unnecessary steroid use.

SLE,

Severe: corticosteroids are the mainstay (e.g. prednisolone initially 25–60 mg (o) daily then 7.5–15 mg (o) daily); immunosuppressive steroid-sparing drugs (e.g. azathioprine, methotrexate with folic acid, bDMARDs (e.g. rituximab, belimumab) may be used for severe arthralgia and IV or oral cyclophosphamide for organ damage

SLE

This can present as a polyarthritis affecting the fingers in 25% of patients, especially in the early stages. Soft tissue swelling produces a ‘sausage finger’ pattern. Scleroderma mainly affects the skin with fibrotic thickening. It presents with Raynaud phenomenon in over 85% of patients

Systemic sclerosis (scleroderma)

There are three clinical variants: 1 limited cutaneous disease, e.g. morphea 2 cutaneous with limited organ involvement (CREST) 3 diffuse systemic disease (systemic sclerosis)

Systemic sclerosis (scleroderma)

Female to male ratio = 3:1 A progressive disease of multiple organs Raynaud phenomenon Stiffness and tightness of fingers and other skin areas (see FIG. 21.4 ) ‘Bird-like’ facies (mouth puckered) Dysphagia and diarrhoea (malabsorption) Oesophageal dysmotility Respiratory symptoms: pulmonary fibrosis Cardiac symptoms: vasculopathy, pericarditis, pulmonary arterial hypertension, etc. Look for tight skin on chest (Roman breastplate)

Systemic sclerosis (scleroderma)

DxT finger discomfort + arthralgia + GORD (± skin tightness) →

Systemic sclerosis (scleroderma)

ESR may be raised Normocytic normochromic anaemia may be present ANA test—up to 90% positive (relatively specific) Rheumatoid factor—positive in 30% Anticentromere antibodies—specific (positive in 90% with limited disease and 5% with diffuse) Antitopoisomerase I (anti-Scl-70) antibody is specific but only positive in 20–30% Skin biopsy—increase in dermal collagen

Systemic sclerosis (scleroderma)

Empathic explanation, patient education Analgesics and NSAIDs for pain Avoid vasospasm (no smoking, beta blockers, ergotamine); calcium-channel blockers such as nifedipine may help Raynaud Monitor blood pressure Treat malabsorption if present; skin emollients D-penicillamine can help if there is significant systemic or cutaneous involvement

Systemic sclerosis (scleroderma)

``` Calcinosis Raynaud phenomenon Oesophageal dysmotility Sclerodactyly Telangiectasia Anticentromere antibody (invariably positive) ```

CREST syndrome

is an uncommon systemic disorder with inflammation of skin and muscle whose main feature is symmetrical muscle weakness and wasting involving the proximal muscles of the shoulder and pelvic girdles.

Polymyositis

Any age group Peak incidence 40–60 years Female to male ratio = 2:1 Muscle weakness and wasting proximal limb muscles Main complaint is weakness Muscle pain and tenderness in about 50% Arthralgia or arthritis in about 50% (resembles distribution of rheumatoid arthritis) Dysphagia in about 50% due to oesophageal involvement Raynaud phenomenon Consider associated malignancy: lung and ovary

Polymyositis

DxT weakness + joint and muscle pain + violaceous facial rash →

dermatomyositis

rash shows features of photosensitivity. There is heliotrope (violet) discolouration of the eyelids (see FIG. 21.5 ), forehead and cheeks, and possible erythema resembling sunburn and peri-orbital oedema. A classic sign is a macular rash over the upper chest, back and shoulders. There is a characteristic rash on the hands, especially the fingers and nail folds. The knees and elbows are commonly involved.

dermatomyositis

Muscle enzyme studies (serum creatine kinase and aldolase) | Antibody associations, e.g. anti-Jo1

dermatomyositis

Biopsies—skin and muscle | EMG studies—show characteristic pattern

dermatomyositis

Treatment includes corticosteroids, hydroxychloroquine and cytotoxic drugs. Early referral is appropriate. Malignancy surveillance is important due to an increased risk of common cancers.

dermatomyositis

The underdiagnosed syndrome of dry eyes (keratoconjunctivitis sicca) in the absence of rheumatoid arthritis or any other autoimmune disease is known as primary Sjögren syndrome (SS). There is lymphoid infiltration of the exocrine glands

Sjögren syndrome

primary SS—limited or multisystem secondary SS—occurs in association with other CTDs including rheumatoid arthritis (accounts for 50%) or systemic sclerosis

Sjögren syndrome

Fatigue Sicca (xerostomia, dry eyes, dry vagina) Difficulty swallowing food Increased dental caries; denture dysfunction Salivary gland enlargement; reduced salivation Xerotrachea → chronic dry cough; hoarseness Dyspareunia Arthralgia ± non-erosive arthritis

Sjögren syndrome

DxT dry eyes + dry mouth + arthritis →

Sjögren syndrome

Autoantibody tests—positive ANA(ENA), Ro (SSA), La (ss-B) | Elevated ESR, +ve RA factor, possibly anaemia

Sjögren syndrome

Schirmer tear test (measures conjunctival dryness)

Sjögren syndrome

Referral to rheumatologist Treatment is symptomatic for dry eyes, mouth and vagina; arthralgia NSAIDs, hydroxychloroquine or steroids for arthritis

Sjögren syndrome

It is classified as either primary (without associated disease) or secondary (when associated with any CTD).

Raynaud phenomenon

Patients with primary Raynaud may progress to a CTD but the likelihood is low (5–15%) and the delay to diagnosis is long (average of 10 years).2 The more severe the Raynaud, the more likely it is to progress to systemic disease.

Raynaud phenomenon

``` is a clinical syndrome of episodic arteriolar vasospasm usually involving the fingers and toes (one or two at a time). ```

Raynaud phenomenon

are a heterogeneous group of disorders involving inflammation and necrosis of blood vessels, the clinical effects and classification depending on the size of the vessels involved

The vasculitides or vasculitis syndromes

Small vessel vasculitis is the common type encountered in practice. Medium vessel vasculitis includes polyarteritis nodosa and large vessel vasculitis includes giant cell arteritis

The vasculitides or vasculitis syndromes

Symptoms suggestive of vasculitis include systemic (malaise, fever, weight loss, arthralgia), skin lesions (e.g. purpura, ulcers, infarction), respiratory (wheeze, cough, dyspnoea), ENT (epistaxis, sinusitis, nasal crusting), chest pain (angina), kidney (haematuria, proteinuria, CKF) and neurological (various, e.g. sensorimotor).

The vasculitides or vasculitis syndromes

This is associated with many important disorders, such as rheumatoid arthritis, SLE, bacterial endocarditis, Henoch–Schönlein purpura and hepatitis B. Skin lesions are usually associated with these disorders and the most common presentation is painless, palpable purpura, such as occurs with Henoch–Schönlein purpura.

Small vessel vasculitis

disease is suspected, early diagnosis is life-saving because of sinister kidney damage. Perform a urine examination for haematuria and proteinuria. If positive, order an ANCA test. If positive, refer urgently

If a serious ANCA-associated

Known as ‘pulseless disease’ or ‘aortic arch syndrome’, this vasculitis involves the aortic arch and other major arteries. It typically affects young Japanese female adults. Features include absence of peripheral pulses and hypertension

Takayasu arteritis2

The hallmark of PN is necrotising vasculitis of the small and medium arteries leading to skin nodules, infarctive ulcers and other serious manifestations. The cause is unknown but associations are found with drug abusers (especially adulterated drugs), B-cell lymphomas, other drugs and hepatitis B surface antigen. It should be suspected in any multisystemic disease of obscure aetiology

Polyarteritis nodosa

Young to middle-aged men Constitutional symptoms: fever, malaise, myalgia, weight loss Migratory arthralgia or polyarthritis Subcutaneous nodules along arterial lines Livedo reticularis and skin ulcers Kidney impairment and hypertension Cardiac disorders: arrhythmia, failure, infarction Diagnosis confirmed by biopsy or angiogram ESR raised Treatment is with corticosteroids and immunosuppressants. Refer for specialist care. Meticulous control of blood pressure is essential

Polyarteritis nodosa

DxT arthralgia + weight loss + fever (± skin lesions) →

polyarteritis nodosa

The basic pathology of this very important disease complex is GCA (synonyms: temporal arteritis, cranial arteritis).

Giant cell arteritis

The clinical manifestations of polymyalgia rheumatica invariably precede those of temporal arteritis, of which there is about a 50% association. The diagnosis is based on clinical grounds. No definite cause has been found.

Giant cell arteritis and polymyalgia rheumatica

Pain and stiffness in proximal muscles of shoulder and pelvic girdle, cervical spine (refer FIG. 21.7 ) Symmetrical distribution Typical ages 60–70 years (rare <50) Both sexes: more common in women Early morning stiffness lasting >45 minutes May be systemic symptoms: weight loss, malaise, anorexia, fever

Clinical features (polymyalgia rheumatica)

Painful restriction of movement of shoulders and hips (other joints not usually involved) Signs may be absent later in day ESR typically >40 but may be normal

Clinical features (polymyalgia rheumatica)

DxT malaise + painful shoulder girdle + morning stiffness (>50 years) →

Clinical features (polymyalgia rheumatica)

``` Age >50 New headache—unilateral, throbbing (see CHAPTER 45 ) Visual symptoms, e.g. diplopia Temporal artery tenderness Polymyalgia rheumatica Loss of pulsation of temporal artery Jaw claudication Biopsy of temporal artery (5 cm) is diagnostic ```

Clinical features (temporal arteritis)

DxT fatigue/malaise + headache + jaw claudication →

Clinical features (temporal arteritis)

No specific test for polymyalgia rheumatica ESR—extremely high, >50 mm/hr C-reactive protein—elevated Mild anaemia (normochromic, normocytic)

polymyalgia rheumatica

Refer any patient with suspected _________urgently.

GCA

Prednisolone Starting dose: ____________________: 1 mg/kg (usually 60 mg) (o) daily initially for 4 weeks (+ aspirin 100 mg/day) then gradual reduction according to ESR/CRP

temporal (giant cell) arteritis

Prednisolone ____________________: 15 mg (o) daily for 4 weeks, then reduce daily dose by 2–5 mg every 4 weeks to 10 mg/day, then 1 mg every 4–8 weeks to zero

polymyalgia rheumatica

Taper down gradually to the minimum effective dose (often <5 mg daily) according to the clinical response and the ESR and CRP. Aim for treatment for 2 years. Relapses are common. If complicated (e.g. evolving visual loss) give IV methylprednisolone for 3 days prior to oral agents.

Prednisolone

Azathioprine or methotrexate can be used as steroid-sparing agents.

Giant cell arteritis and polymyalgia rheumatica

In ____________________, a delay in diagnosis after presenting with amaurosis fugax and non-specific symptoms can have tragic consequences, in the form of ischaemic events such as blindness and strokes.

giant cell arteritis

is a systemic (multiorgan) vasculitis of unknown aetiology, affecting veins and arteries of all sizes. The main feature is painful oral ulceration and the hallmark is the ‘pathergy’ reaction whereby simple trauma such as a pinprick can cause a papule or pustule to form within a few hours at the site.

Behçet syndrome2

``` Male to female ratio = 2:1 Recurrent oral and/or genital ulceration Arthritis (usually knees) Skin changes, e.g. erythema nodosum Ocular symptoms—pain, reduced vision, floaters (ocular inflammation) There is no specific diagnostic test. ```

Behçet syndrome2

Associated problems/complications: repeated uveitis and retinitis → blindness, colitis, venous thrombosis, meningoencephalitis. Treatment: high-dose steroids and specific ulcer treatment. DMARDs or bDMARDs may be required.

Behçet syndrome

Patients with Behçet eye disease should be referred promptly for an ophthalmological opinion, which may be sight-saving

Behçet syndrome

this rare vasculitis of unknown cause has a classic triad: upper respiratory tract (URT) granuloma, fleeting pulmonary shadows (nodules) and glomerulonephritis. Without treatment it is invariably fatal and sometimes the initial diagnosis is that made at autopsy. It is difficult to diagnose, especially as the patient (usually young to middle-aged) presents with a febrile illness and respiratory symptoms, but early diagnosis is essential. It usually gets confused with benign nasal conditions.

Granulomatosis2 with polyangiitis

Adolescence to elderly, mean age 40–45 years Constitutional symptoms (as for PN) Lower respiratory tract (LRT) symptoms (e.g. cough, dyspnoea) Oral ulcers Upper respiratory symptoms: rhinorrhoea, epistaxis, sinus pain, nasal septum loss, ear dysfunction Eye involvement—orbital mass Polyarthritis Kidney involvement—usually not clinically apparent (about 75% get glomerulonephritis) Chest X-ray points to diagnosis—multiple nodes, cavitations Antineutrophil antibodies (c-ANCA) are a useful diagnostic marker (not specific) Diagnosis confirmed by biopsy, usually an open l

Granulomatosis2 with polyangiitis

DxT malaise + URTs (e.g. rhinitis, sinusitis) + LRTs (e.g. wheeze, cough) →

Granulomatosis2 with polyangiitis

DxT asthma + rhinitis + vasculitis + hypereosinophilia →

Churg−Strauss | vasculitis

It is invariably binocular, which usually results from extraocular muscular imbalance or weakness.

Diplopia

Test for double vision with each eye occluded. If diplopia persists, it is uniocular. If, however, double vision disappears when either eye is covered, there is a defect of one of the muscles moving the eyeball. Determine whether diplopia occurs in any particular direction of gaze. It is most marked when moved in the direction of action of the weak muscle. Ask the patient to follow your finger, red pin or penlight with both eyes and move it in an H pattern. 3rd nerve—eye turned out: divergent squint 6th nerve—failure to abduct: convergent squint (see FIG. 22.1 )

Diplopia

signs occur when a lesion has interrupted a neural pathway at a level above the anterior horn cell.2 Examples include lesions in motor pathways in the cerebral cortex, internal capsule, brain stem or spinal cord.

UMN

Clinical examples include stroke (thrombosis, embolism or haemorrhage in the brain), tumours of the various pathways, demyelinating disease (e.g. multiple sclerosis)

UMN signs

occur when a lesion interrupts peripheral neural pathways from the anterior horn cell, that is, the spinal reflex arc.

Lower motor neurone lesions

Clinical examples include peripheral neuropathy, Guillain–Barré syndrome, poliomyelitis and a thickened peripheral nerve (e.g. leprosy).

Lower motor neurone lesions

is a progressive neuromuscular disorder resulting in muscular limb and bulbar weakness due to death of motor neurones in the brain, brain stem and spinal cord

Motor neurone disease (MND)

The sensory system is not involved, nor the cranial nerves to the eye muscles.

Motor neurone disease (MND)

Five to 10% of MND is inherited with an | autosomal dominant pattern; the rest is sporadic.

Motor neurone disease (MND)

amyotrophic lateral sclerosis (Lou Gehrig disease)—combined LMN muscle atrophy plus UMN hyper-reflexia, leading to progressive spasticity. This is the most common type.

Motor neurone disease (MND)

progressive muscle atrophy—wasting beginning in the distal muscles; widespread fasciculation

Motor neurone disease (MND)

progressive bulbar (LMN) palsy and pseudobulbar palsy (LMN lesions in the brain stem motor nuclei). Results in wasted fibrillating tongue, weakness of chewing and swallowing, and of facial muscles.

Motor neurone disease (MND)

Weakness or muscle wasting—first noticed in hands (weak grip) or feet Stumbling (spastic gait, foot drop) Difficulty with swallowing Difficulty with speech, for example, slurring, hoarseness Fasciculation (twitching) of skeletal muscles and fibrillating tongue Cramps Emotional instability, depression ± Muscle pain

Motor neurone disease (MND)

is incurable and progresses to death usually within 3–5 years from ventilatory failure/aspiration pneumonia.

Motor neurone disease (MND)

No treatment is proven to influence outcome although riluzole, a sodium channel blocker, appears to slow progression slightly. Baclofen 10 mg bd may help symptoms of cramp. Botulinum toxin may help spasticity and propantheline or amitriptyline for drooling. Multidisciplinary care is essential. Management is supportive.

Motor neurone disease (MND)

The tremor of PD is present at rest. The hand tremor is most marked with the arms supported on the lap and during walking. The characteristic movement is ‘pill-rolling’ where movement of the fingers at the metacarpophalangeal joints is combined with movements of the thumb.

Resting tremor—Parkinsonian

The resting tremor decreases on finger–nose testing. The best way to evoke the tremor is to distract the patient, such as focusing attention on the left hand with a view to ‘examining’ the right hand or by asking the patient to turn the head from side to side.

Resting tremor—Parkinsonian

This fine tremor is noted by examining the patient with the arms outstretched and the fingers apart. The tremor may be rendered more obvious if a sheet of paper is placed over the dorsum of the hands. The tremor is present throughout movement, being accentuated by voluntary contraction.

Action or postural tremor

Essential tremor (also called familial tremor or benign essential tremor) Senile tremor Physiological Anxiety/emotional Hyperthyroidism Alcohol Drugs, for example, drug withdrawal (e.g. heroin, cocaine, alcohol), amphetamines, lithium, sympathomimetics (bronchodilators), sodium valproate, heavy metals (e.g. mercury), caffeine, amiodarone Phaeochromocytoma

Action or postural tremor

This coarse oscillating tremor is absent at rest but exacerbated by action and increases as the target is approached. It is tested by ‘finger–nose–finger’ touching or running the heel down the opposite shin, and past pointing of the nose is a feature. It occurs in cerebellar lobe disease, with lesions of cerebellar connections and with some medications.

Intention tremor (cerebellar disease)

A flapping or ‘wing-beating’ tremor is observed when the arms are extended with hyperextension of the wrists. It involves slow, coarse and jerky movements of flexion and extension at the wrists. Note: Flapping (asterixis) is not strictly a tremor

Flapping (metabolic tremor)

``` Wilson syndrome Hepatic encephalopathy Uraemia Respiratory failure Lesions of the red nucleus of the midbrain (the classic cause of a flap) ```

Flapping (metabolic tremor)

which is probably the most common movement disorder (2–5% prevalence), has been variously called benign, familial, senile or juvenile tremor.

Essential tremor

Autosomal dominant disorder (variable penetrance) Often begins in early adult life, even adolescence Usually begins with a slight tremor in both hands May involve head (titubation), chin and tongue and rarely trunk and legs Interferes with writing (not micrographic), handling cups of tea and spoons, etc. Tremor most marked when arms held out (postural tremor); less evident at rest Tremor exacerbated by anxiety May affect speech if it involves bulbar musculature Relieved by alcohol Can swing arm and gait normal

Essential tremor

Positive family history Tremor with little disability Normal gait

Essential tremor

This is not always easy as a postural tremor can be present in PD, although the hand tremor is most marked at rest with the arms supported on the lap. Parkinsonian tremor is slower at 4–6 Hz while essential tremor is much faster at around 8–13 Hz. Imaging is unnecessary

Distinguishing essential tremor from Parkinson disease

A most useful way to differentiate the two causes is to observe the gait. It is normal in essential tremor but in PD there may be loss of arm swing and the step is usually shortened with stooped posture and shuffling gait.

Distinguishing essential tremor from Parkinson disease

use propranolol (first choice) or primidone 62.5 mg nocte (up to 250 mg).3 A typical starting dose of propranolol is 10–20 mg bd; many require 120–240 mg/day.3 If the tremor is only intrusive at times of increased emotional stress, intermittent use of benzodiazepines (e.g. lorazepam 1 mg) 30 minutes before exposure to the stress may be all that is required. Modest alcohol intake (e.g. a glass of whisky) is very effective. A standard drink of alcohol often alleviates the tremor. Larger doses of alcohol have no additional effect. If drugs fail, deep brain stimulation to the thalamus can be used.

Essential tremor

is a disorder of the automatic processor of the brain which relies on dopamine to maintain movements at a selected size and speed. Loss of dopamine causes movements to become smaller and slower. The pathological features are loss of dopamineproducing neurones from the substantia nigra in the brain stem together with Lewy bodies in the neurones.4 Genetic factors occur in 5% of individuals.

Parkinson disease

One of the most important clinical aspects of PD, which has a slow and insidious onset, is the ability to make an early diagnosis. Sometimes this can be very difficult, especially when the tremor is absent or mild, as occurs with the atherosclerotic degenerative type of Parkinsonism. The lack of any specific abnormality on special investigation leaves the responsibility for a diagnosis based on the history and examination. As a general rule of thumb the diagnosis of PD is restricted to those who respond to levodopa (L-dopa)—the rest are termed Parkinsonism or ‘Parkinson plus’.

Parkinson disease

1. Tremor (at rest) 2. Rigidity 3. Bradykinesia/hypokinesia 4. Postural instability 5. Gait freezing ≥2 signs = Parkinson disease

Parkinson disease

PD is a most common and disabling chronic neurological disorder. About 90% are idiopathic. The prevalence in Australia is 120–150 per 100 000.5 Lifetime risk is 1 in 40.

Parkinson disease

The incidence rises sharply over 70 years of age (peak 65 years).5 The diagnosis is based on the history and examination. Always think of PD in an older person presenting with falls. A reduced sense of smell is one of the first symptoms. Others that may precede PD include constipation, REM sleep disorders and orthostatic hypotension. Non-motor automatic dysfunctions: cognition, behaviour, mood. Hemi-parkinsonism can occur; all the signs are confined to one side and thus must be differentiated from hemiparesis. In fact, most cases of PD start unilaterally. Always consider drug-induced Parkinsonism. The usual drugs are phenothiazines, butyrophenones and reserpine. Tremor is uncommon but rigidity and bradykinesia may be severe. Other causes include vascular (atherosclerosis) and normal pressure hydrocephalus.

Parkinson disease

Power, reflexes and sensation are usually normal. Muscle tone is increased: patients display cogwheel or lead-pipe rigidity when tested at wrist. The earliest abnormal physical signs to appear are loss of dexterity of rapid alternating movements and absence of arm swing, in addition to increased tone with distraction. Positive frontal lobe signs, such as grasp and glabellar taps (only allow three blinks), are more common with Parkinsonism. Note: There is no laboratory test for PD—it is a clinical diagnosis. Hypothyroidism and depression, which also cause slowness of movement, may cause confusion with diagnosis. Note: The Steele–Richardson–Olszewksi syndrome (also known as progressive supranuclear palsy—PSP parkinsonism, mild dementia and vertical gaze dysfunction) is worth considering

Parkinson disease

``` Walking sticks (which spread the centre of gravity) with appropriate education into their use may be necessary to help prevent falls, and constant care is required. Admission to a nursing home for end-stage disease may be appropriate. Correct dopamine deficiency and/or block cholinergic excess in the brain ```

Parkinson disease

Avoid postponing treatment. It should be commenced as soon as symptoms interfere with working capacity or the patient’s enjoyment of life. This will be apparent only if the correct questions are asked as the patient may accept impaired enjoyment without appreciating that it is due to PD. Start low—L-dopa 100/25 (½ tab bd) and go slow. There is usually no difference between the L-dopa preparations. The dosage should be tailored so that the patient neither develops side effects nor is on an inadequate dose of medication without significant therapeutic benefit (see TABLE 22.6 ). The dose usually progresses to 1 tab bd, then consider add-on therapy.

Parkinson disease

The older drugs, such as anticholinergics and amantadine, still have a place in modernmanagement but L-dopa, which basically counters bradykinesia, is the best drug and the baseline of treatment. With the onset of disability (motor disturbances), L-dopa in combination with a decarboxylase inhibitor (carbidopa or benserazide) in a 4:1 ratio should be introduced. L-dopa therapy does not significantly improve tremor but improves rigidity, dyskinesia and gait disorder. It is preferred in those >70 years.10 Consider benzhexol or benztropine if tremor is the feature, especially in young patients. The new non-ergot derivative dopamine agonists (e.g. pramipexole and rotigotine) can be used in treatment, especially with the L-dopa ‘on–off’ phenomenon (fluctuations throughout the day), and also as first-line monotherapy in early PD in certain circumstances and with caution.8 They are preferred to the ergot derivatives because of a superior adverse effect profile. They appear to be most effective when used in combination. The ergot derivatives can have serious adverse effects, including cardiac valve damage, and are no longer recommended. Selegiline is an effective second-line drug, especially in combination with Sinemet. If there is associated pain, depression or insomnia, the tricyclic agents (e.g. amitriptyline) can be effective

Parkinson disease

Mild (minimal disability): L-dopa preparation (low dose), e.g. L-dopa 100 mg + carbidopa 25 mg (½ tab bd—increase gradually as necessary to 1 tab (o) tds) or amantadine 100 mg (o) daily may help the young or the elderly for up to 12 months—if inadequate response selegiline up to 5 mg bd can be added to L-dopa if necessary Moderate (independent but disabled, e.g. writing, movements, gait): L-dopa preparation selegiline 1 mg bd and/or add if necessary—non-ergot

Parkinson disease

Severe (disabled, dependent on others): L-dopa (to maximum tolerated dose) + non-ergot dopamine agent add entacapone 200 mg (o) with each dose of L-dopa, e.g. Stalevo consider antidepressants

Parkinson disease

After 3–5 years of L-dopa treatment, side effects may appear in about one-half of patients:5 involuntary movements—dyskinesia end-of-dose failure (reduced duration of effect to 2–3 hours only)—consider entacapone ‘on–off’ phenomenon (sudden inability to move, with recovery in 30–90 minutes) early morning dystonia, such as clawing of toes (due to disease—not a side effect) Specialist advice is appropriate.

Parkinson disease

apomorphine can be used for severe akinesia not responsive to L-dopa for nausea and vomiting side effects: domperidone 20 mg (o) tds 24 hours prior to apomorphine better control may also be achieved with: amantadine 100 mg (o) bd duodopa—levodopa into jejunum

Parkinson disease

The preferred method is high-frequency deep brain stimulation via electrodes into the subthalamic nucleus, which may benefit all major features of the disease. The indication for surgery such as thalamotomy is erratic and disabling responses to prolonged L-dopa therapy, especially for annoying dyskinesias. It is considered more appropriate for younger patients with a unilateral tremor

Parkinson disease

One of the simplest diagnostic tools for PD, as compared with Parkinsonism, is a trial of therapy with L-dopa. The response is excellent while that for Parkinsonism is poor. L-dopa is the gold standard for therapy. Ensure that a distinction is made between drug-induced involuntary movements and the tremor of PD. Keep the dose of L-dopa as low as possible to avoid these drug-induced involuntary movements.

Practice tips for Parkinson disease

In the elderly with a fractured hip always consider PD (a manifestation of disequilibrium). Remember the balance of psychosis and PD in treatment. Keep in mind the ‘sundown’ effect—patients often go psychotic as the sun goes down. Don’t fail to attend to the needs of the family, who often suffer in silence. If drugs are to be withdrawn they should be withdrawn slowly.

Practice tips for Parkinson disease

is the most common cause of progressive neurological disability in the 20–50 year age group

Multiple sclerosis (MS)

It is generally accepted that MS is an autoimmune disorder. Genetic and environmental factors are believed to play a role

Multiple sclerosis (MS)

Early diagnosis is difficult because MS is characterised by widespread neurologic lesions that cannot be explained by a single anatomical lesion, and the various symptoms and signs are subject to irregular exacerbations and remissions.

Multiple sclerosis (MS)

The lesions are ‘separated in time and space’. The most important issue in diagnosis is the need for a high index of suspicion. The use of MRI has revolutionised the diagnosis of MS.

Multiple sclerosis (MS)

is a primary demyelinating disorder with demyelination occurring in plaques throughout the white and grey matter of the brain, brain stem, spinal cord and optic nerves. The clinical features depend on their location. There is a loss of brain volume

Multiple sclerosis (MS)

There is a variety of types of MS—relapsing remitting (most common), secondary progressive, progressive relapsing and primary progressive—together with ‘benign’ and ‘malignant’ forms.

Multiple sclerosis (MS)

More common in females (3:1) Peak age of onset is in the fourth decade Transient motor and sensory disturbances UMN signs Symptoms develop over several days but can be sudden Monosymptomatic initially in about 80% Only 20% have a benign disease

multiple sclerosis

Multiple symptoms initially in about 20% Common initial symptoms include: visual disturbances of optic neuritis (blurred vision or loss of vision in one eye—sometimes both); central scotoma with pain on eye movement (looks like unilateral papilloedema) diplopia (brain-stem lesion) weakness in one or both legs, paraparesis or monoparesis sensory impairment in the lower limbs and trunk: numbness, paraesthesia; band-like sensations; clumsiness of limb (loss of position sense); feeling as though walking on cotton wool vertigo (brain-stem lesion)

multiple sclerosis

Subsequent remissions and exacerbations that vary from one individual to another 80% have a relapsing remitting disease There is a progressive form, esp. in women around 50 years Anxiety, depression and other mood disorders are common

multiple sclerosis

Bladder disturbances, including retention of urine and urgency ‘Useless hand’ due to loss of position sense Facial palsy Trigeminal neuralgia Psychiatric symptoms In established disease, common symptoms are fatigue, impotence and bladder disturbances

multiple sclerosis

The diagnosis is clinical along with the MRI and depends on the following determinants

multiple sclerosis

Lesions are invariably UMN. >1 part of CNS is involved, although not necessarily at time of presentation. Episodes are separated in time and space. Practically MS can only be diagnosed after a second relapse or when the MRI shows new lesions.11 An early diagnosis requires evidence of contrast-enhancing lesions or new T2 lesions on the MRI indicating dissemination in time. The diagnostic criteria is based on the internationally accepted 2010 McDonald criteria

multiple sclerosis

Lumbar puncture: oligoclonal IgG detected in CSF in 90% of cases14 (only if necessary) Visual evoked potentials: abnormal in about 90% of cases MRI scan: usually abnormal, demonstrating MS lesions in about 90% of cases14

multiple sclerosis

The course is variable and difficult to predict. An early onset (<30 years) is usually ‘benign’ while a late onset (≥50 years) is often ‘malignant’. MS follows a classic history of relapses and remissions in 80–85% of patients.14 The rate of relapse is about once in 2 years. About 20% have a progressive course from the onset with a progressive spastic paraparesis (applies mainly to late-age onset). The average duration of MS is about 40 years from diagnosis to death.14 A ‘benign’ course occurs in about 30% of patients with 10–20% never suffering major disability. The median time to needing a walking aid is 15 years.8 The likelihood of developing MS after a single episode of optic neuritis is about 60%.

multiple sclerosis

All patients should be referred to a neurologist for confirmation of the diagnosis, which must be accurate. Explanation about the disorder and its natural history should be given. Acute relapses require treatment if causing significant disability. Depression and anxiety, which are common, require early treatment, e.g. paroxetine. CBT or mindfulness-based interventions.

multiple sclerosis

Mild relapses Mild symptoms, such as numbness and tingling, require only confirmation, rest and reassurance. Moderate relapses Prednisolone—in outpatient setting Severe relapses or attacks8,15 These attacks include optic neuritis, paraplegia or brain-stem signs. Admit to hospital for IV therapy: methylprednisolone 1 g in 200 mL saline by slow IV infusion (1 hour) daily for 3 days Plasma exchange may be used. Observe carefully for cardiac arrhythmias

multiple sclerosis

Currently first-line immunomodulators are the interferons, glatiramer acetate and the monoclonal antibodies natalizumab and alemtuzumab, or others. Interferon beta-1b (SC injection) and beta-1a (IM injection) appear to be effective (but expensive) for those with frequent and severe attacks. New agents being evaluated include teriflunomide, siponimod, daclizumab, ocrelizumab and Biotin.

multiple sclerosis

``` Physiotherapy Baclofen 10–25 mg (o) nocte For continuous drug therapy: baclofen 5 mg (o) tds, increasing to 25 mg (o) tds + diazepam 2–10 mg (o) tds An alternative is dantrolene Paroxysmal (e.g. neuralgias) Carbamazepine or gabapentin ```

multiple sclerosis

``` The reported efficacy of the cannabis-based medicine Sativex for relaxation, pain and bladder function is still being debated. One RCT showed a positive effect on detrusor activity ```

multiple sclerosis

refers to all conditions causing nerve damage outside the central nervous system.

Peripheral neuropathy

It can be a mononeuropathy, such as carpal tunnel syndrome; mononeuropathy multiplex involving multiple single nerves in an asymmetric pattern (as in vasculitides); or a polyneuropathy, which is a diffuse symmetric disorder best referred to as PN. It can be classified according to clinical progression as acute, subacute or chronic. The manifestations can be sensory, motor, autonomic or mixed (sensorimotor).

Peripheral neuropathy

Sensory symptoms: tingling, burning, numbness in extremities, unsteady gait (loss of position sense) Motor symptoms (LMN): weakness or clumsiness in hands, foot/wrist drop Signs: may be classic ‘glove and stocking’ sensory loss, sensory ataxia, LMN signs—distal muscle wasting, muscle weakness, reflexes absent or depressed, fasciculations

Peripheral neuropathy

Mostly sensory: diabetes mellitus, vitamin deficiency (folate, B1, B6, B12), alcohol, various neurotoxic drugs, leprosy, uraemia (CKF), amyloidosis, malignancy Mostly motor: lead poisoning, porphyria, various neurotoxic drugs, Charcot–Marie–Tooth syndrome (peroneal muscle atrophy), acquired inflammatory polyneuropathies—acute (Guillain–Barré syndrome) and chronic (chronic inflammatory demyelinating polyneuropathy)

Peripheral neuropathy

which is a rapidly progressive and treatable cause of PN or ascending radiculopathy, is potentially fatal. Early diagnosis of this serious disease by the family doctor is crucial as respiratory paralysis may lead to death. The underlying pathology is segmental demyelination of the peripheral nerves and nerve roots

Acute inflammatory polyradiculoneuropathy (Guillain– | Barré syndrome)

Weakness in the limbs (usually symmetrical) Paraesthesia or pain in the limbs (less common) Both proximal and distal muscles affected, usually starts peripherally and moves proximally Facial and bulbar paralysis (rare) Weakness of extraocular muscles (rarely) Reflexes depressed or absent Variable sensory loss but rare Within 3–4 weeks the motor neuropathy, which is the main feature, progresses to a maximum disability, possibly with complete quadriparesis and respiratory paralysis

Acute inflammatory polyradiculoneuropathy (Guillain– | Barré syndrome)

CSF protein is elevated; cells are usually normal. | Motor nerve conduction studies are abnormal

Acute inflammatory polyradiculoneuropathy (Guillain– | Barré syndrome)

Admit to hospital. Respiratory function (vital capacity) should be measured regularly (2–4 hours at first). Tracheostomy and artificial ventilation may be necessary. Physiotherapy to prevent foot and wrist drop and other general care should be provided.

Acute inflammatory polyradiculoneuropathy (Guillain– | Barré syndrome)

Treatment is with plasma exchange or IV immunoglobulin (0.4 g/kg/day for 5 days), which may need to be continued monthly.8 Corticosteroids are not generally recommended.

Acute inflammatory polyradiculoneuropathy (Guillain– | Barré syndrome)

About 80% of patients recover without significant disability. Approximately 5% relapse

Acute inflammatory polyradiculoneuropathy (Guillain– | Barré syndrome)

This is an inherited autosomal dominant polyneuropathy with an insidious onset from puberty. Clinical features include weakness in the legs, variable distal sensory loss and muscle atrophy giving the ‘inverted champagne bottle’ appearance of the legs. The features vary according to the various subgroups. Refer for electrodiagnostic studies and specific genetic testing.

Charcot–Marie–Tooth syndrome

is an acquired autoimmune disorder that usually affects muscle strength. Patients have fluctuating symptoms and variable distribution of muscle weakness. All degrees of severity, ranging from occasional mild ptosis to fulminant quadriplegia and respiratory arrest, can occur20 (see TABLE 22.8 ). It is associated with thymic tumour and other autoimmune diseases, for example, RA, SLE, thyroid and pernicious anaemia.

Myasthenia gravis

Painless fatigue with exercise Weakness also precipitated by emotional stress, pregnancy, infection, surgery Variable distribution of weakness: ocular: ptosis (60%) and diplopia (see FIG. 22.7 ); ocular myasthenia only remains in about 10% bulbar: weakness of chewing, swallowing, speech (ask to count to 100), whistling and head lolling limbs (proximal and distal) generalised respiratory: breathlessness, ventilatory failure Note: The classic MG image is ‘the thinker’—the hand used to hold the mouth closed and the head up.

Myasthenia gravis

Serum anti-acetylcholine receptor antibodies Electrophysiological tests if antibody test negative CT scan to detect thymoma Edrophonium test still useful but potentially dangerous (atropine is the antidote)

Myasthenia gravis

Refer for consultant management. Detect possible presence of thymoma with CT or MR scan of thorax. If present, removal is recommended. Thymectomy is recommended early for generalised myasthenia, especially in all younger patients with hyperplasia of the thymus, even if not confirmed preoperatively. Plasmapheresis is useful for acute crisis or where temporary improvement is required or patients are resistant to treatment. Avoid drugs that are relatively contraindicated. Pharmacological agents: anticholinesterase inhibitor drugs, first-line (e.g. pyridostigmine, neostigmine or distigmine), should be used only for mild-to-moderate symptoms corticosteroids are useful for all

Myasthenia gravis

The combination of ocular and facial weakness should alert the family doctor to the possibility of a neuromuscular disorder, especially MG or mitochondrial myopathy.19 Look for weakness and fatigue. Beware of facioscapulohumeral dystrophy.

Practice tips for myasthenia gravis

Ptosis may develop only after looking upwards for a minute or longer. Smiling may have a characteristic snarling quality.

Practice tips for myasthenia gravis

It is worth remembering that the four major causes of ptosis are: 1. 3rd cranial nerve palsy—ptosis, eye facing ‘down and out’, dilated pupil, sluggish light reflex 2. Horner syndrome—ptosis, miosis (constricted pupil), ipsilateral loss of sweating 3. Mitochondrial myopathy—progressive external ophthalmoplegia or limb weakness, induced by activity—no pupil involvement 4. Myasthenia gravis—ptosis and diplopia, no pupil involvement

Ptosis

are sustained or intermittent abnormal repetitive movements or postures resulting from alterations in muscle tone. The dystonic spasms may affect one (focal) or more (segmental) parts of the body or the whole body (generalised).

Dystonia

Misdiagnosis is common as transient symptoms may be mistaken for an emotional or psychiatric disorder. Many cases take years to diagnose. Dystonias are often regarded as nervous tics. The cause is thought to be disorders of the basal ganglia of the brain, but mainly there is no known specific cause. Neuroleptic and dopamine receptor blocking agents (e.g. L-dopa, metoclopramide) can induce a severe generalised dystonia (e.g. oculogyric crisis) which is treated with benztropine 1–2 mg IM or IV.8 However, L-dopa is the drug of choice in some L-dopa responsive dystonias

Dystonia

Motor and vocal tics are a feature of Tourette disorder. If socially disabling, treat with: haloperidol 0.25 mg (o) nocte, very gradually increasing to 2 g (max.) daily7 or clonidine 25 mcg (o) bd for 2 weeks, then 50–75 mcg bd

Tics

Idiopathic facial (7th nerve) palsy, which is an acute unilateral lower motor neurone paresis or paralysis, is the commonest cranial neuropathy. The classic type is Bell palsy, which is usually idiopathic although attributed to an inflammatory swelling involving the facial nerve in the bony facial canal. In Ramsay–Hunt syndrome, which is due to infection with herpes zoster causing facial nerve palsy, vesicles may be seen on the ipsilateral ear.

Facial nerve (Bell) palsy15

``` Associations: herpes simplex virus (postulated) diabetes mellitus hypertension thyroid disorder, e.g. hyperthyroidism ```

Facial nerve (Bell) palsy

Abrupt onset (can worsen over 2–5 days) Weakness in the face (complete or incomplete) Preceding pain in or behind the ear Impaired blinking Bell phenomenon—when closing the eye it turns up under the half-closed lid Less common: difficulty eating loss of taste—anterior two-thirds of tongue hyperacusis

Facial nerve (Bell) palsy

prednisolone 1 mg/kg (o) up to 75 mg (usually 60 mg) daily in the morning for 5 days (start within 48 hours of onset) Note: This is controversial, but recent randomised trials and a Cochrane review support the use of prednis(ol) one. No good evidence for antiviral drugs, but low-grade evidence for benefit if combining with a corticosteroid. Patient education and reassurance Adhesive patch or tape over eye if corneal exposure (e.g. windy or dusty conditions, during sleep) Artificial tears if eye is dry and at bedtime

Facial nerve (Bell) palsy

Massage and facial exercises during recovery Note: At least 70–80% achieve full spontaneous recovery; higher if mild. Remission should begin within 1 week of onset. Electromyography and nerve excitability or conduction studies are a prognostic guide only. No evidence that nucleoside analogue, for example, aciclovir, is useful but should be used for Ramsay–Hunt syndrome. No evidence that surgical procedures to decompress the nerve are beneficial

Facial nerve (Bell) palsy

dysarthria + intention tremor + nystagmus

→ cerebellar disease | typical of MS

``` visual disturbance (blurred or transient loss) + weakness in limbs ± paraesthesia in limbs ```

→ multiple sclerosis

rigidity + bradykinesia + resting tremor

→ Parkinson disease

tremor (postural or action) + head tremor + absence of | Parkinsonian features

→ essential tremor

fatiguable and weakness of eyelids and eye movements + limbs + bulbar muscles (speech and swallowing)

→ myasthenia gravis

ascending weakness of limbs + of face + areflexia*

→ Guillain–Barré | syndrome (GBS)

(episodic) vertigo + tinnitus + hearing loss

→ Ménière syndrome

dementia + myoclonus + ataxia

→ Creutzfeldt–Jakob | disease

drowsiness + vomiting + headache (waking)

→ ↑ intracerebral | pressure

enophthalmos + meiosis + ptosis ± anhydrosis

→ Horner syndrome

blank spell + lip-smacking (or similar automation) + | olfactory/gustatory hallucination

→ complex partial | seizure

gradual spread (Jacksonian march) of focal jerking (mouth, arm or leg) or sensory disturbance or (rarely) visual field disturbance

→ simple partial | seizure

↑ intracranial pressure +/or focal signs +/or epilepsy

→ cerebral tumour

dysphagia + dysphonia/dysarthria + spastic tongue

→ pseudobulbar | palsy

recurrent: headache (often unilateral) + nausea (± | vomiting) + visual aura*

→ migraine with aura | (formerly ‘classical

recurrent: severe retro-orbital headache + rhinorrhoea | + lacrimation*

→ cluster headache

instantaneous: headache ± vomiting ± neck stiffness

→ subarachnoid haemorrhage until disproven

headache + visual obscurations + papilloedema (often | in obese young female)

→ benign intracranial | hypertension

acute and transient: amaurosis fugax or dysphasia or | hemiplegia*

→ TIA (carotid)

``` typical facies (temporalis atropy and frontal balding) + muscle weakness esp. hands (± myotonia) + cataracts ```

→ dystrophia myotonica (myotonic dystrophy)

vertigo + provoked by movement (especially rolling in | bed) + Hallpike test +ve

→ BPPV

UMN signs + LMN signs + fasciculations

→ motor neurone | disease

leg weakness + ataxic gait + clumsiness (appears | about 12 years)

→ Friedreich ataxia

limb weakness + flaccid paralysis (day after exercise in | a young person)

→ familial periodic | paralysis

which is a disorder of iron overload, is the most common | serious single gene genetic disorder in our population.

Hereditary haemochromatosis (HHC),

It is a common condition in which the total body iron concentration is increased to 20–60 g (normal 4 g). The excess iron is deposited in and can damage several organs: liver—cirrhosis (10% develop cancer) pancreas—‘bronze’ diabetes

Hereditary haemochromatosis (HHC),

skin—bronze or leaden grey colour heart—restrictive cardiomyopathy pituitary—hypogonadism, impotence joints—arthralgia (especially hands), chondrocalcinosis It is usually hereditary (autosomal recessive = AR) or may be secondary to chronic haemolysis and multiple transfusions. Note: Hereditary haemochromatosis is the genetic condition; haemosiderosis is the secondary condition.

Hereditary haemochromatosis (HHC),

Being an autosomal recessive disorder, the patient must inherit two altered (mutated) copies of the gene. It is a problem mainly affecting Caucasians, usually from middle age onwards. About 1 in 10 people are silent carriers of one mutated gene, while 1 in 200 are homozygous and are at risk of developing haemochromatosis. These people can have it to a variable extent (the penetrance factor), and some are asymptomatic while others have a serious problem. It is rare for symptoms to manifest before the third decade.

Hereditary haemochromatosis (HHC),

homozygous C282Y—high risk for HHC homozygous H63D—unlikely to develop clinical HHC heterozygous C282Y and H63D—milder form of HHC The key diagnostic sensitive markers are serum transferrin saturation and the serum ferritin level. The serum iron level is not a good indicator. An elevated ferritin level is not diagnostic of HHC but is the best serum marker of iron overload.

Hereditary haemochromatosis (HHC),

Most patients are asymptomatic but may have extreme lethargy, abdominal discomfort, signs of chronic liver disease, polyuria and polydipsia, arthralgia, erectile dysfunction, loss of libido and joint signs. Signs: look for hepatomegaly, very tanned skin, cardiac arrhythmias, joint swelling, testicular atrophy.

Hereditary haemochromatosis (HHC),

Increased serum transferrin saturation: >50% (F); >60% (M)

Hereditary haemochromatosis (HHC),

Increased serum ferritin level: >200 mcg/L (F); >300 mcg/L (M) (see CHAPTER 13 ) CT, MRI or FerriScan—increased iron deposition in liver Liver biopsy (if liver function test enzymes are abnormal or ferritin >1000 mcg/L or hepatomegaly)—FerriScan now preferred Genetic studies: HFE gene—a C282Y and/or H63D mutation Screen first-degree relatives (serum ferritin levels and serum transferrin saturation in older relatives and genetic testing in younger ones). No need to screen before adulthood. HbEPG gene for pregnant patient and partner. Routine screening not recommended Note: Full blood count (FBE) and erythrocyte sedimentation rate are normal.

Hereditary haemochromatosis (HHC),

Refer for specialist care Weekly venesection 500 mL (250 mg iron) until serum iron stores are normal (may take at least 2 years), then every 3–4 months to keep serum ferritin level <100 mcg/L (usually 40–80 mcg/L), serum transferrin saturation <50% and iron levels normal Desferrioxamine can be used but not as effective as venesection Normal, healthy low-iron diet Avoid or limit alcohol Avoid iron tablets and vitamin C Life expectancy is normal if treated before cirrhosis or diabetes develops

Hereditary haemochromatosis (HHC),

is the result of a defect in an ion channel protein, the cystic fibrosis transmembrane receptor, which is found in the membranes of cells lining the exocrine ducts. The defect affects the normal transport of chloride ions, leading to a decreased sodium and water transfer, thus causing viscid secretions that affect the lungs, pancreas and gut.

Cystic fibrosis

The most common AR paediatric illness | About 1 in 2500 Caucasians affected

Cystic fibrosis

``` About 1 in 20–25 are carriers A mutation (δ-F508) of chromosome 7 is the most common of some 500 possible mutations of the gene. This deletes a single phenylalanine residue from a 1480-amino acid chain. ```

Cystic fibrosis

General: malaise, failure to thrive, exercise intolerance Chronic respiratory problems: cough, recurrent pneumonia, bronchiectasis, sinus tenderness, nasal polyps Gastrointestinal: malabsorption, pale loose bulky stools, jaundice (pancreatic effect), meconium ileus (10% of newborn babies) Infertility in males (atrophy of vas deferens) Pancreatic insufficiency Early mortality but improving survival rates (mean age now 31 years)

Cystic fibrosis

DxT failure to thrive + chronic cough + loose bowel actions →

Cystic fibrosis

Screening for immunoreactive trypsin/trypsinogen in newborns detects 75% Sweat test for elevated chloride and sodium levels DNA testing for carriers identifies only the most common mutations (70–75%)

cystic fibrosis

Early diagnosis and multidisciplinary team care are important Physiotherapy for drainage of airway secretions Hypertonic saline solution (by nebuliser) preceded by a bronchodilator Treatment of infections: therapeutic and prophylactic antibiotics Oral pancreatic enzyme replacement Dietary manipulation Lung and liver transplantation are considerations

cystic fibrosis

NF1—peripheral neurofibromatosis (von Recklinghausen disorder) NF2—central type, bilateral acoustic neuromas (schwannomas) (rare) The gene for NF1 is carried on chromosome 17 and NF2 on chromosome 22. Diagnostic genetic testing is not routinely available. Diagnosis is by clinical examination.

Neurofibromatosis

DxT light-brown skin patches + skin tumours + axillary freckles →

NF1

Six or more café-au-lait spots (increasing with age) Freckling in the axillary or inguinal regions Flesh-coloured cutaneous tumours (appear at puberty) Hypertension Eye features (iris hamartomas) Learning difficulty Musculoskeletal problems (e.g. scoliosis, fibrous dysplasia, pseudoarthrosis) Optic nerve gliomas

NF1

One-third asymptomatic, only have skin stigmata One-third minor problems, mainly cosmetic One-third significant problems (e.g. neurological tumours)

NF1

No special treatment available Surgical excisions of neurofibromas as appropriate Refer to a special clinic, including neurofibroma clinic Careful surveillance—report new symptoms Yearly examination for children and adults, including blood pressure, neurological, skeletal and ophthalmological examination

NF1

is a progressive proximal muscle weakness disorder with replacement of muscle by connective tissue. Becker muscular dystrophy is a less severe variant. Early diagnosis is important. First signs are delayed motor development, speech and language.

Duchenne muscular dystrophy (DMD)

DMD is an X-linked recessive condition. It is caused by a mutation in the gene coding for dystrophin, a protein found inside the muscle cell membrane.

Duchenne muscular dystrophy (DMD)

Usually diagnosed from 2–5 years Weakness in hip and shoulder girdles Walking problems: delayed onset or starting in boys aged 3–7 Waddling gait, falls, difficulty standing and climbing steps Pseudohypertrophy of muscles, especially calves Most in wheelchair by age 10–12 ± Intellectual retardation/learning difficulties Most die of respiratory problems by age 25 Gower sign: patient uses ‘trick’ method by using hands to climb up his or her legs when rising to an erect position from the floor

Duchenne muscular dystrophy (DMD)

DxT male child + gait disorder + bulky calves →

Duchenne muscular dystrophy (DMD)

Elevated serum creatinine kinase level Electromyography Direct dystrophin gene testing Muscle biopsy

Duchenne muscular dystrophy (DMD)

Counselling, especially genetic counselling, education, screening (especially mother) No specific treatment available; support; corticosteroids delay progression

Duchenne muscular dystrophy (DMD)

Claimed to be the leading genetic cause of infant death, SMA includes several types, all manifesting as progressive muscle wasting and leading to early death in the more severe types

Spinal muscular atrophy (SMA)

SMA is autosomal recessive and due to mutation in SMN1 gene on chromosome 5. Prevalence 1 in 6000–10 000; carriers 1 in 40.

Spinal muscular atrophy (SMA)

Muscle weakness, poor tone and floppiness Feeding difficulties and feeble cry in babies Weak swallowing, coughing and breathing Normal intelligence and sensory modalities Diagnosis is by DNA screening at birth and EEG studies. There is no cure at present and treatment is mainly supportive. Zolgensma gene therapy is given as a single IV injection into children <2 years before symptoms appear. Intrathecal injections of nusinersen are available.

Spinal muscular atrophy (SMA)

About 1 in 25 Ashkenazi Jews is a carrier of Tay–Sachs disease (gangliosidosis), an AR disorder caused by a total deficiency of hexosaminidase A resulting in an accumulation of gangliosides in the brain.

Tay–Sachs disease

This autosomal recessive disorder of the catabolism of the amino acid, phenylalanine, is caused by a deficiency of phenylalanine hydroxylase activity, leading to an elevation of plasma phenylalanine, which if untreated can cause intellectual disability (often very severe) and other neurological symptoms, such as seizures. Neonatal screening for high blood phenylalanine levels (the Guthrie test) is performed routinely.

Phenylketonuria (PKU)10

Tourette syndrome appears to be a genetic condition since a child of a person with TS has a 50% chance of developing it (possibly AD with variable penetrance).

Tourette syndrome

Inherited as an AD disorder. The responsible mutant gene has been located on the short arm of chromosome 4. One genetic mutation accounts for the vast majority of cases, which means that there is an accurate diagnostic test. Both sexes are equally affected.

Huntington disease10

DxT chorea + abnormal behaviour + dementia + family history →

Huntington disease

Insidious onset and progression of chorea Onset most often between 35 and 55 years Mental changes—change in behaviour (can be as early as childhood or in very late life), intellectual deterioration leading to dementia Family history present in the majority Motor symptoms: flicking movements of arms, lilting gait, facial grimacing, ataxia, dystonia Usually a fatal outcome 15–20 years from onset

Huntington disease

This is available, sensitive and important because offspring have a 1 in 2 risk and the onset may be late—after child-bearing years. It is appropriate to refer to expert centres for those seeking it. Of interest is that only 20% have undergone testing since it became available, indicating that those at risk generally prefer the uncertainty of not knowing the reality.

Huntington disease

Early-onset familial Alzheimer disease (EoFAD), which accounts for less than 1% of all Alzheimer disease, is defined as the presence of two or more affected people with onset age <65 years in more than one generation of a family, with postmortem pathologically proven Alzheimer disease in at least one person. There are two forms of FAD: early onset (EoFAD <65 years) and late onset (LoFAD). Mutations in any one of three different forms (alleles) of the susceptible APOE gene are known to cause FAD

Familial Alzheimer disease (FAD)

Most cases are sporadic, and the majority of cases with a family history do not have a clear inheritance pattern and could be the result of several factors including a genetic predisposition or simply a chance aggregation. Consider referral to a neurogenetics clinic for families with unusual features, such as familial aggregation and/or early-onset Parkinson disease.

Parkinson disease

Five to 10% of motor neurone disease is inherited, with an autosomal dominant inheritance pattern. Inherited MND shows familial aggregation and an earlier age of onset than average (40s or younger); otherwise clinical features are essentially the same as the sporadic form (see CHAPTER 22 ). If more than one family member presents with MND consider referral to a neurogenetic clinic.

Motor neurone disease (MND) (amyotrophic lateral | sclerosis)

the most common human single-gene disorders in the world, are a group of hereditary disorders characterised by a defect in the synthesis of one or more of the globin chains (α or β)—there are two of each (α2, β2). This causes defective haemoglobin synthesis leading to hypochromic microcytic anaemia. α-thalassaemia is usually seen in people of Asian origin while β-thalassaemia is seen in certain ethnic groups from the Mediterranean, the Middle East, South- East Asia and the Indian subcontinent. However, in our multicultural communities one cannot assume a person’s origins. It is recommended that all women of child-bearing age be screened for thalassaemia. The thalassaemias are described as ‘trait’ when there are laboratory features without clinical expression.

Thalassaemia

α-thalassaemia is usually due to the deletion of one or more of the four genes for α-globin, the severity depending on the number of genes deleted: deletion of all four genes—α-thalassaemia (hydrops fetalis); of three genes—haemoglobin H disease, which results in lifelong anaemia of mild-to-moderate degree; of one or two genes—a symptomless carrier. In β-thalassaemia, the β-chains are produced in decreased quantity rather than having large deletions. People who have two mutations (one in each β-globin gene) have β-thalassaemia major. β-thalassaemia minor—a single mutation (heterozygous)—the carrier or trait state β-thalassaemia major—two mutations (homozygous)—the person who has the disorder

Thalassaemia

If both parents are carriers, there is a 1 in 4 chance that their child will have the disorder. Clinical features Carriers are clinically asymptomatic and do not need treatment apart from counselling. Patients with thalassaemia major present with symptoms of severe anaemia (haemolytic anaemia). Without treatment, children with thalassaemia major are lethargic and inactive, show a failure to thrive or to grow normally, and delayed puberty, hepatosplenomegaly and jaundice. Signs usually appear after 6 months and death from cardiac failure used to be common but with regular blood transfusions and iron-chelating treatment people can now live in good health

Thalassaemia

DxT pallor + jaundice + hepatosplenomegaly →

thalassaemia major

FBE: in most carriers the mean corpuscular haemoglobin/mean corpuscular volume is low but can be normal. There is usually mild hypochromic microcytic anaemia but this is severe with the homozygous type. Haemoglobin electrophoresis: measures relative amounts of normal adult haemoglobin (HbA) and other variants (e.g. HbA2, HbF). This will detect most carriers. Serum ferritin level: helps distinguish from iron deficiency, which has a similar blood film. DNA analysis: for mutation detection (mainly used to detect or confirm carriers).

thalassaemia major

Treatment is based on a regular blood transfusion schedule for anaemia. Avoid iron supplements. Folate supplementation and a low-iron diet are advisable. Excess iron is removed by iron chelation (e.g. desferrioxamine). Allogeneic bone marrow transplantation has been used with success.16 Splenectomy may be appropriate.

Treatment for thalassaemia major

The most important abnormality in the haemoglobin (Hb) chain is sickle-cell haemoglobin (HbS), which results from a single base mutation of adenine to thymine, leading to a substitution of valine for glutamine at position 6 on the β-globin chain. The defective Hb causes the red cells to become deformed in shape—‘sickled’. The sickled cells tend to flow poorly and clog the microcirculation, resulting in hypoxia, which compounds the sickling. Such attacks, which result in tissue infarction, are called ‘crises’. Sickling is precipitated by infection, hypoxia, dehydration, cold and acidosis, and may complicate operations. The autosomal recessive disorder occurs mainly in Africans (25% carry the gene), but it is also found in India, South-East Asia, the Middle East and southern Europe.

Sickle-cell disorders

Heterozygous state for HbS = sickle-cell trait | Homozygous state = sickle-cell anaemia/disease

Sickle-cell disorders

This varies from being mild or asymptomatic to a severe haemolytic anaemia and recurrent painful crises. It may present in children with anaemia and mild jaundice. Children may develop digits of varying lengths from the hand-and-foot syndrome due to infarcts of small bones. Features of infarctive sickle crises include: bone pain (usually limb bones) abdominal pain chest—pleuritic pain kidney—haematuria spleen—painful infarcts precipitated by cold, hypoxia, dehydration or infection Hb electrophoresis is needed to confirm the diagnosis.

Sickle-cell anaemia

Hb electrophoresis is needed to confirm the diagnosis. Long-term problems include chronic leg ulcers, susceptibility to infection, aseptic necrosis of bone (especially head of femur), blindness and chronic kidney disease. The prognosis is variable. Children in Africa often die within the first year of life. Infection is the commonest cause of death.

Sickle-cell anaemia

People with this usually have no symptoms unless they are exposed to prolonged hypoxia, such as anaesthesia and flying in non-pressurised aircraft. The disorder is protective against malaria

Sickle-cell trait

This is the commonest cause of inherited haemolytic anaemia in northern Europeans. It is an autosomal dominant disorder of variable severity, although in 25% of patients neither parent is affected, suggesting spontaneous mutation in some instances. Jaundice may present at birth or be delayed or occur not at all. Splenomegaly is a feature and splenectomy is considered to be the treatment of choice in severe cases. Maintenance of folic acid levels is important

Hereditary spherocytosis

is a common disorder affecting over 400 million people worldwide. It is the most common red cell enzyme defect that causes episodic haemolytic anaemia because of the decreased ability of red blood cells to cope with oxidative stresses. It is an X-linked recessive inherited disorder with a high prevalence among people of African, Mediterranean or Asian ancestry. In some countries such as Malaysia there is a national screening program.

Glucose-6-phosphate dehydrogenase deficiency

The important clinical features are: asymptomatic in many neonatal jaundice—infants at risk should be observed after delivery (at least 5 days) episodic acute haemolytic anaemia—triggered by antioxidants and infections, and drugs, especially antimalarials, sulfonamides, nitrofurantoin, quinolones, traditional medicines, vitamins C and K, high dose aspirin, fava (broad) beans and naphthalene (e.g. moth balls) There is no specific treatment. Known precipitants should be avoided. Avoid penicillin and probenecid. Diagnosis is by G6PD assay and a blood film during an attack.

Glucose-6-phosphate dehydrogenase deficiency

is an inborn error of metabolism in which the body is unable to metabolise galactose to glucose. There are three clinical syndromes caused by differing enzyme deficiencies, one of which is galactose-1-phosphate uridyl transferase, which causes the classic syndrome. It is an autosomal recessive disorder with an incidence of about 1 in 60 000 births. As lactose is the major source of galactose, the infant becomes anorexic and jaundiced within a few days or weeks of taking breast milk or lactose-containing formula. It can be rapidly fatal. Management is with a galactose (mainly lactose)-free formula such as soy with added calcium and vitamins.

Galactosaemia

In inherited bleeding deficiency disorders, there are deficiencies of vital factors (see CHAPTER 29 ). The common significant disorders are: haemophilia A (factor VIII deficiency)—X-linked recessive haemophilia B (factor IX deficiency)—X-linked recessive von Willebrand disease (deficiency of factor VIII:C + defective platelet factor)—autosomal dominant Others to consider are: hereditary haemorrhagic telangiectasia (Osler–Weber–Rendu disease) inherited thrombocytopenia

Bleeding disorders

This is an autosomal dominant disorder of the development of vasculature. A strong family history aids diagnosis. Key features: mucocutaneous telangiectasia (Osler–Weber–Rendu syndrome) recurrent epistaxis in children and adolescents visceral arteriovenous malformations, e.g. GIT, lips diagnosis is clinical, aided by imaging to detect AVMs

Hereditary haemorrhagic telangiectasia

This should be considered in patients with a past and/or family history of DVT or other thrombotic episodes (see CHAPTER 122 ). There are several causes, including important inherited factors, which are: factor V Leiden gene mutation (activated protein C resistance) prothrombin gene mutation protein C deficiency protein S deficiency antithrombin deficiency It is important to be aware of these factors, especially in people with a past history of unexplained thrombotic episodes. Prescribing the oral contraceptive pill (OCP) is an issue but preliminary screening for thrombophilias is not recommended. In factor V Leiden, the most common factor in this group, there is a 35-fold increased risk of thrombosis for those taking the OCP.

Thrombophilia

______________________ is based on typical facial features (flat facies, slanting eyes, prominent epicanthic folds, small ears), hypotonia, intellectual disability and a single palmar crease.

Down syndrome (trisomy 21)

DxT typical facies + hypotonia + single palmar crease →

Down syndrome

95% have extra chromosome of maternal origin (trisomy 21) Remainder due to either unbalances, translocations or mosaicism Prenatal screening tests include early ultrasound (nuchal translucency) and maternal serum screening in first trimester (serum maternal and fetal DNA). Karyotyping of chorionic villus sampling on amniocytes for pregnancies at risk is available. Prevalence 1 in 650 live births

Down syndrome

``` Seizures (usually later onset) Impaired hearing Leukaemia Hypothyroidism Congenital anomalies (e.g. heart, duodenal atresia, Hirschsprung, TOF) Alzheimer-like dementia (fourth–fifth decade) Atlantoaxial instability Coeliac disease Diabetes ```

Down syndrome

Assess child’s capabilities Refer to agencies for assessment (e.g. hearing, vision, developmental disability unit) Advise on sexuality, especially for females (i.e. menstrual management, contraception) as fertility must be presumed

Down syndrome

Trisomy 18 Clinical features These include: incidence 1 in 2000 live births (approx.) microcephaly facial abnormalities, e.g. cleft lip/palate malformations of major organs, e.g. heart malformations of hands and feet—clenched hand posture neural tube defect Prognosis is poor—about one-third die in first month, <10% live beyond 12 months. Prenatal diagnosis is available

Edward syndrome10

``` Trisomy 13 Clinical features These include: incidence 1 in 7000 (approx.) microcephaly brain and heart malformation ```

Patau syndrome10

presents as a classic physical phenotype with large prominent ears, long narrow face, macro-orchidism and intellectual disability. It is the most common inherited cause known of developmental disability and should always be considered. The cause is the result of an increase in the size of a trinucleotide repeat in the FMR-I gene on the X chromosome (the number of sequences determines carrier or full mutant status). Any individual with significant development delay should be tested for FXS.

Fragile X syndrome (FXS)

DxT characteristic facies + intellectual disability + large testes →

FXS

M:F ratio 2:1 Prevalence of full mutation 1 in 4000 Variable spectrum of characteristic features, making detection difficult in some cases 1 in 250 are pre-mutation carriers Family history of intellectual disability Affects all ethnic groups Females may appear normal but may be affected

FXS

``` Cytogenetic testing (karyotyping) DNA test (specific for full mutation as well as carriers) ```

FXS

``` Autism or autistic-like behaviour Attention deficit in 10% (with or without hyperactivity) Seizures (20%) Connective tissue abnormalities Learning disability and speech delay Coordination difficulty Primary ovarian insufficiency Late-onset tremor/ataxia syndrome ```

FXS

Careful genetic appraisal and counselling Assessment of child’s capabilities Multidisciplinary assessment, including developmental disability unit Referral for integration of speech and language therapy, special education, behaviour management Pharmacological treatment of any epilepsy, or attention or mood behaviour disorders Medications may determine whether the child remains in the community or not

FXS

This uncommon disorder (1 in 10 000–15 000) has classic features, especially a bizarre appetite and eating habits, of which the GP should be aware. It is probable that there are many undiagnosed cases in the community. The most common cause is a deletion of the short arm of chromosome 15.

Prader–Willi syndrome

DxT neonatal hypotonia + failure to thrive + obesity (later) →

Prader–Willi syndrome

Hypotonic infants with weak suction and failure to thrive, then voracious appetite causing morbid obesity Usually manifests at 3 years

Prader–Willi syndrome

Intellectual disability Narrow forehead and turned-down mouth Small hands and feet Hypogonadism

Prader–Willi syndrome

Early diagnosis and referral Multidisciplinary approach Expert dietetic control With proper care and support, longevity into the eighth decade is a reality

Prader–Willi syndrome

This is a systemic connective tissue disorder characterised by abnormalities of the skeletal, cardiovascular and ocular systems. It has variable expressions and is a potentially lethal disorder. If untreated, death in the 30s and 40s is common.

Marfan syndrome10

DxT tall stature + dislocated lens and myopia + aortic root dilatation →

Marfan syndrome

Mutations in the fibrillin gene on chromosome 15 | Autosomal dominant

Marfan syndrome

``` Disproportionally tall and thin Long digits—arachnodactyly Kyphoscoliosis Joint laxity (e.g. genu recurvatum) Myopia and ectopic ocular lens High arched palate Aortic dilatation and dissection Mitral valve prolapse ```

Marfan syndrome

Needs surveillance of eyes, heart and thoracic aorta Echocardiography, possibly aortic root dilatation Long-term beta blockade therapy reduces rate of dilatation Consider prophylactic cardiovascular surgery Genetic counselling for the family

Marfan syndrome

This is an AD disorder with mutation of chromosome 11. It has been described as a male Turner syndrome but affects both sexes

Noonan syndrome

DxT facies + short stature + pulmonary stenosis →

Noonan syndrome

Characteristic facies—down-slanting palpebral fissures, widespread eyes, low-set ears ± ptosis Short stature

Noonan syndrome

``` Pulmonary valve stenosis Webbed neck Failure to thrive, usually mild Abnormalities of cardiac conduction and rhythm ± Intellectual disability ```

Noonan syndrome

This is due to an extra X chromosome, resulting in a male phenotype and occurring in 1 in 800 live births. Approximately 2 out of 3 are never recognised.

Klinefelter syndrome10

DxT lanky men + small testes + infertility →

Klinefelter syndrome10

47, XXY genotype The extra X chromosome is usually of maternal origin About 30 or more variants of the disorder

Klinefelter syndrome

tall men with long limbs small firm testes ≤2 cm (10 mL) infertility (azoospermia) There may be: sparse facial hair reduced libido learning difficulties, especially reading intellectual ability may range from normal to disability increased risk of DVT, breast cancer and diabetes (screening indicated)

Klinefelter syndrome

Increased gonadotrophin, low to normal testosterone

Klinefelter syndrome

Transdermal testosterone

Klinefelter syndrome

This is due to only one X chromosome, occurring in 1 in 4000 live female newborns; 99% of conceptions are miscarried.

Turner syndrome (gonadal dysgenesis)

DxT short stature + webbed neck + facies →

Turner syndrome

45 chromosomes of XO karyotype (typical Turner karyotype in 50% of cases) Many are mosaics (e.g. 45X/46XX chromosomes) Phenotypes vary

Turner syndrome

Short stature—average adult height 143 cm Primary amenorrhoea in XO patient; infertility Webbing of neck Typical facies: micrognathia, low hairline Lymphoedema of extremities Cardiac defects (e.g. coarctation of aorta) Mental deficiency is rare.

Turner syndrome

Hormone-based (e.g. growth hormone, hormone replacement therapy)

Turner syndrome

DxT abnormal facies + growth retardation + microcephaly + history of alcohol intake during pregnancy →

fetal alcohol spectrum disorder

``` Markedly underweight until puberty Learning difficulties Microcephaly Characteristic facies (needs 2 of *) shortened palpebral fissures* long, smooth featureless philtrum ```

Fetal alcohol syndrome

Hyperactivity Congenital heart disease often seen Skeletal abnormalities Diagnosis based on alcohol history in pregnancy

Fetal alcohol syndrome

This is an autosomal dominant condition with predisposition to ventricular arrhythmias, syncopal/fainting spells and sudden death, particularly during exercise. Confirm or exclude by ECG when suspected—interval 0.5–0.7 seconds. Management includes sports restrictions, beta blockers and pacemaker or AICD.

Congenital long QT syndrome

This is an AD disorder with several genetic mutations. It is the most common cause of sudden cardiac death among athletes.

Familial hypertrophic cardiomyopathy

Fatigue Exertional dyspnoea and chest pain Palpitations Dizziness/syncope Diagnosis by ECG (LV hypertrophy) and doppler echocardiography. Insertion of AICD may prevent sudden death.

Familial hypertrophic cardiomyopathy

There are several types of genetic disorder of lipid metabolism including the better-known familial hypercholesterolaemia and familial combined hyperlipidaemia. The former is identified by elevated cholesterol, corneal arcus juvenalis, tendon xanthomas in the patient or their firstand second-degree relatives and also by a DNA mutation. Homozygous patients present with atherosclerosis disease in childhood and early death from myocardial infarction. Heterozygotes may develop the disorder in their 30s or 40s

Familial hyperlipoproteinaemia20

Mutations in either of the two genes—BRCA1 and BRCA2—result in a strong predisposition for both breast and ovarian cancer Mutations present in about 1 in 800 of the general population (male and female), who are carriers Dominant inheritance The risk of developing breast cancer is 10-fold and 40–80% of cases occur before the age of 70 years22 The prognosis in these women is the same as for sporadic cases Early age of onset of breast cancer Male breast cancer (6% in males with BRCA2 gene mutation) Coexistence of ovarian and breast cancer in the same family Carriers of mutations may be at an increased risk of prostate cancer, pancreatic cancer and colorectal cancer, although this is controversial for the latter two

Features of breast–ovarian cancer syndrome

Two first-degree or second-degree relatives on one side of the family with cancer Individuals with age of onset of cancer <50 years Individuals with bilateral or multifocal breast cancer Individuals with ovarian cancer Breast cancer in a male relative Jewish ancestry

Risk indicators for familial breast–ovarian cancer

Both sexes have a risk of approximately 5% of developing bowel cancer in their lifetime. In some this risk is increased due to an inherited predisposition. The two key disorders are HNPCC and FAP.

Colorectal cancer21

Caused by a defect in one of the genes responsible for DNA mismatch repair Affects 1 in 1000 individuals Autosomal dominant Early age of onset Increased risk of certain extracolonic cancers, including endometrial, stomach, ovary and kidney tract cancers Screening should occur every 1–2 years from 25 years of age or 5 years earlier than affected family member developed it

Lynch syndrome (hereditary non-polyposis colorectal cancer)

Less common than HNPCC; affects about 1 in 10 000 Caused by a mutation in the APC gene Usually hundreds or thousands of polyps Eventually almost 100% of cases develop colon cancer without prophylactic colectomy Median age of diagnosis 40 years Small increased risk of other cancers (e.g. thyroid, cerebral) Screening should occur annually from between 12–15 and 30–35 years of age, and then every 3 years

Familial adenomatous polyposis

For Lynch syndrome (HNPCC): Three or more close relatives with bowel cancer Two or more close relatives with bowel cancer and: more than one bowel cancer in same relative

Individuals at risk Familial adenomatous polyposis

an inherited mutation in certain genes (e.g. BRAF gene) is considered to be involved in up to 5% of melanomas. Having a first-degree relative affected almost doubles a person’s risk.

Melanoma:

family history is a risk factor; some genes (e.g. BRAC1 and BRAC2) are susceptible. Refer if a significant family history

Prostate:

which is due to a deficiency of the lysosomal enzyme glucocerebrosidase, leads to anaemia and thrombocytopenia as a result primarily of hypersplenism. There is chronic bone pain and ‘crises’ of bone pain. Consider it in children with fatigue, bone pain, delayed growth, epistaxis, easy bruising and hepatosplenomegaly. Replacement enzyme therapy is available.

Gaucher disease

This is a group of inherited disorders caused by a deficiency of one or more enzymes involved in glycogen breakdown, leading to the deposition of abnormal amounts of glycogen in tissues, especially the liver. The best-known type is 1A (von Gierke disorder), an autosomal recessive disorder due to deficiency of glucose-6-phosphatase (G-6-P). It is seen in several ethnic groups. It typically causes growth retardation, hepatomegaly, renomegaly, hypoglycaemia (can be severe), lactic acidosis and hyperlipidaemia. Children have characteristic morphological features —short, doll-like facies with fat cheeks, thin extremities and large abdomen (hepatomegaly

Glycogen storage disease (liver glycogenoses)

Diagnosis is by abnormal plasma lactate and lipid levels, liver biopsy and recently by gene analysis for the G-6-P gene. Treatment is aimed to prevent hypoglycaemia and lactic acidosis via frequent carbohydrate feedings, such as uncooked cornstarch and overnight nasogastric glucose infusion. The prognosis is poor.

Glycogen storage disease (liver glycogenoses)

The three most common porphyrias are acute intermittent porphyria, porphyria cutanea tarda (the

The porphyrias

DxT severe abdominal pain + abnormal illness behaviour + ‘red’ urine →

acute intermittent porphyria

Approximately 2% of births are associated with congenital abnormalities, of which 1 in 7 are chromosomal, the most common of which is Down syndrome (trisomy 21). Antenatal screening tests that can now be performed for several conditions are mainly

Prenatal screening and diagnosis of genetic | disorders24

screening tests for Down syndrome and other trisomies screening tests for thalassaemias/haemoglobinopathies second-trimester ultrasound scans for fetal abnormalities, such as neural tube defects (NTD) and abdominal wall defects (AWD)

Prenatal screening and diagnosis of genetic | disorders24

This has a live birth incidence of 1.4 per 1000 in Australia.20 The risk of conceiving a child with Down syndrome increases proportionally with age. For a woman aged 21, it is 1 in 1000, while for a woman aged 35, it is 1 in 275 and for a woman aged 45, it is 1 in 20. The tests available to test for Down syndrome include the following’:5,25,26 1. combined first-trimester screening tests (maternal serum screening/MSST; cell-free fetal DNA at 10–12 weeks gestation; nuchal translucency ultrasound at 11–14 weeks) 2. second-trimester MSST (4 analytes): alpha fetoprotein, oestriol, free beta hCG, inhibin A. This test is basically for women presenting later in pregnancy. A final risk is calculated by a computer program which combines other factors such as EDD age and age of gestation 3. non-invasive prenatal test (NIPT) from 10–21 weeks maternal serum. This cell-free DNA screening should be offered as a choice to women. This aneuploidy test usually covers three trisomies: 21 Down syndrome, 18 Edward syndrome, 13 Patau syndrome. A follow-up ultrasound is recommended for Down syndrome. It has the potential to screen multiple disorders as it examines the genetic material of the fetus in maternal serum 4. diagnostic tests (chorionic villus sampling, amniocentesis). The most reliable method is obtaining fetal tissue by these last means but there is a significant risk of miscarriage (1 in 100 for chorionic villus sampling and 1 in 200 for amniocentesis)

Screening for Down syndrome

DxT odour + hypertonicity + seizures (infancy) →

maple syrup urine | disease

Fish-like’ mouth with micrognathia

Turner syndrome

‘Chipmunk’ facies

thalassaemia major

``` The commonest causes of the acute abdomen in a general practice series were: acute appendicitis (21%), the colics (16%) and mesenteric adenitis (16%). ```

acute abdomen

Colicky midline umbilical abdominal pain (severe) → vomiting → distension = small bowel obstruction (SBO). Midline lower abdominal pain → distension → vomiting = large bowel obstruction (LBO). If cases of acute abdomen have a surgical cause, the pain nearly always precedes the vomiting (contrast with gastroenteritis) Mesenteric artery occlusion must be considered in an older person with arteriosclerotic disease or in those with atrial fibrillation presenting with severe abdominal pain or following myocardial infarction. Up to one-third of presentations of abdominal pain have no specific cause found.

acute abdomen

Common reasons are common: gastroenteritis/food poisoning accounts for so many GP presentations that occasionally a case will have examination findings of an acute abdomen. The other most common causes of acute abdomen are acute appendicitis, irritable bowel syndrome, the various ‘colics’ and ovulation pain (mittelschmerz). Mesenteric adenitis is common in children. The various causes of chronic or recurrent abdominal pain are presented in TABLE 24.2 . A study on chronic abdominal pain3 showed that the commonest reasons (approximate percentages) were no discoverable causes (50%), minor causes including muscle strains (16%), irritable bowel syndrome (12%), gynaecological causes (8%), peptic ulcers and hiatus hernia (8%).

acute abdomen

Most of the causes of the acute abdomen are serious and early diagnosis is mandatory to reduce mortality and morbidity.

Serious disorders not to be missed

It is vital not to misdiagnose a _________________________, which causes lower abdominal or suprapubic pain of sudden onset, or the life-threatening vascular causes, such as a ruptured or dissecting aortic aneurysm, mesenteric artery occlusion and myocardial infarction (which can present as epigastric pain).

ruptured ectopic pregnancy

Perforated ulcers (now uncommon) and strangulated bowel, such as volvulus of the sigmoid and entrapment of the small bowel in a hernial orifice or around adhesions, also demand an early diagnosis.

acute abdomen

rapid hypovolaemic shock

Ectopic pregnancy → rapid hypovolaemic shock | Ruptured AAA

peritonitis/pelvic abscess

Gangrenous appendix → peritonitis/pelvic abscess Perforated ulcer → peritonitis Obstructed bowel → gangrene

A very common pitfall is missing acute appendicitis, especially in the elderly, in children, in pregnancy and in those taking steroids, where the presentation may be ____________.

atypical

Early _______________presents typically with central abdominal pain that shifts to the right iliac fossa (RIF) some 4–6 hours later. It can be difficult to diagnose early on. It can cause diarrhoea with abdominal pain, especially if a pelvic appendix, and can be misdiagnosed as acute gastroenteritis.

appendicitis

________________deficiencies, such as lactase deficiency, are associated with cramping abdominal pain, which may be severe. The pain follows some time, maybe hours, after the ingestion of milk and is accompanied by the passage of watery stool. The association with milk may go unrecognised.

Disaccharidase

_________________, especially in the older person with unilateral abdominal pain in the dermatomal distribution, is a trap. Referred pain from conditions above the diaphragm, such as myocardial infarction, pulmonary embolism and pneumonia, can be misleading. The rare general medical causes—such as diabetes ketoacidosis, acute porphyria, Addison disease, lead poisoning, tabes dorsalis, sickle-cell anaemia, haemochromatosis and uraemia—often create a diagnostic dilemma.

Herpes zoster

Misdiagnosing a ruptured ectopic pregnancy in a woman using contraception or with a history of normal menstruation or where the brownish vaginal discharge is mistaken for a normal period.

acute abdomen

Failing to examine hernial orifices in a patient with intestinal obstruction. Misleading temporary improvement (easing of pain) in perforation of gangrenous appendix or perforated peptic ulcer. Overlooking acute mesenteric artery obstruction in an older person with colicky central abdominal pain. Attributing abdominal pain, frequency and dysuria to a urinary infection when the cause could be diverticulitis, pelvic appendicitis, salpingitis or a ruptured ectopic pregnancy. Failing to examine testes.

acute abdomen

__________________ is hospital admission by deception, often with severe abdominal pain without convincing clinical signs or abnormal investigation. Diagnosis requires a high level of suspicion.

Munchausen syndrome

History The urgency of the history will depend on the manner of presentation, whether acute or chronic. Pain has to be analysed according to its quality, quantity, site and radiation, onset, duration and offset, aggravating and relieving factors and associated symptoms and signs. Special attention has to be paid to: anorexia, nausea or vomiting micturition bowel function menstruation/contraception drug intake

acute abdomen

consider mesenteric artery obstruction

Atrial fibrillation:

Pallor and ‘shock’:

acute blood loss

If distension, consider the six Fs:

fat, fluid, flatus, faeces, fetus, frightening growths

haemoglobin—anaemia with chronic blood loss (e.g. peptic ulcer, cancer, oesophagitis) blood film—abnormal red cells with sickle-cell disease WCC—leucocytosis with appendicitis (75%),4 acute pancreatitis, mesenteric adenitis (first day only), cholecystitis (especially with empyema), pyelonephritis ESR—raised with cancer, Crohn disease, abscess (but non-specific) C-reactive protein (CRP)—use in diagnosing and monitoring infection, inflammation (e.g. pancreatic). Preferable to ESR liver function tests—hepatobiliary disorder serum amylase and/or lipase (preferable)—if raised to greater than three times normal upper level acute pancreatitis is most likely; also raised partially with most intra-abdominal disasters (e.g. ruptured ectopic pregnancy, perforated peptic ulcers, ruptured empyema of gall bladder, ruptured aortic aneurysm) faecal elastase—chronic pancreatitis pregnancy tests—urine or serum β-HCG: for suspected ectopic Helicobacter pylori testing urine: blood: ureteric colic (stone or blood clot), urinary infection white cells: urinary infection, appendicitis (bladder irritation) bile pigments: gall bladder disease porphobilinogen: porphyria (add Ehrlich aldehyde reagent) ketones: diabetic ketoacidosis air (pneumaturia): fistula (e.g. diverticulitis, other pelvic abscess, pelvic cancer) faecal blood—mesenteric artery occlusion, intussusception (‘redcurrant jelly’), colorectal cancer, diverticulitis, Crohn disease and ulcerative colitis

Investigations acute abdomen

``` The two main screening tests are ultrasound and CT scan.5 Plain abdominal X-ray is an alternative, if more readily available. The following tests can be considered according to the clinical presentation: ultrasound: good for hepatobiliary system, kidneys and female pelvis. Look for: gallstones ectopic pregnancy pancreatic pseudocyst aneurysm aorta/dissecting aneurysm hepatic metastases and abdominal tumours thickened appendix paracolic collection Note: can be affected by gas shadows ```

acute abdomen

CT scan: gives excellent survey of abdominal organs including masses and fluid collection: pancreatitis (acute and chronic) undiagnosed peritoneal inflammation (best) trauma diverticulitis leaking aortic aneurysm retroperitoneal pathology appendicitis (especially with oral contrast)

acute abdomen

plain X-ray abdomen (erect and supine): look for (see FIG. 24.1 ): kidney/ureteric stones—70% opaque4 biliary stones—only 10–30% opaque air in biliary tree calcified aortic aneurysm marked distension sigmoid → sigmoid volvulus

acute abdomen

distended bowel with fluid level → bowel obstruction enlarged caecum with large bowel obstruction blurred right psoas shadow → appendicitis ‘coffee bean’ sign → volvulus a sentinel loop of gas in left upper quadrant (LUQ) → acute pancreatitis chest X-ray: air under diaphragm → perforated ulcer IVP contrast-enhanced CT or X-ray (e.g. Gastrografin meal): diagnosis of bowel leakage barium enema HIDA nuclear scan—diagnosis of acute cholecystitis (good when US unhelpful) ERCP: shows bile duct obstruction and pancreatic disease MRI scan (especially useful with contrast) Other tests: ECG endoscopy upper GIT sigmoidoscopy and colonoscopy

acute abdomen

Upper abdominal pain is caused by lesions of the upper GIT. Lower abdominal pain is caused by lesions of the lower GIT or pelvic organs. Early severe vomiting indicates a high obstruction of the GIT. Acute appendicitis features a characteristic ‘march’ of symptoms: pain → anorexia, nausea → vomiting.

acute abdomen Diagnostic guidelines

Colicky pain is a rhythmic pain with regular spasms of recurring pain building to a climax and fading. It is virtually pathognomonic of intestinal obstruction. Ureteric colic is a true colicky abdominal pain, but so-called biliary colic and kidney colic are not true colics at all.

acute abdomen

Typical pain sites of abdominal pain (general guidelines only) are presented in FIGURE 24.3 . Epigastric pain usually arises from disorders of the embryologic foregut, such as the oesophagus, stomach and duodenum, hepatobiliary structures, pancreas and spleen. However, as some disorders progress the pain tends to shift from the midline to the right (gall bladder and liver) or left (spleen). Periumbilical pain usually arises from disorders of structures of the embryologic midgut, while structures from the hindgut tend to refer pain to the lower abdomen or suprapubic region.

acute abdomen

The intra-abdominal sensory receptors can be considered as innervating visceral or parietal peritoneum. Visceral mechanoreceptors are triggered by intestinal distension or tension on mesentery or blood vessels while nociceptors are triggered by mechanical, thermal and chemical stimuli. The pain from viscera is felt as diffuse and poorly localised, while stimulation of parietal peritoneal nociceptors gives a pain that is experienced directly at the site of insult.

acute abdomen

Abdominal pain is a common complaint in children, especially recurrent abdominal pain, which is one of the most common complaints in childhood. The problem causes considerable anxiety in parents and it is important to differentiate the severe problems demanding surgery from nonsurgical problems. About one in 15 will have a surgical cause for pain.6 A good rule is to rule out a urinary infection with urinalysis.

acute abdomen Abdominal pain in children

The causes of abdominal pain can be considered in the diagnostic model category. 1 Common causes/probability diagnosis: infant ‘colic’

acute abdomen Abdominal pain in children

``` gastroenteritis (all ages) mesenteric adenitis 2 Serious causes, not to be missed: intussusception (peaks at 6–9 months) acute appendicitis (mainly 5–15 years) bowel obstruction/strangulated hernia ```

acute abdomen Abdominal pain in children

``` Pitfalls: child abuse constipation/faecal impaction torsion of testes lactose intolerance peptic ulcer infections: mumps, tonsillitis, pneumonia (esp. right lower lobe), EBM, UTI adnexal disorders in females (e.g. ovarian) acute pancreatitis 4 Rarities: Meckel diverticulitis Henoch–Schönlein purpura sickle crisis lead poisoning 5 Seven masquerades checklist: type 1 diabetes drugs UTI 6 Psychogenic consideration: important cause ```

acute abdomen Abdominal pain in children

This is the occurrence in a well baby of regular, unexplained periods of inconsolable crying and fretfulness, usually in the late afternoon and evening, especially between 2 weeks and 16 weeks of age. No apparent cause can be found, and the word ‘colic’ refers to the historical assumption that the crying is caused by abdominal pain. It is very common, occurring in about one-third of infants and lasting for a period of at least three weeks.

Infant ‘colic’ (period of infant distress)

Reassure and explain. Advise the parents: Use gentleness (such as subdued lighting where the baby is handled, soft music, speaking softly, quiet feeding times). Avoid quick movements that may startle the baby. Make sure the baby is not hungry—avoid underfeeding. Provide demand feeding (in time and amount). Make sure the baby is burped, and give posture feeding. Provide comfort from a dummy or pacifier. Provide plenty of gentle physical contact. Cuddle and carry the baby around (e.g. take a walk around the block). A carrying device such as ‘snuggly’ or ‘Mei Tai Sling’ allows the baby to be carried around at the time of crying. Make sure the mother gets plenty of rest during this difficult period. Do not worry about leaving a crying child for 10 minutes or so after 15 minutes of trying consolation. Medication Drugs are not generally recommended, but some preparations have tradition, if not much science, behind them (e.g. simethicone [Infacol wind drops]).

Infant ‘colic’ (period of infant distress)

is the diagnosis that should be foremost in one’s mind with a child aged between 3 months and 2 years presenting with sudden onset of severe colicky abdominal pain, coming at intervals of about 15 minutes and lasting for 2–3 minutes. Early diagnosis, within 24 hours of onset, is essential, for after this time there is a significant rise in morbidity and mortality. A segment of bowel telescopes into the adjoining distal segment (e.g. ileocaecal segment), resulting in intestinal obstruction. It is usually idiopathic but can have a pathological lead point (4–12 years) (e.g. polyp, Meckel diverticulum).

Intussusception

Male babies > female Range: birth to school age, usually 5–24 months Sudden-onset acute pain with shrill cry Vomiting

Intussusception

Lethargy Pallor with attacks Intestinal bleeding: redcurrant jelly (60%)7

Intussusception

DxT pale child + severe ‘colic’ + vomiting →

acute intussusception

Signs Pale, anxious and unwell Sausage-shaped mass in right upper quadrant (RUQ) anywhere between the line of colon and umbilicus, especially during attacks (difficult to feel) Signe de dance (i.e. emptiness in RIF to palpation) Alternating high-pitched active bowel sounds with absent sounds Rectal examination: ± blood ± hard lump

acute intussusception

Diagnosis Ultrasound Enema using oxygen or barium (with caution) used for diagnosis and treatment Treatment7 Hydrostatic reduction by air or oxygen from the ‘wall’ supply (preferred) or barium enema Surgical intervention may be necessary

acute intussusception

Differential diagnosis Acute gastroenteritis: can be difficult in those cases where there is some loose stool with intussusception and with blood and mucus without much watery stool in gastroenteritis. However, usually attacks of pain are of shorter duration, and there is loose watery stool, fever and no abdominal mass. If doubtful, refer as possible intussusception. Impacted faeces can lead to spasms of colicky abdominal pain—usually an older child with a history of constipation. Other causes of intestinal obstruction (e.g. irreducible inguinal hernia, volvulus, intraabdominal band).

acute intussusception

Drugs In any child complaining of acute abdominal pain, enquiry should be made into drug ingestion. A common cause of colicky abdominal pain in children is cigarette smoking (nicotine); consider other drugs such as marijuana, cocaine and heroin.

acute intussusception

This may occur at any age, being more common in children of school age (10–12 years) and in adolescence, and uncommon in children under 3 years of age. Special problems of early diagnosis occur with the very young (younger than 3 years) and in intellectually disabled children, many of whom present with peritonitis.

Acute appendicitis in children

Vomiting occurs in at least 80% of children with appendicitis and diarrhoea in about 20%. The temperature is usually only slightly elevated but in about 5% of cases it exceeds 39°C.

Acute appendicitis in children

In children the physical examination, especially eliciting abdominal (including rebound) tenderness, and the rectal examination demand considerable tact, patience and gentleness. Jumping or hopping induces pain

Acute appendicitis in children

A serious point of confusion can occur between pelvic appendicitis, causing diarrhoea and vomiting, and acute gastroenteritis. A high CRP level >50 mg/L is a feature of appendicitis.6 A particularly severe case of apparent gastroenteritis, especially if persistent, should be regarded as pelvic appendicitis until proved otherwise. Ultrasound is the preferred imaging.

Acute appendicitis in children

This presents a difficult problem in differential diagnosis with acute appendicitis because the history can be very similar. At times the distinction may be almost impossible. In general, with mesenteric adenitis localisation of pain and tenderness is not as definite, rigidity is less of a feature, the temperature is higher, and anorexia, nausea and vomiting are also lesser features. The illness lasts about five days followed by a rapid recovery. Comparisons between the two are presented in TABLE 24.5 , but if in any doubt it is advisable to consider the problem as acute appendicitis, admit for observation and be prepared for laparoscopy/laparotomy.

Mesenteric adenitis

can sometimes present an anaesthetic risk and patients are usually quite ill in the immediate postoperative period. Treatment is symptomatic and includes ample fluids and paracetamol.

Mesenteric adenitis

can suffer from a wide spectrum of disorders. Ischaemic events, emboli, cancer (in particular) and diverticulae of the colon are more common in old age; duodenal ulcer is less so. Those causes of abdominal pain that occur with more frequency include: vascular catastrophies: ruptured AAA, mesenteric artery occlusion perforated peptic ulcer biliary disorders: biliary pain and acute cholecystitis diverticulitis sigmoid volvulus strangulated hernia

Abdominal pain in older people

intestinal obstruction cancer, especially of the large bowel herpes zoster, causing unilateral root pain constipation and faecal impaction Problems arise with management because the pain threshold is raised (colic in particular is less severe) and there is an attenuated response to infection so that fever and leucocytosis can be absent. Non-specific signs, such as confusion, anorexia and tachycardia, might be the only systemic evidence of infection.

Abdominal pain in older people

An AAA may be asymptomatic until it ruptures or may present with abdominal discomfort and a pulsatile mass noted by the patient. There tends to be a family history and thus screening is appropriate in such families. Ultrasound screening is advisable in first-degree relatives over 50 years.

Abdominal aortic aneurysm

The risk of rupture is related to the diameter of the AAA and the rate of increase in diameter. The normal diameter of the abdominal aorta, which is palpated just above the umbilicus, is 10–30 mm, being 20 mm on average in the adult; an aneurysm is greater than 30 mm in diameter.9 Refer if ≥40 mm. Greater than 50 mm is significantly enlarged and is chosen as the arbitrary reference point to operate because of the exponential rise in risk of rupture with an increasing diameter. Refer all cases. The patency of a Dacron graft after 5 years is approximately 95% (see FIG. 24.5 ). Newer techniques include endovascular aneurysm repair.

Abdominal aortic aneurysm

Investigations Ultrasound (good for screening) in relatives >50 years (obesity a problem) CT scan (clearer imaging). Helical/spiral scan is investigation of choice MRI scan (best definition)

Abdominal aortic aneurysm

This is a real surgical emergency in an elderly person who presents with acute abdominal and perhaps back pain with associated circulatory collapse (see FIG. 24.6 ). The patient often collapses at toilet because they feel the need to defecate and the resultant Valsalva manoeuvre causes circulatory embarrassment.

Rupture of aneurysm

The patient should be transferred immediately to a vascular surgical unit, which should be notified in advance. Two important emergency measures for the ‘shocked’ patient are intravenous access for plasma expanding fluid (a central venous line is best if possible) and swift action.

Rupture of aneurysm

DxT intense abdominal pain + pale and ‘shocked’ ± back pain →

Rupture of aneurysm

Acute intestinal ischaemia arises from superior mesenteric artery occlusion from either an embolus or a thrombosis in an atherosclerotic artery. Another cause is an embolus from atrial fibrillation. Necrosis of the intestine soon follows if intervention is delayed.

Mesenteric artery occlusion

Clinical features Central periumbilical abdominal pain—gradually becomes intense. Patients develop a ‘fear of eating’ Profuse vomiting Watery diarrhoea—blood in one-third of cases (eventually) (refer to CHAPTER 34 ) Patient becomes confused

Mesenteric artery occlusion

DxT anxiety and prostration + intense central pain + profuse vomiting ± bloody diarrhoea →

Mesenteric artery occlusion

Signs Localised tenderness, rigidity and rebound over infarcted bowel (later finding) Absent bowel sounds (later) Shock develops later Tachycardia (may be atrial fibrillation and other signs of atheroma)

Mesenteric artery occlusion

Investigations CRP may be elevated intestinal alkaline phosphatase. X-ray (plain) shows ‘thumb printing’ due to mucosal oedema on gas-filled bowel. CT scanning gives the best definition while mesenteric arteriography is performed if embolus is suspected. However, it is commonly only diagnosed at laparotomy.

Mesenteric artery occlusion

Management Early surgery may prevent gut necrosis but massive resection of necrosed gut may be required as a life-saving procedure. Early diagnosis (within a few hours) is essential. Note: Mesenteric venous thrombosis can occur but usually in people with circulatory failure. Inferior mesenteric artery occlusion is less severe and survival more likely.

Mesenteric artery occlusion

with a volume of 600+ mL usually causes severe lower abdominal pain, which may not be apparent in a senile or dementing person. Find and treat the cause. Apart from the common cause of an enlarged prostate or prostatitis, it can also result from bladder neck obstruction by faecal loading or other pelvic masses or anticholinergic drugs.

Acute retention of urine

Management Perform a rectal examination and empty rectum of any impacted faecal material. Catheterise with size 14 Foley catheter to relieve obstruction and drain (give antibiotic cover). Have the catheter in situ and seek a urological opinion. Send specimen for MCU. If there is any chance of recovery (e.g. if the problem is drug-induced), withdraw drug, leave catheter in for 48 hours, remove and give trial of prazosin 0.5 mg bd or terazosin. In some instances, it may be worth giving analgesics, ambulating the patient and attempting voiding by standing up to the sound of running water. A hot bath may also provide a simple solution. Check for prostate cancer and renal impairment. Perform neurological examination of lower limbs and perianal area.

Acute retention of urine

is encountered typically in the aged, bedridden, debilitated person. Its clinical presentation may closely resemble malignant obstruction.10 Spurious diarrhoea can occur, which is known as ‘faecal incontinence’

Faecal impaction

is mainly a condition of young adults but it affects all ages (although uncommon under 3 years). Despite its declining incidence, it is the commonest surgical emergency and special care has to be taken with the very young and the very old. The symptoms can vary because of the different positions of the appendix. It is basically a clinical diagnosis.

Acute appendicitis

Clinical features See FIGURE 24.7 . Typical clinical features are: usually under 30 years of age initial pain is central abdominal (sometimes colicky)

Acute appendicitis

increasing severity and then continuous shifts and localises to RIF within 6 hours may be aggravated by walking (causing a limp) or coughing sudden anorexia nausea and vomiting a few hours after the pain starts ± diarrhoea and constipation

Acute appendicitis

DxT localised RIF pain + a/n/v + guarding →

Acute appendicitis

Signs Patient looks unwell Flushed at first, then pale Furred tongue and halitosis May be febrile—low-grade fever Tenderness in RIF, usually at McBurney point Local rigidity and rebound tenderness Guarding ± Superficial hyperaesthesia ± Psoas sign: pain on resisted flexion of right leg, on hip extension or on elevating right leg (due to irritation of psoas especially with retrocaecal appendix) ± Obturator sign: pain on the examiner flexing patient’s right thigh at the hip with the knee bent and then internally rotating the hip (due to irritation of internal obturator muscle) Rovsing sign: rebound tenderness in RIF while palpating in LIF PR: anterior tenderness to right, especially if pelvic appendix or pelvic peritonitis

Acute appendicitis

Abscess formation → localised mass and tenderness Retrocaecal appendix: pain and rigidity less and may be no rebound tenderness; loin tenderness; positive psoas test Pelvic appendix: no abdominal rigidity; urinary frequency; diarrhoea and tenesmus; very tender PR; obturator tests usually positive Elderly patients: pain often minimal and eventually manifests as peritonitis; can simulate intestinal obstruction Pregnancy (occurs mainly during second trimester): pain is higher and more lateral; harder to diagnose; peritonitis more common Perforation more likely in those who are very young, elderly or have diabetes

Acute appendicitis

Investigations Investigations, including imaging, are of limited value: blood cell count shows a leucocytosis (75%) with a left shift urea and electrolytes—to assess hydration prior to surgery

Acute appendicitis

CRP—elevated ultrasound shows a thickened appendix (86% sensitivity, 81% specificity);11 affected by gas shadow plain X-ray may show local distension, blurred psoas shadow and fluid level in caecum CT scan (94% sensitivity, 98% specificity) also allows other causes, especially in the female pelvis, to be evaluated12 laparoscopy β-HCG

Acute appendicitis

Management Immediate referral for surgical removal—the gold standard. If perforated, cover with cefotaxime and metronidazole. If abscess, radiologic drainage, antibiotics ± interval appendicectomy. It is reasonable to offer a conservative approach for uncomplicated, low-grade cases, with careful monitoring and antibiotics in selected patients. One detailed study showed that surgery was the safest option

Acute appendicitis

The symptoms depend on the level of the obstruction (see TABLE 24.6 ). The more proximal the obstruction, the more severe the pain.

Small bowel obstruction

``` Main causes Outside obstruction (e.g. adhesions—commonest cause, previous laparotomy), strangulation in hernia or pockets of abdominal cavity (see FIG. 24.8 )—this may lead to a ‘closed loop’ obstruction.14 Lumen obstructions (e.g. foreign body, trichobezoar, gallstones, intussusception, malignancy). ```

Small bowel obstruction

Clinical features Severe colicky epigastric and periumbilical (mainly) pain (see FIG. 24.9 ) Spasms every 3–10 minutes (according to level), lasting about 1 minute Vomiting Absolute constipation (nil after bowel emptied)

Small bowel obstruction

DxT colicky central pain + vomiting + distension →

Small bowel obstruction

Signs and tests Patient weak and sitting forward in distress Visible peristalsis, loud borborygmi Abdomen soft (except with strangulation) Tender when distended Increased sharp, tinkling bowel sounds Dehydration rapidly follows, especially in children and elderly

Small bowel obstruction

PR: empty rectum, may be tender Note: check all hernial orifices, including umbilicus X-ray: plain erect film confirms diagnosis—‘stepladder’ fluid levels (4–5 for diagnosis) in 3–4 hours Gastrografin follow-through for precise diagnosis with caution. It can cause severe diarrhoea and may be therapeutic in adhesive obstruction. ± CT scan (especially if extrinsic causation)

Small bowel obstruction

Management IV fluids and bowel decompression with nasogastric tube hernia repair

Small bowel obstruction

``` Temporary arrest of peristalsis is common after abdominal surgery. Other causes include drugs, e.g. opioids, TCAs. Symptoms Nausea Vomiting Vague abdominal discomfort Distension Constipation/obstipation ```

Paralytic ileus

``` Signs Silent abdomen ↓ Bowel sounds Tests X-ray: air accumulation in small bowel and colon ```

Paralytic ileus

The cause is commonly colorectal cancer (75% of cases), especially on the left side, but it can occur in diverticulitis or in volvulus of the sigmoid colon (10% of cases) and caecum.10 Sigmoid volvulus is more common in older men and has a sudden and severe onset. The pain is less severe than in SBO. Be wary of the non-surgical causes, simple constipation or acute pseudoobstruction of the colon (Ogilvie syndrome). Consider ileus.

Large bowel obstruction

Clinical features Sudden-onset colicky pain (even with cancer) Each spasm lasts less than 1 minute Usually hypogastric midline pain (see FIG. 24.10 ) Vomiting may be absent (or late) Absolute constipation (obstipation), no flatus

Large bowel obstruction

DxT colicky pain + distension ± vomiting →

Large bowel obstruction

Signs and tests Increased bowel sounds, especially during pain Distension early and marked Local tenderness and rigidity PR: empty rectum; may be rectosigmoid cancer or blood. Check for faecal impaction X-ray: distension of large bowel with separation of haustral markings, especially caecal distension

Large bowel obstruction

``` sigmoid volvulus shows a distended loop and ‘coffee bean’ sign Gastrografin enema confirms diagnosis Management Drip and suction Surgical referral ```

Large bowel obstruction

can cause acute abdominal pain both with and without a prior history of peptic ulcer. It is an acute surgical emergency requiring immediate diagnosis. Consider a history of drugs, especially NSAIDs. Perforated ulcers may follow a heavy meal. There is usually no back pain. May be painless with steroids. The maximal incidence is 45–55 years and more common in males, and a perforated duodenal ulcer is more common than a gastric ulcer. Consider the clinical syndrome in three stages: 1. prostration 2. reaction (after 4 hours)—symptoms may improve 3. peritonitis (after 4 hours)—severe pain

Perforated peptic ulcer

Clinical features See FIGURE 24.11 . Typical clinical features are: sudden-onset severe epigastric pain continuous pain but lessens for a few hours epigastric pain at first, and then generalised to whole abdomen pain may radiate to one or both shoulders (uncommon) or right lower quadrant nausea and vomiting (delayed) hiccough is a common late symptom

Perforated peptic ulcer

DxT sudden severe pain + anxious, still, ‘grey’, sweaty + deceptive improvement →

Perforated peptic ulcer

``` Signs and tests (typical of peritonitis) Patient lies quietly (pain aggravated by movement and coughing) Pale, sweating or ashen at first Guarding, board-like rigidity Maximum signs at point of perforation No abdominal distension ```

Perforated peptic ulcer

Contraction of abdomen (forms a ‘shelf’ over lower chest) Bowel sounds reduced (silent abdomen) Shifting dullness may be present Pulse, temperature and BP usually normal at first Tachycardia (later) and shock later (3–4 hours) Breathing is shallow and inhibited by pain PR: pelvic tenderness X-ray: chest X-ray may show free air under diaphragm (in 75%)—need to sit upright for prior 15 minutes limited Gastrografin meal can confirm diagnosis CT scan preferable, if available and safe

Perforated peptic ulcer

Management Pain relief Drip and suction (immediate nasogastric tube) Broad-spectrum antibiotics Immediate surgery after resuscitation Conservative treatment may be possible (e.g. later presentation and Gastrografin swallow indicates sealing of perforation)

Perforated peptic ulcer

Kidney (renal) colic is not a true colic but a constant pain due to blood clots or a stone lodged at the pelvic–ureteric junction; ureteric colic, however, presents as severe true colicky pain due to stone movement, dilatation and ureteric spasm. Fortunately, the majority of urinary calculi are small and will pass spontaneously.

Ureteric colic

Guidelines: loin pain—stone in kidney kidney/ureteric colic—ureteric stone

Ureteric colic

``` strangury—stone in bladder Clinical features Maximum incidence 30–50 years (M > F) Intense colicky pain: in waves, each lasting 30 seconds with 1–2 minutes respite Begins in loin and radiates around the flank to the groin, thigh, testicle or labia (see FIG. 24.12 ) Usually lasts <8 hours ± Vomiting ```

Ureteric colic

DxT intense pain (loin) → groin + microscopic haematuria →

Ureteric colic

``` Signs Restlessness: may be writhing in pain Pale, cold and clammy Tenderness at costovertebral angle ± Abdominal and back muscle spasm Smoky urine due to haematuria ```

Ureteric colic

Diagnosis Urine: microscopy; blood testing strip (negative does not exclude calculus) Plain X-ray: most stones—kidney, ureter, bladder (75%)—are radio-opaque (calcium oxalate and phosphate) IVP: confirms opacity, level of obstruction, kidney function and any anatomical abnormalities Ultrasound: may locate calculus but will exclude obstruction Non-contrast spiral KUB-CT is the ‘gold standard’ (sensitivity 97%, specificity 96%) (will show easily missed radiolucent11 uric acid stones)

Ureteric colic

Management If the diagnosis is in doubt (especially if narcotic addiction is suspected) get the patient to pass urine in the presence of an examiner and test for haematuria. While awaiting passage of urine, an indomethacin suppository may be tried for pain relief.

Ureteric colic

Routine treatment (average size adult) Morphine 2.5 to 5 mg IV15 statim then titrate to effect or fentanyl 50–100 mcg IV then titrate to effect. Avoid high fluid intake, especially IV fluids—provokes distension of ureter and aggravates pain. Most cases settle and the patient can go home when pain relief is obtained and an IVP arranged for the next day. Further pain can be alleviated by indomethacin suppositories but should be limited to two a day. An effective alternative treatment is diclofenac 75 mg IM injection, then 50 mg (o) tds for 1 week. Several clinical trials have shown that NSAIDs by IM injection, including ketorolac (10–30 mg IM [or IV] 4–6 hourly), are effective and at least as efficacious as opioids.15,16,17

Ureteric colic

The calculus is likely to pass spontaneously if <5 mm (90% <4 mm pass spontaneously).16 If >7 mm, intervention will usually be required by extracorporeal shock wave lithotripsy or surgery. If the person passes the calculus, he or she should retrieve it and present it for analysis. A repeat IVP may be necessary if there is evidence of obstruction for more than 3 weeks. Persistent obstruction causes sepsis. The cause of the ‘stone’ should be considered. Search for causes such as hyperparathyroidism, hypercalcaemia, hyperoxaluria and UTI. Fever with ureteric colic indicates an obstructed infected kidney.

Ureteric colic

``` Any of the following: stone >7 mm in diameter high-grade or bilateral obstruction gross hydronephrosis fever/UTI unremitting pain stone fails to progress type 2 diabetes staghorn calculus presence of solitary kidney ```

When to refer16

``` Investigations Serum electrolytes, urea, creatinine Serum calcium, phosphate, uric acid, magnesium Serum alkaline phosphatase Urine sample—microbiology and culture At least two consecutive 24-hour urine samples Stone analysis IVP Dietary advice is given in ```

Recurrent urinary calculi

``` Abdominal pain can be produced by contraction of the biliary tree upon an obstructing stone or inspissated bile (sludge). Although the stereotyped higher-risk person is female, 40, fat, fair and fertile, it can occur from adolescence to old age and in both sexes. ```

Biliary pain

``` Typical clinical features are: acute onset severe pain postprandial or at night (often wakes 2–3 am) constant pain (not colicky) lasts 20 minutes to 2–6 hours ```

Biliary pain

maximal RUQ or epigastrium Page 271 may radiate to tip of right shoulder or scapula painful episode builds to a crescendo for about 20 minutes; may recede or last for hours some relief by assuming flexed posture ± nausea and vomiting with considerable retching often a history of biliary pain (may be mild) or jaundice often precipitated by a fatty meal

Biliary pain

DxT severe pain + vomiting + pain radiation →

Biliary pain

Signs Patient anxious and restless, usually in a flexed position or rolling in agony Localised tenderness (Murphy sign) over fundus of gall bladder (on transpyloric plane) Slight rigidity Diagnosis Abdominal ultrasound (to diagnose gallstones) Helical CT Intravenous cholangiography if previous cholecystectomy LFTs may show elevated bilirubin and alkaline phosphatase

Biliary pain

Management Pain relief:18 morphine 2.5–5 mg IV statim then titrate to effect (age-dependent; use lower end of range if ≥70 years) or fentanyl 50–100 mcg IV statim then titrate to effect or

Biliary pain

ketorolac 10–30 mg IM 4–6 hourly (max. 90 mg daily) Gallstone dissolution with ursodeoxycholic acid or lithotripsy (in those unable to have surgery) Laparoscopic cholecystectomy (main procedure)

Biliary pain

form from bile in the gall bladder and sometimes in the bile duct (especially postcholecystectomy) Two main types—cholesterol and pigment (bilirubin) Lifetime risk in first world countries is 12–20% 70% of people with gall bladder stones are asymptomatic, but risk of developing symptoms is about 15% over 20 years Cholecystectomy almost never indicated for asymptomatic stones Complications: acute cholecystitis (may lead to empyema, perforation, cholecystoenteric fistula), obstructive jaundice, cholangitis (infection with pain) and acute pancreatitis (pancreatic duct obstruction)

Gallstone facts

This condition, which causes biliary ‘colic’ due to spasm of the sphincter of Oddi, often follows prolonged fasting. Cholecystectomy may be necessary

Microlithiasis (biliary ‘sludge’)

is associated with gallstones in over 90% of cases18 and there is usually a past history of biliary pain. It occurs when a calculus becomes impacted in the cystic duct and inflammation develops. It is very common in the elderly. The acute attack is often precipitated by a large or fatty meal. The causative organisms are usually aerobic bowel flora (e.g. E. coli, Klebsiella species and Enterococcus faecalis).

Acute cholecystitis

Clinical features Steady severe pain and tenderness Localised to right hypochondrium or epigastrium May be referred to the right infrascapular area Anorexia, nausea and vomiting (bile) in about 75%

Acute cholecystitis

``` Aggravated by deep inspiration Signs Patient tends to lie still Localised tenderness over gall bladder (positive Murphy sign) Muscle guarding Rebound tenderness Palpable gall bladder (approximately 15%) Jaundice (approximately 15%) ± Fever ```

Acute cholecystitis

``` Diagnosis Ultrasound: gallstones but not specific for cholecystitis HIDA scan: demonstrates obstructed cystic duct—the usual cause WCC and CRP: can be elevated Treatment Bed rest IV fluids Nil orally Analgesics Antibiotics Cholecystectomy If evidence of sepsis, use amoxi/ampicillin 1 g IV, 6 hourly plus gentamicin 4–6 ```

Acute cholecystitis

With acute pancreatitis there may be a past history of previous attacks or a past history of alcoholism (35%) or gallstone disease (40–50%). It is commonly precipitated by fatty foods and alcohol, mumps, hypertriglyceridaemia and some antidiabetic medications, e.g. gliptins.

Acute pancreatitis

``` Typical clinical features are: sudden onset of severe constant deep epigastric pain but onset can be steady lasts hours or a day or so pain may radiate to back pain may be relieved by sitting forwards ```

Acute pancreatitis

nausea and vomiting | sweating and weakness

Acute pancreatitis

DxT severe pain + nausea and vomiting + relative lack of abdominal signs →

Acute pancreatitis

Signs Patient is weak, pale, sweating and anxious Tender in epigastrium Lack of guarding, rigidity or rebound Reduced bowel sounds (may be absent if ileus) ± Abdominal distension Fever, tachycardia ± shock

Acute pancreatitis

Diagnosis WCC—leucocytosis Serum lipase (preferred as more sensitive and specific) or serum amylase CRP—elevated Serum glucose ↑, calcium ↓ Blood gases: PaO2 (?pulmonary complications) LFTs: ?obstructive pattern Plain X-ray, may be sentinel loop CT scan, best after 48 hours (especially for complications) Ultrasound better for detecting cysts and unsuspected gallstones

Acute pancreatitis

Management19 Arrange admission to hospital (but many cases are mild). Basic treatment is bed rest, nil orally, nasogastric suction (if vomiting), IV fluids and analgesics (morphine). Treat hyperglycaemia or hypocalcaemia.

Acute pancreatitis

Use morphine 2.5–5 mg IV or fentanyl 30–100 mcg IV statim then titrate to effect. May require ERCP if obstructive LFTs.

Acute pancreatitis

This IgG4-related disorder presents with abdominal pain, jaundice and weight loss. Diagnosis is by a pancreatic mass or enlargement on imaging and serology (IgG4). Treatment is with corticosteroids.

Autoimmune pancreatitis

In comparison to acute pancreatitis, the pain of chronic pancreatitis is milder but more persistent. There may be epigastric pain boring through to the back. Symptoms may relapse and worsen. Investigate with CT scan and ultrasound and faecal elastase (N >200 μg/g stool: pancreastic exocrine insufficiency < 200 μg/g stool). MRCP is the most sensitive imaging study. The person with this problem is often labelled as ‘gastritis’, ‘ulcer’ or even ‘neurotic’ because of the indeterminate nature of the pain. Malabsorption and diabetes may result from pancreatitis. Weight loss and steatorrhoea become prominent features.

Chronic pancreatitis

Pain associated with pancreatic cancer is indistinguishable from that of chronic pancreatitis but generally tends to be more severe and more prominent in the back. Use paracetamol for pain. Give pancreatic enzyme supplements (e.g. pancrelipase) for malabsorption.

Chronic pancreatitis

The person with acute diverticulitis is usually over 40 years of age, with longstanding, grumbling, left-sided abdominal pain and constipation, but can have an irregular bowel habit. It occurs in less than 10% of those with diverticular disorder

Acute diverticulitis

Typical clinical features are: acute onset of pain in the left iliac fossa pain increased with walking and change of position usually associated with constipation

Acute diverticulitis

DxT acute pain + left-sided radiation + fever →

Acute diverticulitis

Signs Tenderness, guarding and rigidity in LIF Fever

Acute diverticulitis

``` Investigations FBE: leucocytosis Elevated ESR Pus and blood in stools Abdominal ultrasound/CT scan (especially—can detect fistula, abscess or perforation) Erect chest X-ray Erect and supine abdominal X-ray ```

Acute diverticulitis

``` Complications Bleeding (can be profuse, especially in elderly) Perforation (high mortality) Abscess Peritonitis Fistula (bladder, vagina, small bowel) Intestinal obstruction ```

Acute diverticulitis

Treatment19 Hospital admission (unless mild) Rest the GIT: nil orally, drip and suction One landmark study showed that a ‘wait and see’ approach without antibiotics can be considered appropriate in patients with an uncomplicated initial attack of diverticulitis20 Analgesics Antibiotics: mild cases: amoxicillin + clavulanate 875/125 mg (o) 12 hourly for 5 days or metronidazole + cephalexin

Acute diverticulitis

``` severe cases: amoxi/ampicillin 1 g IV 6 hourly + gentamicin 5–7 mg/kg IV/day + metronidazole 500 mg IV 12 hourly or metronidazole + ceftriaxone 1 g IV/day Surgery for complications Screening colonoscopy after acute episode ```

Acute diverticulitis

Can be generalised due to intra-abdominal sepsis following perforation of a viscus, e.g. peptic ulcer, appendix, diverticulum. Typical signs are as for perforated peptic ulcer. Key investigations are peritoneal fluid culture and CT scan. Surgical intervention is usually required. Usual antibiotic treatment is IV cephalosporins or amoxi/ampicillin + gentamicin + metronidazole.21 Spontaneous bacterial peritonitis can occur in any patient with ascites.

Peritonitis

``` Older person Nocturnal pain or diarrhoea Progressive symptoms Rectal bleeding Fever Anaemia Weight loss Abdominal mass Faecal incontinence or urgency (recent onset) ```

Red flags for organic disease12

It is possible to have recurrent episodes of subacute inflammation of the appendix. If suspected, laparoscopy performed during or soon after an attack is diagnostic.

Chronic appendicitis

There is no firm evidence that intra-abdominal adhesions are painful apart from complications such as bowel obstruction. Sometimes patients are ‘cured’ by laparoscopic divisions of adhesions.

Adhesions

Usually central epigastric pain Burning pain Relieved by antacids or food or milk DU: usually 2–3 hours after meals or wakes from sleep GU: may occur after meals but inconsistent relationship to eating

Peptic ulcer (gastric or duodenal

Special caution is required at the extremes of age when the symptoms and signs do not often reflect the seriousness of the underlying pathology. If an elderly person presents with intense acute abdominal pain, inadequately relieved by strong parenteral injections, likely causes include mesenteric artery occlusion, acute pancreatitis and ruptured or dissecting aortic aneurysm. When an inflamed appendix ruptures, the abdominal pain improves for a significant period of time. Consider gallstones and duodenal ulcer if the person is woken (e.g. at 2–3 am) with abdominal pain. Pus cells and red cells may be present in the urine with appendicitis when a pelvic appendix involves the bladder and a retrocaecal appendix involves the ureter. Consider diabetic ketoacidosis in a person with abdominal pain, tenderness and rigidity and deep sighing respiration.

Practice tips acute abdomen

The commonest cause was osteoarthritis (OA), which affects 5–10% of the population.

Arthritis

Almost 2% of Australians report having rheumatoid arthritis (RA).

Arthritis

Systemic diseases that may predispose to, or present with, an arthropathy include the connective tissue disorders, diabetes mellitus, a bleeding disorder, previous tuberculosis, the spondyloarthropathies such as psoriasis, SBE, hepatitis B, rheumatic fever, the various vasculitic or arteritic syndromes (the vasculitides) such as Wegener granulomatosis, HIV infection, lung cancer, haemochromatosis, sarcoidosis, hyperparathyroidism, Whipple disease and

Arthritis

The pain of inflammatory disease is worse at rest (e.g. on waking in the morning, also with stiffness) and improved by activity

Arthritis

Early diagnosis and management of RA results in considerably better outcomes. Causes of monoarthritis include crystal deposition disease, sepsis, osteoarthritis, trauma and spondyloarthritis.

Arthritis

Gout and septic arthritis have a recognised cause and cure. Acute gout is 4–6 times more prevalent in men than women; however, it becomes more common in postmenopausal women, particularly those on thiazide diuretics.

Arthritis

OA is very common in general practice. It may be primary, which is usually symmetrical, and can affect many joints. This clinical pattern is different from secondary OA, which follows injury and other wear-and-tear causes.

Arthritis

``` Acute onset Polyarthritis Symmetric inflammation Mainly hands and feet Rash—persists for 24 hours minimum Terminates rapidly—over days FBE: lymphopaenia, lymphocytosis, ± atypical lymphocytes ```

Clinical features (viral arthritis)

``` It tends to terminate quickly and spontaneously without permanent damage to joints. It is caused by many viruses, including those causing influenza, mumps, rubella, varicella, hepatitis B and C, infectious mononucleosis (more muscle aching), cytomegalovirus, parvovirus, Australian epidemic polyarthritis due to the alphaviruses, Ross River virus and Barmah Forest virus. Adenovirus is common in children. COVID-19 causes arthralgia in around 15% of cases ```

Clinical features (viral arthritis)

``` Fever Weight loss Profuse rash Lymphadenopathy Cardiac murmur Severe pain and disability Malaise and fatigue Vasculitic signs Two or more systems involved ```

Red flag pointers for polyarthritis

A common pitfall is ________, particularly in older women taking diuretics, whose osteoarthritic joints, especially of the hand, can be affected. The condition is often referred to as nodular gout and does not usually present as acute arthritis.

gout

Another ‘trap’ is ______________in a patient with a bleeding disorder.

haemarthrosis

__________________________ usually affects the hands and is generally symmetrical. The drugs may induce autoantibodies (e.g. ANA, ANCA). Those that induce a lupus syndrome include the antiepileptics, chlorpromazine and some cardiac drugs. Various antibiotics have been associated with arthralgia, e.g. minocycline, while diuretics, especially frusemide and thiazides, can precipitate gout. The problem usually resolves promptly after withdrawal of the agent

Drug-induced arthritis

Intravenous drug abuse may be associated with septic arthritis, hepatitis B and C, HIV-associated arthropathy, SBE with arthritis and serum sickness reactions.

Drug-induced arthritis

A very hot, red, swollen joint suggests either infection or _______________arthritis.

crystal

also known as juvenile chronic arthritis and juvenile rheumatoid arthritis (US), is defined as a chronic arthritis persisting for a minimum of 6 weeks (some criteria suggest 3 months) in one or more joints in a child younger than 16 years.8 It is rare, affecting only about 1 in 1000 children, but produces profound medical and psychosocial problems.

Juvenile idiopathic arthritis

The commonest types of JIA are oligoarticular (pauciarticular) arthritis, affecting four or fewer joints (about 50%), and polyarticular arthritis, affecting five or more joints (about 40%). Systemic onset arthritis, previously known as Still syndrome, accounts for about 10% of cases.

Juvenile idiopathic arthritis

is usually seen in children under the age of 5 but can occur throughout childhood. The child can present with a high remittent fever and coppery red rash, plus other features, including lymphadenopathy, splenomegaly and pericarditis. Arthritis is not an initial feature but develops ultimately, usually involving the small joints of the hands, wrists, knees, ankles and metatarsophalangeal joints.

Juvenile idiopathic arthritis

These children should be referred once the problem is suspected or recognised. JIA is not a benign disease—50% have persistent active disease as adults.

Juvenile idiopathic arthritis

is an inflammatory disorder that typically occurs in children and young adults following a group A Streptococcus pyogenes infection. It is common in developing countries and among Aboriginal and Torres Strait Islander people (see CHAPTER 127 ) but uncommon in first world countries

Rheumatic fever

Age 5–15 years (can be older) Acute-onset fever, joint pains, malaise Flitting arthralgia mainly in leg (knees, ankles) and arm (elbows and wrists) One joint settles as the other is affected May follow a sore throat However, the symptoms depend on the organs affected and arthritis may be absent

Rheumatic fever

``` Based on clinical criteria: 2 or more major criteria or 1 major + 2 or more minor criteria in the presence of supporting evidence of preceding Group A streptococcal (GAS) infection. ```

Rheumatic fever

Major criteria Carditis Polyarthritis Chorea (involuntary abnormal movements) Subcutaneous nodules—in crops on elbows, wrists, knees or ankles Erythema marginatum—spread in a circular fashion

Rheumatic fever

``` Minor criteria Fever (≥38°C) Previous RF or rheumatic heart disease Monoarthralgia Raised ESR >30 mm/hr or CRP >30 mg/L ECG—prolonged PR interval ```

Rheumatic fever

``` Investigations A selective combination of: FBC throat swab for GAS ESR/CRP streptococcal ASOT streptococcal anti-DNase B (repeat in 10–14 days) plus ECG and echocardiogram (if ↑ PR) and CXR ```

Rheumatic fever

Treatment Rest in bed (if carditis, for up to 2 weeks) GAS sensitive antibiotics, e.g. benzathine penicillin 900 mg IM (450 mg in child <20 kg) statim or phenoxymethylpenicillin 500 mg (o) bd 10 days Paracetamol 15 mg/kg (o) 4 hourly (max. 60 mg/kg/day); aspirin or naproxen for arthritis Diuretics for carditis (may be ACE inhibitor and corticosteroids) Prophylactic long-term penicillin

Rheumatic fever

can affect any joint at any age, although it is more common in children. It evolves over hours or days and can rapidly destroy a joint structure. It is an emergency in the hip joint of children. Check for IV drug use. The commonest organisms are S. aureus, Streptococci, Kingella kingae and N. gonorrhoea. Diagnosis is by blood culture and synovial fluid analysis and culture. Treatment is with drainage and washout of the joint and IV followed by oral antibiotics, e.g. di/flucloxacillin. Orthopaedic referral recommended

Septic arthritis

OA is very common with advancing age and for this reason care has to be taken not to simply attribute other causes of arthritis to OA. Other musculoskeletal conditions that become more prevalent with increasing age are:

Arthritis in the elderly

``` polymyalgia rheumatica Paget disease of bone avascular necrosis gout pseudogout (pyrophosphate arthropathy) malignancy (e.g. bronchial carcinoma) ```

Arthritis in the elderly

This crystal deposition arthropathy (chondrocalcinosis) is noted by its occurrence in people over 60 years. It usually affects the knee joint but can involve other joints

Pseudogout

Although it usually begins between the ages of 30 and 40 it can occur in older people, when it occasionally begins suddenly and dramatically. This is called ‘explosive’ RA and fortunately tends to respond to small doses of prednisolone and has a good prognosis.13 RA in the elderly can present as a polymyalgia rheumatica syndrome.

Rheumatoid arthritis

is the most common type of arthritis, occurring in about 10% of the adult population and in 50% of those aged over 60.12 It is a degenerative disease of cartilage and may be primary idiopathic or secondary to causes such as trauma and mechanical problems, septic arthritis, crystallopathy or previous inflammatory disorders, or structural disorders such as SCFE and Perthes disorder. OA of the hips and knees has a strong association with being overweight or obese.

Osteoarthritis

Primary OA is usually symmetrical and can affect many joints. Unlike other inflammatory disease the pain is worse on initiating movement and loading the joint, and eased by rest. OA is usually associated with stiffness, especially after activity, in contrast to RA.

Osteoarthritis

``` In primary OA all the synovial joints may be involved, but the main ones are: first carpometacarpal (CMC) joint of thumb first metatarsophalangeal (MTP) joint of great toe distal interphalangeal (DIP) joints of hands Other joints that are affected significantly are the proximal interphalangeal joints, the knees, hips, acromioclavicular joints and joints of the spine, especially the facet joints of the cervical (C5–6, C6–7) and lumbar regions (L3–4, L4–5, L5–S1) ```

Osteoarthritis

Pain: worse by the end of the day, aggravated by use, relieved by rest, worse in cold and damp Variable morning stiffness Variable disability

Osteoarthritis

Hard and bony swelling Crepitus Signs of inflammation (mild), warmth, pain Restricted movements; inability to weight bear Joint deformity Note: There should be no systemic manifestations

Osteoarthritis

Crystal arthropathy can complicate OA, especially in the fingers of people taking diuretics (e.g. nodular gout).

Osteoarthritis

OA does not exhibit the typical inflammatory pattern. The clinical diagnosis is based on: gradual onset of pain after activity (worse towards the end of the day) the pattern of joint involvement the lack of soft tissue swelling the transient nature of the joint stiffness or gelling takes <30 minutes to settle after rest while inflammatory arthritis takes at least 30 minutes

Osteoarthritis

X-ray findings Joint space narrowing with sclerosis of subchondral bone Formation of osteophytes on the joint margins or in ligamentous attachments Cystic areas in the subchondral bone Altered shape of bone ends

Osteoarthritis

Provide explanation and reassurance, including patient education hand-outs Correct modifiable risk factors: obesity, injury, overuse Control pain and maintain function with appropriate drugs Suggest judicious activity, exercise and physical therapy: regular exercise has strong evidence of benefit for hip and knee OA; discourage exercise avoidance14 For weight-bearing joints, there is evidence for weight loss of at least 5–7.5% for those with BMI >25 kg/m2 Consider factors lowering the coping threshold (e.g. stress, depression, anxiety, overactivity)

Osteoarthritis

Referral for surgery should be used judiciously, as surgeons differ in their enthusiasm for following the best independent evidence for surgical interventions. For example, the Australian Knee Society’s arthroscopy ‘position statement’15 recommends against arthroscopy for knee OA except in a small number of circumstances (particularly knee locking), which goes against the vast majority of those having had debridement or meniscectomies in the age of arthroscopies. Refer for consideration of joint replacement and for advice on joints causing intractable pain or disability. Hand surgery can offer good pain relief and functional improvement. Osteotomies have a limited place for a varus or valgus deformity of the knee.

Osteoarthritis

Explanation. Provide patient education and reassurance that arthritis is not the crippling disease perceived by most patients. Exercise. A graduated exercise program is essential to maintain joint function. Aim for a good balance of relative rest with sensible exercise. It is necessary to stop or modify any exercise or activity that increases the pain. Systematic reviews have found that both exercise and education may help reduce the pain and disability in people with OA of the hip or knee.16 Diet. If overweight it is important to reduce weight to ideal level. Obesity increases the risk of OA of the knee approximately fourfold and weight loss may slow progression;17 otherwise, no specific diet has been proven to cause or improve OA.

Osteoarthritis

Rest. Prolonged bed rest is contraindicated, and exercise is important. However, rest during an active bout of inflammatory activity is reasonable as a pain reduction strategy. Heat. Recommended is a hot-water bottle or other heat pack, warm bath or electric blanket to soothe pain and stiffness. Advise against getting too cold. Do not advise using local cold packs, as they have been shown not to help. Physiotherapy. Referral should be made for specific purposes such as: correct posture and/or leg length disparity (but beware of the increasing unscientific use of this term) supervision of a hydrotherapy program heat therapy and advice on simple home heat measures teaching and supervision of isometric strengthening exercises (e.g. for the neck, back, quadriceps muscle) therapeutic ultrasound, kinesio taping and electrical or laser stimulation have not been demonstrated to work; discourage such practices. Occupational therapy. Refer for advice on aids in the home, more efficient performance of daily living activities, protection of joints and on the wide range of inexpensive equipment and

Osteoarthritis

Braces, orthotics, walking aids. A walking stick or wheelie walker may help. However, realignment braces for medial compartment or patellofemoral OA have not been shown to be helpful, nor have lateral wedge shoe insoles or knee taping. Advise sensible, supportive footwear.

Osteoarthritis

Paracetamol. Use paracetamol (acetaminophen) regularly, or before activity. Avoid combinations containing codeine or dextropropoxyphene. The newer 665 mg products marketed specifically for OA have no great advantage over the traditional 500 mg tablets; use either.

Osteoarthritis

NSAIDs and COX-2 specific inhibitors (CSIs). These are second-line drugs for more persistent pain not relieved by paracetamol or where there is evidence of inflammation, such as pain worse with resting and nocturnal pain. Systematic reviews found that oral NSAIDs probably reduce the pain of OA but there is no good evidence that NSAIDs are superior to paracetamol or that any one of the many NSAIDs is more effective than others.16 The risk versus benefit equation always has to be weighed carefully. As a rule, use the lowest effective dose for a short period, then discontinue use if not effective. Evidence shows CSIs (celecoxib, etoricoxib) have a similar efficacy to other NSAIDs and a modest absolute reduction in GIT complications.18 Significant risks of NSAIDs are: gastric ulceration, erosion with bleeding depression of kidney function (check kidney function beforehand) hepatotoxicity Topical NSAIDs and capsaicin have been shown to have a small benefit in pain relief over topical placebo preparations.12 Note: Change to a suppository form will not necessarily render the upper GIT safe from irritation.

Osteoarthritis

Intra-articular (IA) corticosteroids. Corticosteroid injections have a modest place for offering short-term pain relief, as an adjunct to other measures. They can be particularly useful during an inflammatory episode of distressing pain and disability (e.g. a flare-up in an osteoarthritic knee), or where a joint replacement is either under consideration or contraindicated due to comorbidities or age.

Osteoarthritis

Surgery. Refer for surgical intervention if debilitating and intractable pain or disability, and when considering joint replacement. However, keep up to date with evidence from blinded ‘surgery vs sham-surgery trials’ and systematic reviews that suggest that the historic enthusiasm for knee and shoulder arthroscopies is no longer justifiable except in limited circumstances

Osteoarthritis

Glucosamine, chondroitin, vitamin D, omega-3 fatty acids. Evidence originally supporting oral glucosamine was from small trials prone to bias, including publication bias. Systematic

Osteoarthritis

Bisphosphonates. These are used to prevent osteoporotic fractures, where appropriate, but do not advise they will have any impact on OA symptoms. Contraindicated drugs. For OA these include the immunosuppressive and disease-modifying drugs such as oral corticosteroids, gold, antimalarials and cytotoxic agents. Avoid long-term opioids, which won’t help but will harm.

Osteoarthritis

which is an autoimmune symmetrical polyarticular systemic disease of unknown aetiology, is the commonest chronic inflammatory polyarthritis and affects about 1–2% of the population. The disorder can vary from a mild to a most severe debilitating expression. About 10–20% of patients have a relentless progression and require aggressive drug therapy.21 Urgent referral to a specialist is recommended. Genetic factors may represent a risk of 15–70% of developing RA.

Rheumatoid arthritis

generally presents with the insidious onset of pain and stiffness of the small joints of the hands and feet. The pain is persistent rather than fleeting and mainly affects the fingers where symmetrical involvement of the PIP joints produces spindling while the metacarpophalangeal joints develop diffuse thickening, as does the wrist (see FIG. 25.8 ). In 25% of cases RA presents as arthritis of a single joint such as the knee,13 a situation leading to confusion with a spondyloarthropathy. Differential diagnosis is polyarticular gout.

Rheumatoid arthritis

``` Hands: MCP and PIP joints, DIP joints (30%) Wrist and elbows Feet: MTP joints, tarsal joints (not IP joints), ankle Knees (common) and hip (delayed—up to 50%) Shoulder (glenohumeral) joints Temporomandibular joints Cervical spine (not lumbar spine) ```

Rheumatoid arthritis

Clinical features Insidious onset but can begin acutely (explosive RA) Any age 10–75 years: peak 30–50 years but bimodal 25–50 (peak age) and 65–75 Female to male ratio = 3:1 Joint pain: worse on waking, nocturnal pain, disturbed sleep; relieved with activity

Rheumatoid arthritis

Morning stiffness—can last hours Rest stiffness (e.g. after sitting) General: malaise, weakness, weight loss, fatigue Disability according to involvement

Rheumatoid arthritis

Soft swelling (effusion and synovial swelling), especially of wrist, MCP and PIP joints, nodules Warmth Tenderness on pressure or movement Limitation of movement Muscle wasting Later stages: deformity, subluxation, instability or ankylosing Look for swan necking, boutonnière and z deformities, ulnar deviation

Rheumatoid arthritis

``` Check for a number of everyday functions, for example: power grip (lifting a jug of water) precision grip (using a key or pen), undoing buttons hook grip (carrying a bag) ```

Rheumatoid arthritis

Investigations ESR/CRP usually raised according to activity of disease Anaemia (normochromic and normocytic) may be present Rheumatoid factor positive in about 70–80% (less frequent in early disease) 15–25% of RA patients will remain negative21

Rheumatoid arthritis

``` Anti-cyclic citrullinated peptide (anti-CCP) antibodies: more specific for RA (94% specificity)12 X-ray changes: erosion of joint margin loss of joint space (may be destruction) juxta-articular osteoporosis cysts advanced: subluxation or ankylosing MRI—helpful for early diagnosis ```

Rheumatoid arthritis

Family history of inflammatory arthritis Symptom duration of >6 weeks Early-morning stiffness of >1 hour Arthritis in three or more regions Swelling in five or more joints Bilateral compression tenderness of the metatarsophalangeal joints Symmetry of the areas affected Presence of rheumatoid nodules Rheumatoid factor positivity Raised inflammatory markers (ESR/CRP) in absence of infection Anticyclic citrullinated peptide antibody positivity Bony erosions evident on radiographs of the hands or feet, although these are uncommon in early disease

Rheumatoid arthritis

If the RA factor is positive, it is non-specific—order the anti-CCP antibody to confirm the diagnosis. RA has a strong cardiovascular risk factor.

Rheumatoid arthritis

Give patient education support and appropriate reassurance. The diagnosis generally has distressful implications, and so the patient and family require careful explanation and support. Some have little or no long-term problems but even in mild cases, continuing care and medical supervision is important. There has been a radical shift from palliation to early induction of disease remission, to prevent joint damage and reduce morbidity from malignancy (especially lymphoma) and cardiovascular disease. Since many studies show disease progression in the first 2 years, relative aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) from the outset is advisable, rather than to start stepwise with analgesics and NSAIDs only.23 Use a team approach where appropriate, including an early specialist referral for obvious or suspected RA or positive anti-CCP for diagnosis and collaborative support. Fully assess the person’s functional impairment and impact on home life, work and social activity. Involve the family in decision making. Make judicious use of pharmaceutical agents. For serious cases, consultant collaboration is essential. Review regularly, continually assessing progress and drug tolerance. The disease activity can be monitored with plain X-rays, ultrasound of hands (especially if hands are thick), CRP ± ESR.

Rheumatoid arthritis

Rest and splinting. This is necessary where practical for any acute flare-up of arthritis.

Rheumatoid arthritis

Exercise. It is important to have regular exercise, especially walking and swimming. Have hydrotherapy in heated pools.

Rheumatoid arthritis

Smoking cessation. This is strongly recommended. Referral. Referring to physiotherapists and occupational therapists for expertise in exercise supervision, physical therapy and advice regarding coping in the home and work is important.

Rheumatoid arthritis

Joint movement. Each affected joint should be put daily through a full range of motion to keep it mobile and reduce stiffness. Diet. Although there is no special diet that seems to cause or cure RA, a nourishing, wellbalanced diet is common sense and obesity must be avoided. Some evidence supports both a

Rheumatoid arthritis

``` Education (rest, literature, weight loss, joint protection advice) NSAIDs Simple analgesics DMARDs: Conventional synthetic DMARDs Immunosuppressants: azathioprine cyclosporin leflunomide methotrexate Biological DMARDs Cytokine inhibitors anti-TNF α agents: abatacept, adalimumab, certolizumab, etanercept, infliximab, golimumab, rituximab anti-interleukin-1 agents; tocilizumab ```

Rheumatoid arthritis

``` Gold salts Quinolones: hydroxychloroquine chloroquine Others: D-penicillamine sulfasalazine Glucocorticoids: oral prednisolone intra-articular intravenous (steroid ‘pulses’) Fish body oil Physical therapy (hydrotherapy, isometric exercises) Occupational therapy (splints, aids and appliances) Orthopaedic surgery (synovectomy, joint replacement, arthrodesis, plastic hand surgery) ```

Rheumatoid arthritis

Beware of the increased risk of infection in patients on combination DMARD regimes. When indicated, vaccination for pneumococcus, influenza, hepatitis A and B and HPV is recommended for all DMARDs. Any pain should be managed with paracetamol or NSAIDs. Avoid opioid analgesics if possible. Glucocorticoids are appropriate for flares of RA.

Rheumatoid arthritis

NSAIDs are effective and still have a place, but the adverse effects are a problem. The use of DMARDs and biological DMARDs improves long-term outcomes. Methotrexate is the ‘backbone’ of treatment, and should be continued when starting other DMARDs. Supplementation with folic acid can improve gastrointestinal symptoms and reduce the risk of liver dysfunction.

Rheumatoid arthritis

Oral use should be considered in those with severe disease as a temporary adjunct to DMARD therapy and where other treatments have failed or are contraindicated. The dose is prednisolone 10 mg (o) daily. Avoid doses higher than 15 mg daily if possible. Intra-articular injections of depot preparations are effective in larger joints.

Rheumatoid arthritis

These agents target synovial inflammation and prevent joint damage. The choice depends on several factors, but is best left to the specialist coordinating care. In most patients with recently diagnosed RA, methotrexate is the cornerstone of management and should be commenced as early as possible. Initial dose: methotrexate 5–10 mg (o) once weekly on a specified day, increasing to maximum of 25 mg weekly or SC depending on clinical response and toxicity. Add folic acid 5–10 mg twice weekly (not on the day methotrexate is given).12 Biological DMARDs (bDMARDs) are the newer agents, which should be considered if remission is not achieved with appropriate methotrexate monotherapy, ‘triple therapy’ or other combinations. All bDMARDs are more effective when combined with methotrexate. As a rule, don’t use two biologicals together

Rheumatoid arthritis

Monotherapy with methotrexate (or occasionally another DMARD) is standard. Less than 20% will reach disease remission; if not achieved, increase the dose or consider combination therapy. Many people are managed on conventional DMARDs. Combination therapy Consider standard triple therapy: methotrexate + sulfasalazine + hydroxychloroquine. Triple therapy can be used if methotrexate monotherapy has failed or initially on diagnosis, depending on the severity of the disease. Monitoring for FBE, LFTs and annual eye checks is necessary. Several other double combinations may be used (e.g. methotrexate with cyclosporin, leflunomide or a bDMARD).

Rheumatoid arthritis

``` Arthritis, which can be acute, chronic or asymptomatic, is caused by a variety of crystal deposits in joints. The three main types of crystal arthritis are monosodium urate (gout), calcium pyrophosphate dihydrate (CPPD) and calcium phosphate (usually hydroxyapatite). ```

Crystal arthritis

is an abnormality of uric acid metabolism resulting in hyperuricaemia and urate crystal deposition.