Rheumatology

Question 1

What is JIA?

Answer 1

Juvenile idiopathic arthritis (JIA) refers to a condition affecting children and adolescents where autoimmune inflammation occurs in the joints.

It is diagnosed where there is arthritis without any other cause, lasting more than 6 weeks in a patient under the age of 16.

It has also been known as juvenile chronic arthritis and juvenile rheumatoid arthritis.

Question 2

When is JIA diagnosed?

Answer 2

Arthritis without any other cause

Lasting more than 6 weeks

In a patient under the age of 16

Question 3

Key features of JIA

Answer 3

Inflammatory arthritis

Joint pain

Swelling

Stiffness

Question 4

Five key subtypes of JIA

Answer 4

Systemic JIA

Polyarticular JIA

Oligoarticular JIA

Enthesitis related arthritis

Juvenile psoriatic arthritis

Question 5

What condition is commonly known as Still’s disease?

Answer 5

Systemic juvenile idiopathic arthritis

Question 6

Clinical features of systemic JIA

Answer 6

Subtle salmon-pink rash

High swinging fevers

Enlarged lymph nodes

Weight loss

Joint inflammation and pain

Splenomegaly

Muscle pain

Pleuritis and pericarditis

Question 7

Blood abnormalities in systemic JIA?

Answer 7

Antinuclear antibodies and rheumatoid factors are typically negative.

There will be raised
- inflammatory markers, with raised CRP, ESR
- platelets and serum ferritin.

Question 8

Key complication of Systemic JIA, and its presentation?

Answer 8

A key complication is macrophage activation syndrome (MAS), where there is severe activation of the immune system with a massive inflammatory response.

It presents with an acutely unwell child with disseminated intravascular coagulation (DIC), anaemia, thrombocytopenia, bleeding and a non-blanching rash. It is life threatening.

A key investigation finding is a low ESR.

Question 9

What is polyarticular JIA and what pattern does it follow?

Answer 9

Polyarticular JIA involves idiopathic inflammatory arthritis in 5 joints or more.

The inflammatory arthritis tends to be symmetrical and can affect the small joints of the hands and feet, as well as the large joints such as the hips and knees.

Question 10

Polyarticular JIA - systemic symptoms

Answer 10

There are minimal systemic symptoms, but there can be mild fever, anaemia and reduced growth. Systemic symptoms are mild, unlike systemic onset JIA.

Question 11

Polyarticular JIA vs RA

Answer 11

Polyarticular JIA is the equivalent of rheumatoid arthritis in adults.

Most children are negative for rheumatoid factor and are described as “seronegative”.

When rheumatoid factor is positive they are described as “seropositive”. Seropositive patients tend to be older children and adolescents and the disease pattern is more similar to rheumatoid arthritis in adults.

Question 12

What is oligoarticular JIA and what pattern does it follow?

Answer 12

This is also knowns as pauciarticular JIA. It involves 4 joints or less. Usually it only affects a single joint, which is described as a monoarthritis. It tends to affect the larger joints, often the knee or ankle.

Question 13

In which patients does oligoarticular JIA occur more frequently?

Answer 13

Girls under 6 years

Question 14

Blood abnormalities in oligoarticular JIA?

Answer 14

Patients tend not to have any systemic symptoms and inflammatory makers will be normal or mildly elevated.

Antinuclear antibodies are often positive

Rheumatoid factor is usually negative

Question 15

What is a classic associated feature with oligoarticular JIA and who should patients with this be seen by?

Answer 15

Anterior uveitis

Patients should be referred to an ophthalmologist for management and follow up of uveitis.

Question 16

Which patients are affected by enthesitis related arthritis?

Answer 16

Enthesitis-related arthritis is more common in male children over 6 years. It can be thought of as the paediatric version of the seronegative spondyloarthropathy group of conditions that affect adults

Question 17

What is enthesitis-related arthritis?

Answer 17

An enthesis is the point at which the tendon of a muscle inserts into a bone. Enthesitis is inflammation of this insertion point.

Patients have inflammatory arthritis in the joints as well as enthesitis.

Question 18

Why might enthesitis occur?

Answer 18

Traumatic stress e.g. repetitive strain during sports

Autoimmune inflammatory process

Question 19

Investigating enthesitis-related arthritis?

Answer 19

MRI scan of the affected joint can demonstrate enthesitis (but cannot distinguish between an enthesitis due to stress or an autoimmune process)

GENETIC TESTING: The majority of patients with enthesitis-related arthritis have the HLA B27 gene.

OPTHAMOLOGY SCREENING: Patients with enthesitis-related arthritis are prone to anterior uveitis, and should see an ophthalmologist for screening, even if they are asymptomatic.

CONSIDER: When assessing patients for enthesitis-related arthritis, consider signs and symptoms of psoriasis (psoriatic plaques and nail pitting) and inflammatory bowel disease (intermitted diarrhoea and rectal bleeding)

Question 20

When assessing patients for enthesitis-related arthritis, consider signs and symptoms of what other conditions?

Answer 20

Psoriasis

IBD

Anterior uveitis

Question 21

Patients with enthesitis will be tender to localised palpation of the entheses. Therefore it is worth palpating key areas to elicit tenderness of the entheses at which points?

Answer 21

Interphalangeal joints in the hand
Wrist
Over the greater trochanter on the lateral aspect of the hip
Quadriceps insertion at the anterior superior iliac spine
Quadriceps and patella tendon insertion around the patella
Base of achilles, at the calcaneus
Metatarsal heads on the base of the foot

Question 22

Juvenile psoriatic arthritis is associated with what signs on examination?

Answer 22

Plaques of psoriasis on the skin
Pitting of the nails (nail pitting)
Onycholysis, separation of the nail from the nail bed
Dactylitis, inflammation of the full finger
Enthesitis, inflammation of the entheses, which are the points of insertion of tendons into bone

Question 23

Patten of join involvement in Juvenile Psoriatic Arthritis?

Answer 23

The pattern of joint involvement varies. Patients can have a symmetrical polyarthritis affecting the small joints similar to rheumatoid, or an asymmetrical arthritis affecting the large joints in the lower limb.

Question 24

What is Psoriatic arthritis?

Answer 24

Psoriatic arthritis is an seronegative inflammatory arthritis associated with psoriasis, the skin condition.

Question 25

Management of Juvenile Idiopathic Arthritis

Answer 25

The management should be coordinated by a specialist in paediatric rheumatology, with a specialist multi-disciplinary team. The aim of treatment is to reduce inflammation within the joints, minimise symptoms and maximise function. Medical treatment depends on the severity and response, and involves: NSAIDs, such as ibuprofen Steroids, either oral, intramuscular or intra-artricular in oligoarthritis Disease modifying anti-rheumatic drugs (DMARDs), such as methotrexate, sulfasalazine and leflunomide Biologic therapy, such as the tumour necrosis factor inhibitors etanercept, infliximab and adalimumab

Question 26

What is EDS?

Answer 26

Ehlers-Danlos syndrome (EDS) is an umbrella term that encompasses a group of genetic conditions that cause defects in collagen, resulting in hypermobility of the patient’s joints and abnormalities in connective tissue such as the skin, bones, blood vessels and organs. There are several types of Ehlers-Danlos syndrome.

Question 27

Types of Ehlers-Danlos syndrome?

Answer 27

Hypermobile Classical Ehlers-Danlos syndrome Vascular Ehlers-Danlos syndrome Kyphoscoliotic Ehlers-Danlos syndrome

Question 28

Hypermobile EDS - features and inheritance

Answer 28

Hypermobile Ehlers-Danlos syndrome represents most cases of EDS It is the most common and least severe type of Ehlers-Danlos syndrome. The key feature is joint hypermobility, but patients also have soft and stretchy skin. The gene for hypermobile EDS has not been identified and there is no single mode of inheritance.

Question 29

Classical Ehlers-Danlos syndrome features and inheritance

Answer 29

Classical Ehlers-Danlos syndrome features remarkably stretchy skin that feels smooth and velvety to touch. They also have severe joint hypermobility, joint pain and abnormal wound healing. They often develop lumps over pressure points, such as the elbows. They are prone to hernias, prolapses, mitral regurgitation and aortic root dilatation. Inheritance is autosomal dominant.

Question 30

Vascular Ehlers-Danlos syndrome - features and inheritance?

Answer 30

Vascular Ehlers-Danlos syndrome is the most dangerous form of EDS, where the blood vessels are particularly fragile as a result of defective collagen. Patients have characterise thin, translucent skin that you can almost see through. The skin, internal organs and arteries are fragile and prone to rupturing. Patients are monitored for vascular abnormalities and told to seek urgent medical attention for sudden unexplained pain or bleeding. Inheritance is autosomal dominant.

Question 31

Kyphoscoliotic Ehlers-Danlos syndrome features and inheritance

Answer 31

Kyphoscoliotic Ehlers-Danlos syndrome is characterised initially by poor tone (hypotonia) as a neonate and infant, followed by kyphoscoliosis as they grow. There is significant joint hypermobility. Patients tend to be tall and slim. There is a risk of rupture in the medium sized arteries. Inheritance is autosomal dominant.

Question 32

Which types of Ehlers-Danlos syndrome are inherited by an autosomal dominant pattern?

Answer 32

Classical Ehlers-Danlos syndrome Vascular Ehlers-Danlos syndrome Kyphoscoliotic Ehlers-Danlos syndrome

Question 33

What is the most dangerous form of EDS?

Answer 33

Vascular - skin, internal organs and arteries are fragile and prone to rupture

Question 34

Thin, translucent skin is a characteristic of which type of EDS?

Answer 34

Vascular

Question 35

Abnormal wound healing is a charecteristic of which type of EDS?

Answer 35

Classical EDS

Question 36

Which type of EDS is initially characterised by hypotonia?

Answer 36

Kyphoscoliosis EDS

Question 37

The most common presenting complaint for hypermobile EDS is joint pain and hypermobility, however abnormalities in collagen make it a multi-system disorder leading to symptoms across multiple areas of the body, such as what?

Answer 37

Soft stretchy skin Easy bruising Poor wound healing Bleeding Headaches Autonomic dysfunction causing dizziness and syncope GORD Abdo pain IBS Menorrhagia and dysmenorrhea PROM in pregnancy Urinary incontience Pelvic organ prolapse TMJ dysfunction Myopia

Question 38

Joint features in hypermobile EDS?

Answer 38

Hypermobility Joint pain after exercise or inactivity Joint dislocations (e.g. shoulders of hips)

Question 39

What tool is used to assess patients with hypermobility and how is it calculated?

Answer 39

The Beighton score is used to assess the extent of hypermobility and support the diagnosis of hypermobility syndrome. One point is scored for each side of the body, with a maximum score of 9: Palms flat on floor with straight legs (score 1) Elbows hyperextend Knees hyperextend Thumb can bend to touch the forearm Little finger hyperextends past 90 degrees

Question 40

Diagnosing hypermobile EDS

Answer 40

Diagnosis is made using the Beighton score

Question 41

What should be excluded when diagnosing EDS?

Answer 41

It is important to exclude Marfan syndrome, which also features hypermobility, by examining for features such as high arch palate, arachnodactyly and arm span.

Question 42

There is no cure for Ehlers-Danlos syndrome. Management focuses on maintaining health joints, monitoring for complications and minimising symptoms. Management involves what?

Answer 42

Follow up with relevant specialties depending on the associated complications Physiotherapy to strengthen and stabilise the joints Occupational therapy to maximise function Maintaining good posture in the joints Moderating the intensity of activity to minimise flares Psychology may be required to a help manage the chronic condition and pain

Question 43

Postural orthostatic tachycardia syndrome (POTS) can occur with hypermobile Ehlers-Danlos syndrome - what is it?

Answer 43

POTS is a result of autonomic dysfunction. This causes inappropriate tachycardia on sitting or standing up, resulting in distressing symptoms such as presyncope, syncope, headaches, disorientation, nausea and tremor.

Question 44

What common condition associated with aging are patients with EDS more likely to develop at an earlier age?

Answer 44

Hypermobility in the joints leads to additional wear and tear on the joint. This means patients with hypermobility often develop generalised osteoarthritis at an earlier age.

Question 45

What is Henoch-Schonlein Purpura?

Answer 45

Henoch-Schonlein Purpura (HSP) is an IgA vasculitis that presents with a purpuric rash affecting the lower limbs and buttocks in children. Inflammation occurs in the affected organs due to IgA deposits in the blood vessels.

Question 46

What causes inflammation in HSP?

Answer 46

Inflammation occurs in the affected organs due to IgA deposits in the blood vessels.

Question 47

Which organs are affected by Henoch-Schonlein Purpura?

Answer 47

Skin (purpuric rash) Kidneys (IgA nephritis) GI tract (abdominal pain)

Question 48

What is Henoch-Scholein Purpura often triggered by?

Answer 48

The condition is often triggered by an upper airway infection or gastroenteritis.

Question 49

In what ages is HSP most common?

Answer 49

It is most common in children under the age of 10 years.

Question 50

What are the four classic features of HSP?

Answer 50

Purpura (100%), Joint pain (75%), Abdominal pain (50%) Renal involvement (50%)

Question 51

What causes the rash in HSP?

Answer 51

The rash is caused by inflammation and leaking of blood from small blood vessels under the skin (due to IgA deposits in the blood vessels) forming purpura.

Question 52

What are purpura?

Answer 52

Purpura are red-purple lumps under the skin containing blood.

Question 53

The majority of patients with HSP have purpura - what is purpura, where do patients get affected by this, and what complication can occur?

Answer 53

They are red-purple in colour and are palpable under the skin. Typically they start on the legs and spread to the buttocks. They can also affect the trunk and arms. In severe cases, skin ulceration and necrosis can develop.

Question 54

HSP - joint manifestations?

Answer 54

75% of patients with HSP develop arthralgia or arthritis, mostly affecting the knees and ankles. The joints can become swollen and painful, with a reduced range of movement.

Question 55

HSP - GI manifestations?

Answer 55

Abdominal pain is indicative of gastrointestinal involvement. This affects around 50% of patients with HSP. In severe cases, it can lead to gastrointestinal haemorrhage, intussusception and bowel infarction.

Question 56

HSP - renal manifestations?

Answer 56

HSP affects the kidneys in around 50% of patients, causing an IgA nephritis. This is sometimes referred to as HSP nephritis. This can lead to microscopic or macroscopic haematuria and proteinuria. If there is more than 2+ of protein on the urine dipstick the child has developed nephrotic syndrome and will have a degree of oedema.

Question 57

The most important initial step in ?Henoch-Schonlein Purpura is to exclude other serious pathology, such as what?

Answer 57

- Meningococcal septicaemia and leukaemia - Idiopathic thrombocytopenic purpura and haemolytic uraemic syndrome are also differentials for a non-blanching rash

Question 58

HSP - investigations to exclude other pathology nd to assess for organ involvement?

Answer 58

Full blood count and blood film for thrombocytopenia, sepsis and leukaemia Renal profile for kidney involvement Serum albumin for nephrotic syndrome CRP for sepsis Blood cultures for sepsis Urine dipstick for proteinuria Urine protein:creatinine ratio to quantify the proteinuria Blood pressure for hypertension

Question 59

EULAR/PRINTO/PRES criteria for diagnosis of Henoch-Schonlein Purpura?

Answer 59

Palpable purpura (not petichiae) + at least one of: Diffuse abdominal pain Arthritis or arthralgia IgA deposits on histology (biopsy) Proteinuria or haematuria

Question 60

Henoch-Schonlein Purpura - management and monitoring?

Answer 60

Management is supportive, with simple analgesia, rest and proper hydration. The use of steroids is debatable, with evidence suggesting they may shorten the duration of the illness but not affect long term outcomes or rate of recurrence. Steroids may be considered by specialist doctors in patients with severe gastrointestinal pain or renal involvement. It is important that patients with HSP are monitored closely whilst the illness is active. They need close monitoring with repeated: Urine dipstick monitoring for renal involvement Blood pressure monitoring for hypertension

Question 61

HSP prognosis

Answer 61

Abdominal pain usually settles within a few days. Patients without kidney involvement can expect to fully recover within 4 to 6 weeks. A third of patients have a recurrence of the disease within 6 months. A very small proportion of patients will develop end stage renal failure.

Question 62

What is Kawasaki disease also known as?

Answer 62

Mucocutaneous lymph node syndrome.

Question 63

What type of vasculitis is mucocutaneous lymph node syndrome (Kawasaki disease)?

Answer 63

It is a systemic, medium-sized vessel vasculitis.

Question 64

In which patients is Kawasaki disease/mucocutaneous lymph node syndrome more common?

Answer 64

It affects young children, typically under 5 years. There is no clear cause or trigger. It is more common in Asian children, particularly Japanese and Korean children. It is also more common in boys

Question 65

Clinical features of Kawasaki disease (mucocutaneous lymph node syndrome)

Answer 65

Persistent high fever (above 39ºC) for more than 5 days Widespread erythematous maculopapular rash and desquamation (skin peeling) on the palms and soles Strawberry tongue (red tongue with large papillae) Cracked lips Cervical lymphadenopathy Bilateral conjunctivitis

Question 66

A rash, strawberry tongue, lymphadenopathy, conjunctivitis and a fever persisting more than 5 days in a child suggest what?

Answer 66

Kawasaki disease?

Question 67

What investigations should be performed in suspected Kawasaki disease and what might they show?

Answer 67

Full blood count can show anaemia, leukocytosis and thrombocytosis Liver function tests can show hypoalbuminemia and elevated liver enzymes Inflammatory markers (particularly ESR) are raised Urinalysis can show raised white blood cells without infection Echocardiogram can demonstrate coronary artery pathology

Question 68

Key complications of Kawasaki disease?

Answer 68

coronary artery aneurysm

Question 69

Kawasaki disease: acute phase

Answer 69

The child is most unwell with the fever, rash and lymphadenopathy. This lasts 1 – 2 weeks.

Question 70

Kawasaki disease: subacute phase

Answer 70

The acute symptoms settle (fever, maculopapular rash, lymphadenopathy), the desquamation and arthralgia occur and there is a risk of coronary artery aneurysms forming. This lasts 2 – 4 weeks

Question 71

Kawasaki disease - convalescent stage

Answer 71

The remaining symptoms settle, the blood tests slowly return to normal and the coronary aneurysms may regress. This last 2 – 4 weeks

Question 72

Management of Kawasaki disease?

Answer 72

There are two first line medical treatments given to patients with Kawasaki disease: High dose aspirin to reduce the risk of thrombosis IV immunoglobulins to reduce the risk of coronary artery aneurysms Patients will need close follow up with echocardiograms to monitor for evidence of coronary artery aneurysms.

Question 73

Kawasaki disease is one of the few scenarios where aspirin is used in children - why?

Answer 73

Aspirin is usually avoided due to the risk of Reye’s syndrome.

Question 74

What is Rheumatic fever and why does it occur?

Answer 74

Acute rheumatic fever is an autoimmune condition triggered by streptococcus bacteria. It is caused by antibodies created against the streptococcus bacteria that also target tissues in the body. It is a multi-system disorder that affects the joints, heart, skin and nervous system. It is rare in the UK due to early treatment of streptococcus with antibiotics.

Question 75

Rheumatic fever - pathophysiology

Answer 75

Rheumatic fever is caused by group A beta-haemolytic streptococcal, typically streptococcus pyogenes causing tonsillitis. The immune system creates antibodies to fight the infection. These antibodies not only target the bacteria, but also match antigens on the cells of the person’s body, for example the muscle cells in the myocardium in the heart. This results in a type 2 hypersensitivity reaction, where the immune system begins attacking cells throughout the body. This process is usually delayed 2 – 4 weeks after the initial infection.

Question 76

What organism causes Rheumatic fever?

Answer 76

Rheumatic fever is caused by group A beta-haemolytic streptococcal, typically streptococcus pyogenes causing tonsillitis.

Question 77

What type of hypersensitivity reaction occurs in rheumatic fever?

Answer 77

Type 2 hypersensitivity

Question 78

How long after initial streptococcal infection does rheumatic fever occur?

Answer 78

2-4 weeks

Question 79

Presentation of rheumatic fever?

Answer 79

The typical presentation of rheumatic fever occurs 2 – 4 weeks following a streptococcal infection, such as tonsillitis. Symptoms affect multiple systems, causing: Fever Joint pain Rash Shortness of breath Chorea Nodules

Question 80

Joint involvement in rheumatic fever?

Answer 80

Rheumatic fever causes a migratory arthritis affecting the large joints, with hot, swollen, painful joints. It is migratory because different joints become inflamed and improve at different times, giving the appearance that the arthritis is moving from one joint to the next.

Question 81

Heart involvement in rheumatic fever?

Answer 81

Carditis, or inflammation throughout the heart, with pericarditis, myocarditis and endocarditis, leads to: Tachycardia or bradycardia Murmurs from valvular heart disease, typically mitral valve disease Pericardial rub on auscultation Heart failure

Question 82

Skin involvement in rheumatic fever?

Answer 82

There are two key skin findings with rheumatic fever: Subcutaneous nodules Erythema marginatum rash Firm painless nodules occur over extensor surfaces of joints, such as the elbows. The erythema marginatum rash involves pink rings of varying sizes affecting the torso and proximal limbs.

Question 83

CNS involvement in rheumatic fever

Answer 83

Chorea is the key nervous system symptom. This involves irregular, uncontrolled and rapid movements of the limbs. This is also known as Sydenham chorea and historically as St Vitus’ Dance.

Question 84

?Rheumatic fever - investigations?

Answer 84

Throat swab for bacterial culture ASO antibody titres Echocardiogram, ECG and chest xray can assess the heart involvement

Question 85

What antibody titres are used to help support a diagnosis of rheumatic fever?

Answer 85

Anti-streptococcal antibodies (ASO)

Question 86

ASO levels following acute infection

Answer 86

Rise over 2 – 4 weeks Peak around 3 – 6 weeks Gradually falls over 3 – 12 months ASO levels are usually repeated after 2 weeks to: Confirm a negative test Assess whether levels are rising or falling

Question 87

Rheumatic fever - Jones Criteria for diagnosis

Answer 87

A diagnosis of rheumatic fever can be made when there is evidence of recent streptococcal infection, plus: Two major criteria OR One major criteria plus two minor criteria The mnemonic for the Jones criteria is JONES – FEAR. Major Criteria: J – Joint arthritis O – Organ inflammation, such as carditis N – Nodules E – Erythema marginatum rash S – Sydenham chorea Minor Criteria: Fever ECG Changes (prolonged PR interval) without carditis Arthralgia without arthritis Raised inflammatory markers (CRP and ESR)

Question 88

Jones criteria for diagnosing rheumatic fever - major

Answer 88

J – Joint arthritis O – Organ inflammation, such as carditis N – Nodules E – Erythema marginatum rash S – Sydenham chorea x2 minor + 1 major + evidence of recent streptococcal infection required for diagnosis of RF

Question 89

Jones criteria for diagnosing rheumatic fever - minor?

Answer 89

Fever ECG Changes (prolonged PR interval) without carditis Arthralgia without arthritis Raised inflammatory markers (CRP and ESR) x2 minor + 1 major + evidence of recent streptococcal infection required for diagnosis of RF

Question 90

Management of rheumatic fever?

Answer 90

Treatment of streptococcal infections with antibiotics helps prevent the development of rheumatic fever. Tonsillitis caused by streptococcus should be treated with phenoxymethylpenicillin (penicillin V) for 10 days. Patients with clinical features of rheumatic fever should be referred immediately for specialist management. Management involves medications and follow up: NSAIDs (e.g. ibuprofen) are helpful for treating joint pain Aspirin and steroids are used to treat carditis Prophylactic antibiotics (oral or intramuscular penicillin) are used to prevent further streptococcal infections and recurrence of the rheumatic fever. These are continued into adulthood. Monitoring and management of complications

Question 91

Complications of rheumatic fever?

Answer 91

Recurrence of rheumatic fever Valvular heart disease, most notably mitral stenosis Chronic heart failure

Question 92

What kind of murmur is associated with rheumatic fever?

Answer 92

Mitral stenosis potential complication: Mitral stenosis is associated with a low-pitched, rumbling, mid-diastolic murmur heard loudest over the apex. Mitral stenosis (MS) involves narrowing of the mitral valve, which results in decreased filling of the left ventricle during systole and increased left atrial pressure (due to incomplete left atrial emptying).