inflammatory conditions Flashcards
What is Systemic lupus erythematous ?
Chronic multi system Autoimmune condition - immune attacks healthy body tissue e.g o skin o joints o kidneys o brain o other organs
RISK FACTORS
0 Female sex (particulary during reproductive years)
0 Age - 15-45 years
0 Asian & African descent
0 Drugs - isoniazid,
terbinafine,
phenytoin,carbamazepine,
sulfasalazine (presumed due to its sulfonamide component)
Most common cause of clubbing in the fingers ?
Respiratory causes are the most common cause of this e.g
0 lung carcinoma
0 chronic suppurative lung disease
Suppurative - discharge or production of pus)
(used when referring to paedriatrics
– Cystic fibrosis
–Bronchiectasis (Irreversible dilation of bronchial tree - abnormal) – Primary cillary dyskinesa (congenital defect where cilia are unable to move)
0 cystic fibrosis
0 asbestos exposure
Investigation - chest radiograph
0 can have abdominal cause - less frequent.
Signs / symptoms of SLE ?
Malar / butterfly rash - raised rash across cheeks and bridge of nose .
- Photosensitive rash - appears after sun exposure .
- discoid rash
- fatigue ( found in 80 - 100 % - other SLE symptoms need to be present )
- weight loss
- fever ( present in less 50 % of pl )
0 PL with pre - existing SL with fever treated with immunosuppressants should be checked for opportunistic infections ) - oral ulcers ( 10 -45 % of people )
- alopecia - non scarring
(scarring alopecia - more common in chronic discoid lupus ) - arthralgia ( joint paint ) / arthritis ( normally multi joints )
- monoarthritis - more likely to have infective cause or avascular necosis.
- fibromyalgia - widespread musculoskeletal pain.
- Raynauds phenomenon - colour changes in the tip (Typically - from white to blue to red ) ( occurs in 50 %) - often less severe than Systemic sclerosis )
*- venous / arterial thrombosis
( presence of antiphospholipid increases risk of clots )
- Pleuritis - inflammation of lining btw lungs.
( sharp chest pain upon breathing )
Libman–Sacks endocarditis
( not caused by bacteria I.e. infective endocarditis)
pericarditis
Renal involvement is usually subclinical
- Hypertension - can be caused by underlying lupus nephritis ( inflammation of kidneys by SLE )
abdominal pain , vominting & nausea
- gastrointestinal manifestation - caused by lupus peritonitis or mesenteric artery occulsion.
Diagnosis of SLE ?
0 FBC
o leukopenia - reduced WBC ( immune system destroys them ) - In SLE - lymphopenia (more common ) & neutropenia o anaemia
o thrombocytopenia
(They don’t have to occur )
0 ESR & CRP
0 Activated PTT - (partial thromboplastin time )- Prolonged ( due to antiphospolipid antibodies.
PTT - measures how long it takes for blood clot to form - checks function of coagulation factors.
( also used to monitor pl taking heparin (coagulant medication )
0 Antinuclear anitbody (ANA) - positive - raised
0 Antibodies to dsDNA - raised - postive
0 U & E
0 Urinalysis - assess renal involvement
o Antiphospholipid test
o lupus anticoagulant (type of antiphospholipd antibody found in many people with lupus )
IF cardiopulmonary symptoms present - Chest Xray . ECG
What does a raised CRP usually indicate ?
Raised CRP - usually indicates that there is inflammation caused by infection.
e.g Raised CRP & ESR - infection
Raised ESR - inflammation - non infective.
Mostly ..
What is antiphospholipid syndrome ?
CAPS - meaning ?
Hughes syndrome / Antiphospholipid syndrome (APS )
disorder of immune system - causes increased risk of clots - Autoimmune condition
(production of antiphospholipid antibodies (abnormal ) - attach to fat phospholipid - cause blood to clot.
- greater risk of developing :
o DVT
(superfical thrombophlebitis - looks similar to DVT - but as severe , inflammation of veins under skin (usually in leg).
o arterial thrombosis - can cause High BP , Strokes, Myocardial infarction , Pulmonary emobolism.
o Blood clots in brain - problems with balance , mobility , vision , speech and memory.
(also can develop Livedo reticularis (small blood clots in the BV of skin - skin can become blotchy red or blue. - can develops sores or ulcers as a result. (often more severe in cold weather. )
Livedo - skin discoulouration
AUTOANTIBODIES CAN TARGET BLOOD COMPONENETS
Platelets - thrombocytopenia
RBC - Anaemia
CAPS - catastrophic antiphospholipid syndrome - blood clots form suddenly throughout body causing multiple organ failure
if block renal veins /arteries - lead to renal failure
- emergency , high dose anticoagulants needed.
Diagnosis
Meet Clinical and Laboratory threshold
0 History of thrombosis
0 History of Pregnancy complications e.g miscarriage
LAB
Either presence of ;
ANTI - PHOSPHOLIPID ANTIBODIES
0 Lupus anticoagulant
0 Anticardiolipin (also present in syphilis - leading to false positive test for syphilis)
0 Anti - beta 2 glycoprotein I antibodies
( these prevent excessive platelet aggregation - not the antibodies ex- beta 2 glycoprotein I )
if Anti - nuclear antibodies - suggest underlying SLE.
Treatment of SLE ?
Steriods
Immunosuppressants - Azathiopine , Hydroxychoroquine
joint pain and serositis (inflammation of serous tissue e.g pleura of lungs , heart , periotenium )
0 1st line - hydroxychloroquine
0 Corticosteroids
o Adjunct - methotrexate & folinic acid therapy (help reduce steriod use/ dose )
Mucocnatenous disease - disease of the mouth / skin ?
- sunscreen - SPF > 15 - prevent rashes / skin lesions.
- mouthwashes- Chlorohexidine , dental appointments , oral hygeine.
Lupus nephritis induction therapy - immunosuppression o - cyclophosphamide: - tacrolimus: - mycophenolate mofetil: - ciclosporin: o predisolone o hydroxychloroquine.
induction therapy - first treatments given.
What is lupus nephritis ?
inflammation of the kidney due to SLE .
- commonly presents as nephrotic syndrome.
(proteinuria , hypoalbuminemia , oedema , hyperlipidaemia , lipiduria ( less protein in blood / more fat )
can present as nephritic syndrome - damage to Glomerulus causes blood to be filtered in urine.
Type 3 Hypersensitivity reaction
SLE - half will develop this during course of condition.
can be focal or diffuse
- focal - deposition of antibody - antigen complex in one area
diffuse - in mulple areas / nephrons.
DIAGNOSIS
- Liver biopsy
TREATMENT
Immunosuppressants
Steriods.
What is nephritic syndrome ?
Nephritis - kidney disease involving inflammation , glomerulonephritis - nephritis in the glomerulus.
Glomerulonephritis - inflammation of the glomerulus ( capillaries and basement membrane )
- haematuria - microscopic most common ( only seen under microscope )
- proteinuria
- Hypertension -
reduced GFR + slat and water retention cause this. - oliguria - small amounts of urine - usually happens at later stage (unless renal failure develops early )
if there is a vascultic ( inflammation f the BV )cause.
- nausea
- malaise
- weight loss
- skin rash
- arthralgia
- haemoptysis
post-streptococcal Glomerulonephtotis ( inflammation caused by immune system fighting off Group A streptococcus throat infection / skin )
- abdominal pain
- sore throat - PSGN usually develops 10 days after strept throat / scarlet fever.
(Group A strept cause scarlet fever , strept throat , impetigo )
for a skin infection - PSGN usually develops 3 weeks after.
Fever - infectious cause
Diagnosis of nephritic syndrome ?
Urine analysis & microscopy
0 GFR
0 FBC
0 lipid profile
0 Comprehensive metabolic profile - test 14 substances in the blood - provide info on chemical balance & metabolism
o liver enzymes e.g ALT , ALP , AST - may be related to hepatits virus
o Glucose
o Creatine - elevated - indicates severe/ advanced disease
o Albumin - hypalbuminaemia - indicates nephrotic syndrome instead.
o Billirubin
o Electrolytes + C02
o Total protein etc.
0 Spot urine albumin : creatine ratio.
- > 220 mg / mmol (Elevated 0 - commonly used in diabetes to test renal function,
0 Ultrasound of kidenys.
Treatment of Nephritic syndrome ?
mild disease (e.g isolated haematuria , no or minimal proteinuria , normal GFR )
- treat underlying cause ( treat systemic cause e.g antimicrobials , withdrawal of causative drug. )
- salt restriction may be needed.
Moderate to severe - present with haematuria, proteinuria, and reduced GFR
1st line- ACE inhibitor / angiotensin II RB - to decrease proteinuria
Adjunct - Furosemide - loop diuretic - if still hypertensive
rapidly progressive - plasmapheresis
Steriod
Immunosuppressant
- when renal function is altered - plasmapheresis - urgent
(decision to stop this determined by anti - glomerular basement membrane titres )anti - GBM ) and clincal status.
What is Henoch - Scholein purpura ?
common form of vasculitis (inflammation of the blood vessels )
o effects small vessels
o occurs in childhood
Classic tetrad of symptoms
0 rash
0 abdominal pain
0 athritis / arthalgia , Glomerulonephritis .
or other signs of renal disease.
(progressive nephritis , nephrotic syndrome etc. )
Diagnosis
serum cretaine & electrolyte levels - elevated creatine (indicates renal impairment/ failure )
0 IgA - raised
0 Skin biposy - affected area will show leukocytoclastic vasculitis with IgA deposition.
(leukocytoclastic vasculitis - small BV inflammation )
renal biospy - shows IgA deposition to confirm diagnosis .
Ultrasound abdomen - indicated for severe abdominal pain
ultrasound testicles - if this region is involved.
Treatment
WITHOUT NEPHROTIC RANGE PROTEINURIA OR DECLINING GFR
with joint pain alone
1st line – analgesics
o Paracetamol
o ibuprofen
with severe oedema or scrotal involvement
1st line –
oral corticosteroids
with mild to moderate abdominal pain
1st line –
analgesics and supportive care
with severe abdominal pain
1st line –
corticosteroids
Adjunct –
surgical consultation
NEPHROTIC RANGE PROTEINURIA OR DECLINING GFR
without rapidly progressive nephritis
1st line –
corticosteroids
- IV methylprednisolone sodium succinate for 3 days
- oral pnednisolone after (3 months )
with rapidly progressive nephritis
1st line –
corticosteroids plus immunosuppressants
- azathoprine / cyclophosphaminde
Adjunct –
plasmapheresis
Adjunct –
consultation for renal dialysis or transplant
What is Sjogren syndrome ?
Chronic inflammatory and systemic auto-immune disorder characterised by diminished lacrimal and salivary gland secretion (sicca complex).
P resent with
0 dry eyes (keratoconjunctivitis sicca)
0 dry mouth (xerostomia).
Can occur on it own (Primary )
- Secondary to another auto immune disease - RA , SLE etc.
other signs
- Fatigue
- vasculitis (can present as rash )
- destruction of necks of teeth etc - tooth damage
- there are other less common signs .
Diagnosis of Sjogen’s syndrome ?
Anti RO antibodies e.g anti 60 kD Ro
0 Anti - La
plus other other signs pointing to sjogen’s syndrome .
Schrimer’s test - filter paper plced under eye - less than 5mm of the paper wetted after 5 mins - positive
Treatment of Sjogens sydrome ?
Dry eyes
1st line –
artificial tears alone
2nd line –
ophthalmic ciclosporin drops
ADJUNCTS
0 spectacle eye shields
0 humidifiers
0 punctal plugs or thermal punctal occlusion
3rd line –
cholinergic drug
salivary substitutes alone
2nd line – cholinergic drug
Primary options
- pilocarpine: 5 mg orally three times daily
- cevimeline: 30 mg orally three times daily
(Cholinergic drugs stimulate secretion by exocrine glands.)
ADJUNCTS
salivary substitutes
humidifiers and moisturisers
Musculosketetal problems -
1st line - paracetamol
2nd - NSAIDS
Adjunct - immunosuppression - but 1st & 2nd line preferred safer
corticosteriod - prednisolone
if peripheral neuropathy - IV immunoglobulin.
What is limited cutaeous systemic sclerosis / CREST syndrome / systemic scleroderma?
CREST
type of scleroderma
- Chronic Autommune condition - immune system attacks skin an d internal organs leading to excess production of collagen ————————————>thickened and hard skin & build up of scar tissue (Fibrosis )
also can causes obliteration of BV.
C- calcinosis - formation of calcium deposits in soft tissue
(ex -can be felt as painful bumps under the skin (not always ))
R - Raynauds sydrome
E - esophagael dysmolitily
S - Sclerodactyly - hardening of skin in hand - fingers curl inward like a claw.
(Shiny skin can also occur )
T - telangiectasia - enlarged BV under skin.
swelling of hands & tightness
( can cause carpal tunnel syndrome )
- prayers sign - hand cannot touch each other flat - make an O
Fibrosis of internal organs - can cause organ impairment . 0 oesophagus - dysmolitity & dysphagia 0 Heart - Hypertension 0 Lungs - SOB 0 Kidneys 0 impairment of muscle contractions moving food through GI. - GORD
What is systemic sclerosis ?
type of scleroderma
(MEANS - hardening (sclero) of skin (Derma)
- Chronic Autommune , inflammatory , fibrotic condition - immune system attacks skin and internal organs leading to excess production of collagen ————————————>thickened and hard skin & build up of scar tissue (Fibrosis )
also can causes damage to organs & obliteration of BV.
Types
- Limited cutaneous systemic sclerosis / scleroderma
(Effects only skin - (not really systemic just called that )
ORIGINALLY CALLED CREST SYNDROME
C - Calcinosis (calcium deposits under skin)- mostly at finger tips .
R - Raynauds Phenonomon (in response to cold - finger tips go white —> blue —–> black)
E - Esophageal dysmotility ( connective tissue issue - cases Dysphagia , Acid reflux , Oesophagitis)
S - Sclerodactyly ( shiny tiny skin - lacks folds - restricts range of movement of joints - limited use of hand —> eventually skin can break & ulcerate )
T- telanglectasia ( small dilated blood vessels - mainly found on face , cheeks - but other areas too)
- Diffuse cutaneous systemic sclerosis / scleroderma
(CREST syndrome + affects on internal organs)
AFFECT ON ORGANS
- Heart
0 Hypertension
0 Coronary - Lungs
0 Pulmonary HTN
0 Fibrosis
( Patient presents with gradual onset SOB & Dry cough - Pulmonary fibrosis makes lungs stiffer & harder ————–> more difficult to expand and let in air ( restrictive) - Kidney
0 Glomerulonephritis
0 Scleroderma renal crisis ( severe HTN + A cute renal failure)
(Kidney problems worsen HTN problems)
RISK FACTORS
0 Hx of Scleroderma
0 Immune dysregulation - Positive ANA
Diagnosis of Systemic sclerosis?
0 FBC
- anaemia of chronic disease
- iron deficiency anaemia
( reduced RBC , thrombocytosis - too much )
0 Serum creatine - normal or elevated
- check kidney function - increased may indicated issue - worsen diffuse systemic sclerosis - risk of scleroderma renal crisis.
0 urine microscopy
(if protein in urine - may indicate scleroderma with renal crisis)
0 ESR , CRP (inflammation)
serum antinuclear antibody - non specific
- positive but negative does not rule out.
0 other auto- antibodies
- anti - Scl 70 (anti DNA topoisomerase I) , Anti RNA polymerase I,II,III also occur in diffuse cutaneous type. more associated with diffuse type)
0 Anti - centromere - more asscoiated with limited.
0 ECG
0 Echocardiogram
0 PFTs
( if dyspnoea, dry cough , decreased exercise tolerance —–> prompt investigation of heart and lungs)
0 Chest Xray - if PFT abnormal.
Then CT scan to confirm pulmonary fibrosis
0 Barium swallow - if dysphagia , reflux etc. ( should be done - if reflux symptoms dont improve with treatment)
- those diagnosed with scleroderma often also diagnosed with sjogrens syndrome.
Treatment of Anti - phospholipid syndrome?
NOT PREGNANT
1st line- UFLWH
PLUS - Warfarin , management of risk factors
(encourage to stop smoking)
PREGNANT
1st line - UFLWH
PLUS - Foetal monitoring , warfarin post delivery
- if they have obstetric APS ( features
O recurrent early miscarriage,
O fetal death at or beyond 10 weeks of gestation
O early delivery for severe preeclampsia or placental insufficiency.)
give VTE (venous thrombosis embolism ) thromboprophylaxis post delivery
if incidental APL ( acute promyelotic leukemia ) - give aspirin - 1st line , plus -VTE thrombo…
Catosphophic APS - NOT OR PREGNANT
0 unfractionated or low weight heparin (UFLWH)
(end in parins e.g heparin , dalteparin , enoxaparin)
ADJUNCT - Immunosuppressive therapy e.g 1st -Prednisolone 2nd - plasma exchange or/and immunoglobulin 3rd - Rituximab - monoclonal antibody.
ADJUCNT - if pregnant foetal monitoring.
What is Immune Thrombocytopenia (ITP) ?
- TYPES
- APPEARENCE
- DIAGNOSTIC FACTORS
- DIAGNOSIS
also Immune Thromboctopenic purpura
Platelet count below 100 x 10^9/L - isolated thrombocytopenia ( ie. other figures in blood count normal) in the absence of identifiable cause—————> can cause bleeding (formation of Petechiae - rash formed by bleeding into the skin
0 Two types - Primary (isolated ) vs Secondary ( underlying cause)
APPEARANCE / CHARACTERISTICS
Signs of bleeding 1. Bruising ,
2. Petechiae
(indicate small capillary haemorrages - if thrombocytopenia is severe (normally) - found most commonly on lower limbs,
3. Haemorrhagic bullae
(IF HISTORY OFF BLEEDING POINTS TO ANOTHER DIAGNOSIS)
OTHER DIAGNOSITIC FACTORS - COMMON
0 absence of systemic symptoms e.g. weight loss , fever , ( symptoms of autoimmune conditions -skin rash , alopecia , DVT . (SUGGEST OTHER CONDITION)
0 Absence of medicines that cause thrombocytopenia
0 Absence of spleno/ hepatomegaly
or lymphadenopathy - if present could indicate infection , autoimmune or lymphoplofierative conditions.
DIAGNOSIS
0 FBC and peripheral blood smear.
Risk factors for ITP?
0 Women of child bearing age
0 Age - below 10 , above 65
Treatment of ITP?
ALL - life /organ threatening bleeding
1ST LINE
- Intravenous immunoglobulin (IVIG) + Corticosteriod (Prednisolone / methypred , dexamethasone) + platelet transfusion.
ADJUNCT
Aminocaproic acid or, Tranexamic acid.
(antifibrinolytic)
NEWLY DIAGNOSED CHILD
Asymptomatic /minor bleeding
1ST LINE
- observation
Major bleeding
1ST LINE
- Prednisolone
2ND LINE (if 1st line contraindicated or not working)
- IVIG or Anti - D immunoglobulin
(IF USED - EVALUATE FOR BLOOD BOURNE VIRAL INFECTIONS - HEP B)
NEWLY DIAGNOSED ADULT
0 platelet above 30 x 10^9 or equal & asymptomatic - no additional risk factors
1ST LINE
- Observation
0 platelet above 30 x 10^9 or equal & symptomatic - additional risk factors or platelet below 30 x 10^9
1ST LINE
Corticosteriod and / or IVIG
or anti D - in RH positive pateints or non splenectomised (spleen still present).
CHILD - chronic / persistent
1ST LINE
Mycophenolate mofetil (DMARD - disease modifying drug)
or Rituximab or thrombopoietin agonist receptor e.g. eltombrag , romiplostim
(if one does not work tty others)
2ND LINE
- Splenectomy + IVIG or pred
CHRONIC/ PERSISTENT ADULT- NON PREGNANT
1ST LINE - Low dose steriof (Pred) -repeat IVIG infusions 2ND LINE (1st line chronic childrens treatment) 3RD LINE - Splenectomy.
Pregnant - chronic
1ST LINE
-high dose methylprednisolone
ADJUNCT
IVIG or /and azathoprine
Splenectomy
