Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
76 Cards in this Set
- Front
- Back
|
Define antiphospholipid syndrome |
Autoimmune hypercoagulopathy characterised by arterial and venous thrombosis, adverse pregnancy outcomes and raised levels of antiphospholipid (aPL) antibodies |
|
|
Antiphospholipid syndrome may be secondary to the following autoimmune conditions |
- SLE - RA - Behcet's disease - GCA - Sjogren's syndrome - Psoriatic arthritis |
|
|
Antiphospholipid syndrome diagnostic criteria |
At least one of the clinical criteria and at least one of the lab criteria: - Clinical criteria: - Vascular thrombosis: >/=1 arterial, venous or small vessel thrombosis - Pregnancy morbidity: recurrent miscarriage, >/=1 unexplained miscarriage or preterm birth - Lab criteria: autoantibodies raised on >/=2 occasions 12 weeks apart: - Lupus anticoaguant (LA) - Anticardiolipin (aCL) - Anti-b2-glycoprotein 1 |
|
|
Antiphospholipid syndrome occurs most commonly in.... |
Young women of fertile age |
|
|
Antiphospholipid syndrome presentation |
- PAD, DVT, PE - Cerebrovascular disease, sinus thrombosis - Pregnancy loss, recurrent miscarriage - Pre-eclampsia, IUGR - Livedo reticularis, purpura, skin ulceration - Thrombocytopenia, haemolytic uraemia - Endocarditis, cardiac valve disease, MI - Retinal thrombosis - Budd-Chiari - Nephropathy, adrenal infarction - Avascular necrosis of bone |
|
|
Antiphospholipid syndrome investigations |
- aPL antibodies: LA, aCL, anti-beta2 GP1 - Bloods: FBC, clotting - CT/MRI if indicated: brain (stroke), chest (PE), abdo (Budd-chiari) - Doppler USS if ?DVT |
|
|
Antiphospholipid syndrome management |
- Reduce CV risk factors: smoking cessation, regular exercise, lose weight if overweight, avoid excessive alcohol, manage DM, HTN, hyperlipidaemia - Thrombosis prophylaxis: long-term warfarin or NOAC (LMWH + aspirin if contraindicated or pregnant) |
|
|
Type 1 hypersensitivity reaction |
Antigen reacts with IgE bound to mast cells |
|
|
Examples of type 1 hypersensitivity reaction |
- Anaphylaxis - Atopy e.g. asthma, eczema, hayfever |
|
|
Type II hypersensitivity reaction |
IgG or IgM binds to antigen on cell surface |
|
|
Examples of type II hypersensitivity reaction |
- Autoimmune haemolytic anaemia - ITP - Goodpasture's syndrome - Pernicious anaemia - Acute haemolytic transfusion reactions - Rheumatic fever - Pemphigus vulgaris/bullous pemphigoid |
|
|
Type III hypersensitivity reaction |
Immune complex-mediated: free antigen and antibody (IgG, IgA) combine |
|
|
Examples of type III hypersensitivity reaction |
- Serum sickness - SLE - Post-streptococcal glomerulonephritis - Extrinsic allergic alveolitis |
|
|
Type IV hypersensitivity reaction |
Delayed hypersensitivity: T-cell mediated |
|
|
Examples of type IV hypersensitivity reaction |
- Tuberculosis - Graft versus host disease - Allergic contact dermatitis - Scabies - Extrinsic allergic alveolitis (chronic phase) - MS - Guillain-Barre syndrome |
|
|
Type V hypersensitivity reaction |
Antibodies that recognise and bind to cell surface receptors - stimulate or block them |
|
|
Examples of type V hypersensitivity reaction |
- Graves' disease - Myaesthenia gravis |
|
|
Define immune thrombocytopenia |
- Autoimmune disorder in which the number of circulating platelets is reduced (due to increased destruction, sometimes reduced production) - Antibodies bind to platelet antigens - Platelet count is <100 x 10^9/L |
|
|
Types of immune thrombocytopenia |
- Primary (occurs in isolation) - Secondary: occurs in a/w other disorders e.g. - Autoimmune disorders e.g. APLS, SLE - Viral infection e.g. CMV, VZV, hep C, HIV - Infection with H. pylori - Medication - Lymphoproliferative disorders |
|
|
Most common cause of immune thrombocytopenia in children |
Post-viral: usually self-limiting and recovers spontaneously after 6-8 weeks |
|
|
Immune thrombocytopenia presentation |
- May be none - Petechiae, bruising - Nosebleeds - Menorrhagia - Cranial haemorrhage - Less commonly: haematuria, GI bleed |
|
|
Immune thrombocytopenia investigations |
- FBC - Peripheral blood smear - Screen for HIV and hep C - Bone marrow biopsy: only if atypical features or diagnosis in doubt |
|
|
Immune thrombocytopenia blood smear findings |
- Decreased number of platelets - No immature leukocytes (c.f. leukaemia) - No fragmented erythrocytes (c.f. TTP) |
|
|
Immune thrombocytopenia management |
- Observational monitoring, trauma prevention, avoid aspirin/NSAIDs - Further treatment initiated in specialist setting: - Oral prednisolone, IV immunoglobulin if C/I - Platelet transfusion - Splenectomy if chronic/severe |
|
|
Polymyositis and dermatomyositis are types of |
Idiopathic inflammatory myopathies - chronic autoimmune conditions characterised by inflammation of skeletal muscles (esp. proximal muscles) |
|
|
Cause of myositis |
- Idiopathic autoimmune - May be a paraneoplastic phenomenon (10-20%): especially from breast, lung, ovarian, pancreatic and bowel malignancies |
|
|
Dermatomyositis clinical features |
- Gradual onset proximal muscle weakness: difficulty standing, sitting, climbing steps, combing hair - Fatigue, myalgia, muscle cramps/tenderness - Pharyngeal weakness - dysphagia - Rash - Dilated capillary loops at fingernail bases - Sensation preserved and tendon reflexes normal - PUD - AV malconduction |
|
|
Dermatomyositis rash |
- Heliotrope discolouration on upper eyelids and periorbital oedema - Macular rash over face and trunk - Purple-red scaly patches over extensor surfaces of joints and fingers with interdigital sparing - Rash may be exacerbated by sunlight |
|
|
Dermatomyositis investigations |
- Muscle enzymes e.g. CK, LDH, SGOT, SGPT, aldolase - Autoantibodies: ANA, Anti-Mi2, Anti-Jo1 (more common in polymyositis) - Electromyogram: fibrillation potentials - Muscle biopsy: diagnostic - Screen for malignancy |
|
|
Polymyositis clinical features |
- Gradual onset proximal muscle weakness: difficulty standing, sitting, climbing steps, combing hair - Weakness may vary week-to-week - Fatigue, myalgia, muscle cramps/tenderness - Pharyngeal weakness - dysphagia - One-third have pain - No rash - Sensation preserved and tendon reflexes normal |
|
|
Polymyositis investigations |
- Muscle enzymes: CK (up to 50xNR), LDH, SGOT, SGLT, aldolase - Autoantibodies: Anti-Jo1 (20%) - Electromyogram: fibrillation potentials - Muscle biopsy: diagnostic - Screen for malignancy |
|
|
Myositis management |
- Sun block, physiotherapy, SALT - Monitoring: CK - Steroids: topical if mild, PO if severe - Immunosuppressants e.g. azathioprine, cyclophosphamide |
|
|
Myositis complications |
- GI ulceration - Malignancy - AV defects - Cardiomyopathy - CCF - Interstitial lung disease |
|
|
Define systemic lupus erythematous |
Heterogeneous, inflammatory, multisystem autoimmune disease in which antinuclear antibodies (ANA) occur |
|
|
SLE: - Peak onset - F:M |
- 20s-30s - F:M = 9:1 |
|
|
SLE risk factors |
- HLA DR2 and DR3 - Environmental factors: UV light, some viruses (e.g. EBV), drugs (e.g. chlorpromazine, methyldopa, isoniazid, hydralazine) |
|
|
SLE associated diseases |
- APLS - Scleroderma - Polymyositis - RA - Sjogren's |
|
|
SLE clinical features |
- Fatigue, malaise, fever, splenomegaly, lymphadenopathy, weight loss - Arthralgia: similar to RA - Myalgia - Raynaud's phenomenon - Mucocutaneous: malar (butterfly) rash, discoid rash, livedo reticularis, mouth ulcers, alopecia - Pulmonary: pleurisy, bilateral pleural effusions, pneumonitis, fibrosing alveolitis - CVS: pericaritis, endocarditis - Nephritis, glomerulonephritis - Anxiety, depression, psychosis, seizures |
|
|
SLE investigations |
- Bloods: FBC, ESR, CRP, U&Es - Urine: detect proteinuria and cell casts - Immunology: - ANA (+ve in 95%): non-specific - Anti-dsDNA - Anti-Sm (most specific) - Anti-Ro and anti-La - Complement: low C3 and C4 - APLS antibodies (LA, aCL - Skin/renal biopsies |
|
|
SLE management |
- Avoid sun exposure - Reduce risk of atherosclerosis: lifestyle, statins, BP - NSAIDs for arthralgia, myalgia - Mild SLE: hydroxychloroquine (DMARD) - takes 6-12 weeks to have effect - Severe: oral steroids, immunosuppressants (azathioprine, methotrexate) - Refractory: B-cell depletion (retuximab, belimumab) - Life-threatening: plasma exchange |
|
|
Define systemic sclerosis |
Multisystem autoimmune disease in which there is increased fibroblast activity resulting in abnormal growth of connective tissue - vascular damage and fibrosis |
|
|
Types of systemic sclerosis |
- Limited cutaneous systemic sclerosis (more common) - Diffuse cutaneous systemic sclerosis |
|
|
Limited cutaneous systemic sclerosis was previously known as... |
CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) |
|
|
Areas of skin affected in limited cutaneous systemic sclerosis |
- Face - Forearms - Lower legs below knee |
|
|
Systemic sclerosis clinical features |
- Skin: calcinosis, sausage-like digits, sclerodactyly, Raynaud's phenomenon, digital ulcers, telangiectasia, 'salt and pepper' appearance of skin - Face: tightening of facial skin, microstomia - Arthralgia, myalgia - GI: heartburn, oesophagitis, 'watermelon stomach' - GI bleed, diarrhoea/constipation - Pulmonary fibrosis, myocardial fibrosis, glomerulonephritis |
|
|
Systemic sclerosis investigations |
- Bloods: FBC, ESR, CRP, U&Es, LFTs - Autoantibodies: - ANA - Anti-topoisomerase 1 (anti-Scl 70) - Anti-centromere (ACA) - Anti-RNA polymerase III |
|
|
Systemic sclerosis management |
- Monitoring: BP, renal function, lung function, ECG, echo - Conservative: education, physio, smoking cessation, nutrition, emollients (+/- topical steroids/antihistamines) - Symptomatic: nifedipine (Raynaud's), NSAIDs (myalgia/arthralgia), ACEi (renal crisis), PPI, metoclopramide, laxatives - Immunotherapy: cyclophosphamide, methotrexate - Surgical: release contractures |
|
|
Systemic sclerosis complications |
- Pulmonary fibrosis, PAH - CCF, arrhythmias - Renal crisis: HTN, oliguria, oedema, proteinuria - GI obstruction - Malignancy e.g. lung, breast, haematological |
|
|
Causes of vasculitis |
- Idiopathic (50%) - Direct toxicity: irradiation, infection (e.g. HSP, septic vasculitis), drugs (e.g. sulphonamides, beta-lactams, quinolones, NSAIDs, thiazides) - Neoplastic (paraproteinaemia or lymphoproliferative disorder) - Immune-mediated: deposition of immune complexes, autoantibodies - Pauci-immune |
|
|
Define pauci-immune vasculitis |
- No immune complexes or autoantibodies - Immune response against neutrophils via anti-neutrophil cytoplasmic antibodies (ANCA) - stimulates neutrophils to bind to and activate endothelial cells to release oxygen radicals and matrix metalloproteases -> vessel wall destruction - E.g. granulomatosis with polyngiitis, Churg-Strauss syndrome, microscopic polyangiitis |
|
|
Vasculitis clinical features |
- Lethargy, arthralgia, fever, weight loss - Small vessels: palpable purpura, splinter haemorrhages, urticaria, vesicles - Medium vessels: ulcers, digital infarcts, nodules, HTN, chronic sinusitis, levido reticularis - Large vessels: end-organ ischaemia, HTN, aneurysm, dissection - Digits: Raynaud's, splinter haemorrhages, digital pulp loss, pulse loss at extremities - Ocular: retinitis vasculitis, scleritis, uveitis, conjunctivitis |
|
|
Define giant cell arteritis |
Immune-mediated vasculitis affecting medium and large sized arteries, usually the external carotids and extra-cranial branches |
|
|
Giant cell arteritis: - Onset - F:M |
- >50yo - F>M |
|
|
Giant cell arteritis clinical features |
- Temporal headache - Scalp tenderness - Facial pain - Transient visual symptoms - Jaw/tongue claudication - Abnormal temporal artery: absent, tender, enlarged - 50% have features of PMR |
|
|
Giant cell arteritis investigations |
- Urgent temporal artery biopsy (must be within 2 weeks of starting steroids) - ESR/CRP: ESR usually >50 (normal value doesn't exclude GCA) |
|
|
Giant cell arteritis management |
- Immediate high dose corticosteroids e.g. prednisolone: 40mg/day if no claudication symptoms, 60mg/day if jaw/tongue claudication or visual symptoms - reduce step-wise over a year - Aspirin 75mg/day - Osteoporosis prophylaxis + GI protection (PPI) |
|
|
Define polyarteritis nodosa |
- Necrotising arteritis that causes aneurysms and thrombosis in medium-sized arteries -> infarction in affected organs - Spares pulmonary and renal arteries |
|
|
Polyarteritis nodosa aetiology |
- Usually idiopathic - May be triggered by viral infection (hep B) |
|
|
Polyarteritis nodosa: - Onset - M:F |
- Peak: 10yo, adults 40-50yo - M:F = 2:1 (children 1:1) |
|
|
Polyarteritis nodosa presentation |
- Weakness, weight loss, malaise, fever - Skin: rashes (purpura, livedoid, nodules), ulcers, gangrene - GI: abdo pain, ischaemia - Myalgia - Renal: AKI, HTN - Neurological: mononeuritis multiplex - Cardiac: coronary arteritis -> MI, HF |
|
|
Polyarteritis nodosa investigations |
- Bloods: FBC (^WCC, anaemia), ESR - ANCA: usually -ve - Hep B surface antigen +ve in 30% - Angiography: renal, intestinal, hepatic microaneurysms - Biopsy of affected organs - Diagnosis: ACR criteria |
|
|
Polyarteritis nodosa biopsy of affected organs findings |
Fibrinoid necrosis of vessel walls with microaneurysm formation, thrombosis and infarction |
|
|
Polyarteritis nodosa management |
- Corticosteroids e.g. prednisolone - Second-line: cyclophosphamide, azathioprine - Hep B +ve: antivirals and plasma exchange |
|
|
Types of pauci immune vasculitis |
- Granulomatosis with polyangiitis (Wegener's) - Churg-Strauss syndrome - Microscopic polyangiitis |
|
|
Define granulomatosis with polyangiitis |
Rare vasculitis that can affect many parts of the body, but most commonly the ear/nose/throat, lungs and kidneys (ELK) |
|
|
Granulomatosis with polyangiitis peak age of onset |
35-55yo |
|
|
Granulomatosis with polyangiitis presentation |
- Fatigue, fever, night sweats, weight loss - ENT: rhinorrhoea (+/- blood), nasal ulcers/sores/crusting, saddle nose, sinusitis, hoarseness, subglottic stenosis, ear infections - Lungs: cough, dyspnoea, wheeze, haemoptysis - Kidneys: haematuria - Rashes: purpura, ulcers, nodules - Arthralgia, conjunctivitis, scleritis, mononeuritis multiplex |
|
|
Granulomatosis with polyangiitis serology |
- c-ANCA positive - Not generally associated with eosinophilia (c.f. Churg Strauss) |
|
|
Granulomatosis with polyangiitis management |
- Prednisolone + cyclophosphamide - Consider methotrexate if ineffective after 3-6 months |
|
|
Define Churg Strauss syndrome |
- Rare vasculitis that affects small and medium vessels - Characterised by the presence of 4 of the following: asthma, paranasal sinusitis, eosinophilia >10%, pulmonary infiltrates, mononeuritis/polyneuropathy, histological evidence of vasculitis with extravascular eosinophils |
|
|
Churg Strauss syndrome presentation |
- Fatigue, fever, weight loss - Asthma - Paranasal sinusitis - Pulmonary infiltrates: cough, dyspnoea - Mononeuritis/polyneuropathy - Cardiac: HF, MI, myocarditis - Skin rashes - GI: bleed, ischaemia, pancreatitis, appendicitis |
|
|
Churg Strauss syndrome serology |
- p-ANCA positive - Raised IgE |
|
|
Churg Strauss syndrome biopsy findings |
Small necrotising granulomas |
|
|
Churg Strauss syndrome management |
- High dose prednisolone - Cyclophosphamide if severe |
|
|
Define microscopic polyangiitis |
Vasculitis with pulmonary infiltrates and often musculoskeletal, neuropathic, CNS abnormalities |
|
|
Microscopic polyangiitis serology |
p-ANCA positive |
