Multi-system Autoimmune Disease Flashcards
What are the different major connective tissue disorders?
Systemic Lupus Erythematosus (SLE). Systemic sclerosis. Sjorgen’s syndrome. Auto-immune myositis. Mixed connective tissue disease.
What are the major systemic vasculitides?
Giant cell arteritis. Granulomatosis with polyangiitis (Wegeners). Microscopic polyangiitis. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome
What is the prevalence of SLE?
UK prevalence: 28/100,000; F> M; onset 15-50 years. Afro-Caribbean>Asian>Caucasian.
What are the aetiological factors for SLE?
Genetic factors. Hormonal factors. Environmental factors – UV light, drugs, infections.
Describe the pathogenesis of SLE
Immune response against endogenous nuclear antigens (break in immunological tolerance). Immune complex formation. Complement activation. Tissue injury.
Describe the clinical presentation of SLE and its classification criteria
Malar rash (butterfly rash), Discoid rash (raised, scaly centre + dark rim).
Photosensitivity
Oral ulcers
Arthritis (2 joints at least)
Serositis (pleurisy or pericarditis)
Renal (significant proteinuria or cellular casts in urine)
Neurological (unexplained seizures or psychosis)
Classification criteria – any of the above 4 (+ from haematological, immunological and ANA)
How would you diagnose SLE?
Clinical features
Haematological (low WCC, platelets, lymphocytes, haemolytic anaemia)
Immunological (anti ds-DNA, SM, cardiolipin, lupus anticoagulant, low complement)
ANA (anti-nuclear antibody; seen in 95% of SLE although not specific for SLE, autoimmune diseases)
How may SLE manifest clinically?
Skin – butterfly rash + red patches; lungs – pleuritic, pneumonitis, pulmonary emboli + haemorrhage; Kidneys – haematuria; heart – endocarditis, atherosclerosis, inflammation of fibrous sac; blood – anaemia, high BP; Muscles and joints – pain, swollen joints.
What are the different classifications for scleroderma?
Localised scleroderma. Systemic sclerosis (SSc) – Limited cutaneous systemic sclerosis (CREST) + Diffuse cutaneous systemic sclerosis. (autoimmune condition attacking/tightens skin, connective tissue and internal organs)
Describe the epidemiology and aetiology of systemic sclerosis
UK prevalence 24/100,000; onset 30-50years; F>M. Environmental – silica, solvents, viral infections; Genetic predisposition.
What is the pathogenesis of systemic sclerosis?
Vascular damage (microcirculation). Immune system activation/inflammation, Fibrosis.
Describe the presentation of morphea (localised scleroderma)
Discoloured oval patches on the skin. Can appear anywhere on the body. Usually itchy. Patches may be hairless and shiny.
Describe the presentation of linear (localised scleroderma)
Thickened skin occurs in line across the face, scalp, legs or arms. Occasionally affects underlying bone and muscle. May improve after few years, although can cause permanent growth problems, such as shortened limbs.
Describe the presentation of limited cutaneous + diffuse systemic sclerosis
A milder form that only affects skin on the hands, lower arms, lower legs and face, although it can eventually affect the lungs and digestive system too.
Often starts as Raynaud’s (a circulation problem where finger and toes turn white in the cold). Other typical symptoms include thickening of the skin over hand, feet and face, red spots on the skin, hard lumps under the skin, heartburn and problems swallowing (dysphagia).
How is scleroderma diagnosed?
Antinuclear antibodies (ANA) blood test Biopsy of skin Pulmonary function tests CT chest ECHO Laser Doppler test
What are the manifestations of the different subsets of systemic sclerosis?
Limited – pulmonary hypertension, GI.
Diffuse – pulmonary fibrosis, renal crisis, small bowel bacterial overgrowth.
What is the presentation of Sjorgen’s syndrome?
Dry eyes and mouth. Anti Ro (SSA), anti LA (SSB) antibodies. Parotid gland enlargement. 1/3 have systemic upset: fatigue, fever, myalgia, arthralgia, dry skin. Salivary gland biopsy.
What are complications of Sjorgen’s syndrome?
Lymphoma. Neuropathy. Cutaneous vasculitis. Interstitial lung disease. Renal tubular acidosis.
Describe the presentation of polymyositis
Insidious onset of progressive symmetrical proximal muscle weakness. Autoimmune-mediated striated muscle inflammation (myositis). Myalgia +/- arthralgia. Muscle weakness may also cause dysphagia, dysphonia (i.e. poor phonation), or respiratory weakness.
Describe the presentation of dermatomyositis
Myositis plus skin signs: macular rash (shawl sign is +ve if over back and shoulders); lilac-purple rash on eyelids often with oedema; nailfold erythema (dilated capillary loops); Gottron’s papules: roughened red papules over knuckles, also seen on elbow + knees.
How is polymyositis and dermatomyositis diagnosed?
- Muscle enzymes (ALT, AST, LDH, CK + aldolase) increased in plasma
- EMG shows characteristic fibrillation potentials
- Muscle biopsy confirms diagnosis (and excludes mimicking conditions)
- Autoantibody associations: anti-Mi2, anti-Jo1 – associated with acute onset and interstitial lung fibrosis (treated aggressively).
What are some clinical manifestations of polymyositis and dermatomyositis?
Cancer. Interstitial lung disease.
How do you diagnose Giant Cell Arteritis (clinical features)?
3 of the following (classic temporal arteritis):
- Age of onset ≥ 50 years
- New headache
- Temporal artery tenderness/reduced pulsation
- ESR ≥ 50
- Abnormal temporal biopsy
What are complications of giant cell arteritis?
Irreversible visual loss. Aortic aneurysms. Arterial stenosis and limb ischaemia. Stroke.
What is the treatment for giant cell arteritis?
Urgent initiation of high dose Prednisolone, 40-60mg per day, gradually tapered, PPI, Bone protection, steroid sparing medication.
How would you manage multisystem autoimmune disease?
Organ threat:
- Mild – hydroxychloroquine
- Moderate – azathioprine, methotrexate or mycophenolate
- Severe – cyclophosphamide or rituximab
