Multi-system Autoimmune Disease

Question 1

What are the different major connective tissue disorders?

Answer 1

Systemic Lupus Erythematosus (SLE). Systemic sclerosis. Sjorgen’s syndrome. Auto-immune myositis. Mixed connective tissue disease.

Question 2

What are the major systemic vasculitides?

Answer 2

Giant cell arteritis. Granulomatosis with polyangiitis (Wegeners). Microscopic polyangiitis. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome

Question 3

What is the prevalence of SLE?

Answer 3

UK prevalence: 28/100,000; F> M; onset 15-50 years. Afro-Caribbean>Asian>Caucasian.

Question 4

What are the aetiological factors for SLE?

Answer 4

Genetic factors. Hormonal factors. Environmental factors – UV light, drugs, infections.

Question 5

Describe the pathogenesis of SLE

Answer 5

Immune response against endogenous nuclear antigens (break in immunological tolerance). Immune complex formation. Complement activation. Tissue injury.

Question 6

Describe the clinical presentation of SLE and its classification criteria

Answer 6

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)

Question 7

How would you diagnose SLE?

Answer 7

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)

Question 8

How may SLE manifest clinically?

Answer 8

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.

Question 9

What are the different classifications for scleroderma?

Answer 9

Localised scleroderma. Systemic sclerosis (SSc) – Limited cutaneous systemic sclerosis (CREST) + Diffuse cutaneous systemic sclerosis. (autoimmune condition attacking/tightens skin, connective tissue and internal organs)

Question 10

Describe the epidemiology and aetiology of systemic sclerosis

Answer 10

UK prevalence 24/100,000; onset 30-50years; F>M. Environmental – silica, solvents, viral infections; Genetic predisposition.

Question 11

What is the pathogenesis of systemic sclerosis?

Answer 11

Vascular damage (microcirculation). Immune system activation/inflammation, Fibrosis.

Question 12

Describe the presentation of morphea (localised scleroderma)

Answer 12

Discoloured oval patches on the skin. Can appear anywhere on the body. Usually itchy. Patches may be hairless and shiny.

Question 13

Describe the presentation of linear (localised scleroderma)

Answer 13

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.

Question 14

Describe the presentation of limited cutaneous + diffuse systemic sclerosis

Answer 14

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).

Question 15

How is scleroderma diagnosed?

Answer 15

Antinuclear antibodies (ANA) blood test 
Biopsy of skin 
Pulmonary function tests 
CT chest 
ECHO 
Laser Doppler test

Question 16

What are the manifestations of the different subsets of systemic sclerosis?

Answer 16

Limited – pulmonary hypertension, GI.

Diffuse – pulmonary fibrosis, renal crisis, small bowel bacterial overgrowth.

Question 17

What is the presentation of Sjorgen’s syndrome?

Answer 17

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.

Question 18

What are complications of Sjorgen’s syndrome?

Answer 18

Lymphoma. Neuropathy. Cutaneous vasculitis. Interstitial lung disease. Renal tubular acidosis.

Question 19

Describe the presentation of polymyositis

Answer 19

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.

Question 20

Describe the presentation of dermatomyositis

Answer 20

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.

Question 21

How is polymyositis and dermatomyositis diagnosed?

Answer 21

• 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).

Question 22

What are some clinical manifestations of polymyositis and dermatomyositis?

Answer 22

Cancer. Interstitial lung disease.

Question 23

How do you diagnose Giant Cell Arteritis (clinical features)?

Answer 23

3 of the following (classic temporal arteritis):

• Age of onset ≥ 50 years
• New headache
• Temporal artery tenderness/reduced pulsation
• ESR ≥ 50
• Abnormal temporal biopsy

Question 24

What are complications of giant cell arteritis?

Answer 24

Irreversible visual loss. Aortic aneurysms. Arterial stenosis and limb ischaemia. Stroke.

Question 25

What is the treatment for giant cell arteritis?

Answer 25

Urgent initiation of high dose Prednisolone, 40-60mg per day, gradually tapered, PPI, Bone protection, steroid sparing medication.

Question 26

How would you manage multisystem autoimmune disease?

Answer 26

Organ threat:

• Mild – hydroxychloroquine
• Moderate – azathioprine, methotrexate or mycophenolate
• Severe – cyclophosphamide or rituximab