Sneddon Syndrome

Sneddon syndrome is a rare non-inflammatory arteriopathy of small and medium arteries that causes generalised livedo racemosa with recurrent ischaemic stroke or transient ischaemic attack. Onset is usually in women aged 20 to 40 years.

About 40 to 50% have antiphospholipid antibodies. The remainder are called seronegative or primary, and some have ADA2 deficiency.

Pathophysiology. Endothelial injury with intimal proliferation and thrombosis narrows small and medium arteries of skin and brain. Antiphospholipid antibodies promote thrombosis.

Livedo racemosa (broken, irregular net like violaceous rash, fixed and not cold dependent) often precedes stroke by years. Others are recurrent ischaemic stroke, transient ischaemic attack, headache, progressive cognitive decline, hypertension, valvular heart disease, seizures and, in antiphospholipid cases, miscarriage and venous thrombosis.

Red flags.

• Stroke in a young person with livedo.
• Cognitive decline with multiple infarcts.
• Pregnancy loss or thrombosis.

Skin biopsy (deep, wedge, from a white centre of the net) shows arteriolar endothelial change. MRI shows multiple infarcts, small vessel disease and white matter lesions. Antiphospholipid testing: lupus anticoagulant, anticardiolipin and anti-beta-2 glycoprotein I antibodies, repeated after 12 weeks. Check antinuclear antibodies, antineutrophil cytoplasmic antibodies, complement, thrombophilia, echocardiography and ADA2 activity. Angiography is often normal.

Differential diagnosis.

• Systemic lupus erythematosus, vasculitis and cholesterol emboli.
• Cerebral autosomal dominant arteriopathy, endocarditis and atrial myxoma.
• Livedo reticularis (physiological) and polycythaemia.

Antithrombotic therapy.

• Antiphospholipid antibody positive: warfarin with a target INR of 2.0 to 3.0, indefinitely. Avoid direct oral anticoagulants in triple positive antiphospholipid syndrome.
• Seronegative: aspirin 75 to 100 mg daily, or clopidogrel 75 mg daily, with warfarin if stroke recurs.

Vascular risk. Treat hypertension, lipids and smoking. Stop oestrogen containing contraceptives.

Immunosuppression. Hydroxychloroquine 200 to 400 mg daily may be added, and steroids or other drugs for coexisting lupus.

ADA2 deficiency. Tumour necrosis factor inhibitor, under specialist care.

Monitoring. INR, blood pressure, cognition and MRI as needed.

Referral and escalation. Refer to neurology, rheumatology and dermatology.

Special groups. In pregnancy, replace warfarin with therapeutic low molecular weight heparin before 6 weeks (enoxaparin 1 mg/kg SC twice daily) with aspirin 75 mg daily.