Sneddon's Syndrome

Synonyms: Ehrmann-Sneddon syndrome

Sneddon's syndrome is a non-inflammatory arteriopathy in which livedo reticularis is associated with cerebrovascular disease.^1,2 It is slowly progressive and often unrecognised,³ and may be seen in patients with an autoimmune disorder (e.g. antiphospholipid syndrome or SLE).

• Incidence is estimated at four cases per million population per year.
• Although initially thought to have a genetic aetiology (one family cluster displayed autosomal dominant inheritance),² further studies have failed to demonstrate any family history in most affected patients.³

• The condition develops slowly over a variable time frame.
• Non-specific prodromal symptoms (headache, dizziness) often precede livedo reticularis by several years and this is followed by the development of focal neurological symptoms and then progressive cognitive impairment.
• Involvement of fundi, peripheral nerves, heart, and kidneys is frequent but usually asymptomatic.
• Livedo reticularis is a bluish mottling of skin, usually on the legs, and the appearance may be aggravated by exposure to cold.

• Sneddon's syndrome has been classified as primary if there is no clear cause, or secondary, which occurs mainly as part of an autoimmune disorder (polyarteritis nodosa, systemic lupus erythematosus) or in a thrombophilic state (e.g. thrombocythaemia).⁴
• Other associations include hypertension, systemic ischaemia (including ischaemic heart disease), heart valve lesions and venous thrombosis.

• Anti-phospholipid and anti-prothrombin antibodies have been associated in some but not all cases.
• Neuroimaging, including MRI, histological, immunohistochemical and ultrasound evaluation may be useful for diagnosis.⁵
• Skin biopsy specimens reveal inflammatory changes of small- to medium-sized arteries followed by subendothelial proliferation and fibrosis.³

• In patients without any prior history of thromboembolism, minimise risk factors (stop smoking and/or combined oral contraceptives, control any hypertension, treat any hyperlipidaemia).
• Consider prophylaxis with low dose aspirin (clopidogrel if unable to take aspirin), particularly in patients with antiphospholipid or anti-prothrombin antibodies.⁶ It may be appropriate for all patients but more research is needed.⁷
• Patients with a history of thrombosis are treated indefinitely with anticoagulation (with warfarin ± low dose aspirin).
• Hydroxychloroquine has been used in patients with SLE (it may have intrinsic antithrombotic properties).⁷

• Some symptoms tend to resolve over a very variable time course.
• Prevention of further vascular events with anticoagulation is the key to a good prognosis.
• Hypertension is associated with a more severe course of the disease.³