Sneddon’s syndrome: a comprehensive review of the literature

Abstract

Sneddon’s syndrome (SS) is a rare non-inflammatory thrombotic vasculopathy characterized by the combination of cerebrovascular disease with livedo racemosa(LR). The Orpha number for SS is ORPHA820. It has been estimated that the incidence of SS is 4 per 1 million per annum in general population and generally occurs in women between the ages of 20 and 42 years. LR may precede the onset of stroke by years and the trunk and/or buttocks are involved in nearly all patients. The cerebrovascular manifestations are mostly secondary to ischemia (transient ischemic attacks and cerebral infarct). Other neurological symptoms range from headache, cerebral hemorrhage, seizures, cognitive and psychiatric disturbances. The involved internal organs include heart, kidney, and eyes. Histological findings of skin are characteristic and the involved vessels are small to medium-sized arteries at the border of dermis to subcutis with a distinct histopathological time course. The main diagnostic criteria are general LR with typical histopathological findings on skin biopsy and focal neurological deficits. The pathogenesis is related to hypercoagulable state and intrinsic small-vessel vasculopathy. The optimal management remains an unsolved problem and long-term anticoagulation have been recommended for cerebral ischemic events based on the presumed pathogenesis. There are controversial results in treatment of SS with immunomodulatory agents. The aim of this review is to comprehensively discuss this disease.

Sneddon's syndrome: it is all in the ectoderm

“…Sneddon, a British dermatologist, described the syndrome in 1964 as a non-inflammatory thrombotic vasculopathy characterised by the combination of cerebrovascular disease and livedo racemosa or reticularis 1. Its incidence is four per million per year and it usually occurs in women (83% female in one cohort) 1.…”

“…Sneddon, a British dermatologist, described the syndrome in 1964 as a non-inflammatory thrombotic vasculopathy characterised by the combination of cerebrovascular disease and livedo racemosa or reticularis 1. Its incidence is four per million per year and it usually occurs in women (83% female in one cohort) 1. A history of stroke is a diagnostic hallmark of Sneddon's syndrome, while headache is the most frequent non-specific symptom and cognitive impairment occurs in up to 77% patients 1.…”

“…Its incidence is four per million per year and it usually occurs in women (83% female in one cohort) 1. A history of stroke is a diagnostic hallmark of Sneddon's syndrome, while headache is the most frequent non-specific symptom and cognitive impairment occurs in up to 77% patients 1. It is a multisystem disorder and cardiac manifestations including valvulopathy are well described 1.…”

Cryptogenic stroke

“…The disease may be suggested by the presence, at conventional MRI, of flow void signals (resulting from basal collaterals) at the level of basal ganglia and thalami or by the presence of the ivy sign (linear high signal following a sulcal pattern at fluid attenuated inversion recovery sequences supposed to represent slow flow in poorly perfused cortical circulation), by bilateral stenosis at the apices of the internal carotid arteries at brain CT or MRA (even if unilateral findings may be present during the early course of the condition) and thereafter confirmed by the characteristic puff of smoke appearance of collateral vessels at brain angiography. More rare causes of ischemic stroke are represented by Sneddon syndrome characterized by livedo racemosa and stroke, 38 Susac's syndrome characterized by branch retinal artery occlusion, hearing loss, encephalopathy and stroke 39 and migrainous stroke.…”

Adenosine Deaminase Two and Immunoglobulin M Accurately Differentiate Adult Sneddon’s Syndrome of Unknown Cause

“…SnS is rare and it occurs mainly sporadically [3]. In 2014, 2 independent teams [4,5] described a new genetic disorder with childhood-onset, which was called Deficiency of adenosine deaminase (DADA2), characterized by recurrent fevers and vascular pathologic features that included LR and stroke.…”