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Clinical Observation

Sneddon Syndrome Presenting With Unilateral Third Cranial Nerve Palsy

Jiménez-Gallo, David MD; Albarrán-Planelles, Cristina MD; Linares-Barrios, Mario PhD, MD; González-Fernández, Julio A. PhD, MD; Espinosa-Rosso, Raúl MD; Báez-Perea, José M. PhD, MD

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Journal of Neuro-Ophthalmology: March 2014 - Volume 34 - Issue 1 - p 50-52
doi: 10.1097/WNO.0b013e3182a3060d
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Abstract

Sneddon syndrome (SS) is a rare systemic vasculopathy affecting the skin as livedo racemosa (LR) and the central nervous system as stroke. It predominantly affects young women, and neurological involvement usually appears years after the appearance of skin findings (1,2).

Definitive diagnosis requires correlation of clinical symptoms with skin histopathology. It is essential to make an early diagnosis of SS and begin anticoagulant or antiplatelet treatment promptly to reduce the morbidity and mortality of this disorder (3).

CASE REPORT

A 31-year-old man, with an unremarkable medical history, came to the emergency department with sudden onset of left eyelid ptosis and diplopia. He denied fever, headache, and eye pain but reported purple spots on the skin of his legs and trunk of 4-year duration. Skin lesions were accompanied by ulceration in distal areas of both lower limbs. There was no family history of similar skin lesions.

The patient had ptosis of the left eye and limited eye movement consistent with a third nerve palsy. Visual acuity, pupils, slit-lamp examination, and funduscopy were normal. The skin on the patient's trunk and legs showed a reticulated pattern with irregular and open trabeculae. There were ulcerations in the distal third of both lower limbs (Fig. 1). The remainder of the physical and neurological examinations were normal.

FIG. 1
FIG. 1:
Livedo racemosa affecting the lower limbs. Inset: cribiform ulceration in the distal third of the left leg.

Laboratory testing included complete blood count, serum chemistries, thyroid panel, protein immunoglobulin and complement levels, and hypercoagulability studies that were all normal. Autoimmunity studies, including antinuclear antibody, anti-neutrophil cytoplasm, cryoglobulins, anti-DNA, anti-Sm, anti-Ro, anti-La, anti-RNP, anti-citrullinated peptide, anti-mitochondrial, and anti-phospholipid antibodies, were negative. Serological analysis for hepatitis B virus, hepatitis C, human immunodeficiency virus, syphilis, and borrelia was negative. Unremarkable imaging studies included chest x-ray, abdominal ultrasound, echocardiography, single photon emission computed tomography, and magnetic resonance angiography of the brain. Examination of the cerebrospinal fluid was normal. Skin biopsy was taken from the edge of one of the leg ulcers. Histopathological findings included signs of endotheliitis and obliteration of the lumen of dermal blood vessels due to intimal proliferation and fibrin thrombi, with no signs of vasculitis (Fig. 2).

FIG. 2
FIG. 2:
Histology of skin biopsy at the edge of the ulcer.A. Fibrin thrombus in a dermal blood vessel (hematoxylin and eosin, × 200). B. Endotheliitis and intimal proliferation (hematoxylin and eosin, × 600).

Correlating the neurological symptoms (third nerve palsy), the presence of LR, the negative studies for autoimmune and infectious causes, and pathological findings on skin biopsy, we reached the diagnosis of SS. We began treatment with acetylsalicylic acid, 300 mg/day. No new neurological symptoms developed in 2 years of follow-up and the skin ulcerations resolved. The patient's third nerve palsy completely recovered within 3 months.

DISCUSSION

SS is a rare systemic, progressive, noninflammatory vasculopathy, characterized by the presence of generalized LR and cerebrovascular symptoms due to involvement of small- and medium-sized skin and brain blood vessels (1,4). This association was first described in a patient by Champion and Rook (5) and, in 1965, Sneddon (6) documented these findings in 6 additional patients. The incidence is 4 cases/1,000,000/y with a mortality of approximately 9.5% (3). The disease is more common in women aged 20–40 years (2) and appears spontaneously (7). When SS appears in men, it usually occurs at a later age (7). Isolated familial cases have been reported, suggesting a genetic predisposition (6).

Neurological involvement typically appears after the onset of livedo racemosa. Findings include headache, dizziness, seizures, and progressive dementia (8). The most common neurological manifestations are transient ischemic attack and stroke usually affecting the middle cerebral artery. Reported ophthalmologic complications include central retinal artery occlusion, central retinal vein occlusion, retinal neovascularization, homonymous visual field defects, and internuclear ophthalmoloplegia (9–13).

The pathogenesis of SS is not fully understood and its association with autoimmune disease, such as primary anti-phospholipid antibody syndrome, systemic lupus erythematosus, and hypercoagulable states, such as mutation in the factor V Leiden, is in dispute (1).

Skin biopsy is useful for the diagnosis, although it may require multiple biopsies to reach a diagnostic yield of 80%. The biopsy should be performed in the central area of the LR reticle. Histologic findings are endotheliitis, vascular occlusion by fibrin thrombi, and the proliferation of the intima and media without evidence of vasculitis primarily involving arteries of the reticular dermis (7,14). The differential diagnosis of SS includes anti-phospholipid antibody syndrome, multiple sclerosis, coagulopathy, and infectious conditions, such as syphilis and Lyme disease (3).

Forty to fifty percent of patients with SS have positive anti-phospholipid antibodies (15). If they are negative, platelet antiaggregant therapy is indicated, and if positive, the patient should be anticoagulated. Cardiovascular risk factors should be treated and the patient should avoid tobacco use and oral contraceptives (3). The efficacy of immunosuppressive therapy is controversial (1).

Our patient with SS developed the microvascular complication of a third nerve palsy. It is essential that SS be recognized and treated appropriately to avoid more severe vascular involvement that can be life-threatening.

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