Background

This is a rare disorder characterized by livedoid eruption and cerebrovascular defects. There is a distinct association with the Antiphospholipid Antibody syndrome and Lupus erythematosus. Indeed, some investigators believe that this syndrome is a variant of the Antiphophospholipid Antibody Syndrome.

Outline

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Differential Diagnosis
Prognosis and Treatment
Commonly Used Terms

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS	Ehrmann-Sneddon syndrome
INCIDENCE	Estimated at 4/1,000,000

 

DISEASE ASSOCIATIONS	CHARACTERIZATION
ANTIPHOSPHOLIPID ANTIBODY SYNDROME
Livedo reticularis and cerebrovascular accidents (Sneddon's syndrome) as a clinical expression of antiphospholipid syndrome. Gantcheva M, Tsankov N.	J Eur Acad Dermatol Venereol 1999 Mar;12(2):157-60 Abstract quote We present two patients with livedo reticularis and cerebrovascular accidents (Sneddon's syndrome) and positive anticardiolipin antibodies. We suggest that these antibodies may be pathophysiologically related to the clinical manifestation observed in some patients with this syndrome. When Sneddon's syndrome is associated with positive anticardiolipin antibodies it could be regarded as antiphospholipid syndrome and fall into this category of nosological entity.
The mystery of Sneddon syndrome: relationship with antiphospholipid syndrome and systemic lupus erythematosus. Frances C, Piette JC. Service de Medecine Interne, Hopital de la Pitie, Paris cedex 13, France.	J Autoimmun 2000 Sep;15(2):139-43 Abstract quote Since its description in 1965, Sneddon syndrome (SNS) is usually characterized by the association of an ischemic cerebrovascular disease and a widespread livedo reticularis. The presence of many other manifestations suggests that it is a systemic syndrome. The prevalence of anti-phospholipid antibodies (aPL) is highly variable, 41% in our experience. Comparison of patients with or without aPL showed that the fishnet of the livedo was clearly larger in aPL-negative patients who nevertheless, did not develop thrombocytopenia. Seizures and clinically audible mitral regurgitation were more frequently observed in aPL-positive patients. These data lead to consider that SNS is not a unique entity. As patients with primary anti-phospholipid syndrome (APS) and SNS did not differ from those with livedo reticularis, ischemic cerebral events and APS within systemic lupus erythematosus (SLE), there is no reason today to exclude patients with SLE. On one hand, SNS might cover a continuum spectrum joining diverse clinico-biological entities ranging from aPL-negative to SLE-related cases, with primary APS-SNS standing amidst. On the other hand, one might speculate that SNS should be regarded as a nearly similar clinical expression of two distinct disorders, i.e. a peculiar form of APS characterized by preferential arteriolar involvement or on the opposite a primary non-aPL related small artery disease mainly involving brain and skin vessels.
ADDITIONAL ASSOCIATIONS
Annular atrophic lichen planus and Sneddon's syndrome. Lipsker D, Piette JC, Laporte JL, Maunoury L, Frances C. Service de Medecine Interne, Hopital Pitie-Salpetriere, Paris, France	Dermatology 1997;195(4):402-3 Abstract quote We report the case of a patient who had 2 rare diseases, annular atrophic lichen planus (AALP) and Sneddon's syndrome (SNS). This patient had also digital nodules with histological abnormalities suggestive of SNS vasculopathy, which have not been reported so far. AALP is the most rare of all varieties of lichen planus since this case is the third reported to date. The association of livedo racemosa and cerebrovascular disease is the hallmark of SNS, the incidence of which is estimated to be 4 cases per year per million inhabitants. In both diseases, an abnormal production of elastic-tissue-degrading enzymes or a constitutional abnormality of the elastic tissue can be postulated, since SNS is characterized by arteriolar changes with deterioration of the internal elastic lamina and AALP by destruction of the dermal elastic tissue.
Sneddon's syndrome and antithrombin III. Bolayir E, Kececi H, Akyol M, Tas A, Polat M. Department of Neurology, Cumhuriyet University, Sivas, Turkey.	J Dermatol 1999 Aug;26(8):532-4 Abstract quote Sneddon's syndrome, an uncommon disorder, is characterized by multiple cerebrovascular accidents along with ideopathic livedo reticularis. In this article, two cases who had increased amounts of antithrombin III and were diagnosed with Sneddon's syndrome are presented.
Sneddon syndrome, arylsulfatase A pseudodeficiency and impairment of cerebral white matter. Parmeggiani A, Posar A, De Giorgi LB, Sangiorgi S, Mochi M, Monari L, Patrizi A, Rossi PG. Department of Child Neurology and Psychiatry, Neurological Institute, University of Bologna, via Ugo Foscolo 7, 40123, Bologna, Italy.	Brain Dev 2000 Sep;22(6):390-3 Abstract quote We describe a 11 year-old-boy with Sneddon syndrome, confirmed by skin biopsy, and MR evidence of diffuse cerebral hyperintensity of white matter; he also suffered from pre-perinatal hypoxic-ischemic distress. Arylsulfatase A activity was found reduced because of arylsulfatase A pseudodeficiency. We suggest that the association of pre-perinatal distress, Sneddon syndrome and arylsulfatase A pseudodeficiency is responsible for the diffuse impairment of cerebral white matter, never reported in Sneddon syndrome and similar to described cases of delayed posthypoxic demyelination and arylsulfatase A pseudodeficiency.

 

PATHOGENESIS	CHARACTERIZATION
May be a variant of Antiphospholipid Antibody syndrome

 

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
Cerebral blood flow-SPECT in a patient with Sneddon's syndrome. Sumi Y, Ozaki Y, Itoh S, Katayama H, Tanaka S. Department of Radiology, Juntendo University Urayasu Hospital, Chiba, Japan	Ann Nucl Med 1999 Apr;13(2):109-12 Abstract quote We report a 50-year-old woman diagnosed with Sneddon's syndrome and examined by CBF scintigraphy several times for follow-up of the disease. There were no significant changes in her CBF scintigraphic findings or neurological status during the 6-year follow-up period. Sneddon's syndrome is a slowly progressive disorder in which livedo reticularis precedes cerebrovascular accidents. Because small cortical arteries are predominantly affected in Sneddon's syndrome, MR and conventional angiography often fail to show any abnormal findings, and MR imaging may not visualize decreased CBF in the early stage. Therefore, CBF scintigraphy should be performed in patients who have or are suspected of having Sneddon's syndrome.
LABORATORY MARKERS
Antibodies to prothrombin in patients with Sneddon's syndrome. Kalashnikova LA, Korczyn AD, Shavit S, Rebrova O, Reshetnyak T, Chapman J. Institute of Neurology, Moscow, Russia.	Neurology 1999 Jul 13;53(1):223-5 Abstract quote Antiprothrombin antibodies (aPT), a new serologic marker of antiphospholipid syndrome, were studied in 46 patients randomly selected from 73 with Sneddon's syndrome and 20 matched normal controls. aPT were elevated in 26 patients (57%) and were not found in any of the controls. The addition of aPT data increased the proportion of Sneddon's syndrome patients with at least one type of antiphospholipid syndrome marker from 65 to 78%. The finding that aPT are common in Sneddon's syndrome supports the hypothesis that Sneddon's syndrome is a form of antiphospholipid syndrome.

 

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
Classification of Sneddon's syndrome. Schellong SM, Weissenborn K, Niedermeyer J, Wollenhaupt J, Sosada M, Ehrenheim C, Lubach D. Department of Angiology, Hannover Medical School.	Vasa 1997 Aug;26(3):215-21 Abstract quote BACKGROUND: The combination of generalized broken ("racemose") livedo and cerebrovascular accidents is referred to as "Sneddon's syndrome". Although several pathogenetic factors have been suggested the aetiology of Sneddon's syndrome is unknown. Furthermore, considerable variability of patient characteristics gives rise to the question whether "Sneddon's syndrome" denotes a homogeneous disease entity at all. We hypothesized that the diagnosis "Sneddon's syndrome" can be broken down into different subgroups according to possible aetiologic factors. PATIENTS AND METHODS: Thirty-two patients with the combination of generalized broken livedo and cerebrovascular accidents were evaluated by clinical examination, routine diagnostic procedures, MRI of the brain, echocardiography, vascular ultrasound, immunologic and haemostaseologic testing. Patient groups were formed, depending on (1) whether or not an additional feature with a possibly aetiologic role for Sneddon's syndrome was present, and (2) which kind of feature it was. RESULTS: In 16 out of 32 patients, diagnostic features with an implication for the pathogenesis of Sneddon's syndrome could be identified. An autoimmune disorder was diagnosed in six patients. A thrombophilic state was detected in six patients. Three patients had preexisting atherosclerosis. One patient suffered from an embolizing atrial myxoma. Extent and kind of cerebral pathology differed between patient groups as did the kind of cardiac involvement. CONCLUSION: Sneddon's syndrome is not a homogeneous disease entity. Patients should be classified as "primary Sneddon's syndrome" if no aetiologic factor can be detected. On clinical grounds, this from differs from several varieties of "secondary Sneddon's syndrome" which occurs mainly as part of an autoimmune disorder or in a thrombophilic state.
VARIANTS
Sneddon's syndrome with bilateral peripheral retinal neovascularization. Gobert A. Ophthalmology department, University Hospital, Ghent, Belgium.	Bull Soc Belge Ophtalmol 1995;255:85-90 Abstract quote A 27-year old woman is presented with a five year old history of Sneddon's syndrome in whom recently peripheral retinal neovascularization in both eyes was discovered. Sneddon's syndrome is a rare clinical entity first described in 1965 and characterized by typical skin lesions (livedo reticularis) and cerebrovascular lesions occurring at early age. Central retinal artery occlusions have been reported twice in Sneddon-patients, but peripheral retinal capillary occlusions and neovascularization have not yet been reported. The role of the antiphospholipid antibodies in this association is discussed.
Neuropsychological deficits in patients with Sneddon's syndrome. Weissenborn K, Ruckert N, Ehrenheim C, Schellong S, Goetz C, Lubach D. Neurologische Klinik mit Klinischer Neurophysiologie, Medizinische Hochschule Hannover, Germany.	J Neurol 1996 Apr;243(4):357-63 Abstract quote The results of a neurological, neuropsychological and MRI study of the brain in 21 patients (aged 18-59 years) with Sneddon's syndrome are reported. The predominant findings were marked neuropsychological deficits in two-thirds of the patients. While sensorimotor deficits after stroke in these patients had a good prognosis, neuropsychological deficits persisted. Of the 21 patients, 14 were incapable of gainful employment, 10 because of severe cognitive dysfunction.
Sneddon's syndrome in a patient with homonymous hemianopia with macular sparing. Narbay G. Ophthalmology department, University Hospital, Ghent, Belgium.	Bull Soc Belge Ophtalmol 1996;263:103-7 Abstract quote A 48-year-old women is described with the infrequent association of generalized livedo reticularis and cerebrovascular accident of idiopathic origin (Sneddon's syndrome-SS). Visual field testing revealed a left homonymous hemianopia with macular sparing. Though visual field impairments in SS have been reported, the type could usually not be specified precisely because of the dementia and lack of cooperation of the patients.
Sneddon's syndrome: a vascular systemic disease with kidney involvement? Macario F, Macario MC, Ferro A, Goncalves F, Campos M, Marques A. Renal Unit, University Hospital of Coimbra, Portugal.	Nephron 1997;75(1):94-7 Abstract quote Sneddon's syndrome is a systemic disease characterized by livedo reticularis and cerebrovascular disease. Other organs may be involved as well. Typical vascular lesions in the skin biopsy and/or digital arteries biopsy can be found. Arterial hypertension, cardiac pathology (ischemic disease, myocardial infarction, valvulopathy), venous thrombosis and even fetal death are also found sometimes. We present a case of Sneddon's syndrome in which typical vascular lesions in the kidney were demonstrated for the first time unequivocally confirming the systemic nature of this syndrome.
Sneddon's syndrome: neuro-ophthalmologic manifestations in a possible autosomal recessive pattern. Rehany U, Kassif Y, Rumelt S. Department of Ophthalmology, Western Galilee-Nahariya Medical Center, Nahariya, Israel.	Neurology 1998 Oct;51(4):1185-7 Abstract quote Sneddon's syndrome is a rare neurodermatologic disorder that is manifested by multiple cerebrovascular accidents and livedo reticularis. The authors describe two siblings from one family with Sneddon's syndrome, suggesting autosomal recessive inheritance. The propositus presented with internuclear ophthalmoplegia and ophthalmic artery occlusion. These manifestations as well as the autosomal recessive inheritance have not yet been reported in Sneddon's syndrome.
Superior mesenteric artery stenting for mesenteric ischaemia in Sneddon's syndrome. Khoo LA, Belli AM. Department of Diagnostic Radiology, St George's Hospital, London, UK.	Br J Radiol 1999 Jun;72(858):607-9 Abstract quote Mesenteric ischaemia is a rare but serious cause of abdominal pain. We present the case of a man with Sneddon's syndrome, who had symptomatic mesenteric ischaemia secondary to a superior mesenteric artery stenosis in conjunction with a hepatic artery stenosis. As far as the authors are aware, this has not previously been described in Sneddon's syndrome, which is a vascular systemic disease characterized by an association between cerebrovascular accidents and a livedo reticularis skin rash. He was treated with balloon angioplasty and stent insertion, with good symptomatic improvement. This has implications for other stenoses in this condition should they become symptomatic.
Gradually progressive dementia without discrete cerebrovascular events in a patient with Sneddon's syndrome. Wright RA, Kokmen E. Department of Neurology, Mayo Clinic Rochester, MN 55905, USA.	Mayo Clin Proc 1999 Jan;74(1):57-61 Abstract quote A 37-year-old man sought medical advice because of an 8-year history of a slowly progressive dementing illness with no clinically apparent discrete strokelike episodes. Cognitive functioning was markedly, globally impaired without lateralizing or localizing features. Widespread livedo reticularis led to a diagnosis of Sneddon's syndrome. Antiphospholipid antibodies and lupus anticoagulant were negative. Magnetic resonance imaging showed widespread cerebral atrophy, cortical and subcortical cerebral infarcts, and extensive periventricular white matter abnormalities. Cerebral angiography revealed diffuse medium- and small-vessel occlusive disease, with numerous collaterals in the mid and distal circulation but no evidence of atherosclerosis or vasculitis. No other cause of a dementing illness was found. We postulate that our patient's dementia was due to the cumulative effects of multiple cerebral infarcts.

 

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL
Diagnostic impact and sensitivity of skin biopsies in Sneddon's syndrome. A report of 15 cases. Wohlrab J, Fischer M, Wolter M, Marsch WC. Department of Dermatology and Venereology, Martin Luther University Halle-Wittenberg, Ernst-Kromayer-Str. 5-6, D-06097 Halle, Saale, Germany.	Br J Dermatol 2001 Aug;145(2):285-8 Abstract quote BACKGROUND: Sneddon's syndrome is defined as a combination of idiopathic livedo racemosa generalisata and symptoms of cerebrovascular defect. The disease usually starts with vascular symptoms in the epidermis, with neurological deficits becoming evident later. For this reason, histological examination of skin biopsies and determination of arteriolar occlusion is of particular importance for reliable categorization and early diagnosis. To date, these methods have been considered to be too insensitive. OBJECTIVES: To evaluate the sensitivity of skin biopsies in Sneddon's syndrome. METHODS: We took a total of five deep punch biopsies (4 mm) from different areas of the livedo (three from white and two from red areas) in 15 patients. Present knowledge of the pathogenic relationships and the particular anatomical features of the skin were taken into account. RESULTS: The method had a sensitivity of 27% with one biopsy, 53% with two biopsies and 80% with three biopsies taken from white areas in all cases. CONCLUSIONS: Skin biopsies using the method presented achieved a high sensitivity, suggesting that the diagnosis in clinically suspected cases could be confirmed in the majority of cases with this technique.

 

DIFFERENTIAL DIAGNOSIS

KEY DIFFERENTIATING FEATURES

Atrial myxoma syndrome mimicking Ehrmann-Sneddon syndrome. Weisshaar E, Claus G, Friedl A, Gollnick H. Department of Dermatology and Venereology, University of Magdeburg, Germany.

Dermatology 1997;195(4):404-7 Abstract quote Livedo racemosa with cerebrovascular lesions has been described as Ehrmann-Sneddon syndrome. The etiopathogenetic factors provoking the vascular lesions, however, are of high diversity reaching from mechanical to autoimmune causes. We present a male patient with typical livedo racemosa, muscle pain and feeling of coldness of the forearms. By dermatohistopathology and magnetic resonance tomography of the brain, Ehrmann-Sneddon syndrome could be confirmed. At this time a chronic streptococcal infection could be diagnosed. Antibiotics, anticoagulants and vascularity-supplying therapy improved the clinical and subjective symptoms. Six months later, the patient developed dizziness, vision disorder, hypesthesia of the right forehead, malaise and weight loss. A further diagnostic workup including echocardiography revealed a myxoma of the left atrium. This report illustrates the association of Ehrmann-Sneddon syndrome with cardiac myxoma and points out that cardiac diagnostic examination should be included when dealing with small-vessel involvement of the brain.

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
The natural course of cerebral lesions in Sneddon syndrome. Tourbah A, Piette JC, Iba-Zizen MT, Lyon-Caen O, Godeau P, Frances C. Federation de Neurologie, Groupe Hospitalier Pitie-Salpetriere, Paris, France.	Arch Neurol 1997 Jan;54(1):53-60 Abstract quote OBJECTIVES: To characterize the clinical, biological, and neuroradiological findings in Sneddon syndrome; to correlate magnetic resonance imaging abnormalities with disability, presence of hypertension and other vascular risk factors, presence of heart valvulopathy on echography, and titer of antiphospholipid antibodies; and to compare these findings in antiphospholipid-positive and antiphospholipid-negative patients. DESIGN: Retrospective review of the records of 32 consecutive patients with livedo reticularis and neurological events, followed up in our institution between January 1991 and August 1995. PATIENTS: Twenty-six patients (20 women and 6 men) who had at least 1 cerebral ischemic arterial event associated with generalized and pathological livedo reticularis. RESULTS: The age at the first cerebral ischemic event ranged from 22 to 58 years. Motor deficit was the most frequent sign (found in 73% of cases). Disability was found in 50%, systemic hypertension in 65%, heart valvulopathy in 61%, and antiphospholipid antibodies in 42% of cases. Patients were classified in 6 groups according to magnetic resonance imaging findings. No correlation was found between the presence of hypertension or other vascular risk factors, valvulopathy, antiphospholipids, and magnetic resonance imaging abnormalities. There was no significant difference between antiphospholipid-positive and antiphospholipid-negative patients except for the presence of antinuclear antibodies. There was a significant correlation between the extent of magnetic resonance imaging abnormalities and disability. CONCLUSION: The severity of the disease seems to be correlated with magnetic resonance imaging aspects, but not to the presence of antiphospholipid antibodies. Magnetic resonance imaging may help to understand the natural course of the cerebral involvement of the disease.
Sneddon syndrome with or without antiphospholipid antibodies. A comparative study in 46 patients. Frances C, Papo T, Wechsler B, Laporte JL, Biousse V, Piette JC. Service de Medecine Interne, Hopital de la Pitie, Paris, France.	Medicine (Baltimore) 1999 Jul;78(4):209-19 Abstract quote Sneddon syndrome is characterized by the association of livedo reticularis and cerebral ischemic arterial events (stroke or transient ischemic attack). Reported prevalence of antiphospholipid antibodies is highly variable. We conducted this study to compare the clinical and pathologic features of patients with Sneddon syndrome according to the presence or absence of antiphospholipid antibodies. Forty-six consecutive patients with Sneddon syndrome were analyzed. All were examined by the same dermatologist who classified the livedo of the trunk according to the regularity of the fishnet reticular pattern and according to the thickness of the fishnet reticular pattern (> or = 10 mm = large; < 10 mm = fine). Skin biopsies were systematically performed, from both the center and the violaceous netlike pattern in 38 patients. Antiphospholipid antibodies-positive Sneddon syndrome was defined by the presence of lupus anticoagulant or abnormal titers of anticardiolipin antibodies on repeated determinations. Group I consisted of 27 antiphospholipid antibodies-negative patients and Group II, of 19 antiphospholipid antibodies-positive patients. All patients except I in Group II had irregular livedo reticularis. Large livedo racemosa was more frequently observed in Group I (89%) than in Group II (21%, p < 0.001). On skin biopsy, arteriolar obstruction was detected in only 8 patients (4 in each group). The following parameters were not statistically different between the 2 groups: gender, mean age at detection of livedo, mean age at first clinical cerebral event, hypertension, Raynaud phenomenon, patients with extracerebral and extracutaneous arterial or arteriolar thrombosis or stenosis, patients with venous thrombosis, and women with 2 fetal losses or more. In contrast, seizures (11% in Group I versus 37% in Group II, p < 0.05), mitral regurgitation on echocardiogram (19% versus 53%, p = 0.02), and thrombocytopenia < 150,000/muL (0% versus 42%, p < 0.005) were more frequently observed in Group II. The number of events per year of follow-up was lower with antiplatelet therapy (0.08 versus 0.5) in Group I, but was not different with anticoagulation (0.056 versus 0.06). Antiphospholipid antibodies-negative and -positive patients with Sneddon syndrome belong to close but different subsets of Sneddon syndrome.

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Weedon D. Weedon's Skin Pathology. Churchill Livingstone. 1997.
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.

Antiphospholipid Antibody Syndrome

Vasculitis

Last Updated 12/11/2001