Sneddon's Syndrome Research Articles

Sneddon's syndrome: case report and review of its relationship with antiphospholipid syndrome

The Sneddon's syndrome is a rare disorder characterized by the occurrence of cerebrovascular disease associated with livedo reticularis. The antiphospholipid syndrome is the most frequent type of acquired thrombophilia, defined by the occurrence of thrombosis or pregnancy morbidity in the presence of persistently positive antiphospholipid antibodies. Approximately 80% of Sneddon's syndrome patients have an antiphospholipid antibody marker. These antibodies may play a pathogenetic role in some cases of Sneddon's syndrome, and many authors consider these two syndromes as the same entity. Although clinical features of antiphospholipid syndrome and Sneddon's syndrome may overlap, there is a distinction between clinical and laboratory evidence suggesting that these two entities are different diseases. A recent finding of coagulopathies, including elevated levels of coagulation factor VII, decreased levels of protein S, and activated protein C in Sneddon's syndrome patients suggested a possible biological link between the vasculopathy and a primary coagulopathy. Moreover, the clinical course seems to be progressive in Sneddon's syndrome patients and includes increase of disability and cognitive deterioration, more arterial involvement, and the antiphospholipid syndrome shows a more benign course. Both syndromes share clinical and laboratory features, and whether Sneddon's syndrome represents a spectrum of antiphospholipid syndrome remains unclear. Sneddon's syndrome patients have a worse prognosis and may represent a subgroup of patients who demands more rigorous follow-up. It is important to recognize the Sneddon's syndrome, particularly because stroke episodes may be prevented through appropriate treatment.

Le syndrome de Sneddon

Sneddon's syndrome is still raising some nosological and etiopathogenic questions. The occurrence of ischemic stroke in young adults especially in the presence of livedo racemosa should suggest the diagnosis and encourage to perform a skin biopsy, which could strengthen the diagnosis. Management begins with prevention of vascular risk factors and treatments based primarily on anti-thrombotic. Large series of studies over several years could provide clarification of the etiopathogenesis of this syndrome and pave the way for the development of diagnostic criteria and new effective therapies in order to prevent progression to irreversible cognitive impairment.

Sneddon Syndrome without Antiphospholipid Antibodies in 55 Cases: Clinical, Radiological and Pathophysiological Features (S43.005)

Objective: To study the pathophysiological mechanisms of ischemic strokes (IS) and the prognosis of a cohort of patients with a Sneddon syndrome without antiphospholipid antibodies (SSAPL-). Background SS is characterized by the association of a livedo reticularis (LR) with strokes. The clinical and radiological features of the neurological manifestations, its prognosis and the frequency of associated cardiac injury remain poorly known, particularly in the absence of APL. Design/Methods: Review of clinical data and brain imaging in 55 consecutive patients (83% women) with SSAPL-, followed up at our institution between 1991 and 2011. Results: LR was first noticed at a mean age of 32 years and the first stroke at 43; 53% had hypertension. Seventy-four strokes were reported, including 76% of IS, 15% of TIA and 9% of hemorrhagic strokes. A mitral or aortic valvulopathy was found in 52% of the 42 patients with an echocardiography. Brain imaging showed 177 IS of 3 different types: large territorial (43%), small distal cortical subcortical (14%) and lacunar (23%) IS; 70% of the IS were located in the superficial territory of the middle cerebral artery. No significant link was found between the valvulopathy and the presence of territorial IS. Other brain abnormalities were frequent: cortical and subcortical atrophy (>90%) and slight leucopathy. After a mean follow-up of 7.4 years, 82% of patients had a modified Rankin score ≤2. Global IS recurrence rate was 12% with a similar annual rate in the antiplatelet group (1.6%) compared to the anticoagulation group (1.5%). Conclusions: SSAPL- is not only a neuro-cutaneous disorder, frequently involving a valvulopathy. This one does not influence the IS type suggesting IS being caused by the small and medium cerebral arteries vasculopathy. Our results show no progression to a serious handicap in the majority of cases and a small recurrence rate under antiplatelet therapy. Disclosure: Dr. Bottin has nothing to disclose. Dr. Frances has nothing to disclose. Dr. De Zuttere has nothing to disclose. Dr. Boelle has nothing to disclose. Dr. Muresan has nothing to disclose. Dr. Alamowitch has nothing to disclose.

Transient retinal venous and arterial occlusive events in a case of sneddon syndrome.

We report a case with venous and arterial occlusive events in Sneddon syndrome and describe the accompanying fluorescein angiographic findings. Observational case report. This 27-year-old white woman developed acute visual loss and a central scotoma in her right eye in consequence of a central retinal vein occlusion and, 2 years later, a paracentral scotoma in her left eye in consequence of an incomplete branch retinal artery occlusion. Fluorescein angiography revealed an unusual laminar hyperfluorescence downstream to the arterial obstruction. Patient became seropositive for anticardiolipin antibodies in the course of the 2 years. Eventually, the ocular together with neurologic and cardiac manifestations led to the diagnosis of Sneddon syndrome. Sneddon syndrome should be considered in any ocular vascular occlusive event under the age of 50 years. In addition, this case reports for the first time unusual fluorescein angiographic findings of incomplete branch retinal arterial occlusions, possibly associated with endothelial damage in Sneddon syndrome.

Sneddon syndrome associated with Protein S deficiency

Sneddon syndrome (SS) is rare, arterio-occlusive disorder characterized by generalized livedo racemosa of the skin and various central nervous symptoms due to occlusion of medium-sized arteries of unknown. Seizure, cognitive impairment, hypertension, and history of repetitive miscarriages are the other symptoms seen in this disease. Livedo racemosa involves persisting irreversible skin lesions red or blue in color with irregular margins. Usually, SS occurs in women of childbearing age. Protein S deficiency is an inherited or acquired disorder associated with an increased risk of thrombosis. We present a 33-year-old woman with SS with diffuse livedo racemosa, recurrent cerebrovascular diseases, migraine-type headache, sinus vein thrombosis, and protein S deficiency. Protein S deficiency and with Sneddon syndrome rarely encountered in the literature.

Sneddon's Syndrome: Unusual Features and Associations

A 43-year-old Caucasian female, with known 46XY chromosome pure gonadal agenesis and systemic hypertension, presented with upper motor neuron weakness of the right face and upper limb. She was also noted to have livedo reticularis and advanced finger clubbing. Left-sided cerebral infarction was confirmed on brain computed tomography (CT) and, following further investigations, a diagnosis of Sneddon’s s syndrome (SS) was made. Three years later, she went on to develop adenocarcinoma of the right lung, which sadly claimed her life within 4 months. To our knowledge, this is the first reported case of SS in association with finger clubbing and pure gonadal agenesis.

Reticulate eruptions. Part 1: Vascular networks and physiology

Reticulate pattern is one of the most important dermatological signs of a pathological process involving the superficial vascular networks. Vascular malformations, such as cutis marmorata congenita telangiectasia and benign forms of livedo reticularis, and sinister conditions, such as meningococcal meningitis or Sneddon's syndrome, can all present with a reticulate pattern. The clinical presentation and morphology is determined by the nature and extent of the underlying pathology and the involvement of a particular vascular network. This review has been divided into four instalments. In the present paper, we discuss the anatomy and physiology of the complex network of vascular structures that support the function of the skin and subcutis.

Livedo Reticularis and Related Disorders

Livedo reticularis is a violaceous mottling of the skin with a "fishnet" reticular appearance. Primary and secondary etiologies exist, including a pathologic variant termed livedo racemosa. No evidence-based medicine exists to guide therapy for this disorder, but most patients with primary and secondary livedo reticularis are asymptomatic and do not require treatment. In the rare instance that a patient with primary livedo reticularis experiences mild symptoms such as episodic numbness and tingling, avoidance of cold and vasoconstricting substances should be encouraged. Lastly, judicious dosing of a vasodilator such as a calcium channel blocker can be prescribed. Patients with secondary livedo reticularis or livedo racemosa may benefit from these same therapeutic suggestions; however, treating the proximate cause of livedo with a systemic association is encouraged and is most likely to yield cutaneous improvement. Although antiplatelet and/or anticoagulant therapy is often required when treating a patient with the antiphospholipid antibody syndrome or Sneddon's syndrome, the attendant livedo racemosa typically remains unchanged or progresses despite this treatment.

P63 Sneddon's syndrome

P63 Sneddon's syndrome

Cognitive impairment of vascular origin: Neuropathology of cognitive impairment of vascular origin

The term cognitive impairment of vascular origin is used to designate global cognitive deficits as well as focal neurological deficits such as aphasia, apraxia and agnosia of vascular/circulatory origin. It has been useful for identifying early clinical and neuroradiological alterations that might permit therapeutic strategies geared to curbing the progression of cerebrovascular disease. Multi-infarct encephalopathy, infarcts in strategic areas, lacunae and lacunar status, Binswanger's encephalopathy, hippocampal sclerosis, cortical granular atrophy and watershed infarcts are common lesions. Hypertension and vascular diseases such as arteriosclerosis, small blood vessel disease, inflammatory diseases of the blood vessels, Sneddon syndrome, cerebral amyloid angiopathies, cerebral autosomic dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and Maeda's syndrome are causative of cognitive impairment of vascular origin. Other less common causes are hereditary endotheliopathy with retinopathy, neuropathy and strokes (HERNS), cerebro-retinian vasculopathy (CRV), hereditary vascular retinopathy (HVR) (all three linked to 3p21.1–p21.3), hereditary infantile hemiparesis with arteriolar retinopathy and leukoencephalopathy (HIHRATL) (not linked to 3p21), fibromuscular dysplasia, and moya-moya disease. Lack of uniformity of clinical manifestations, the variety of vascular diseases and circulatory factors, the diverse, but often convergent, neuropathological substrates, and the common association with unrelated neurodegenerative diseases in the elderly, make it hard to assume a single clinical approach in the diagnosis and treatment of cognitive impairment of vascular origin. Rather, environmental and genetic risk factors, underlying vascular diseases, associated systemic, metabolic and neurodegenerative diseases and identification of extent and distribution of lesions with morphological and functional neuroimaging methods should be applied in every individual patient.

Improvement of neurological symptoms and memory and emotional status in a case of seronegative Sneddon syndrome with cyclophosphamide

Sneddon syndrome (SS) is characterized by livedo racemosa, recurrent ischemic strokes, and often progressive vascular dementia. Treatment options for SS center on either anticoagulation or immunosuppression to prevent strokes and to dissipate the skin findings, with these modalities based historically on the presence or absence of antiphospholipid antibodies (APA) respectively. However, few effective treatments have been reported to reverse the cognitive decline in SS. We report a case of a woman with seronegative SS (absence of APA) with cognitive decline who demonstrated objective and subjective improvements in her memory and emotional functioning after treatment with cyclophosphamide.

Influence of gender on the clinical and laboratory spectra of patients with primary antiphospholipid syndrome

The objectives of this cross-sectional study were to evaluate the differences between males and females in the clinical and biochemical manifestations of primary antiphospholipid antibody syndrome (PAPS). The method involved 49 patients (38 premenopausal females and 11 males) diagnosed with PAPS (according to the Sapporo criteria) and their demographic data, clinical data, medications used and antiphospholipid antibodies were analyzed. The results of this study are as follows. Both the groups of patients were statistically similar regarding age, race, weight and body mass index. However, males were significantly taller than females (172 ± 8.9 vs. 159.2 ± 6.2 cm, p < 0.0001). The duration of disease was similar for females and males. The prevalence of pulmonary thromboembolism was higher in females than in males (34.2 vs. 0.0%, p = 0.024). Regarding other PAPS manifestations (arterial events, venous events, deep venous thrombosis, thrombocytopenia, acute myocardial infarction, angina, cerebrovascular accidents and Sneddon syndrome), comorbidities (arterial hypertension and dyslipidemia), lifestyle (physical activity, previous smoking and current smoking) and the use of medications (current and previous use of corticosteroids, as well as the use of statins or chloroquine), both groups were statistically similar (p > 0.05). More females than males tested positive for IgM anticardiolipin antibodies (76.3 vs. 36.4%, p = 0.025) or for at least one of the antiphospholipid antibodies tested (either IgM anticardiolipin or IgG anticardiolipin 84.2 vs. 45.5%, p = 0.016). However, both groups were similar regarding the frequency of positivity for lupus anticoagulant and isolated IgG anticardiolipin, as well as regarding mean levels of IgG and IgM anticardiolipin (p > 0.05). We concluded that, among PAPS patients, the frequency of pulmonary thromboembolism and of positivity for IgM anticardiolipin is higher in females than in males. Our findings show that there are gender differences in PAPS, differences that might be related to alterations in sex hormones.

Antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease with recurrent thromboses and pregnancy complications (90% are female patients) that can be primary and secondary (with concomitant autoimmune disease). Antiphospholipid antibodies are prothrombotic but also act directly with brain tissue. One clinical and one laboratory criterion is necessary for the diagnosis of APS. Positive serological tests have to be confirmed after at least 12 weeks. Clinical picture consists of thromboses in many organs and spontaneous miscarriages, sometimes thrombocytopaenia and haemolytic anaemia, but neurological cases are the most frequent: headaches, stroke, encephalopathy, seizures, visual disturbances, Sneddon syndrome, dementia, vertigo, chorea, balism, transitory global amnesia, psychosis, transversal myelopathy and Guillain-Barre syndrome. About 50% of strokes below 50 years of age are caused by APS. The first line of therapy in stroke is anticoagulation: intravenous heparin or low-weight heparins. In chronic treatment, oral anticoagulation and antiplatelet therapy are used, warfarin and aspirin, mostly for life. In resistant cases, corticosteroids, intravenous immunoglobulins and plasmapheresis are necessary. Prognosis is good in most patients but some are treatment-resistant with recurrent thrombotic events and eventually death.

Microembolic signals in systemic lupus erythematosus and other cerebral small vessel diseases

Microembolic signals (MES) are detected by transcranial Doppler (TCD), and are mainly observed in cardiac and large-artery diseases; however they might also be observed in conditions affecting small vessels of the brain. We aimed to review the current medical literature related to MES assessed by TCD in patients with cerebral small vessel disease. We conducted a systematic review in PubMed and selected the articles with information on this topic. Systemic lupus erythematosus (SLE) is the disease with more articles; pooled data showed a frequency of MES of 14.9%. MES were more frequent in SLE patients with antiphospholipid antibodies and ischemic stroke. MES have also been described in other diseases such as primary antiphospholipid syndrome, Sneddon's syndrome, and Behçet's disease. Further studies assessing the significance of MES in the pathogenesis of neurological manifestations of these disorders is warranted.

Primary antiphospholipid syndrome with and without Sneddon’s syndrome

The main objective of this study was to compare clinical and laboratory data obtained from patients with primary antiphospholipid syndrome (PAPS) with and without Sneddon's syndrome (SS). A transverse study with 54 (85.2% female) PAPS patients (Sapporo criteria) was performed. Demographic, drug use, and antiphospholipid antibodies data were evaluated, as well as clinical and laboratory findings of SS. Patients were subdivided into one of two groups: PAPS with SS and PAPS without SS. Both groups were similar with respect to age (p=0.05), gender (p=0.34), race (p=0.31), weight (p=0.93), height (p=0.27), and body mass index (p=0.75); however, the SS group exhibited higher disease duration (96.0±54.9 vs. 55.2±52.0months, p=0.01). By definition, all PAPS with SS patients suffer from stroke, an arterial event; the frequency of stroke events (28.5 vs. 7.5%, p=0.04), as well as of limb ischemia (100 vs. 30.0%, p<0.0001) was higher in this group than in the PAPS without SS group. On the other hand, patients in the PAPS without SS group had more venous events, such as deep venous thrombosis, than those in the PAPS with SS group (80.0 vs. 50.0%, p=0.03). In conclusion, an understanding of the relationship between APS and SS is important in order to identify a subgroup for which more rigorous accompaniment and therapy may be necessary.

FP27-TU-03 Antiphospholipid-antibody-negative Sneddon's syndrome: study of 26 cases with cerebral angiography

FP27-TU-03 Antiphospholipid-antibody-negative Sneddon's syndrome: study of 26 cases with cerebral angiography

A rarely seen syndrome in rehabilitation of hemiplegia: antiphospholipid antibody-negative Sneddon’s syndrome

Sneddon's syndrome is a rarely seen disorder and it is characterized by livedo reticularis (LR) and neurologic findings. Some systematic findings may also be seen with neurologic and cutaneous findings. In this case, we aimed to present a 28-year-old female patient with diffuse LR, cardiac valve disease and migraine-type headache who had a right hemiplegic attack.

Livedo, dementia, thrombocytopenia, and endotheliitis without antiphospholipid antibodies: Seronegative antiphospholipid-like syndrome

We report a 51-year-old woman who presented with dementia, livedo racemosa, polyarthralgia, mild renal insufficiency, proteinuria, and thrombocytopenia. Cutaneous and renal biopsy specimens both showed an identical specific occlusive arteriolopathy consistent with Sneddon syndrome and antiphospholipid syndrome. However, no antiphospholipid antibodies were detected and we, therefore, diagnosed seronegative antiphospholipid-like syndrome. We discuss the nosology of this entity and its association with non-antiphospholipid antibody-related Sneddon syndrome. The common denominator of Sneddon syndrome and antiphospholipid syndrome with or without antiphospholipid antibodies seems to be the endothelial damage and occlusive arteriolopathy. Skin biopsy is useful to confirm the diagnosis of seronegative antiphospholipid-like syndrome.

Sneddon's syndrome

The risk of recurrence of stroke in patients with systemic lupus erythematosus (SLE) is much higher than in other stroke patients, and the preventative treatment is influenced by the underlying systemic disease. Microinfarcts and microhemorrhages are seen frequently in autopsy specimens of SLE patients. Asymptomatic microinfarcts are common, and are now diagnosed due to the high sensitivity of MRI. Occlusions of large arteries and major strokes also occur in lupus patients. Atherosclerosis may be more frequent in SLE patients than in the general population. The major causes of stroke in lupus are cardiogenic emboli and hypercoagulable (including hypofibrinolytic) states, and the mainstay of stroke prevention is long-term warfarin, with an international normalized ratio (INR) of approximately 3.0. Although stroke is an important problem in lupus patients, leading to significant morbidity in young patients, SLE is relatively uncommon in young patients presenting with strokes or transient ischemic attacks (TIAs).

Livedo racemosa as a marker of increased risk of recurrent thrombosis in patients with negative anti-phospholipid antibodies

Background and objective Livedo reticularis racemosa and cerebrovascular lesions characterize Sneddon's syndrome. We report 23 patients with livedo racemosa and describe the association with thrombotic events. Our objective was to determine whether livedo racemosa may be an independent clinical marker for the development of thrombotic events in patients who test negative for anti-phospholipid antibodies. Methods Twenty-three patients with widespread livedo racemosa were studied. None of the patients were positive for anti-phospholipid antibodies. The clinical protocol included a register of thrombotic events, fetal death or miscarriages, hypertension, and valvular heart disease. Cerebral MRI and echocardiography were systematically performed in all patients. Results Nineteen patients (82.60%) had thrombotic events. Fifteen (65.21%) had arterial thrombosis and eleven (47.82%) presented venous occlusions. Seven patients (30.43%) had both arterial and venous thrombosis. Fetal losses were recorded in seven cases (30.43%), with a total number of 33; five patients had 3 or more fetal losses. Eleven out of 23 patients (47.82%) had valvular heart disease. Arterial hypertension was detected in 16 (69.56%) patients. Four patients did not have thrombotic events but had other clinical manifestations. After anti-coagulation therapy was withdrawn, a new thrombotic event was observed in 9 out of the 14 treated patients (64.28%). Conclusions Livedo racemosa seems to be a good clinical marker for the detection of hypercoagulable states even in the absence of anti-phospholipid antibodies or other known biologic markers of thrombosis. Long-term anti-coagulation is probably warranted in patients with livedo racemosa and a previous thrombotic event.