Combination therapy for Sneddon syndrome to reduce the incidence of cerebrovascular complications.

BACKGROUND: Sneddon syndrome is an occlusive vasculopathy that presents clinically with generalized livedo racemosa on the skin and transient ischemic attacks, strokes, and cognitive or motor deficits in the central nervous system. Antiplatelet or anticoagulant therapy is recommended. Due to the limited therapeutic efficacy and the resulting serious complications, we propose combination therapy with additional infusion cycles of alprostadil and captopril and report initial long-term results. PATIENTS AND METHODS: We performed a systematic retrospective analysis of all patients with primary Sneddon syndrome who received combination therapy in our clinic between 1995 and 2020. Therapeutic outcomes were evaluated using descriptive statistics compared to historical controls receiving monotherapy. We also analyzed the event rate of complications when combination therapy was discontinued. RESULTS: During the 99.7 patient-years of follow-up, there were no transient ischemic attacks and the stroke rate dropped to 0.02 per patient-year. In comparison, the rates of transient ischemic attacks and strokes in the historical controls ranged from 0.08 to 0.035 per patient-year. After discontinuation of alprostadil therapy, eight events occurred in three patients. CONCLUSIONS: Combination therapy reduces the long-term incidence of ischemic events in patients with primary Sneddon syndrome.

Antiphospholipid-negative Sneddon's syndrome: A comprehensive overview of a rare entity.

The term Sneddon's syndrome (SS) has been used since 1965 to describe a vasculopathy characterized by a combination of cerebrovascular disease with livedo racemosa. SS may be classified as antiphospholipid+ (aPL+) or antiphospholipid- (aPL-). Little is known about aPL- SS; in this review we describe the epidemiology and pathogenesis of aPL- SS, as well as the clinical and histologic features. We discuss recent findings in terms of neurologic and cardiac involvement. Moreover, differential diagnoses of conditions that may present with both livedo racemosa and stroke are discussed. Finally, we discuss real-life practical issues such as the initial investigations to be performed, long-term follow-up, and therapeutic management of aPL- SS patients.

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 ± 52.0 months, 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.

Sneddon syndrome: a comprehensive clinical review of 53 patients.

BACKGROUND: The presence of livedo reticularis in patients with ischaemic stroke is associated with Sneddon syndrome (SS). Our objective was to present the clinical features of SS patients and to assess the role of antiphospholipid antibodies (APL). METHODS: Consecutive patients, diagnosed with SS between 1996 and 2017, were retrospectively reviewed for their demographic, neurological, dermatological, cardiac and extracerebral vascular features. Diagnosis of SS was made only if other causes of stroke were excluded. Patients with and without APL were included and compared for their clinical features. RESULTS: Fifty-three patients (79% female) were included, of whom 14 patients were APL-positive. Median age at diagnosis was 40 years. Approximately 60% of the patients had ≥ 3 cardiovascular risk factors. There were 129 previous vascular events (66 ischaemic strokes, 62 TIAs and 1 amaurosis fugax) during a median period of 2 years between the first event and diagnosis of SS. Skin biopsy was positive for SS in 29 patients (67%), mostly showing a thickened vessel wall with neovascularization in the deep dermis. After a median follow-up of 28 months, 4 patients, either on antiplatelet or oral anticoagulation therapy, had a recurrent stroke. There were few statistically significant differences between APL-negative and APL-positive patients, including the number of vascular events before diagnosis. CONCLUSIONS: SS predominantly affects young women with a relatively large number of cardiovascular risk factors. Clinical features of SS are comparable across different studies. We found no differences in the main clinical features between APL-positive and APL-negative patients.

Sneddon syndrome with or without antiphospholipid antibodies. A comparative study in 46 patients.

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.

[Ischemic stroke at the young age: the role of antiphospholipid antibodies]. / Ishemicheskii insul't v molodom vozraste: rol' antifosfolipidnykh antitel.

Output of antiphospholipid antibodies (aPL) coupled with arterial and/or venous thromboses, miscarriage and some other clinical manifestations is denoted as antiphospholipid syndrome (APS). The syndrome is primary (PAPS) in the absence of other autoimmune diseases. Arterial thromboses occur most frequently in the cerebral arteries, leading to ischemic disorders of cerebral circulation (DCC). The present work summarises the results of our own studies and of the reported data on DCC in PAPS. Their characteristic features Include the relationship with occlusion of the intracerebral or intracranial rather than of the great vessels of the head, liability for recurrences in the absence of secondary prophylaxis, frequently occurring association with primary disorder of cerebral circulation (PDCC), good restoration of the focal neurologic deficit after the first stroke, more frequent development in women. The clinical recognition of DCC which stem from aPL output is favoured by the presence in the patients of the basic non-cerebral signs of PAPS (miscarriage peripheral venous thrombosis, myocardial infarction) as well as by the presence of the additional evidence of PAPS (livedo, induration of heart valves according to the EchoCG data, epileptic syndrome, migraine-like headaches, chorea in the anamnesis, and so forth). In most cases, they precede the first DCC by several years or months. The secondary prophylaxis of DCC in PAPS includes the intake of indirect anticoagulants and. small doses of aspirin.

Sneddon's syndrome: a comprehensive review of the literature.

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]. / 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.

[Neurological appearances of primary antiphospholipid syndrome].

Neurological disturbances frequently emerge in antiphospholipid syndrome (APS). One hundred and twenty four patients (100 women, 24 men, mean age 37.5 +/- 11.3 years) with primary APS (PAPS), including 76 patients with Sneddon's syndrome and positive antibodies to phospholipids (aPL), have been studied. A structure of neurological disturbances was as follows: ischemic lesions of cerebral blood flow (LCBF) which comprised stroke and transient LCBF (91%); thrombosis of brain venous sinuses (3%); epileptic seizures (24%); headache (65%); chorea (15%); visual neuropathy (9%); peripheral neuropathy (6%); multiple-sclerosis-like syndrome (10%); myasthenia syndrome (1%); syndrome of parkinsonism of non-vascular genesis (1%) and psychotic disorders (2%). 84% patients had main systemic APS symptoms (fetal loss, thrombosis), which preceded neurological appearances in 78% cases. All the patients had aPL: aPL to cardiolipin (aCL) and/or lupus coagulant (LC) and/or aPL to phosphatidyl serine, phosphatidyl inositol, phosphatidyl ethanolamine. In some patients, aCL titres ranged from positive to negative values and LC was not consistently detected. Thus, the presence of clinical symptoms of PAPS including neurological disturbances demands an investigation of different aPL types as well as a replicate study for immunological confirmation of PAPS.

[Sneddon's syndrome and systemic lupus erythematosus with cerebrovascular disturbances and widespread livedo].

A comparative clinical and instrumental analysis of 97 patients with Sneddon's syndrome (SS), a combination of cerebrovascular ischemic disturbances with widespread livedo, and 12 patients with systemic lupus erythematosus (SLE) with the same combination, has been conducted. Despite the presence of similar features related to antiphospholipid syndrome (APS)--cerebrovascular disturbances, livedo, fetal loss, peripheral venous thrombosis, thrombocytopenia, antibodies to phospholipids, etc--there were distinct differences between SS and SLE. In SS, no skin lesions ("butterfly", discoid lupus, photosensibilization) typical for SLE as well as sores of mucous oral cavity, polyarthritis, serosity, diagnostically significant titers of antinuclear factor and antibodies to DNA were observed. SS emerged with livedo (44%), cerebrovascular disturbances (24%) and systemic APS appearances (32%). SLE in 75% cases began with its classical symptoms and in 25% with systemic APS signs and never with livedo or cerebrovascular disturbances. For 10.5 +/- 8.0 years, no cases of SS were featured by typical SLE symptoms. Pathomorphological study indicated that SS and SLE were independent diseases. Their similarity was due to development of secondary APS, including cerebrovascular disturbances and livedo, in some patients with SLE.

Síndrome de sneddon y anticoagulante lúpico: presentación de un caso

Se presenta un caso de Síndrome de Sneddon (livedo recticularis, enfermedad cerebrovascular e hipertensión arterial). Se presentó como demencia precedida de episodios de isquemia cerebral transitoria. La hipertensión se pudo originar por los numerosos infartos renales. Se encontró el tiempo parcial de tromboplastina prolongado, cuyo comportamiento con las diluciones sugiere un "anticoagulante lúpico". Este hallazago concuerda con la hipótesis del papel patogénico de los anticuerpos antifosfolípidos en este síndrome