Sneddon syndrome: under diagnosed disease, complex clinical manifestations and challenging diagnosis. A case-based review.

Herein, we report a case-based review of the Sneddon Syndrome (SS), a rare chronic condition which affects small to medium blood vessels. It is known by its skin presentation, livedo racemosa (LRC), and the relapsing cerebrovascular events. However, neither LRC nor cerebrovascular events are exclusive to SS. A 36-year-old female with history of mitral valve prolapse, hypothyroidism, Raynaud phenomenon, hypertension, migraines, and four episodes of transient ischemic attacks (TIA), presented to our clinic with new skin findings, suggestive of LRC. Based on her previous history, current presentation and skin biopsy results, she was diagnosed with SS secondary to antiphospholipid syndrome. The present report illustrates the difficulty in recognizing SS and how the heterogeneity of the disease may be contributing to the difficulty making a distinct diagnosis.

Sneddon Syndrome: A Comprehensive Overview.

Sneddon syndrome (SS) is an episodic or chronic, slowly progressive disorder and characterized by generalized livedo racemosa (patchy, violaceous, skin discoloration) and recurrent cerebrovascular events. The histopathology of skin and brain is remarkable for a noninflammatory thrombotic vasculopathy involving medium- and small-sized dermal and cerebral arteries, respectively. Approximately 80% of the SS patients are women with a median age of diagnosis at 40 years. However, the onset of the disease during childhood have been reported. Etiopathogenesis of SS is unknown with 2 primary mechanisms proposed - autoimmune/inflammatory versus thrombophilia. SS is primarily classified as antiphospholipid positive or negative type. Neurological manifestations usually occur in 3 phases: (1) prodromal symptoms such as headaches, dizziness, and vertigo, (2) recurrent strokes, and (3) early onset dementia. Livedo racemosa precedes the onset of recurrent strokes by more than 10 years, but in many instances, the significance of the skin lesion is recognized only after the appearance of the stroke. The involvement of the heart valves, systolic labile hypertension, and retinal changes are also commonly associated with this syndrome. Treatment of SS is primarily based on anecdotal reports. Antiplatelet and antithrombotic agents are used for secondary stroke prophylaxis, and a recent study showed a relatively lower stroke recurrence rate with the universal use of antiplatelet/antithrombotic agents. Routine use of anti-inflammatory or immunosuppressive therapies is controversial. Neuropsychiatric prognosis of SS is relatively poor with predominant deficits in the concentration, attention, visual perception, and visuospatial skills.

Sneddon syndrome: rare disease or under diagnosed clinical entity? Review of the literature related to a clinical case.

Sneddon syndrome is defined by the association of livedo racemosa and recurrent cerebrovascular ischemic lesions. The annual incidence is 4/1,000,000. This syndrome particularly affects young women, some reports suggesting a family predisposition. It is a chronic, progressive, arterio-occlusive disease of unknown etiology that involves small and medium-sized arteries. It is usually associated with antiphospholipid antibodies. We report the case of a female patient with Sneddon syndrome with significant family history, personal history of stroke, epilepsy, migraine, cardiovascular involvement, three miscarriages, cognitive decline, noncompliant to therapy, in the absence of antiphospholipid antibodies. This paper aims to analyze the main characteristic features and management of Sneddon syndrome by conducting a literature review related to a clinical case.

Sneddon's syndrome presenting with neuropathic pain.

A 55-year-old man was admitted to us with a sense of numbness, tingling, and burning in his feet and headache, characterized as a feeling of pressure all around his head, for 1 year and aggravated in the past 3 months. The patient's neurologic examination was normal and he had no other known diseases except for hypertension according to his medical history. During the examination, we recognized purplish lesions on the patient's body. His kidney, liver, and thyroid function test results and vitamin B12 levels were all normal. His hematocrit level was 41.8%, platelet value was 234,000 (150,000-500,000); and sedimentation rate was 9 mm/h (0-20). Electromyography was performed and results were found to be normal. The patient was diagnosed as having small fiber neuropathy. Dermatologic examination revealed reddish blue mottling of the skin with fishnet reticular pattern on his back, on the front side of the body, and on both arms and legs, and the lesions were classified as livedo racemosa (Figure 1). Brain magnetic resonance imaging (MRI) showed subcortical hyperintense ischemic-gliotic signal changes on T2-FLAIR in the deep white matter of bilateral frontoparietal vertex, centrum semiovale, and corona radiata (Figure 2). FLAIR sequence axial MRI of the brain of our patient showed subcortical hyperintense lesions in both cerebral hemispheres. His cardiac examination was normal and minimal aortic regurgitation was seen on echocardiography. His cognitive assessment Minimental Test Score was 22, and Montreal Cognitive Assessment score was 18. Laboratory values for inflammatory markers and autoimmune antibodies including syphilis serology, lupus anticoagulants, and anticardiolipin antibodies were negative. Factor V Leiden mutation was not detected in the patient. The patient was diagnosed with Sneddon's syndrome with the above signs and symptoms and small fiber neuropathy. Clopidogrel 75 mg and gabapentin 1200 mg was started once a day and blood pressure regulation was achieved.

[Sneddon syndrome: a rare cause of vascular dementia]. / Le syndrome de Sneddon: une cause rare de démence vasculaire.

Few vascular dementias are diagnosed in memory clinic consultations. One type, a rare etiology, Sneddon syndrome, can lead patients to consult for an isolated memory complaint. We report the cases of two patients, aged 63 and 66 years, who presented frontocortical cognitive profile and behavior disorders. Seronegative Sneddon syndrome, complicated with dementia, was diagnosed in each case by noticing an association between, on MRI, an atrophy and several ischemic cerebrovascular accident aftermaths, and a livedo racemosa. Management of vascular risks factors improves the prognosis.

Intravenous thrombolysis in Sneddon's syndrome.

Sneddon's syndrome (SS) is an uncommon disorder, characterized by the association of ischemic stroke and widespread livedo reticularis. The treatment options for SS to prevent stroke recurrence and future disability include antiplatelet therapy, anticoagulation, or immunosuppression. We describe a patient with SS who presented with an acute ischemic stroke, and was treated with intravenous recombinant tissue-plasminogen activator with significant neurologic improvement. To our knowledge this is the first report of the use of thrombolysis in SS patients with acute ischemic stroke. It suggests that thrombolytic therapy might be safe and effective in these patients.

[Dermatologic aspects of anticoagulation]. / Antikoagulation in der Dermatologie.

The coagulation system protects the body from uncontrolled blood loss by means of highly regulated processes. In case of an injury the coagulation system instantly switches from controlled blood flow to acute coagulation and thrombus formation with the goal of stopping the blood loss. Minor changes in this well-maintained equilibrium of coagulation and blood flow tip the balance towards uncontrolled blood loss or even fatal thromboembolic events. Iatrogenic manipulation of this highly regulated system is possible with a variety of therapeutic agents. We review the basics of coagulation physiology and then discuss dermatologically relevant aspects of thrombosis prevention, as well as the use of anticoagulants to treat dermatologic diseases.

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.

[Characteristics of the kidney lesion in a patient with Sneddon's syndrome].

This case report draws attention to renal damage in a young patient with Sneddon's syndrome, analyses a course of nephropathy and methods of its diagnosis, shows efficacy of anticoagulant therapy, demonstrates possible development of generalized affection of the microcirculatory bed with involvement not only of the skin and brain vessels suggesting that Sneddon's syndrome is a systemic ischemic pathology the manifestations of which in many cases mask polyorganic impairment.

Síndrome de Sneddon: a propósito de un caso / Sneddon syndrome: a case report

El síndrome de Sneddon (SS) es una vasculopatía oclusiva poco frecuente, de etiología no bien precisada, que compromete principalmente la piel (livedo reticularis), el sistema nervioso central (accidentes vasculares isquémicos) y el sistema cardiovascular (hipertensión arterial). Se describe una forma idiopática primaria, una trombótica y una asociada a patologías autoinmunes como el síndrome antifosfolípidos. La livedo reticularis suele preceder al resto de las manifestaciones. La biopsia de piel tomada del centro del retículo es característica. El estudio de laboratorio incluye la búsqueda de algunas mesenquimopatías y la pesquisa serológica del síndrome antifosfolípidos. Entre las posibilidades terapéuticas se incluyen la anticoagulación, la administración de antiagregantes plaquetarios y el evitar agentes protrombóticos. Presentamos el caso de un hombre de 45 años con deterioro cognitivo, accidentes cerebrovasculares trombóticos, hipertensión arterial y livedo reticularis, en el que se diagnostica SS. Es manejado con aspirina y antihipertensivos, evolucionando favorablemente. Destacamos la importancia de reconocer los hallazgos cutáneos del SS para un oportuno diagnóstico y tratamiento.

Sneddon’s syndrome (SS) is a rare vasculopathy of partially known etiology affecting mainly the skin (livedo reticularis), central nervous system (ischemic cerebrovascular episodes) and cardiovascular system. A primary idiopathic form, a thrombotic form and one associated with autoimmune diseases such as the antiphospholipid syndrome, are described. Livedo reticularis is commonly the first manifestation. Skin biopsy taken from the center of the reticulum is characteristic. Laboratory study includes a screening of antiphospholipid syndrome and mesenquimopathies. Possible treatments are anticoagulation, administration of platelet antiagregants and avoidance of pro-thrombotic agents. We present the case of a 45 year old man with dementia, thrombotic cerebrovascular disease, hypertension and livedo reticularis, who is diagnosed with SS. The patient is managed with aspirin and antihypertension drugs, with good response. We reinforce the importance of SS skin manifestations for a proper and quick diagnosis and treatment.

[Sneddon's syndrome: 15 cases with cerebral angiography]. / Le syndrome de Sneddon: étude de 15 cas avec artériographie cérébrale.

Sneddon's syndrome is a rare disease defined by the presence of ischemic cerebrovascular events associated with livedo reticularis. We report a retrospective study of fifteen cases, thirteen women and two men, mean age of 37.93+/-9.77 years. All patients presented one or more cerebral infarcts. Six patients had dementia. Brain magnetic resonance imaging showed several cortical infarcts with white matter involvement. Cerebral angiography performed in all patients, showed a distal arteriopathy in twelve and thrombosis of the right carotid internal artery in one. One patient had antiphospholipid antibodies. Ten patients were treated with antiplatelet agents and five with anticoagulants. The course was favorable in eight patients and stationary in three. Four patients had several recurrent infarcts, one when anticoagulants were discontinued, one taking an anti-sludge-platelet agent and two who were not initially taking any treatment.

Atypical movement disorders in antiphospholipid syndrome.

Movement disorders have only rarely been reported in association with antiphospholipid syndrome (APS). In such cases, chorea is the most common disorder observed, with occasional reports of hemidystonia, Parkinsonism, and hemiballism. We report here on 3 cases of APS (3 women ages 16, 46, and 56 years) who presented with movement disorders, including tics, tremor, myoclonus, and a corticobasal syndrome, never or rarely reported in association with this disease. Mild executive dysfunction was observed in all 3 patients. We also report the successful treatment of two of these patients with mild oral anticoagulation (INR 2-3). Movement disorders in APS seem more clinically heterogeneous than previously thought. Oral anticoagulation should be considered in the treatment of movement disorders associated with APS.

Tremor as the first neurological manifestation of Sneddon's syndrome.

We report on a 54-year-old woman with Sneddon's syndrome manifested by livedo reticularis, fetal losses, hypertension, and high antinuclear antibody titres. At the age of 42 years she developed tremor of the trunk, limbs, and head only in the standing position that interfered with walking, followed some years later by cognitive decline and a parkinsonian syndrome. T2-weighted brain magnetic resonance imaging showed high signal in cortical areas, basal ganglia, midbrain, and cerebellum.