Sneddon's syndrome

Overview

Sneddon's syndrome is a rare, progressive, non-inflammatory arteriopathy characterized by the combination of livedo reticularis (a mottled, purplish skin discoloration) and recurrent cerebrovascular events such as strokes or transient ischemic attacks (TIAs). It primarily affects young to middle-aged adults and is more common in women than in men.

Sneddon's syndrome lies at the intersection of dermatology and neurology, reflecting systemic vascular dysfunction. It can occur sporadically or be associated with autoimmune conditions, particularly antiphospholipid syndrome (APS). Early recognition and long-term management are crucial to reduce stroke risk and improve quality of life.

Causes

The exact cause of Sneddon's syndrome remains unclear, but several mechanisms have been proposed:

• Primary (idiopathic) form: Arises without an identifiable underlying condition. It is thought to involve a non-inflammatory, thrombotic vasculopathy of small- and medium-sized arteries.

• Secondary form: Associated with autoimmune disorders, most notably antiphospholipid antibody syndrome (APS). In this form, antiphospholipid antibodies promote abnormal blood clotting and vascular injury.

Genetic predisposition and endothelial dysfunction may also contribute to the development of the syndrome. Some familial cases have been reported, suggesting a possible hereditary component in select individuals.

Symptoms

Sneddon's syndrome presents with a combination of skin and neurological symptoms. Key clinical features include:

Cutaneous Symptoms

• Livedo reticularis: A net-like, purplish discoloration of the skin, often persistent and more pronounced in cold temperatures. It typically appears on the trunk, buttocks, and limbs.

• Livedo racemosa: A more irregular and broken variant of livedo, considered more characteristic of Sneddon's syndrome.

Neurological Symptoms

• Ischemic strokes: Recurrent strokes are a hallmark feature, often leading to progressive neurological impairment.

• Transient ischemic attacks (TIAs): Brief episodes of neurological dysfunction due to temporary blood flow interruption.

• Headaches or migraines: Common and may precede cerebrovascular events.

• Cognitive decline: Progressive memory loss and cognitive dysfunction may develop over time due to repeated strokes.

• Seizures or visual disturbances: May occur in some cases.

Other Possible Symptoms

• Hypertension

• Heart valve abnormalities (in APS-associated cases)

• Psychiatric symptoms such as depression or personality changes

Diagnosis

Diagnosis of Sneddon's syndrome is primarily clinical and requires a combination of dermatological and neurological findings. Investigations may include:

• Skin examination: Observation of livedo reticularis or livedo racemosa patterns.

• Neurological imaging:

  • MRI: Detects ischemic lesions, often in multiple vascular territories.

  • MRA or CTA: May reveal arterial narrowing or occlusions.

• Laboratory testing:

  • Antiphospholipid antibodies (anticardiolipin, lupus anticoagulant, anti-beta-2 glycoprotein I)

  • Coagulation profiles to assess clotting abnormalities

  • Autoimmune panels to screen for systemic lupus erythematosus (SLE) or related conditions

• Skin biopsy: Can confirm non-inflammatory thrombotic vasculopathy in affected skin areas.

• Cardiac evaluation: Echocardiogram to assess for potential embolic sources or valve abnormalities.

Diagnosing Sneddon's syndrome requires ruling out other causes of livedo and stroke, such as vasculitis, embolic disease, and systemic autoimmune disorders.

Treatment

Treatment of Sneddon's syndrome aims to prevent further strokes and manage underlying clotting abnormalities. Management strategies may include:

Antithrombotic Therapy

• Antiplatelet agents: Aspirin is commonly prescribed to reduce the risk of stroke in idiopathic cases.

• Anticoagulants: Warfarin is used in patients with positive antiphospholipid antibodies or a history of recurrent strokes.

Immunosuppressive Therapy

• Considered in cases associated with systemic autoimmune diseases, although benefits remain uncertain.

Symptomatic and Supportive Care

• Antihypertensives: To control high blood pressure, which may exacerbate vascular damage.

• Migraine treatments: For headache management

• Cognitive rehabilitation and psychological support: For patients with cognitive or psychiatric symptoms

Lifestyle Modifications

• Smoking cessation, regular exercise, and maintaining a healthy weight may help reduce cardiovascular risk.

Prognosis

The prognosis of Sneddon's syndrome varies based on the frequency and severity of cerebrovascular events and the presence of antiphospholipid antibodies. In some patients, the disease remains stable with minimal progression, while in others, repeated strokes may lead to cumulative neurological damage and significant disability.

With early diagnosis and appropriate antithrombotic therapy, the risk of recurrent strokes can be reduced. Lifelong monitoring and management are often necessary to control symptoms and prevent complications. Quality of life can be preserved with comprehensive care, especially when initiated early in the disease course.