CANDLE syndrome

A rare autoinflammatory genetic disorder

CANDLE syndrome (Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature) is a rare autoinflammatory disease characterized by recurrent fevers, skin rashes, and joint pain. It is caused by mutations in the PSMB8 gene and is inherited in an autosomal recessive manner.

Genetics

Diagram of autosomal recessive inheritance.

CANDLE syndrome is associated with mutations in the PSMB8 gene, which encodes a component of the immunoproteasome. This gene is located on chromosome 6. The syndrome follows an autosomal recessive pattern of inheritance, meaning that an affected individual must inherit two copies of the mutated gene, one from each parent.

Clinical Features

Patients with CANDLE syndrome typically present in infancy or early childhood. The main clinical features include:

• Recurrent fevers
• Skin rashes, often with a neutrophilic dermatosis appearance
• Lipodystrophy, which is the abnormal distribution of body fat
• Joint pain and swelling
• Muscle weakness

Pathophysiology

The PSMB8 gene mutations lead to a dysfunctional immunoproteasome, which is crucial for the degradation of proteins and the regulation of the immune response. The impaired function results in the accumulation of protein aggregates and an inappropriate inflammatory response, contributing to the symptoms of CANDLE syndrome.

Diagnosis

Diagnosis of CANDLE syndrome is based on clinical presentation, family history, and genetic testing to identify mutations in the PSMB8 gene. Laboratory tests may show elevated inflammatory markers and abnormal immune cell function.

Treatment

There is no cure for CANDLE syndrome, and treatment is primarily supportive. Management strategies include:

• Anti-inflammatory medications, such as corticosteroids
• Immunosuppressive agents
• Biologic therapies targeting specific inflammatory pathways

Prognosis

The prognosis for individuals with CANDLE syndrome varies. Early diagnosis and management can improve quality of life, but the condition can be chronic and debilitating.

Related pages

• Autoinflammatory disease
• Lipodystrophy
• Neutrophilic dermatosis