Nakajo-Nishimura syndrome

Nakajo-Nishimura syndrome (NNS), also known as Japanese autoinflammatory syndrome with lipodystrophy (JASL) or nodular erythema with digital changes, is an extremely rare autosomal recessive autoinflammatory disorder caused by mutations in the PSMB8 gene, which encodes the β5i subunit of the immunoproteasome. This condition belongs to a group of disorders collectively termed proteasome-associated autoinflammatory syndromes (PRAAS) or chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) spectrum disorders. The disease typically presents in early childhood with recurrent episodes of fever and nodular erythema-like skin lesions, often beginning as pernio-like (chilblain-like) lesions on the fingers and toes. Over time, patients develop progressive lipodystrophy (loss of subcutaneous fat), particularly affecting the face and upper body, giving a characteristic aged or emaciated appearance. Joint contractures, muscle wasting, and elongated clubbed fingers are prominent features. Hepatosplenomegaly, basal ganglia calcification, and elevated liver enzymes may also occur. Patients frequently develop secondary metabolic complications including hypertriglyceridemia and insulin resistance. Nakajo-Nishimura syndrome has been reported predominantly in Japanese patients. There is no definitive cure, and treatment is largely supportive. Immunosuppressive therapies, including corticosteroids and JAK inhibitors (such as baricitinib), have shown some benefit in managing the autoinflammatory manifestations. The disease is progressive and can lead to significant disability and reduced life expectancy due to systemic inflammation and organ involvement.

Common questions about Nakajo-Nishimura syndrome