Nakajo–Nishimura syndrome

Nakajo-Nishimura Syndrome (NNS) is a rare autoinflammatory disease characterized by a triad of progressive skin rash, partial lipodystrophy, and joint contractures. It is a genetic condition that falls under the umbrella of proteasome-associated autoinflammatory syndromes (PRAAS), which also includes conditions such as Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated Temperature (CANDLE) syndrome and Joint Contractures, Muscle Atrophy, Microcytic Anemia, and Panniculitis-Induced Lipodystrophy (JMP) syndrome. NNS is caused by mutations in the PSMB8 gene, which encodes a subunit of the immunoproteasome, leading to an accumulation of ubiquitinated proteins and an inflammatory response.

Symptoms and Diagnosis

The clinical manifestations of Nakajo-Nishimura Syndrome typically begin in early childhood. Patients present with a persistent fever, skin rash, and nodular erythema, followed by the development of lipodystrophy, particularly in the face and upper extremities, leading to a characteristic facial appearance. Over time, joint contractures develop, particularly affecting the fingers and toes, which can severely impair mobility and quality of life. Muscle atrophy and weakness are also common, and some patients may experience growth delay.

Diagnosis of NNS is based on clinical presentation, family history, and genetic testing confirming mutations in the PSMB8 gene. Differential diagnosis includes other autoinflammatory syndromes and conditions with similar symptoms, such as lupus, rheumatoid arthritis, and other forms of lipodystrophy.

Treatment and Management

There is no cure for Nakajo-Nishimura Syndrome, and treatment is primarily supportive and aimed at managing symptoms and improving quality of life. Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are commonly used to control inflammation and fever. Immunosuppressive drugs and biologic agents targeting specific inflammatory pathways may also be beneficial in some cases. Physical therapy is recommended to maintain joint mobility and prevent contractures. Regular follow-up with a multidisciplinary team including rheumatologists, dermatologists, and physical therapists is essential for optimal management of the disease.

Epidemiology

Nakajo-Nishimura Syndrome is extremely rare, with only a small number of cases reported worldwide. It was first described in Japan, but cases have since been identified in other populations. The exact prevalence is unknown.

Genetics

NNS is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disease. Carriers of one mutated gene typically do not show symptoms of the disease. Genetic counseling may be beneficial for affected individuals and their families.

Conclusion

Nakajo-Nishimura Syndrome is a challenging condition due to its rarity, complex symptomatology, and lack of a cure. Advances in understanding the genetic and molecular basis of the disease have led to improvements in diagnosis and the development of targeted therapies, offering hope for better management and quality of life for affected individuals.