Periodic fever syndrome: a modern view on etiology, pathogenesis, diagnosis and treatment

Abstract

Background. Periodic disease is an autoinflammatory disorder associated with a mutation in the pyrin gene. Historically, the disease is endemic and affects the Mediterranean region. Its genetic determinism has been proven. In our country, this disease is quite rare and poorly studied. Due to the insufficient study of the etiology, pathogenesis, diagnosis, and treatment of periodic disease, an analysis of new information on this issue is relevant. This disease is not accompanied by an increase in antibody titers or cellular immune response. It is associated with increased production of IL-1β, a pro-inflammatory biologically active substance. The mutation that leads to the development of this disease appeared approximately in the 15th century in the Mediterranean during the plague epidemic. Patients with this mutation were more resistant to the epidemic, therefore, had a better chance of survival and having offspring. Thus, this mutation spread in the Mediterranean and became endemic.
Results. Diagnosis of the disease involves collecting a family history and clinical manifestations of polyserositis, arthritis, myalgia, and fever. Particular attention is paid to laboratory criteria, such as levels of inflammatory markers (CRP, SAA). Treatment involves long-term colchicine or targeted therapy with canakinumab, a drug that blocks IL-1β. This disease has been shown to be congenital and associated with a genetic mutation, making it an autoinflammatory rather than an autoimmune disorder. It has been determined that patients with this disease have increased secretion of interleukins (primarily IL-1β) due to abnormal pyrin inflammasome activity associated with a defect in the pyrin gene. In this case, treatment is conservative. The drug of choice is colchicine, however, increasing attention is being paid to a drug that blocks IL-1β – targeted therapy using monoclonal antibodies.
Conclusion. When we review the current data concerning etiology and pathogenesis of the disease, diagnostic therapeutic aspects are considered.