In recent years, the proportion of infectious diseases and malignant tumors in cases of fever of unknown origin has decreased, while noninfectious inflammatory diseases and undiagnosed diseases have increased. Autoinflammatory diseases are included in noninfectious inflammatory diseases and undiagnosed diseases and are considered the fourth most common cause of fever of unknown origin, after infectious diseases, malignant tumors, and collagen diseases. When encountering a case of fever of unknown origin, the three major causes—infectious diseases, malignant tumors, and collagen diseases—should be checked. If these are ruled out, autoinflammatory diseases should also be considered in the differential diagnosis. Because the clinical symptoms of autoinflammatory diseases often include fever, joint pain, muscle pain, chest pain, abdominal pain, and skin rash, differentiating them from collagen diseases and related disorders, which have similar clinical symptoms, can be extremely difficult.
When there are characteristic clinical symptoms in periodic fevers, or when there is a family history of fever of unknown origin or a history of fever of unknown origin, autoinflammatory diseases should be considered, but the characteristic clinical presentation should be examined in detail. Furthermore, the presence or absence of disease gene mutations is important for diagnosis. Clinical symptoms differ for each disease, but fever is common. The pattern of fever can also help in infer the disease. In typical familial Mediterranean fever (FMF), the fever subsides within 3 days, but in TNF receptor-associated periodic syndromes (TRAPS), it often lasts for more than 3 days. However, this is not always the case in atypical FMF, and diagnosis is difficult based solely on the duration of fever. Diagnosis must be made in conjunction with other clinical symptoms.
Currently, many genetic tests for autoinflammatory diseases are covered by insurance in Japan. Diagnosing autoinflammatory diseases requires a combination of genetic testing and clinical symptoms.
