TNF receptor 1-associated periodic fever syndrome

TNF receptor 1-associated periodic fever syndrome is a condition marked by recurrent fevers that last from one to three weeks, accompanied by joint pain, muscle aches, and distinctive skin lesions. It is classified as a periodic fever syndrome and is associated with inflammatory involvement of the skin, joints, eyes, and serosal surfaces, sometimes leading to secondary amyloidosis. The condition has a known genetic basis, resulting from pathogenic variants in the TNFRSF1A gene, and is inherited in an autosomal dominant pattern. Precise prevalence estimates are not well established and the clinical presentation can vary considerably between affected individuals.

Individuals with TNF receptor 1-associated periodic fever syndrome typically experience recurrent episodes of fever accompanied by elevated inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate. Prominent clinical features include abdominal pain, skin rashes, myalgia, and joint discomfort, with additional symptoms like diarrhea, vomiting, headache, and signs of serosal inflammation such as pericarditis and pleuritis seen in many cases. Other findings, including lymphadenopathy, splenomegaly, and various skin manifestations (such as erythema, erysipelas, and macules), may also be present, though not all individuals experience every feature. Not all individuals experience all features, and severity varies considerably.

TNF receptor 1-associated periodic fever syndrome is caused by pathogenic variants in the TNFRSF1A gene, which plays an important role in regulating the inflammatory response. The condition is inherited in an autosomal dominant manner, meaning that a single altered copy of the gene is sufficient to predispose an individual to the disorder. Even within the same family, the severity and specific symptoms can vary considerably, reflecting variable expressivity.

Currently, management of TNF receptor 1-associated periodic fever syndrome focuses on supportive care and symptom management. As there are no treatments specifically approved for this condition, therapy is tailored to the individual and typically involves a multidisciplinary team approach. Regular surveillance is an essential part of long-term care, helping to identify potential complications such as secondary amyloidosis early. Patients should discuss treatment options with their healthcare team and are encouraged to seek genetic counseling to better understand the condition and family planning options.

Outcomes for TNF receptor 1-associated periodic fever syndrome vary depending on symptom severity, age at diagnosis, and access to specialized care. With current standards of care, many individuals experience stabilization of their symptoms and can maintain a good quality of life into adulthood despite recurrent inflammatory episodes. The clinical course is highly variable, and not all individuals experience the same complications or progression. Outcomes described in medical literature continue to evolve as standards of care improve, and families often find it helpful to connect with specialists and seek genetic counseling for guidance on long-term management.

Clinical trials are underway exploring new treatment approaches for TNF receptor 1-associated periodic fever syndrome. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.