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Intermittent TNF receptor-associated syndrome (TNF receptor-related syndrome)
Medical expert of the article
Last reviewed: 07.07.2025
Familial Irish fever (a periodic syndrome associated with tumor necrosis factor (TNF) receptors) is an inherited disorder characterized by recurrent episodes of fever and migratory myalgia with painful erythema of the overlying skin. TNF type I receptor levels are low. Treatment is with glucocorticosteroids and etanercept.
TNF receptor-associated periodic syndrome has been described in a family of Irish and Scottish descent, but has also been reported in many other ethnic groups. It is caused by mutations in the gene encoding the TNF receptor. Defects in this receptor are thought to lead to excessive, unchecked activation, with inflammation developing as a result.
Attacks of this rare disease usually begin before the age of 20. They can last from 1-2 days to a week or more. The most prominent signs are muscle pain and swelling of the extremities. Other symptoms of TNF receptor-associated periodic syndrome may include headache, abdominal pain, diarrhea or constipation, nausea, painful conjunctivitis, joint pain, rash, and testicular pain. Male patients are more likely to develop inguinal hernias. There are reports of renal amyloidosis in a small number of families.
Diagnosis is based on history, examination, and low TNF type I receptor levels when measured interictally. Nonspecific features include neutrophilia, elevated acute-phase reactants, and polyclonal gammopathy during attacks. Patients should have regular urine tests to detect proteinuria early.
TNF receptor-associated periodic syndrome has a good prognosis with treatment, but should be done more cautiously if renal amyloidosis develops. Attacks can be effectively treated with prednisolone at doses of at least 20 mg orally once daily. Doses may need to be increased over time. Early results with etanercept, a TNF-binding and -inactivating drug, are promising. The recommended dose is 0.4 mg/kg subcutaneously in children and 25 mg subcutaneously in adults, administered twice weekly.
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