Tumor necrosis factor receptor 1-associated periodic syndrome without fever: cytokine profile before and during etanercept treatment

The objectives of this study are autoinflammatory syndromes which are usually characterized by repeated attacks of fever, especially in children. The presentation of these diseases, however, varies between entities and between patients of a particular syndrome. We report a 16-year-old female patient, who suffered from periodic erythema and myositis/fasciitis. She experienced at least nine attacks of dermatitis and myositis, while no fever episodes were noted over a 3-year period. A delay of puberty with amenorrhea and a short stature were also present. Laboratory investigations consistently showed markedly increased inflammatory parameters (especially a high serum amyloid A) and dysproteinemia. Because the patient′s mother complained about chronic and periodic abdominal pain with also persistently elevated inflammatory parameters, the differential diagnosis included hereditary disorders resulting in chronic inflammation. The diagnosis of an inherited tumor necrosis factor receptor (TNFR) 1-associated periodic syndrome (TRAPS) was confirmed by genetic analyses. Long-term anti-inflammatory treatment with etanercept resulted in a significant clinical improvement and reduction of the inflammatory parameters ESR, CRP, interleukin-6, TNF-α, and soluble TNF-α receptor 1, but not of interleukin-12. Monitoring of the cytokine profile suggested partial effectiveness of etanercept in the treatment of TRAPS. Hereditary fever syndromes have to be considered in case of chronic unexplained inflammation even if fever is no presenting symptom.