This article reports a case of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) misdiagnosed as Kawasaki disease and summarizes the clinical features and therapeutic progress of TRAPS and the relationship between its clinical manifestations and gene mutations. We retrospectively analyzed a patient with tumor necrosis factor receptor superfamily member 1A (TNFRSF1A) -mutated auto-inflammatory disease who was misdiagnosed with Kawasaki disease in another hospital. The clinical features and therapeutic progress of TRAPS were analyzed by combining clinical features and gene reports of this case and literature review. TRAPS onset occurred in a female pediatric patient at the age of 4 months. The child and in his father at the age of 6 years, both of whom manifested periodic fever, and recurrent rash, as well as elevated leukocytes, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) during episodes but normal between episodes. This child carried a heterozygous mutation in TNFRSF1A located in the region 6442923-6442931 on chromosome 12. The nucleic acid alteration was: c.298 (exon3) _c.306 (exon3) 291 delCTCAGCTGC, resulting in a 3 amino acid deletion p.L100_C 102del 292 (p.Leu100_Cys102del) (NM_001065). After etanercept treatment, the symptoms of fever and rash disappeared, and the levels of ESR, CRP, interleukin (IL)-1, IL-6, and TNF-α levels were normal. Subsequently, no liver, kidney, or cardiac amyloidosis and severe etanercept-related adverse events were observed at 1-year follow-up. TRAPS pathogenesis is associated with TNFRSF1A mutation, which is characterized by periodic episodes of fever, mostly accompanied by recurrent rashes, periorbital edema, abdominal pain, and serious complications of organ amyloidosis. Moreover, etanercept can effectively alleviate the clinical symptoms and high inflammation level of TRAPS.

OBJECTIVE: TNF receptor-1-associated periodic syndrome (TRAPS) is a rare autosomal dominant autoinflammatory disorder associated with mutations in the TNF receptor super family 1 A (TNFRSF1A) gene. AA amyloidosis (AA) is the most severe complication of TRAPS. To study the occurrence and prognosis of AA in TRAPS, we conducted a retrospective study of all French cases and a systematic literature review.
METHODS: This case series includes TRAPS patients followed by our centre from 2000 to 2020 presenting with histologically confirmed AA. We conducted a systematic literature review on the PubMed and EMBASE databases for articles published up to February 2021 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and using the keywords: amyloidoisis, amyloid, TNF receptor-associated periodic syndrome, TNF receptor-associated periodic syndrome, tumor necrosis factor receptor-associated periodic syndrome, TRAPS, TNFRSF1A, familial hibernian fever and hibernian familial fever.
RESULTS: A total of 41 TRAPS with AA were studied: three new patients and 38 cases from the literature. AA diagnosis preceded that of TRAPS in 96% of cases, and 17/36 (47%) required renal replacement therapy. Death occurred in 5/36 (14%) with a median follow-up of 23 months. Effect of biologics on AA were available for 21 regimens in 19 patients: 10 improved renal function, seven stabilized and four worsened. Four patients (36% of transplanted patients) relapse AA on kidney graft (only one under etanercept).
CONCLUSIONS: TRAPS is revealed by AA in most cases. Therefore, clinical features of TRAPS should be screened for in AA patients. IL-1 antagonist can help to normalize inflammation and to preserve renal function.