THU0593 CLINICAL AND GENETIC FEATURES OF CHINESE ADULT PATIENTS WITH TUMOR NECROSIS FACTOR RECEPTOR-ASSOCIATED PERIODIC SYNDROME

Abstract

Background: Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) is an autosomal dominant autoinflammatory disase, associated with the mutation of tumor necrosis receptor superfamily member 1A (TNFRSF1A) gene, located on chromosome12p13. TRAPS is usually diagnosed during pediatric age. However, adult-onset disease or diagnosis during adulthood has been occasionally described. Moreover, TRAPS has been hardly reported in the Chinese population. Herein, we aimed to characterize the clinical and genetic features of Chinese adult patients with TRAPS. Objectives: Adult patients (≥16 years) suspected monogenic autoinflammatory diseases during the period April 2015 to October 2018, at the adult autoinflammatory disease center, Department of Rheumatology, Peking Union Medical College Hospital (PUMCH). Methods: Clinical data were evaluated. Gene sequencing was performed in each patient to support the diagnosis and exclude other monogenic autoinflammatory diseases. Finally we compared the data with those from Japan and Europe. Results: During the study period, 8 patients with TRAPS were diagnosed and follow-up. The ratio of male to female was 3: 1. The median age of disease onset was 4 (0.5–38.5), and adult-onset was observed in 2 (25%) patients. The median time of diagnosis delay was 17.8 (1.5-50.5) years. There were seven Chinese Han and one Manchu patients. One patient had a family history of TRAPS. The most frequent symptom was fever (8, 100%). The attacks of 5 (62.5%) patients lasted more than 1 week, and the intervals of 7 (87.5%) patients were longer than 2 weeks. Skin involvement occurred in 6 (75%) patients, with maculopapular mentioned in 6 and erythema annulare presented in 3. Four (50%) patients had arthralgia, while one had polyarthritis. 4 (50%) patients complained respectively of myalgia or headache. 4 (50%) patients experienced abdominal pain and one (12.5%) had vomiting. One (12.5%) patient had periorbital edema, while 3 (37.5%) had conjunctivitis. Up to 5 (62.5%) patients got nonspecific pharyngitis. No patient suffered from chest pain or amyloidosis. Eight gene variants were detected in TNFRSF1A gene. Heterozygous gene variants were found in 7 Chinese Han patients, and homozygous (c.769-23, T>C) happened to the Manchu patient. The variants included C58 (exon 2), G65E (exon 3), F89L (exon 3), C99G (exon 3), V202G (exon 6), c.769-23T>C (IVS8), S290I (exon 9) and m.1735A>G (non-coding region). NSAIDs were given to 2 patients, glucocorticoid or immunosuppressive agents given to 3 patients respectively, and etanercept to 5 patients. A complete response was found in all the 5 patients received etanercept. The effectiveness of other drugs were 50% in NSAIDs, 66.7% in glucocorticoid and immunosuppressive agents. Conclusion: This is the first and largest case series of TRAPS in Chinese adult patients. It highlights the importance of screening TNFRSF1A gene in patients with unexplained periodic fever syndrome. Four novel TNFRSF1A variants, S290I, F89L, V202G and m.1735A>G in non-coding region, have been identified. The atypical clinical manifestations of our patients compared to those from Europe might be related to their low-penetrance TNFRSF1A variants. Further studies are needed to explore the more accurate phenotypes and genotypes of the Chinese patients with TRAPS.