Yichao Hua1, Di Wu2, Min Shen3, Keyi Yu4, Wen Zhang5, Xiaofeng Zeng6. 1. Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing 100730, China; Laboratory for Tumor Microenvironment and Therapeutic Resistance, VIB-KU Leuven Center for Cancer Biology, Department of Oncology, KU Leuven, Leuven, Belgium. Electronic address: huayc09@hotmail.com. 2. Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing 100730, China. Electronic address: med_wudi@sina.com. 3. Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing 100730, China. Electronic address: shenmpumch@163.com. 4. Orthopedic Department, Peking Union Medical College Hospital, Beijing, China. Electronic address: yukeyi009@126.com. 5. Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing 100730, China. Electronic address: zhangwen91@sina.com. 6. Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing 100730, China. Electronic address: xiaofeng.zeng@cstar.org.cn.
Abstract
OBJECTIVE: We aimed to characterize the phenotypes and genotypes of Chinese adult patients with systemic autoinflammatory diseases (SAIDs). METHODS: We prospectively evaluated clinical and genetic features of 92 adult patients (≥16 years) suspected of SAIDs in the period from April 2015 to October 2017, at the adult SAIDs center, Peking Union Medical College Hospital. The definite diagnosis of each disease was deemed to be present if both clinical phenotypes and genetic confirmation were met. Clinical manifestations of these patients were compared with those from the pediatric populations and patients from other countries. RESULTS: A final diagnosis of SAIDs was reached in 50 patients, including 13 familial Mediterranean fever (FMF), 10 NLRP12-associated autoinflammtory disease (NLRP12-AID), 7 NLRP3-associated autoinflammatory disease (NLRP3-AID), 5 tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), 3 Blau syndrome, 3 Yao syndrome (YAOS) and 9 periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA). First disease onset during adulthood was observed in 30 patients, and the final diagnosis was delayed with a median time of 9 years. Adult monogenic SAIDs patients usually carried low-penetrance mutations and all gene variants were presented as heterozygosis or compound heterozygosis. Frequencies of clinical manifestations in Chinese adult SAIDs patients were similar with adult patients in other countries, but different from pediatric populations. CONCLUSIONS: FMF, NLRP3-AID, and NLRP12-AID are relatively common monogenic SAIDs in Chinese adults. Adult-onset SAIDs may be related to the presence of low-penetrance mutations, characterized by nonspecific, incomplete or atypical disease patterns compared with child-onset SAIDs, leading to a delay of diagnosis.
OBJECTIVE: We aimed to characterize the phenotypes and genotypes of Chinese adult patients with systemic autoinflammatory diseases (SAIDs). METHODS: We prospectively evaluated clinical and genetic features of 92 adult patients (≥16 years) suspected of SAIDs in the period from April 2015 to October 2017, at the adult SAIDs center, Peking Union Medical College Hospital. The definite diagnosis of each disease was deemed to be present if both clinical phenotypes and genetic confirmation were met. Clinical manifestations of these patients were compared with those from the pediatric populations and patients from other countries. RESULTS: A final diagnosis of SAIDs was reached in 50 patients, including 13 familial Mediterranean fever (FMF), 10 NLRP12-associated autoinflammtory disease (NLRP12-AID), 7 NLRP3-associated autoinflammatory disease (NLRP3-AID), 5 tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), 3 Blau syndrome, 3 Yao syndrome (YAOS) and 9 periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA). First disease onset during adulthood was observed in 30 patients, and the final diagnosis was delayed with a median time of 9 years. Adult monogenic SAIDspatients usually carried low-penetrance mutations and all gene variants were presented as heterozygosis or compound heterozygosis. Frequencies of clinical manifestations in Chinese adult SAIDspatients were similar with adult patients in other countries, but different from pediatric populations. CONCLUSIONS:FMF, NLRP3-AID, and NLRP12-AID are relatively common monogenic SAIDs in Chinese adults. Adult-onset SAIDs may be related to the presence of low-penetrance mutations, characterized by nonspecific, incomplete or atypical disease patterns compared with child-onset SAIDs, leading to a delay of diagnosis.
Authors: Micol Romano; Z Serap Arici; David Piskin; Sara Alehashemi; Daniel Aletaha; Karyl Barron; Susanne Benseler; Roberta A Berard; Lori Broderick; Fatma Dedeoglu; Michelle Diebold; Karen Durrant; Polly Ferguson; Dirk Foell; Jonathan S Hausmann; Olcay Y Jones; Daniel Kastner; Helen J Lachmann; Ronald M Laxer; Dorelia Rivera; Nicola Ruperto; Anna Simon; Marinka Twilt; Joost Frenkel; Hal M Hoffman; Adriana A de Jesus; Jasmin B Kuemmerle-Deschner; Seza Ozen; Marco Gattorno; Raphaela Goldbach-Mansky; Erkan Demirkaya Journal: Arthritis Rheumatol Date: 2022-05-27 Impact factor: 15.483