Clinical characteristics of adult patients with autoinflammatory diseases presenting as recurrent fever of unknown origin

Abstract

Objective To analyze the clinical characteristics of adult patients with autoinflammatory diseases (AUID) presenting as recurrent fever of unknown origin (FUO). Methods The clinical and genetic features of 51 adult patients with recurrent FUO, who were suspected of monogenic AUID admitted in adult AUID center Department of Rheumatology, Peking Union Medical College Hospital from April 2015 to March 2017, were prospectively studied. The clinical phenotypes were compared between patients with pathogenic gene mutations and diagnosed as monogenic AUID (gene-positive group), and those without pathogenic gene mutations (gene-negative group). Results Among 51 patients, there were 26 patients with positive monogenic mutations (51.0%); in addition 6 patients were diagnosed as periodic fever-aphthous stomatitis-pharyngitis-adenitis (PFAPA) syndrome. Finally 32 patients (63.0%) were diagnosed as AUID, including 11 cases of familial Mediterranean fever (34.4%), 5 cases of cryopyrin-associated periodic syndrome (15.6%), 5 cases of NLRP12-autoinflammtory disease (15.6%), 2 cases of Blau syndrome (6.3%), 2 cases of Yao syndrome (6.3%), 1 case of tumor necrosis factor-receptor associated periodic syndrome (3.1%), and 6 cases of PFAPA syndrome (18.8%). Among 25 gene-negative patients except 6 cases of PFAPA syndrome, 9 were diagnosed as other diseases, and the diagnosis of AUID was not confirmed in 10 cases (40.0%). Compared with gene-negative group, gene-positive group had more common childhood-onset (30.8% vs. 8.0%, P=0.041), longer disease duration (11.2±10.1 vs. 6.1±5.9, P=0.031), and more common abdominal pain/diarrhea (42.3% vs.12.0%, P=0.015). There were no significant differences in manifestations such as rash, arthralgia/arthritis, thoracic pain, eye inflammation and oral ulcers between two groups. One patient had family history of AUID, and finally diagnosed as Blau syndrome with NOD2 gene mutation. Conclusion AUID is one of the main causes of adult patients with recurrent FUO. Childhood-onset, long disease duration, abdominal pain/diarrhea, and family history of AUID are more common in patients with AUID pathogenic gene variations. Recognizing these symptom patterns can provide the clues, leading to the initiation of gene testing for patients with recurrent FUO. Adults patients with recurrent FUO suspected of AUID should be referred to specialist physicians in adult AUID center. Key words: Fever of unknown origin; Autoinflammatory diseases; Disease attributers