Diagnostic Rate of Autoinflammatory Diseases Evaluated by Fever Patterns in Pediatric- and Adult-Onset Patients.

Abstract

This is a noncomparative study performed to determine if fever pattern is related to a diagnosis of autoinflammatory disease (AID) in pediatric- and adult-onset patients. The final diagnosis of patients suspected to have AID was evaluated against gene polymorphisms known to be responsible for AID, clinical manifestations, and fever pattern, in our institute from 2005 to 2016. Genomic DNA was isolated from patients' peripheral blood, and polymerase chain reaction was used to amplify the indicated exons of 12 genes: MEFV, TNFRSF1A, MVK, NLRP3, NOD2, LI1RN, IL36RN, PSMB8, NALP12, PSTPIP1, TNFAIP3, and NLRC4. Genetic polymorphisms of the above genes were examined. All 210 individuals (135 pediatric onset and 75 adult onset) were classified into the following 3 subgroups: (1) periodic fever (n = 74 and 25 for pediatric and adult onset, respectively), (2) recurrent fever lacking a regular period (n = 47 and 41), and (3) persistent fever (n = 14 and 9). Diagnosis of AID was highest in subgroup 1 (70.2% and 36.0% for pediatric and adult onset, respectively), followed by subgroup 2(29.8% and 17.1%), including PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) (n = 34 and 1), familial Mediterranean fever (n = 22 and 13), cryopyrin-associated periodic syndrome (n = 6 and 1), and tumor necrosis factor receptor-associated periodic syndrome (n = 3 and 1 for pediatric and adult onset, respectively). None were diagnosed with AID in subgroup 3. Autoinflammatory disease was more likely to be diagnosed in pediatric-onset patients compared with adult-onset patients. In both age-onset groups, AID was primarily identified in patients with periodic fever and never diagnosed in patients with persistent fever. Our findings indicate that fever pattern is a useful factor to estimate the probability of AID.