PAPA syndrome: novelties from the Eurofever registry

Abstract

Introduction: PAPA syndrome is a very rare autoinflammatory condition. Few data are nowadays available about the clinical characteristic, the response to treatment and the outcome of this disease. Objectives:To analyse the data of the PAPA patients enrolled to the Eurofever registry. Methods: the data analysed in the study were extracted from the Eurofever registry, which is hosted in the PRINTO website (www.printo. it). The patients were included in the study in the presence of mutations in the PSTPIP1 gene or, in genetically negative patients, in the presence of at least two of the following clinical manifestation: recurrent pyogenic arthritis, pyoderma gangrenousm or skin abscess with negative cultural tests. Demographic data, clinical manifestations and response to treatment were analysed. Results: In may 2018 baseline and clinical information were available of near 4000 patients in the Eurofever registry. Of the 36 patients classified as PAPA syndrome, 2 were excluded from the study. 34 PAPA patients, from 11 different centers, were analysed: the genotype was confirmatory in 29 patients, while in 5 was not available. 10 patients were of the same family, in 4 cases one parent was affected (2 included in the registry), while in other 8 patients the family history was negative. At the time of enrolment, 15 patients were in the paediatric age, while 19 were adults. The mutations detected in the PSTPIP1 gene were E250Q (13 pts), E250K (5 pts), A230T (3 pts), G258A (3 pts), E277D (2 pts), E257G (1 pt), G940A (1pts) and R365W (1 pts). The disease course was recurrent in 24 patients, while the other 10 presented a chronic disease course with periodic recrudesces. Joint and skin involvement were present at disease onset in 24 and 9 patients respectively. In other 12 patients skin involvement appeared over time. 20 out of the 34 patients presented clinical manifestations not typical of PAPA syndrome (psoriasis, uveitis, osteolytic bone lesions, chronic renal failure, muscular abscesses, gastrointestinal symptoms anaemia and hepatosplenomegaly). 10 patients were treated with NSAID with partial and poor response in 6 and 4 patients respectively, while steroids caused a complete or partial control of disease manifestations in 6 and 10 patients respectively. Five patients were treated with methotrexate with partial response. Etanercept was used in 6 patient with complete response in 2 and partial in 4, adalimumab in 4 patients (1 partial and 1 complete responders, 2 failure) and anakinra in 9 patients (3 partial and 6 complete responders). 2 patients were treated with Canakinumab with complete response. Conclusion: This study enlightens the phenotypic variability of PAPA syndrome. The unusual clinical manifestations and the lack of the clinical triad of the disease may be responsible for the under recognition of this disease. Between biologic drugs, IL-1 inhibitors were more effective in the analysed cohort of patients.