Ancestry, Demographic and Clinical Features of Israeli Periodic Fever Aphthous Stomatitis, Pharyngitis and Adenitis (PFAPA) Syndrome – A Multi-Center Cohort Study - הכינוס השנתי של החברה הישראלית לפדיאטריה קלינית

גיל אמריליו ^1,2 Liora Harel ^1,2 Sabreen Abu Ahmad ⁴ Maryam Abu Rumi ^3,4 Riva Brik ^3,4 Nofar Hezkelo ² Orli Ohana ¹ Yoel Levinsky ^1,2 Gabriel Chodick ² Yonatan Butbul Aviel ^3,4

¹Pediatric Rheumatology Unit, Schneider Children's Medical Center of Israel, ישראל
²Sackler Faculty of Medicine, Tel Aviv University, ישראל
³The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, ישראל
⁴Pediatric Rheumatology Service, Ruth Rappaport Children's Hospital, Rambam Medical Center, ישראל

Background: PFAPA syndrome is an autoinflammatory disease of unknown etiology. Recently, we showed that PFAPA and FMF may present concomitantly. Since we have noted higher prevalence of PFAPA among children from Mediterranean ancestry (MA) in our clinic, we have conducted a multi-center clinical study which aimed to identify their ancestry and compare them to asthmatic patients (a disease with no ancestry predilection).

Methods: Medical records from 2 tertiary Israeli medical centers were reviewed between 3/2019-3/2019 with exclusion of patients with concomitant FMF. The Mediterranean group was defined as children from Arabic or Sephardic ancestry. Children from both MA and Non-MA were defined as multiethnic ancestry.

Results: Overall 303 PFAPA patients were included (after exclusion of 51 patients with concomitant FMF disease) and were compared to 475 asthmatic patients. Among PFAPA patients 17 (5.8%) were from Non MA group – all were Ashkenazy Jews. 178 (58.7%) patients had pure MA and 96 (33.0%) had multiethnic ancestry. The distribution of the asthmatic patients by ancestry was similar among 3 groups (about third in each group). PFAPA patients were significantly more likely to be from a MA compared to Asthmatic patients (P<0.0001). In addition, Mediterranean PFAPA Patients had significantly earlier disease onset and were diagnosed earlier (P<0.04). In all PFAPA groups there was an average of delay of about 2 years from onset to diagnosis.

Conclusion: About 60% of our PFAPA patients were of MA and only 6% were of Ashkenazy ancestry. Future studies are needed to determine the genetic background of these findings.