ArticlePediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology2026
Allergic but not autoimmune comorbidities in children with PFAPA: A nationwide matched case-control cohort study.
Article in Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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- Allergic but not autoimmune comorbidities in children with PFAPA: A nationwide matched case-control cohort study.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2026Article
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Abstract
backgroundPeriodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) is the most common autoinflammatory syndrome of childhood. Although immune dysregulation is central to its pathogenesis, the broader burden of allergic and autoimmune comorbidities in PFAPA remains incompletely characterized. We aimed to evaluate the prevalence of allergic and autoimmune diseases in children with PFAPA.
methodsWe conducted a nationwide matched case-control study using electronic health records from Leumit Health Services in Israel between 2000 and 2024. Children with PFAPA were identified using a dedicated ICD-9 code and matched 1:20 with controls by age, sex, socioeconomic status, ethnicity, and year of first record. Allergic and autoimmune diagnoses were identified using predefined ICD-9 codes. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated, with false discovery rate correction for multiple testing.
resultsThe cohort included 1641 PFAPA patients and 32,820 matched controls with a mean follow-up of 8.6 years. PFAPA patients had increased prevalence of asthma (49.6% vs. 37.5%; OR 1.64), allergic rhinitis (15.7% vs. 9.8%; OR 1.71), atopic dermatitis (23.0% vs. 19.9%; OR 1.21), urticaria (18.8% vs. 15.0%; OR 1.32), drug allergy (1.22% vs. 0.57%; OR 2.15), and anaphylaxis (0.55% vs. 0.20%; OR 2.78). In contrast, autoimmune diseases were uncommon and showed no consistent enrichment. Similar associations were observed for diagnoses recorded before PFAPA diagnosis.
conclusionsPFAPA is associated with a broad atopic comorbidity profile but not with classical autoimmune disease. These findings suggest that PFAPA may represent a distinct immune phenotype in which episodic autoinflammation coexists with atopic susceptibility.
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