Attention-Deficit/Hyperactivity Disorder Symptoms in School-Aged Children with a History of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Denitis Syndrome: A Comparative Evaluation with Healthy Peers.
Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome of childhood, and growing evidence links early-life inflammation to neurodevelopment, but whether PFAPA affects attention and behavior at school age is unknown. This study compared parent-reported attention-deficit/hyperactivity disorder (ADHD) symptoms in school-aged children with a preschool PFAPA diagnosis with those of healthy peers and examined associations with PFAPA-related clinical characteristics. This cross-sectional study included 96 children (mean age 10.84 ± 1.64 years) diagnosed with PFAPA during the preschool years and followed at a pediatric rheumatology clinic and 81 healthy controls (10.40 ± 1.88 years) without chronic disease or tonsillectomy. Attention-deficit/hyperactivity disorder symptoms were assessed with the Revised Conners' Parent Rating Scale-Short Form (CPRS-R:S). The groups did not differ in age or sex. No significant between-group difference was found on any CPRS-R:S subscale. Within the PFAPA group, an earlier age at symptom onset was weakly but significantly correlated with a higher ADHD Index (ρ = -0.317, P = .002), and this association remained significant after false discovery rate correction (false discovery rate-adjusted P value [pFDR] = 0.048) and multivariable adjustment (β = -0.295, P = .004); subgroup analyses by comorbidity, tonsillectomy, and medication use showed no differences. Children with a preschool diagnosis of PFAPA did not show increased parentreported ADHD symptoms at school age. The weak association with earlier onset warrants cautious interpretation. These findings suggest that the immune-neurodevelopment relationship should be considered in a disease-specific manner, distinguishing PFAPA's benign, episodic course from chronic autoinflammatory diseases.