A protracted diagnostic journey of pediatric PAPA syndrome and subsequent response to tofacitinib therapy: a case report and literature review.

PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne) is a rare autosomal dominant autoinflammatory disorder caused by mutations in the PSTPIP1 gene. In pediatric patients, arthritis often precedes cutaneous manifestations by several years, leading to frequent misdiagnosis as septic arthritis. Treatment is challenging, with IL-1 inhibitors being the most pathophysiology-based first-line therapy, but their accessibility is limited by high costs. We reported an 11-year-old Chinese boy with a 7-year history of recurrent, migratory arthritis. Trio whole-exome sequencing identified a heterozygous PSTPIP1 c.770A>G (p.Glu257Gly) variant, classified as likely pathogenic. The father carried the same variant; he had experienced arthralgias in early childhood but became asymptomatic after age 10 without any treatment, demonstrating incomplete penetrance. This variant is extremely rare, reported in only one of 16 patients in the Eurofever registry, all of European descent, making this the first Asian case. Due to financial constraints, IL-1 inhibitors were inaccessible. Tofacitinib (3.5 mg twice daily, adjusted from adult dose based on body surface area) was initiated in February 2026. After 2 months, joint swelling and pain decreased significantly. As of July 10, 2026, no recurrence of joint swelling and pain had been observed during follow-up. However, radiography revealed irreversible structural damage (bone demineralization, joint space narrowing, osteophyte formation), and the patient still had limited mobility. Rehabilitation specialists advised against aggressive range-of-motion exercises and recommended home-based ultrasound and electrical stimulation to prevent muscle atrophy. Long-term follow-up is ongoing. PAPA syndrome should be considered in children with culture-negative, antibiotic-unresponsive recurrent arthritis, even without skin findings. Early genetic diagnosis can prevent unnecessary procedures. For patients who cannot access IL-1 inhibitors, tofacitinib may reduce inflammation, but it cannot reverse established joint damage. Given the relatively short follow-up duration, the long-term durability of response, safety, and impact of tofacitinib on disease progression remain to be determined. This report provides early, preliminary evidence of JAK inhibitor use in this population, contributing initial data to the limited Asian literature.