Autoimmune and lymphoproliferative outcomes after Kawasaki disease: a 20-year population-based cohort study

Kawasaki disease (KD) is an acute systemic vasculitis of childhood associated with profound immune dysregulation that may persist beyond the acute inflammatory phase. The long-term risks of autoimmune diseases and lymphoproliferative malignancies in children with KD remain incompletely defined. To determine whether children with KD carry increased 20-year risks of autoimmune and lymphoproliferative outcomes compared with matched controls. We conducted a retrospective matched cohort study using the Clalit Health Services database (2002-2022). Children with KD (n = 2,126) were matched 1:5 to controls (n = 10,630) by sex and birthdate (± 30 days) and followed through December 2024. Outcomes comprised psoriasis, vitiligo, hypothyroidism, type 1 diabetes mellitus (T1DM), celiac disease, inflammatory bowel disease (IBD), immune thrombocytopenia (ITP), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL). Adjusted hazard ratios (AHRs) with 95% confidence intervals were estimated using Cox proportional hazards models at 2, 5, 10, 15, and 20 years. KD was associated with a significantly increased risk of psoriasis from 2 years (AHR 3.03, 95% CI 1.19-7.73) through 15 years (AHR 1.50, 95% CI 1.01-2.23), attenuating to non-significance at 20 years. Vitiligo reached statistical significance at 10 years (AHR 1.38, 95% CI 1.03-1.86). A nominally significant elevation in HL risk was observed from 15 years onward (AHR 14.99, 95% CI 1.55-145.12, at 15 years; AHR 7.95, 95% CI 1.32-48.00, at 20 years); however, these estimates are based on three events in the KD group versus one to two in controls, yielding confidence intervals spanning nearly two orders of magnitude, and must be interpreted as exploratory signals only. No significant associations were found for hypothyroidism, T1DM, ITP, celiac disease, IBD, or NHL.

KD was associated with a sustained increase in psoriasis risk and a consistent trend toward increased vitiligo risk, reaching statistical significance at 10 years. An exploratory HL signal emerged during long-term follow-up but was based on very few events. Overall, these findings support selective long-term immune dysregulation following KD and highlight the importance of dermatologic awareness during long-term follow-up.

• Kawasaki disease (KD) causes profound immune dysregulation that may persist beyond the acute phase. • Whether KD increases long-term risks of autoimmune and lymphoproliferative disease remains unclear.

• Over 20 years, KD was associated with sustained psoriasis risk and a significant rise in vitiligo risk at 10 years. • No increased risk was found for hypothyroidism, type 1 diabetes, celiac disease, IBD, or ITP, indicating selective rather than generalized immune dysregulation.