Jak Inhibitor Therapy in Candle Syndrome: A Systematic Review of Clinical Outcomes in 46 Patients Publisher Pubmed



Vahabi S M ; Pourgholi E ; Leblebici C B ; Crisler W J ; Heidari S ; Tung J K
Source: European Journal of Pediatrics Published:2026

Abstract

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome is a rare autosomal recessive autoinflammatory disorder caused by mutations affecting proteasome function. Given the absence of standard therapy, we reviewed the therapeutic potential of Janus kinase inhibitors (JAK-Is) in CANDLE syndrome. Following PRISMA guidelines, PubMed/MEDLINE, Scopus, Web of Science, and Embase were searched through September 2025. Eligible studies included patients with CANDLE or CANDLE-like disease treated with JAK-Is. Risk of bias was assessed using NHLBI and JBI tools, and findings were summarized descriptively. Sixteen articles including 46 patients were analyzed. The median age was 4.5 years, and all patients presented with skin rash. Common manifestations included fever (91.3%), lipodystrophy (73.9%), failure to thrive (56.5%), arthralgia/arthritis (43.4%), and panniculitis (39.1%). Multisystem involvement and elevated inflammatory markers were frequent. Corticosteroid use before JAK-I therapy was reported in 73.9% of patients. Baricitinib was the most commonly used JAK-I (73.9%), followed by tofacitinib (23.9%) and ruxolitinib (2.1%). Primary efficacy analysis in 26 patients of full-text publications showed complete response in 42.3%, significant response 11.5%, partial response in 38.5%, and no response in 7.6%. The most common adverse events were upper respiratory tract infections and BK virus infection. Conclusion: Available evidence suggests that JAK-Is may improve clinical and laboratory outcomes in patients with CANDLE syndrome, although these findings are based on a small number of patients and predominantly low-level evidence. Infections were the most commonly reported adverse events. Further prospective studies are needed to confirm these findings and establish the long-term efficacy and safety of JAK-Is in CANDLE syndrome. (Table presented.) © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2026.