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 Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> What is Known: • CANDLE syndrome is a rare autoinflammatory disease with limited treatment options and significant multisystem morbidity. • JAK inhibitors have been increasingly used due to their role in interferon-mediated inflammation. </entry> </row> <row> <entry nameend="c2" namest="c1"> What is New: • This systematic review summarizes outcomes of 46 reported CANDLE patients treated with JAK inhibitors. • Most patients showed clinical improvement, while infections were the most commonly reported adverse events. </entry> </row> </tbody> </tgroup> </Table>

JAK inhibitor therapy in CANDLE syndrome: a systematic review of clinical outcomes in 46 patients

期刊论文
发表日期：

2026年8月4日

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Seyed Mohammad Vahabi,
Elnaz Pourgholi,
Can Berk Leblebici,
William J. Crisler,
Sama Heidari,
Joe K. Tung

摘要

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.

What is Known:

• CANDLE syndrome is a rare autoinflammatory disease with limited treatment options and significant multisystem morbidity.

• JAK inhibitors have been increasingly used due to their role in interferon-mediated inflammation.

What is New:

• This systematic review summarizes outcomes of 46 reported CANDLE patients treated with JAK inhibitors.

• Most patients showed clinical improvement, while infections were the most commonly reported adverse events.