Interleukin-36 receptor antagonist deficiency patient with a novel mutation - 10/03/26

Doi : 10.1016/j.arcped.2025.12.005

Müge Sezer ^a,^⁎ , Fatma Aydın ^b, Eda Özaydın ^c, Elif Çelikel ^d, Ahu Yorulmaz ^e, Resul Karakuş ^f, Banu Acar ^d

^a University of Health Sciences, Ankara Training and Education Hospital, Department of Pediatric Rheumatology, Ankara, Turkey

^b Ankara University Faculty of Medicine, Department of Pediatric Rheumatology, Ankara, Turkey

^c University of Health Sciences, Ankara City Hospital, Department of Pediatric, Ankara, Turkey

^d University of Health Sciences, Ankara City Hospital, Department of Pediatric Rheumatology, Ankara, Turkey

^e University of Health Sciences, Ankara City Hospital, Department of Dermatology, Ankara, Turkey

^f Gazi University Faculty of Medicine, Department of Immunology, Ankara, Turkey

^⁎ Corresponding author at: University of Health Sciences, Ankara Training and Education Hospital, Department of Pediatric Rheumatology, Ankara, Turkey. University of Health Sciences Ankara Training and Education Hospital, Department of Pediatric Rheumatology Ankara Turkey

Abstract

Background

The deficiency of interleukin-36 receptor antagonist (DITRA) is a monogenic autoinflammatory condition associated with generalized pustular psoriasis (GPP). Diagnostic criteria and treatment recommendations for DITRA are inadequate. The diagnosis is established by detecting a biallelic loss-of-function mutation in IL36RN, which leads to activation of the IL36 pathway.

Observation and discussion

We present a pediatric case of GPP with a novel IL36RN mutation that supports the diagnosis of DITRA. In patients with DITRA unresponsive to IL-1 targeted therapies, favorable results may be achieved with the administration of TNF-α inhibitors, particularly IL-36 pathway inhibitors. Twenty-nine papers, encompassing 55 pediatric cases, were synthesized to contextualize treatment responses.

Conclusion

Novel DITRA-associated mutations continue to be discovered. Given the rarity of the disease, it will be possible to reveal the genotype-phenotype relationship in the future with the publication of larger DITRA case series.

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Keywords : Autoinflammatory disorder, Deficiency of interleukin-36 receptor antagonist, DITRA, generalized pustular psoriasis, TNF-α inhibitors