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. 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. 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.

Spesolimab is an IL-36 receptor monoclonal antibody antagonist approved for generalized pustular psoriasis in patients 12 years and older. While it has demonstrated promising results in this population, there is limited literature exploring spesolimab efficacy and dosing in younger patients. We report the cases of a 5-year-old female with generalized pustular psoriasis in the setting of autosomal recessive deficiency of interleukin-36 receptor antagonist (DITRA) as well as a 6-year-old female with generalized pustular psoriasis of unknown genetic status, both successfully treated with spesolimab.

Secukinumab is an IL-17A inhibitor that selectively binds to IL-17A and inhibits its interaction with IL-17 receptors, thereby reducing the production of pro-inflammatory cytokines, chemokines, and tissue-damaging mediators. Secukinumab has been proven to rapidly improve erythema and pustules in adult and paediatric generalized pustular psoriasis (GPP) patients. Here, we report a case study of erythema multiforme-like drug eruption induced by secukinumab and provide an overview of all cases reported so far. A systematic literature search of publications was conducted from inception to September 2024 via PubMed and Web of Science Core Collection, in order to identify all cases of drug hypersensitivity reactions associated with secukinumab. We conducted a search for retrospective and prospective studies, case series, case reports, and data from Phase II and III clinical trials related to immune-related (or potentially immune-related) adverse events associated with the use of secukinumab. In total, four cases of drug hypersensitivity reactions associated with secukinumab were identified. Drug hypersensitivity reactions associated with secukinumab are relatively rare. The recognition of potential rare adverse events by clinicians is important and may expand our understanding of immune-mediated diseases.

Deficiency of IL-36 Receptor Antagonist (DITRA) is a rare monogenic autoinflammatory disease, characterized by dysregulation of IL-36 signaling and phenotypically classified as a subtype of generalized pustular psoriasis. This study aimed to explore the role of potentially coding and non-coding RNAs (ncRNAs) in the IL36RN interactome to identify putative pathogenic mechanisms, biomarkers, and therapeutic targets for DITRA. A systems biology approach was applied using the STRING database to construct the IL36RN protein-protein interaction network. Key ncRNA interactions were identified using RNAInter. The networks were visualized and analyzed with Cytoscape v3 and the CytoHubba plugin to identify central nodes and interaction hubs. Pathway enrichment analysis was then performed to determine the biological relevance of candidate ncRNAs and genes. Analysis identified thirty-eight ncRNAs interacting with the IL36RN network, including six lncRNAs and thirty-two miRNAs. Of these, thirty-three were associated with key DITRA-related signaling pathways, while five remain to be validated. Additionally, seven protein-coding genes were highlighted, with three (TINCR, PLEKHA1, and HNF4A) directly implicated in biological pathways related to DITRA. Many of the identified ncRNAs have prior associations with immune-mediated diseases, including psoriasis, supporting their potential relevance in DITRA pathogenesis. This study provides novel insights into the ncRNA-mediated regulation of IL36RN and its network in the context of DITRA. The findings support the potential utility of specific ncRNAs and genes, such as TINCR, PLEKHA1, and HNF4A, as key genomic elements warrant further functional characterization to confirm their mechanistic roles and may inform biomarker discovery and targeted therapeutic development in DITRA.

Pediatric generalized pustular psoriasis (GPP) is a rare, severe, and potentially life-threatening variant of childhood psoriasis. Early-onset GPP has a well-known association with deficiency of the interleukin-36 receptor antagonist (DITRA). We present a case of a pediatric patient diagnosed with GPP found to have a heterozygous variant in the Mediterranean fever gene (MEFV) that was successfully treated with adalimumab. MEFV variants are a newly identified genetic risk factor for GPP. Our case highlights the need for ongoing genomic studies for childhood autoinflammatory diseases and the call for evidence-based management for these challenging cases.