Infantile-onset generalized pustular psoriasis in two Indonesian siblings revealing deficiency of interleukin-36 receptor antagonist

Generalized pustular psoriasis (GPP) is a rare, severe form of psoriasis that may be associated with monogenic autoinflammatory disorders such as deficiency of interleukin-36 receptor antagonist (DITRA). We report 2 Indonesian siblings with infantile-onset erythrodermic GPP caused by homozygous IL36RN c.115 + 6T>C mutations, representing the first genetically confirmed familial DITRA cases from Indonesia. The elder sister developed recurrent pustular flares from early infancy that progressed to chronic erythroderma with acrodermatitis continua of Hallopeau (ACH). The younger sibling presented at 8 months of age with widespread pustular eruptions and early ACH. Genetic testing confirmed homozygosity for the pathogenic variant in both siblings, while their parents and brother were heterozygous carriers. Both patients demonstrated hallmark features of DITRA, including early onset, acral pustulosis, and chronic relapsing disease. Conventional systemic therapies provided only partial control, highlighting therapeutic limitations in resource-limited settings where biologics such as secukinumab remain inaccessible. These cases add to the limited reports of DITRA from Southeast Asia and underscore the importance of genetic testing in early-onset GPP for accurate diagnosis, family counseling, and consideration of targeted therapy.