Clinical Responses and Transcriptomic Analysis of Spesolimab in a Girl With Severe Dermatitis, Multiple Allergies and Metabolic Wasting Syndrome

Abstract

Severe dermatitis, multiple allergies, and metabolic wasting syndrome (SAM) is a rare inherited disorder caused by biallelic loss-of-function mutations in the desmoglein-1 (DSG1) or desmoplakin (DSP) genes. Previous studies have demonstrated that acitretin and systemic biologics targeting IL-17, IL-12/IL-23, and IL-4 are effective in treating SAM syndrome. We report the case of an 8-year-old girl diagnosed with SAM syndrome who suffered from recurrent rash episodes due to infections and achieved remission with a combination therapy of Spesolimab and acitretin. Comprehensive diagnostic workup, including serum inflammatory factor assays, flow cytometry, skin immunohistochemical staining, and skin RNA sequencing (RNA-seq), revealed elevated IL-36G levels in SAM syndrome, which may be associated with the pathogenesis of generalised pustular psoriasis (GPP) through shared IL-36-mediated mechanisms. This case highlights the therapeutic potential of targeting the IL-36 pathway in SAM syndrome and supports the use of skin RNA-seq for personalised selection of anti-inflammatory biologics in rare dermatological disorders. This report marks the first clinical application of Spesolimab in SAM syndrome, offering a novel therapeutic approach.