Etiology and Treatment of Refractory Atopic Dermatitis with Alopecia and Growth Impairment

Abstract

Atopic dermatitis (AD), a chronic inflammatory skin condition characterized by pruritus, can affect the patient’s quality of life. The pathogenesis of AD involves epidermal barrier dysfunction and inflammatory cytokines, with the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway playing a role in cytokine signaling. Although topical corticosteroids remain the mainstay of AD treatment, novel therapeutic agents, such as biologics and molecular-targeted drugs targeting cytokines and JAKs have been developed recently. AD has a complex multifactorial pathogenesis combining genetic and environmental factors. However, recent reports indicate that monogenic mutations may cause some atopic diseases. Recently, we encountered a father-son pair with severe AD, alopecia, and growth impairment, showing no response to conventional treatments. Genetic analysis revealed a JAK1 variant suspected of gain-of-function mutation. Subsequent treatment with upadacitinib, a selective JAK1 inhibitor, led to remarkable improvements in eczema and alopecia in both patients. This case highlights the potential of targeted therapies focusing on proteins derived from specific genes in cases caused by monogenic abnormalities, where molecular-targeted drugs could dramatically improve the symptoms. Thus, in severe AD patients exhibiting poor responses to conventional treatments or having growth impairment and atypical symptoms, considering the possibility of monogenic mutations is crucial for their diagnosis and management.