Hailey-hailey disease: atp2c1 mutations and therapeutic options

Hailey-Hailey disease, also known as benign familial pemphigus, is a rare autosomal dominant genodermatosis, clinically manifested by recurrent vesiculobullous and erosive lesions, predominantly in flexural and intertriginous areas. The pathophysiology of the disease is intrinsically linked to mutations in the ATP2C1 gene, which encodes the hSPCA1 protein (secretory pathway Ca2+/Mn2+-ATPase), essential for calcium and manganese homeostasis in the Golgi apparatus, resulting in suprabasal acantholysis and fragility of cellular adhesion. This study aimed to conduct a systematic review of the literature on the role of hSPCA1 dysfunction in the pathogenesis of the disease and emerging therapeutic strategies in the Brazilian context. The methodology was based on a bibliographic analysis of scientific studies published in the last decade, prioritizing evidence on the efficacy of conventional treatments and new modular interventions. The results demonstrate that, although there is no definitive cure, therapeutic management has evolved from purely symptomatic management to therapies that seek to stabilize desmosomal adhesion and control secondary infections. It is concluded that an in-depth understanding of protein dysfunction is crucial for targeting therapeutic interventions, and multidisciplinary management is essential to reduce the chronicity of lesions and improve the psychosocial impact on patients' lives.(AU)