家族性良性慢性天疱瘡

This report describes a case of primary cutaneous mucormycosis in a patient with Hailey-Hailey Disease (benign familial pemphigus). The diagnosis of primary cutaneous mucormycosis was confirmed via microbiological culture as well as histopathology. Our patient improved with prompt surgical debridement and excision of infected, necrotic tissue with complementary antifungal therapy. To the best of our knowledge this is the first reported case of cutaneous mucormycosis in a patient with Hailey-Hailey Disease and contributes to the literature regarding pathophysiology, management and treatment for each of these rare entities.

The secretory pathway Ca2+-ATPase, SPCA1 (gene name ATP2C1), is a Golgi-localized calcium pump defective in the autosomal dominant cutaneous disorder known as Hailey-Hailey disease (HHD). Although clinically well characterized by suprabasal acantholysis and intertriginous blistering of the skin, the mechanistic underpinnings of the disease are still unclear. Here we use CRISPR/Cas9-mediated single- and biallelic ATP2C1 knockouts in immortalized human N/TERT keratinocytes to show that SPCA1 is required for dynamic reorganization of actin cytoskeleton in keratinocyte spreading, which is the primary mechanism driving skin reepithelialization. We identify an insulin-activated PI3K-AKT-Rac1 signaling pathway required for lamellipodia formation and keratinocyte spreading, defective in SPCA1 knockout cell lines. Our findings may explain the poor wound healing and impaired keratinocyte migration observed in HHD and may be relevant to the observed effect of insulin on wound healing, including diabetic wounds and burns, reported for nearly a century. Transgenic expression of hSPCA1 or treatment with CDN1163, a small molecule Ca2+-ATPase agonist, restored defective phenotypes in the HHD model, paving the way for future therapeutic approaches to treat this disorder.NEW & NOTEWORTHY Keratinocytes spread and change shape dynamically to maintain skin integrity and facilitate the rapid repair of the skin barrier after injury. Defects in these processes are characteristic of Hailey-Hailey disease (HHD), an ulcerative skin disorder caused by mutations in the Golgi Ca2+-ATPase SPCA1. By developing new keratinocyte HHD models, we uncover a role for SPCA1 in an insulin-activated signaling pathway that drives lamellipodia formation and keratinocyte spreading, linking Ca2+ regulation to actin cytoskeleton reorganization.

Congenital hemidysplasia with ichthyosiform erythroderma and limb defects syndrome is a rare disorder in which atypical presentations may delay diagnosis. We report a molecularly confirmed case mimicking Hailey-Hailey disease without classical unilateral involvement or skeletal abnormalities. This case highlights an important diagnostic pitfall, emphasizes the value of NSDHL genetic testing, and demonstrates the clinical benefit of pathogenesis-directed topical simvastatin/cholesterol therapy.

BACKGROUND: Hailey-Hailey disease (HHD) is an autosomal dominantly inherited blistering dermatosis caused by mutations in the ATP2C1 gene, which encodes the human secretory pathway Ca2⁺/Mn2⁺ ATPase protein (hSPCA1). METHODS: We collected a four-generation Chinese HHD family with 6 affected patients. Genomic DNA was isolated from family members and a matched control cohort. All 27 exons and flanking intronic sequences of the ATP2C1 gene were amplified by PCR and subjected to direct sequencing. RESULTS: A novel heterozygous nonsense mutation, c.2395C>T (p.R799X), was identified in exon 25 of the ATP2C1 gene. This mutation co-segregated with the disease phenotype in the family and was absent in 100 unrelated healthy controls. CONCLUSION: This finding expands the mutation spectrum of ATP2C1 underlying HHD and provides a molecular basis for genetic counseling and early diagnosis of at-risk family members.