Acantholytic disorders: Update on pathophysiology, diagnosis, and management

Area of Science:

• Dermatology
• Cell Biology
• Genetics

Background:

• Acantholytic skin disorders disrupt intercellular adhesion in keratinocytes.
• Genetic forms include Darier disease (DD) and Hailey-Hailey disease (HHD); Grover disease (GD) pathogenesis is unclear.
• These rare conditions often present diagnostic challenges and lack standardized treatment guidelines.

Purpose of the Study:

• To provide physicians with diagnostic criteria for acantholytic disorders.
• To review current and emerging therapeutic strategies for these conditions.
• To offer expert treatment recommendations based on recent evidence.

Main Methods:

• Literature review of acantholytic skin disorders.
• Analysis of current treatment modalities, including topical steroids, retinoids, biologics, and small molecule inhibitors.
• Exploration of novel therapeutic targets and agents.

Main Results:

• Established treatments like topical steroids and retinoids have variable efficacy.
• Emerging therapies include biologics (e.g., dupilumab, TNF-α inhibitors), JAK inhibitors, and apremilast for refractory cases.
• Low-dose naltrexone shows potential as monotherapy or adjunctive treatment.
• Targeting IL-17/23, IL-4/13 axes, MAPK/ERK pathways, and SERCA activators represent novel strategies.

Conclusions:

• Accurate diagnosis of acantholytic disorders is crucial due to diagnostic challenges.
• Treatment selection should consider disease severity and emerging evidence.
• Novel therapeutic avenues offer promise for managing refractory and severe cases.