Pemphigus Is not Associated with an Increased Risk of Psychiatric Disorders during the Course of the Disease

Pemphigus is a rare, severe autoimmune blistering disease caused by autoantibodies targeting desmosomal proteins, leading to intraepithelial blistering and painful erosions of the skin and mucous membranes. Although 10-15% of dermatology patients are diagnosed with psychiatric disorders, the association between pemphigus and psychiatric disorders remains unclear owing to limited large-scale evidence. We conducted a retrospective cohort study using the United States TriNetX Collaborative Network, analyzing data from over 120 million electronic health records. Adults (aged ≥18 years) with pemphigus were identified and matched 1:1 with comparators (n = 5753 individuals per group) using propensity score matching for age, sex, ethnicity, and major comorbidities. Outcomes were the incidence of psychiatric disorders diagnosed after the index event, including suicidal ideation, suicide attempts, depression, psychotic disorders, bipolar disorder, substance use disorders, anxiety, eating disorders, borderline personality disorder, attention-deficit hyperactivity disorder, and stress-related disorders, defined by International Classification of Diseases, Tenth Revision, Clinical Modification codes. Three sensitivity analyses addressed variations in follow-up time, baseline data completeness, and long-term outcome stability. No increased risk of psychiatric disorders was observed in patients with pemphigus over the course of the disease, with consistent results across all sensitivity analyses. In conclusion, these findings challenge prior assumptions and highlight the importance of large-scale, well-controlled studies in clarifying psychiatric comorbidities in autoimmune blistering diseases.