AbstractBackgroundWhile clustering of bullous pemphigoid (BP) with neuropsychiatric diseases is well‐established, the clinical and immunological profile of BP patients with this comorbidity remains to be decisively determined.ObjectivesTo evaluate the burden of neurological and psychiatric comorbidities among patients with BP and to elucidate the clinical, immunological and immunopathological features of patients with BP and comorbid neuropsychiatric conditions.MethodsWe performed a retrospective study encompassing patients diagnosed with BP throughout the years 2009–2020 in a specialized tertiary referral centre. Multivariate logistic regression model was used to identify predictors of neuropsychiatric conditions among patients with BP.ResultsThe study included 273 patients with BP, of whom 123 (45.1%) presented with comorbid neuropsychiatric disease. Compared to the remaining patients with BP (n = 150), those with pre‐existing neuropsychiatric diseases demonstrated older mean [standard deviation (SD)] age [81.7 (9.1) vs. 76.9 (10.1); P < 0.001], female preponderance (65.0% vs. 49.3%; P = 0.009), higher seropositivity rate of anti‐BP230 (67.7% vs. 36.5%; P = 0.006) and higher levels of anti‐BP180 NC16A IgG [651.3 (1279.6) vs. 370.4 (818.6) U/mL; P = 0.039]. In multivariate analysis, anti‐BP230 seropositivity was independently associated with coexistence of BP with neuropsychiatric conditions [adjusted odds ratio (OR), 3.43; 95% CI, 1.24–9.52; P = 0.018]. In a sensitivity analysis confined to patients with neurological diseases (n = 103), older age [82.1 (8.4) vs. 77.2 (10.3); P < 0.001] and increased anti‐BP230 seropositivity (68.0% vs. 39.7%; P = 0.018) were identified.ConclusionsThe coexistence of BP with neuropsychiatric diseases is independently associated with the generation of anti‐BP230 antibodies.