We sought to investigate the association between bullous pemphigoid (BP) and its neurological comorbidities.

BP is an uncommon autoimmune blistering disorder characterized by tense bullae and pruritis on physical examination. Afflicting primarily the elderly, BP impairs quality of life and mortality. The BPAG1 gene encodes epithelial and neuronal isoforms of a collagen, COL XVII, that imparts key cytoskeletal functions as a component of the hemidesmosomes scaffolding the epithelial-skin junction. In BP, autoantibodies attack the subepidermal basal membrane, inciting an immune response. Various neurodegenerative disorders (NDs) have been reported to be significantly associated with BP, but it is unclear whether this is due to their common risk factor of aging or if other influences are involved.

Several studies highlighting the association between BP and NDs were evaluated. This review analyzed pathophysiology, prevalence, temporal relationships, and other outcomes.

Pathogenic mechanisms in BP include loss of immunological tolerance and development of cross-reactivity between the epithelial and neuronal isoforms of BP antigens. Other proposed theories of a neuro-dermatomal connection include epitope spreading, immunosenescence, early exposure to autoantigens, and brain parenchymal compromise. NDs typically precede BP development and have been found in at least one-third of BP patients. BP patients with comorbid NDs have reduced functional status compared to BP-only cohorts. Elevated risks of dementia, stroke, multiple sclerosis, and Parkinson’s disease in BP patients have been consistently demonstrated across case-control studies in various countries. Further associations with BP include epilepsy, amyotrophic lateral sclerosis, and neuropsychiatric disorders. 

A close tie exists between BP and co-occurring NDs, although more comprehensive evaluations are needed to assess causality and shared biological mechanisms. As the population ages, BP symptoms should be frequently screened for in neurological clinics, stroke floors, and nursing homes. Guidelines such as cognitive screening should also be developed for dermatologists to assess for NDs in BP patients.