Neurological and psychiatric associations in bullous pemphigoid—more than skin deep?

In elderly patients, bullous pemphigoid (BP) is associated with several comorbidities; the strongest association occurs between BP and neurological diseases. Different types of dementia, Parkinson's disease, cerebrovascular disorders and epilepsy all have a significant association with BP, but patients with multiple sclerosis have the highest risk of BP. An existing neurological disorder appears to increase the risk for subsequent BP, but an increased risk for developing some neurological diseases has also been reported following BP diagnosis. BP seems to be associated with several psychiatric diseases such as schizophrenia, uni- and bipolar disorder, schizotypal and delusional disorders, and personality disorders, but the risk ratios are usually lower than with neurological diseases. In addition to the skin, the BP autoantigens BP180 and BP230 are expressed in the central nervous system. This finding together with the strong epidemiological association between neurological disorders and BP has led to an assumption that neurodegeneration or neuroinflammation could lead to a cross-reactive immunoresponse between neural and cutaneous antigens and the failure of self-tolerance. A subpopulation of patients with Alzheimer's disease or Parkinson's disease have circulating IgG autoantibodies against BP180, but currently their significance for the development of BP is unclear, because these antineural BP180 antibodies neither bind to the cutaneous basement membrane nor cause BP-like symptoms. Further studies analysing large and well-characterized populations of neurological and psychiatric patients are required to understand better the role of autoimmunization against neural BP autoantigens in the pathogenesis of BP.