There is emerging data on the increased prevalence of neurological diseases in patients with bullous pemphigoid (BP). Neuronal isoforms of the major antigens, BP180 and BP230, involved in the pathogenesis of bullous pemphigoid have also been identified and are hypothesised to underlie this association.
To conduct a systematic review of the literature to examine the experimental and epidemiological evidence for the association between neurological disease and bullous pemphigoid.
The literature search was performed using two online databases via the OvidSP search interface: MEDLINE and EMBASE (1946-2017). The following search terms were used: [‘Pemphigoid, Bullous’] in variable combinations with [‘neurological disease’, ‘nervous system disease’, ‘Parkinson’s disease’, ‘Alzheimer’s disease’, ‘dementia’, ‘stroke’, ‘cerebrovascular disease’, ‘brain tumour’, ‘brain malignancy’, ‘epilepsy’, ‘seizure’, ‘multiple sclerosis’].
The search yielded 341 results including 61 duplicates which were deleted. Screening the titles and abstracts of the remaining 280 articles, 141 articles were deemed relevant. Following review of the full-length articles, 44 fulfilled the inclusion criteria and were critically appraised. Articles were excluded based on specificity and relevance to the topic. Case reports and abstract-only articles were excluded. Studies of all languages were included.
Selected articles for review included experimental reports, case-control studies, cohort studies, meta-analyses, and review articles. These found significant associations between bullous pemphigoid and various neurological diseases including stroke, dementia, Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, and epilepsy, particularly where the onset of neurological disease precedes that of bullous pemphigoid
There is considerable evidence supporting an association between neurological disease and bullous pemphigoid. However, there is still conflicting evidence regarding the temporal nature of this relationship and the contributing pathogenic mechanisms are yet to be confirmed. Larger prospective cohort studies are needed in order to establish a stronger causality and better understanding of the common pathological processes.