Patients with bullous pemphigoid have a high prevalence of neurologic disorders, particularly cerebrovascular disease and dementia, according to a report in the November issue of the Archives of Dermatology.
Given the timing of the onset of the two disorders, "it is tempting to speculate that certain neurologic conditions can predispose to BP [bullous pemphigoid]," noted Dr. Kathy Taghipour of the department of dermatology at Oxford (England) Radcliffe Hospitals and her associates.
Bullous pemphigoid is a debilitating autoimmune skin disease characterized by large, tense blisters, which typically affect the elderly. In case reports, various neurologic disorders have been described in association with the disease, including stroke, dementia, multiple sclerosis, epilepsy, Parkinson’s disease, Shy-Drager syndrome (Multiple system atrophy), and amyotrophic lateral sclerosis. However, "robust epidemiological evidence for the association is lacking," Dr. Taghipour and her colleagues reported.
Therefore, the investigators performed what they described as the first case-control study to examine a possible link, enrolling 90 consecutive patients diagnosed with BP at a single specialist outpatient center for immunobullous diseases between 2004 and 2008. A total of 141 age- and sex-matched patients attending a nearby skin tumor clinic served as a control group. None of the control patients had inflammatory skin disease.
The medical records of all the study patients were reviewed for the presence of neurologic disease.
A total of 42 BP patients (46.7%) had at least one neurologic disorder confirmed by a hospital physician, psychiatrist, or neurologist. In contrast, only 16 of the control subjects (11.3%) had neurologic disorders. Six patients with BP had more than one neurologic disorder.
Two particular neurologic disorders – cerebrovascular disease and dementia – accounted for almost all of the difference. Compared with control subjects, patients with BP were at significantly increased odds of having cerebrovascular disease or dementia, with adjusted odds ratios of 6.0 and 7.9, respectively.
It was possible to determine the date of onset of the neurologic disorders in 36 of the patients with BP (85.7%); in 26 (72.2%), the neurologic disorder preceded BP. In another five patients, both disorders were diagnosed within the same year. The neurologic disorder was diagnosed after BP in five cases, Dr. Taghipour and her associates reported (Arch. Dermatol. 2010;146:1251-4).
The median interval between diagnosis of the neurologic disease and diagnosis of BP was 5.5 years.
Although the underlying mechanism for this association is not yet known, it "could potentially be explained by the presence of an immunologic cross-reactivity between the skin and the brain," the investigators reported.
"It is plausible to postulate that neurologic disorders may expose [certain neuronal] antigens to the immune system and trigger a subsequent immune response. Many neurologic conditions, in particular cerebrovascular diseases, lead to damage in the blood-brain barrier, which may in turn facilitate autoimmunity toward neuronal antigens and cross-reaction with skin," they wrote.