Bullous pemphigoid and comorbidities: a case-control study in Portuguese patients

BACKGROUND: Although rare, bullous pemphigoid (BP) is the most common autoimmune blistering disease. Recent studies have shown that patients with bullous pemphigoid are more likely to have neurological and psychiatric diseases, particularly prior to the diagnosis of bullous pemphigoid. OBJECTIVE: The aims were: (i) to evaluate the demographic and clinical features of bullous pemphigoid from a database of patients at a Portuguese university hospital and (ii) to compare the prevalence of comorbid conditions before the diagnosis of bullous pemphigoid with a control group. METHODS: Seventy-seven patients with bullous pemphigoid were enrolled in the study. They were compared with 176 age- and gender-matched controls, which also had the same inpatient to outpatient ratio, but no history of bullous or cutaneous malignant disease. Univariate and multivariate analyses were used to calculate odds ratios for specific comorbid diseases. RESULTS: At least one neurologic diagnosis was present in 55.8% of BP patients compared with 20.5% controls (p<0.001). Comparing cases to controls, stroke was seen in 35.1 vs. 6.8%, OR 8.10 (3.80-17.25); dementia in 37.7 vs. 11.9%, OR 5.25 (2.71-10.16); and Parkinson's disease in 5.2 vs. 1.1%, OR 4.91 (0.88-27.44). Using multivariate analysis, all diseases except Parkinson's retained their association with BP. Patients under systemic treatment were eight times more likely to have complications than those treated with topical steroids (p< 0.017). CONCLUSIONS: The results of this study substantiate the association between BP and neurological diseases. In addition, they highlight the potential complications associated with the treatment of BP

Prevalence of pemphigus and pemphigoid autoantibodies in the general population

Background: Mucocutaneous blistering is characteristic of autoimmune bullous dermatoses (AIBD). Blisters are caused by autoantibodies directed against structural components of the skin. Hence, detection of specific autoantibodies has become a hallmark for AIBD diagnosis. Studies on prevalence of AIBD autoantibodies in healthy individuals yielded contradictory results. Methods: To clarify this, samples from 7063 blood donors were tested for presence of anti-BP180-NC16A, anti-BP230 and anti-Dsg1/3 IgG by indirect immunofluorescence (IF) microscopy using a biochip. Results: Cumulative prevalence of these autoantibodies was 0.9 % (CI: 0.7-1.1 %), with anti-BP180-NC16A IgG being most prevalent. Validation of IF findings using ELISA confirmed presence of autoantibodies in 7/15 (anti-Dsg1), 6/7 (anti-Dsg3), 35/37 (anti-BP180-NC16A) and 2/3 (anti-BP230) cases. Moreover, in 16 samples, anti-BP180-NC16A autoantibody concentrations exceeded the cut-off for the diagnosis of bullous pemphigoid. Interestingly, these anti-BP180-NC16A autoantibodies from healthy individuals formed immune complexes with recombinant antigen and dose-dependently activated neutrophils in vitro. However, fine-epitope mapping within NC16A showed a different binding pattern of anti-BP180-NC16A autoantibodies from healthy individuals compared to bullous pemphigoid patients, while IgG subclasses were identical. Conclusions: Collectively, we here report a low prevalence of AIBD autoantibodies in a large cohort of healthy individuals. Furthermore, functional analysis shows differences between autoantibodies from healthy donors and AIBD patients

Oral autoimmune vesicobullous diseases: Classification, clinical presentations, molecular mechanisms, diagnostic algorithms, and management

Mucocutaneous blistering autoimmune diseases are a group of systemic, rare, chronic disorders characterized by humoral-mediated immunologic mechanisms against epithelial, basement membrane, and subepithelial tissues. Morbidity and mortality can be completely different among these diseases, with outcome being dependent on an early and accurate diagnosis, systemic comorbidities, and the patient's response to treatment. Definitive diagnosis is based on clinical and histopathologic findings. Because clinical presentations among these diseases are often similar, different immunofluorescence tests and ELISAs are used to confirm the specific diagnosis. Oral mucosa may often be the first site of clinical manifestation from which the disease spreads to other mucosal surfaces and skin. Thus, often dentists and oral medicine specialists may be the first to encounter patients with such diseases. In this review we discuss the most frequent autoimmune vesicobullous disorders, namely pemphigus vulgaris, mucous membrane pemphigoid, bullous pemphigoid, and linear IgA disease