Background Bullous pemphigoid (BP) is an autoimmune blistering disease that is associated with an increased mortality rate. Objective To determine the incidence and mortality rate of patients with bullous pemphigoid. Methods Eighty-seven residents of Olmsted County, Minnesota, were identified who had their first lifetime diagnosis of BP from January 1960 – December 2009. Incidence and mortality rate were compared to age- and sex-matched control patients from the same geographic area. Results The adjusted incidence of BP was 2.4 per 100,000 person-years (95% CI, 1.9–2.9). Incidence of BP increased significantly with age (P<.001) and over time (P=0.034). Trend tests indicate increased diagnosis of localized disease (P=.006) may be a contributing factor. Survival observed in the incident BP cohort was significantly poorer than expected (P<.001). Survival was not different among patients with multisite vs localized disease (P=.90). Limitations Retrospective study design and study population from a small geographic area. Conclusion Incidence of BP in the United States is comparable to that found in Europe and Asia. The mortality rate of BP is lower in the United States than Europe, but higher than previous estimates.

Multiprotein complexes transduce cellular signals through extensive interaction networks, but the ability to analyze these networks in cells from small clinical biopsies is limited. To address this, we applied an adaptable multiplex matrix system to physiologically relevant signaling protein complexes isolated from a cell line or from human patient samples. Focusing on the proximal T cell receptor (TCR) signalosome, we assessed 210 pairs of PiSCES (proteins in shared complexes detected by exposed surface epitopes). Upon stimulation of Jurkat cells with superantigen-loaded antigen-presenting cells, this system produced high-dimensional data that enabled visualization of network activity. A comprehensive analysis platform generated PiSCES biosignatures by applying unsupervised hierarchical clustering, principal component analysis, an adaptive nonparametric with empirical cutoff analysis, and weighted correlation network analysis. We generated PiSCES biosignatures from 4-mm skin punch biopsies from control patients or patients with the autoimmune skin disease alopecia areata. This analysis distinguished disease patients from the controls, detected enhanced basal TCR signaling in the autoimmune patients, and identified a potential signaling network signature that may be indicative of disease. Thus, generation of PiSCES biosignatures represents an approach that can provide information about the activity of protein signaling networks in samples including low-abundance primary cells from clinical biopsies.

Background Bullous pemphigoid has been reported in association with neurologic disorders. Objective To analyze the association between bullous pemphigoid and neurologic disorders. Methods We retrospectively identified residents of Olmsted County, Minnesota, with a first lifetime diagnosis of bullous pemphigoid between January 1, 1960, and December 31, 2009. Three age- and sex-matched Olmsted County residents without bullous pemphigoid were selected as controls for each patient. We compared history of or development of neurologic disorders (dementia, Alzheimer disease, Parkinson disease, multiple sclerosis, cerebrovascular disease, and seizures) between groups using case-control and cohort designs. Results A total of 87 patients with bullous pemphigoid were identified and matched to 261 controls. The odds of a previous diagnosis of any neurologic disorder or a history of dementia were significantly increased among cases compared with controls (odds ratios: 6.85 (3.00–15.64); P<.001, and 6.75 (2.08–21.92); P=.002, respectively). Both Parkinson disease (hazard ratio, 8.56 (1.55–47.25); P=.01) and any type of neurologic disorder (hazard ratio, 2.02 (1.17–3.49); P=.01) were significantly more likely to develop during follow-up in patients with bullous pemphigoid than in those without bullous pemphigoid. Limitations Small geographic area; retrospective study design. Conclusion Our study confirmed an association of bullous pemphigoid with neurologic disorders, especially dementia and Parkinson disease.

Immune checkpoint inhibitors are approved for select cancer treatment and have shown survival benefit in patients with advanced melanoma. Adverse events, including immune-related adverse events, are common and potentially life-threatening. We describe cases of 2 patients with scleroderma (patient 1 had diffuse scleroderma, and patient 2 had limited scleroderma) that developed while they were receiving pembrolizumab therapy for metastatic melanoma. Prompt recognition and treatment of immune-related adverse events may improve tolerance to immune checkpoint inhibitors and contribute to an understanding of the manifesting autoimmune disease.