Case Report: A Rare Case of Pembrolizumab-Induced Bullous Pemphigoid

The programmed cell death protein 1 inhibitor pembrolizumab, an immune checkpoint inhibitor, has subsequently been approved for the treatment of a wide variety of malignant tumors. Compared with conventional chemotherapy, immunotherapy is associated with a unique set of immune reactions, known collectively as immune-related adverse events. Although often mild, dermatologic toxicity can occasionally be high grade and potentially life-threatening. Here we describe a rare case of bullous pemphigoid (BP) associated with pembrolizumab. A 79-year-old male patient presented with scattered erythema, papules, blisters, and pruritus after pembrolizumab treatment. Then, the rash gradually aggravated and spread to the whole body. The extensive edematous erythema, blisters, bullae, and blood blisters were loose and easy to rupture, forming an erosive surface and with pruritus and obvious pain. The hemidesmosomal protein BP180 (type XVII collagen) was detectable in the serum, and the histological examination diagnosis was bullous pemphigoid. After 10 days of glucocorticoid (methylprednisolone, iv, 80 mg/day) treatment, new blister formation ceased. We need to increase the awareness on and facilitate the earlier identification of the cutaneous adverse effects of BP with immunotherapy so that treat can begin early in order to limit the duration and severity of toxicity.

Identification of two novel bullous pemphigoid- associated alleles, HLA-DQA1*05:05 and -DRB1*07:01, in Germans

Bullous pemphigoid (BP) is the most common autoimmune skin blistering disease characterized by autoimmunity against the hemidesmosomal proteins BP180, type XVII collagen, and BP230. To elucidate the genetic basis of susceptibility to BP, we performed the first genome-wide association study (GWAS) in Germans. This GWAS was combined with HLA locus targeted sequencing in an additional independent BP cohort. The strongest association with BP in Germans tested in this study was observed in the two HLA loci, HLA-DQA1*05:05 and HLA-DRB1*07:01. Further studies with increased sample sizes and complex studies integrating multiple pathogenic drivers will be conducted.

Personalized Development of Antisense Oligonucleotides for Exon Skipping Restores Type XVII Collagen Expression in Junctional Epidermolysis Bullosa

Intermediate junctional epidermolysis bullosa caused by mutations in the COL17A1 gene is characterized by the frequent development of blisters and erosions on the skin and mucous membranes. The rarity of the disease and the heterogeneity of the underlying mutations renders therapy developments challenging. However, the high number of short in-frame exons facilitates the use of antisense oligonucleotides (AON) to restore collagen 17 (C17) expression by inducing exon skipping. In a personalized approach, we designed and tested three AONs in combination with a cationic liposomal carrier for their ability to induce skipping of COL17A1 exon 7 in 2D culture and in 3D skin equivalents. We show that AON-induced exon skipping excludes the targeted exon from pre-mRNA processing, which restores the reading frame, leading to the expression of a slightly truncated protein. Furthermore, the expression and correct deposition of C17 at the dermal–epidermal junction indicates its functionality. Thus, we assume AON-mediated exon skipping to be a promising tool for the treatment of junctional epidermolysis bullosa, particularly applicable in a personalized manner for rare genotypes.