Dipeptidyl peptidase-4 inhibitor (DPP4i) is a widely used antidiabetic agent. Emerging cases of DPP4i-associated bullous pemphigoid (DBP), whose pathogenesis remains unclear, have been reported. Thus, a retrospective study was conducted from January 2016 to June 2021 to determine the clinical, laboratory, and histopathological features of DBP and idiopathic bullous pemphigoid (IBP). We set up in vitro experiments using vildagliptin-treated HaCaT keratinocytes to validate what we found by analyzing published RNA sequencing data about the genes related to the dermal–epidermal junction. We also observed IL-6 expression by HaCaT cells treated with vildagliptin. We enrolled 20 patients with DBP and 40 patients with IBP. The total Bullous Pemphigoid Disease Area Index (BPDAI) score was similar in both groups. However, the BPDAI score of erosions and blisters in DBP was significantly higher than that in IBP (24.6 vs. 16.68, p = 0.0189), and the score for urticaria and erythema was lower in DBP (12 vs. 19.05, p = 0.0183). The pathological features showed that the mean infiltrating eosinophil number per high-power field was significantly lower in DBP than in IBP (16.7 vs. 27.08, p = 0.023). The expression of LAMA3, LAMB3, LAMC2, DST, and COL17A1 decreased significantly in vildagliptin-treated human keratinocytes. On the other hand, IL-6, the hallmark cytokine of bullous pemphigoid (BP) severity, was found to be upregulated in HaCaT cells by vildagliptin. These experimental findings imply less of a requirement for eosinophil infiltration to drive the inflammatory cascades in DBP blistering. Both immunologic and non-immunologic pathways could be employed for the development of DBP. Our findings may help explain the higher incidence of non-inflammatory BP that was observed in DBP.
Hormone replacement therapy (HRT) is widely used to relieve symptoms of menopause with proven efficacy. However, there has been significant controversy surrounding the use of HRT because of its potential link with an increased risk of cancer, particularly female reproductive organ cancers. That HRT increases the risk of melanoma is also disputed, and several cohort studies have produced variable results. To delineate the association between HRT and melanoma in Taiwan, we conducted a population‐based retrospective cohort study on 14 291 patients who had received HRT and 57 164 population controls in Taiwan between 2000 and 2013. Multivariate odds ratios (ORs) were calculated utilizing conditional logistic regression. Overall, the use of HRT was not significantly correlated with a higher risk of developing melanoma in Taiwan (95% confidence interval 0.386–1.099; p = 0.341). The hazard ratio analysis of melanoma and different HRTs showed there was no significant association between melanoma and the use of oral or external estrogens alone, including conjugated estrogens, estradiol, and estriol. Estrogen plus progesterone combined therapy was associated with a lower risk of melanoma. Only one case of melanoma was observed among the 2880 patients in this subgroup.
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