IMPORTANCE Recent studies suggest that dipeptidyl peptidase 4 (DPP-4) inhibitors are associated with an increased risk of developing bullous pemphigoid (BP). Population-based studies on the association between DPP-4 inhibitors and BP are limited. OBJECTIVE To characterize the potential association between the use of DPP-4 inhibitors and an increased risk of developing BP. DESIGN, SETTING, AND PARTICIPANTS This retrospective, nationwide, population-based, case-control study using Korean insurance claims data from January 1, 2012, to December 31, 2016, included patients with newly diagnosed BP and diabetes. Control patients with diabetes (and without BP) were randomly obtained after matching for age, sex, and year of diagnosis within the same period. MAIN OUTCOMES AND MEASURES The number of patients with newly diagnosed BP and diabetes per year and annual changes in the proportion of patients with diabetes among all patients with BP were measured. The association between use of DPP-4 inhibitors and risk of developing BP was analyzed using univariate and multivariate logistic regression analyses. RESULTS The study included 670 case patients (with diabetes and BP) and 670 control patients (with only diabetes) (mean [SD] age, 75.3 [10.0] years in each group; 342 [51.0%] male in each group). The number of patients with diabetes and BP more than doubled during the study period (from 77 in 2012 to 206 in 2016). The proportion of patients with diabetes among all patients with BP also increased (from 0.18 in 2012 to 0.33 in 2016). The use of DPP-4 inhibitors was associated with a significant increase in the risk of developing BP (adjusted odds ratio [aOR], 1.58; 95% CI, 1.25-2.00; P < .001); among all DPP-4 inhibitors used in Korea, the highest aOR was associated with the use of vildagliptin (aOR, 1.81; 95% CI, 1.31-2.50; P < .001). Subgroup analyses revealed a significant association in male patients (aOR, 1.91; 95% CI, 1.39-2.63; P < .001) and that vildagliptin was the most high-risk DPP-4 inhibitor (aOR, 2.70; 95% CI, 1.73-4.34; P < .001). CONCLUSIONS AND RELEVANCE The findings suggest that DPP-4 inhibitors are associated with a significantly increased risk of the development of BP in patients with diabetes. Of the DPP-4 inhibitors available in Korea, vildagliptin was associated with the highest risk, particularly in male patients. Practitioners should consider that DPP-4 inhibitors, particularly vildagliptin, may be associated with the development of BP in patients with diabetes. These nationwide, population-based results may serve as a foundation for further studies seeking to understand how DPP-4 inhibitors contribute to the development of BP.

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Fig. 1. (A) Honeycombing and intralobular interstitial thickening on chest computed tomography (B) Initial chest X-ray showed no active disease. (C) Peribronchial and reticulonodular opacity in both lungs was developed after the fifth injection of ustekinumab.

Background: Rosacea is a common skin disease associated with increased expression of cathelicidin, kallikrein 5 (KLK5), toll-like receptor (TLR) 2, and abnormal barrier function. Recently, it was reported that hyaluronan (HA) could influence immune function via various receptors and HA oligosaccharides (oligo-HAs) could suppress TLR-dependent cytokine expression. Objective: We investigated if oligo-HAs could influence on inflammation and epidermal barrier induced by LL-37, which had a major role in rosacea. Methods: We cultured normal human keratinocytes and treated them with LL-37 and oligo-HAs or the LL-37 alone. A rosacea-like BALB/c mouse model injected with LL-37 was used to determine the role of oligo-HAs in rosacea in vivo. Results: Interleukin-8 (IL-8) and tumor necrosis factor (TNF)-α release was suppressed when keratinocytes were co-treated with oligo-HAs and LL-37 compared with keratinocytes treated with LL-37 only. Treatment with oligo-HAs resulted in decreased transepidermal water loss as well as improved redness. Decreased inflammatory cell infiltration, IL-17A and KLK5 expression and increased CD44 and filaggrin expression were also noted. Conclusion: Our findings suggest that oligo-HA improves rosacea-like phenotype through anti-inflammatory and epidermal barrier improving effect. (Ann Dermatol 32(3) 189∼196, 2020