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      Bullous pemphigoid associated with dipeptidyl peptidase‐4 inhibitors: A report of five cases

      case-report

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          Abstract

          Bullous pemphigoid ( BP) is an autoimmune blistering skin disorder. Recently, BP induced by dipeptidyl peptidase‐4 ( DPP‐4) inhibitors has been a concern. Although DPP‐4 inhibitors are commonly used in the Asian population because of their safety and efficacy, BP associated with DPP‐4 inhibitors is sometimes seen in clinical settings. Here, we report five Japanese cases of BP associated with the agents. In the present cases, BP occurred in older adults using four different DPP‐4 inhibitors, which showed various clinical manifestations in terms of latency period for BP, sex, glycemic control and diabetes duration. Withdrawal of DPP‐4 inhibitors was effective in improving BP, and achieved remission even in cases requiring oral steroid administration and intravenous immunoglobulin therapy. Clinicians should note the importance of early diagnosis of this clinical condition and initiate prompt withdrawal of DPP‐4 inhibitors.

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          Most cited references7

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          Autoantibody Profile Differentiates between Inflammatory and Noninflammatory Bullous Pemphigoid.

          Bullous pemphigoid (BP) is a major autoimmune blistering skin disorder, in which a majority of the autoantibodies (autoAbs) target the juxtamembranous extracellular noncollagenous 16A domain (NC16A) domain of hemidesmosomal collagen XVII. BP-autoAbs may target regions of collagen XVII other than the NC16A domain; however, correlations between epitopes of BP-autoAbs and clinical features have not been fully elucidated. To address correlations between the clinical features and specific epitopes of BP-autoAbs, we evaluated the epitope profiles of BP-autoAbs in 121 patients. A total of 87 patients showed a typical inflammatory phenotype with erythema and autoAbs targeting the anti-NC16A domain, whereas 14 patients showed a distinct noninflammatory phenotype, in which autoAbs specifically targeted the midportion of collagen XVII, but not NC16A. Interestingly, this group clinically showed significantly reduced erythema associated with scant lesional infiltration of eosinophils. Surprisingly, 7 of the 14 cases (50.0%) received dipeptidyl peptidase-IV inhibitors for the treatment of diabetes. Dipeptidyl peptidase-IV inhibitors were used in 3 of 76 (3.9%) typical cases of BP with autoAbs targeting NC16A; thus, dipeptidyl peptidase-IV inhibitors are thought to be involved in the development of atypical noninflammatory BP. This study shows that the autoAb profile differentiates between inflammatory and noninflammatory BP, and that noninflammatory BP may be associated with dipeptidyl peptidase-IV inhibitors.
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            Screening Tool for Older Persons' Appropriate Prescriptions for Japanese: Report of the Japan Geriatrics Society Working Group on "Guidelines for medical treatment and its safety in the elderly".

            In 2005, the Japan Geriatrics Society published a list of potentially inappropriate medication that was an extract from the "Guidelines for medical treatment and its safety in the elderly 2005." The 2005 guidelines are due for a revision, and a new comprehensive list of potentially inappropriate medications is required.
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              Bullous pemphigoid and dipeptidyl peptidase IV inhibitors: a case-noncase study in the French Pharmacovigilance Database.

              Inhibitors of dipeptidyl peptidase (DPP)-IV have been suspected in the onset of bullous pemphigoid for several years now. However, comparative studies assessing the link between DPP-IV inhibitor exposure and bullous pemphigoid have not yet been performed.
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                Author and article information

                Contributors
                inagaki@kuhp.kyoto-u.ac.jp
                Journal
                J Diabetes Investig
                J Diabetes Investig
                10.1111/(ISSN)2040-1124
                JDI
                Journal of Diabetes Investigation
                John Wiley and Sons Inc. (Hoboken )
                2040-1116
                2040-1124
                26 June 2017
                March 2018
                : 9
                : 2 ( doiID: 10.1111/jdi.2018.9.issue-2 )
                : 445-447
                Affiliations
                [ 1 ] Department of Diabetes Endocrinology and Nutrition Kyoto University Graduate School of Medicine Kyoto Japan
                [ 2 ] Department of Endocrinology and Metabolism Rakuwakai Otowa Hospital Kyoto Japan
                Author notes
                [*] [* ] Correspondence

                Nobuya Inagaki

                Tel.: +81‐75‐751‐3560

                Fax: +81‐75‐751‐4244

                E‐mail address: inagaki@ 123456kuhp.kyoto-u.ac.jp

                Author information
                http://orcid.org/0000-0002-5334-7687
                http://orcid.org/0000-0001-8261-2593
                Article
                JDI12695
                10.1111/jdi.12695
                5835473
                28520234
                e948d6fb-d6be-4206-baba-3f6657045eec
                © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 10 April 2017
                : 15 May 2017
                : 15 May 2017
                Page count
                Figures: 1, Tables: 1, Pages: 3, Words: 1965
                Categories
                Case Report
                Articles
                Clinical Science and Care
                Custom metadata
                2.0
                jdi12695
                March 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.2.2 mode:remove_FC converted:04.03.2018

                bullous pemphigoid,dipeptidyl peptidase‐4 inhibitors,elderly

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