Thewjitcharoen Yotsapon, Wanothayaroj Ekgaluck, Thammawiwat Chattip, Porramatikul Sriurai, Vorayingyong Chuleekorn, Nakasatien Soontaree, Krittiyawong Sirinate, Chanprapaph Kumutnart, Himathongkam Thep
Diabetes and Thyroid Center, Theptarin Hospital, Bangkok, Thailand.
Department of Dermatology, Theptarin Hospital, Bangkok, Thailand.
Case Rep Endocrinol. 2020 Oct 10;2020:8832643. doi: 10.1155/2020/8832643. eCollection 2020.
The use of dipeptidyl peptidase-4 inhibitors (DPP4i) appears to be associated with a small but significantly elevated risk of bullous pemphigoid (BP). Although the pathogenic mechanism of DPP4i-associated BP remains unclear, this adverse event is reported with multiple gliptins, suggesting a class effect. However, previous studies from various countries showed that vildagliptin had been implicated in most cases. The aim of this study was to illustrate a case series of DPP4i-associated BP in Thai patients. We conducted a retrospective study from consecutive cases of BP in people with type 2 diabetes mellitus (T2DM) from January 2008, the year in which the first DPP4i was introduced in Thailand, until December 2019. During the study period, 10 BP patients with T2DM were identified. A total of 5 DPP4i-associated BP (3 on vildagliptin, 1 on linagliptin, and 1 on sitagliptin) were found. All patients were male with a mean age at BP development of 80.4 years (73-86 years). All patients had a long-standing duration of diabetes (median duration 34 years), and mean A1C was 7.5 ± 1.4%. The median time to BP development after the introduction of DPP4i was 64 months (range 20-128 months). The severity of BP was classified as mild in 2 cases. In all cases, the association between the drug intake and BP onset was classified as "possible" according to the Naranjo causality scale. All of the patients continued taking DPP4i after BP diagnosis, and one patient died of lung cancer 18 months after BP diagnosis. Only 2 patients could achieve complete remission at least 2 months after stopping DPP4i. Our case series demonstrated a potential link between DPP4i and the development of BP, which mainly occurred in very elderly male patients. The latency period from an introduction of DPP-4i could be several years, and the clinical course after DPP4i discontinuation varied. Clinicians prescribing DPP4i should be aware of this association and consider stopping this medication before a refractory disease course ensues.
使用二肽基肽酶 - 4抑制剂（DPP4i）似乎与大疱性类天疱疮（BP）风险小幅但显著升高相关。尽管DPP4i相关BP的致病机制尚不清楚，但多种格列汀类药物都报告了这一不良事件，提示存在类效应。然而，各国既往研究表明，大多数病例都与维格列汀有关。本研究旨在阐述泰国患者中一系列DPP4i相关BP病例。我们对2008年1月（泰国首次引入首个DPP4i的年份）至2019年12月期间2型糖尿病（T2DM）患者中连续的BP病例进行了回顾性研究。研究期间，共确定了10例T2DM合并BP患者。共发现5例DPP4i相关BP（3例使用维格列汀，1例使用利格列汀，1例使用西格列汀）。所有患者均为男性，BP发病时的平均年龄为80.4岁（73 - 86岁）。所有患者糖尿病病程均较长（中位病程34年），平均糖化血红蛋白（A1C）为7.5±1.4%。引入DPP4i后BP发病的中位时间为64个月（范围20 - 128个月）。2例患者的BP严重程度分类为轻度。根据Naranjo因果关系量表，所有病例中药物摄入与BP发病之间的关联均分类为“可能”。所有患者在BP诊断后继续服用DPP4i，1例患者在BP诊断后18个月死于肺癌。仅2例患者在停用DPP4i后至少2个月实现完全缓解。我们的病例系列证明了DPP4i与BP发病之间存在潜在联系，主要发生在老年男性患者中。引入DPP - 4i后的潜伏期可能长达数年，停用DPP4i后的临床病程各不相同。开具DPP4i处方的临床医生应了解这种关联，并在难治性病程出现之前考虑停用该药物。
