Bullous pemphigoid associated with dipeptidyl peptidase‐4 inhibitors. A case series and analysis of cases reported in the Spanish pharmacovigilance database

2019 ◽  
Vol 59 (2) ◽  
pp. 197-206 ◽  
Author(s):  
Alejandra Reolid ◽  
Ester Muñoz‐Aceituno ◽  
Pedro Rodríguez‐Jiménez ◽  
Esperanza González‐Rojano ◽  
Mar Llamas‐Velasco ◽  
...  
Keyword(s):  
Bullous Pemphigoid ◽  
Case Series ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Pharmacovigilance Database ◽  
Analysis Of Cases

scholarly journals Clinical Features and Outcomes of Dipeptidyl Peptidase-4 Inhibitor-Associated Bullous Pemphigoid (DPP4i-Associated BP) in Thai Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Yotsapon Thewjitcharoen ◽  
Ekgaluck Wanothayaroj ◽  
Chattip Thammawiwat ◽  
Sriurai Porramatikul ◽  
Chuleekorn Vorayingyong ◽  
...  
Keyword(s):  
Bullous Pemphigoid ◽  
Case Series ◽  
Latency Period ◽  
Dipeptidyl Peptidase ◽  
Elderly Male ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Potential Link ◽  
Male Patients

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.

scholarly journals Clinical, Laboratory and Histological Features of Dipeptidyl Peptidase-4 Inhibitor Related Noninflammatory Bullous Pemphigoid

2021 ◽  
Vol 10 (9) ◽  
pp. 1916
Author(s):  
Ágnes Kinyó ◽  
Anita Hanyecz ◽  
Zsuzsanna Lengyel ◽  
Dalma Várszegi ◽  
Péter Oláh ◽  
...  
Keyword(s):  
Bullous Pemphigoid ◽  
Clinical Laboratory ◽  
Case Series ◽  
Dipeptidyl Peptidase ◽  
Area Index ◽  
Histological Features ◽  
Dipeptidyl Peptidase 4 ◽  
First Case ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
The Mean

Bullous pemphigoid (BP) is an autoimmune blistering disease of elderly patients that has shown increasing incidence in the last decades. Higher prevalence of BP may be due to more frequent use of provoking agents, such as antidiabetic dipeptidyl peptidase-4 inhibitor (DPP4i) drugs. Our aim was to assess DPP4i-induced bullous pemphigoid among our BP patients and characterize the clinical, laboratory and histological features of this drug-induced disease form. In our patient cohort, out of 127 BP patients (79 females (62.2%), 48 males (37.7%)), 14 (9 females and 5 males) were treated with DPP4i at the time of BP diagnosis. The Bullous Pemphigoid Disease Area Index (BPDAI) urticaria/erythema score was significantly lower, and the BPDAI damage score was significantly higher in DPP4i-BP patients compared to the nonDPP4i group. Both the mean absolute eosinophil number and the mean periblister eosinophil number was significantly lower in DPP4i-BP patients than in nonDPP4i cases (317.7 ± 0.204 vs. 894.0 ± 1.171 cells/μL, p < 0.0001; 6.75 ± 1.72 vs. 19.09 ± 3.1, p = 0.0012, respectively). Our results provide further evidence that DPP4i-associated BP differs significantly from classical BP, and presents with less distributed skin symptoms, mild erythema, normal or slightly elevated peripheral eosinophil count, and lower titers of BP180 autoantibodies. To our knowledge, this is the first case series of DPP4i-related BP with a non-inflammatory phenotype in European patients.

scholarly journals The association of bullous pemphigoid with dipeptidyl-peptidase 4 inhibitors: a ten-year prospective observational study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Vaia Lambadiari ◽  
Aikaterini Kountouri ◽  
Foteini Kousathana ◽  
Emmanouil Korakas ◽  
Georgios Kokkalis ◽  
...  
Keyword(s):  
Bullous Pemphigoid ◽  
Prospective Observational Study ◽  
Dipeptidyl Peptidase ◽  
Dermatology Department ◽  
Steroid Administration ◽  
Dipeptidyl Peptidase 4 ◽  
Increased Risk ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
A Prospective Study

Abstract Background Bullous pemphigoid is the most common bullous chronic autoimmune skin disease. Recent studies have suggested dipeptidyl-peptidase 4 inhibitors as possible predisposing agents of bullous pemphigoid. The objective of our study was to prospectively estimate the association between gliptins and the development of bullous pemphigoid. Methods We conducted a prospective study which included all patients diagnosed with biopsy-proven bullous pemphigoid in the Dermatology Department of our hospital between April 1, 2009 and December 31,2019. The diagnosis of bullous pemphigoid was based on specific clinical, histological and immunological features. Results Overall 113 consecutive patients (age 75 ± 13 years, 62 females) with the diagnosis of bullous pemphigoid were enrolled. Seventy-six patients (67.3%) suffered from type 2 Diabetes and 52 (46%) were treated with dipeptidyl-peptidase 4 inhibitors. The most frequent prescribed gliptin was vildagliptin, being administered to 45 cases (39.8% of total patients enrolled, 86.5% of the patients treated with gliptins). Gliptins were withdrawn immediately after the diagnosis of bullous pemphigoid, which together with steroid administration led to remission of the rash. Conclusions This study revealed that treatment with dipeptidyl-peptidase 4 inhibitors, especially vildagliptin, is significantly associated with an increased risk of bullous pemphigoid development.

scholarly journals Dipeptidyl peptidase 4 inhibitors and bullous pemphigoid − more evidence of a link: a report of three cases

2020 ◽  
Vol 20 (2) ◽  
pp. 147-148
Author(s):  
Amrita Randhawa ◽  
Donna Torley ◽  
Alastair Kerr ◽  
Grant Wylie
Keyword(s):  
Elderly Patients ◽  
Bullous Pemphigoid ◽  
Dipeptidyl Peptidase ◽  
Antidiabetic Medication ◽  
Dermatology Department ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Patients With Diabetes

Recently, dipeptidyl peptidase 4 (DPP-4) inhibitors, an antidiabetic medication, have been implicated in the development of bullous pemphigoid, the most common autoimmune cutaneous blistering disorder. In this report we present three cases of DPP-4 associated bullous pemphigoid in our dermatology department. These cases illustrate the importance for clinicians to consider a drug as a trigger for bullous pemphigoid in elderly patients with diabetes.

scholarly journals Association between dipeptidyl peptidase-4 inhibitors and risk of bullous pemphigoid in patients with diabetes: A population-based cohort study

2020 ◽  
Author(s):  
Chen-Yi Wu ◽  
Chun-Ying Wu ◽  
Chung-Pin Li ◽  
Yiing-Jenq Chou ◽  
Yi-Hsian Lin ◽  
...  
Keyword(s):  
Cohort Study ◽  
Bullous Pemphigoid ◽  
Cumulative Incidence ◽  
Dipeptidyl Peptidase ◽  
Diabetic Patients ◽  
Diabetes Diagnosis ◽  
Dipeptidyl Peptidase 4 ◽  
Duration Of Diabetes ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Diabetes Patients

Abstract Background Higher bullous pemphigoid (BP) risk has been reported to be associated with dipeptidyl peptidase 4 inhibitor (DPP4i). However, large-scale studies to investigate the association between BP and DPP4i treatment are limited. The aim of this study is to examine the association between BP risk and DPP4i treatment in diabetes patients. Methods We conducted a nationwide cohort study based on the Taiwan National Health Insurance Database between 2000 and 2015. 124,619 diabetic patients who were receiving DPP4i therapy were matched 1: 1 with diabetic patients who had never received DPP4i by age, sex, duration of diabetes, insulin usage, and propensity score-matching of comorbidities. Results Of the 124,619 diabetes patients in the two groups, the mean age at diabetes diagnosis was 52.4 ± 10.9 years, with a mean duration of diabetes of 6.0 ± 3.9 years. After adjusting for competing mortality risk, the 6-year cumulative incidence of BP in the DPP4i-treated cohort was significantly higher than that in the non-DPP4i group (0.74 per 1000; 95% confidence interval [CI]: 0.51–1.05 vs 0.38 per 1000; 95% CI: 0.26–0.53, P = .001). The DPP4i and insulin-treated group had the highest 6-year cumulative incidence for BP (0.93; 95% CI: 0.54–1.54 per 1000). Modified Cox regression analysis revealed that DPP4i treatment (HR: 2.15, 95% CI: 1.18–3.91, P = 0.01), age (HR: 1.06, P < .001), renal disease (HR: 2.32, P < .001), and metformin user (HR: 1.93, P = 0.006) were associated with increased BP risk. Conclusion DPP4i users had a 2.2-fold increase in the risk of BP, and the risk was the highest in those with concomitant use of DPP4i and insulin. The use of DPP4is as anti-diabetic medications must be monitored carefully and may be replaced by other anti-diabetic medications in BP patients.

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