A case of bullous pemphigoid ınduced by vildagliptin

Keseroglu, Havva Ozge; Tas-Aygar, Gamze; Gönül, Müzeyyen; Gököz, Özay; Ersoy‐Evans, Sibel

doi:10.1080/15569527.2016.1211670

Cited by 17 publications

(16 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although autoimmune bullous diseases are rare diseases with low annual incidences, among which BP is the least rare, associations have been published between drug intake and many BP ( 6 – 8 ) and LABD cases ( 50 ) but only a few MMPs ( 51 ). Since 2011, an increasing number of reports have suggested that gliptins trigger BP ( 9 – 15 , 17 – 23 ). Last, very recently, four comparative case–non-case studies demonstrated a significant association between gliptin intake and BP onset in diabetic patients ( 16 , 24 – 26 ).…”

Section: Discussionmentioning

confidence: 99%

Gliptin Accountability in Mucous Membrane Pemphigoid Induction in 24 Out of 313 Patients

et al. 2018

View full text Add to dashboard Cite

Mucous membrane pemphigoids (MMPs) and bullous pemphigoid (BP) are autoimmune bullous diseases that share physiopathological features: both can result from autoantibodies directed against BP180 or BP230 antigens. An association has been reported between BP and intake of gliptins, which are dipeptidyl peptidase-IV inhibitors used to treat type 2 diabetes mellitus. Clinical and immunological differences have been reported between gliptin-induced BPs and classical BPs: mucosal involvement, non-inflammatory lesions, and target BP180 epitopes other than the NC16A domain. Those findings accorded gliptins extrinsic accountability in triggering MMP onset. Therefore, we examined gliptin intrinsic accountability in a cohort of 313 MMP patients. To do so, we (1) identified MMP patients with gliptin-treated (challenge) diabetes; (2) selected those whose interval between starting gliptin and MMP onset was suggestive or compatible with gliptin-induced MMP; (3) compared the follow-ups of patients who did not stop (no dechallenge), stopped (dechallenge) or repeated gliptin intake (rechallenge); (4) compared the clinical and immunological characteristics of suggestive-or-compatible-challenge patients to 121 never-gliptin-treated MMP patients serving as controls; and (5) individually scored gliptin accountability as the trigger of each patient’s MMP using the World Health Organization-Uppsala Monitoring Center, Naranjo- and Begaud-scoring systems. 17 out of 24 gliptin-treated diabetic MMP patients had suggestive (≤12 weeks) or compatible challenges. Complete remission at 1 year of follow-up was more frequent in the 11 dechallenged patients. One rechallenged patient’s MMP relapsed. These 17 gliptin-treated diabetic MMP patients differed significantly from the MMP controls by more cutaneous, less buccal, and less severe involvements and no direct immunofluorescence IgA labeling of the basement membrane zone. Multiple autoantibody-target antigens/epitopes (BP180–NC16A, BP180 mid- and C-terminal parts, integrin α6β4) could be detected, but not laminin 332. Last, among the 24 gliptin-treated diabetic MMP patients, five had high (I4–I3), 12 had low (I2-I1) and 7 had I0 Begaud intrinsic accountability scores. These results strongly suggest that gliptins are probably responsible for some MMPs. Consequently, gliptins should immediately be discontinued for patients with a positive accountability score. Moreover, pharmacovigilance centers should be notified of these events.

show abstract

Section: Discussionmentioning

confidence: 99%

Gliptin Accountability in Mucous Membrane Pemphigoid Induction in 24 Out of 313 Patients

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Keseroglu et al [21] 61 F Vildagliptin/ metformin The duration of follow up not mentioned Aouidad et al [23] 61 M Vildagliptin/ metformin Pasmatzi et al [24] 59 F Vildagliptin/ metformin…”

Section: Still In Remission At 1-year Follow-upmentioning

confidence: 99%

Linagliptin-Associated Alopecia and Bullous Pemphigoid

Someili

Azzam

Hilal

2019

European Journal of Case Reports in Internal Medicine

View full text Add to dashboard Cite

Bullous pemphigoid is a chronic autoimmune blistering disease. Recently, several reports suggested dipeptidyl peptidase 4 (DPP-4) inhibitors, also known as gliptins, were a potential cause of drug-induced bullous pemphigoid but not of both bullous pemphigoid and alopecia areata together. Here we describe the case of a 68-year-old man with type 2 diabetes mellitus who developed new onset diffuse alopecia on the scalp with diffuse tense bullae over his body a few months after linagliptin was introduced for better control of his diabetes. DPP-4 inhibitors are not known to increase the risk of alopecia. To the best of our knowledge, this is the first report of linagliptin-associated alopecia areata and bullous pemphigoid, which may help demonstrate if there are any links between DPP-4 inhibitors and alopecia. LEARNING POINTS • This is the first report of linagliptin-associated alopecia areata and bullous pemphigoid (BP), which may help demonstrate a link between DPP-4 inhibitors and alopecia. • Since the time of onset of BP after initiation of a DPP-4 inhibitor varies, a high index of suspicion is needed for diagnosis. • Early diagnosis is essential as DPP-4 inhibitor withdrawal has a significant effect on disease remission.

show abstract

“…The main cutaneous side effects reported with gliptins are cutaneous eruptions, pruritus, urticarial reactions, and some severe but rare reactions, such as toxic epidermal necrolysis or anaphylaxis (Andukuri et al, 2009;Banerji et al, 2010;Desai et al, 2010;Gerrald et al, 2012;Scheen et al, 2010). Forty-one case reports and small case series of gliptin-associated BP have been reported since 2011 (Aouidad et al, 2013;Attaway et al, 2014;Béné et al, 2015;Esposito et al, 2017;Fania et al, 2018;Garcia et al, 2016;Haber et al, 2016;Keseroglu et al, 2017;Mendonça et al, 2016;Pasmatzi et al, 2011;Sakai et al, 2017, Schaffer et al, 2017Skandalis et al, 2012;Yoshiji et al, 2018). Additionally, two case-non-case studies using pharmacovigilance databases reported a signal for an increased risk of BP during DPP-4 inhibitor exposure (Béné et al, 2016;Garcia et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Higher Frequency of Dipeptidyl Peptidase-4 Inhibitor Intake in Bullous Pemphigoid Patients than in the French General Population

Plaquevent

Tétart

Fardet

et al. 2019

Journal of Investigative Dermatology

101

View full text Add to dashboard Cite

Dipeptidyl peptidase-4 inhibitors have been suspected to induce bullous pemphigoid (BP). The objective of this study was to compare the observed frequency of gliptin intake in a large sample of 1,787 BP patients diagnosed between 2012 and 2015 in France, with the expected frequency after indirect age standardization on 225,412 individuals extracted from the database of the National Healthcare Insurance Agency. The secondary objective was to assess the clinical characteristics and the course of gliptin-associated BP, depending on whether gliptin was continued or stopped. The observed frequencies of intake of the whole gliptin class and that of vildagliptin in the BP population were higher than those in the general population after age standardization (whole gliptin class: 6.0%; 95% confidence interval ¼ 4.9e7.1% vs. 3.6%, observed-to-expected drug intake ratio ¼ 1.7; 95% confidence interval ¼ 1.4e2.0; P < 0.0001; vildagliptin ¼ 3.3%; 95% confidence interval ¼ 2.5e4.1% vs. 0.7%, ratio ¼ 4.4; 95% confidence interval ¼ 3.5e5.7; P < 0.0001). The association of any gliptinþmetformin was also higher than in the general population, ratio ¼ 1.8 (95% confidence interval ¼ 1.3e2.4; P < 0.0001). Gliptin-associated BP had no specific clinical characteristics. Gliptin was stopped in 48 (45.3%) cases. Median duration to achieve disease control, rate, and delay of relapse were not different whether gliptin was stopped or continued. This study strongly supports the association between gliptin intake, particularly vildagliptin, and the onset of BP.

show abstract

A case of bullous pemphigoid ınduced by vildagliptin

Cited by 17 publications

References 5 publications

Gliptin Accountability in Mucous Membrane Pemphigoid Induction in 24 Out of 313 Patients

Gliptin Accountability in Mucous Membrane Pemphigoid Induction in 24 Out of 313 Patients

Linagliptin-Associated Alopecia and Bullous Pemphigoid

Higher Frequency of Dipeptidyl Peptidase-4 Inhibitor Intake in Bullous Pemphigoid Patients than in the French General Population

Contact Info

Product

Resources

About