Bullous pemphigoid induced by dipeptidyl peptidase‐4 inhibitors. Eight cases with clinical and immunological characterization

García-Diez, Irene; Ivars, Marta; López-Aventín, Daniel; Ishii, Norito; Hashimoto, Takashi; Iranzo, Pilar; Pujol, Ramón M.; España, Agustín; Herrero-González, Josep E.

doi:10.1111/ijd.14005

Cited by 49 publications

(50 citation statements)

References 32 publications

(47 reference statements)

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“…The mean latency between the initiation of gliptin treatment and diagnosis of BP was approximately 13 months, which is in line with the findings of the recent registry studies (14,16). As in most previous reports (17,23,36) gliptins were withdrawn from most of our patients when they were diagnosed with BP, and all but one, required systemic treatment. Discontinuation of DPP-4i treatment is supported by studies, which demonstrated that gliptin withdrawal was followed by an improvement of BP clinical outcomes (14).…”

Section: Discussionsupporting

confidence: 90%

Gliptin-associated Bullous Pemphigoid and the Expression of Dipeptidyl Peptidase-4/CD26 in Bullous Pemphigoid

Lindgren¹,

Varpuluoma²,

Tuusa³

et al. 2019

Acta Derm Venerol

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Bullous pemphigoid is a blistering skin disease, generally seen in the elderly patients. Bullous pemphigoid is caused by an autoimmune reaction against the BP180 protein, but the exact reason is currently unknown. Several epidemiological studies have shown that the use of gliptins increases the risk for bullous pemphigoid, but it is unclear whether gliptin-associated bullous pemphigoid has specific clinical or immunological characteristics. Our study demonstrates that compared to "classical" bullous pemphigoid, gliptinassociated bullous pemphigoid may have some specific features, but the differences are not as striking as previously reported in Japanese patients. The anti-diabetic medications in bullous pemphigoid patients must be monitored carefully and gliptins should be replaced by another anti-diabetic medication. Dipeptidyl peptidase-4 inhibitors (DPP-4i or gliptins) increase the risk of developing bullous pemphigoid. To clarify, whether gliptin-associated bullous pemphigoid has special features, we analyzed the clinical, histopathological and immunological features of 27 bullous pemphigoid patients, 10 of which previously used gliptin medication. Compared to those who had not previously received gliptins, subjects who had, showed higher BP180-NC16A ELISA (enzyme-linked immunosorbent assay) values, fewer neurological co-morbidities and shorter time to remission, but differences were not statistically significant. The HLA-DQB1*03:01 allele was more commonly present among the bullous pemphigoid patients than the control population, but was not more common in those with gliptin history. To determine the effect of gliptins on the expression of the DPP-4/CD-26 protein we performed immunohistochemistry, which showed that the skin expression of DPP-4/CD-26 was increased in bullous pemphigoid patients, but not affected by prior gliptin treatment. We conclude that DPP-4i medication is common among bullous pemphigoid patients and prior gliptin treatment may be associated with some specific features.

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Section: Discussionsupporting

confidence: 90%

Gliptin-associated Bullous Pemphigoid and the Expression of Dipeptidyl Peptidase-4/CD26 in Bullous Pemphigoid

Lindgren¹,

Varpuluoma²,

Tuusa³

et al. 2019

Acta Derm Venerol

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“…Most BP patients present autoantibodies which bind to the 180-kDa protein immunodominant region, referred to as the non-collagenous domain NC16A [9,10]. However, in patients with gliptin-induced BP, most of these autoantibodies have been reported to react to other sites of the BP180 protein, such as LAD-1 and/or the terminal carboxyl domain [11]. To our knowledge, no specific BP drug-inducing autoantibodies have been identified yet.…”

Section: Introductionmentioning

confidence: 98%

Bullous pemphigoid associated with the use of dipeptidil peptidase-4 inhibitors: analysis from studies based on pharmacovigilance databases

et al. 2020

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Background Bullous pemphigoid has been associated to dipeptidase-4 inhibitors. Objectives Addressing the potential Bullous pemphigoid-dipeptidase-4 inhibitors association based on pharmacovigilance data currently available in Spain in order to obtain a composite disproportionality estimator from all the data generated by the case-non case studies conducted to this date. Setting The Spanish Pharmacovigilance System for Human Use Drugs database. Method Case-non case study based on the Spanish Pharmacovigilance System for Human Use Drugs notifications submitted between 2007 and 2018 (n = 169,280), using the Medical Dictionary for Regulatory Activities term (Preferred Term) 'pemphigoid' for sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin (n = 1952). As negative control, we used acetaminophen, while furosemide was the positive control. A pooled reported odds ratio analysis in the French, Japanese, and Spanish national pharmacovigilance databases was performed. On The Spanish Pharmacovigilance System for Human Use Drugs, we conducted a bullous pemphigoid-metformin association analysis within the period 1982-2018. Main outcome measure Adverse reaction cases in pharmacovigilance databases and the disproportionality through the reporting odds ratio. Results Within The Spanish Pharmacovigilance System for Human Use Drugs, we found 45 cases of bullous pemphigoid in dipeptidase-4 inhibitors patients. Median age was 77 years (range 72-82). The median latency period was 7 months (range 0.23-86). The Bullous pemphigoid-dipeptidase-4 inhibitors association was established with a reporting odd ratio = 70.0 (95% confidence intervals 49.1-10.1). In the combined analysis of the three aforementioned pharmacovigilance databases, the pooled reporting odd ratio was 81.0 (95% confidence intervals 69.5-94.4). Conclusion The composite estimator for the three national pharmacovigilance databases yields clear evidence of a Bullous pemphigoid-dipeptidase-4 inhibitors association, which was statistically significant for both the pharmacological class as a whole and each of the dipeptidase-4 inhibitors agents under investigation. Metformin's role in the incidence of bullous pemphigoid appeared casual rather than causal. No differences between Caucasian and Asian populations were noted.

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“…Among the side effects of gliptins involving the skin, itching, urticaria, and Stevens‐Johnson syndrome stand out. Many research publications have shown the association between gliptins and PB. It has also been described in the literature one case of bullous LP secondary to nivolumab and another one case probably caused by enalapril .…”

Section: Differential Diagnosis Of Lp Pemphigoid and Main Differencesmentioning

confidence: 99%

Pemphigoid lichen planus consequential to vildagliptin: a rare variant of bullous pemphigoid?

et al. 2019

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Bullous pemphigoid induced by dipeptidyl peptidase‐4 inhibitors. Eight cases with clinical and immunological characterization

Cited by 49 publications

References 32 publications

Gliptin-associated Bullous Pemphigoid and the Expression of Dipeptidyl Peptidase-4/CD26 in Bullous Pemphigoid

Gliptin-associated Bullous Pemphigoid and the Expression of Dipeptidyl Peptidase-4/CD26 in Bullous Pemphigoid

Bullous pemphigoid associated with the use of dipeptidil peptidase-4 inhibitors: analysis from studies based on pharmacovigilance databases

Pemphigoid lichen planus consequential to vildagliptin: a rare variant of bullous pemphigoid?

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