Bullous pemphigoid induced by ipilimumab in a patient with metastatic malignant melanoma after unsuccessful treatment with nivolumab

Kuwatsuka, Yutaka; Iwanaga, Akira; Kuwatsuka, Sayaka; Okubo, Yumi; Murayama, Nobuhiro; Ishii, Norito; Hashimoto, Takashi; Utani, Atsushi

doi:10.1111/1346-8138.14043

Cited by 27 publications

(22 citation statements)

References 5 publications

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“…To date, 22 cases of BP associated with PD-1/PD-L1 inhibitors have been reported in the literature [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. In contrast, BP associated with anti-CTLA-4 therapy has only been reported in two cases, suggesting this irAE is more specific to anti-PD-1/ PD-L1 therapy [37,38]. Although the mechanism of PD-1/PD-Panel 1: Rare severe cutaneous toxicities associated with programmed cell death protein-1 inhibitors L1 inhibitor-induced BP is unknown, it is thought to be driven by autoantibody production against hemidesmosomal structural proteins BP180 and BP230 [36,39].…”

Section: Discussionmentioning

confidence: 99%

A Case of Nivolumab-Induced Bullous Pemphigoid: Review of Dermatologic Toxicity Associated with Programmed Cell Death Protein-1/Programmed Death Ligand-1 Inhibitors and Recommendations for Diagnosis and Management

López

Geskin

2018

The Oncologist

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Bullous pemphigoid is an autoimmune subepidermal blistering disease characterized by the development of tense bullae and is most frequently seen in the elderly. PD‐1/PD‐L1‐induced bullous pemphigoid (BP) has emerged as a potentially serious dermatologic toxicity. This article reports a case of a 72‐year‐old woman who developed BP shortly after initiating treatment with the PD‐1 inhibitor nivolumab for metastatic non‐small cell lung cancer.

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Section: Discussionmentioning

confidence: 99%

A Case of Nivolumab-Induced Bullous Pemphigoid: Review of Dermatologic Toxicity Associated with Programmed Cell Death Protein-1/Programmed Death Ligand-1 Inhibitors and Recommendations for Diagnosis and Management

López

Geskin

2018

The Oncologist

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“…Recently, between 2015 and 2018, 18 case reports or small series described 27 patients who developed BP while receiving anti PD-1/PD-L1 therapy, including three with negative DIF ( 35 , 37 ) or without DIF confirmation ( 47 ) but with typical clinical presentations (Tables 1 , 2 ). Fourteen patients received anti PD-1 nivolumab therapy (patients 2, 4, 7, 9, 10, 13, 15, 18, 20, 22, 23, and 25–27) ( 33 , 35 , 38 , 42 , 44 , 46 , 47 , 49 ), 11 received anti PD-1 pembrolizumab therapy (patients 1, 5, 6, 8, 11, 12, 14,16, 19, 21, and 24) ( 32 , 34 – 37 , 39 , 40 , 43 , 45 , 48 ), one received anti-PD-L1 durvalumab therapy (patient 3) ( 33 ), and one received anti-PD-L1 atezolizumab therapy (patient 17) ( 41 ). Six of the 27 patients received ipilimumab therapy before anti PD-1, one received an association of ipilimumab and nivolumab therapy, and one received ipilimumab therapy after treatment with nivolumab.…”

Section: Discussionmentioning

confidence: 99%

Mucous Membrane Pemphigoid, Bullous Pemphigoid, and Anti-programmed Death-1/ Programmed Death-Ligand 1: A Case Report of an Elderly Woman With Mucous Membrane Pemphigoid Developing After Pembrolizumab Therapy for Metastatic Melanoma and Review of the Literature

et al. 2018

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An 83-year-old patient developed erosions and a blister of the gingival mucous membrane, 6 months after discontinuation of the anti-programmed death-1 (anti PD-1) pembrolizumab therapy administered for 10 months for a metastatic melanoma. A diagnosis of mild mucous membrane pemphigoid (MMP) was made. Complete remission of MMP was rapidly obtained with minimal therapy (doxycycline). MMP remained in complete remission after a 3-month follow-up since discontinuation of the doxycycline therapy and no evidence of relapse of the melanoma was observed after a 14-month follow-up since discontinuation of the pembrolizumab therapy. The widespread use of anti PD-1 and anti-programmed death-ligand-1 (PD-L1) in several malignancies reveals new adverse events. MMP describes a group of chronic, inflammatory, mucous membrane-predominant, subepithelial auto-immune blistering diseases. It is clinically distinct from bullous pemphigoid another autoimmune blistering disease but shares some immunological similarities with it. Twenty-nine cases of bullous pemphigoid associated with anti PD-1/PD-L1 have been reported in the literature and one of MMP. Here, we described the case of a MMP developed after pembrolizumab and discussed the accountability of anti PD-1/PD-L1 in our case and the previous reported bullous pemphigoid and MMP cases using the Begaud system scoring.

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“…The ROR of other diabetic drugs, especially metformin, listed as causative drugs for pemphigoid may be greatly affected by concomitant use with DPP4-I. 15,16 Nivolumab and ipilimumab are listed, and safety signals were detected for both drugs. Also, products containing combinations of these agents are available commercially.…”

Section: Discussionmentioning

confidence: 99%

“…These often cause immune-related adverse events, and are also suspected to be associated with BP. 15,16 Nivolumab and ipilimumab are listed, and safety signals were detected for both drugs. Because the use of these drugs is expected to increase, close scrutiny of subsequent reports will be necessary.…”

Section: Discussionmentioning

confidence: 99%

Analysis of patients with drug‐induced pemphigoid using the Japanese Adverse Drug Event Report database

Tanaka

Ishii

2018

The Journal of Dermatology

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To clarify the incidence of drug‐induced pemphigoid in Japan, we conducted a database search and analysis using the Japanese Adverse Drug Event Report database (JADER). Among the cases recorded in JADER between April 2004 and November 2017, we targeted “pemphigoid” and analyzed the patients’ backgrounds, drug involvement, time of pemphigoid onset, outcomes and year reported. For cases where three or more drugs were reportedly involved, the signal index was calculated using the reporting odds ratio (ROR) method. The total number of reported pemphigoid cases was 769. Males accounted for 58% (446 cases) and patients over the age of 60 years accounted for 82% (630 cases). The most frequently reported causative drug was vildagliptin (288 cases), followed in order by sitagliptin phosphate hydrate (102 cases), teneligliptin hydrobromide hydrate (86 cases), linagliptin (64 cases) and furosemide (46 cases). For the 27 causative drugs, the safety signal was detected by the ROR method. The median time to onset tended to be long for these drugs. For vildagliptin with the largest reported number, the value was 508 days (range, 2–1871). Analysis of outcomes demonstrated recovery or improvement in 66.3% of cases. Analysis of the years in which reports had been published revealed that the number of pemphigoid cases has increased rapidly in recent years. Our survey was able to reveal useful data on the incidence of drug‐induced pemphigoid. We expect that these results will aid the early detection and treatment of this condition.

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Bullous pemphigoid induced by ipilimumab in a patient with metastatic malignant melanoma after unsuccessful treatment with nivolumab

Cited by 27 publications

References 5 publications

A Case of Nivolumab-Induced Bullous Pemphigoid: Review of Dermatologic Toxicity Associated with Programmed Cell Death Protein-1/Programmed Death Ligand-1 Inhibitors and Recommendations for Diagnosis and Management

A Case of Nivolumab-Induced Bullous Pemphigoid: Review of Dermatologic Toxicity Associated with Programmed Cell Death Protein-1/Programmed Death Ligand-1 Inhibitors and Recommendations for Diagnosis and Management

Mucous Membrane Pemphigoid, Bullous Pemphigoid, and Anti-programmed Death-1/ Programmed Death-Ligand 1: A Case Report of an Elderly Woman With Mucous Membrane Pemphigoid Developing After Pembrolizumab Therapy for Metastatic Melanoma and Review of the Literature

Analysis of patients with drug‐induced pemphigoid using the Japanese Adverse Drug Event Report database

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