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, Ana M.; Geskin, Larisa J.

doi:10.1634/theoncologist.2018-0128

Cited by 78 publications

(62 citation statements)

References 87 publications

(129 reference statements)

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“…Overall, our data (a) confirmed the variegate pattern of cutaneous toxicity , including nonspecific manifestations such as rash maculopapular and pruritus, as well as serious irAEs and SCARs, thus making a timely consultation with dermatologist pivotal to minimize unnecessary drug interruption ; (b) found a differential reporting between anti‐PD1/PDL1 drugs (psoriasis, dermatitis psoriasiform, pemphigoid, and cutaneous sarcoidosis) and anti‐CTLA4 medications (acute febrile neutrophilic dermatosis and erythema nodosum) ; and (c) recorded a high proportion of death in young adults with SCARs, especially TEN (83% in adults aged 40–49), with a delayed latency as compared with recently published data on anticancer drugs (mean 46 vs. 18 days ), in keeping with immune‐related basis. This conflicts with the algorithm of drug causality for epidermal necrolysis (ALDEN), which was validated on heterogeneous drugs and suggested that late events are unlikely to be drug related ): we invite clinicians to submit complete high‐quality reports, as recommended by the Side Effect Reporting in Immuno‐Oncology (SERIO) working group .…”

Section: Resultssupporting

confidence: 75%

Serious Cutaneous Toxicities with Immune Checkpoint Inhibitors in the U.S. Food and Drug Administration Adverse Event Reporting System

et al. 2019

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Cutaneous toxicities frequently occurred with immune checkpoint inhibitors (ICIs), although clinical and pharmacological features are incompletely characterized. The U.S. Food and Drug Administration Adverse Event Reporting System was queried to describe ICI‐related cutaneous toxicities, focusing on severe cutaneous adverse reactions (SCARs): Stevens‐Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. As compared with other anticancer drugs, a higher proportion of death (11.3% vs. 8.7%) and serious reports (42.7% vs. 34.6%) emerged for ICIs (p < .05). A higher frequency of coreported allopurinol and antiepileptics was recorded among 2,525 total SCARs (17% vs. 10%, ICIs and anticancer agents, respectively; p < .05). Mean times to onset were 47, 48, and 40 days (SJS, TEN, and DRESS, respectively), with comparable mean latency between monotherapy and combination regimens (41 days). This immune‐related pattern advocates for long‐lasting monitoring by oncologists and dermatologists.

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Section: Resultssupporting

confidence: 75%

Serious Cutaneous Toxicities with Immune Checkpoint Inhibitors in the U.S. Food and Drug Administration Adverse Event Reporting System

et al. 2019

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“…Besides melanoma, one case of lichen planus pemphigoides [140] and one of bullous pemphigoid [141] have been reported for patients treated with check-point inhibitor immunotherapy for NSCLC. Besides melanoma, one case of lichen planus pemphigoides [140] and one of bullous pemphigoid [141] have been reported for patients treated with check-point inhibitor immunotherapy for NSCLC.…”

Section: Additional Autoimmune Skin Diseases In Melanoma Patients Trementioning

confidence: 99%

Melanoma and Vitiligo: In Good Company

Failla

Carbone

Fortes

et al. 2019

IJMS

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Cutaneous melanoma represents the most aggressive form of skin cancer, whereas vitiligo is an autoimmune disorder that leads to progressive destruction of skin melanocytes. However, vitiligo has been associated with cutaneous melanoma since the 1970s. Most of the antigens recognized by the immune system are expressed by both melanoma cells and normal melanocytes, explaining why the autoimmune response against melanocytes that led to vitiligo could be also present in melanoma patients. Leukoderma has been also observed as a side effect of melanoma immunotherapy and has always been associated with a favorable prognosis. In this review, we discuss several characteristics of the immune system responses shared by melanoma and vitiligo patients, as well as the significance of occurrence of leukoderma during immunotherapy, with special attention to check-point inhibitors.

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“…The reader should bear in mind that expert opinion is the sole evidence for these agents in immunotherapy‐related cases and not currently included in any guidelines. A recent case also demonstrated the effective use of oral minocycline and oral niacinamide as adjunctive therapies in a case of bullous dermatitis …”

Section: Discussionmentioning

confidence: 99%

Combined immune therapy grade IV dermatitis in metastatic melanoma

Randhawa

Archer

Gaughran

et al. 2019

Asia-Pac J Clncl Oncology

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Précis: There are published cases of use of cyclosporine in dermatological toxicity with monotherapy but not with combination ipilimumab/nivolumab. AbstractCheckpoint inhibition is the mainstay of treatment in metastatic melanoma. More recently combined cytotoxic T-lymphocyte antigen-4 and programmed-death-1 blockade has resulted in improved response rates and overall survival in treatment naïve patients compared to monotherapy albeit with increased rates of adverse events. Dermatologic toxicities are an emerging consequence of the use of checkpoint inhibitors and have reportedly been more prevalent with the use of combined therapy. However, grade 3 and 4 adverse event rates are still less than 5%. Here, we report a case of a 63-year-old Caucasian male with metastatic melanoma treated with first line combined ipilimumab and nivolumab who then developed a steroid refractory, biopsy confirmed pityriasis lichenoides-like, drug related rash that resolved with cyclosporine. Time of onset was 24 days and presenting symptoms demonstrated a maculopapular rash presenting over the back and chest with pruritus. Unfortunately, the patient subsequently had multi-organ failure with acute kidney injury requiring dialysis, hypotension requiring vasopressor support, hepatic dysfunction, and bilateral lung infiltrates resulting in a fatal outcome. This case report highlights the effective use of cyclosporine as an immunomodulatory agent in the management of severe dermatological toxicity due to combination immunotherapy. K E Y W O R D Scutaneous toxicity, cyclosporine, immune therapy, ipilimumab, metastatic melanoma, nivolumab, steroid-refractory rash

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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

Cited by 78 publications

References 87 publications

Serious Cutaneous Toxicities with Immune Checkpoint Inhibitors in the U.S. Food and Drug Administration Adverse Event Reporting System

Serious Cutaneous Toxicities with Immune Checkpoint Inhibitors in the U.S. Food and Drug Administration Adverse Event Reporting System

Melanoma and Vitiligo: In Good Company

Combined immune therapy grade IV dermatitis in metastatic melanoma

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