Histopathological aspects of cutaneous erythematous‐papular eruptions induced by immune checkpoint inhibitors for the treatment of metastatic melanoma

Perret, Raul; Josselin, N.; Knol, Anne-Chantal; Khammari, Amir; Cassecuel, Julie; Peuvrel, L.; Dréno, Brigitte

doi:10.1111/ijd.13540

Cited by 34 publications

(20 citation statements)

References 18 publications

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“…Dysregulation of immune tolerance due to ICIs results in unbridled T-cell infiltration leading to keratinocyte injury [20]. A varying degree of infiltration by eosinophils [21] and peripheral eosinophilia [22,23] has also been previously described.…”

Section: Histopathologymentioning

confidence: 90%

Cases from the irAE Tumor Board: A Multidisciplinary Approach to a Patient Treated with Immune Checkpoint Blockade Who Presented with a New Rash

et al. 2018

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Immune checkpoint inhibitors (ICIs) have revolutionized the treatment paradigms for a broad spectrum of malignancies. Because immune checkpoint inhibitors rely on immune reactivation to eliminate cancer cells, they can also lead to the loss of immune tolerance and result in a wide range of phenomena called immune‐related adverse events (irAEs). At our institution, the management of irAEs is based on multidisciplinary input obtained at an irAE tumor board that facilitates expedited opinions from various specialties and allows for a more uniform approach to these patients. In this article, we describe a case of a patient with metastatic urothelial carcinoma who developed a maculopapular rash while being treated with a programmed death‐ligand 1 inhibitor. We then describe the approach to management of dermatologic toxicities with ICIs based on the discussion at our irAE Tumor Board. Key Points Innocuous symptoms such as pruritis or a maculopapular rash may herald potentially fatal severe cutaneous adverse reactions (SCARs); therefore, close attention must be paid to the symptoms, history, and physical examination of all patients. Consultation with dermatology should be sought for patients with grade 3 or 4 toxicity or SCARs and prior to resumption of immune checkpoint inhibitors for patients with grade 3 or higher toxicity. A multidisciplinary immune‐related adverse events (irAE) tumor board can facilitate timely input and expertise from various specialties, thereby ensuring a streamlined approach to management of irAEs.

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Section: Histopathologymentioning

confidence: 90%

Cases from the irAE Tumor Board: A Multidisciplinary Approach to a Patient Treated with Immune Checkpoint Blockade Who Presented with a New Rash

et al. 2018

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“…A summary of the suprabasal acantholytic dermatologic toxicities associated CPIs reported in the literature (including the two patients in this report) is presented in Table . Overall, 13 patients (including the two in this report) with a median age of 64 years (range: 51‐75 years) developed suprabasal acantholytic dermatologic toxicities (Grover‐like, n = 8; “lichenoid dermatitis with suprabasal acantholysis/intraepithelial vesicle”, n = 4; PNP‐like, n = 1) associated with CPIs (ipilimumab = 4; nivolumab = 2; pembrolizumab = 2; combined CPIs = 5).…”

Section: Discussionmentioning

confidence: 92%

Suprabasal acantholytic dermatologic toxicities associated checkpoint inhibitor therapy: A spectrum of immune reactions from paraneoplastic pemphigus‐like to Grover‐like lesions

et al. 2018

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Checkpoint inhibitors (CPIs) restore the function of effector immunocytes to target and destroy cancer cells. Immune-related adverse events (irAEs) are a consequence of immune reactivation, with unpredictable inflammatory response, loss of self-tolerance, and development of autoimmunity. Adverse events from CPIs that present as dermatologic toxicities have diverse clinical and histopathologic features. CPI-associated dermatologic toxicities may exhibit histopathologic features of lichenoid dermatitis, bullous pemphigoid, and granulomatous/sarcoid-like reactions. Suprabasal acantholytic dermatologic toxicities associated with CPIs are particularly rare but represent an emerging histopathologic pattern and include lichenoid dermatitis with suprabasal acantholysis/vesicle formation to Grover disease (transient acantholytic dermatosis). Here, we report two patients who developed suprabasal acantholytic dermatologic toxicities during CPI therapy. One patient exhibited a CPI-associated autoimmune blistering disease with paraneoplastic pemphigus (PNP)-like features restricted to histopathology and immunofluorescence, while the other patient had Grover-like lesions. A review of the literature revealed a spectrum of suprabasal acantholytic dermatologic toxicities associated CPIs that may present as lichenoid dermatitis with acantholysis/vesicle formation, Grover-like eruptions, and lesions with PNP-like features restricted to histopathology and immunofluorescence. It is important for clinicians and pathologists to recognize the types of dermatologic toxicities associated with CPIs to direct appropriate therapeutic strategies.

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“…A systematic review of extensive GD found recent transplant in 20% of cases, and individual reports have found cases following bone marrow, renal, liver, and heart transplants . Reports of eruptions following initiation of drugs are numerous and include, but are not limited to, sulfadoxine‐pyrimethamine, recombinant IL‐4, BRAF inhibitors, ipilimumab, and other immune checkpoint inhibitors …”

Section: Review Of Etiopathogenesis Of Grover Diseasementioning

confidence: 99%

“…Although several drugs have been associated with the onset of GD, the benefit of these medications often outweighs the risks of discontinuing them. Therefore, in these cases, the inciting drug is usually continued and combined with symptomatic treatment of GD …”

Section: Preventionmentioning

confidence: 99%

Grover disease: review of subtypes with a focus on management options

Aldana

Khachemoune

2019

Int J Dermatology

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Grover disease (GD) is a benign eruption that causes a papulovesicular rash on the trunk and proximal extremities. It often resolves spontaneously but can follow a more chronic and fluctuating course that may last several years. Although the etiology remains unknown, several associated triggers have been identified including heat and sweating, cool and dry air, renal failure, malignancy, and the initiation of several drugs. Since the disease tends to resolve on its own, management is aimed at disease prevention and symptomatic relief. First-line therapy includes topical steroids and vitamin D analogues with adjuvant antihistamines. In more severe cases that are refractory to less aggressive therapy, systemic corticosteroids, retinoids, and phototherapy may lead to successful resolution. Novel therapies are few and have little evidence but involve innovative use of light therapy and immune modulators. Herein, we review the literature and new trends of GD with a focus on established and novel treatments. Historical evolution of our understanding of Grover disease Grover disease was first described in 1970 as a self-limited eruption of pruritic, discrete, and edematous papules and vesicles which appeared on the trunk and extremities following nonspecific irritation. These lesions occurred in six patients without family history of skin disease and had a duration of a few weeks up to several months. Cytology of the lesions revealed focal acantholysis within the epidermis and varying levels of dyskeratosis that resembled changes seen in Darier and Hailey-Hailey ª

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Histopathological aspects of cutaneous erythematous‐papular eruptions induced by immune checkpoint inhibitors for the treatment of metastatic melanoma

Cited by 34 publications

References 18 publications

Cases from the irAE Tumor Board: A Multidisciplinary Approach to a Patient Treated with Immune Checkpoint Blockade Who Presented with a New Rash

Cases from the irAE Tumor Board: A Multidisciplinary Approach to a Patient Treated with Immune Checkpoint Blockade Who Presented with a New Rash

Suprabasal acantholytic dermatologic toxicities associated checkpoint inhibitor therapy: A spectrum of immune reactions from paraneoplastic pemphigus‐like to Grover‐like lesions

Grover disease: review of subtypes with a focus on management options

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