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Pach JJ, Mbonu N, Bhullar S, Cohen JM, Leventhal JS. Immune Checkpoint Inhibitor-Induced Psoriasis: Diagnosis, Management, and a Review of Cases. Dermatol Clin 2024; 42:481-493. [PMID: 38796277 DOI: 10.1016/j.det.2024.02.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/28/2024]
Abstract
Immune checkpoint inhibitors (ICIs) are effective antitumor agents but are associated with immune-related adverse events. ICI-induced psoriasis commonly presents in patients with a history of psoriasis but may occur de novo, and it has a significant physical and psychosocial impact. ICI-induced and non-ICI-induced psoriasis are likely mediated by similar cytokines, and similar treatments are employed. Topical treatment often suffices, and when needed, several systemic treatments appear to be effective without impacting antitumor response. Development of psoriasis may indicate a superior response to ICIs. Thus, recognition and management of ICI-induced psoriasis is essential to avoid ICI interruption and maximize therapeutic potential.
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Affiliation(s)
- Jolanta J Pach
- Department of Dermatology Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
| | - Nina Mbonu
- Meharry Medical College, 1005 Drive Db Todd Jr Boulevard, Nashville, TN 37208, USA
| | - Shaman Bhullar
- Department of Dermatology Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
| | - Jeffrey M Cohen
- Department of Dermatology Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA
| | - Jonathan S Leventhal
- Department of Dermatology Yale School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.
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Zhou MH, Ye MF, Zhang ZX, Tao F, Zhang Y. Cytokine release syndrome triggered by programmed death 1 blockade (sintilimab) therapy in a psoriasis patient: A case report. World J Clin Cases 2024; 12:3555-3560. [PMID: 38983424 PMCID: PMC11229916 DOI: 10.12998/wjcc.v12.i18.3555] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2024] [Revised: 04/10/2024] [Accepted: 05/08/2024] [Indexed: 06/13/2024] Open
Abstract
BACKGROUND In recent years, immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy across diverse malignancies. Notably, in patients with advanced gastric cancer, the use of programmed death 1 (PD-1) blockade has significantly prolonged overall survival, marking a pivotal advancement comparable to the impact of Herceptin over the past two decades. While the therapeutic benefits of ICIs are evident, the increasing use of immunotherapy has led to an increase in immune-related adverse events. CASE SUMMARY This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis. Following sintilimab therapy, the patient developed severe rashes accompanied by cytokine release syndrome (CRS). Fortunately, effective management was achieved through the administration of glucocorticoid, tocilizumab, and acitretin, which resulted in favorable outcomes. CONCLUSION Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.
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Affiliation(s)
- Ming-Hui Zhou
- Department of Gastrointestinal Surgery, Shaoxing People’s Hospital, Shaoxing 312000, Zhejiang Province, China
- School of Medicine, Shaoxing University, Shaoxing 312000, Zhejiang Province, China
| | - Min-Feng Ye
- Department of Gastrointestinal Surgery, Shaoxing People’s Hospital, Shaoxing 312000, Zhejiang Province, China
| | - Zhen-Xing Zhang
- Department of Gastrointestinal Surgery, Shaoxing People’s Hospital, Shaoxing 312000, Zhejiang Province, China
| | - Feng Tao
- Department of Gastrointestinal Surgery, Shaoxing People’s Hospital, Shaoxing 312000, Zhejiang Province, China
| | - Yu Zhang
- Department of Gastrointestinal Surgery, Shaoxing People’s Hospital, Shaoxing 312000, Zhejiang Province, China
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Wan Z, Huang J, Ou X, Lou S, Wan J, Shen Z. Psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. An Bras Dermatol 2024; 99:425-432. [PMID: 38388337 PMCID: PMC11074622 DOI: 10.1016/j.abd.2023.09.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 09/13/2023] [Accepted: 09/19/2023] [Indexed: 02/24/2024] Open
Abstract
PD-1 (programmed Death-1) immune checkpoint inhibitors have provided significant benefits to tumor patients. However, a considerable proportion of the patients develop immune-related adverse events (irAEs), of which cutaneous irAEs (cirAEs, e.g., psoriasis) occur relatively early. This review provides an overview of the current progress in psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. It not only describes the relevant influencing factors but also theoretically analyzes the immunological mechanisms that lead to the onset or exacerbation of psoriasis. Finally, the authors present guidelines for the treatment of psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. The review is intended to assist dermatologists in the early recognition and effective individualized management of such cirAE, which is helpful to continue or adjust the tumor-targeted immunotherapy on the basis of ensuring the quality of life of tumor patients.
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Affiliation(s)
- Zi Wan
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Jiangyuan Huang
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Xiaojie Ou
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Shuang Lou
- Department of Dermatology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Jianji Wan
- Department of Dermatology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Zhu Shen
- Department of Dermatology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
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Popa LG, Giurcaneanu C, Portelli MG, Mihai MM, Beiu C, Orzan OA, Ion A, Anghel TH. Perspectives on Psoriasiform Adverse Events from Immune Checkpoint Inhibitors: Lessons Learned from Our Practice. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:373. [PMID: 38541099 PMCID: PMC10972058 DOI: 10.3390/medicina60030373] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Revised: 02/16/2024] [Accepted: 02/20/2024] [Indexed: 10/24/2024]
Abstract
Background: New oncologic therapies, including immune checkpoint inhibitors (ICIs), have revolutionized the survival and prognosis of cancer patients. However, these therapies are often complicated by immune-related adverse effects (irAEs) that may impact quality of life and potentially limit their use. Among these adverse events are psoriasis and psoriatic arthritis that may develop de novo or flare under treatment with ICIs. Given the exceptional immune status of patients receiving ICIs, managing these conditions without interfering with the effect of the oncologic treatment may prove very challenging. Aim: To review the literature data on ICI-induced psoriasis exacerbation or development, to present our own experience, and to discuss the pathogenic mechanisms underlying this association and the optimal therapeutic approach for these patients. Case Reports: We report three cases of ICI-induced de novo psoriasis and two cases of ICI-induced psoriasis exacerbation that required systemic treatment. Oral acitretin treatment successfully controlled psoriasis lesions in three cases and allowed for the continuation of immunotherapy. Literature Review: We performed a medical literature search across several databases (PubMed, Medline, Google Scholar) using the search terms "immune checkpoint inhibitor-induced psoriasis/psoriasiform dermatitis/psoriasis arthritis". We identified and revised 80 relevant publications that reported 1102 patients with psoriasis and/or psoriasis arthritis induced or exacerbated by ICIs. We assessed the type of cancer, the therapeutic agent involved, the clinical form of psoriasis, the presence or absence of psoriatic arthritis, the personal and family history of psoriasis, the age, the gender, the time until onset or exacerbation of skin lesions, the specific treatment recommended, the need for ICI discontinuation, and the patient's outcome. Conclusions: As ICIs represent a fairly novel therapy, the association with several adverse effects is only now unraveling. Psoriasis exacerbation or onset following the initiation of immunotherapy is one such example, as more and more reports and case series are being published. Awareness of the relationship between psoriasis and treatment with ICIs, prompt recognition, and initiation of adequate skin-directed therapies are essential for the avoidance of skin lesions worsening, the need for systemic treatments that may interfere with ICIs' effects, or the discontinuation of the latter. In the absence of generally accepted guidelines, it is advisable to treat patients with severe, widespread psoriasis with drugs that do not impair the effects of immunotherapy and thus do not alter the patient's prognosis.
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Affiliation(s)
- Liliana Gabriela Popa
- Faculty of Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania; (L.G.P.); (C.G.); (M.G.P.); (M.M.M.); (C.B.); (A.I.); (T.H.A.)
- Department of Dermatology, ‘Elias’ University Emergency Hospital, 011461 Bucharest, Romania
| | - Calin Giurcaneanu
- Faculty of Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania; (L.G.P.); (C.G.); (M.G.P.); (M.M.M.); (C.B.); (A.I.); (T.H.A.)
- Department of Dermatology, ‘Elias’ University Emergency Hospital, 011461 Bucharest, Romania
| | - Mariana Georgiana Portelli
- Faculty of Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania; (L.G.P.); (C.G.); (M.G.P.); (M.M.M.); (C.B.); (A.I.); (T.H.A.)
- Department of Dermatology, ‘Elias’ University Emergency Hospital, 011461 Bucharest, Romania
| | - Mara Mădălina Mihai
- Faculty of Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania; (L.G.P.); (C.G.); (M.G.P.); (M.M.M.); (C.B.); (A.I.); (T.H.A.)
- Department of Dermatology, ‘Elias’ University Emergency Hospital, 011461 Bucharest, Romania
| | - Cristina Beiu
- Faculty of Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania; (L.G.P.); (C.G.); (M.G.P.); (M.M.M.); (C.B.); (A.I.); (T.H.A.)
- Department of Dermatology, ‘Elias’ University Emergency Hospital, 011461 Bucharest, Romania
| | - Olguța Anca Orzan
- Faculty of Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania; (L.G.P.); (C.G.); (M.G.P.); (M.M.M.); (C.B.); (A.I.); (T.H.A.)
- Department of Dermatology, ‘Elias’ University Emergency Hospital, 011461 Bucharest, Romania
| | - Ana Ion
- Faculty of Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania; (L.G.P.); (C.G.); (M.G.P.); (M.M.M.); (C.B.); (A.I.); (T.H.A.)
- Department of Dermatology, ‘Elias’ University Emergency Hospital, 011461 Bucharest, Romania
| | - Teodora Hrista Anghel
- Faculty of Medicine, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania; (L.G.P.); (C.G.); (M.G.P.); (M.M.M.); (C.B.); (A.I.); (T.H.A.)
- Department of Dermatology, ‘Elias’ University Emergency Hospital, 011461 Bucharest, Romania
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Jo W, Won T, Daoud A, Čiháková D. Immune checkpoint inhibitors associated cardiovascular immune-related adverse events. Front Immunol 2024; 15:1340373. [PMID: 38375475 PMCID: PMC10875074 DOI: 10.3389/fimmu.2024.1340373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Accepted: 01/19/2024] [Indexed: 02/21/2024] Open
Abstract
Immune checkpoint inhibitors (ICIs) are specialized monoclonal antibodies (mAbs) that target immune checkpoints and their ligands, counteracting cancer cell-induced T-cell suppression. Approved ICIs like cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), its ligand PD-L1, and lymphocyte activation gene-3 (LAG-3) have improved cancer patient outcomes by enhancing anti-tumor responses. However, some patients are unresponsive, and others experience immune-related adverse events (irAEs), affecting organs like the lung, liver, intestine, skin and now the cardiovascular system. These cardiac irAEs include conditions like myocarditis, atherosclerosis, pericarditis, arrhythmias, and cardiomyopathy. Ongoing clinical trials investigate promising alternative co-inhibitory receptor targets, including T cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT). This review delves into the mechanisms of approved ICIs (CTLA-4, PD-1, PD-L1, and LAG-3) and upcoming options like Tim-3 and TIGIT. It explores the use of ICIs in cancer treatment, supported by both preclinical and clinical data. Additionally, it examines the mechanisms behind cardiac toxic irAEs, focusing on ICI-associated myocarditis and atherosclerosis. These insights are vital as ICIs continue to revolutionize cancer therapy, offering hope to patients, while also necessitating careful monitoring and management of potential side effects, including emerging cardiac complications.
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Affiliation(s)
- Wonyoung Jo
- Department of Biomedical Engineering, Johns Hopkins University, Whiting School of Engineering, Baltimore, MD, United States
| | - Taejoon Won
- Department of Pathobiology, University of Illinois Urbana-Champaign, College of Veterinary Medicine, Urbana, IL, United States
| | - Abdel Daoud
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, United States
| | - Daniela Čiháková
- W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, United States
- Department of Pathology, Johns Hopkins University, School of Medicine, Baltimore, MD, United States
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Sun X, Mei X, Liu Y. Exacerbation of psoriasis induced by Nivolumab in a patient with stage IIIc gastric adenocarcinoma: A case report and literature review. J Transl Autoimmun 2023; 6:100193. [PMID: 36852017 PMCID: PMC9958049 DOI: 10.1016/j.jtauto.2023.100193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 08/19/2022] [Indexed: 02/17/2023] Open
Abstract
Nivolumab, the programmed cell death 1 inhibitor, is a kind of immune checkpoint inhibitor commonly used to treat advanced cancers. Unfortunately, such drugs often induce various immune-related adverse events involving different body systems, with psoriasis being one of the skin toxicities. We report the clinical features of an exacerbated psoriasis induced by using nivolumab after three days in a patient with stage IIIc gastric adenocarcinoma. At the same time, we searched 27 case reports published from 2015 to 2021 over the world and systematically summarized the clinical manifestation of a total of 44 cases with psoriasis caused or exacerbated by Nivolumab. Commonly traditional treatment could be useful, and small molecule drugs such as apremilast are effective among some patients. However, more studies are needed to evaluate the efficacy and safety of biologics or small molecule drugs in treating psoriasis induced by nivolumab.
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Affiliation(s)
- Xiaojie Sun
- Clinical Trial and Cosmetics Testing Center, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, 210042, China
| | - Xiaole Mei
- Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, China.,Key Laboratory of Basic and Translational Research on Immunological Dermatology, Chinese Academy of Medical Sciences, Nanjing, Jiangsu, 210042, China
| | - Yi Liu
- Clinical Trial and Cosmetics Testing Center, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, Jiangsu, 210042, China
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7
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Jfri A, Leung B, Said JT, Semenov Y, LeBoeuf NR. Prevalence of inverse psoriasis subtype with immune checkpoint inhibitors. IMMUNOTHERAPY ADVANCES 2022; 2:ltac016. [PMID: 36196370 PMCID: PMC9525015 DOI: 10.1093/immadv/ltac016] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 05/16/2022] [Accepted: 09/20/2022] [Indexed: 11/14/2022] Open
Abstract
Background Cutaneous immune-related adverse events (irAEs) are the most common irAEs caused by immune-checkpoint inhibitors (ICI). Psoriasiform eruptions, both de novo and flares, may occur. Evidence is lacking on inverse psoriasis subtype. Methods A retrospective study was conducted at Dana-Farber Cancer Institute/Mass General Brigham through February 2020 using databases. Confirmed inverse psoriasis cases pre-/post-ICI initiation either independently or in conjunction with other psoriasis subtypes were included. Known psoriasis cases without flare post-ICI were excluded. Results A total of 262 (3%) individuals with any ICI-mediated psoriasiform cutaneous irAE were identified out of the 8683 DFCI ICI-treated patients. Of these, 13 (5% of psoriasis patients) had inverse psoriasis (mean age 68.7 years; 7/13 male sex). Median (range) time from ICI initiation to inverse psoriasis development or flare was 7 (4-12) and 3.5 (2-6) weeks, respectively. Pruritus occurred in 12/13 (92.30%) cases. 11 (85%) had inguinal involvement; other sites included gluteal cleft (6; 46%), inframammary (3; 23%), perianal (2; 15%), axilla (2; 15%), umbilicus (2; 15%), and infra-abdominal folds (1; 8%). Most (9/13) individuals had more than one site involved. The Common Terminology Criteria for Adverse Events severity was 1 in 10 (76.92%) individuals and 2 in 3 (15.38%) individuals. Six (46.15%) patients were treated initially by oncology with topical (nystatin, econazole, or clotrimazole) or systemic antifungals (fluconazole) for median (range) of 3.5 (1-7) months without improvement, for presumed candida intertrigo. Conclusion Patients on ICI may develop inverse psoriasis, which may be initially confused for fungal intertrigo. Delayed diagnosis can prolong symptoms, while patients are treated ineffectively with topical/systemic antifungals for presumed candida infection. Oncologist and dermatologist awareness is important to improve diagnosis of ICI-mediated inverse psoriasis, its management and affected patients' quality of life.
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Affiliation(s)
- Abdulhadi Jfri
- Dermatology Department, Harvard Medical School, Boston, MA, USA
- Department of Dermatology, Brigham and Women’s Hospital, Boston, MA, USA
- Center for Cutaneous Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
- Division of Dermatology, King Abdulaziz Medical City, Jeddah, Saudi Arabia
- College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
- King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
- Division of Dermatology, Department of Medicine, Ministry of the National Guard-Health Affairs, Jeddah, Saudi Arabia
| | - Bonnie Leung
- Center for Cutaneous Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
- Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA
| | - Jordan T Said
- Dermatology Department, Harvard Medical School, Boston, MA, USA
- Department of Dermatology, Brigham and Women’s Hospital, Boston, MA, USA
- Center for Cutaneous Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Yevgeniy Semenov
- Dermatology Department, Harvard Medical School, Boston, MA, USA
- Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA
| | - Nicole R LeBoeuf
- Dermatology Department, Harvard Medical School, Boston, MA, USA
- Department of Dermatology, Brigham and Women’s Hospital, Boston, MA, USA
- Center for Cutaneous Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
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8
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Minokawa Y, Sawada Y. Exacerbation of pre‐existence psoriasis following immune checkpoint inhibitor treatment. JOURNAL OF CUTANEOUS IMMUNOLOGY AND ALLERGY 2022. [DOI: 10.1002/cia2.12244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Affiliation(s)
- Yoko Minokawa
- Department of Dermatology University of Occupational and Environmental Health Fukuoka Japan
| | - Yu Sawada
- Department of Dermatology University of Occupational and Environmental Health Fukuoka Japan
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New Insights into the Role of PD-1 and Its Ligands in Allergic Disease. Int J Mol Sci 2021; 22:ijms222111898. [PMID: 34769327 PMCID: PMC8584538 DOI: 10.3390/ijms222111898] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 10/26/2021] [Accepted: 10/26/2021] [Indexed: 12/15/2022] Open
Abstract
Programmed cell death 1 (PD-1) and its ligands PD-L1 and PD-L2 are receptors that act in co-stimulatory and coinhibitory immune responses. Signaling the PD-1/PD-L1 or PD-L2 pathway is essential to regulate the inflammatory responses to infections, autoimmunity, and allergies, and it has been extensively studied in cancer. Allergic diseases include asthma, rhinoconjunctivitis, atopic dermatitis, drug allergy, and anaphylaxis. These overactive immune responses involve IgE-dependent activation and increased CD4+ T helper type 2 (Th2) lymphocytes. Recent studies have shown that PD-L1 and PD-L2 act to regulate T-cell activation and function. However, the main role of PD-1 and its ligands is to balance the immune response; however, the inflammatory process of allergic diseases is poorly understood. These immune checkpoint molecules can function as a brake or a kick-start to regulate the adaptive immune response. These findings suggest that PD-1 and its ligands may be a key factor in studying the exaggerated response in hypersensitivity reactions in allergies. This review summarizes the current understanding of the role of PD-1 and PD-L1 and PD-L2 pathway regulation in allergic diseases and how this immunomodulatory pathway is currently being targeted to develop novel therapeutic immunotherapy.
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Nadelmann ER, Yeh JE, Chen ST. Management of Cutaneous Immune-Related Adverse Events in Patients With Cancer Treated With Immune Checkpoint Inhibitors: A Systematic Review. JAMA Oncol 2021; 8:130-138. [PMID: 34709352 DOI: 10.1001/jamaoncol.2021.4318] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Importance There exists a paucity of literature that summarizes the effective management of cutaneous immune-related adverse events (cirAEs) in patients with cancer who are receiving immune checkpoint inhibitors (ICIs). Most published articles are small case series from a single institution. To our knowledge, the spectrum of possible treatments has not been systematically reviewed to highlight the breadth of options when caring for patients with cirAEs. Objective To further characterize the development of subtypes of cirAEs in patients with cancer treated with ICIs and provide recommendations on optimal treatment regimens based on the current literature. Evidence Review A search was performed in PubMed, Embase European, Web of Science, and Google Scholar on June 26, 2020, according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, limited to the years 2010 to 2020. Articles that met predetermined inclusion criteria (published between January 1, 2010, and June 1, 2020; written in the English language; and original articles, brief reports, case reports, and research letters that reported primarily on cirAE management) were selected, and data were abstracted. Articles that met the scope of the review were also added from reference lists. When possible, the results of studies that addressed a similar question were combined quantitatively. Findings In total, 138 studies (87 from the aforementioned literature search and 51 additional studies pulled from the reference lists of included articles) were included that reported on 879 cirAEs. The subtypes of cirAEs included maculopapular, pruritus, lichenoid, immunobullous, psoriasiform, granulomatous, erythema multiforme or Stevens Johnson Syndrome, drug rash with eosinophilia and systemic symptoms, connective tissue disease, hair, oral, and miscellaneous. Treatments for cirAEs included a combination of topical corticosteroids, systemic corticosteroids, steroid-sparing agents, and discontinuation or cessation of immunotherapy. Conclusions and Relevance This systematic review found that treatment with ICIs was associated with many types of skin toxic effects, each with unique treatment options beyond current published guidelines. Further research into key differences between subtypes is critical to improve the care provided to patients with cancer.
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Affiliation(s)
- Emily R Nadelmann
- Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston
| | - Jennifer E Yeh
- Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston
| | - Steven T Chen
- Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston
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11
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Mullangi S, Ponnam S, Lekkala MR, Koya S. A Case of De Novo Psoriasis Secondary to Nivolumab in a Patient With Metastatic Renal Cell Carcinoma. Cureus 2021; 13:e15703. [PMID: 34290912 PMCID: PMC8288591 DOI: 10.7759/cureus.15703] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/20/2021] [Indexed: 01/05/2023] Open
Abstract
Immune-mediated adverse events are commonly seen with immune checkpoint inhibitors like nivolumab. Oncology specialists usually have to screen patients for risk factors for autoimmune diseases, since immune checkpoint inhibitors can potentially exacerbate these events. Some of the immune-mediated side effects include polyneuropathies, colitis, and cutaneous adverse effects. Non-specific maculopapular rash, pruritus, lichenoid reactions, eczema, and vitiligo are the most common dermatologic side effects. It is thought that these adverse events are due to the blocking of the programmed cell death protein-1 (PD-1) pathway and are mediated by the cytotoxic T cells. Psoriasis has been previously reported as a side effect in a few case reports and most commonly presented as an exacerbation of preexisting psoriasis. However, de novo psoriasis occurrence as a result of nivolumab is a rare entity, especially in a non-melanoma patient. Here, we present a case of renal cell carcinoma treated with immunotherapy with nivolumab, who developed de novo psoriasis with palmoplantar involvement.
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Affiliation(s)
| | - Sreeja Ponnam
- Neurosurgery, Oklahoma Surgical Hospital, Tulsa, USA
| | | | - Supriya Koya
- Hematology and Oncology, Hillcrest Medical Center, Tulsa, USA
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12
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Park JH, Yoon D, Lee J, Oh SJ, Kim HJ, Lee JH, Lee DY. Clinical profile of cutaneous adverse events of immune checkpoint inhibitors in a single tertiary center. J Dermatol 2021; 48:979-988. [PMID: 33878219 DOI: 10.1111/1346-8138.15824] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 01/16/2021] [Accepted: 02/06/2021] [Indexed: 01/23/2023]
Abstract
Programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have demonstrated their efficacy in the treatment of various malignancies. Despite their benefits, their immunomodulatory activities can cause unpredictable cutaneous adverse events (CAE). This study aimed to identify characteristics of CAE in patients treated with PD-1/PD-L1 inhibitors through the medical records, photographs, and pathology reports. Fifty CAE occurred in 47 (2.75%) of 1711 patients treated with PD-1/PD-L1 inhibitors. Pruritic, psoriasiform, urticarial, and acneiform eruptions were the four most common types. Melanoma patients showed CAE more frequently than other malignancies. Acneiform eruption occurred more often at ages under 60 years. Urticarial eruption appeared earlier, while keratoacanthoma appeared later after immunotherapy. The overall survival times were not significantly different between the two groups with and without CAE by Kaplan-Meier analysis (p = 0.055). Studies on CAE may provide more information to understand these drugs and to help manage the patients.
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Affiliation(s)
- Ji-Hye Park
- Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dokyoung Yoon
- Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jeeyun Lee
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Se Jin Oh
- Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyun Je Kim
- Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Hee Lee
- Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong-Youn Lee
- Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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13
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Wu C, Zhong L, Wu Q, Lin S, Xie X. The safety and efficacy of immune-checkpoint inhibitors in patients with cancer and pre-existing autoimmune diseases. Immunotherapy 2021; 13:527-539. [PMID: 33715386 DOI: 10.2217/imt-2020-0230] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Objective: This study aims at investigating the safety and efficacy of immune-checkpoint inhibitors (ICIs) in patients with cancer and pre-existing autoimmune disease (AID). Materials & methods: PubMed, Embase and Cochrane Library were searched for relevant studies. The primary end points of the study were immunotoxicity and cancer response. Results: At the early use of ICIs, compared with those with active AID, grade 3-4 AID flare occurred more frequently in patients with inactive AID after treatment with ICIs; and the incidence of grade 3-4 immunotoxic effects was significantly lower in patients undergoing immunosuppressive therapy than those without corresponding treatment. In addition, patients with worsening AID generally obtained a better objective response than those without a flare. Conclusion: This study demonstrates that the toxic effects induced by immunotherapy are generally manageable in patients with cancer and pre-existing AID, some of whom even achieve satisfactory antitumor effects in clinical practice.
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Affiliation(s)
- Chunlan Wu
- Department of Oncology, Molecular Oncology Research Institute, the First Affiliated Hospital, Fujian Medical University, Chazhong Road No 20, Fuzhou 350005, Fujian, PR China
| | - Li Zhong
- Department of Oncology, Molecular Oncology Research Institute, the First Affiliated Hospital, Fujian Medical University, Chazhong Road No 20, Fuzhou 350005, Fujian, PR China
| | - Qing Wu
- Department of Oncology, Molecular Oncology Research Institute, the First Affiliated Hospital, Fujian Medical University, Chazhong Road No 20, Fuzhou 350005, Fujian, PR China
| | - Shaowei Lin
- Department of Epidemiology & Health Statistics, Public Health School of Fujian Medical University, 1th Xueyuan Road, Fuzhou, Fujian 350100, PR China
| | - Xianhe Xie
- Department of Oncology, Molecular Oncology Research Institute, the First Affiliated Hospital, Fujian Medical University, Chazhong Road No 20, Fuzhou 350005, Fujian, PR China.,Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated hospital, Fujian Medical University, Chazhong Road No 20, Fuzhou 350005, Fujian, PR China
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14
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The Clinical and Histopathological Features of Cutaneous Immune-Related Adverse Events and Their Outcomes. J Clin Med 2021; 10:jcm10040728. [PMID: 33673164 PMCID: PMC7918541 DOI: 10.3390/jcm10040728] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 02/01/2021] [Accepted: 02/09/2021] [Indexed: 12/19/2022] Open
Abstract
Immune checkpoint inhibitors (ICIs) cause a variety of inflammatory eruptions. The understanding of ICI-induced inflammatory eruptions with detailed histopathological findings is not adequate, particularly in Asian populations. In this study, we retrospectively reviewed 51 patients who were histopathologically diagnosed with cutaneous immune-related adverse events (irAEs) following ICI therapy between 2014 and 2020 at the Department of Dermatology of Kyushu University Hospital. Of the 51 patients (30 men, 21 women), maculopapular rash (38/51, 74.5%), erythema multiforme (2/51, 3.9%), lichenoid reaction (3/51, 5.9%), psoriasiform reaction (3/51, 5.9%), bullous pemphigoid (3/51, 5.9%), scleroderma-like reaction (1/51, 2.0%), and Stevens–Johnson syndrome (1/51, 2.0%) were observed. The clinical and histopathological findings of these eruptions were equivalent to typical cases of common drug eruptions. The onset of maculopapular rash was relatively early (more than half of events occurred within 1 month), whereas lichenoid reactions and autoimmune diseases occurred relatively late (4–8 months). With appropriate treatment and/or interruption of ICIs, most rashes improved (50/51, 98.0%). The ICI-induced inflammatory eruptions shared similar clinical and histopathological features with classical inflammatory eruptions, but a variety of inflammatory eruptions may occur with different degrees of severity. Dermatologists play an important role in providing specialized care for cutaneous irAEs.
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15
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Muntyanu A, Netchiporouk E, Gerstein W, Gniadecki R, Litvinov IV. Cutaneous Immune-Related Adverse Events (irAEs) to Immune Checkpoint Inhibitors: A Dermatology Perspective on Management. J Cutan Med Surg 2021; 25:59-76. [PMID: 32746624 DOI: 10.1177/1203475420943260] [Citation(s) in RCA: 104] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Immune checkpoint inhibitors have proven to be efficacious for a broad spectrum of solid organ malignancies. These monoclonal antibodies lead to cytotoxic T-cell activation and subsequent elimination of cancer cells. However, they can also lead to immune intolerance and immune-related adverse event (irAEs) that are new and specific to these therapies. Cutaneous irAEs are the most common, arising in up to 34% of patients on PD-1 inhibitors and 43% to 45% on CTLA-4 inhibitors. The most common skin manifestations include maculopapular eruption, pruritus, and vitiligo-like lesions. A grading system has been proposed, which guides management of cutaneous manifestations based on the percent body surface area (BSA) involved. Cutaneous irAEs may prompt clinicians to reduce drug doses, add systemic steroids to the regiment, and/or discontinue lifesaving immunotherapy. Thus, the goal is for early identification and concurrent management to minimize treatment interruptions. We emphasize here that the severity of the reaction should not be graded based on BSA involvement alone, but rather on the nature of the primary cutaneous pathology. For instance, maculopapular eruptions rarely affect <30% BSA and can often be managed conservatively with skin-directed therapies, while Stevens-Johnson syndrome (SJS) affecting even 5% BSA should be managed aggressively and the immunotherapy should be discontinued at once. There is limited literature available on the management of the cutaneous irAEs and most studies present anecdotal evidence. We review the management strategies and provide recommendations for psoriatic, immunobullous, maculopapular, lichenoid, acantholytic eruptions, vitiligo, alopecias, vasculitides, SJS/toxic epidermal necrolysis, and other related skin toxicities.
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Affiliation(s)
- Anastasiya Muntyanu
- 54473507266 Division of Dermatology, McGill University, Montreal, QC, Canada
| | - Elena Netchiporouk
- 54473507266 Division of Dermatology, McGill University, Montreal, QC, Canada
| | - William Gerstein
- 54473507266 Division of Dermatology, McGill University, Montreal, QC, Canada
| | - Robert Gniadecki
- 3158 Division of Dermatology, University of Alberta, Edmonton, AB, Canada
| | - Ivan V Litvinov
- 54473507266 Division of Dermatology, McGill University, Montreal, QC, Canada
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16
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Foti C, Tucci M, Stingeni L, Hansel K, Lospalluti L, Frisario R, Giuffrida R, Romita P. Successful treatment with apremilast of severe psoriasis exacerbation during nivolumab therapy for metastatic melanoma. Dermatol Ther 2020; 34:e14653. [PMID: 33301205 DOI: 10.1111/dth.14653] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Accepted: 11/23/2020] [Indexed: 11/27/2022]
Affiliation(s)
- Caterina Foti
- Department of Biomedical Science and Human Oncology. Dermatological Clinic, University of Bari, Bari, Italy
| | - Marco Tucci
- Section of Medical Oncology, Department of Biomedical Sciences and Clinical Oncology (DIMO), University of Bari 'Aldo Moro', Bari, Italy
| | - Luca Stingeni
- Dermatology Section, Department of Medicine, University of Perugia, Perugia, Italy
| | - Katharina Hansel
- Dermatology Section, Department of Medicine, University of Perugia, Perugia, Italy
| | - Lucia Lospalluti
- Department of Biomedical Science and Human Oncology. Dermatological Clinic, University of Bari, Bari, Italy
| | - Rosa Frisario
- Department of Biomedical Science and Human Oncology. Dermatological Clinic, University of Bari, Bari, Italy
| | - Roberta Giuffrida
- Dermatology Section, Department of Clinical & Experimental Medicine, University of Messina, Messina, Italy
| | - Paolo Romita
- Department of Biomedical Science and Human Oncology. Dermatological Clinic, University of Bari, Bari, Italy
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17
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Seyit MV, Akdogan N, Yalici-Armagan B, Ozdemir DA. New-onset psoriasiform dermatitis in a patient treated with nivolumab for sarcomatoid carcinoma of the head and neck. Dermatol Ther 2020; 34:e14651. [PMID: 33301183 DOI: 10.1111/dth.14651] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 12/04/2020] [Indexed: 01/11/2023]
Affiliation(s)
- Memduh Veysi Seyit
- Department of Dermatology and Venereology, School of Medicine, Hacettepe University, Ankara, Turkey
| | - Neslihan Akdogan
- Department of Dermatology and Venereology, School of Medicine, Hacettepe University, Ankara, Turkey
| | - Basak Yalici-Armagan
- Department of Dermatology and Venereology, School of Medicine, Hacettepe University, Ankara, Turkey
| | - Deniz Ates Ozdemir
- Department of Pathology, School of Medicine, Hacettepe University, Ankara, Turkey
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18
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Çelik U, Aydemir EH, Engin B, Oba MÇ, Yılmaz M, Meşe ŞG. Dermatological side effects of immunotherapy drugs and targeted cancer therapies: Importance of dermatology and oncology collaboration. J Oncol Pharm Pract 2020; 27:1853-1860. [PMID: 33131448 DOI: 10.1177/1078155220970621] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
INTRODUCTION Novel anti-cancer drugs such as targeted cancer therapies and immune check-point inhibitors (ICIs) have adverse events, especially concerning the skin. The aim of this study is to report an overview of the commonly consulted dermatological side effects of ICIs and targeted cancer therapies in clinical practice, along with their management. METHODS In this single-center study, we evaluated consecutive oncological patients who were referred from the oncology outpatient clinic to the dermatology outpatient clinic due to skin side effects of ICIs and targeted therapies. All patients were examined and treated at the same day of referral by experienced dermatologists. Patient characteristics, clinical findings, diagnostic workups and treatments were retrieved from outpatient records. RESULTS Sixty three patients were enrolled. Most common diagnoses were lung carcinoma, melanoma and colon carcinoma. Fifty patients (79%) were using targeted therapies while 13 (21%) were using ICIs. Xerosis was the most common side effect (44%), followed by acneiform rash, paronychia, eczema and pruritus. Majority of the side effects were grade 2 and 3. Psoriasis was a common side effect of ICIs. One patient had a newly developed dysplastic nevus on vemurafenib treatment. Oncological treatment was not withheld in any of the patients. CONCLUSIONS This study revealed the most commonly consulted skin side effects of novel anti-cancer drugs and their management in daily practice. We underlie the importance of collaborative work of oncology and dermatology professionals as early management of cutaneous side effects of targeted therapies and ICIs improves patient outcomes.
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Affiliation(s)
- Uğur Çelik
- Department of Dermatology and Venerology, Cerrahpasa Medical Faculty, Istanbul University-Cerahpasa, Istanbul, Turkey
| | - Ertuğrul H Aydemir
- Department of Dermatology and Venerology, Cerrahpasa Medical Faculty, Istanbul University-Cerahpasa, Istanbul, Turkey
| | - Burhan Engin
- Department of Dermatology and Venerology, Cerrahpasa Medical Faculty, Istanbul University-Cerahpasa, Istanbul, Turkey
| | - Muazzez Ç Oba
- Department of Dermatology and Venerology, Cerrahpasa Medical Faculty, Istanbul University-Cerahpasa, Istanbul, Turkey
| | - Mesut Yılmaz
- Department of Medical Oncology, Cerrahpasa Medical Faculty, Istanbul University-Cerahpasa, Istanbul, Turkey
| | - Şermin Güven Meşe
- Department of Medical Oncology, Cerrahpasa Medical Faculty, Istanbul University-Cerahpasa, Istanbul, Turkey
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19
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Management of Immune-Related Cutaneous Adverse Reactions to PD-1 and PD-L1 Inhibitors for the Inpatient Dermatologist. CURRENT DERMATOLOGY REPORTS 2020. [DOI: 10.1007/s13671-020-00314-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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20
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Vitamin D, autoimmunity and immune-related adverse events of immune checkpoint inhibitors. Arch Dermatol Res 2020; 313:1-10. [PMID: 32519001 DOI: 10.1007/s00403-020-02094-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2020] [Revised: 05/26/2020] [Accepted: 05/29/2020] [Indexed: 12/16/2022]
Abstract
In addition to its quintessential role in bone homeostasis, vitamin D also plays an important role in regulating the immune system. As such, many studies have demonstrated the therapeutic benefit of vitamin D in treating autoimmune diseases. This immunomodulatory activity of vitamin D has recently attracted more attention due to the rapid development of immunotherapies for cancers, including melanoma. Patients on cancer immunotherapies can suffer from immune-related adverse events (irAEs), which can involve any organ system and range from common dermatological reactions to extremely severe cases of fatal myocarditis in metastatic melanoma patients. Since there are currently no effective approaches to predict or prevent irAEs, it is attractive to potentially leverage the intriguing immunomodulatory effects of vitamin D within this context. This review will discuss recent research investigating the possibility of using vitamin D to alleviate autoimmunity and irAEs with the hope of improving outcomes for patients on cancer immunotherapies, especially within the context of dermatology.
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21
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Immune checkpoint inhibitor-related dermatologic adverse events. J Am Acad Dermatol 2020; 83:1255-1268. [PMID: 32454097 DOI: 10.1016/j.jaad.2020.03.132] [Citation(s) in RCA: 262] [Impact Index Per Article: 52.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 03/25/2020] [Accepted: 03/26/2020] [Indexed: 12/17/2022]
Abstract
Immune checkpoint inhibitors have emerged as a pillar in the management of advanced malignancies. However, nonspecific immune activation may lead to immune-related adverse events, wherein the skin and its appendages are the most frequent targets. Cutaneous immune-related adverse events include a diverse group of inflammatory reactions, with maculopapular rash, pruritus, psoriasiform and lichenoid eruptions being the most prevalent subtypes. Cutaneous immune-related adverse events occur early, with maculopapular rash presenting within the first 6 weeks after the initial immune checkpoint inhibitor dose. Management involves the use of topical corticosteroids for mild to moderate (grades 1-2) rash, addition of systemic corticosteroids for severe (grade 3) rash, and discontinuation of immunotherapy with grade 4 rash. Bullous pemphigoid eruptions, vitiligo-like skin hypopigmentation/depigmentation, and psoriasiform rash are more often attributed to programmed cell death-1/programmed cell death ligand-1 inhibitors. The treatment of bullous pemphigoid eruptions is similar to the treatment of maculopapular rash and lichenoid eruptions, with the addition of rituximab in grade 3-4 rash. Skin hypopigmentation/depigmentation does not require specific dermatologic treatment aside from photoprotective measures. In addition to topical corticosteroids, psoriasiform rash may be managed with vitamin D3 analogues, narrowband ultraviolet B light phototherapy, retinoids, or immunomodulatory biologic agents. Stevens-Johnson syndrome and other severe cutaneous immune-related adverse events, although rare, have also been associated with checkpoint blockade and require inpatient care as well as urgent dermatology consultation.
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22
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Coureau M, Meert AP, Berghmans T, Grigoriu B. Efficacy and Toxicity of Immune -Checkpoint Inhibitors in Patients With Preexisting Autoimmune Disorders. Front Med (Lausanne) 2020; 7:137. [PMID: 32457912 PMCID: PMC7220995 DOI: 10.3389/fmed.2020.00137] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Accepted: 03/30/2020] [Indexed: 12/11/2022] Open
Abstract
Immunotherapy is an important armamentarium for cancer treatment nowadays. Apart from their significant effectiveness in controlling disease they also generate potential severe immune related adverse effects. Preexistence of immune related conditions may eventually predispose to the development of more severe complication and extreme caution have been taken in treating these patients. We performed a literature review searching for case reports and case series in order to offer evidence-based data for clinical management of these patients. Preexisting serological-only immune abnormalities or presence of a predisposing genetic background does not seem to confer significant risk but existing data is scarce. Most patients with preexistent autoimmune diseases can probably treated with checkpoint inhibitors as they seem to have at least the same response rate as the general cancer population. Under treatment, a significant part of them (at least 30%) can experience a flare of their baseline disease which can sometime be severe. Life-threatening cases seems rare and disease flare can be generally managed with steroids. The volume of available data is more important for rheumatologic diseases than for inflammatory bowel diseases were more caution should be observed. However, it has to be kept in mind that new immune related adverse effects (IrAE) are seen with a similar frequency as the flare of the baseline disease. Both flare-up's and newly developed IrAE are generally manageable with a careful clinical follow-up and prompt therapy.
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Affiliation(s)
- Michelle Coureau
- Service des Soins Intensifs et Urgences Oncologiques, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Anne-Pascale Meert
- Service des Soins Intensifs et Urgences Oncologiques, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Thierry Berghmans
- Service d'Oncologie Medicale, Unité d'Oncologie Thoracique, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Bogdan Grigoriu
- Service des Soins Intensifs et Urgences Oncologiques, Institut Jules Bordet, Université Libre de Bruxelles (ULB), Brussels, Belgium
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23
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Ellis SR, Vierra AT, Millsop JW, Lacouture ME, Kiuru M. Dermatologic toxicities to immune checkpoint inhibitor therapy: A review of histopathologic features. J Am Acad Dermatol 2020; 83:1130-1143. [PMID: 32360716 DOI: 10.1016/j.jaad.2020.04.105] [Citation(s) in RCA: 103] [Impact Index Per Article: 20.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Revised: 04/03/2020] [Accepted: 04/20/2020] [Indexed: 02/08/2023]
Abstract
Antineoplastic agents that use the immune system have revolutionized cancer treatment. Specifically, implementation of immune checkpoint inhibitors, monoclonal antibodies that block cytotoxic T-lymphocyte-associated antigen-4, programmed cell death protein 1, or programmed cell death ligand 1 show improved and sustained responses in patients with cancer. However, these agents are associated with a plethora of adverse events, many manifesting in the skin. As the clinical application of cancer immunotherapies expands, understanding the clinical and histopathologic features of associated cutaneous toxicities becomes increasingly important to dermatologists, oncologists, and pathologists to ensure timely diagnosis and appropriate care. This review discusses cutaneous reactions to immune checkpoint inhibitors, focusing on histopathologic features.
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Affiliation(s)
- Samantha R Ellis
- Department of Dermatology, University of California, Davis, Sacramento, California; PotozkinMD Skincare Center, Danville, California
| | - Aren T Vierra
- Department of Dermatology, University of California, Davis, Sacramento, California
| | - Jillian W Millsop
- Department of Dermatology, Vacaville Medical Center, The Permanente Medical Group, Vacaville, California
| | - Mario E Lacouture
- Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Maija Kiuru
- Department of Dermatology, University of California, Davis, Sacramento, California; Department of Pathology and Laboratory Medicine, University of California, Davis, Sacramento, California.
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24
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Nigro O, Pinotti G, Gueli R, Grigioni E, Santis MD, Ceribelli A, Selmi C. Psoriatic arthritis induced by anti-PD1 and treated with apremilast: a case report and review of the literature. Immunotherapy 2020; 12:549-554. [PMID: 32321338 DOI: 10.2217/imt-2019-0085] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023] Open
Abstract
Immune checkpoint inhibitors targeting programmed cell death protein 1 pathways are generally well tolerated, but immune-related adverse events have been observed in more than 80% of all patients. Rheumatic and musculoskeletal immune related adverse events have to date not been widely recognized or well characterized. Psoriasic arthritis is a rare entity and it makes management of patients difficult due to the limited therapeutic possibilities and the strong impact on the quality of life. The majority of cases were treated with glucocorticoids, in some cases not enough. We present the case of a patient with psoriasic arthritis and report cases described in literature of patients treated with apremilast, a small oral molecule that inhibits of phosphodiestherase 4.
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Affiliation(s)
- Olga Nigro
- Medical Oncology, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi, Varese, Italy
| | - Graziella Pinotti
- Medical Oncology, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi, Varese, Italy
| | - Rossana Gueli
- Medical Oncology, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi, Varese, Italy
| | - Elena Grigioni
- Medical Oncology, ASST Sette Laghi, Ospedale di Circolo e Fondazione Macchi, Varese, Italy
| | - Maria De Santis
- Humanitas Clinical and Research Center -IRCCS-, Rozzano, Italy
| | | | - Carlo Selmi
- Humanitas Clinical and Research Center -IRCCS-, Rozzano, Italy.,Humanitas University, Department of Biomedical Sciences, Milan, Italy
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25
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Simonsen AB, Kaae J, Ellebaek E, Svane IM, Zachariae C. Cutaneous adverse reactions to anti-PD-1 treatment-A systematic review. J Am Acad Dermatol 2020; 83:1415-1424. [PMID: 32320766 DOI: 10.1016/j.jaad.2020.04.058] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 04/02/2020] [Accepted: 04/06/2020] [Indexed: 02/06/2023]
Abstract
The use of the humanized monoclonal anti-programmed cell death 1 antibodies pembrolizumab and nivolumab as potent anticancer therapies is rapidly increasing. However, since their approval, numerous cases of cutaneous reactions have been reported. Cutaneous adverse reactions to these agents have yet to be fully characterized and range from nonspecific eruptions to recognizable skin manifestations, which may be localized and vary from mild to life threatening. This systematic review article provides an overview of the various adverse cutaneous reactions to pembrolizumab and nivolumab therapy and offers suggestions for their management.
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Affiliation(s)
- Anne Birgitte Simonsen
- Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
| | - Jeanette Kaae
- Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Eva Ellebaek
- Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Inge Marie Svane
- Department of Oncology, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Claus Zachariae
- Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
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26
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Di Altobrando A, Bruni F, Alessandrini A, Starace M, Misciali C, Piraccini BM. Severe de-novo palmoplantar and nail psoriasis complicating Nivolumab treatment for metastatic melanoma. Dermatol Ther 2020; 33:e13363. [PMID: 32239596 DOI: 10.1111/dth.13363] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 03/17/2020] [Accepted: 03/28/2020] [Indexed: 12/18/2022]
Abstract
Nivolumab, a fully human IgG4 immune checkpoint modulator, binds to the programmed cell death 1 (PD-1) receptor on T cells and blocks their inhibition. Thus, it increases the anticancer host immune response by allowing T cells to attack tumor cells. Although anti-PD-1 immunotherapy is typically well accepted, deregulation of immune tolerance caused by nivolumab may determine immune-related adverse events, among which skin toxicities represent the most common. We report a case of severe new-onset palmoplantar and nail psoriasis after receiving nivolumab treatment for metastatic melanoma.
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Affiliation(s)
- Ambra Di Altobrando
- Department of Experimental, Diagnostic and Specialty Medicine-Division of Dermatology, University of Bologna, Bologna, Italy
| | - Francesca Bruni
- Department of Experimental, Diagnostic and Specialty Medicine-Division of Dermatology, University of Bologna, Bologna, Italy
| | - Aurora Alessandrini
- Department of Experimental, Diagnostic and Specialty Medicine-Division of Dermatology, University of Bologna, Bologna, Italy
| | - Michela Starace
- Department of Experimental, Diagnostic and Specialty Medicine-Division of Dermatology, University of Bologna, Bologna, Italy
| | - Cosimo Misciali
- Department of Experimental, Diagnostic and Specialty Medicine-Division of Dermatology, University of Bologna, Bologna, Italy
| | - Bianca M Piraccini
- Department of Experimental, Diagnostic and Specialty Medicine-Division of Dermatology, University of Bologna, Bologna, Italy
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27
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Abstract
OPINION STATEMENT The treatment of advanced melanoma has undergone a dramatic transformation over the last decade with the advent of targeted and immunomodulatory therapies. This transition from cytotoxic chemotherapy has yielded improvements in both survival and quality of life; yet despite their therapeutic advantages, these treatments have been associated with a diverse range of cutaneous adverse events (AEs). These range from relatively benign eczematous conditions to more severe inflammatory and bullous disorders, and can include induction of second malignancies. AEs can result in serious morbidity and risk of mortality if not recognised and managed early. As a consequence of their novelty, and rapid uptake, these agents have been subject to intense scrutiny and there is a general understanding that cutaneous AEs should be anticipated in treatment plans. Dermatologists should be integrated into management teams to assist in the development of treatment protocols for anticipated common AEs and to provide expert management of more severe, rare or unusual AEs. Our experience has shown a reduction in treatment interruptions, more rapid recognition of unusual AEs and improved management pathways for patients suffering cutaneous AEs.
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28
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Melanoma and Vitiligo: In Good Company. Int J Mol Sci 2019; 20:ijms20225731. [PMID: 31731645 PMCID: PMC6888090 DOI: 10.3390/ijms20225731] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 11/10/2019] [Accepted: 11/13/2019] [Indexed: 12/24/2022] Open
Abstract
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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Lu JG, Ji P, French SW. The Major Histocompatibility Complex Class II-CD4 Immunologic Synapse in Alcoholic Hepatitis and Autoimmune Liver Pathology: The Role of Aberrant Major Histocompatibility Complex Class II in Hepatocytes. THE AMERICAN JOURNAL OF PATHOLOGY 2019; 190:25-32. [PMID: 31669415 DOI: 10.1016/j.ajpath.2019.09.019] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Revised: 08/27/2019] [Accepted: 09/24/2019] [Indexed: 12/12/2022]
Abstract
The major histocompatibility complex class II (MHC II)-CD4 immunologic synapse is classically described between the T-cell receptor of CD4-positive lymphocytes and MHC II on antigen-presenting cells. This interaction and others between surrounding costimulatory and checkpoint molecules promote differentiation of naïve CD4 T lymphocytes into helper T cells subtypes, including types 1, 2, and 17 helper T cells, that have more tailored immunologic responses. Although MHC II is mainly produced by professional antigen-presenting cells, it can be aberrantly produced by other cell types, including hepatocytes in various liver pathologies, such as autoimmune hepatitis and alcoholic hepatitis. This can lead to direct targeting of hepatocytes by CD4-positive lymphocytes, which form an immunologic synapse with the hepatocyte. The lymphocytes internalize the MHC II-CD4 complexes in a phagocytosis-like mechanism and in the process eat the hepatocyte piece by piece. We review the evidence for this mechanism and the role of these autoimmune responses in various liver diseases, including alcoholic hepatitis, autoimmune hepatitis, and primary biliary cirrhosis. The role of aberrant MHC II in malignancy, including hepatocellular carcinoma, is also reviewed. Further understanding of this mechanism can lead to better understanding of the immune mechanisms involved in these liver pathologies, with potential diagnostic and therapeutic applications.
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Affiliation(s)
- Jiajie G Lu
- Department of Pathology, Harbor-UCLA Medical Center, Torrance, California.
| | - Ping Ji
- Department of Pathology, Harbor-UCLA Medical Center, Torrance, California
| | - Samuel W French
- Department of Pathology, Harbor-UCLA Medical Center, Torrance, California
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Cutaneous toxicities of antineoplastic agents: data from a large cohort of Greek patients. Support Care Cancer 2019; 27:4535-4542. [PMID: 30919155 DOI: 10.1007/s00520-019-04751-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Accepted: 03/15/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE Cutaneous toxicities from novel anticancer treatments are an emerging problem in dermato-oncology. However, the prevalence of those toxicities and necessity of skin consultations are currently unknown. The purpose of our study was to perform an epidemiologic analysis of cutaneous toxicities that were referred to our cutaneous toxicity clinic in Athens, Greece. METHODS All patients examined at the oncodermatology department over a 42-month period were included. Gender, age, type of cancer, type of antineoplastic treatment, and type of toxicity were recorded and analyzed. RESULTS Four hundred fifty-nine patients (182 males, 277 females) with mean age (SD) 60.6 years (13.05) were included in the analysis. Six hundred seventy-two cutaneous toxicities were recorded. Chemotherapy-induced toxicities were the most commonly recorded incidents, with taxanes being the most commonly involved agent. Immune-related adverse events (IRAEs) have steadily increased over the past 3 years. Treatment modifications due to skin toxicities were more common in patients treated with targeted agents and immune checkpoint inhibitors than in those treated with chemotherapy. The toxicities that led to the most treatment modifications were acneiform eruptions and perionychias. The most common IRAEs recorded were psoriasis in 11 patients, followed by pruritus, macular rash, and lichenoid-type eruptions. In addition, 4 interesting cases of IRAEs are discussed. CONCLUSION Antineoplastic treatments can lead to a wide range of cutaneous toxicities. Our study underlines the need for a multidisciplinary approach in oncologic patients. The dermatologists' role is crucial in effectively managing those reactions and preventing antineoplastic drug dose adjustments or discontinuation of treatment.
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Russo I, Zorzetto L, Chiarion Sileni V, Alaibac M. Cutaneous Side Effects of Targeted Therapy and Immunotherapy for Advanced Melanoma. SCIENTIFICA 2018; 2018:5036213. [PMID: 30693134 PMCID: PMC6332919 DOI: 10.1155/2018/5036213] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 12/04/2018] [Accepted: 12/06/2018] [Indexed: 06/09/2023]
Abstract
Melanoma is one of the most fatal cancers, and its incidence is increasing worldwide. Thanks to the better understanding of the molecular mechanisms involved in the pathogenesis of melanoma, recently new targeted agents have been developed. In this article, we review the current state of knowledge of clinical presentation, mechanisms, and management of the most common cutaneous side effects observed during treatment with targeted and immunological therapies approved for advanced melanoma. We include discussion of BRAF/MEK inhibitors and immune-checkpoint inhibitors, notably CTLA-4 and PD-1 inhibitors.
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Affiliation(s)
- Irene Russo
- Unit of Dermatology, University of Padua, Via Gallucci 4, 35128 Padova, Italy
| | - Ludovica Zorzetto
- Unit of Dermatology, University of Padua, Via Gallucci 4, 35128 Padova, Italy
| | | | - Mauro Alaibac
- Unit of Dermatology, University of Padua, Via Gallucci 4, 35128 Padova, Italy
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De Novo Psoriasis Vulgaris Diagnosed after Nivolumab Treatment for Refractory Hodgkin's Lymphoma, Completely Resolved after Autologous Hematopoietic Stem Cell Transplantation. Case Rep Hematol 2018; 2018:6215958. [PMID: 30410803 PMCID: PMC6206568 DOI: 10.1155/2018/6215958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 09/09/2018] [Accepted: 09/24/2018] [Indexed: 11/17/2022] Open
Abstract
The programmed cell death protein-1 (PD-1) inhibitor nivolumab has been recently approved as an effective and safe treatment for patients with refractory/relapsed Hodgkin's lymphomas. Dermatological adverse events, mainly skin rash, have been reported in 1–5% of patients. We describe a case of de novo psoriasis vulgaris (PsV), diagnosed after nivolumab treatment for refractory Hodgkin's lymphoma. After administration of 6 cycles, skin lesions appeared in the right tibia, forearms, and dorsum of hands, and biopsy confirmed the diagnosis of PsV. The lesions completely resolved after autologous stem cell transplantation (ASCT) which was performed in the context of the treatment for the primary disease. PsV is an inflammatory skin disease, and it is considered to be mediated through cytotoxic T-cells. PD-1 blockage may lead to expansion of such T-cells, resulting thus in PsV appearance. The early published studies showed that nivolumab represents a safe treatment approach. PsV occurrence has not been reported so far in patients treated with nivolumab for hematological diseases, and it seems that long-term follow-up is necessary to fully clarify the entirety of PD-1 inhibitors' skin adverse events. Additionally, this clinical observation provides an evidence for a potential exploitation of ASCT in refractory and severe forms of PsV.
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Differential efficacy of biologic treatments targeting the TNF-α/IL-23/IL-17 axis in psoriasis and psoriatic arthritis. Cytokine 2018; 111:182-188. [PMID: 30172115 DOI: 10.1016/j.cyto.2018.08.025] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2018] [Revised: 08/20/2018] [Accepted: 08/24/2018] [Indexed: 02/08/2023]
Abstract
Psoriasis and psoriatic arthritis cause significant physical and psychological burdens for afflicted individuals. An accelerated TNF-α/IL-23/IL-17 axis is their major pathomechanism; therefore, anti-TNF-α/IL-23/IL-17 biologics are very effective for the treatment of skin and joint lesions in psoriasis and psoriatic arthritis. Given that the IL-17 signature is more upregulated in the skin than in synovium in psoriatic arthritis, anti-IL-23/IL-17 agents seem to be superior to anti-TNF-α remedies in the treatment of skin lesions. In this review, we focus on the differential efficacy of anti-TNF-α/IL-23/IL-17 biologics in psoriasis and psoriatic arthritis.
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Decreased blood CD4+PD-1+ and CD8+PD-1+ T cells in psoriatic patients with and without arthritis. Postepy Dermatol Alergol 2018; 35:344-350. [PMID: 30206445 PMCID: PMC6130132 DOI: 10.5114/ada.2018.75609] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2017] [Accepted: 06/15/2017] [Indexed: 01/07/2023] Open
Abstract
Introduction Psoriasis with and without arthritis have common immunological mechanisms which among others involve the interactions between cytokines produced by T cells, including Th1, Th17 and Th22. Although quite a lot is known about psoriasis pathogenesis, the cause of chronic immune activation and response in the disease remains unclear. One of the negative regulators of the immune system is programmed death 1 (PD-1). Aim To assess the expression level of PD-1 in the peripheral T cells of psoriatic patients with and without arthritis. Material and methods The study included 23 psoriatic patients with arthritis, 52 psoriatic patients without arthritis and 52 healthy controls. The percentages of CD3+, CD4+, CD8+, CD4+PD-1+ and CD8+PD-1+ T cells were analyzed using flow cytometry. Results The percentages of CD4+PD-1+ as well as CD8+PD-1+ T cells in the psoriatic patients both with and without arthritis were significantly lower than in the control group. The percentages of CD4+PD-1+ as well as CD8+PD-1+T cells were not significantly different between the psoriatic patients with and without arthritis. A significant positive correlation between PD-1 expression on the CD4+ and CD8+ T cells was found in the psoriatic patients without arthritis. Conclusions Impairment of the negative co-stimulation from PD-1 may be another common characteristic of psoriasis both with and without arthritis.
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De Bock M, Hulstaert E, Kruse V, Brochez L. Psoriasis Vulgaris Exacerbation during Treatment with a PD-1 Checkpoint Inhibitor: Case Report and Literature Review. Case Rep Dermatol 2018; 10:190-197. [PMID: 30186132 PMCID: PMC6120403 DOI: 10.1159/000491572] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Accepted: 06/27/2018] [Indexed: 12/11/2022] Open
Abstract
Objective The incidence of immune-related adverse events is growing as the use of checkpoint inhibitors is exponentially increasing. Cutaneous adverse events are among the most frequent immune-related adverse events. The purpose of this case report and literature review is to highlight psoriasis as a potential adverse event with need for early recognition. Case Report and Literature Review We describe the case of a 65-year-old woman with psoriasis exacerbation while treated with nivolumab (anti-PD-1) for a stage IV melanoma. She had a history of scalp psoriasis but she presented with psoriatic lesions on both lower and upper limbs. Our patient was treated with topical steroids. So far, 34 other cases with an exacerbation of psoriasis during treatment with anti-PDL-1 or PD-1 therapy have been reported in the literature. A broad range of therapies are described, without any available guidelines for this particular condition. Conclusion Psoriasis exacerbation is an established side effect of PD-1/PDL-1 checkpoint inhibitors with 35 reported cases. Early recognition and management are challenging as there are no clear guidelines available. A close collaboration between oncologist and dermatologist is mandatory to manage this immune-related adverse event.
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Affiliation(s)
- Marlies De Bock
- Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium
| | - Eva Hulstaert
- Department of Dermatology, Ghent University Hospital, Ghent, Belgium
| | - Vibeke Kruse
- Department of Medical Oncology, Ghent University Hospital, Ghent, Belgium
| | - Lieve Brochez
- Department of Dermatology, Ghent University Hospital, Ghent, Belgium
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Babey H, Quéré G, Descourt R, Le Calloch R, Lanfranco L, Nousbaum JB, Cornec D, Tison A, Chouaid C. Immune-checkpoint inhibitors to treat cancers in specific immunocompromised populations: a critical review. Expert Rev Anticancer Ther 2018; 18:981-989. [PMID: 29995451 DOI: 10.1080/14737140.2018.1499468] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Because of their efficacy against numerous cancers, immune-checkpoint inhibitors (ICIs), anti-cytotoxic T-lymphocyte antigen-4, and anti-programmed cell death monoclonal antibodies are being used ever more often in oncology. However, some patients were excluded from clinical trials because of their comorbidities despite their potentially higher cancer frequencies, as is the case for immunocompromised patients. Areas covered: We analyzed reported preclinical and clinical information and evaluated the risk/benefit ratio for four immunocompromised populations: people living with human immunodeficiency virus (PLHs), solid-organ transplant recipients, recipients of hematopoietic stem-cell allografts, and patients with autoimmune diseases. Expert commentary: Information available in the literature is fragmentary and scarce, making it difficult to evaluate the risk/benefit ratio. It can, nonetheless, be noted that ICI use in PLHs seems possible. For solid-organ transplant recipients, the risk for the graft seems elevated. For the other two populations, it is difficult to conclude at this time.
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Affiliation(s)
- Hélène Babey
- a Institut de Cancerologie de Bretagne occidentale , Centre Hospitalier Universitaire de Brest , Brest , France
| | - Gilles Quéré
- a Institut de Cancerologie de Bretagne occidentale , Centre Hospitalier Universitaire de Brest , Brest , France
| | - Renaud Descourt
- a Institut de Cancerologie de Bretagne occidentale , Centre Hospitalier Universitaire de Brest , Brest , France
| | - Ronan Le Calloch
- b Service des maladies du sang, médecine interne, maladies infectieuses (MIIS) , Centre Hospitalier de Quimper Cornouaille , Quimper , France.,c Université de Brest , Fédération Inter Hospitalier d'Immuno-Hématologie de Bretagne Occidentale (FIHBO) , Brest , France
| | - Luca Lanfranco
- d Service de néphrologie , Centre Hospitalier Universitaire de Brest , Brest , France.,e UMR1227, Lymphocytes B et Autoimmunité, Inserm, LabEx IGO , Université de Brest , Brest , France
| | - Jean-Baptiste Nousbaum
- f Service d'Hépato-gastroentérologie , Centre Hospitalier Universitaire de Brest , Brest , France.,g Registre Finistérien des Tumeurs Digestives, EA 7479 SPURBO , Université de Bretagne Occidentale , Brest , France
| | - Divi Cornec
- e UMR1227, Lymphocytes B et Autoimmunité, Inserm, LabEx IGO , Université de Brest , Brest , France.,h Rhumatologie et Centre National de Référence des Maladies Auto-Immunes Rares CERAINO , CHRU de Brest , Brest , France
| | - Alice Tison
- e UMR1227, Lymphocytes B et Autoimmunité, Inserm, LabEx IGO , Université de Brest , Brest , France.,h Rhumatologie et Centre National de Référence des Maladies Auto-Immunes Rares CERAINO , CHRU de Brest , Brest , France
| | - Christos Chouaid
- i Service de pneumologie , Centre Hospitalier Intercommunal de Créteil , Créteil , France
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Boada A, Carrera C, Segura S, Collgros H, Pasquali P, Bodet D, Puig S, Malvehy J. Cutaneous toxicities of new treatments for melanoma. Clin Transl Oncol 2018; 20:1373-1384. [PMID: 29799097 DOI: 10.1007/s12094-018-1891-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2018] [Accepted: 05/09/2018] [Indexed: 12/13/2022]
Abstract
New drugs against advanced melanoma have emerged during last decade. Target therapy and immunotherapy have changed the management of patients with metastatic disease. Along with its generalized use, drug toxicities have appeared and the skin is the target organ of a significant part of them. This revision summarizes the most common side effects and consensus management to improve the compliance of therapies and patients' quality of life. Among the BRAF inhibitors, main cutaneous side effects are photosensitivity, plantar hyperkeratosis, and the appearance of verrucal keratosis or squamous cell carcinoma. Special attention must be paid to the development of new primary melanomas or changes on nevi during BRAF inhibitor therapy. The most common cutaneous side effects of immunotherapy are rash, pruritus, and vitiligo. It remains controversial the possible role of these toxicities as markers of response to therapy.
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Affiliation(s)
- A Boada
- Dermatology Department, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Crta/Canyet s/n., Badalona, 08016, Barcelona, Spain.
| | - C Carrera
- Melanoma Unit, Dermatology Department, Hospital Clinic, Institut d'investigacions biomèdiques August Pi i Sunyer (IDIBAPS), CIBERER, Universitat de Barcelona, Barcelona, Spain
| | - S Segura
- Dermatology Department, Hospital del Mar, Parc de Salut Mar, Fundació Institut Mar d'Investigacions Mèdiques, Barcelona, Spain
| | - H Collgros
- Sydney Melanoma Diagnostic Centre, Royal Prince Alfred Hospital, Sidney, Australia
| | - P Pasquali
- Dermatology Department, Pius Hospital Valls, Institut d'Investigació Sanitària Pere Virgili Valls, Tarragona, Spain
| | - D Bodet
- Dermatology Department, Hospital Universitari Vall d'Hebron, VHIR, Barcelona, Spain
| | - S Puig
- Melanoma Unit, Dermatology Department, Hospital Clinic, Institut d'investigacions biomèdiques August Pi i Sunyer (IDIBAPS), CIBERER, Universitat de Barcelona, Barcelona, Spain
| | - J Malvehy
- Melanoma Unit, Dermatology Department, Hospital Clinic, Institut d'investigacions biomèdiques August Pi i Sunyer (IDIBAPS), CIBERER, Universitat de Barcelona, Barcelona, Spain
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Furue K, Ito T, Tsuji G, Kadono T, Nakahara T, Furue M. Autoimmunity and autoimmune co-morbidities in psoriasis. Immunology 2018; 154:21-27. [PMID: 29315555 PMCID: PMC5904708 DOI: 10.1111/imm.12891] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Revised: 12/18/2017] [Accepted: 12/29/2017] [Indexed: 12/12/2022] Open
Abstract
Psoriasis is characterized by widespread scaly erythematous plaques that cause significant physical and psychological burdens for the affected individuals. Accelerated inflammation driven by the tumour necrosis factor-α/interleukin-23/interleukin-17 axis is now known to be the major mechanism in the development of psoriasis. In addition, psoriasis has an autoimmune nature that manifests as autoreactive T cells and is co-morbid with other autoimmune diseases, such as autoimmune bullous diseases, vitiligo, alopecia and thyroiditis. In this article, we review the recent topics on autoimmunity and autoimmune co-morbidities in psoriasis.
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Affiliation(s)
| | - Takamichi Ito
- Department of DermatologyKyushu UniversityFukuokaJapan
| | - Gaku Tsuji
- Department of DermatologyKyushu UniversityFukuokaJapan
| | - Takafumi Kadono
- Department of DermatologySt Marianna University School of MedicineKawasakiJapan
| | - Takeshi Nakahara
- Department of DermatologyKyushu UniversityFukuokaJapan
- Division of Skin Surface SensingDepartment of DermatologyKyushu UniversityFukuokaJapan
| | - Masutaka Furue
- Department of DermatologyKyushu UniversityFukuokaJapan
- Division of Skin Surface SensingDepartment of DermatologyKyushu UniversityFukuokaJapan
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Safe Administration of Ipilimumab, Pembrolizumab, and Nivolumab in a Patient with Metastatic Melanoma, Psoriasis, and a Previous Guillain-Barré Syndrome. Case Rep Oncol Med 2018; 2018:2783917. [PMID: 29707397 PMCID: PMC5863341 DOI: 10.1155/2018/2783917] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2017] [Accepted: 01/10/2018] [Indexed: 12/26/2022] Open
Abstract
Background Patients with autoimmune diseases were not evaluated in clinical trials with immune checkpoint inhibitors (ICIs), since a history of immune disorders, such as Guillain–Barré syndrome (GBS) and psoriasis, is one of the major risk factors for the development of immune-related adverse events (irAEs). This risk cannot be defined; therefore, physicians are called to manage these patients in clinical practice. Case Report We report the case of a 62-year-old male patient affected by metastatic melanoma, with a history of GBS and psoriasis, and treated with sequential ipilimumab, pembrolizumab, and nivolumab, without significant toxicities. Conclusion This case report supports that although a history of immune disorders is one of the major risk factors for development of irAEs, in some patients, it could be possible to safely administer sequential treatments with ICIs. A proper decision should be made, considering therapeutic options, disease-related risks, and those related to a recurrence of preexisting autoimmune disorders.
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Om A, Cardon B, Cohen G. Psoriasiform eruption on the face and extremities associated with nivolumab therapy. JAAD Case Rep 2018; 4:373-375. [PMID: 29693074 PMCID: PMC5911810 DOI: 10.1016/j.jdcr.2017.11.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2022] Open
Affiliation(s)
- Amit Om
- Florida State University Division of Dermatology, Tallahassee, Florida
| | - Brandon Cardon
- Florida State University College of Medicine, Tallahassee, Florida
| | - George Cohen
- Florida State University Division of Dermatology, Tallahassee, Florida
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Abstract
INTRODUCTION The prognosis of recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (HNSCC) after failure of first line chemotherapy is dismal. Until the publication of the results of CheckMate 141, not a single agent provided any survival benefit as a second line treatment for R/M HNSCC. Areas covered: A comprehensive review of the literature was conducted on the role of nivolumab in HNSCC. Expert commentary: Nivolumab is approved by the Food and Drug Administration for the treatment of patients based on the results of CheckMate 141 showing an overall survival benefit as compared to standard care (single agent docetaxel, methotrexate, or cetuximab). Of particular interest are immune-related adverse events which should be managed according to published guidelines.
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Affiliation(s)
- Pol Specenier
- a Department of Oncology , Antwerp University Hospital , Edegem , Belgium
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Seidel JA, Otsuka A, Kabashima K. Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations. Front Oncol 2018; 8:86. [PMID: 29644214 PMCID: PMC5883082 DOI: 10.3389/fonc.2018.00086] [Citation(s) in RCA: 957] [Impact Index Per Article: 136.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Accepted: 03/12/2018] [Indexed: 12/22/2022] Open
Abstract
Melanoma, a skin cancer associated with high mortality rates, is highly radio- and chemotherapy resistant but can also be very immunogenic. These circumstances have led to a recent surge in research into therapies aiming to boost anti-tumor immune responses in cancer patients. Among these immunotherapies, neutralizing antibodies targeting the immune checkpoints T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) are being hailed as particularly successful. These antibodies have resulted in dramatic improvements in disease outcome and are now clinically approved in many countries. However, the majority of advanced stage melanoma patients do not respond or will relapse, and the hunt for the “magic bullet” to treat the disease continues. This review examines the mechanisms of action and the limitations of anti-PD-1/PD-L1 and anti-CTLA-4 antibodies which are the two types of checkpoint inhibitors currently available to patients and further explores the future avenues of their use in melanoma and other cancers.
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Affiliation(s)
- Judith A Seidel
- Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Atsushi Otsuka
- Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Kenji Kabashima
- Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.,Singapore Immunology Network (SIgN), Institute of Medical Biology, Agency for Science, Technology and Research (ASTAR), Biopolis, Singapore, Singapore
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Troyanova-Slavkova S, Eickenscheidt L, Dumann K, Kowalzick L. [Initially undetected de novo psoriasis triggered by nivolumab for metastatic base of the tongue carcinoma]. Hautarzt 2018; 69:674-680. [PMID: 29330579 DOI: 10.1007/s00105-017-4109-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Nivolumab is a monoclonal antibody that binds to the PD-1 receptor on T cells and inhibits the interaction with the PD-L1 and PD-L2 ligands on cancer cells. Thus, nivolumab has immunostimulatory properties. The known side effects of this therapy include fatigue, skin rash, dysfunction of the thyroid gland and colitis, which are explained by the immunoregulatory mechanisms of the drug. Here we report on the case of a 58-year-old man with metastatic base of tongue carcinoma who developed de novo psoriasis triggered by nivolumab. The patient was treated for months with the diagnosis of a generalized mycosis. This case highlights the importance of vigilance for unexpected cutaneous side effects during immune stimulating therapy with checkpoint inhibitors.
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Affiliation(s)
- S Troyanova-Slavkova
- Klinik für Hautkrankheiten und Allergologie, HELIOS Vogtland-Klinikum Plauen GmbH, Postfach 100153, 08505, Plauen, Deutschland
| | - L Eickenscheidt
- Klinik für Hautkrankheiten und Allergologie, HELIOS Vogtland-Klinikum Plauen GmbH, Postfach 100153, 08505, Plauen, Deutschland
| | - K Dumann
- Dermatohistopathologie, Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Leipzig AöR, Leipzig, Deutschland
| | - L Kowalzick
- Klinik für Hautkrankheiten und Allergologie, HELIOS Vogtland-Klinikum Plauen GmbH, Postfach 100153, 08505, Plauen, Deutschland.
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Voudouri D, Nikolaou V, Laschos K, Charpidou A, Soupos N, Triantafyllopoulou I, Panoutsopoulou I, Aravantinos G, Syrigos K, Stratigos A. Anti-PD1/PDL1 induced psoriasis. Curr Probl Cancer 2017; 41:407-412. [PMID: 29096940 DOI: 10.1016/j.currproblcancer.2017.10.003] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Accepted: 10/16/2017] [Indexed: 11/28/2022]
Abstract
BACKGROUND Immune checkpoint inhibitors are novel agents approved for the treatment of late-stage malignancies. Despite its important clinical benefits, checkpoint inhibition is associated with a unique spectrum of side effects known as immune-related adverse events. Skin toxicities are the most frequent immune-related adverse events during anti-PD1 blockade therapies. Among them, rare cases of psoriasis exacerbation have been reported. METHODS We present the clinical characteristics of exacerbated psoriasis in 5 patients under anti-PD1/PDL1 therapy. RESULTS A total of 5 patients were overall included (4 males, 1 female mean age 65.8 years). Among them, 3 were diagnosed with nonsmall cell lung cancer, 1 with papillary urothelial carcinoma, and 1 with squamous cell carcinoma of the tonsil. Of all, 3 patients were treated with anti-PD1 (1 with pembrolizumab, 2 with nivolumab), whereas the remaining 2 with anti-PDL1 (durvalumab). Only 1 out of 5 patients had active psoriatic lesions at the time of treatment initiation, 2 shared a past history of psoriasis, and 1 reported a strong related family history (3/5 siblings). Four out of 5 patients experienced guttate lesions, though the most severe exacerbation was noted in the durvalumab group. Four out of 5 patients managed to continue treatment after close dermatologic monitoring, whereas 1 patient under durvalumab was forced to treatment delays owing to the severity of the skin reactions. Skin rashes appeared in all patients after the fourth cycle of immunotherapy. CONCLUSIONS Both anti-PD1 and anti-PDL1 therapies can lead to psoriasis exacerbation although more severe flares were noted in patients treated with durvalumab. Not only personal but also related family history of psoriasis are significant risk factors and need to be outlined before treatment initiation. If such related history exists, strict skin surveillance can lead to the early diagnosis and treatment of any psoriatic exacerbations that could otherwise severely affect quality of life or even compromise therapeutic protocols and final prognosis.
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Affiliation(s)
- Dimitra Voudouri
- Dermato Oncology Department, Cutaneous Toxicities Clinic, Andreas Sygros Hospital, University of Athens, Athens, Greece
| | - Vasiliki Nikolaou
- Dermato Oncology Department, Cutaneous Toxicities Clinic, Andreas Sygros Hospital, University of Athens, Athens, Greece.
| | - Konstantinos Laschos
- Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece
| | - Andriani Charpidou
- Third Department of Medicine, Oncology Unit, School of Medicine, Sotiria General Hospital, University of Athens, Athens, Greece
| | - Nikolaos Soupos
- Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece
| | - Ioanna Triantafyllopoulou
- Dermato Oncology Department, Cutaneous Toxicities Clinic, Andreas Sygros Hospital, University of Athens, Athens, Greece
| | - Ioanna Panoutsopoulou
- Dermato Oncology Department, Cutaneous Toxicities Clinic, Andreas Sygros Hospital, University of Athens, Athens, Greece
| | - Gerasimos Aravantinos
- Second Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece
| | - K Syrigos
- Third Department of Medicine, Oncology Unit, School of Medicine, Sotiria General Hospital, University of Athens, Athens, Greece
| | - A Stratigos
- Dermato Oncology Department, Cutaneous Toxicities Clinic, Andreas Sygros Hospital, University of Athens, Athens, Greece
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Yoest JM. Clinical features, predictive correlates, and pathophysiology of immune-related adverse events in immune checkpoint inhibitor treatments in cancer: a short review. Immunotargets Ther 2017; 6:73-82. [PMID: 29067284 PMCID: PMC5644546 DOI: 10.2147/itt.s126227] [Citation(s) in RCA: 115] [Impact Index Per Article: 14.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Identification and characterization of T-cell regulatory mechanisms, or checkpoints, have led to a wave of drug development aimed at inhibiting these targets to "remove the brakes" of the immune system. This class of anticancer therapeutics, termed immune checkpoint inhibitors (ICIs), has harnessed the potential of the body's own immune system to recognize cancerous cells and selectively eliminate them, in some cases with alarming success. This new breakthrough, however, has not been without its drawbacks. Immune-related adverse events (irAEs) are adverse events encountered during treatment with ICIs that are thought to be mediated through the patient's immune system which can manifest with a variety of symptoms which often resemble autoimmunity. These events range widely in presentation and severity and are reported frequently. Here, we will discuss a large selection of case reports in order to inform the clinician, laboratorian, and researcher of the scope of organ systems affected, the severity of the conditions being encountered, and the responses of these events to treatment, as well as explore the use of ICIs in the setting of preexisting autoimmunity. We will also consider the ability to detect autoantibodies before and during irAEs as well as the correlations that irAEs have with clinical outcomes. Finally, we will conclude by exploring the possibility that two distinct pathways may be contributing to the phenomenon of irAEs within this class of drugs, and the role that this might play in future research and clinical practice.
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Affiliation(s)
- Jennifer M Yoest
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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Cutaneous Eruptions in Patients Receiving Immune Checkpoint Blockade: Clinicopathologic Analysis of the Nonlichenoid Histologic Pattern. Am J Surg Pathol 2017; 41:1381-1389. [PMID: 28817405 DOI: 10.1097/pas.0000000000000900] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Cutaneous eruptions are among the most common immune-related adverse events (irAEs) associated with anti-programmed cell death protein 1/programmed cell death ligand 1 therapy, and are often clinically and histologically characterized as lichenoid. Nonlichenoid patterns may also occur and are likely to be encountered by surgical pathologists, given the increasing clinical use of these agents. The purpose of this study is to describe the histopathologic features of nonlichenoid cutaneous irAEs from patients receiving anti-programmed cell death protein 1/programmed cell death ligand 1 therapies for a variety of underlying advanced malignancies. Sixteen patients with 17 biopsied eruptions were included from 2 academic institutions with extensive experience administering and monitoring responses to immune checkpoint blockade as well as treating the potential side effects. Eruptions occurred a median of 10 days (range, 1 d to 11.4 mo) after treatment initiation. Nearly half of specimens demonstrated either a psoriasiform/spongiotic or an urticarial-type reaction pattern on histologic review. Patterns consistent with Grover disease, bullous pemphigoid, and granulomatous dermatitis were also observed. Nearly two-thirds of patients required systemic corticosteroids for treatment of the cutaneous irAE, and 19% of patients discontinued immunotherapy due to their skin eruptions. 75% of patients showed an objective antitumor response. The diverse array of nonlichenoid cutaneous irAE presented here should reflect and inform the scope of histologic patterns encountered by the practicing surgical pathologist. Such eruptions are seen in patients with a variety of underlying tumor types, many of whom ultimately demonstrate a favorable response to immune checkpoint blockade.
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McCarthy MW, Walsh TJ. Checkpoint inhibitors and the risk of infection. EXPERT REVIEW OF PRECISION MEDICINE AND DRUG DEVELOPMENT 2017. [DOI: 10.1080/23808993.2017.1380517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Matthew William McCarthy
- Hospital Medicine, Joan and Sanford I Weill Medical College of Cornell University, New York, NY, USA
| | - Thomas J. Walsh
- Transplantation-Oncology Infectious Diseases Program, Weill Cornell Medical Center, New York, NY, USA
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Abstract
Immunotherapies are changing the landscape of advanced solid tumor treatment. These therapies have different mechanisms of action and include oncolytic viruses, checkpoint inhibitors, such as CTLA-4 or PD1/PD-L1 monoclonal antibodies, and CSF-1R antibodies. Given the growing therapeutic impact of these agents in oncology, it is important to better understand their properties. Immunotherapies generate new toxicity profiles that are called immune-related adverse events and require specific management. This review focuses on the mechanisms of action of such side effects, as well as their description and their general management.
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Ruiz-Bañobre J, Abdulkader I, Anido U, León L, López-López R, García-González J. Development of de novo
psoriasis during nivolumab therapy for metastatic renal cell carcinoma: immunohistochemical analyses and clinical outcome. APMIS 2017; 125:259-263. [DOI: 10.1111/apm.12658] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2016] [Accepted: 12/19/2016] [Indexed: 01/09/2023]
Affiliation(s)
- Juan Ruiz-Bañobre
- Servizo de Oncoloxía Médica & Grupo de Oncoloxía Médica Traslacional; Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS); Complexo Hospitalario Universitario de Santiago de Compostela; Santiago de Compostela Spain
| | - Ihab Abdulkader
- Servizo de Anatomía Patolóxica; Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS); Complexo Hospitalario Universitario de Santiago de Compostela; Santiago de Compostela Spain
| | - Urbano Anido
- Servizo de Oncoloxía Médica & Grupo de Oncoloxía Médica Traslacional; Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS); Complexo Hospitalario Universitario de Santiago de Compostela; Santiago de Compostela Spain
| | - Luis León
- Agencia de conocimiento en salud; SERGAS; Santiago de Compostela; Spain
| | - Rafael López-López
- Servizo de Oncoloxía Médica & Grupo de Oncoloxía Médica Traslacional; Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS); Complexo Hospitalario Universitario de Santiago de Compostela; Santiago de Compostela Spain
| | - Jorge García-González
- Servizo de Oncoloxía Médica & Grupo de Oncoloxía Médica Traslacional; Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS); Complexo Hospitalario Universitario de Santiago de Compostela; Santiago de Compostela Spain
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