Erythema nodosum‐like panniculitis mimicking disease recurrence: A novel toxicity from immune checkpoint blockade therapy—Report of 2 patients
Immunotherapies targeting cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) and the programmed cell death 1 (PD‐1) receptor and its ligand (PD‐L1) have showed substantial therapeutic benefit in patients with clinically advanced solid malignancies. However, autoimmune toxicities are common and oft...
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Veröffentlicht in: | Journal of cutaneous pathology 2017-12, Vol.44 (12), p.1080-1086 |
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creator | Tetzlaff, Michael T. Jazaeri, Amir A. Torres‐Cabala, Carlos A. Korivi, Brinda R. Landon, Genie A. Nagarajan, Priyadharsini Choksi, Adrienne Chen, Leon Uemura, Marc Aung, Phyu P. Diab, Adi Sharma, Padmanee Davies, Michael A. Amaria, Rodabe Prieto, Victor G. Curry, Jonathan L. |
description | Immunotherapies targeting cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) and the programmed cell death 1 (PD‐1) receptor and its ligand (PD‐L1) have showed substantial therapeutic benefit in patients with clinically advanced solid malignancies. However, autoimmune toxicities are common and often significant adverse events with these agents. While rash and pruritus remain the most common cutaneous complications in treated patients, novel dermatologic toxicities related to immune checkpoint blockade continue to emerge as the number of patients exposed to immunotherapy increases. Here, we describe 2 patients treated with combination immunotherapy with ipilimumab and nivolumab who developed painful subcutaneous nodules. Although the findings were clinically concerning for disease recurrence, histopathologic examination of biopsies from the lesions revealed a subcutaneous mixed septal and lobular erythema nodosum‐like panniculitis. Notably, neither patient received immunosuppressive therapy for these lesions, which subsequently remained stable, and both patients’ cancer remained controlled. These cases show that the dermatologic toxicity profile of immune checkpoint blockade is diverse and continues to expand, and illustrates that recognition of such toxicities is critical to optimal patient management. |
doi_str_mv | 10.1111/cup.13044 |
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However, autoimmune toxicities are common and often significant adverse events with these agents. While rash and pruritus remain the most common cutaneous complications in treated patients, novel dermatologic toxicities related to immune checkpoint blockade continue to emerge as the number of patients exposed to immunotherapy increases. Here, we describe 2 patients treated with combination immunotherapy with ipilimumab and nivolumab who developed painful subcutaneous nodules. Although the findings were clinically concerning for disease recurrence, histopathologic examination of biopsies from the lesions revealed a subcutaneous mixed septal and lobular erythema nodosum‐like panniculitis. Notably, neither patient received immunosuppressive therapy for these lesions, which subsequently remained stable, and both patients’ cancer remained controlled. These cases show that the dermatologic toxicity profile of immune checkpoint blockade is diverse and continues to expand, and illustrates that recognition of such toxicities is critical to optimal patient management.</description><identifier>ISSN: 0303-6987</identifier><identifier>EISSN: 1600-0560</identifier><identifier>DOI: 10.1111/cup.13044</identifier><identifier>PMID: 28901560</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adult ; Antibodies, Monoclonal - adverse effects ; Antibodies, Monoclonal - therapeutic use ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents, Immunological - adverse effects ; anti‐CTLA‐4 ; anti‐PD‐1 ; anti‐PD‐L1 ; Apoptosis ; B7-H1 Antigen - drug effects ; Cancer ; Cell death ; CTLA-4 Antigen - antagonists & inhibitors ; CTLA-4 Antigen - drug effects ; CTLA-4 Antigen - metabolism ; CTLA-4 protein ; Cytotoxicity ; dermatologic toxicity ; Drug Eruptions - pathology ; Erythema ; Erythema nodosum ; Erythema Nodosum - chemically induced ; Erythema Nodosum - pathology ; Exanthema ; Female ; Humans ; Immune checkpoint ; immune checkpoint antibody ; Immunosuppressive agents ; Immunotherapy ; Immunotherapy - adverse effects ; Immunotherapy - methods ; Ipilimumab - adverse effects ; Ipilimumab - therapeutic use ; Lymphocytes T ; Middle Aged ; Mimicry ; Monoclonal antibodies ; Neoplasm Recurrence, Local - complications ; Nodules ; Panniculitis - chemically induced ; Panniculitis - pathology ; Patients ; PD-1 protein ; PD-L1 protein ; Programmed Cell Death 1 Receptor - antagonists & inhibitors ; Programmed Cell Death 1 Receptor - metabolism ; Pruritus ; Targeted cancer therapy ; Toxicity</subject><ispartof>Journal of cutaneous pathology, 2017-12, Vol.44 (12), p.1080-1086</ispartof><rights>2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3014-d1ca8b56028089cc2d87bb62979bce9f5a118b322a1d93b09c23baedbca3451d3</citedby><cites>FETCH-LOGICAL-c3014-d1ca8b56028089cc2d87bb62979bce9f5a118b322a1d93b09c23baedbca3451d3</cites><orcidid>0000-0003-0630-6222</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fcup.13044$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fcup.13044$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28901560$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tetzlaff, Michael T.</creatorcontrib><creatorcontrib>Jazaeri, Amir A.</creatorcontrib><creatorcontrib>Torres‐Cabala, Carlos A.</creatorcontrib><creatorcontrib>Korivi, Brinda R.</creatorcontrib><creatorcontrib>Landon, Genie A.</creatorcontrib><creatorcontrib>Nagarajan, Priyadharsini</creatorcontrib><creatorcontrib>Choksi, Adrienne</creatorcontrib><creatorcontrib>Chen, Leon</creatorcontrib><creatorcontrib>Uemura, Marc</creatorcontrib><creatorcontrib>Aung, Phyu P.</creatorcontrib><creatorcontrib>Diab, Adi</creatorcontrib><creatorcontrib>Sharma, Padmanee</creatorcontrib><creatorcontrib>Davies, Michael A.</creatorcontrib><creatorcontrib>Amaria, Rodabe</creatorcontrib><creatorcontrib>Prieto, Victor G.</creatorcontrib><creatorcontrib>Curry, Jonathan L.</creatorcontrib><title>Erythema nodosum‐like panniculitis mimicking disease recurrence: A novel toxicity from immune checkpoint blockade therapy—Report of 2 patients</title><title>Journal of cutaneous pathology</title><addtitle>J Cutan Pathol</addtitle><description>Immunotherapies targeting cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) and the programmed cell death 1 (PD‐1) receptor and its ligand (PD‐L1) have showed substantial therapeutic benefit in patients with clinically advanced solid malignancies. However, autoimmune toxicities are common and often significant adverse events with these agents. While rash and pruritus remain the most common cutaneous complications in treated patients, novel dermatologic toxicities related to immune checkpoint blockade continue to emerge as the number of patients exposed to immunotherapy increases. Here, we describe 2 patients treated with combination immunotherapy with ipilimumab and nivolumab who developed painful subcutaneous nodules. Although the findings were clinically concerning for disease recurrence, histopathologic examination of biopsies from the lesions revealed a subcutaneous mixed septal and lobular erythema nodosum‐like panniculitis. Notably, neither patient received immunosuppressive therapy for these lesions, which subsequently remained stable, and both patients’ cancer remained controlled. These cases show that the dermatologic toxicity profile of immune checkpoint blockade is diverse and continues to expand, and illustrates that recognition of such toxicities is critical to optimal patient management.</description><subject>Adult</subject><subject>Antibodies, Monoclonal - adverse effects</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Antineoplastic Agents - adverse effects</subject><subject>Antineoplastic Agents, Immunological - adverse effects</subject><subject>anti‐CTLA‐4</subject><subject>anti‐PD‐1</subject><subject>anti‐PD‐L1</subject><subject>Apoptosis</subject><subject>B7-H1 Antigen - drug effects</subject><subject>Cancer</subject><subject>Cell death</subject><subject>CTLA-4 Antigen - antagonists & inhibitors</subject><subject>CTLA-4 Antigen - drug effects</subject><subject>CTLA-4 Antigen - metabolism</subject><subject>CTLA-4 protein</subject><subject>Cytotoxicity</subject><subject>dermatologic toxicity</subject><subject>Drug Eruptions - pathology</subject><subject>Erythema</subject><subject>Erythema nodosum</subject><subject>Erythema Nodosum - chemically induced</subject><subject>Erythema Nodosum - pathology</subject><subject>Exanthema</subject><subject>Female</subject><subject>Humans</subject><subject>Immune checkpoint</subject><subject>immune checkpoint antibody</subject><subject>Immunosuppressive agents</subject><subject>Immunotherapy</subject><subject>Immunotherapy - adverse effects</subject><subject>Immunotherapy - methods</subject><subject>Ipilimumab - adverse effects</subject><subject>Ipilimumab - therapeutic use</subject><subject>Lymphocytes T</subject><subject>Middle Aged</subject><subject>Mimicry</subject><subject>Monoclonal antibodies</subject><subject>Neoplasm Recurrence, Local - complications</subject><subject>Nodules</subject><subject>Panniculitis - chemically induced</subject><subject>Panniculitis - pathology</subject><subject>Patients</subject><subject>PD-1 protein</subject><subject>PD-L1 protein</subject><subject>Programmed Cell Death 1 Receptor - antagonists & inhibitors</subject><subject>Programmed Cell Death 1 Receptor - metabolism</subject><subject>Pruritus</subject><subject>Targeted cancer therapy</subject><subject>Toxicity</subject><issn>0303-6987</issn><issn>1600-0560</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kM9u1DAQhy0EokvLgRdAljj1kNaOd7Nxb9Wq_JEqFaH2HNnjCXU3toPtQHPrIyDEE_ZJMN3SG3OZyze_n-Yj5A1nR7zMMUzjERdsuXxGFrxhrGKrhj0nCyaYqBrZrvfIq5RuGONN26xekr26lYwXZkF-ncU5X6NT1AcT0uTu734Odot0VN5bmAabbaLOOgtb679SYxOqhDQiTDGiBzyhp-X2Ow40h1sLNs-0j8FR69zkkcI1wnYM1meqhwBbZZCWwqjG-f7u9xccQ8w09LQujdmiz-mAvOjVkPD1494nV-_PLjcfq_OLD582p-cVCMaXleGgWl2eqFvWSoDatGutm1qupQaU_Upx3mpR14obKTSTUAut0GhQYrniRuyTd7vcMYZvE6bc3YQp-lLZcdk0kslitFCHOwpiSCli343ROhXnjrPur_2u2O8e7Bf27WPipB2aJ_Kf7gIc74AfdsD5_0nd5urzLvIPNYaT3w</recordid><startdate>201712</startdate><enddate>201712</enddate><creator>Tetzlaff, Michael T.</creator><creator>Jazaeri, Amir A.</creator><creator>Torres‐Cabala, Carlos A.</creator><creator>Korivi, Brinda R.</creator><creator>Landon, Genie A.</creator><creator>Nagarajan, Priyadharsini</creator><creator>Choksi, Adrienne</creator><creator>Chen, Leon</creator><creator>Uemura, Marc</creator><creator>Aung, Phyu P.</creator><creator>Diab, Adi</creator><creator>Sharma, Padmanee</creator><creator>Davies, Michael A.</creator><creator>Amaria, Rodabe</creator><creator>Prieto, Victor G.</creator><creator>Curry, Jonathan L.</creator><general>Blackwell Publishing Ltd</general><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><orcidid>https://orcid.org/0000-0003-0630-6222</orcidid></search><sort><creationdate>201712</creationdate><title>Erythema nodosum‐like panniculitis mimicking disease recurrence: A novel toxicity from immune checkpoint blockade therapy—Report of 2 patients</title><author>Tetzlaff, Michael T. ; Jazaeri, Amir A. ; Torres‐Cabala, Carlos A. ; Korivi, Brinda R. ; Landon, Genie A. ; Nagarajan, Priyadharsini ; Choksi, Adrienne ; Chen, Leon ; Uemura, Marc ; Aung, Phyu P. ; Diab, Adi ; Sharma, Padmanee ; Davies, Michael A. ; Amaria, Rodabe ; Prieto, Victor G. ; Curry, Jonathan L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3014-d1ca8b56028089cc2d87bb62979bce9f5a118b322a1d93b09c23baedbca3451d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Antibodies, Monoclonal - adverse effects</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Antineoplastic Agents - adverse effects</topic><topic>Antineoplastic Agents, Immunological - adverse effects</topic><topic>anti‐CTLA‐4</topic><topic>anti‐PD‐1</topic><topic>anti‐PD‐L1</topic><topic>Apoptosis</topic><topic>B7-H1 Antigen - drug effects</topic><topic>Cancer</topic><topic>Cell death</topic><topic>CTLA-4 Antigen - antagonists & inhibitors</topic><topic>CTLA-4 Antigen - drug effects</topic><topic>CTLA-4 Antigen - metabolism</topic><topic>CTLA-4 protein</topic><topic>Cytotoxicity</topic><topic>dermatologic toxicity</topic><topic>Drug Eruptions - pathology</topic><topic>Erythema</topic><topic>Erythema nodosum</topic><topic>Erythema Nodosum - chemically induced</topic><topic>Erythema Nodosum - pathology</topic><topic>Exanthema</topic><topic>Female</topic><topic>Humans</topic><topic>Immune checkpoint</topic><topic>immune checkpoint antibody</topic><topic>Immunosuppressive agents</topic><topic>Immunotherapy</topic><topic>Immunotherapy - adverse effects</topic><topic>Immunotherapy - methods</topic><topic>Ipilimumab - adverse effects</topic><topic>Ipilimumab - therapeutic use</topic><topic>Lymphocytes T</topic><topic>Middle Aged</topic><topic>Mimicry</topic><topic>Monoclonal antibodies</topic><topic>Neoplasm Recurrence, Local - complications</topic><topic>Nodules</topic><topic>Panniculitis - chemically induced</topic><topic>Panniculitis - pathology</topic><topic>Patients</topic><topic>PD-1 protein</topic><topic>PD-L1 protein</topic><topic>Programmed Cell Death 1 Receptor - antagonists & inhibitors</topic><topic>Programmed Cell Death 1 Receptor - metabolism</topic><topic>Pruritus</topic><topic>Targeted cancer therapy</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tetzlaff, Michael T.</creatorcontrib><creatorcontrib>Jazaeri, Amir A.</creatorcontrib><creatorcontrib>Torres‐Cabala, Carlos A.</creatorcontrib><creatorcontrib>Korivi, Brinda R.</creatorcontrib><creatorcontrib>Landon, Genie A.</creatorcontrib><creatorcontrib>Nagarajan, Priyadharsini</creatorcontrib><creatorcontrib>Choksi, Adrienne</creatorcontrib><creatorcontrib>Chen, Leon</creatorcontrib><creatorcontrib>Uemura, Marc</creatorcontrib><creatorcontrib>Aung, Phyu P.</creatorcontrib><creatorcontrib>Diab, Adi</creatorcontrib><creatorcontrib>Sharma, Padmanee</creatorcontrib><creatorcontrib>Davies, Michael A.</creatorcontrib><creatorcontrib>Amaria, Rodabe</creatorcontrib><creatorcontrib>Prieto, Victor G.</creatorcontrib><creatorcontrib>Curry, Jonathan L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of cutaneous pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tetzlaff, Michael T.</au><au>Jazaeri, Amir A.</au><au>Torres‐Cabala, Carlos A.</au><au>Korivi, Brinda R.</au><au>Landon, Genie A.</au><au>Nagarajan, Priyadharsini</au><au>Choksi, Adrienne</au><au>Chen, Leon</au><au>Uemura, Marc</au><au>Aung, Phyu P.</au><au>Diab, Adi</au><au>Sharma, Padmanee</au><au>Davies, Michael A.</au><au>Amaria, Rodabe</au><au>Prieto, Victor G.</au><au>Curry, Jonathan L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Erythema nodosum‐like panniculitis mimicking disease recurrence: A novel toxicity from immune checkpoint blockade therapy—Report of 2 patients</atitle><jtitle>Journal of cutaneous pathology</jtitle><addtitle>J Cutan Pathol</addtitle><date>2017-12</date><risdate>2017</risdate><volume>44</volume><issue>12</issue><spage>1080</spage><epage>1086</epage><pages>1080-1086</pages><issn>0303-6987</issn><eissn>1600-0560</eissn><abstract>Immunotherapies targeting cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA‐4) and the programmed cell death 1 (PD‐1) receptor and its ligand (PD‐L1) have showed substantial therapeutic benefit in patients with clinically advanced solid malignancies. However, autoimmune toxicities are common and often significant adverse events with these agents. While rash and pruritus remain the most common cutaneous complications in treated patients, novel dermatologic toxicities related to immune checkpoint blockade continue to emerge as the number of patients exposed to immunotherapy increases. Here, we describe 2 patients treated with combination immunotherapy with ipilimumab and nivolumab who developed painful subcutaneous nodules. Although the findings were clinically concerning for disease recurrence, histopathologic examination of biopsies from the lesions revealed a subcutaneous mixed septal and lobular erythema nodosum‐like panniculitis. Notably, neither patient received immunosuppressive therapy for these lesions, which subsequently remained stable, and both patients’ cancer remained controlled. These cases show that the dermatologic toxicity profile of immune checkpoint blockade is diverse and continues to expand, and illustrates that recognition of such toxicities is critical to optimal patient management.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>28901560</pmid><doi>10.1111/cup.13044</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-0630-6222</orcidid></addata></record> |
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subjects | Adult Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal - therapeutic use Antineoplastic Agents - adverse effects Antineoplastic Agents, Immunological - adverse effects anti‐CTLA‐4 anti‐PD‐1 anti‐PD‐L1 Apoptosis B7-H1 Antigen - drug effects Cancer Cell death CTLA-4 Antigen - antagonists & inhibitors CTLA-4 Antigen - drug effects CTLA-4 Antigen - metabolism CTLA-4 protein Cytotoxicity dermatologic toxicity Drug Eruptions - pathology Erythema Erythema nodosum Erythema Nodosum - chemically induced Erythema Nodosum - pathology Exanthema Female Humans Immune checkpoint immune checkpoint antibody Immunosuppressive agents Immunotherapy Immunotherapy - adverse effects Immunotherapy - methods Ipilimumab - adverse effects Ipilimumab - therapeutic use Lymphocytes T Middle Aged Mimicry Monoclonal antibodies Neoplasm Recurrence, Local - complications Nodules Panniculitis - chemically induced Panniculitis - pathology Patients PD-1 protein PD-L1 protein Programmed Cell Death 1 Receptor - antagonists & inhibitors Programmed Cell Death 1 Receptor - metabolism Pruritus Targeted cancer therapy Toxicity |
title | Erythema nodosum‐like panniculitis mimicking disease recurrence: A novel toxicity from immune checkpoint blockade therapy—Report of 2 patients |
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