{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T01:58:01Z","timestamp":1789178281708,"version":"build-2803163510"},"reference-count":8,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Palliat Med"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Immunotherapy is increasingly used in the management of early and advanced malignancy. There is limited data regarding the associations between immunotherapy, malignancy, pain and haemophagocytic lymphohistiocytosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case:<\/jats:title>\n                    <jats:p>A 40-year-old woman was diagnosed with advanced melanoma, with metastases to her brain, liver, lung, adrenal glands and bone. She had moderate opioid requirements prior to the initiation of therapy. Following doublet immunotherapy with nivolumab and ipilimumab, she experienced a severe pain crisis associated with pyrexia and haemophagocytic lymphohistiocytosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Possible courses of action:<\/jats:title>\n                    <jats:p>Management dilemmas included whether or not to initiate non-steroidal and steroidal anti-inflammatory therapies, how to address the patient\u2019s nociceptive, neuropathic and inflammatory pain, and how to manage the haemophagocytic lymphohistiocytosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Formulation of management plan:<\/jats:title>\n                    <jats:p>The patient required rapid up-titration of analgesia, including methadone, ketamine, hydromorphone, pregabalin and benzodiazepines. Ketorolac and high dose steroid therapy were administered for pain management and to mitigate treatment associated inflammation and haemophagocytic lymphohistiocytosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcome:<\/jats:title>\n                    <jats:p>The patient\u2019s pain was inadequately managed despite multimodal analgesia, and stigmata of inflammation progressed. She died 14\u2009days following treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Lessons:<\/jats:title>\n                    <jats:p>The case demonstrates that severe pain may be a consequence of immunotherapy given for advanced, high volume melanoma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Research avenues:<\/jats:title>\n                    <jats:p>There is laboratory evidence suggesting an association between immunotherapy, malignancy, pain and haemophagocytic lymphohistiocytosis. Further clinical evidence is required in order to understand these intersecting phenomena.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02692163211001295","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T02:45:28Z","timestamp":1616640328000},"page":"972-976","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Immunotherapy associated pain crisis and the haemophagocytic lymphohistiocytosis syndrome in advanced melanoma: Case report and review of the literature"],"prefix":"10.1177","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6287-3593","authenticated-orcid":false,"given":"Michael","family":"Krasovitsky","sequence":"first","affiliation":[{"name":"Comprehensive Cancer Centre, Prince of Wales Hospital, Randwick, NSW, Australia"},{"name":"Cancer Care Centre, St. George Hospital, Kogarah, NSW, Australia"},{"name":"Faculty of Medicine, Prince of Wales Clinical School, University of New South Wales, Randwick, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4542-7097","authenticated-orcid":false,"given":"Jessica","family":"Borbasi","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Centre, Prince of Wales Hospital, Randwick, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,3,24]]},"reference":[{"key":"bibr1-02692163211001295","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709684"},{"key":"bibr2-02692163211001295","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4571"},{"key":"bibr3-02692163211001295","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf8924"},{"key":"bibr4-02692163211001295","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4569-09.2009"},{"key":"bibr5-02692163211001295","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003335"},{"key":"bibr6-02692163211001295","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21039"},{"key":"bibr7-02692163211001295","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-018-0365-3"},{"key":"bibr8-02692163211001295","doi-asserted-by":"publisher","DOI":"10.1038\/nature22396"}],"container-title":["Palliative Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02692163211001295","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/02692163211001295","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02692163211001295","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:31:06Z","timestamp":1777660266000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/02692163211001295"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,24]]},"references-count":8,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,5]]}},"alternative-id":["10.1177\/02692163211001295"],"URL":"https:\/\/doi.org\/10.1177\/02692163211001295","relation":{},"ISSN":["0269-2163","1477-030X"],"issn-type":[{"value":"0269-2163","type":"print"},{"value":"1477-030X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,24]]}}}