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      Gemcitabine-induced skin necrosis

      case-report

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          Abstract

          Since its emergence as a chemotherapy agent, gemcitabine has been associated with cutaneous adverse reactions. Rash is reported to be the most common cutaneous adverse effect. Other reported cutaneous reactions in the literature include bullous dermatosis, pseudocellulitis, subacute cutaneous lupus alopecia, and palmar–plantar erythrodysesthesia. Skin necrosis is a very rare adverse effect of this otherwise well-tolerated chemotherapeutic agent. In searching the literature, only one other case has been reported. In our report, we present a 74-year-old male with adenocarcinoma of the pancreas, status-post pancreaticoduodenectomy (Whipple procedure), who developed a rare case of skin necrosis of the lower leg 2 weeks after completing six cycles of monotherapy gemcitabine treatment.

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          Gemcitabine: vascular toxicity and prothrombotic potential.

          Constantin A Dasanu (2008)
          Gemcitabine has been associated with important thrombotic and vascular side effects. As indications for its use in oncology and hematology are expanding, comprehensive characterization of these complications becomes imperative. This article reviews the prothrombotic potential and other vascular effects of gemcitabine and experience accrued through its use in research laboratories, clinical trials and clinical practice. The most relevant publications were identified through the PubMed database and by reviewing the drug information released by the FDA. In the author's opinion, the incidence of thrombotic and vascular toxicity with gemcitabine is higher than previously estimated. Venous thromboembolism (VTE) and acute arterial events, digital ischemia and necrosis, vasculitis and thrombotic microangiopathy, potentially fatal systemic capillary leak and reversible posterior leukoencephalopathy syndromes are only a few items on the long list of vascular-toxic effects of gemcitabine. These toxicities seem to be more frequent with the use of gemcitabine-platinum doublets than with gemcitabine alone. Careful consideration of gemcitabine use should be given in the setting of pre-existing arterial vascular disease, venous thromboembolism, collagenoses, heart failure, liver damage and advanced hepatic metastases. Specific treatment requirements of individual patients, their comorbidities and the gemcitabine risk:benefit ratio should be always sought before using this agent in antineoplastic therapy.
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            Digital ischemic events related to gemcitabine: Report of two cases and a systematic review

            Cvetka Kuhar, Tanja Mesti, Branko Zakotnik (2010)
            Background Gemcitabine is a potent cytotoxic agent used in the treatment of many solid tumours, sarcomas and lymphomas. Vascular toxicity and thrombotic events related to gemcitabine seem to be underreported. Case report We report two cases of gemcitabine related digital ischemic events. Case 1. A 65-year-old man was given the first-line treatment with gemcitabine for the advanced adenocarcinoma of pancreas. After four weekly doses of gemcitabine (total dose 4000 mg/m2) he presented with Raynaud’s like phenomenon and ischemic fingertips necrosis in five digits of both hands. Symptoms resolved in all but one digit after stopping chemotherapy and treatment with iloprost trometamol infusion. Case 2. A 77-year-old man, ex-smoker, was administered a combination of gemcitabine and cisplatin as the first-line treatment for the locally advanced bladder cancer. After 4 cycles of the treatment (total dose of gemcitabine 4000 mg/m2) the patient suffered digital ischemia and necrosis on two digits of a right leg. Arteriography revealed preexisting peripheral arterial occlusive disease (PAOD) of both legs with very good peripheral collateral circulation and absent microcirculation of affected two digits. The gemcitabine treatment was stopped and the patient was treated with iloprost trometamol infusion and percutaneous transluminal angioplasty with dilatation of the right superficial femoral artery. Digital changes resolved without consequences. Severe thrombocytosis (platelet count 1211 × 109/L) might have also contributed to the ischemic digital event in the second case. Conclusions Digital ischemic events associated with gemcitabine chemotherapy seem to be more common in patients with tobacco-associated cancers, especially when used in combination with platinum salt. The treatment with gemcitabine in patients with evolving Raynaud’s phenomenon and/or preexisting PAOD should be done with caution.
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              Pathogenesis of leukocytoclastic vasculitis.

              A Claudy (1998)
              There is compelling animal and human experimental evidence that leukocytoclastic vasculitis is a hypersensitivity vasculitis, similar in nature to the experimental Arthus reaction. The immune complexes formed in antigen excess circulate until some event occurs that cause deposition in blood vessel walls. Adhesion molecules and cytokines released by endothelial cells and activated neutrophils represent a key factor in this process. The membrane attack complex of complement plays a significant role in altering the endothelial cell membrane integrity. Activated neutrophils release proteolytic enzymes, especially collagenases and elastases, along with free oxygen radicals that damage the vessel walls and the surrounding tissues. It remains uncertain whether antineutrophilic cytoplasmic antibodies, anti-endothelial antibodies and anti-cardiolipin antibodies are epiphenomena or are directly involved in the disease process. Apoptotic cell death mediated by the Fas/Bc12 system is a feature of leucocytoclastic vasculitis. In conclusion, the post-capillary venule is the active orchestrator of neutrophils in leukocytoclastic vasculitis which mediate a complex series of endothelial/leukocyte interactions.
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                Author and article information

                Journal
                Journal ID (nlm-ta): SAGE Open Med Case Rep
                Journal ID (iso-abbrev): SAGE Open Med Case Rep
                Journal ID (publisher-id): SCO
                Journal ID (hwp): spsco
                Title: SAGE Open Medical Case Reports
                Publisher: SAGE Publications (Sage UK: London, England )
                ISSN (Electronic): 2050-313X
                Publication date (Electronic): 30 October 2018
                Publication date Collection: 2018
                Volume: 6
                Electronic Location Identifier: 2050313X18809268
                Affiliations
                [1 ]Gloucestershire Hospitals NHS Foundation Trust, Cheltenham, UK
                [2 ]Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
                Author notes
                [*]Maria Monica Haydock, Gloucestershire Hospitals NHS Foundation Trust, Sanford Road, Cheltenham GL53 7AN, UK. Email: mtalag@ 123456gmail.com
                Author information
                https://orcid.org/0000-0002-6420-6855
                Article
                Publisher ID: 10.1177_2050313X18809268
                DOI: 10.1177/2050313X18809268
                PMC ID: 6207959
                SO-VID: 1f6dc82a-33fc-4e99-9828-a3d16272d447
                Copyright © © The Author(s) 2018
                License:

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                Date received : 9 March 2018
                Date accepted : 4 October 2018
                Categories
                Subject: Case Report
                Custom metadata
                cover-date January-December 2018

                Keywords: oncology,gastroenterology/hepatology,pharmacoepidemiology/drug safety,chemotherapy,gemcitabine,pancreatic cancer,adverse skin reactions
                Data availability:
                Keywords: oncology, gastroenterology/hepatology, pharmacoepidemiology/drug safety, chemotherapy, gemcitabine, pancreatic cancer, adverse skin reactions

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