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      Anticancer Drugs Induced Severe Adverse Cutaneous Drug Reactions: An Updated Review on the Risks Associated with Anticancer Targeted Therapy or Immunotherapies

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          Abstract

          Cutaneous adverse drug reactions are commonly seen in patients with anticancer drug treatment. Anticancer drugs, including chemotherapy, target therapy, and recent immunotherapy causing skin reactions ranging from mild skin rash to life-threatening severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) with increase morbidity and mortality while they are receiving cancer treatments, have been proposed to be a result of direct skin toxicity or drug hypersensitivity reactions (these are proposed mechanism, not definite). Differentiating SCARs from other more commonly seen reactions with a better outcome help prevent discontinuation of therapy and inappropriate use of systemic immunosuppressants for presumable allergic reactions, of which will affect the clinical outcome. In this article, we have reviewed published articles from 1950 to August 2017 for SJS/TEN associated with anticancer drugs, including chemotherapy, targeted therapy, and immunotherapy. We aimed to provide an overview of SJS/TEN associated with anticancer drugs to increase clinician recognition and accelerate future studies on the pathomechanism and managements.

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          SCORTEN: a severity-of-illness score for toxic epidermal necrolysis.

          S Bastuji-Garin, N Fouchard, M. Bertocchi … (2000)
          The mortality of toxic epidermal necrolysis is about 30%. Our purpose was to develop and validate a specific severity-of-illness score for cases of toxic epidermal necrolysis admitted to a specialized unit and to compare it with the Simplified Acute Physiology Score and a burn scoring system. A sample of 165 patients was used to develop the toxic epidermal necrolysis-specific severity-of-illness score and evaluate the other scores, a sample of 75 for validation. Model development used logistic regression equations that were translated into probability of hospital mortality; validation used measures of calibration and discrimination. We identified seven independent risk factors for death and constituted the toxic epidermal necrolysis-specific severity-of-illness score: age above 40 y, malignancy, tachycardia above 120 per min, initial percentage of epidermal detachment above 10%, serum urea above 10 mmol per liter, serum glucose above 14 mmol per liter, and bicarbonate below 20 mmol per liter. For each toxic epidermal necrolysis-specific severity-of-illness score point the odds ratio was 3.45 (confidence interval 2.26-5.25). Probability of death was: P(death) = elogit/1 + elogit with logit = -4.448 + 1.237 (toxic epidermal nec-rolysis-specific severity-of-illness score). Calibration demonstrated excellent agreement between expected (19. 6%) and actual (20%) mortality; discrimination was also excellent with a receiver operating characteristic area of 82%. The Simplified Acute Physiology Score and the burn score were also associated with mortality. The discriminatory powers were poorer (receiver operating characteristic area: 72 and 75%) and calibration of the Simplified Acute Physiology Score indicated a poor agreement between expected (9.1%) and actual (26.7%) mortality. This study demonstrates that the risk of death of toxic epidermal necrolysis patients can be accurately predicted by the toxic epidermal necrolysis-specific severity-of-illness score. The Simplified Acute Physiology Score and burn score appear to be less adequate.
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            ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson Syndrome and toxic epidermal necrolysis: comparison with case-control analysis.

            A Dunant, Anh Le, D Vieluf … (2010)
            Epidermal necrolysis (EN)--either Stevens-Johnson syndrome (SJS) or toxic EN (TEN)--is a severe drug reaction. We constructed and evaluated a specific algorithm, algorithm of drug causality for EN (ALDEN), in order to improve the individual assessment of drug causality in EN. ALDEN causality scores were compared with those from the French pharmacovigilance method in 100 cases and the case-control results of the EuroSCAR study. Scores attributed by ALDEN segregated widely. ALDEN pointed to a "probable" or "very probable" causality in 69/100 cases as compared to 23/100 with the French method (P < 0.001). It scored "very unlikely" causality for 64% of medications vs. none with the French method. Results of ALDEN scores were strongly correlated with those of the EuroSCAR case-control analysis for drugs associated with EN (r = 0.90, P < 0.0001), with probable causality being reported in 218/329 exposures. ALDEN excluded causality in 321 drugs that the case-control analysis had described as "probably not associated" and in 22/233 drugs that had been described as inconclusive exposures. Being more sensitive than a general method, ALDEN, which correlates well with case-control analysis results, can be considered a reference tool in SJS/TEN.
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              The lymphocyte transformation test in the diagnosis of drug hypersensitivity.

              W Pichler, J Tilch (2004)
              Diagnosis of drug hypersensitivity is difficult, as an enormous amount of different drugs can elicit various immune-mediated diseases with distinct pathomechanism. The lymphocyte transformation test (LTT) measures the proliferation of T cells to a drug in vitro--from which one concludes to a previous in vivo reaction due to a sensitization. This concept of the LTT has been confirmed by the generation of drug-specific T-cell clones and the finding that drugs can directly interact with the T-cell receptor, without previous metabolism or need to bind to proteins. In this review, technical aspects and usefulness of this test for the diagnosis of drug hypersensitivity are discussed. The main advantage of this test is its applicability with many different drugs in different immune reactions, as drug-specific T cell are almost always involved in drug hypersensitivity reactions. Its main disadvantages are that an in vitro proliferation of T cells to a drug is difficult to transfer to the clinical situation and that the test per se is rather cumbersome and technically demanding. In addition, its sensitivity is limited (for beta-lactam allergy it is in the range of 60-70%), - although at least in our hands - it is higher than of other tests for drug hypersensitivity diagnosis. Consequently, drug hypersensitivity diagnosis needs to rely on a combination of history and different tests, as none of the single tests available has per se a sufficiently good sensitivity. Within this setting, the LTT has proven to be a useful test for the diagnosis of drug hypersensitivity reactions and helped to better understand these reactions. Further work on the simplification of this test and systematic evaluation of its sensitivity and specificity in some main groups of drugs are necessary to make this test more widely available.
              Article 0 comments Cited 141 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Chun-Wei Lu:
                ORCID: http://orcid.org/0000-0002-9341-4012
                Journal
                Journal ID (nlm-ta): J Immunol Res
                Journal ID (iso-abbrev): J Immunol Res
                Journal ID (publisher-id): JIR
                Title: Journal of Immunology Research
                Publisher: Hindawi
                ISSN (Print): 2314-8861
                ISSN (Electronic): 2314-7156
                Publication date Collection: 2018
                Publication date (Electronic): 17 January 2018
                Volume: 2018
                Electronic Location Identifier: 5376476
                Affiliations
                1Department of Dermatology, College of Medicine, Chang Gung Memorial Hospital, Keelung, Linkou, Taipei, Taiwan
                2Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Taipei, Taiwan
                3School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
                4Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan
                Author notes

                Academic Editor: Riichiro Abe

                Author information
                http://orcid.org/0000-0001-7576-963X
                http://orcid.org/0000-0002-7378-4235
                http://orcid.org/0000-0002-9341-4012
                Article
                DOI: 10.1155/2018/5376476
                PMC ID: 5822766
                PubMed ID: 29577050
                SO-VID: 283fd9f2-0138-43ab-b20f-86fa70768d68
                Copyright © Copyright © 2018 Chau Yee Ng et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 31 August 2017
                Date revision received : 7 November 2017
                Date accepted : 8 November 2017
                Categories
                Subject: Review Article

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