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J Allergy Clin Immunol Pract. 2017 May - Jun;5(3):547-563. doi: 10.1016/j.jaip.2017.01.025.

Severe Delayed Cutaneous and Systemic Reactions to Drugs: A Global Perspective on the Science and Art of Current Practice.

Author information

1
Division of Allergology and Clinical Immunology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
2
Division of Dermatology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
3
Division of Infectious Diseases, Department of Medicine, University of Cape Town, Cape Town, South Africa.
4
Division of Allergy, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
5
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn.
6
Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tenn.
7
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tenn; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tenn; Institute for Immunology & Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia. Electronic address: elizabeth.j.phillips@vanderbilt.edu.

Abstract

Most immune-mediated adverse drug reactions (IM-ADRs) involve the skin, and many have additional systemic features. Severe cutaneous adverse drug reactions (SCARs) are an uncommon, potentially life-threatening, and challenging subgroup of IM-ADRs with diverse clinical phenotypes, mechanisms, and offending drugs. T-cell-mediated immunopathology is central to these severe delayed reactions, but effector cells and cytokines differ by clinical phenotype. Strong HLA-gene associations have been elucidated for specific drug-SCAR IM-ADRs such as Stevens-Johnson syndrome/toxic epidermal necrolysis, although the mechanisms by which carriage of a specific HLA allele is necessary but not sufficient for the development of many IM-ADRs is still being defined. SCAR management is complicated by substantial short- and long-term morbidity/mortality and the potential need to treat ongoing comorbid disease with related medications. Multidisciplinary specialist teams at experienced units should care for patients. In the setting of SCAR, patient outcomes as well as preventive, diagnostic, treatment, and management approaches are often not generalizable, but rather context specific, driven by population HLA-genetics, the pharmacology and genetic risk factors of the implicated drug, severity of underlying comorbid disease necessitating ongoing treatments, and cost considerations. In this review, we update the basic and clinical science of SCAR diagnosis and management.

KEYWORDS:

DRESS; HLA; Immune-mediated adverse drug reactions; SJS/TEN; Severe cutaneous adverse drug reactions; T-cell

PMID:
28483310
PMCID:
PMC5424615
DOI:
10.1016/j.jaip.2017.01.025
[Indexed for MEDLINE]
Free PMC Article

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