Document Detail


Phenotypic diversity in delayed drug hypersensitivity: an immunologic explanation.
MedLine Citation:
PMID:  17008937     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Drug hypersensitivity reactions are a significant cause of iatrogenic-induced illness. (They were originally classified as type IV hypersensitivity, to describe the tuberculin skin reaction.) It now appears that the T-cell directs the entire inflammatory cascade induced by delayed drug allergy. Delayed drug hypersensitivity, usually manifested in the skin, is triggered when drug-specific CD4+ and CD8+ T cells recognize drugs through their T-cell receptors in a process that is dependent on a major histocompatibility complex. Drugs stimulate T-cell receptors by either covalently binding to peptides or using their structural features to interact via a more direct approach. Immunohistochemical and functional analysis of drug-reactive T-cell clones has shown that the phenotypic pattern of delayed drug hypersensitivity depends on the cytokine pattern induced. For example, maculo-papular exanthema may be either TH-1 or TH-2 in nature, depending on whether they are interferon- g /tumor necrosis factor- a or interleukin-4, 5 and 13 driven. Bullous reactions to drugs (i.e., Stevens-Johnson syndrome or toxic epidermal necrolysis) are characterized by widespread keratinocyte apoptosis, a consequence of high CD8+ T-cell involvement and the molecular cytotoxicity of Fas, perforin and granzyme B. Pustular exanthema reactions to medications are stimulated via the T-cell release of IL-8 and granulocyte-monocyte colony-stimulating factor (GM-CSF). With better understanding of these unique inflammatory cascades, delayed type IV hypersensitivity reactions have been re-classified into four main subtypes: IVa (TH-1/monocyte directed), IVb (TH-2/eosinophil directed), IVc (CD8+/ Fas/perforin/Granzyme B directed) and IVd (IL-8/GM-CSF/neutrophil directed). Clinically, delayed hypersensitivity eruptions are often an overlap of cytokine pathways, with one preferential reaction dominating the final picture.
Authors:
Marc J Meth; Kirk E Sperber
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Publication Detail:
Type:  Clinical Conference; Journal Article; Review    
Journal Detail:
Title:  The Mount Sinai journal of medicine, New York     Volume:  73     ISSN:  0027-2507     ISO Abbreviation:  Mt. Sinai J. Med.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-09-29     Completed Date:  2006-11-28     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0241032     Medline TA:  Mt Sinai J Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  769-76     Citation Subset:  IM    
Affiliation:
Department of Allergy/Immunology, Mount Sinai School of Medicine, Box 1089, One Gustave L. Levy Place, New York, NY 10029, USA.
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MeSH Terms
Descriptor/Qualifier:
Drug Hypersensitivity / genetics*,  immunology
Genetic Variation*
Humans
Phenotype*
T-Lymphocytes
Time Factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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