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Received Jan 11, 2018; Accepted Apr 29, 2018
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1. Introduction
Adverse immunologically mediated oral mucosal reactions to systemic medications are not uncommon, are variable in nature, and appear to be genetically determined. Most are mild, but some can be severe and even life threatening; so, prompt diagnosis, immediate withdrawal of the offending drug, and appropriate treatment are crucial [1].
The phenotypic diversity of drug-induced immune hypersensitivity reactions is the outcome of a complex and dynamic pathogenic process. Depending on their molecular concentration and on the context of the microenvironment, different molecular signals can mediate different or sometimes similar immunological effects; and there are interactions between multiple genes, cellular pathways, and cells. The aggregate of this integrated activity is not linear and cannot be derived from summation of the activities of the singular pathways, genes, or cells [2–4].
Susceptibility to adverse drug reactions may be increased by genetic factors determining drug metabolism, such as genetic polymorphism of cytochrome p450 enzymes, drug acetylation and methylation, and the genetic variants determining the type and magnitude of certain immune responses. These determinants include the specific human leukocyte antigen (HLA) haplotype, the T cell receptor (TCR) repertoire, or the toll-like receptor activity [1, 5]. Subjects with vascular collagen diseases, with Epstein–Barr or human immunodeficiency virus (HIV) infections, and recipients of bone marrow grafts are at increased risk of adverse drug reactions, probably because of their related immune suppression or immune dysregulation [1, 6].
Systemic medications may induce different drug-specific immunoinflammatory hypersensitivity responses including type I immunoglobulin E- (IgE-) mediated, type II IgG-mediated, type III immune complex, and type IV T cell-mediated reactions [1]. Each of these may cause a variety of oral mucosal drug eruptions [7].
In the context of drug-induced allergic reactions, the allergen may be the drug itself, a drug metabolite, a vehicle, or a preservative of the medicine. The allergen functions as a hapten, forming immunological conjugates with tissue proteins, which may then on occasion act as immunogens. In genetically predisposed subjects, allergenic medications may de novo induce immune-mediated oral mucosal diseases, may unmask latent subclinical diseases,...