Drug Hypersensitivity: Epidemiology and Risk Factors

Abstract

Drug allergies are heterogeneous and multifactorial diseases and are always the consequence of an exaggerated immune-mediated reaction. Previously described models of immunologic mechanisms (mainly based on Gell and Combs' classification) cannot fully explain the physiopathology of these diseases; it seems therefore important to identify risk factors. Clinical and biologic tests are helpful diagnostic tools but are limited in their sensitivity and reliability and are certainly not predictive. Epidemiologic data supply information concerning the prevalence of drug hypersensitivity: female gender, concomitant infections (HIV, herpes) and concurrent illnesses (systemic lupus erythematosus) are all significant risk factors. Another host-related factor is the genetic predisposition of patients and is currently under investigation in our laboratory. Most genetic studies concern HLA haplotype association or polymorphism in genes encoding drug-metabolising enzymes. A current study by our group seems to implicate polymorphisms within the promoter of IL-10, a cytokine with anti-inflammatory properties. The chemical properties of the drug and the treatment regimen also influence the development of drug allergies.

Direct interaction between HLA-B and carbamazepine activates T cells in patients with Stevens-Johnson syndrome

“…The drug hypersensitivity reactions in patients might be manifested by many cofactors, such as individual medical history, coadministered drugs, underlying diseases, viral infections, regulatory T-cell population/function, genetic polymorphisms of metabolic enzymes/immune-related genes, or autoimmune disorders. 39,40 Therefore the results presented in this study could not be extrapolated simply to the clinical situations of patients.…”

Shared and restricted T-cell receptor use is crucial for carbamazepine-induced Stevens-Johnson syndrome

“…For example, subjects with a prior medical history of viral infection (eg, HIV and human herpesvirus) or autoimmune disorders (eg, systemic lupus erythematosus) have been noted to be more susceptible to drug hypersensitivity. 33,34 Because OXC is the prodrug of CBZ and they share structural similarity, the cross-reactivity between CBZ and OXC to T cells has been examined in patients, and it has been reported that 33% of the patients who had a CBZ-induced rash also had OXC hypersensitivity. 35 T cells isolated from patients with CBZ hypersensitivity showed cross-reactivity to OXC in vitro.…”

Drug Allergies May Be More Frequent in Systemic Lupus Erythematosus Than in Rheumatoid Arthritis

“…Among these are women, HIV and herpes-infected patients, and systemic patients with lupus erythematosus (SLE). 2 As a general principle, patients with SLE seem to have higher frequencies of hypersensitivity reactions to antibiotics than healthy populations. 3 In this study, we compared the frequency of drug allergies between 2 autoimmune diseases from the same urban population.…”