TABLE 1.
Classification, Clinical Features, and Management of Classic Hypersensitivity Reactions to Antibiotics
| Gell and Coombs Classification | Immune Mechanism | Clinical Features | Timing |
|---|---|---|---|
| Type I: immediate-type hypersensitivity | Mast cell and/or basophil mediator release directed by drug interaction and/or cross-linking of drug-specific IgE bound to these cells | Anaphylaxis, urticaria, angioedema, gastrointestinal, respiratory, cardiovascular, and neurologic symptoms | Immediate: <1 h after drug exposure |
| Type II: cytotoxic or antibody dependent, hypersensitivity | Natural killer cells and macrophages kill IgG- or IgM-coated cells that are directed against the drug or drug metabolite on the patient’s cells | Drug-induced hemolytic anemia, thrombocytopenia | 1–2 wk after exposurea |
| Type III: immune complex–mediated hypersensitivity | Antibody (IgG>IgM) binds to soluble antigen (often a drug or drug metabolite), forming a circulating immune complex | Serum sickness, vasculitis | 1–2 wk after exposurea |
| Type IV: delayed-type hypersensitivities | An antigen-presenting cell expressing HLA bound to a peptide interacts with a T-cell receptor in the presence of a drug or drug metaboliteb,61 | Benign, delayed skin rashes | Nonimmediate: differs according to the specific phenotype (Table 3) but generally 24 h to 1 wk after first exposure and can be quicker (h) on rechallenge exposure |
| Type IVa | Allergic contact dermatitis, maculopapular exanthema, FDE, EM (typically infection, not drug) | ||
| Type IVb | More severe cutaneous skin rashes | ||
| Type IVc | Acute generalized exanthematous pustulosis, DRESS syndrome, SJS and/or TEN, generalized-bullous FDE | ||
| Type IVd |
EM, erythema multiforme; FDE, fixed drug eruption; HLA, human leukocyte antigen; IgG, immunoglobulin G; IgM, immunoglobulin M.
a
May be sooner if preformed antibodies.
b
Multiple models have been proposed including hapten/prohapten model, pharmacological interaction (p-i) model and altered peptide repertoire model. In the hapten/prohapten model, a drug/drug metabolite covalently bound to larger protein undergoes intracellular processing to generate modified peptides that are incorporated onto HLA proteins for presentation to T cells.61