Description

• An adverse cutaneous reaction in response to administration of a drug. Rashes are the most common form of adverse drug reaction (ADR).
• Severity can range from mild eruptions that resolve within 24 hours after the removal of the inciting agent, to severe skin damage with multiorgan involvement.
• Morbilliform and urticarial eruptions are the most common, accounting for approximately 94% of cutaneous drug reactions.
• Approximately 2% are severe and life-threatening.

Epidemiology

• All ages affected; immunosuppressed individuals at increased risk
• Increased likelihood of severe cutaneous and systemic reactions in geriatric population; unclear if due to polypharmacy or change in drug metabolism
• Difficult to distinguish from viral exanthems in pediatric patients

Incidence
In the United States, incidence of 1–3% in hospitalized patients; estimated 1/1,000 hospitalized patients has had a severe cutaneous reaction.

Etiology and Pathophysiology

Two classifications of ADR:

• Predictable (type A): dose dependent, known pharmacologic effect of drug, and drug–drug interaction
• Unpredictable (type B): drug intolerance, drug idiosyncrasy secondary to abnormality in metabolism, drug allergy, and drug pseudoallergy
• Immunologically mediated reaction: immunoglobulin (Ig) E–mediated reaction (type I hypersensitivity), cytotoxic/IgG/IgM induced (type II), immune complex reactions (type III), and delayed-type hypersensitivity (type IV) with T cells, eosinophils, neutrophils, and monocytes
• The most common medications causing adverse cutaneous reactions are carbamazepine and phenytoin.
• >700 drugs are known to cause cutaneous drug reactions.

Genetics
Genetics may play a role because certain HLA antigens have been associated with increased predisposition to specific drug eruptions:

• HLA-B*5801, HLA-B*5701, and HLA-B*1502 have been linked to allopurinol-induced and carbamazepine-induced SJS/TEN, respectively; CYP2C9*3 variants linked to phenytoin-induced SJS/TEN
• HLA-DQB1*0301 allele found in 66% of patients of erythema multiforme compared with 31% of control subjects

General Prevention

Always ask the patients about prior adverse drug events. Be aware of medications with higher incidence of reactions as well as drug–drug reaction.