Cutaneous Drug Reactions

Descriptive text is not available for this image BASICS

DESCRIPTION

  • Defined as an adverse cutaneous reaction in response to administration of a drug. Rashes are the most common form of adverse drug reaction (ADR) (1).
  • Severity can range from mild eruption that resolves within 24 hours after the removal of the inciting agent, to severe skin damage with multiorgan involvement.
  • Morbilliform and urticarial eruptions are most common, accounting for approximately 94% of cutaneous drug reactions
  • Approximately 2% are life-threatening.

EPIDEMIOLOGY

  • All ages are affected; immunosuppressed individuals are at increased risk
  • Increased likelihood of severe cutaneous and systemic reactions in the 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%; 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. These make up the majority of cutaneous drug reactions.
  • Unpredictable (type B): drug intolerance, drug idiosyncrasy (due to metabolism abnormality), 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; immune mediated is the least common.
  • Most common medications causing cutaneous drug reactions: carbamazepine and phenytoin.
  • >700 drugs are known culprits.

Genetics

Genetics may play a role; 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 Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).
  • HLA-DQB1*0301 allele found in 66% of patients of erythema multiforme compared with 31% of control subjects

RISK FACTORS

The most common risk factor is immunosuppression; Genetic predisposition or autoimmunity are less frequent risk factors.

GENERAL PREVENTION

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

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