Cutaneous Drug Reactions

Basics

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.

There's more to see -- the rest of this topic is available only to subscribers.