Rash, Drug Eruption

Key Features

Essentials of Diagnosis

• Usually, abrupt onset of widespread, symmetric erythematous eruption

• May mimic any inflammatory skin condition

• Constitutional symptoms (malaise, arthralgia, headache, and fever) may be present

General Considerations

• Only a minority of cutaneous drug reactions result from allergy

• Penicillin and other β-lactam antibiotics and trimethoprim-sulfamethoxazole are the most common causes of urticarial and maculopapular reactions

• Drug-induced hypersensitivity reaction (also known as drug eruption with eosinophilia and systemic symptoms [DRESS]) is most often caused by

  • Anticonvulsants

  • Allopurinol

  • Sulfonamides

• Stevens-Johnson syndrome/toxic epidermal necrolysis most commonly occur in response to

  • Antibiotics

  • Sulfonamides

  • Anticonvulsants

  • Allopurinol

  • NSAIDs

• Phenolphthalein, pyrazolone derivatives, tetracyclines, NSAIDs, trimethoprim-sulfamethoxazole, and barbiturates are the major causes of fixed drug eruptions

• Calcium channel blockers are a common cause of pruritus and eczemas in the elderly

Demographics

• Rashes are among the most common adverse reactions to drugs and occur in 2–3% of hospitalized patients

Clinical Findings

Symptoms and Signs

• Drug eruptions are generally classified as "simple" or "complex"

• Simple drug eruptions

  • Involve an exanthem

  • Usually appear in the second week of drug therapy

  • Have no associated constitutional or laboratory findings

  • Antibiotics, including the penicillins and quinolones, are most common causes

• Complex drug eruptions

  • Occur during the third week of treatment on average

  • Have constitutional and laboratory findings, including fevers, chills, hematologic abnormalities (especially eosinophilia), and abnormal liver chemistries or kidney function tests

  • A mnemonic for complex eruptions is "DRESS" (DRug Eruption with Eosinophilia and Systemic Symptoms)

  • Most common causes are the long-acting sulfonamides, allopurinol, and anticonvulsants

  • In patients of certain races, polymorphisms of antigen presenting major histocompatibility (MHC) loci increases risk for the development of severe drug eruptions

  • Coexistent reactivation of Epstein-Barr virus, HHV-6, or cytomegalovirus is often present and may be important in the pathogenesis of these complex drug eruptions

• See Table 6–3