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SECTION 23: ADVERSE CUTANEOUS DRUG REACTIONS

ADVERSE CUTANEOUS DRUG REACTIONS ICD:10: T88.7

  • Adverse cutaneous drug reactions (ACDRs) are unpredictable They affect 2 to 3% of inpatients and lead to 0.1 to 0.3% of hospital fatalities1.

  • In the United States, adverse drug events account for up to 140,000 deaths and $136 billion in costs annually.

  • Most reactions are mild, accompanied by pruritus, and resolve promptly after the offending drug is discontinued.

  • Drug eruptions can mimic virtually all the morphologic expressions in dermatology and must be the first consideration in the differential diagnosis of a suddenly appearing eruption.

  • Drug eruptions are caused by immunologic or nonimmunologic mechanisms and are provoked by systemic or topical administration of a drug.

  • The majority are based on a hypersensitivity mechanism and are thus immunologic and may be of types I, II, III, or IV.

CLASSIFICATION

IMMUNOLOGICALLY MEDIATED ACDR (see Table 23-1) It should be noted that in most reactions both cellular and humoral immune reactions are involved. Nonimmunologic reactions are summarized in Table 23-2.

TABLE 23-1Immunologically Mediated Adverse Cutaneous Drug Reactions*
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TABLE 23-1 Immunologically Mediated Adverse Cutaneous Drug Reactions*
Type of Reaction Pathogenesis Examples of Causative Drug Clinical Patterns
Type I IgE-mediated; immediate-type immunologic reactions Penicillin, other antibiotics Urticaria/angioedema of skin/mucosa, edema of other organs, and anaphylactic shock
Type II Drug + cytotoxic antibodies cause lysis of cells such as platelets or leukocytes Penicillin, sulfonamides, quinidine, isoniazid Petechiae due to thrombocytopenic purpura, drug-induced pemphigus
Type III IgG or IgM antibodies formed to drug; immune complexes deposited in small vessels activate complement and recruitment of granulocytes Immunoglobulins, antibiotics, rituximab, infliximab Vasculitis, urticaria, serum sickness
Type IV Cell-mediated immune reaction; sensitized lymphocytes react with drug, liberating cytokines, which trigger cutaneous inflammatory response** Sulfamethoxazole, anticonvulsants, allopurinol Morbilliform exanthematous reactions, fixed drug eruption, lichenoid eruptions, Stevens–Johnson syndrome, toxic epidermal necrolysis

*After the Gell and Coombs classification of immune reactions.

**For contact sensitivity see Section 2.

TABLE 23-2Nonimmunologic Drug Reactions
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TABLE 23-2 Nonimmunologic Drug Reactions
Idiosyncrasy Reactions due to hereditary enzyme deficiencies
Individual idiosyncrasy to a topical or systemic drug Mechanisms not yet known
Cumulation Reactions are dose dependent, based on the total amount of drug ingested: pigmentation due to gold, amiodarone, or minocycline
Reactions due to combination of a drug with ultraviolet irradiation (photosensitivity) Reactions have a toxic pathogenesis but can also be immunologic in nature (see Section 10)
Irritancy/toxicity of a topically applied drug 5-Fluorouracil, imiquimod
Atrophy by topically applied drug Glucocorticoids

GUIDELINES FOR ASSESSMENT OF POSSIBLE ACDRS

  • Exclude alternative causes, especially infections (most commonly viral).

  • Examine interval between introduction of a drug and onset of the reaction.

  • Note any improvement after drug withdrawal.

  • Determine whether similar reactions have been associated with the same compound.

  • Note any reaction on ...

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