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Section 23: Adverse Cutaneous Drug Reactions

ADVERSE CUTANEOUS DRUG REACTIONS ICD-10: T88.7

  • Adverse cutaneous drug reactions (ACDRs) are unpredictable1. They affect 2% to 3% of inpatients and lead to 0.1% to 0.3% of hospital fatalities.

  • 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)

TABLE 23-1Immunologically Mediated Adverse Cutaneous Drug Reactionsa
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TABLE 23-1 Immunologically Mediated Adverse Cutaneous Drug Reactionsa
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 responseb

Sulfamethoxazole, anticonvulsants, allopurinol

Morbilliform exanthematous reactions, fixed drug eruption, lichenoid eruptions, Stevens–Johnson syndrome, toxic epidermal necrolysis

aAfter the Gell and Coombs classification of immune reactions.

bFor contact sensitivity see Section 2.

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 23-2Nonimmunologic Drug Reactions
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TABLE 23-2 Nonimmunologic Drug Reactions

Idiosyncrasy

Reactions due to hereditary enzyme deficiencies. Atopy may be a risk factor (aspirin) and concomitant use of β-blockers (radiocontrast media)

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; may be related to infusion rate (vancomycin)

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 ...

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