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A 20-year-old college student was seen for fatigue and an upper respiratory infection and started on amoxicillin for a sore throat. Six days later she broke out with a red rash all over her body (Figure 212-1). She went to see her family physician back home with the rash and lymphadenopathy. A monospot was drawn and found to be positive. This morbilliform rash (like measles) is typical of an amoxicillin drug eruption in a person with mononucleosis. Amoxicillin was stopped, and diphenhydramine was used for the itching.

FIGURE 212-1

Amoxicillin rash in a young woman with mononucleosis. This is a morbilliform eruption. (Reproduced with permission from Richard P. Usatine, MD.)


Cutaneous drug reactions are the visible skin manifestations of a drug hypersensitivity and can present in a wide myriad of dermatosis. This includes the most common manifestation as a morbilliform exanthem but also includes urticaria/angioedema, acneiform or pustular, fixed drug eruption, eruptions, and the Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) spectrum. The primary morphology often elucidates a typical time course for its occurrence which can help identify the culprit drug for discontinuation. One should also quickly identify the more serious life-threatening drug-induced conditions or severe cutaneous adverse reactions (SCARs).

Drug hypersensitivity may be defined as symptoms or signs initiated by a drug exposure at a dose normally tolerated by non-hypersensitive persons.1 An adverse drug reaction (ADR) is defined by the World Health Organization as a noxious and unintended response to a drug at doses and indications normally used for treatment. They can be a predictable side effect of the pharmacologic action of the drug, type A (80%), or as an idiosyncratic reaction, which occurs only in susceptible patients, type B (10%–15%).2 Cutaneous drug reactions range from mild skin eruptions (e.g., exanthem, urticaria, and angioedema) to SCARs, the latter category including acute generalized exanthematous pustulosis (AGEP); drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS); SJS; and TEN.3 Other serious adverse reactions include anticoagulant-induced skin necrosis, drug-induced vasculitis, and generalized fixed drug eruption. Features suggestive of a complicated or severe SCAR include fever, facial swelling, bullae or skin shedding, mucosal involvement, and systemic symptoms.4


Cutaneous adverse reactions, drug reactions, medication reactions, adverse effects to drugs, hypersensitivity reactions.


  • Cutaneous drug reactions are common complications of drug therapy occurring in 2% to 3% of hospitalized patients.5

  • One study found that 4% to 5% of all adverse drug reactions were manifested in the skin.5 Approximately 1 in 6 adverse drug reactions represents drug hypersensitivity and can be either allergic or non–immune-mediated (pseudoallergic) reactions.2

  • Maculopapular eruptions, also known as exanthematous drug eruptions, are the most frequent ...

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