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Drug Eruptions and Reactions

by Wingfield E. Rehmus, MD, MPH

Drugs can cause multiple skin eruptions and reactions. The most serious of these are discussed elsewhere in T he M anual and include Stevens-Johnson syndrome and toxic epidermal necrolysis, hypersensitivity syndrome, serum sickness, exfoliative dermatitis, angioedema and anaphylaxis, and drug-induced vasculitis. Drugs can also be implicated in hair loss, lichen planus, erythema nodosum, pigmentation changes, SLE, photosensitivity reactions, pemphigus, and pemphigoid. Other drug reactions are classified by lesion type ( Types of Drug Reactions and Typical Causative Agents).

Symptoms and Signs

Symptoms and signs vary based on the cause and the specific reaction ( Types of Drug Reactions and Typical Causative Agents).

Types of Drug Reactions and Typical Causative Agents

Type of Reaction

Description and Comments

Typical Causative Agents

Acneiform eruptions

Resemble acne but lack comedones and usually begin suddenly

Corticosteroids, iodides, bromides, hydantoins, androgenic steroids, lithium, isoniazid, phenytoin, phenobarbital, vitamins B 2 , B 6 , and B 12

Acral cyanosis

Appears as gray-blue discoloration of tips of the fingers, toes, nose, and ears

Bleomycin

Acute generalized exanthematous pustulosis

Rapidly appearing and spreading pustular eruption

Aminopenicillins (ampicillin, amoxicillin, and bacampicillin), Ca channel blockers, cephalosporins, tetracyclines

Blistering eruptions

Appear with widespread vesicles and bullae resembling autoimmune bullous disorders (see Bullous Diseases)

Penicillamine and other thiol-containing drugs (eg, ACE inhibitors, gold Na thiomalate)

Cutaneous necrosis

Appears as demarcated, painful, erythematous or hemorrhagic lesions progressing to hemorrhagic bullae and full-thickness skin necrosis with eschar formation

Warfarin, heparin, barbiturates, epinephrine, norepinephrine, vasopressin, levamisole (contaminant in street preparations of cocaine)

Drug-induced lupus

Appears as lupuslike syndrome, although often without the rash

Hydrochlorothiazide, minocycline, hydralazine, procainamide, anti-TNF agents

Drug reaction with eosinophilia and systemic symptoms or drug hypersensitivity syndrome

Manifests as fever, facial edema, and rash 2–6 wk after 1st dose of a drug

Patients may have elevated eosinophils, atypical lymphocytes, hepatitis, pneumonitis, lymphadenopathy, and myocarditis

Anticonvulsants, allopurinol, sulfonamides

Erythema nodosum

Characterized by tender red nodules, predominantly in the pretibial region, but occasionally involving the arms or other areas

Sulfonamides, oral contraceptives

Exfoliative dermatitis

Characterized by redness and scaling of the entire skin surface (see Exfoliative Dermatitis)

May be fatal

Penicillin, sulfonamides, hydantoins

Fixed drug eruptions

Appear as frequently isolated, well-circumscribed, circinate or ovoid dusky red or purple lesions on the skin or mucous membranes (especially of the genitals) and reappear at the same sites each time the drug is taken

Tetracyclines, sulfonamides, NSAIDs

Lichenoid or lichen planus–like eruptions

Appear as angular papules that coalesce into scaly plaques (see Lichen Planus)

Antimalarials, chlorpromazine, thiazides

Morbilliform or maculopapular eruptions (exanthems)

Range in appearance from a morbilliform disease to an eruption resembling pityriasis rosea

Mildly pruritic, typically appearing 3 to 7 days after start of the drug

Almost any drug (especially barbiturates, analgesics, sulfonamides, ampicillin, and other antibiotics)

Mucocutaneous eruptions

Vary from a few small oral vesicles or urticaria–like skin lesions to painful oral ulcers with widespread bullous skin lesions (see Erythema Multiforme and see Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN))

Penicillin, barbiturates, sulfonamides (including derivatives used to treat hypertension and diabetes)

Photosensitivity eruptions

Appear as areas of dermatitis or gray-blue hyperpigmentation (phenothiazines and minocycline) on skin exposed to the sun or other ultraviolet light source

Phenothiazines, tetracyclines, sulfonamides, chlorothiazide, artificial sweeteners

Purpuric eruptions

Appear as nonblanching hemorrhagic macules that vary in size

Most common on the lower extremities but may occur anywhere and may indicate a more serious purpuric vasculitis

May occur as type II cytotoxic reactions, type IV cell-mediated delayed-type allergic reactions, or type III humoral allergic immune complex vasculitis

Chlorothiazide, meprobamate, anticoagulants

Serum sickness–type drug reaction

A type III immune complex reaction

Acute urticaria and angioedema more common than morbilliform or scarlatiniform eruptions

Possibly polyarthritis, myalgias, polysynovitis, fever, and neuritis

Penicillin, insulin, foreign proteins

Stevens-Johnson syndrome

Characterized by focal areas of skin necrosis and involvement of mucosa (see Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN))

Lips develop hemorrhagic crusts and ulcerations

Overlaps with toxic epidermal necrolysis

Anticonvulsants, NSAIDs, penicillin, sulfonamides

Toxic epidermal necrolysis

Characterized by large areas of loosened, easily detached epidermis that give the skin a scalded appearance (see Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN))

May be fatal in 30 to 40% of patients

Resembles staphylococcal scalded skin syndrome (see Staphylococcal Scalded Skin Syndrome), a similar disorder that occurs in infants, young children, and immunosuppressed patients

Overlaps with Stevens-Johnson syndrome

Anticonvulsants, barbiturates, hydantoins, penicillin, sulfonamides

Urticaria

Common

Classically but not always IgE-mediated

Easily recognized by typical well-defined edematous wheals

Occasionally the first sign of impending serum sickness, with fever, joint pain, and other systemic symptoms developing within days

Penicillin, aspirin, sulfonamides, ACE inhibitors

Diagnosis

  • Clinical evaluation and drug exposure history

  • Sometimes skin biopsy

A detailed history is often required for diagnosis, including recent use of OTC drugs. Because the reaction may not occur until several days or even weeks after first exposure to the drug, it is important to consider all new drugs and not only the one that has been most recently started. No laboratory tests reliably aid diagnosis, although biopsy of affected skin is often suggestive. Sensitivity can be definitively established only by rechallenge with the drug, which may be hazardous and unethical in patients who have had severe reactions.

Treatment

  • Discontinuation of offending drug

  • Sometimes antihistamines and corticosteroids

Most drug reactions resolve when drugs are stopped and require no further therapy. Whenever possible, chemically unrelated compounds should be substituted for suspect drugs. If no substitute drug is available and if the reaction is a mild one, it might be necessary to continue the treatment under careful watch despite the reaction. Pruritus can be controlled with antihistamines and topical corticosteroids. For IgE-mediated reactions (eg, urticaria), desensitization (see Desensitization) can be considered when there is critical need for a drug.

When progression from urticaria to anaphylaxis is a concern, treatment is with aqueous epinephrine (1:1000) 0.2 mL sc or IM and with the slower-acting but more persistent soluble hydrocortisone 100 mg IV, which may be followed by an oral corticosteroid for a short period (see also Atopic and Allergic Disorders : Treatment).

Key Points

  • Because drugs can cause a wide variety of reactions, drugs should be considered as causes of almost any unexplained skin reaction.

  • Base the diagnosis primarily on clinical criteria, including a detailed history of prescription and OTC drugs.

  • Stop the suspected offending drug and treat symptoms as needed.

Resources In This Article

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • LEVOPHED
  • MINOCIN
  • No US brand name
  • MICROZIDE
  • LANIAZID
  • AMOXIL
  • PANHEPRIN
  • ADRENALIN
  • DIURIL
  • COUMADIN
  • ZYLOPRIM
  • DILANTIN
  • CUPRIMINE
  • VASOSTRICT
  • LITHOBID

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