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Drug Eruptions and Reactions

Drugs can cause multiple skin eruptions and reactions. The most serious of these are discussed elsewhere in The Manual 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 (see Table 1: Hypersensitivity and Inflammatory Disorders: Types of Drug Reactions and Typical Causative AgentsTables).

Symptoms and Signs

Symptoms and signs vary based on the cause and the specific reaction (see Table 1: Hypersensitivity and Inflammatory Disorders: Types of Drug Reactions and Typical Causative AgentsTables).

Table 1

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, lithiumSome Trade Names
ESKALITH
LITHOBID
LITHONATE
Click for Drug Monograph
, isoniazidSome Trade Names
INH
NYDRAZID
Click for Drug Monograph
, phenytoinSome Trade Names
DILANTIN
Click for Drug Monograph
, phenobarbitalSome Trade Names
LUMINAL
Click for Drug Monograph
, vitamins B2, B6, and B12

Acral cyanosis

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

BleomycinSome Trade Names
BLENOXANE
Click for Drug Monograph

Blistering eruptions

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

PenicillamineSome Trade Names
CUPRIMINE
Click for Drug Monograph
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

WarfarinSome Trade Names
COUMADIN
Click for Drug Monograph
, heparinSome Trade Names
HEPFLUSH-10
Click for Drug Monograph
, barbiturates, epinephrineSome Trade Names
ADRENALIN
PRIMATENE MIST
Click for Drug Monograph
, norepinephrineSome Trade Names
LEVOPHED
Click for Drug Monograph
, vasopressinSome Trade Names
PITRESSIN
Click for Drug Monograph

Drug-induced lupus

Appears as lupus-like syndrome, although often without the rash

HydrochlorothiazideSome Trade Names
ESIDRIX
HYDRODIURIL
Click for Drug Monograph
, minocyclineSome Trade Names
MINOCIN
Click for Drug Monograph
, hydralazineSome Trade Names
APRESOLINE
Click for Drug Monograph
, procainamideSome Trade Names
PROCAN SR
PRONESTYL
Click for Drug Monograph

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, scaling, and thickening of the entire skin surface (see Dermatitis: 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

Phenolphthalein, tetracyclineSome Trade Names
ACHROMYCIN V
TETRACYN
TETREX
Click for Drug Monograph
, sulfonamides

Lichenoid or lichen planus–like eruptions

Appear as angular papules that coalesce into scaly patches (see Psoriasis and Scaling Diseases: Lichen Planus)

Antimalarials, gold, chlorpromazineSome Trade Names
THORAZINE
Click for Drug Monograph
, 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, ampicillinSome Trade Names
OMNIPEN
PRINCIPEN
Click for Drug Monograph
, 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 Hypersensitivity and Inflammatory Disorders: Erythema Multiforme; see Hypersensitivity and Inflammatory Disorders: 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 minocyclineSome Trade Names
MINOCIN
Click for Drug Monograph
) on skin exposed to the sun or other ultraviolet light source

Phenothiazines, tetracyclines, sulfonamides, chlorothiazideSome Trade Names
DIURIL
SODIUM DIURIL
Click for Drug Monograph
, 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

ChlorothiazideSome Trade Names
DIURIL
SODIUM DIURIL
Click for Drug Monograph
, meprobamateSome Trade Names
EQUANIL
MILTOWN
Click for Drug Monograph
, 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, insulinSome Trade Names
HUMULIN
NOVOLIN
Click for Drug Monograph
, foreign proteins

Stevens-Johnson syndrome

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

May be fatal in 30 to 40% of patients

Resembles staphylococcal scalded skin syndrome (see Bacterial Skin Infections: 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

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, aspirinSome Trade Names
BUFFERIN
ECOTRIN
GENACOTE
Click for Drug Monograph
, sulfonamides

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 Allergic and Other Hypersensitivity Disorders: 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 epinephrineSome Trade Names
ADRENALIN
PRIMATENE MIST
Click for Drug Monograph
(1:1000) 0.2 mL sc or IM and with the slower-acting but more persistent soluble hydrocortisoneSome Trade Names
CORTEF
SOLU-CORTEF
Click for Drug Monograph
100 mg IV, which may be followed by an oral corticosteroid for a short period (see also Allergic and Other Hypersensitivity Disorders: Treatment).

Last full review/revision October 2009 by Wingfield E. Rehmus, MD, MPH

Content last modified October 2009

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