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, anaphylaxis, and drug-induced vasculitis.
Drugs can also be implicated in hair loss, lichen planus, erythema nodosum, pigmentation changes, systemic lupus erythematosus, photosensitivity reactions, pemphigus, and pemphigoid. Other drug reactions are classified by lesion type (see Table: Types of Drug Reactions and Typical Causative Agents).
Symptoms and Signs
Symptoms and signs vary based on the cause and the specific reaction (see Table: 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, epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (MEK) inhibitors, iodides, bromides, hydantoins, androgenic steroids, lithium, isoniazid, phenytoin, phenobarbital, vitamins B2, B6, and B12 |
|
Acute generalized exanthematous pustulosis |
Rapidly appearing and spreading pustular eruption |
Most commonly antibiotics, including macrolides and penicillins |
|
Blistering eruptions |
Appear with widespread vesicles and bullae |
Pemphigus: Penicillin, penicillamine, and other thiol compounds Bullous pemphigoid: Penicillamine and furosemide (most common) Linear immunoglobulin A (IgA) bullous dermatosis: Vancomycin (most common) |
|
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 lupus-like syndrome, although often without the rash |
Procainamide, minocycline, hydralazine, anti-tumor necrosis factor (TNF) drugs, penicillamine, isoniazid, quinidine, interferon, methyldopa, chlorpromazine, practolol |
|
Drug reaction with eosinophilia and systemic symptoms or drug hypersensitivity syndrome |
Manifests as fever, facial edema, and rash 2–6 weeks after first dose of a drug Patients may have elevated eosinophils, atypical lymphocytes, hepatitis, pneumonitis, lymphadenopathy, and myocarditis Thyroiditis can be a sequela |
Antiseizure drugs, allopurinol, sulfonamides, minocycline, vancomycin |
|
Flagellate dermatitis |
Linear erythematous wheals |
Bleomycin |
|
Characterized by tender red nodules, predominantly in the pretibial region, but occasionally involving the arms or other areas |
Sulfonamides, oral contraceptives, penicillin, bromides, iodides |
|
|
Exfoliative dermatitis/erythroderma |
Characterized by redness and scaling of the entire skin surface May be fatal |
Penicillin, sulfonamides, beta-lactams, hydantoins, allopurinol, barbiturates, carbamazepine, phenobarbital |
|
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 |
Antibiotics, NSAIDs, acetaminophen, barbiturates, antimalarials, antiseizure drugs |
|
Lichenoid or lichen planus–like eruptions |
Appear as angular papules that coalesce into scaly plaques |
Angiotensin-converting enzyme inhibitors, beta-blockers, methyldopa, quinidine, thiazides, penicillamine, quinacrine |
|
Morbilliform or maculopapular eruptions (exanthems) |
Most common hypersensitivity drug reaction 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 Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis) |
Penicillin, barbiturates, sulfonamides (including derivatives used to treat hypertension and diabetes) |
|
Palpable purpura |
Nonblanching purpuric papules most commonly on the lower extremities |
Antibiotics (eg, sulfonamides and beta-lactams, hydralazine, propylthiouracil, phenytoin, allopurinol) |
|
Phototoxic reactions: Occur after direct damage of the tissue by exposure to the sunlight and drug and occur shortly after exposure and can look like a burn, including blistering; eruptions limited to sun-exposed skin Photoallergic reactions: Cell-mediated, can occur later, often with skin changes similar to those of eczema, and can spread to nonexposed skin |
Drugs that can cause phototoxic or photoallergic reactions: NSAIDs, chlorpromazine, phenothiazines, and sulfonamides Drugs that tend to cause only phototoxic reactions: Antibiotics (eg, tetracyclines, fluoroquinolones) |
|
|
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 (SJS)/toxic epidermal necrolysis (TEN) |
Characterized by focal areas of dusky red lesions, skin pain, and epidermal detachment of < 10% of BSA in SJS and > 30% of BSA in TEN* Skin and mucosa are involved; lips can develop hemorrhagic crusts and ulcerations Severe forms resemble staphylococcal scalded skin syndrome, a staphylococcal toxin–mediated disorder that occurs in infants, young children, and immunosuppressed patients May be fatal |
Antiseizure drugs, NSAIDs, penicillin, sulfonamides, antiretroviral drugs |
|
Common Classically but not always IgE-mediated Easily recognized by typical well-defined edematous wheals May be accompanied by angioedema or other manifestations of anaphylaxis Occasionally the first sign of impending serum sickness, with fever, joint pain, and other systemic symptoms developing within days |
NSAIDs can worsen urticaria, and urticaria can be a sign of many other drug reactions |
|
|
* When epidermal detachment occurs on 10 to 30% of BSA, the term SJS/TEN overlap is used. |
||
|
BSA = body surface area; NSAIDs = nonsteroidal anti-inflammatory drugs. |
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Diagnosis
A detailed history is often required for diagnosis, including recent use of over-the-counter 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. Occasionally, patch testing can be helpful in patients with fixed drug eruptions.
Treatment
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 and urticaria can be controlled with oral antihistamines and topical corticosteroids. For IgE-mediated reactions (eg, urticaria), desensitization can be considered when there is critical need for a drug.
If anaphylaxis occurs, treatment is with aqueous epinephrine (1:1000) 0.2 mL subcutaneously or IM, parenteral antihistamines, 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.
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 over-the-counter drugs.
-
Stop the suspected offending drug and treat symptoms as needed.
Drugs Mentioned In This Article
| Drug Name | Select Trade |
|---|---|
propylthiouracil |
No US brand name |
norepinephrine |
LEVOPHED |
hydrocortisone |
CORTEF, SOLU-CORTEF |
penicillamine |
CUPRIMINE |
acetaminophen |
TYLENOL |
carbamazepine |
TEGRETOL |
allopurinol |
ZYLOPRIM |
minocycline |
MINOCIN |
epinephrine |
ADRENALIN |
vasopressin |
VASOSTRICT |
furosemide |
LASIX |
Vancomycin |
VANCOCIN |
methyldopa |
No brand name |
phenytoin |
DILANTIN |
isoniazid |
LANIAZID |
Warfarin |
COUMADIN |
heparin |
PANHEPRIN |
lithium |
LITHOBID |
