Types of Drug Reactions and 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, halogens (eg, iodides, bromides), hydantoins, androgenic steroids, lithium, isoniazid, phenytoin, phenobarbital, vitamins B2, B6, and B12

Acute generalized exanthematous pustulosis

Rapidly appearing and spreading pustular eruption

Mainly antibiotics but some other medications

Blistering eruptions

Appear with widespread vesicles and bullae

Pemphigus: Antibiotics, penicillamine, and other thiol compounds (including antihypertensives)

Bullous pemphigoid: Penicillamine and furosemide (most common), immune checkpoint inhibitors, typically PD-1 inhibitors

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), xylazine (often added to fentanyl in illicit drug mixtures)), xylazine (often added to fentanyl in illicit drug mixtures)

Medication-induced lupus

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

Procainamide, minocycline, hydralazine, anti-tumor necrosis factor (TNF) medications, penicillamine, isoniazid, quinidine, interferon, methyldopa, chlorpromazine

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 medication

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

Thyroiditis can be a sequela

Antiseizure medications, allopurinol, sulfonamides, minocycline, vancomycin

Immune checkpoint inhibitors†

Flagellate dermatitis

Linear erythematous wheals

Bleomycin and other antineoplastic agents

Erythema nodosum

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

Sulfonamides, oral contraceptives, penicillin, halogens (eg, bromides, iodides)

Exfoliative dermatitis/erythroderma

Characterized by erythema and scaling of the entire skin surface

May be fatal

Antibiotics, antiseizure medications, antihypertensives, many others

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 medication is taken

Antibiotics, NSAIDs, acetaminophen, barbiturates, antimalarials, antiseizure medications

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

Immune checkpoint inhibitors†

Morbilliform or maculopapular eruptions (exanthems)

Most common hypersensitivity drug reaction

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

Almost any medication (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, antiseizure medications, sulfonamides, NSAIDs, antibiotics, allopurinol, nevirapine, vaccinesPenicillin, barbiturates, antiseizure medications, sulfonamides, NSAIDs, antibiotics, allopurinol, nevirapine, vaccines

Palpable purpura

Nonblanching purpuric papules most commonly on the lower extremities

Antibiotics, NSAIDs, antihypertensives, antiseizure medications, allopurinol

Photosensitive eruptions

Phototoxic reactions: Occur after direct damage of the tissue by exposure to the sunlight and medication 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

Medications that can cause phototoxic or photoallergic reactions: NSAIDs, chlorpromazine, phenothiazines, and sulfonamides

Medication 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 patients with immunosuppression

May be fatal

Antiseizure medications, NSAIDs, penicillin, sulfonamides, antiretroviral medications

Immune checkpoint inhibitors†

Urticaria

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.