Allergic vasculitis | The primary lesion is typically a 2–3 mm purpuric papule. Other morphologies include urticaria that lasts over 24 hours, vesicles, bullae, or necrotic ulcers. | Most severe on the legs. | Sulfonamides, phenytoin, propylthiouracil. |
Drug exanthem | Morbilliform, maculopapular, exanthematous reactions. | The most common skin reaction to medications. Initially begins on trunk 7–10 days after the medication has been started. Spreads to extremities and begins to clear on the trunk over 3–5 days. In previously exposed patients, the rash may start in 2–3 days. Fever may be present. | Antibiotics (especially ampicillin and TMP-SMZ), sulfonamides and related compounds (including thiazide diuretics, furosemide, and sulfonylurea hypoglycemic agents), and barbiturates. |
Drug-related subacute cutaneous lupus erythematosus (Drug-induced SLE rarely produces a skin reaction) | May present with a photosensitive rash, annular lesions, or psoriasis on upper trunk. | Less severe than SLE, sparing the kidneys and central nervous system. Recovery often follows medication withdrawal. | Diltiazem, etanercept, hydrochlorothiazide, infliximab, lisinopril, terbinafine. |
Erythema nodosum | Inflammatory cutaneous nodules. | Usually limited to the extensor aspects of the legs. May be accompanied by fever, arthralgias, and pain. | Oral contraceptives. |
Exfoliative dermatitis and erythroderma (Drug-induced hypersensitivity syndrome) | Red and scaly. | Entire skin surface. Typically associated with elevated liver biochemical tests, eosinophilia, and acute kidney injury. Eruption begins between 2 and 6 weeks after first dose of medication. | Allopurinol, sulfonamides, isoniazid, anticonvulsants, or carbamazepine. |
Fixed drug eruptions | Single or multiple demarcated, round, erythematous plaques that often become hyperpigmented. | Recur at the same site when the medication is repeated. Hyperpigmentation, if present, remains after healing. | Antimicrobials, analgesics (acetaminophen, ibuprofen, and naproxen), barbiturates, heavy metals, antiparasitic agents, antihistamines, phenolphthalein. |
Lichenoid and lichen planus–like eruptions | Pruritic, erythematous to violaceous polygonal papules that coalesce or expand to form plaques. | May be in photo- or nonphotodistributed pattern. | Carbamazepine, furosemide, hydroxychloroquine, phenothiazines, beta-blockers, quinidine, quinine, sulfonylureas, tetracyclines, thiazides, and triprolidine. |
Photosensitivity: increased sensitivity to light, often of ultraviolet A wavelengths, but may be due to UVB or visible light as well | Sunburn, vesicles, papules in photodistributed pattern. | Exposed skin of the face, the neck, and the backs of the hands and, in women, the lower legs. Exaggerated response to ultraviolet light. | Sulfonamides and sulfonamide-related compounds (thiazide diuretics, furosemide, sulfonylureas), tetracyclines, phenothiazines, sulindac, amiodarone, voriconazole, and NSAIDs. |
Pigmentary changes | Flat hyperpigmented areas. | Forehead and cheeks (chloasma, melasma). The most common pigmentary disorder associated with drug ingestion. Improvement is slow despite stopping the medication. | Oral contraceptives are the usual cause. Diltiazem causes facial hyperpigmentation that may be difficult to distinguish from melasma. |
| Blue-gray discoloration. | Light-exposed areas. | Chlorpromazine and related phenothiazines. |
| Brown or blue-gray pigmentation. | Generalized. | Heavy metals (silver, gold, bismuth, and arsenic). |
| Blue-black patches on the shins. | | Minocycline, chloroquine. |
| Blue-black pigmentation of the nails and palate and depigmentation of the hair. | | Chloroquine. |
| Slate-gray color. | Primarily in photoexposed areas. | Amiodarone. |
| Brown discoloration of the nails. | Especially in more darkly pigmented patients. | Hydroxyurea. |
Pityriasis rosea–like eruptions | Oval, red, slightly raised patches with central scale. | Mainly on the trunk. | Barbiturates, bismuth, captopril, clonidine, methopromazine, metoprolol, metronidazole, and tripelennamine. |
Psoriasiform eruptions | Scaly red plaques. | May be located on trunk and extremities. Palms and soles may be hyperkeratotic. May cause psoriasiform eruption or worsen psoriasis. | Antimalarials, lithium, beta-blockers, and TNF inhibitors. |
SJS/TEN | Target-like lesions. Bullae may occur. Mucosal involvement. | Usually trunk and proximal extremities. | Sulfonamides, anticonvulsants, allopurinol, NSAIDs, lamotrigine. |
Urticaria | Red, itchy wheals that vary in size from < 1 cm to many centimeters. May be accompanied by angioedema. | Chronic urticaria is rarely caused by medications. | Acute urticaria: penicillins, NSAIDs, sulfonamides, opioids, and salicylates. Angioedema is common in patients receiving ACE inhibitors and angiotensin receptor blockers. |