Drug-Induced Urticaria (Hives)
Hives associated with medication are termed "drug-induced urticaria" or "drug-induced hives," representing the second most common cutaneous manifestation of drug allergy after maculopapular rashes. 1, 2
Terminology and Classification
The medical literature uses several interchangeable terms for this condition:
- Drug-induced urticaria - the most commonly used clinical term 1, 3
- Drug-induced hives - lay terminology for the same condition 4
- Medication-associated urticaria - alternative descriptor in clinical practice 5
These terms specifically describe transient, pruritic wheals (raised, erythematous lesions) that develop in response to medication exposure. 2, 5
Clinical Context and Epidemiology
Drug-induced urticaria occurs in approximately 0.16% of hospitalized medical patients and accounts for 9% of chronic urticaria cases seen in dermatology clinics. 1 The condition typically manifests within 24 hours of drug ingestion, though timing can vary based on the underlying mechanism. 1
Most Common Causative Agents
The medications most frequently implicated include:
- Penicillins and other antibiotics - leading cause across multiple studies 1, 5
- Nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin - can cause both acute urticaria and exacerbate chronic urticaria through pharmacologic mechanisms 6, 1, 3
- Sulfonamides - well-documented urticaria trigger 1
- Aspirin specifically - FDA labeling warns that "aspirin may cause a severe allergic reaction which may include hives" 4
Mechanistic Subtypes
Understanding the mechanism helps clarify terminology:
IgE-Mediated Drug-Induced Urticaria
This represents a Type I hypersensitivity reaction where the drug triggers IgE antibody-mediated mast cell degranulation, releasing histamine and other mediators. 7, 2, 3 This is the classic "allergic" mechanism.
Non-IgE-Mediated Drug-Induced Urticaria
Several non-allergic mechanisms can produce identical clinical urticaria:
- Direct mast cell activation without antibody involvement 2, 3
- Immune complex formation with complement activation (as in serum sickness) 2, 3
- Pharmacologic mechanisms - particularly with NSAIDs that inhibit COX-1, causing arachidonic acid metabolism dysfunction 6, 3
Important Clinical Distinctions
Acute vs. Chronic Drug-Induced Urticaria
Most drug-induced urticaria is acute, lasting less than 24 hours per individual lesion and resolving within 6 weeks total. 1, 3 True chronic urticaria (>6 weeks duration) is rarely caused directly by drugs, with the notable exception of NSAIDs and aspirin, which can exacerbate or trigger chronic urticaria through ongoing pharmacologic effects rather than immune mechanisms. 6, 3
Associated Conditions
Drug-induced urticaria may occur in isolation or as part of more serious systemic reactions:
- Anaphylaxis - urticaria with systemic involvement including respiratory or cardiovascular compromise 1, 2
- Angioedema - deeper tissue swelling often accompanying urticaria 1, 5
- Serum sickness - urticaria with immune complex deposition 2
Critical Pitfall
Do not confuse drug-induced urticaria with other drug eruptions that may superficially resemble hives, such as:
- Maculopapular drug eruptions (most common drug rash, but not urticarial) 1, 2
- Erythema multiforme with target lesions (fixed, lasting >24 hours) 8
- Urticarial vasculitis (painful rather than pruritic, leaves residual pigmentation) 8
The key distinguishing feature of true urticaria is that individual wheals are transient, migratory, and resolve within 24 hours without leaving marks. 8, 5