Urticaria multiforme represents a morphologic subset of urticarial reactions. It is a common, benign hypersensitivity reaction mediated by histamine that predominantly affects children between 4 months and 4 years of age. This entity often manifests after a preceding illness, medication exposure, or vaccination. It can be mistaken for more concerning entities, namely erythema multiforme or serum sickness.

Reported culprit medications include furazolidone, amoxicillin, palivizumab, albuterol, topiramate, nitrofurantoin, aspirin, pyrazolone, and mesalamine / 6-mercaptopurine / omeprazole, and reported vaccines include those against varicella, rotavirus, Haemophilus influenza, diphtheria, tetanus, and pertussis.

On physical exam, patients appear nontoxic and systemic findings are typically limited to a low-grade fever. Cutaneous findings include large polycyclic, annular, erythematous wheals on the face, trunk, and extremities. The wheals may develop an ecchymotic or dusky center. Although the dusky appearance can be concerning for erythema multiforme, there are no true target lesions, blistering, or necrosis of the skin and/or mucous membranes. The lesions are often pruritic but not painful. Individual lesions typically do not last longer than 24 hours.

Other key associated findings include dermatographism, acral and facial angioedema without associated laryngoedema, and symptoms of a preceding or concomitant illness such as low-grade fever, cough, or diarrhea.

The cutaneous eruption is self-limited and lasts about 1-2 weeks without any intervention. The lesions heal without post-inflammatory hyperpigmentation or scarring.