Blue Wheals and Blue Angioedema Induced by Blue Dyes: A Systematic Review.

Background: Blue wheals and blue angioedema, the adverse reactions to blue dye injections with or without anaphylaxis, are poorly defined.

Objective: The objective is to review the characteristics (ie, sex and age at onset, interval between blue dye injection and symptom onset, clinical manifestations, duration of blue wheals or angioedema), natural courses, and treatments of blue dye adverse reactions.

Methods: A review of the articles published through July 2021 was performed per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations.

Results: Across 523 patients (175 studies) with any adverse reactions to blue dye injections, wheals, angioedema, or both occurred in 193 patients (36.9%). Of these 193 patients, 68 patients (35.2%) developed blue wheals or angioedema, 118 (61.1%) had ordinary wheals or angioedema (nonbluish), and 7 had both (3.6%). We reviewed 169 patients with available data (99 with ordinary lesions and 70 with blue lesions). Patent blue violet had the highest rate of inducing blue wheals or angioedema (odds ratio 4.9). Almost half of the patients with blue wheals or angioedema developed systemic symptoms; and of those with systemic symptoms, all except 1 progressed to anaphylaxis. On-demand treatments with antihistamines, corticosteroids, and epinephrine were commonly used and effective.

Conclusions: Using blue dyes can lead to blue wheals or angioedema and systemic reactions. In patients with a history of a severe allergic reaction to a blue dye, repeat administration of a blue dye should be used only after carefully weighing all the risks and benefits.