Vitamin B12 Hypersensitivity: A Retrospective Multicenter Study

Abstract

Background: Vitamin B₁₂ (Vit B₁₂) deficiency affects approximately 20% of those above the age of 60 years in the United Kingdom and United States. If untreated, it leads to detrimental health outcomes.

Objective: To investigate a cohort of patients with Vit B₁₂ hypersensitivity (VB12H) referred to 3 UK allergy centers and design a pathway for the investigation of VB12H.

Methods: A total of 29 patients seen between 2014 and 2022 underwent skin prick testing (1 mg/mL) with cyanocobalamin (CC) and hydroxycobalamin (HC) and intradermal testing (0.1 and 0.01 mg/mL). Patients with negative skin tests underwent a Vit B₁₂ drug provocation test (DPT) with either the index or the alternative drug.

Results: Of 29 patients, 18 (62%) presented with immediate VB12H. Eight experienced anaphylaxis (4 to HC and 4 to CC) and had positive skin tests to the index drug. One patient reacted to oral and 7 patients to injectable Vit B₁₂. Seven patients sensitized to one form of Vit B₁₂-tolerated DPT with an alternative Vit B₁₂. One patient with immediate VB12H reacted to polyethylene glycol (PEG) in oral cobalamin. Of 29 patients, 8 presented with delayed hypersensitivity reaction; 4 patients tolerated the intramuscular index formulation, whereas 2 patients tolerated the per oral formulation. One patient presented with symptoms consistent with symmetrical drug-related intertriginous and flexural exanthema. Three patients were referred because of cobalt allergy.

Conclusion: Confirmed VB12H is rare. We propose a comprehensive evaluation protocol that includes Vit B₁₂ skin tests and considers PEG allergy in patients presenting with VB12H.

Keywords: Cobalt allergy; Cyanocobalamin; Desensitization; Excipient; Hydroxycobalamin; PEG; SDRIFE; Skin testing; Vit B(12) allergy.