Can vitamin B12 (B12) injections cause eczema?

Can B12 Injections Cause Eczema?

Yes, vitamin B12 injections can cause eczema and other dermatological reactions, though this is rare. The FDA drug label for cyanocobalamin explicitly lists "itching" and "transitory exanthema" as known dermatological adverse reactions to parenteral vitamin B12 administration 1.

Evidence of B12-Induced Skin Reactions

Documented Hypersensitivity Reactions

• Immediate hypersensitivity occurs in approximately 62% of confirmed B12 allergy cases, with 8 patients experiencing anaphylaxis in a recent UK multicenter study 2.
• Delayed hypersensitivity reactions manifested as eczematous lesions have been documented, with positive patch testing confirming vitamin B12 as the causative agent 3.
• The UK study found that 8 of 29 patients (28%) presented specifically with delayed hypersensitivity reactions to B12, including eczematous presentations 2.

Mechanism and Clinical Presentation

• Eczematous and exanthematic skin lesions can develop after long-term, high-dose B12 intake, confirmed by positive patch testing with vitamin B12 3.
• One patient in the UK cohort presented with symptoms consistent with symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), a specific pattern of drug-induced eczema 2.
• Polyethylene glycol (PEG) in oral cobalamin formulations can also trigger reactions that may be mistaken for B12 allergy itself 2.

Critical Diagnostic Approach

When to Suspect B12-Induced Eczema

• Consider B12 hypersensitivity if eczematous lesions develop or worsen temporally related to B12 injections, particularly if the patient has no prior history of atopic dermatitis 3, 2.
• Look for distribution patterns consistent with drug reactions rather than typical atopic dermatitis (flexural areas, symmetrical presentation) 2.
• Distinguish between true B12 allergy and cobalt allergy, as cobalt is structurally related to cobalamin and can cause cross-reactivity 2.

Recommended Testing Protocol

If B12 hypersensitivity is suspected, refer to allergy/immunology for comprehensive evaluation including:

• Skin prick testing with cyanocobalamin and hydroxycobalamin at 1 mg/mL 2
• Intradermal testing at 0.1 and 0.01 mg/mL if skin prick tests are negative 2
• Drug provocation testing with alternative B12 formulations if skin tests are negative 2
• Consider PEG allergy testing if reactions occurred with oral formulations 2

Management Strategy

If B12-Induced Eczema is Confirmed

• Seven of eight patients sensitized to one form of B12 tolerated an alternative B12 formulation (switching between cyanocobalamin and hydroxycobalamin) 2.
• Four patients with delayed hypersensitivity to injectable B12 tolerated intramuscular formulations, while two tolerated oral formulations 2.
• Do not discontinue B12 supplementation without allergy evaluation, as untreated B12 deficiency leads to serious neurological and hematological complications 2.

Treatment of the Eczematous Reaction

• Manage the eczema itself according to standard atopic dermatitis guidelines: low-potency topical corticosteroids (hydrocortisone 1%) for acute flares plus liberal emollient use 4.
• For facial involvement, consider topical calcineurin inhibitors (pimecrolimus or tacrolimus) as steroid-sparing alternatives 5, 4.
• Watch for secondary bacterial infection (crusting, weeping, worsening despite treatment) requiring oral antibiotics 5, 4.

Important Caveats

Paradoxical Therapeutic Role

Interestingly, vitamin B12 supplementation has also been studied as a treatment for eczema, creating potential confusion:

• Topical vitamin B12 significantly improved eczema in children compared to placebo (p=0.01 at 4 weeks) 6.
• A meta-analysis showed SCORAD index decreased with vitamin B12 supplementation (mean difference -3.19,95% CI: -4.27 to -2.10) 7.
• One case report documented severe atopic dermatitis improvement with oral B12 supplementation 8.

This means B12 can both cause and potentially treat eczema in different contexts—the key distinction is whether the patient has true B12 hypersensitivity (rare) versus B12 deficiency contributing to eczema severity (more common) 3, 2, 8, 7.

Risk Stratification

• Confirmed B12 hypersensitivity is rare—only 29 cases were identified across three major UK allergy centers over 8 years 2.
• The general population prevalence of B12 allergy is unknown, but it represents a small fraction of patients receiving B12 therapy 2.
• Anaphylaxis risk exists and has been reported with fatal outcomes in the FDA drug label 1.