What are the next steps for a patient with a history of vitamin B12 (B12) deficiency, being treated with weekly B12 injections, who develops severe itching and bruising after an increase in B12 levels?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: November 21, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Severe Itching and Bruising After B12 Injections

Stop the B12 injections immediately and evaluate for a hypersensitivity reaction to the B12 formulation or its excipients. This patient is experiencing severe pruritus with bruising, which represents a significant adverse reaction requiring prompt intervention.

Immediate Management Steps

Discontinue the current B12 injection regimen immediately 1. Severe itching (pruritus) is a recognized sign of hypersensitivity reactions to vitamin B12 preparations, and the presence of bruising suggests the patient is causing self-trauma from scratching 2.

Symptomatic Treatment

  • Administer antihistamines for pruritus control: second-generation antihistamines like loratadine 10 mg PO or cetirizine 10 mg PO/IV are preferred 2
  • Consider corticosteroids if symptoms are moderate to severe: hydrocortisone 100-200 mg IV or oral prednisone equivalent 2
  • Monitor for progression to more severe hypersensitivity features including angioedema, bronchospasm, or hypotension 2

Diagnostic Evaluation

Refer to an allergy specialist for comprehensive skin testing to determine the specific allergen 1. The evaluation should include:

  • Skin prick testing (1 mg/mL) with both cyanocobalamin and hydroxocobalamin 1
  • Intradermal testing (0.1 and 0.01 mg/mL) if skin prick tests are negative 1
  • Evaluation for polyethylene glycol (PEG) allergy, as PEG in oral or injectable formulations can cause hypersensitivity reactions 1

Confirmed vitamin B12 hypersensitivity is rare but well-documented, with approximately 62% presenting as immediate reactions and pruritus being a cardinal symptom 1.

Alternative B12 Replacement Strategies

Switch Formulations

If sensitized to one form of B12, trial the alternative formulation 1. The evidence shows:

  • Patients sensitized to hydroxocobalamin may tolerate cyanocobalamin, and vice versa 1
  • Seven of eight patients with confirmed hypersensitivity to one injectable form tolerated drug provocation testing with the alternative B12 formulation 1

Consider Oral High-Dose B12

Oral cyanocobalamin 1000-2000 mcg daily is therapeutically equivalent to parenteral therapy for most patients, including those with malabsorption 3, 4, 5, 6. This approach:

  • Achieves adequate absorption even in pernicious anemia when given at high doses 5, 6
  • Avoids injection-related hypersensitivity reactions 7
  • Requires monitoring to ensure therapeutic response 3

Important caveat: One patient in the literature reacted to PEG in oral cobalamin, so oral formulations are not universally safe 1.

Ongoing B12 Management

Do not abandon B12 replacement therapy 3. Untreated B12 deficiency leads to irreversible neurological damage 4. Once the acute reaction resolves:

If Alternative Injectable B12 is Tolerated:

  • Resume with the alternative formulation (switch from hydroxocobalamin to cyanocobalamin or vice versa) 1
  • Standard maintenance dosing: 1 mg intramuscularly every 2-3 months for life if no neurological involvement 2, 3
  • Consider premedication with antihistamines and corticosteroids for subsequent injections if mild reactions recur 2

If All Injectable Forms Cause Reactions:

  • Switch to oral high-dose therapy: 1000-2000 mcg daily indefinitely 3, 4, 6
  • Monitor response closely: Check serum B12, homocysteine, and methylmalonic acid every 3 months until stabilization 3, 4

Critical Monitoring

Watch for signs of anaphylaxis during any rechallenge 1. Eight patients in the largest case series experienced anaphylaxis to B12 injections 1. If rechallenge is attempted:

  • Perform in a monitored setting with emergency equipment available 2
  • Have epinephrine 0.3 mg IM immediately available 2
  • Monitor for at least 30-60 minutes post-injection 2

Common Pitfall to Avoid

Never discontinue B12 supplementation entirely, even if levels have normalized 3. Patients with malabsorption require lifelong therapy, and stopping treatment will lead to recurrent deficiency with potential for irreversible neurological complications 3, 4.

References

Research

Vitamin B12 Hypersensitivity: A Retrospective Multicenter Study.

The journal of allergy and clinical immunology. In practice, 2024

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Approach to Vitamin B12 Deficiency

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

B12 Injection Frequency for B12 Deficiency

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Vitamin B12 replacement therapy: how much is enough?

Wisconsin medical journal, 1994

Research

Vitamin B12 Deficiency: Recognition and Management.

American family physician, 2017

Research

[Allergic reaction after intravenous application of vitamin B12].

Medizinische Monatsschrift fur Pharmazeuten, 2010

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.