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Letters

Allergy to hydroxycobalamin, with tolerance of cyanocobalamin

David Heyworth-Smith and Patrick G Hogan
MJA 2002 177 (3): 162-163

To the Editor: Cyanocobalamin and hydroxycobalamin are synthetically derived preparations of vitamin B12. Allergy to vitamin B12 injection is infrequent, but may be serious. We describe a patient with allergy to hydroxycobalamin, without cross-reaction to cyanocobalamin.

Our patient was a 45-year-old woman with vitamin B12 deficiency. She had positive antiparietal cell antibodies and normal results of Schilling's test after addition of intrinsic factor. Otherwise she was in good health, with no other evidence of autoimmune disease.

Her allergy commenced after an intramuscular injection of hydroxycobalamin, with onset of mild generalised pruritus. Subsequent monthly 1 mg injections of hydroxycobalamin were followed by incrementally worsening pruritus, and then frank urticaria. The last of nine injections was followed by urticaria, bronchospasm and oropharyngeal angioedema, which responded to administration of adrenalin.

The patient underwent skinprick and intradermal testing with hydroxycobalamin and cyanocobalamin. Wheal-and-flare reactions occurred with injection of dilutions of hydroxycobalamin, suggesting an IgE-mediated response. No reactions were evident with dilutions of cyanocobalamin (Box). Subsequently, the patient had no reaction to a challenge of subcutaneously administered cyanocobalamin 0.1 mL (100 μg), and then intramuscularly administered cyanocobalamin 0.5 mL (500 μg). Her macrocytic anaemia resolved with ongoing monthly injections.

After one year of treatment, the patient described an episode of delayed urticaria after a routine cyanocobalamin injection. The skinprick and intradermal tests were repeated, with negative reactions to cyanocobalamin, and wheal-and-flare reactions to hydroxycobalamin. She has since tolerated monthly intramuscular cyanocobalamin for over 12 months.

Vitamin B12 allergy is rare, but has been reported.1-3 Positive results of basophil histamine release assay and skin testing suggest an IgE-mediated mechanism.2 Desensitisation is therefore theoretically possible; however, anaphylaxis during desensitisation has occurred.3

In Australia, both hydroxycobalamin (Neo-cytamen, David Bull) and cyanocobalamin (Cytamen, David Bull) are available. The excipients of each preparation are identical — sodium chloride, glacial acetic acid, and sterile water.

Although the risk of severe allergy is low, adequate facilities for resuscitation should be available when parenteral vitamin B12 is administered. One approach to dealing with vitamin B12 allergy is to use the alternative compound after skin testing to exclude cross-reactivity. If cross-reactivity occurs, then desensitisation may be considered. Alternatively, oral administration of vitamin B12 may also be used.4

Results of skinprick and intradermal testing with hydroxycobalamin and cyanocobalamin*

Dilution

Saline (negative control)

Morphine (positive control)

Hydroxycobalamin

Cyano-cobalamin


Skinprick 1 : 1000

Negative

Positive

Positive

Negative

Intradermal 1 : 100

Negative

Positive

Positive

Negative

Intradermal 1 : 10

Negative

Positive

Positive

Negative


* A positive reaction was a wheal greater than that of the positive control.

  1. Woodliff HJ. Allergic reaction to cyanocobalamin injection. Med J Aust 1986; 144: 223. <PubMed>
  2. De Blay F, Sager MF, Hirth C, et al. IgE mediated reaction to hydroxycobalamin injection in a patient with pernicious anaemia. Lancet 1992; 339: 1535-1536.
  3. Vidal C, Lorenzo A. 1998 Anaphylactoid reaction to hydroxycobalamin with tolerance of cyanocobalamin. Postgrad Med J 1998; 74: 702. <PubMed>
  4. Cobcroft R, Cobcroft S. Oral vitamin B12 for B12 deficiency [letter]. Med J Aust 1999; 170: 451. <PubMed>

(Received 7 May 2002, accepted 24 Jun 2002)

Division of Immunology, Queensland Health Pathology Service, Princess Alexandra Hospital, Woolloongabba, QLD.

David Heyworth-Smith, Immunology Registrar; Patrick G Hogan, Director.

Correspondence: Dr David Heyworth-Smith, Division of Immunology, Queensland Health Pathology Service, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, QLD 4102. David_Heyworth-SmithAThealth.qld.gov.au

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©The Medical Journal of Australia 2002 www.mja.com.au PRINT ISSN: 0025-729X ONLINE ISSN: 1326-5377