What is thiomersal hypersensitivity? Which vaccines contain thiomersal?
(Expiry:14th January 2004)

Answer
The very low thiomersal concentrations present in pharmacological and biological products are relatively non-toxic in adults, but may be toxic in utero and during the first 6 months of life. The reported rate of hypersensitivity to thiomersal, in mostly selected populations, varies from 1% to 18%. There is no difference in incidence between gender, but young adults aged between 20 and 30 years seem to have the highest risk (1).

It is likely that the ethylmercury radical of the thiomersal molecule is the prominent sensitiser and cause of allergic reactions which are delayed type IV hypersensitivity reactions. Hypersensitivity to thiomersal does not imply a true allergy to mercury and cannot be considered a practical indicator for hypersensitivity to it. However, cross-sensitisation between thiomersal and some organic mercurials, and even a few inorganic and metallic mercurials, has been reported (2).

Topical hypersensitivity to thiomersal can present as contact dermatitis, dyshidrotic dermatitis (pompholyx) on the hands and feet, conjunctivitis and several combinations of different ocular symptoms in contact lens wearers, and contact urticaria. Systemic administration can cause acute disseminated or systemic reactions such as urticaria, exanthema, dermatitis, lymphadenopathy and associated fever. Pre-existing atopic dermatitis may also be exacerbated. Systemic reactions related to thiomersal hypersensitivity seem to occur very rarely but may be undiagnosed and, as in many cases of drug reactions, under-reported (1,3). Anaphylaxis or other life-threatening conditions have not been reported from administration of thiomersal-containing vaccines.

A large number of patients without demonstrable sensitivity still show a positive routine patch test to thiomersal. Consequently such tests are of low clinical relevance and necessary vaccinations containing thiomersal should not be considered contra-indicated (1,2). Even where clinical hypersensitivity has been described, repeat exposure to thiomersal does not necessarily cause hypersensitivity to recur (1).

Hypersensitivity to thiomersal may also cause photo-hypersensitivity to piroxicam. This is probably because of an immunochemical relationship between thiosalicylic acid and a degraded photoproduct of piroxicam. Cross-reactivity with the related drug, meloxicam, is unclear (4).

The table below lists common vaccines available within the United Kingdom. Those vaccines highlighted in blue contain thiomersal. This list is not exhaustive.
 

Note About Trace Amounts
In products where thiomersal is declared as a trace amount, thiomersal is not present as an official pharmaceutical excipient, i.e. preservative, but is used in the manufacturing process. Therefore very small amounts of thiomersal may be present in the final product at a much lower concentration than when used as an excipient.

Summary
Thiomersal has traditionally been used in the UK as a preservative in vaccines and currently there are many that still contain thiomersal. Hypersensitivity to thiomersal does exist although it is not life-threatening. However, patients with clinically apparent hypersensitivity should not receive products containing thiomersal unless such products are deemed vital. They should also avoid the anti-inflammatory drug piroxicam (and possibly meloxicam until more data are available).

Limitations
This list of vaccines is not exhaustive for all products available in the UK.

References

1. van ‘t Veen, A. Vaccines without thiomersal. Why so necessary, why so long coming? Drugs, 2001; 61 (5): 565 – 572.
2. Audicana MT et al. Allergic contact dermatitis from mercury antiseptics and derivatives: Study protocol of tolerance to intramuscular injections of thimerosal. American Journal of Contact Dermatitis. Vol 13(1) (pp 3-9), 2002.
3. Crockett RE, Lockey RF. Vaccine hypersensitivity. Immunology & Allergy Clinics of North America, 2001; 21 (4): 707 – 743.
4. Trujillo MJ, et al. Piroxicam-induced photodermatitis. Cross-reactivity among oxicams. A case report. Allergol Immunopathol (Madr), 2001; 29 (4): 133 – 136.
    

Prepared by
Mark Cheeseman, Wessex Drug and Medicines Information Centre, Southampton University Hospitals Trust

Contact
mark.cheeseman@suht.swest.nhs.uk

Date Prepared
21st October 2002

Checked by
Simon Wills, Wessex Drug and Medicines Information Centre, Southampton University Hospitals Trust

Date of check
8th November 2002

Search strategy
British National Formulary (No.43)
Embase
Medline
PharmLine
In-house Database
Electronic Medicines Compendium
Cochrane
All Suppliers contacted October/November 2002
Department of Health. Immunisation against infectious disease. London: HMSO; 1996.