Hypersensitivity Reactions to Vaccine Components

Noushin Heidary; David E. Cohen


Dermatitis. 2005;16(3):115-120. 

In This Article


Thimerosal, or sodium ethylmercurithiosalicylate, is a preservative used in low concentrations mainly in vaccines, cosmetics, ophthalmic and otolaryngolic medications, antitoxins, topical and intramuscular steroid preparations, and intradermal tests.[14] Thimerosal has two distinctive components, an organic mercury compound and thiosalicylate, both of which are involved in thimerosal allergy.

Thimerosal is the fifth most common allergen, according to the North American Contact Dermatitis Group (NACDG).[15] The rate of reactivity is 10.2% with a designated clinical relevance of 7.2%, making it one of the least clinically relevant of the 65 allergens tested by the NACDG.[16] Most patients with a clinically relevant thimerosal allergy are women with a periorbital dermatitis from thimerosal in eye cosmetics or contact lens solutions.[17] Thimerosal has rarely been associated with systemic reactions, including generalized eczema or urticaria[18]; one case of airway obstruction was reported as a delayed-type hypersensitivity reaction to thimerosal in throat spray.[19]

Despite the low clinical relevance of thimerosal allergy, the rate of thimerosal sensitivity has increased during the last decade, probably because of the increase in vaccines administered during infancy. With the initiation of a mass vaccination campaign in Austria in 1981, the administration of thimerosal-containing vaccines for tick-borne encephalitis (TBE) increased from 6% in 1980 to 86% in 2001. The growing number of people immunized to TBE has been concomitant with an increase in thimerosal-sensitized individuals in Austria.[14,20] Bruckner and colleagues investigated the prevalence of positive patch-test results using the TRUE Test system (Mekos Laboratories A/S, Hillerød, Denmark) on children under 5 years of age to determine whether sensitization to contact allergens was common in infancy.[21] In this study, 24.5% of asymptomatic children from 6 months to 5 years of age were sensitized to one or more contact allergens, and thimerosal was the second most prevalent allergen (after nickel). Vaccines thus appear to sensitize children to thimerosal at a younger age than expected, given the unlikeliness of contact exposure in this age group to other thimerosal-containing products. Osawa and colleagues also demonstrated this phenomenon by associating DTP vaccination with thimerosal sensitivity in a guinea pig model.[22]

To determine whether patients with thimerosal allergy could tolerate vaccination, Audicana and colleagues evaluated tolerance to thimerosal-containing vaccines in 125 patients sensitized to mercury derivatives and/or thimerosal.[23] Patch-test results in this patient population revealed that 45% of patients had positive reactions to thimerosal (0.05% in petrolatum), 74% had positive reactions to metallic mercury (0.5% in petrolatum), and 70% had positive reactions to mercury chloride (0.1% in water). In 10 cases, of all mercury derivatives tested, thimerosal yielded the only positive patch-test result. A questionnaire revealed that the likely source of sensitization in the 57 thimerosal patch-test-positive patients was vaccination. Thimerosal-allergic patients were challenged with three intramuscular injections of thimerosal solution (100 µg/mL) into the arm; if no reaction was observed, the dosage was increased (to 0.1 mL, 0.5 mL, and 1.0 mL) every 48 hours, alternating between the right and left arm. Challenge tests resulted in no cutaneous reactions in 91% of thimerosal-allergic patients whereas 9% had a mild reaction characterized by local induration and micropapules that resolved with the third intramuscular dose of thimerosal. Thus, this study demonstrated that vaccination of thimerosal-sensitized individuals may be considered when the benefits outweigh the risks of these local reactions.

In a retrospective case-control study, Cox and Forsyth demonstrated that patients with positive patch-test reactions to thimerosal did not have more vaccination reactions than patch-test negative controls had.[24] The conditions of thimerosal delivery in routine vaccines may be sufficient to induce sensitization but insufficient to evoke elicitation.

Much of the controversy around thimerosal in vaccines has centered on the theoretical risk of mercury poisoning. Since 2000, all pediatric hepatitis vaccines in the United States have been thimerosal free. Some vaccines have trace levels of thimerosal left over from the manufacturing process (less than 1 µg thimerosal per 0.5 mL dose of vaccine),[25] an amount that is considered insignificant.


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