A multicentre study by the University of Trieste, conducted by Luca Cegolon (Department of Hygiene and Preventive Medicine) and Francesca Larese Filon (Department of Occupational Medicine), has just been published in the scientific journal Vaccines. The study examined sensitisation to Thimerosal in 31,948 patients who underwent patch testing between 1997 and 2023 for suspected allergic contact dermatitis, across four centres in the Triveneto area: Trieste, Pordenone, Padua and Trento-Bolzano.

Thimerosal (also known as Merthiolate) is a mercury-based compound consisting of ethylmercury and thiosalicylic acid. It was developed in 1927 as a preservative with antimicrobial properties and widely used from the 1930s onwards in vaccines and various medical products, including topical antiseptics, ointments, nasal sprays, eye drops, and more.

Immune-mediated reactions to mercury-containing products are well documented, the most common being allergic contact dermatitis. Thimerosal was named “Allergen of the Year” in 2002 by the American Contact Dermatitis Society, due to the high prevalence of sensitisation combined with its low clinical relevance.

Most clinically relevant allergic reactions to Thimerosal occur through exposure to cosmetics or ophthalmic preparations, often resulting in facial dermatitis. For this reason, Thimerosal sensitivity is more frequent in women, due to cosmetic use, and in occupational groups such as healthcare workers, who may be exposed through vaccination.

Concerns over potential neurological side effects of Thimerosal began to emerge in the early 1980s, leading to its removal from vaccines in Denmark (1992) and Sweden (1993). Thimerosal-containing vaccines were alleged to impair children's neurodevelopment, increasing the risk of autism, attention deficit disorder and language delay.

In 1999, several major U.S. bodies – in particular the American Academy of Pediatrics, the Centers for Disease Control and Prevention (CDC) in Atlanta, and the Food & Drug Administration (FDA) – recommended that Thimerosal be removed from all vaccines as soon as possible on a precautionary basis, out of concern for exceeding the cumulative exposure limits to methylmercury set by the U.S. Environmental Protection Agency.

Although no scientific evidence confirmed these concerns, both the World Health Organization (WHO) and the European Medicines Evaluation Agency (EMEA) aligned with these recommendations. In the early 2000s, many EU member states, including Italy, removed Thimerosal from vaccines. On 24th June 2005, the Council of the European Union recommended its removal from all vaccine preparations and medicinal products, as part of the European Commission's Mercury Strategy of 28th January 2005.

As a result of these restrictive policies, both the prevalence and clinical significance of positive Thimerosal reactions in patch testing have declined sharply in Europe. For example, a European study conducted between 2015 and 2018 reported a Thimerosal patch test reaction rate of 2.5%. In the United States, however, Thimerosal sensitisation remains much higher (10–20%), likely due to its continued use as a preservative in certain vaccines, including influenza vaccines.

The University of Trieste study shows a decreasing trend in Thimerosal sensitisation, from 8.13% in 1997 to 0.95% in 2023, with an average rate of 8.41% between 1997 and 2015, and 4.01% during the period 2010–2023.

Sensitisation to Thimerosal was significantly more frequent in patients born between 1981 and 1990, when the substance was still widely used in pharmaceuticals and childhood vaccines. The higher prevalence of positive patch test reactions in healthcare workers likely reflects greater adherence to influenza vaccination in this occupational group compared to others. In fact, until at least 2008, many vaccine formulations authorised in the European Union still contained Thimerosal.

However, patch test reactions to Thimerosal detected after 2000 are likely to be of little or no clinical relevance.