Staphylococcal toxic shock syndrome: still a problem

Toxic shock syndrome was first described in 1978,1 and a strong association with Staphylococcus aureus, menstruation and tampon use was established in 1980.2 Toxic shock syndrome toxin-1 (TSST-1), a protein secreted by S. aureus, was the first of many toxins associated with the syndrome to be identified. The term “superantigen” was adopted to describe the ability of these toxins to cause a remarkable expansion of T lymphocytes displaying specific β chain variable regions of the T-cell antigen receptor. Superantigens bypass normal antigen presentation and can stimulate over 20% of all T cells, whereas a conventional antigen stimulates only in the order of 1 in 10 000 T cells. The signature feature of superantigen activity is the expansion of lymphocyte populations bearing the particular Vβ chains that bind the superantigen. In the case of TSST-1, this is Vβ2.3

Our patient consented to blood being sampled to investigate the Vβ profile of her T cells at follow-up. This investigation was part of a broader study on superantigens in sepsis that was approved by the Ethics Committee of the Royal Melbourne Hospital. The blood was stained with monoclonal antibodies against 24 Vβ families4 and analysed by flow cytometry. This showed a massive expansion of Vβ2 cells, which accounted for 28% of all CD4 lymphocytes (Box).

Currently, there is no diagnostic test for toxic shock syndrome. Toxin production from cultured organisms can be established in vitro by some laboratories, but does not confirm toxin production in vivo. Detection of a “skewed” Vβ repertoire is a potential diagnostic test. Clearly, the sensitivity and specificity of the assay would need to be established before general application. To date, we have found skewed Vβ T-cell profiles in six independent cases of toxic shock syndrome.

This patient had used tampons appropriately, including replacing tampons at least every 4 hours and not using them overnight, but nevertheless developed a life-threatening disease. The incidence of toxic shock syndrome peaked in the United States in 1980 and has since fallen substantially, as a result of factors including changed tampon absorbency. However, the incidence may be now increasing.5 Our case serves to remind us all to be vigilant for toxic shock syndrome in association with menstruation, and to consider the diagnosis in all patients with severe sepsis.

Vβ profile of the T-cell antigen receptor of CD4 lymphocytes in a patient with toxic shock syndrome

Vβ profile of CD4 cells from a patient 21 days after onset of toxic shock syndrome compared with the mean profile from 11 adult intensive-care patients with no evidence of infection. Note the massive expansion of cells carrying Vβ 2, for which toxic shock syndrome toxin-1 has known affinity.