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Editor,—In their recent review article on staphylococcal scalded skin syndrome, Ladhani and Evans provide a detailed and comprehensive review of the physiochemical properties of the staphylococcal exfoliative toxins and discuss their role as proteolytic agents in skin pathogenesis.1 However, the superantigenic properties of these toxins2 were not mentioned and the similarities with other desquamating conditions in childhood were overlooked. Superantigens bypass conventional antigen processing and recognition by directly binding to class II major histocompatibility molecules on the surface of antigen presenting cells. They induce massive polyclonal stimulation of T lymphocytes causing proliferation and release of cytokines. Superantigen mediated conditions include scarlet fever and toxic shock syndrome,3 and may include Kawasaki disease.4Desquamation is a recognised feature of these conditions and usually occurs during the later stages of the illness. It seems that the organisms concerned have evolved an ingenious mechanism to induce a state of immune chaos in the host, followed by desquamation and a lowering of the shield of skin defences to their obvious advantage.
Drs Ladhani and Evans comment:
The superantigenic activity of the exfoliative toxins (ETs) of Staphylococcus aureus is still controversial—as a consequence, its discussion was not within the scope of our article. ETs have been shown to stimulate both Vβ-bearing murine and human T cells characteristic of superantigens as well as skin associated lymphoid tissue.1-1 However, Fleischer’s group provide a strong argument against the toxins being superantigens.1-2 They observed that most of the studies on the toxins’ superantigenic activity used commercial preparations and showed that, although the commercially prepared ETs did possess superantigenic activity, recombinant ETs did not.1-2 They speculated that the previous observations may be caused by contamination by minute quantities of other staphylococcal superantigens as has previously been shown—for example, with staphylococcal protein A.1-2 The authors also argue that the ETs seem unable to bind MHC class II molecules and are even able to stimulate MHC class II deficient murine T cells.1-2Similarly, biopsies of scalded skin blisters do not show any inflammatory cells, a characteristic feature of other superantigens.
The superantigenic activity of the ETs is therefore not certain and more research is required, which must take all necessary precautions to ensure the purity of the toxins. However, we agree with Dr Qasim on the similarities of the scalded skin syndrome with other superantigen mediated syndromes, and our own work on the ETs and that of others who have used recombinant toxin preparations1-3 does suggest that the toxins do possess superantigenic activity, which may have different characteristics to conventional superantigens. If this is true, the toxins may play an important part in many human dermatological and other diseases, including cutaneous T cell lymphoma, atopic dermatitis, Kawasaki disease, and psoriasis as well as sudden infant death syndrome, staphylococcal nephritis and septic arthritis, rheumatoid arthritis, multiple sclerosis, contact dermatitis, and various autoimmune diseases.
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