[Autoimmune dermatoses: new therapeutic strategies]

In the recent past, advances in both basic and clinical research have considerably contributed to the understanding of the cellular and molecular events that lead to autoimmune diseases. Nevertheless, current treatment protocols are essentially confined to systemic corticosteroids and cytotoxic agents. These are effective in controlling inflammation, however the occurrence of relapses after the treatment is stopped and the risks of toxicity and long-term immunosuppression necessitate the search for more selective strategies of immunointervention. Major efforts are directed towards therapies with increased cellular selectivity and, ideally, autoantigen specificity. Cyclosporine A, monoclonal antibodies (anti-CD4) and immunotoxins (IL-2 fusion toxins) currently constitute the main clinical orientation. At the experimental level, strategies are directed towards antigen-specific manipulation of costimulatory pathways (anti-gp39, CTLA4Ig), peptide therapy (MHC antagonism, TCR vaccination), and tolerance induction to the autoantigen (oral tolerization). Alternatively, intervention in the cytokine cascade of the inflammatory response by means of cytokine-induced immunomodulation (IL-4, IL-10) or cytokine antagonism (anti-TNF alpha) are strategies with a therapeutic potential. However, it must be borne in mind, that in animal models of antigen-induced autoimmune disease, it is simple to intervene in the development of autoimmunity, since the induction events are designed by the investigator. In contrast, in the majority of patients with autoimmune disease, we do not know whether a specific autoantigen initiated the disease, nor do we know the time point at which the antigenic challenge occurred. As clinicians we are faced with late-term manifestations of the immunologic events that lead to clinical disease. Finally, in limited forms of cutaneous autoimmune disease, it is important to recognize distinct subsets with a favorable prognosis, for which less aggressive therapeutic modalities may be used.