Systemic toxicity following administration of sirolimus (formerly rapamycin) for psoriasis - Association of capillary leak syndrome with apoptosis oflesional lymphocytes

Background: Sirolimus (formerly rapamycin) is an immunosuppressive agent th at interferes with T-cell activation. After 2 individuals with psoriasis de veloped a capillary leak syndrome following treatment with oral sirolimus, lesional skin cells and activated peripheral blood cells were analyzed for induction of apoptosis. Observations: A keratome skin specimen from 1 patient with sirolimus-induce d capillary leak syndrome had a 2.3-fold increase in percentage of apoptoti c cells (to 48%) compared with an unaffected sirolimus-treated patient with psoriasis (21%). Activated peripheral blood T cells from patients with pso riasis tended to exhibit greater spontaneous or dexamethasone-induced apopt osis than did normal T cells, particularly in the presence of sirolimus. Conclusions: Severe adverse effects of sirolimus include fever, anemia, and capillary leak syndrome. These symptoms may be the result of drug-induced apoptosis of lesional leukocytes, especially activated T lymphocytes, and p ossibly release of inflammatory mediators. Because patients with severe pso riasis may develop capillary leak from various systemic therapies, clinical monitoring is advisable for patients with inflammatory diseases who are tr eated with immune modulators.