Department of Medicine, Section of Dermatology, University of Chicago, Chicago, Illinois.

While often life-saving for many complex diseases, iatrogenic immunosuppression has been associated with life-threatening infections and malignancies. Among these malignancies is skin cancer. Skin cancer is the most common form of cancer in the United States; the nonmelanoma skin cancers have an annual incidence of greater than 1,000,000 people in the US. It is well documented that the risk of nonmelanoma skin cancer (NMSC) is increased in those who are immunosuppressed. While many articles have been published on skin cancer risk in organ transplant recipients, little has been written regarding the incidence of nonmelanoma skin cancer in inflammatory bowel disease. A review of the literature of patients who are immunosuppressed for autoimmune disorders, and specifically, inflammatory bowel diseases, is discussed, as well as clinical presentations and treatment options.(Inflamm Bowel Dis 2008).

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Department of Clinical Chemistry, Leiden University Medical Center, Leiden, The Netherlands.

Calcineurin (Cn) is the target of the immunosuppressive drugs cyclosporine A (CsA), tacrolimus (Trl), and pimecrolimus (Prl). Trl and Prl are often used topically for treatment of various skin diseases. The Cn inhibitors CsA and Trl are mostly used for maintenance therapy of transplant patients. Their long-term use, however, causes a dramatic increase in skin cancer risk. By using a newly developed assay for Cn measurement in blood, we were able to demonstrate Cn activity in total skin homogenates. A significantly higher activity was found in epidermis compared to dermis. In skin cell cultures, fibroblasts showed the highest activity as compared to keratinocytes and melanocytes. Of the Cn inhibitors, Trl showed stronger inhibition than CsA and Prl (57 and 55% in fibroblast and keratinocyte cultures, respectively). Also, the lowest IC(50) (the half maximal inhibitory concentration) values were found for Trl (0.5 and 1.3 nM in two different fibroblast cultures). Cn activity and its inhibition can thus be studied in dermatological samples. The effects of Cn inhibition in fibroblasts and keratinocytes may be of influence on the overall functioning of the skin immune system.Journal of Investigative Dermatology advance online publication, 17 January 2008; doi:10.1038/sj.jid.5701244.

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