IMMUNOSUPPRESSION - TIGHTROPE WALK BETWEE N IATROGENIC SIDE-EFFECTS AND THERAPY

The therapeutic effect of-most immunosuppressive agents is unspecific and therefore often limited by an increased risk of infection by viral , bacterial or fungal organisms as well as by an increased incidence o f-malignant neoplasms. This short review includes the most commonly us ed immunosuppressants such as corticosteroids, azathioprine, methotrex ate, cyclophosphamide and cyclosporine. The most common risks of long- term corticosteroide treatment are Cushing-like changes, decreased glu cose tolerance and the usually benign steroid diabetes. Also clinicall y important is osteoporosis, since it can be prevented by physical tra ining, calcium supplementation and treatment with vitamin D if necessa ry. Although there is still no proof of a significantly increased risk of peptic ulcer during steroid therapy, patients may develop gastroin testinal hemorrhage and even perforation without producing pain while being treated with corticosteroids. Mineralocorticoid effects, such as salt and water retention, are seen only with hydrocortisone and predn isone, whereas with synthetic steroids such as dexamethasone, sodium r etention is absent despite their strong antiphlogistic activity. The m ost important side effect of the cytotoxic agents azathioprine, methot rexate and cyclophosphamide is marrow suppression. Due to the high tur nover of neutrophils, patients most frequently suffer neutropenia rath er than thrombocytopenia or anemia. Neutropenia, as well as impaired h umoral and cellular immune mechanisms, are responsible for increased s usceptibility to bacterial, viral or parasitic diseases during immunos uppressive therapy. Hepatotoxicity has been reported among patients re ceiving azathioprine (cholestatic hepatitis) and methotrexate (elevate d AST levels and, rarely, liver fibrosis or cirrhosis). Cyclophosphami de causes hemorrhagic cystitis in a substantial proportion of patients , as well as an increased incidence of urothelial neoplasms. Both thes e side effects may be prevented by Mesna. The most important side effe cts of-cyclosporine are acute and chronic nephrotoxicity usually assoc iated with significantly elevated plasma levels of the drug. It must b e borne in mind that severe nephrotoxicity may occur in patients recei ving cyclosporine and ketoconazole together, since the latter may inap propriately increase the plasma cyclosporine level.