Solid-organ transplantation immunosuppressive therapy

A patient developed atorvastatin-induced severe autoimmune hepatitis and a lupus-like syndrome. Although the drug was immediately withdrawn, the disease persisted and deteriorated to a fulminant form with acute hepatic failure. There was no response to conventional immunosuppression with glucocorticoids and azathioprine. Only the introduction of intense immunosuppressive therapy, as used in solid organ transplantation, led to a complete and sustained recovery. The patient had the HLA haplotypcs DR3 and DR4, which are well-known genetic factors associated with autoimmune diseases. 

Ganciclovir therapy (5 mg/kg every 12 hours for 14 to 21 days) may benefit other CMV syndromes in AIDS patients or solid-organ-transplant recipients. Response rates of 67% or higher have been found in combination with a decrease in immunosuppressive therapy. The duration of therapy depends on demonstrating clearance of viremia an early switch from intravenous ganciclovir to oral valganciclovir is feasible. Recurrent CMV disease occurs commonly after initial treatment. In bone marrow transplant... 

Clinical uses and pharmacokinetics Use of these immunosuppressants is a major factor in the success of solid organ transplantation. Cyclosporine is used in solid organ transplantation and in graft-versus-host syndrome in bone marrow transplants. Tacrolimus is used in liver and kidney transplant recipients and may be effective as rescue therapy in patients who fail standard therapy. Sirolimus is used alone or in combination with cyclosporine in kidney and heart transplantation. The agents, particularly cyclosporine, may also be effective in immune diseases, including rheumatoid arthritis, uveitis, psoriasis, asthma, and type 1 diabetes. 

After these initial approaches in animal models, ECP has been used in humans for the prevention and/or treatment of several solid organ transplant rejections, including kidney, heart, lung, pancreas, and liver. The year of introduction of ECP for treating rejection of each type of transplant is indicated in Table 5. Importantly, ECP is effective for patients resistant to conventional treatment, particularly if started early. Besides reversal of allograft rejection, a reduction in immunosuppressive therapy has also been frequently achieved [173,174]. 

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