Sarcoidosis, Liver Transplantation, and Cyclosporine

IN RESPONSE:

Cyclosporine inhibits T-helper cells, reduces interleukin-2 secretion and interleukin-2 receptor expression, and inhibits a wide range of inflammatory responses; T-helper cells and interleukin-2 are believed to be important in the pathogenesis of sarcoidosis.

Our nine patients did well while receiving cyclosporine after liver transplantation. In contrast, in the patient described by Dr. Bain and colleagues, the disease was exacerbated. Although they suggest that immunosuppression may have participated in the reactivation of disease, their comment that post-transplant immunosuppression with cyclosporine and low-dose steroids was insufficient to prevent reactivation may be closer to the mark. Their report does not include crucial data on the dose and blood levels of cyclosporine during the period before exacerbation. Maintaining cyclosporine levels within an acceptable range might have prevented exacerbation.

Dr. Papo and colleagues raise two important points. First, we used a control group that fit our purpose to examine the effect of preexisting sarcoid on post-transplant survival and quality of life. Using as controls patients with sarcoid who had not had transplantation would answer the different question of the effect of transplantation plus immunosuppression in patients with advanced end-stage liver disease and sarcoidosis. Because liver transplantation is done only in patients likely to survive less than a year, randomization of comparably ill patients to a nontherapeutic arm seems inappropriate.

Second, the two reports [1, 2] cited by Papo and colleagues to support their contention that cyclosporine may be deleterious in sarcoidosis are not convincing. The patient described by Cunnah and colleagues [1] appears to have had tuberculosis rather than sarcoidosis. Even if the patient had sarcoidosis, cyclosporine was unlikely to alter the course of her disease given the time the drug was instituted.

In contrast, the report of York and colleagues may support the use of cyclosporine. In their first patient, cyclosporine suppressed conventional markers of inflammation and there was clinical improvement the disease recurred when (cyclosporine) therapy was discontinued. The second patient experienced side effects of nausea and vomiting that caused inadequate serum levels, which were lower than those that had been associated with a previous therapeutic response to cyclosporine.

• Copyright 2004 by the American College of Physicians