Cyclosporine is an immunosuppressive agent that has been shown to be effective in the treatment of psoriasis. However, its serious side effects in transplant patients have hindered many dermatologists from exploiting its therapeutic capabilities. The literature contains reports of lymphomas, internal malignancies, skin cancers, and serious infections in psoriasis patients on cyclosporine therapy. However, no study has evaluated the relative risk of these side effects in relation to the general population, nor monitored the patients for years after cyclosporine was discontinued. The recently published 5-year cohort study is the most rigorous data to date on the long-term safety of cyclosporine and shows no increased risk of lymphoma or internal malignancies. The study, however, illustrates increased risk of non-melanoma skin cancers, especially squamous cell carcinoma. Review of the literature does not suggest any increased risk of opportunistic infections or tuberculosis reactivation. These data suggest that cyclosporine in dermatologic dosage (3-5 mg/kg/d) is safe and dermatologists may consider using it.

Patients with severe psoriasis often require treatment with systemic therapy to control their disease. Cyclosporine, an immunosuppressive agent that inhibits T-lymphocytes, has been widely used in transplant patients. Since cyclosporine’s initial report of clearing psoriatic lesions in 1979, many controlled studies have confirmed its efficacy in the treatment of psoriasis. (1-3) There are, however, concerns regarding its toxicity. In transplant patients, long-term treatment with cyclosporine is associated with serious side effects, including increased risk of lymphoma, internal malignancies, skin cancers, and infections. (4-7) Although the risk appears to be less in non-transplant patients, these possible long-term side effects have hindered many dermatologists from exploiting its therapeutic capabilities in treating psoriasis patients. For years, dermatologists were worried about the lack of long-term data on cyclosporine in psoriasis patients. Now, there are data available that examine the long-term safety of cyclosporine therapy in the psoriasis population. This article reviews the safety data of cyclosporine use in the past decade according to dermatologic guidelines. A review of the anecdotal studies on cyclosporine will be presented first, followed by more rigorous clinical studies of cyclosporine in dermatology patients.

Methods

A literature review of all articles in English from 1979 to 2003 was performed using Medline searching for case reports, clinical trials, epidemiological studies, cohort studies, randomized controlled trials, letters, meta-analyses, and review articles. The year 1979 was used as a starting point since that was when the first study illustrating the efficacy of cyclosporine in psoriasis was published. The literature search was performed with an emphasis on the use of cyclosporine in dermatology settings. Keywords used included cyclosporine/Neoral adverse effects, cyclosporine/Neoral therapeutic use, cyclosporine/Neoral and malignancy, lymphoma, leukemia, skin neoplasm, basal cell carcinoma, squamous cell carcinoma, melanoma, lung cancer, liver cancer, mycosis fungoides, tuberculosis reactivation, and opportunistic infections. Out of all the articles captured, only 26 provided us with relevant data. Limitations of the study include the fact that not all cases of neoplasm and infections are reported and that articles written in languages other than English were not reviewed.

Results

Anecdotal Reports

Koo et al published one of the first case reports of a psoriasis patient who developed a B-cell lymphoma 7 months after discontinuation of a 9-month course of cyclosporine. (8) Since this initial report, there have been several other case reports of lymphomas diagnosed after various latency periods following discontinuation of cyclosporine therapy. Zijlmans et al reported a case of Epstein Barr virus-associated lymphoma in a rheumatoid arthritis patient 5 months after discontinuation of cyclosporine at a dosage of less than 5 mg/kg per day. (9) Masouye, Salamon, and Saurat reported a B-cell immunoblastic lymphoma 4 months after discontinuation of a 5-month course of cyclosporine 5 mg/kg per day in a keratosis lichenoides chronica patient. (10)

In addition to cases of lymphomas occurring after cyclosporine discontinuation, there have also been several case reports of lymphomas while on cyclosporine therapy for psoriasis. Cliff et al reported a psoriasis patient with a history of methotrexate treatment who developed a B-cell lymphoma while on cyclosporine therapy. (11) The patient had been on cyclosporine therapy for 6 years, but it is not clear from the report whether the treatment was intermittent or continuous. The patient required an average dose of 4 mg/kg per day and at times required up to 10 mg/kg per day. There was no spontaneous regression after discontinuation of cyclosporine. Cockburn and Krupp reported 3 patients with autoimmune diseases who developed lymphomas with a mean latency period of 14.7 months after initiating cyclosporine therapy. (7) No information is disclosed as to the types of autoimmune diseases and lymphomas or the dosage of cyclosporine.