Cyclosporine in the treatment of dermatologic disease

Cyclosporine in the treatment of dermatologic disease – Tips from Other Journals

Richard Sadovsky

Cyclosporine has been primarily used for the prevention and treatment of organ transplant rejection and graft-versus-host disease. However, recently it has been used in the management of dermatologic disease and has become more popular than other immunosuppressive agents because of weak myelotoxicity, rapid therapeutic action and selectivity for helper T cells. Lim and colleagues review the use of cyclosporine for dermatologic diseases and discuss efficacy, dosage, safety and monitoring.

Cyclosporine interferes with the effective immune response by preventing the generation of antigen-specific population of T cells capable of coordinating an immune response. This function is efficacious in the treatment of many dermatologic diseases related to helper T cells. The most pronounced response to therapy with cyclosporine occurs with psoriasis, with significant resolution of plaque-type psoriasis as well as other forms of the disease. Initial doses of 2.5 to 5 mg per kg daily for three months are used. Cyclic therapy has been promising, especially when other topical modalities–such as steroids, tar, emollients or ultraviolet B therapy–are used. Cyclic therapy with 2.5 to 3 mg per kg of cyclosporine daily has been administered for clinical relapse of psoriasis.

Other dermatologic conditions successfully treated with cyclosporine include lichen planus, Behcet disease, atopic dermatitis, pyoderma gangrenosum, epidermolysis bullosa acquisita, alopecia areata, scleroderma, photodermatoses, blistering disorders, lupus erythematosus and dermatomyositis. Appropriate treatment dosages vary slightly up to 10 mg per kg per day.

Adverse effects of cyclosporine include renal toxicity. Cyclosporine is metabolized predominantly in the liver by the cytochrome [P.sub.450] pathway, so its half-life (usually eight to 24 hours) can be prolonged in patients with liver disease. No dosage adjustment is needed in persons with renal disease. Blood levels can be easily measured, and higher levels (greater than 200 to 300 ng per mL) generally predict toxicity.

Vasoconstriction and renovascular injury can lead to renal dysfunction, and an increasing creatinine level is considered a potential risk factor for permanent structural renal damage. Irreversible renal changes have been seen in patients treated with cyclosporine for psoriasis and Behcet’s disease. Nephropathy appears to be dose-related and occurs almost exclusively in patients receiving more than 5 mg per kg of cyclosporine daily. Most patients can receive lower dosages for up to five years without the occurrence of major structural abnormalities.

Hypertension is another complication of cyclosporine, with increases in arterial pressure often noted days after initiation of therapy. Nocturnal headaches are also common during nighttime pressure increases. Hypertension is thought to be caused by increased systemic vascular resistance. Dose reduction often lowers the blood pressure but may not in some cases. Care in using angiotensin-converting enzyme inhibitors, beta-adrenergic blockers and diuretics concomitantly with cyclosporine is required because of enhancement of renal vasoconstrictive effects by depleting the extracellular fluid volume.

The risk-to-benefit analysis depends on review of efficacy, toxicity, economic effect, acceptability to the patient and availability of alternative options. Often, cyclosporine is considered in a patient with severe disease refractory to other treatment. Contraindications include renal insufficiency, severe infection, immunodeficiency, malignancy, uncontrolled hypertension or drug or alcohol abuse. After the disease is well controlled, discontinuation of treatment can be attempted. Intermittent therapy and adjunctive treatments are clearly more desirable to decrease the potential for nephrotoxicity. Drugs that may inhibit cyclosporine metabolism by competing for the [P.sub.450] cytochrome system need to be minimized. Monitoring should include creatinine levels, blood pressure determinations and intermittent whole blood concentrations. (See the accompanying table.)

Assessment of Patients Receiving Cyclosporine

Basic screening tests before initiation of cyclosporine treatment

Measurement of blood pressure

Complete blood cell count with differential count

Liver function tests

Urinalysis

Creatinine clearance test or glomerular filtration rate

Serum electrolytes, blood urea nitrogen, creatinine, magnesium

Suggested follow-up investigations

Blood pressure recording and laboratory tests every two weeks initially and

every three to four months thereafter: cyclosporine trough level, complete

blood cell count with differential count, serum electrolytes, blood urea

nitrogen, creatinine, magnesium, urinalysis

Creatinine clearance test or glomerular filtration rate every six months

From Lim KK, Su WP, Schroeter CJ, Abraham RT, Pittelkow MR. Cyclosporine in the treatment of dermatologic disease: an update. Mayo Clin Proc 1996;71:1182-91. Used with permission.

The authors conclude that cyclosporine is beneficial for several dermatologic conditions refractory to other treatments. Careful monitoring is necessary during its use. Topical administration appears to have very limited benefit.

Richard Sadovsky, M.D. Lim KK, et al. Cyclosporine in the treatment of dermatologic disease: an update. Mayo Clin Proc 1996;71:1182-91.

COPYRIGHT 1997 American Academy of Family Physicians

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