Cyclosporine consensus conference: With emphasis on the treatment of psoriasis☆,☆☆,★
Section snippets
INDICATIONS FOR THE USE OF CYCLOSPORINE
Patients for whom cyclosporine is considered should have severe skin conditions and, in general, should have tried other therapies first. For all patients in whom cyclosporine is used, short-term therapy is best when possible.
Cyclosporine is particularly useful in patients who have sudden, severe flares of dermatosis. Cyclosporine may result in rapid improvement. Subsequently, other treatments to which the patient was previously unresponsive may be effective. Most chronic skin conditions
DISORDERS TREATED WITH CYCLOSPORINE
Cyclosporine is indicated for the treatment of severe, recalcitrant, plaque psoriasis in adults who are immunocompetent.1 There are many studies indicating an impressive response to adequate doses of systemic cyclosporine.2, 3, 4, 5, 6 Indeed, there are patients with psoriasis that cannot be controlled by any other therapy but that can be cleared with cyclosporine treatment.
Many patients with atopic dermatitis have also been treated with cyclosporine in open and blinded clinical trials.7 The
MONITORING FOR CYCLOSPORINE THERAPY
In the evaluation of patients’ conditions for cyclosporine therapy, key issues include patient selection, preliminary evaluation, and continued monitoring throughout therapy. The patient should have a dermatosis that is severe enough to warrant treatment with a major systemic agent. It is reasonable to evaluate the patient’s response to less toxic therapies first. Furthermore, the expected results need to justify the risks assumed by the patient.
A personal and family history of significant
DOSAGE
The starting dose of cyclosporine for the treatment of psoriasis should depend, in part, on the clinical state of the patient (Table IV).
Starting dose: 2.5 to 5 mg/kg/d in 1 or 2 divided doses Adjust by 0.5 to 1 mg/kg/d each week as needed
CONTRAINDICATIONS
Contraindications to the use of cyclosporine are largely based on avoiding adverse effects on the kidney and on the ability of the patient’s immune system to fight infection and cancer. These contraindications can be divided into contraindications and relative contraindications (Table V).
* Renal disease * Poorly controlled hypertension * Severe infections Internal malignancy Immunodeficiency Noncompliant patient Concomitant nephrotoxic drugs Interacting drugs
RELATIVE CONTRAINDICATIONS
This category allows more individualization of treatment. Patients taking drugs that are also metabolized by the cytochrome P-450 complex must be cautioned that the concurrent use of cyclosporine may raise or lower blood levels of the interacting drug. Conversely, cyclosporine levels may be either raised or lowered depending on the identity of the interacting drug (Table VI).45Drugs that may potentiate renal dysfunction Antibiotics Gentamicin
ADVERSE EFFECTS
Adverse events are summarized in the package insert1 (Table VII).
Renal dysfunction Hypertension Hirsutism Tremor Gingival hyperplasia Musculoskeletal pain Paresthesia Microangiopathic hemolytic anemia Thrombocytopenia Headache Leg cramps Dizziness Abdominal pain Diarrhea Dyspepsia Hyperkalemia Hypomagnesemia Hyperuricemia Hypoglycemia Bilirubinemia Leukopenia Hyperlipidemia
LONG-TERM USE OF CYCLOSPORINE IN THE TREATMENT OF PSORIASIS: EFFICACY VERSUS COMPLICATIONS
In patients with psoriasis, cyclosporine has been a relatively easy drug to use during the short term. Psoriasis rapidly clears in a high percentage of patients (approximately 60% to 86% clearing at 8 to 12 weeks, respectively). These levels of clearance are generally maintained as long as the clearing dose is held relatively constant.43
To minimize possible complications, reduction in dose to a maintenance dose after improvement in an induction phase of a higher dose (5 mg/kg/d) has been used.
CONCOMITANT USE OF CYCLOSPORINE WITH OTHER PSORIASIS TREATMENTS
Although cyclosporine is effective as a single agent in the management of plaque-type psoriasis, there are many situations in which concomitant use of other agents can be considered. First is the use of topical agents for lesions that are anticipated to demonstrate resistance (eg, treating a severely thickened plaque on the elbow and/or knee with a topical superpotent corticosteroid, which can be further enhanced by adding topical tazarotene or calcipotriene). Second is the use of topical
INTERACTIONS OF CYCLOSPORINE WITH OTHER TREATMENTS FOR PSORIASIS
In a recent study, 40 patients with relapsing plaque psoriasis involving more than 20% body surface were treated with other cyclosporine plus PUVA or rePUVA. The conditions cleared within comparable periods of time. However, the cumulative UVA dose required for clearance and the incidence of severe and early relapses were significantly higher in the cyclosporine cohort.64 Neither the combination of PUVA and cyclosporine nor the combination of cyclosporine with sunlight or UVB has gained
ROTATIONAL THERAPY
To avoid increasing the chances of unwanted side-effects associated with the longer cumulative use of any single treatment, rotational therapy is often used. This involves rotating between UVB, PUVA, methotrexate, retinoids, and cyclosporine at intervals of approximately 1 to 2 years. The exact details of the rotations are based on the intensity and duration of treatments, individual patient response, and side-effect profiles.71
The question arises as to whether and how cyclosporine would fit
DISCUSSION
The package insert warns that “only physicians experienced in management of systemic immunosuppressive therapy for indicated disease should prescribe Neoral.” Such a warning is bound to be daunting to many dermatologists. However, most physicians feel proficient in the systemic use of corticosteroids and are therefore experienced with management of systemic immunosuppressive therapy. Under some circumstances, cyclosporine is safer than high-dose corticosteroids, especially for chronic
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Cited by (0)
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Supported by a grant from Novartis Pharmaceuticals, Inc.
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Reprint requests: Mark Lebwohl, MD, Mt. Sinai Medical Center, Department of Dermatology, 5E 98th St, New York, NY 10029-6574.
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