The Use of Cyclosporine in Dermatology

August 2012 | Volume 11 | Issue 8 | Original Article | 979 | Copyright © August 2012

Cyclosporine had been shown to reduce the numbers of helper/ inducer T-cells and the number of activated cells expressing Interleukin- 2 (IL-2), IL-4, and IL-5. It also inhibits the growth and differentiation of B-lymphocytes and the functional activities of mononuclear phagocytes, Langerhan's cells, and eosinophils. Furthermore, recently immunohistochemical study showed that cyclosporine may play a therapeutic role via effects on the cutaneous nervous system through altered innervations and neuropeptide expression in lesional skin of AD. In addition to these, cyclosporine inhibits mast cells (MC) activation by altering the topographical relationship between MCs and the cutaneous nerves in lesional skin, suggesting a new aspect of the effects of cyclosporine in the management of the DA.46
In terms of cyclosporine dosage, some studies suggested the dose of 5 mg/kg/day for 2 weeks with gradual tapering as dictated by the clinical response over the ensuing 3 months to a dose of 1.5 mg/kg/day. Other studies had reported a starting dose of 1.0 mg/kg/day to 4.2 mg/kg/day and whenever possible dosing titrated to a minimal clinically effective dose. In general these dosages showed an objective decrease in 50% of the lesions at 6 to 8 weeks of treatment correlated with the improvement in the disease severity score, lichenification score, disease extent score, itch, loss of sleep, and overall benefit in the quality of life.
The response with the use of higher dose is faster than with the lower dose when cyclosporine is used as a short-term treatment in crisis intervention for AD.47
There are studies showing that cyclosporine can be used intermittently, but when comparing these studies with those using continuous therapy, the results showed more consistent results (long term remission) when the continuous therapy had been used.1,48
Similar to psoriasis, when maintenance therapy is needed, the lowest effective dose should be used to ensure maximum safety.1,47
Most of the trials concluded that using the continued and lowdose therapy has been safe and effective for the long-term treatment of atopic dermatitis in children and adults. Close follow up and routine laboratory monitoring must be performed.1,46,48,49
In regards to withdrawal of cyclosporine treatment, Granlund et al showed rapid relapses within 2 weeks after discontinuation of therapy (50% of the patients); other studies have found high incidence of relapse, however, the time to relapse was longer. Harper found 86% of relapses after 9 months of discontinuation of treatment and Atakam and Erdem reported 75% of patients relapsed at 24 weeks post cyclosporine treatment. Thus, there is an expectation that the disease will worsen upon cessation of cyclosporine. However, the extent of disease and symptoms scores remain better than at baseline in the post treatment period, suggesting a possible sustained remission in some patients.1,46
Schmitt et al, showed in a meta-analysis that there was no evidence of a rebound phenomenon on withdrawn of cyclosporine, but there are isolated retrospective studies that did report a rebound phenomenon in a small number of patients.1
Chronic Urticaria
Urticaria is a cutaneous vascular reaction induced by immunological and nonimmunological mechanism. The mainstays for the treatment of chronic urticaria are antihistamines and occasionally short courses of corticosteroids.
Cyclosporine may be used for the treatment of severe chronic idiopathic urticaria as an alternative to corticosteroid therapy, either as a steroid-sparing agent or as monotherapy in chronic urticaria that is refractory to corticosteroid therapy.1,50
Guidelines from the British Association of Dermatology have recommended cyclosporine for the treatment of severe chronic idiopathic urticaria to be unresponsive to antihistamines, while stating that optimal patient selection, dose, and duration of treatment remain to be defined. However, long term use of cyclosporine is not recommended.1
A study reported by Tsutomu in 2010, showed in all of the patients, activated B cells (CD19+, CD23+ cells) and among the CD19+ cells, 20% were CD5+. Serum IL-2, TNF-α, and IL-5 levels of patients before cyclosporine treatment were statistically higher than those of the control group and after 4 weeks of cyclosporine therapy, IL-2, TNF-α, and IL-5 levels were significantly decreased.51,52
In the last decade, cyclosporine was reported to be beneficial in 27 studies, some of which were doubled-blind controlled studies. In some of them the dose of cyclosporine was between 4 mg/kg/day to 5 mg/kg/day whereas a low dose (2 mg/kg/day to 3 mg/kg/day) was given in other studies. When lower dose of cyclosporine was administered (2 mg/kg/day to 3 mg/kg/ day, most studies reported a very low incidence of side effects (mostly gastrointestinal or peripheral neuropathy).51,52 In all of these studies, the responses indicated clinical improvement.
Consequently, when lower doses of cyclosporine treatment (2.5 mg/kg/day) were given for 4 weeks, it lowered the serum levels of IL-2R, IL-5, and TNF-α, which are frequently increased in patients with chronic idiopathic urticaria.1,50
There are other studies that have attempted to answer not only the question of the dose but also the duration of cyclosporine treatment for chronic urticaria. Several authors recommended a starting dose between 3 mg/kg/day to 5 mg/kg/day for 6 weeks followed by 3 weeks at 2 mg/kg/day and then 3 weeks at 1 mg/kg/day before discontinuing. That regimen has resulted in remission or significant improvement while maintaining a good safety profile.1