The Use of Cyclosporine in Dermatology

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

Combination Therapy
The goal of combination therapy in psoriasis is to increase the efficacy of the treatments while reducing their toxicities,19 which is especially important in the case of cyclosporine, as its complications, such as hypertension and nephrotoxicity, are dose-related.
Cyclosporine has been used effectively in combination with multiple topical therapies including topical corticosteroids,20,21 vitamin D3 analogues,22 and anthralin.23 These combinations are safe and effective as topical therapies improve the response to cyclosporine allowing reduction of the cyclosporine dose and its associated toxicity.
In contrast to topical agents, the combination of cyclosporine with phototherapy is more controversial. Although cyclosporine has been combined with ultraviolet B,24 and PUVA,25,26 there is an increased risk of skin cancer (squamous cell carcinomas). Therefore, the combination with these therapeutic modalities should be avoided, whenever possible.27,28
Cyclosporine has also been combined with other systemic therapies such as acitretin, methotrexate, mycophenolate mofetil, and biologics to achieve greater efficacy and safety. Among these, the most extensively studied are the combination of cyclosporine with Biologics and Methotrexate. The use of cyclosporine with methotrexate is controversial because cyclosporine is nephrotoxic and methotrexate is excreted by the kidneys, and because methotrexate is hepatotoxic and cyclosporine is metabolized by the liver. However, several studies using this combination for psoriasis and psoriatic arthritis seem to demonstrate benefits without a significant increase in side effects, at least with a short-term treatment.29-34
The combination with Acitretin has not evidenced additional benefits, 45 and in these cases a careful monitoring of triglycerides is warranted, as both agents alone can cause hypertriglyceridemia. This combination may play a role in the treatment of patients with multiple squamous cell carcinomas, as low doses of Acitretin have showed efficacy in preventing recurrences of the skin cancer.35,36
The combination with biologics has been discussed extensively in the literature, but the long-term risks and side effects are not well studied.37-39 Opportunistic infections have been reported in patients treated with biologics in conjunction with other systemic immunosuppressive agents.40 Therefore, it is advisable to minimize the overlap period.
Although not optimal for the treatment of psoriatic arthritis, there is some evidence of benefit with the use of cyclosporine, either alone or in combination with methotrexate.41,42
Adverse Drug Reactions/Safety
The most frequently reported adverse effects associated with the use of cyclosporine as short term in dermatology (maximum dose 5 mg per kg) including increases in serum creatinine, increase in blood urea nitrogen, arterial hypertension, decreased magnesium, increased bilirubin, increased liver enzymes, gingival hyperplasia, paresthesias, headache, muscle aches, and generalized hypertrichosis.6
Other adverse effects have also been reported in long-term studies including the developed of lymphoproliferative disorders and other malignant tumors.43 However, the majority of these studies did not evaluate the risk in the general population or in psoriasis populations and did not evaluate the patients for years after discontinuation of the drug. The largest study (over 1200 subjects) evaluating the long-term safety of cyclosporine in dermatologic patients concluded that there was no evidence that cyclosporine at dermatologic doses (maximum 5 mg/kg/day) with no additional immunosuppresion increased the risk of lymphomas or internal malignancies.44 However, the same study demonstrated a significant increase in the incidence of non-melanoma skin cancers (especially squamous cell carcinomas). Another adverse event associated with the long-term treatment is the developed of opportunistic infections. Like other immunosuppressive therapies, cyclosporine may increase the risk of various bacterial, parasitic, viral, and fungal infections, as well as the risk of infections with opportunistic pathogens.
In our opinion, even with recent developments of new therapeutic modalities, cyclosporine remains an effective systemic therapy for moderate to severe psoriasis. Current American Academy of Dermatology guidelines suggests that intermittent therapy with cyclosporine for psoriasis is preferable to longterm treatment. In long-term therapy, the risks and benefits for each individual patient must be weighed carefully due to adverse drug reactions, especially nephrotoxicity and increases in blood pressure, as well as a potentially increased risk of non melanoma skin cancer. In cases in which long-term treatment is needed, the duration of continuous treatment should not exceed 1 year whenever possible.
Atopic Dermatitis
Atopic dermatitis (AD) is a chronic relapsing skin disease. Therefore successful treatment of AD requires systematic, multifaceted approach incorporating skin hydration, pharmacologic therapy and identification and elimination of trigger factors. In patients refractory to conventional forms of therapy, anti-inflammatory and immunosuppressive agents may be necessary.45
Cyclosporine has been recommended by the AAD as being effective for the treatment of atopic dermatitis refractory to conventional therapy. Unfortunately there is no statement as to the recommended dosage although the dosage employed for psoriasis is conventionally used. Cyclosporine has been used widely in adults and children with AD.1