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.
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
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.
Summary
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.
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
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
