**9. Conclusions**

Cyclosporin was first approved for the treatment of severe psoriasis in the 1990s, and indeed, it is one of the most effective antipsoriatic agents available because of its fast onset of action and potent immunosuppressive activity. Besides psoriasis, other dermatological disorders — most notably, pyoderma gangrenosum and refractory chronic idiopathic urticaria — have seen substantial off-label cyclosporin use in recent years. Nonetheless, concerns remain among some dermatologists about the safety of cyclosporin, even though a growing evidence base exists of a favourable benefit : risk profile for the compound, especially in the management of psoriasis, psoriatic arthritis, and atopic dermatitis.

Perhaps the most frequent safety concerns, and those potentially explaining underutilisation of cyclosporin by some dermatologists, are hypertension and renal impairment. However, it should be remembered that psoriasis itself is associated with increased cardiovascular morbidity, and any new hypertension emerging during cyclosporin therapy can be managed effectively by dosage reduction and/or antihypertensive therapy. Moreover, persistent renal dysfunction during cyclosporin therapy is usually associated with dosages >5 mg/kg/day, or treatment periods of >2 years; usually, if the dosage is kept

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at ≤5 mg/kg/day, and if renal function is monitored closely so that plasma creatinine levels remain ≤30% above baseline, any renal side effects occurring during cyclosporin therapy will be reversible when treatment is stopped.

Safety concerns may also exist about possible malignancies during cyclosporin administration. Again, however, it should be emphasised that the disease itself leads to long-term immunological overstimulation, such that psoriatic patients have greater risks of lymphoma and other malignancies compared to the general population. Any risk of nonmelanoma skin cancer during cyclosporin administration appears to be minimised if the duration of continuous therapy is kept to ≤2 years, and if PUVA is avoided; and some studies suggest that cyclosporin plus other immunosuppressant therapy may actually reduce the risks of some cancers (e.g. breast, rectal).

Additional well-designed assessments of various cyclosporin schedules are now warranted in the treatment of psoriasis. Such assessments should include:


In summary, the immunosuppressive properties of cyclosporin in the transplant and nontransplant settings have been widely recognised for approximately 3½ decades. As such, there is much clinical knowledge and experience of cyclosporin use in non-dermatological settings, but in the dermatological arena, clinical experience is 'catching up'. Cyclosporin has now been used in the treatment of psoriasis for almost 15 years, and with the relatively low doses used, dermatologists appear to be moving beyond any potential safety concerns about the compound, and are increasingly embracing the established antipsoriatic efficacy of the drug. As further clinical, economic, and quality-of-life data accrue from wellconducted clinical trials of cyclosporin monotherapy and combination therapy schedules, dermatologists, policy makers, and patients are likely to gain even more confidence in the favourable efficacy and tolerability profiles of cyclosporin in the treatment of psoriasis and other dermatological disorders.
