**7.2 Renal dysfunction**

Though renal dysfuntion is recognized as a cyclosporin-related side effect, the real impact of cyclosporin on kidney function may need to be reassessed. The experience in transplant patients, particularly in kidney transplant recipients where cyclosporin is used at higher doses in life-long regimens shows, that these regimens are well tolerated (Cho & Terasaki, 1988; Opelz, 1994). An Italian study conducted in 573 kidney transplant recipients showed that creatinine plasma levels remain constant and around 1.5 mg/dl over 15 years after the intervention, a clear indication of stable kidney function ( Sandrini, data presented at SIN 2003 Bologna).

When renal dysfunction persists during cyclosporin therapy, it is usually related to higher doses (>5 mg/kg/day) or extended treatment (>2 years), and both of these factors may lead to structural renal damage. Renal dysfunction may also comprise functional impairment (i.e. vascular or tubular dysfunction), which may be evident soon after starting treatment. The consequences of vascular dysfunction are reduced glomerular filtration rate and renal blood flow, and reduced creatinine clearance, whereas the consequences of tubular dysfunction may include hypomagnesaemia, reduced plasma bicarbonate levels, hyperuricaemia, and hyperkalaemia. Acute functional impairment is generally reversible when cyclosporin treatment is discontinued; thus, the risk of renal toxicity is minimised when intermittent

Systemic Cyclosporin in the Treatment of Psoriasis 301

involving 631 psoriatic patients reveals rates of 2.3%, 2.0%, 2.0%, 3.8%, and 1.1%,

Gingival hyperplasia may occur in up to 30% of patients taking cyclosporin and is often linked with poor oral hygiene (Ryan et al., 2010). Thanks to increased oral health awareness, improved oral hygiene, and better public health service this condition occurs rarely in developed countries. If it occurs, this side effect usually manifests within the first 3–6

Hypertriglyceridaemia (>750 mg/dL) occurs in approximately 15% of cyclosporin-treated patients, and hypercholesterolaemia in <3% (Neoral® Prescribing Information, 2011). Importantly, hyperlipidaemia normalizes when cyclosporin therapy is stopped (Shupack

Severe psoriasis is associated with increased cardiovascular morbidity and mortality (see section 7.1.1); thus, hyperlipidaemia should be actively managed in cyclosporin-treated patients with psoriasis. If cyclosporin therapy is continued, the initial intervention is a lipidlowering diet. If this is unsuccessful, the cyclosporin dosage should be reduced, or treatment with a lipid-lowering agent started. Fluvastatin was shown to be well tolerated in association with cyclosporin (Holdaas et al., 1995; Launay-Vacher 2005). In general, however, statins should be used with caution because of the risk, albeit very low, of rhabdomyolysis, as reported in a few cases of transplanted patients treated with cyclosporin

In large-scale clinical trials and meta-analyses in cyclosporin-treated patients with psoriasis, the incidence of hypertrichosis has varied widely from 1–27% (Table 2); the cause of this side effect is unclear, but it is unlikely to be an altered endocrine status (Ryan et al., 2010).

Cyclosporin-induced infections occur rarely, and are rarely severe; controlled studies in psoriasis report no difference in the incidence of infections between cyclosporin and placebo recipients. Moreover, an overview of 20 years' safety data for cyclosporin in dermatology patients revealed no increases in the risks of opportunistic infections or tuberculosis

B- and T-cell lymphomas have rarely been reported in cyclosporin-treated patients with psoriasis (Ryan et al., 2010). For instance, 2/842 patients (0.2%) developed these lymphomas

and lovastatin or simvastatin (Ryan et al., 2010; Corpier et al., 1988).

respectively (Krupp & Monka, 1990).

**7.5 Gingival hyperplasia** 

months of treatment.

**7.6 Hyperlipidaemia** 

**7.7 Hypertrichosis** 

**7.8 Infections** 

**7.9 Malignancies 7.9.1 Lymphomas** 

reactivation (Ryan et al., 2010).

et al., 1997).

cyclosporin therapy is prescribed in psoriasis, since such therapy is associated with normalisation of renal function between treatment courses (Ryan et al., 2010).

Besides raised plasma creatinine levels, other predictors of cyclosporin-related nephropathy include advanced age, obesity, new-onset or pre-existing hypertension or renal disorders, and other nephrotoxic treatments. Altogether, as relatively low cyclosporin dosages are now used in psoriasis, tubulopathic changes are rare and reversible (Ryan et al., 2010).
