Calcineurin inhibitors in chronic urticaria

The purpose of the review is to review the pathophysiology, available data, and our current recommendations for calcineurin inhibitor (cyclosporine and tacrolimus) treatment in antihistamine refractory chronic idiopathic urticaria (CIU) patients.

Low-dose cyclosporine (<5  mg/kg per day) may have unique immunological modulating properties beyond mast cell and basophil stabilization in CIU. Starting CIU treatment with very low cyclosporine dosages (1 mg/kg per day) and titrating based on response and side-effects may decrease adverse events while preserving efficacy. In cyclosporine responsive patients failing cyclosporine taper, case series data support the safety and efficacy of long-term (5-10 years), very low dose (1-2 mg/kg per day) cyclosporine treatment with appropriate clinical monitoring.

For CIU patients refractory to antihistamines, low-dose cyclosporine therapy (<3 mg/kg per day) with appropriate laboratory monitoring provides an alternative with an acceptable side-effect profile. Long-term (>12 months) moderate-dose (2.5-5 mg/kg per day) cyclosporine treatment may cause longitudinal increases in serum creatinine. However, decreasing or stopping cyclosporine dosing reverses measured nephrotoxicity in the vast majority of patients, and some patients with careful monitoring can tolerate very low-dose cyclosporine (<2 mg/kg per day) for longer periods. Tacrolimus is an alternative to cyclosporine with a slightly different adverse effect profile. Minimal data are available on its use in chronic urticaria.