Abstract and Introduction
Abstract
Purpose of review 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.
Recent findings 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.
Summary 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.
Introduction
The etiological enigma, significant morbidity, and commonplace antihistamine treatment failure complicate chronic urticaria management. With a lifetime prevalence of 1.8–2.9% and without an identifiable cause in 75–90% of cases, chronic idiopathic urticaria (CIU) affects a significant portion of the population and often provokes unnecessary dietary modifications and laboratory testing. Chronic urticaria's unpredictable attacks, sleep disruption, and decreased work productivity decrease quality-of-life scores similar to patients awaiting a coronary artery bypass.
As a first-line therapy, second generation H1-antihistamines at up to four times the standard dose provide only 38–55% of CIU patients symptom resolution, and sedation limits dosing in 10–15% of patients. Antihistamine resistant CIU patients typically respond to corticosteroids; however, corticosteroid's long-term utility is limited by significant side-effects such as hyperglycemia, osteoporosis, weight gain, osteonecrosis, and glaucoma. Some guidelines suggest adding leukotriene receptor antagonist; however, efficacy evidence is considered low. Dapsone, sulfasalazine, methotrexate, interferon, plasmapheresis, phototherapy, doxepin, cyclosporine A (CsA), tacrolimus, and omalizumab have all been proposed as next line treatment for H1-antihistamines refractory CIU. Other than a handful of randomized CsA studies and a few recent industry sponsored omalizumab trials, very few data exist to support most of these interventions. This article will review calcineurin inhibitors (cyclosporine A, tacrolimus) use in CIU management.