Fels Edward, Sundy John S
Departments of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.
Curr Opin Rheumatol. 2008 Mar;20(2):198-202. doi: 10.1097/BOR.0b013e3282f4eff5.
The purpose of this review is to discuss the defining characteristics of refractory gout and the pharmacological management of this problem.
Refractory gout refers to those patients who have ongoing symptoms of active disease and cannot maintain a target serum urate less than 6 mg/dl. Patients with refractory gout have reduced quality of life, functional impairment, and joint destruction. Multiple factors contribute to refractory gout, and they often relate to delayed or insufficient dosing with allopurinol. Chronic kidney disease imparts a dose limitation on allopurinol that further impairs the effectiveness of urate-lowering therapy. Febuxostat, a novel xanthine oxidase inhibitor, represents a potential alternative to allopurinol in refractory gout patients. Uricase, the enzyme that catalyzes conversion of uric acid into allantoin, is showing promise with its ability to rapidly diminish serum urate levels. The recently defined role of the NALP3 inflammasome in the inflammatory phase of gout suggests a potential role for interleukin-1 inhibition in urate crystal-induced inflammation.
Refractory gout occurs when urate levels are not adequately controlled. Emerging therapies may improve the clinical course of patients with recalcitrant disease.
本综述旨在探讨难治性痛风的定义特征以及该问题的药物治疗。
难治性痛风指那些存在活动性疾病持续症状且无法将血清尿酸水平维持在低于6mg/dl目标值的患者。难治性痛风患者的生活质量下降、功能受损且关节遭到破坏。多种因素导致难治性痛风,且这些因素常与别嘌醇给药延迟或剂量不足有关。慢性肾脏病对别嘌醇的剂量有一定限制,这进一步削弱了降尿酸治疗的效果。非布司他,一种新型黄嘌呤氧化酶抑制剂,为难治性痛风患者提供了一种潜在的别嘌醇替代药物。尿酸酶,一种催化尿酸转化为尿囊素的酶,因其能迅速降低血清尿酸水平而展现出前景。最近确定的NALP3炎性小体在痛风炎症期的作用提示白细胞介素-1抑制在尿酸盐结晶诱导的炎症中可能发挥作用。
当尿酸水平未得到充分控制时即发生难治性痛风。新出现的疗法可能改善难治性疾病患者的临床病程。