Hyams Jeffrey S, Markowitz James F
Division of Digestive Diseases and Nutrition, Connecticut Children's Medical Center, Hartford, CT 06106, USA.
J Pediatr Gastroenterol Nutr. 2005 Mar;40(3):262-72. doi: 10.1097/01.mpg.0000154660.62359.fe.
The natural history of Crohn disease is characterized by recurrent bouts of active disease, the consequences of which can severely impair sufferers' physical and social functioning. Not only does the illness cause day-to-day morbidity for children but the consequence of the chronic inflammatory process also commonly results in the need for major intestinal surgery. The present challenge facing physicians treating children with Crohn disease is to alleviate symptoms and prolong periods of remission via the use of specifically targeted therapies while minimizing toxicity and promoting normal growth and development. Although systemic corticosteroids are effective in inducing clinical remission, they are of little or no benefit in maintaining remission and can contribute to linear growth retardation. Immunomodulating drugs such as azathioprine, 6-mercaptopurine and methotrexate have proved effective for inducing and maintaining remission of active Crohn disease. These agents are now commonly prescribed in children at diagnosis, after a severe attack or after surgery or in those who become corticosteroid-dependent or corticosteroid-resistant. Their use is not without potential adverse effects and not all patients respond well to these agents. With the introduction of biologic agents, notably the tumor necrosis factor-alpha monoclonal antibody infliximab, progress has been made in targeting specific pathogenetic mechanisms of Crohn disease and potentially altering the underlying disease process. Published experience in children is currently limited, but infliximab has been shown to improve symptoms and achieve corticosteroid independence in this age group. Unresolved issues with infliximab and other emerging biologic agents, including long-term safety, necessitate a degree of caution in selecting appropriate patients for treatment and with careful monitoring of their effects. The collection of contemporary natural history data is crucial to facilitate the better integration of current and emerging therapies in an attempt to alter the natural history of Crohn disease in children.
克罗恩病的自然病程特点是疾病活动反复发作，其后果会严重损害患者的身体和社交功能。这种疾病不仅会导致儿童日常发病，而且慢性炎症过程的后果通常还会导致需要进行大型肠道手术。目前，治疗儿童克罗恩病的医生面临的挑战是，通过使用特异性靶向疗法来缓解症状并延长缓解期，同时将毒性降至最低，并促进正常生长发育。虽然全身用皮质类固醇在诱导临床缓解方面有效，但在维持缓解方面作用甚微或没有作用，且会导致线性生长迟缓。免疫调节药物，如硫唑嘌呤、6-巯基嘌呤和甲氨蝶呤，已被证明对诱导和维持活动性克罗恩病的缓解有效。现在，这些药物通常在儿童诊断时、严重发作后、手术后或那些对皮质类固醇产生依赖或耐药的患者中使用。它们的使用并非没有潜在的不良反应，而且并非所有患者对这些药物反应良好。随着生物制剂的引入，尤其是肿瘤坏死因子-α单克隆抗体英夫利昔单抗的出现，在针对克罗恩病的特定发病机制以及潜在改变潜在疾病进程方面取得了进展。目前关于儿童的已发表经验有限，但英夫利昔单抗已被证明可改善该年龄组的症状并实现皮质类固醇非依赖。英夫利昔单抗和其他新兴生物制剂尚未解决的问题，包括长期安全性，使得在选择合适的治疗患者时需要一定程度的谨慎，并仔细监测其效果。收集当代自然病程数据对于促进更好地整合当前和新兴疗法以试图改变儿童克罗恩病的自然病程至关重要。
