Hyams Jeffrey S
Division of Digestive Diseases, Hepatology, and Nutrition, Connecticut Children's Medical Center, University of Connecticut School of Medicine, Hartford, CT 06106, USA.
Dig Dis. 2009;27(3):291-6. doi: 10.1159/000228563. Epub 2009 Sep 24.
Clinicians caring for children with Crohn's disease must consider the long-term implications of therapeutic interventions and cumulative diagnostic studies in their patients whose disease duration will be measured in decades. There is evidence of the increased severity of pediatric Crohn's disease compared to its adult counterpart, its frequent co-morbid growth disturbances, and the frequent need for aggressive medical therapies including immunomodulators and biological agents. The initial management of most children diagnosed with Crohn's disease involves enteral nutritional support, corticosteroids, and immunomodulators. Corticosteroids, while initially helpful in decreasing signs and symptoms of disease, are occasionally ineffective, generally do not heal mucosa, impair growth, and are frequently associated with a state of corticosteroid dependency. Immunomodulators are effective maintenance therapies with corticosteroid sparing effects, but have no value in the acutely ill child. The emergence of biological therapy with its impressive record of rapid efficacy and use as maintenance therapy has prompted discussion of its incorporation into initial management, but has also raised concerns about who are the most suitable candidates, which if any medications can be used concomitantly, and long-term safety. The combined use of thiopurines and anti-TNF agents may predispose to a rare and uniformly fatal lymphoma. Identification of children at high risk for complicated disease may allow us to better evaluate risk/benefit in newly diagnosed children, and biologic agents are likely to assume an increasing role in primary therapy in those deemed at highest risk. Long-term observations will determine whether biologics will change natural history and demonstrate adequate safety.
照顾克罗恩病患儿的临床医生必须考虑治疗干预措施和累积诊断研究对其患者的长期影响,这些患者的疾病病程将以数十年计。有证据表明,与成人克罗恩病相比,小儿克罗恩病病情更严重,常伴有生长发育障碍等共病,且频繁需要包括免疫调节剂和生物制剂在内的积极药物治疗。大多数被诊断为克罗恩病的儿童的初始治疗包括肠内营养支持、皮质类固醇和免疫调节剂。皮质类固醇虽然最初有助于减轻疾病的体征和症状,但偶尔无效,通常无法治愈黏膜,会损害生长,且常与皮质类固醇依赖状态相关。免疫调节剂是有效的维持治疗方法,具有节省皮质类固醇的作用,但对急病患儿无价值。生物疗法因其快速起效的出色记录以及作为维持治疗的应用,引发了关于将其纳入初始治疗的讨论,但也引发了对谁是最合适的候选者、哪些药物(如果有的话)可以联合使用以及长期安全性的担忧。硫嘌呤类药物和抗TNF药物联合使用可能会引发一种罕见且一致致命的淋巴瘤。识别出疾病复杂风险高的儿童可能使我们能够更好地评估新诊断儿童的风险/益处,生物制剂可能会在那些被认为风险最高的儿童的初始治疗中发挥越来越大的作用。长期观察将确定生物制剂是否会改变自然病程并证明具有足够的安全性。