Thorbinson Colin, Oni Louise, Smith Eve, Midgley Angela, Beresford Michael W
Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Institute in the Park, Alder Hey Children's NHS Foundation Trust Hospital, Eaton Road, Liverpool, L12 2AP, UK.
Paediatr Drugs. 2016 Jun;18(3):181-95. doi: 10.1007/s40272-016-0170-8.
Systemic lupus erythematosus (SLE) is a rare, severe, multisystem autoimmune disorder. Childhood-onset SLE (cSLE) follows a more aggressive course with greater associated morbidity and mortality than adult-onset SLE. Its aetiology is yet to be fully elucidated. It is recognised to be the archetypal systemic autoimmune disease, arising from a complex interaction between the innate and adaptive immune systems. Its complexity is reflected by the fact that there has been only one new drug licensed for use in SLE in the last 50 years. However, biologic agents that specifically target aspects of the immune system are emerging. Immunosuppression remains the cornerstone of medical management, with glucocorticoids still playing a leading role. Treatment choices are led by disease severity. Immunosuppressants, including azathioprine and methotrexate, are used in mild to moderate manifestations. Mycophenolate mofetil is widely used for lupus nephritis. Cyclophosphamide remains the first-line treatment for patients with severe organ disease. No biologic therapies have yet been approved for cSLE, although they are being used increasingly as part of routine care of patients with severe lupus nephritis or with neurological and/or haematological involvement. Drugs influencing B cell survival, including belimumab and rituximab, are currently undergoing clinical trials in cSLE. Hydroxychloroquine is indicated for disease manifestations of all severities and can be used as monotherapy in mild disease. However, the management of cSLE is hampered by the lack of a robust evidence base. To date, it has been principally guided by best-practice guidelines, retrospective case series and adapted adult protocols. In this pharmacological review, we provide an overview of current practice for the management of cSLE, together with recent advances in new therapies, including biologic agents.
系统性红斑狼疮（SLE）是一种罕见、严重的多系统自身免疫性疾病。儿童期起病的系统性红斑狼疮（cSLE）病情进展更为迅猛，相较于成人期起病的SLE，其相关发病率和死亡率更高。其病因尚未完全阐明。它被认为是典型的系统性自身免疫性疾病，由先天免疫系统和适应性免疫系统之间的复杂相互作用引发。其复杂性体现在过去50年中仅有一种新药获批用于SLE治疗这一事实上。然而，特异性针对免疫系统各方面的生物制剂正在不断涌现。免疫抑制仍然是药物治疗的基石，糖皮质激素仍发挥着主导作用。治疗选择取决于疾病的严重程度。免疫抑制剂，包括硫唑嘌呤和甲氨蝶呤，用于轻至中度症状。霉酚酸酯广泛用于狼疮性肾炎。环磷酰胺仍是重症器官疾病患者的一线治疗药物。尽管生物疗法在重度狼疮性肾炎或伴有神经和/或血液系统受累的患者的常规治疗中越来越多地被使用，但尚无生物疗法获批用于cSLE。影响B细胞存活的药物，包括贝利尤单抗和利妥昔单抗，目前正在cSLE中进行临床试验。羟氯喹适用于所有严重程度的疾病表现，在轻度疾病中可作为单一疗法使用。然而，cSLE的管理因缺乏有力的证据基础而受到阻碍。迄今为止，主要是依据最佳实践指南、回顾性病例系列和改编的成人治疗方案来进行指导。在本药理学综述中，我们概述了cSLE管理的当前实践，以及包括生物制剂在内的新疗法的最新进展。
