King Catherine, Harper Lorraine
Centre for Translational Inflammation Research University of Birmingham Research Laboratories, Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham, B15 2WB UK.
Curr Treatm Opt Rheumatol. 2017;3(4):230-243. doi: 10.1007/s40674-017-0082-y. Epub 2017 Nov 13.
With established immunosuppressant treatment regimens for anti-neutrophil cytoplasm antibody-associated vasculitides (AAV), prognosis has significantly improved. The mainstay of treatment still comprises high-dose corticosteroids and cyclophosphamide for severe forms, although rituximab is being increasingly utilised instead of cyclophosphamide as induction therapy. AAV patients experience an excess of infections, malignancies and cardiovascular events as compared to the general population, which is a combination of the systemic inflammatory process associated with vasculitis and the adverse events from treatment. Successful therapy should focus on suppressing disease activity and minimising treatment-related toxicity. Infection is the largest contributor to morbidity and mortality in the first year of treatment, and annual pneumococcal and influenza vaccinations, prophylaxis and tuberculosis (TB) and Hepatitis B virus screening are advised. Patients on high-dose corticosteroid treatment should have regular blood sugar monitoring, a FRAX assessment with vitamin D and calcium supplementation, consideration of prophylaxis for gastric ulcers and a cardiovascular risk assessment. Patients who are treated with cyclophosphamide could also receive MESNA to reduce the risk of chemical cystitis. Cyclophosphamide, methotrexate and azathioprine all require blood monitoring schedules due to the risk of bone marrow suppression, liver and renal toxicity. Hypogammaglobulinaemia is a recognised risk of rituximab treatment. Patients of reproductive age need to be counselled on the infertility risks with cyclophosphamide and the teratogenicity associated with it, methotrexate and mycophenolate mofetil. A greater focus on identifying clinical and biological markers that will help identify those patients at greatest risk of relapse, e.g. GPA and PR3-ANCA specificity, from those patients at greatest risk of toxicity, e.g. increasing age and declining GFR, is required to allow treatment to be tailored accordingly.
随着抗中性粒细胞胞浆抗体相关性血管炎（AAV）既定免疫抑制治疗方案的应用，预后有了显著改善。尽管利妥昔单抗作为诱导疗法正越来越多地被用于替代环磷酰胺，但对于重症形式的治疗，主要手段仍然包括大剂量糖皮质激素和环磷酰胺。与普通人群相比，AAV患者感染、恶性肿瘤和心血管事件的发生率更高，这是血管炎相关的全身炎症过程与治疗不良事件共同作用的结果。成功的治疗应着重于抑制疾病活动并将治疗相关毒性降至最低。感染是治疗第一年发病和死亡的最大原因，建议每年接种肺炎球菌和流感疫苗、进行预防以及筛查结核病（TB）和乙型肝炎病毒。接受大剂量糖皮质激素治疗的患者应定期监测血糖，进行FRAX评估并补充维生素D和钙，考虑预防胃溃疡并进行心血管风险评估。接受环磷酰胺治疗的患者也可接受美司钠以降低化学性膀胱炎的风险。由于存在骨髓抑制、肝毒性和肾毒性风险，环磷酰胺、甲氨蝶呤和硫唑嘌呤都需要进行血液监测。低丙种球蛋白血症是利妥昔单抗治疗公认的风险。需要对育龄期患者进行咨询，告知其环磷酰胺导致不育的风险以及环磷酰胺、甲氨蝶呤和霉酚酸酯相关的致畸性。需要更加关注识别临床和生物学标志物，以帮助区分复发风险最高的患者（例如GPA和PR3-ANCA特异性）与毒性风险最高的患者（例如年龄增长和肾小球滤过率下降），从而能够相应地调整治疗方案。
