背景:肉芽肿性多血管炎(GPA),以前被称为韦格纳肉芽肿病,是一种自身免疫性疾病,其特征是坏死性肉芽肿性炎症和影响小血管的血管炎。它通常影响肾脏和呼吸系统。
方法:这项回顾性病例系列抽样于2023年5月至2024年4月在三级医院进行,检查了6名新诊断的GPA患者,这些患者为蛋白酶3细胞质-抗核细胞质抗体(PR3c-ANCA)阳性,并伴有呼吸道感染。他们都没有任何先前的免疫抑制条件。年龄范围为18-47岁,平均为35.0(标准偏差:11.83)。所有患者均有肺炎(N=6,100%)。最重要的是,5例细菌性肺炎(N=5,83.3%),1例结核性肺炎(N=1,16.7%).在4例患者中发现高水平的PR3c-ANCA(>150RU/mL)(N=4,66.7%)。常见症状包括干咳(N=5,83.3%),体重和食欲下降(N=2,33.3%),发热(N=2,33.3%)。三名患者患有中耳炎和/或鼻息肉病(N=3,50%)。两名危及生命的器官功能障碍患者(N=2,33.3%)同时给予抗生素和类固醇;随后根据培养和敏感性结果对抗生素进行了修改。其中一名患者接受了抗结核治疗,因为在分枝杆菌生长指示剂管肉汤中孵育27天后检测到结核分枝杆菌(MTB)。其余四名患者(N=4,66.7%)最初接受抗生素治疗5-7天,直至肺炎临床消退。最终,在治疗后3-6个月内,它们均显示出临床和放射学分辨率(N=6,100%)。
结果:患者表现出发热和体重减轻等全身症状;下气道疾病症状包括干咳和咯血;鼻和耳部疾病症状,如鼻出血,耳朵疼痛,和耳朵分泌物;和肾脏疾病症状,血尿.胸部计算机断层扫描显示双侧合并,其中大多数是空化的。支气管肺泡灌洗培养物生长大肠杆菌,洋葱伯克霍尔德菌,铜绿假单胞菌,肺炎克雷伯菌,和MTB,而来自中耳炎的脓液拭子培养物生长了铜绿假单胞菌,金黄色葡萄球菌,和凝固酶阴性葡萄球菌。
结论:本研究强调了GPA并发并发感染的治疗挑战。患者表现出典型的GPA体征,通过PR3c-ANCA水平证实。并发感染在开始免疫抑制治疗之前需要谨慎的抗生素治疗。除了危及生命的器官功能障碍。一个独特的病例同时患有结核病和GPA。结合抗生素和免疫抑制剂的量身定制的治疗方案,包括皮质类固醇,甲氨蝶呤,利妥昔单抗,导致所有患者在3-6个月内的临床和放射学改善。复方新诺明的加入降低了非重度GPA复发的发生率。
结论:针对感染和自身免疫方面的量身定制的治疗计划对于合并感染的GPA的最佳护理至关重要。这项研究强调了需要一种涉及肺科医师的多学科方法,风湿病专家,微生物学家,和诊断和治疗GPA的病理学家,强调针对特定临床情况量身定制的个性化治疗计划的重要性。
BACKGROUND: Granulomatosis with polyangiitis (GPA), formerly termed Wegener\'s granulomatosis, is an autoimmune disease marked by necrotizing granulomatous inflammation and vasculitis affecting small-sized vessels. It commonly impacts the renal and respiratory systems.
METHODS: This retrospective
case series sampling conducted in a tertiary care hospital between May 2023 and April 2024 examined six newly diagnosed GPA patients who were proteinase 3 cytoplasmic-antinuclear cytoplasmic antibody (PR3 c-ANCA) positive and had concurrent respiratory infections. None of them had any prior immunosuppressive conditions. The age range was 18-47 years with a mean of 35.0 (standard deviation: 11.83). All the patients had pneumonia (N=6, 100%). Out of all, five had bacterial pneumonia (N=5, 83.3%) and one had tuberculous pneumonia (N=1, 16.7%). A high level of PR3 c-ANCA (>150 RU/mL) was noted in four patients (N=4, 66.7%). Common symptoms included dry cough (N=5, 83.3%), loss of weight and appetite (N=2, 33.3%), and fever (N=2, 33.3%). Three patients had otitis media and/or nasal polyposis (N=3, 50%). Two patients (N=2, 33.3%) with life-threatening organ dysfunction were given concurrent antibiotics and steroids; the antibiotics were later modified based on culture and sensitivity results. One of these patients received antituberculosis therapy as Mycobacterium tuberculosis (MTB) was detected after 27 days of incubation in mycobacterial growth indicator tube broth. The remaining four patients (N=4, 66.7%) received antibiotics initially for 5-7 days until clinical resolution of pneumonia. Ultimately, they all showed clinical and radiological resolution (N=6, 100%) within 3-6 months of treatment.
RESULTS: The patients exhibited constitutional symptoms such as fever and weight loss; lower airway disease symptoms including dry cough and hemoptysis; nasal and ear disease symptoms like epistaxis, ear pain, and ear discharge; and a renal disease symptom, hematuria. Computed tomography of the thorax revealed bilateral consolidations, most of which were cavitating. Bronchoalveolar lavage cultures grew Escherichia coli, Burkholderia cepacia, Pseudomonas aeruginosa, Klebsiella pneumoniae, and MTB, whereas pus swab cultures from otitis media grew Pseudomonas aeruginosa, Staphylococcus aureus, and coagulase-negative staphylococci.
CONCLUSIONS: This study highlights the therapeutic challenges of GPA complicated by concurrent infections. Patients exhibited typical GPA signs, confirmed by PR3 c-ANCA levels. Concurrent infections require cautious antibiotic treatment before starting immunosuppressive therapy, except in life-threatening organ dysfunction. A unique
case presented with both tuberculosis and GPA. Tailored treatment regimens combining antibiotics and immunosuppressives, including corticosteroids, methotrexate, and rituximab, resulted in clinical and radiological improvement in all the patients within 3-6 months. The addition of co-trimoxazole reduced the incidence of non-severe GPA relapses.
CONCLUSIONS: Tailored treatment plans addressing both infectious and autoimmune aspects are essential for optimal care in GPA complicated by concurrent infections. This study highlights the need for a multidisciplinary approach involving pulmonologist, rheumatologist, microbiologist, and pathologist in the diagnosis and treatment of GPA, emphasizing the importance of individualized treatment plans tailored to the specific clinical scenario.