儿童粒细胞缺乏性小肠结肠炎的诊断和处理

目的 粒细胞缺乏性小肠结肠炎在临床上以粒细胞缺乏、腹痛和高热为三大主症.本文回顾了粒细胞缺乏性小肠结肠炎患儿17例,对其临床特征、治疗和预后进行分析.方法 总结复旦大学附属儿科医院2004至2009年5年间粒细胞缺乏性盲肠炎息儿的临床资料,并进行文献复习.结果 17例患儿,男11例,女6例,平均年龄7.2岁.2例淋巴瘤,11例白血病,1例再生障碍性贫血,1例神经母细胞瘤,2例单纯性粒细胞缺乏而无明显的基础性疾病证据.所有患儿均有典型的临床表现,4例有弥漫性腹膜炎,中毒性休克,其中3例需要呼吸机辅助通气治疗.体检发现有右下腹压痛和肌紧张.伴有CRP的升高和电解质的紊乱.血培养阳性率47%.CT、B超提示肠壁增厚,盲肠或右侧结肠充气减少,气腹等.13例患儿接受内科保守治疗,4例手术干预.2例死亡.结论 粒细胞缺乏性小肠结肠炎是由粒细胞缺乏所引起的危及生命的消化道并发症,临床及CT表现可明确诊断.早期发现和积极的内科治疗可减少病死率.大多数的患儿可通过保守治疗,避免外科手术而获得良好的预后.

Abstract：

Objective To summarize our experience with disgnosis and treatment of neutropenic enterocolitis in children. Methods From 2004 to 2009, 17 patients were diagnosed with neutropenic enterocolitis, and treated at this center. Their clinical data were retrospectively analyzed to summarize the clinical features, managment experience and evaluate the outcome of neutropenic enterocolitis. Results Among the 17 patients, 11 were males and 6 were females. Their avergae age at diagnosis was 7. 2 years old. The primary diseases that caused neutropenia in these patients were lyphoma in 2 patients, leukemia in 11 patients,aplastic anemia in 1, neuroblastoma in 1, and primary neutropenia in 2. All the patients presented enterocolitis symptoms like fever, vomitting, and diarrhea. Physical examination found lower right abdominal pain and abdominal rigidity. C-reactive protein (CRP) and electrolyte disorder were also noted in these patients. The postive culture rate of blood bacterial was 47%.Computered tomography and ultrasonography revealed intestinal wall thickening, decreased air content in cecum and right colon, and peumoperitoneum. Four patients had diffused peritonitis and sepsis shock. Three of them need mechical ventilation. Among the 17 patients, 4 had surgery. Two patients died. Conclusions Neutropenic enterocolitis is a life-threatening gastrointestinal complication of neutropenia. Early diagnosis and intervention can reduce mortality and improve the prognose of these patients.     

Agranulocytosis associated with parvovirus B19 infection in otherwise healthy patients

In the course of 6 years, 23 otherwise healthy patients with acute febrile illness and leukopenia were diagnosed as having acute parvovirus B19 infection. Five of these patients had agranulocytosis associated with acute parvovirus B19 infection and one had chronic agranulocytosis due to persistent parvovirus B19 infection. The diagnosis was made after positive anti-parvovirus B19 IgM antibodies were found in all of the patients and viral DNA was detected by PCR in four patients. Neutropenia and agranulocytosis appear to be much more frequently associated with parvovirus B19 infection than previously reported.     

临床药师对1例头孢他啶致中性粒细胞缺乏病例的治疗干预

摘 要1例30岁男性患者因皮肤软组织感染,给予头孢他啶2 g,ivd,bid,用药21 d后出现发热、咽痛症状,血常规示白细胞计数（WBC）1.3×109·L-1、中性粒细胞绝对数（NEUT）0.4×109·L-1,管床医师要求临床药师介入,临床药师建议停用头孢他啶,给予地榆升白片0.2 g,po,tid。停药第2 d复查血常规：WBC 2.5×109·L-1、NEUT 0.28×109·L-1,给予万古霉素0.5 g,ivd,q8h、重组人粒细胞刺激因子注射液300 μg,ih,qd。停药第3日,患者体温恢复正常,WBC 8.9×109·L-1、NEUT 5.71×109·L-1。患者出院后1年内随访血常规均正常。     

Fournier's gangrene after hemorrhoidectomy: Association with drug-induced agranulocytosis

An unusual case of Fournier's gangrene after hemorrhoidectomy and drug-induced agranulocytosis, as the predisposing condition, is described. The patient had severe granulocytopenia that was attributed to the recent use of dipyrone. Together with hemodynamic resuscitation, broad-spectrum antibiotic and recombinant human granulocyte colony-stimulating factor were started. Wide surgical excision of all the gangrenous tissues, in addition to laparoscopic formation of a defunctioning sigmoid loop colostomy, was performed. The white blood cell count rose steadily and the patient experienced a rapid recovery. We emphasize that radical surgery must be accompanied by pharmacologic interventions for a successful outcome in such cases.     

Agranulocytosis following infectious mononucleosis

A girl developed acute agranulocytosis (45/mm³), 37 days after the onset of infectious mononucleosis. The bone marrow showed myeloid hyperplasia with maturation arrest and erythroid hypoplasia. A normal amount of colony forming units of granulocytes and macrophages (CFU-GM) colonies with a relative high number of clusters was observed. Neither anti-neutrophil antibodies nor circulating inhibitors of colony growth were found in serum. Granulocyte and macrophage colony stimulating factor (GM-CSF) activity in the patient's serum rose at this time. The agranulocytosis lasted 5 days and her clinical state soon improved. These results suggested that agranulocytosis was presumably not due to serum factors, including auto-antibodies and/or suppressive substances, and that Epstein-Barr virus (EBV) had some direct or indirect effect on the marrow cells of the myeloid series.     

Leukemia in severe congenital neutropenia: defective proteolysis suggests new pathways to malignancy and opportunities for therapy

Severe congenital neutropenia (SCN), a heterogeneous disorder that includes Kostmann syndrome, predisposes to myelodysplasia and acute myelogenous leukemia. Recently identified heterozygous mutations in the gene ELA2, encoding neutrophil elastase on human chromosome 19pter, account for the majority of autosomal dominant cases of SCN, including those demonstrating neoplastic progression. The involvement of the serine protease neutrophil elastase, localized to the granules of neutrophils and monocytes, implies an unexpected role for proteolytic regulation of hematopoiesis. Continued elucidation of the clinical features, molecular genetics, and biochemistry is likely to provide insight into novel pathways of leukemia induction with attendant prospects for new avenues of therapy.     

降阶梯治疗在急性髓细胞白血病化疗后粒细胞缺乏期的应用

目的 探讨降阶梯治疗在急性髓细胞白血病化疗后粒细胞缺乏期应用的重要性.方法 将急性髓细胞白血病化疗后粒细胞缺乏期经验性抗感染284例,分为降阶梯组126例和升阶梯组158例,比较二组发热持续时间、感染控制率、感染相关死亡率及真菌感染率.结果 降阶梯治疗与升阶梯治疗的其感染控制率分别为77.8%和63.5% 发热持续时间分别为（7.23±2.47） d和（8.97±3.16） d,两组比较均有显著性差异,P〈0.05 但两组感染相关死亡率分别为4.76%和5.70%,差异无统计学意义,P=0.795 两组真菌感染率分别为25.4%和24.7%,差异无统计学意义,P=0.99.结论 降阶梯治疗能明显提高感染控制率,减少发热时间,且不会增加继发真菌感染,值得临床推广应用.     

肿瘤患者化疗致粒细胞缺乏性发热及感染的调查分析与相关性研究

目的了解肿瘤患者化疗致粒细胞缺乏性发热及感染的发生情况,并探讨二者之间的关系。方法因化疗致粒细胞缺乏的肿瘤患者,对其中发生的发热及感染病例进行临床分析,并对二者之间关系行一致性检验。结果 384例患者中,发热154例(40.1%),感染69例(18.0%);发热者体温(39.0±0.6)℃;感染部位主要见于咽部(43.5%)、口腔(20.3%)和下呼吸道(14.5%)。发热与感染患者一致性检验的Kappa值为0.4572(P<0.001),一致率为0.7630。结论化疗致粒细胞缺乏症患者,发热及感染的发生率较高,且发热与感染呈中度一致。     

甲巯咪唑片引起重度粒细胞缺乏症1例并文献分析

目的　分析甲巯咪唑片致重度粒细胞缺乏症的一般规律和临床特点。方法　基于1例甲巯咪唑片致重度粒细胞缺乏症的病例,检索中国知网、万方数据库和Pubmed数据库建库至2022年2月公开发表的文献,分析甲巯咪唑致重度粒细胞缺乏症的一般规律及临床特点。结果　共纳入文献44篇,包含患者49例,其中男性7例（14.3%）,女性42例（85.7%）,年龄（39.3±15.5）岁,日剂量为（29.9±11.9）mg,重度粒细胞缺乏症多发生于用药后1～3个月内,常有高热、咽痛等症状,大部分患者经积极治疗可好转,但仍有部分患者因感染性休克、呼吸衰竭而死亡。结论　甲巯咪唑可导致罕见的重度粒细胞缺乏症,临床医生应注意合理用药,以减少和避免重度粒细胞缺乏症的发生。