16岁女孩中与元唑治疗相关的致命农业细胞增多症

Agranulocytosis is one of the common reasons of consultation in hematology. It’s life-threatening because of an infection risk. The metamizole is a drug, known for its potential rare danger of inducing a severe agranulocytosis. However, it remains widely used because of its beneficial effect analgesic and antipyretic. We report in this study, a case of a girl who was 16 years old, referred for severe agranulocytosis, and appeared two weeks after treatment with Novalgin. The clinico-biological symptoms were dominated by Streptococcal septicemia with an infectious pulmonary and digestive focus. The blood cell count confirmed a severe agranulocytosis with total disappearance of neutrophils. Despite broad-spectrum antibiotic therapy and stimulation with hematopoietic growth factor, the clinical evolution was fatal in the short term. What motivates us to add this case to those of the literature in order to remind practitioners about the danger of this drug, and to promote has doubled of vigilance during use.

术语农业细胞增多症表明外周血中完全没有中性粒细胞。实际上，当这个数字较小到0.5 g/l [1]时使用它。这是与各种病因进行血液学咨询的最大原因之一。在原因中，药物诱导的农业细胞增多症很常见。自1922年以来，Novalgin被称为Metamizole，一直在销售[2]。自1977年以来，食品药品监督管理局（Food and Drug Administration）自1977年以来一直在美国禁止其使用，因为它的潜在危险能够诱导致命的脂肪细胞增多症[3,4]。但是，由于其镇痛和抗精热作用，许多医学专业仍在非洲，亚洲和欧洲的许多国家使用。我们在这项研究中报道说，败血症患有严重的农业细胞增多症的病例，肺和消化焦点是16岁女孩的致命性。通过此案例报告，我们希望促进医生对这种已知致命药物的警惕。

一名16岁的女学生在体育运动后患有脚踝疼痛。她咨询了最接近她所在地区的保健中心，该中心每天开处方1500毫克。两周后，出现了发烧，身体无症，全身不适和肌痛。她再次咨询了她所在的综合医院。生物学检查指出，高度大于96 mg/l的高水平的造成反应性蛋白。疟疾的测试为阴性。血细胞计数检查出人意料地注意到，白细胞数量为3,78 g/L的总缺乏中性粒细胞。血红蛋白的水平为14 g/dL，血小板数为30 g/l。后来她被转介给我们的管理部门。临床检查指出，患者的意识为平均州普通。 Index performance status of World Health Organization (WHO) was 2. We noted a fever with 40 °C, a sclerotic jaundice and a respiratory rate at 30 cycle/min. Examination of the digestive tract noted an oral candidiasis with no particularity in abdomen exam (Figure 1). We noted a splenomegaly type I according to Hacket stadification. Pulmonary examination revealed crackling rales in both lungs.

从生物学上讲，新的血细胞计数检查证实了粒细胞增多症，中性粒细胞的总消失为3,99 g/L的白细胞数，一种在7 g/dl时具有血小板的血红蛋白水平的贫血，是血小板细胞增多症，血小板减少症，血小板数为30 G/L和of 30 g/l和o190 g/l的网状细胞。表I总结了我们患者的一系列血细胞计数检查。生化报告证实了溶血综合征，其血液水平为10 mg/L，总胆红素为26 mg/l的血液水平。肾功能和肝功能的检查严格正常。血液上的促蛋白质水平非常高至12 mg/l。血液培养分离出肺炎链球菌。X射线照相记录了两个肺的肺部不透性（图2）。

These biological results allowed us to evoke a septicemia with an infectious lung and digestive focus. We had hospitalized the patient in the isolation room and treated with triple antibiotic combining amoxicillin-clavulanic acid 3 g/days, a gentamycin 160 mg/days and Metronidazole 1500 mg/days. This treatment was accompanied by a vascular filling with cristaloid 1 l/day, a blood transfusion 500 ml and the stimulation of hematopoiesis with injection of G-CSF 300 mg/day. The evolution three day after was marked by persistence of clinical symptoms, an increase in the number of neutrophils at 0.1 g/l, leukocytes number at 4 g/l, hemoglobin at 9 g/dl, and number of platelets at 100 g/l. the patient had died on the 4th day in a severe septicemia chart and renal failure (Table 1).

术语的农业细胞增多症是由中性粒细胞在外周血中的总消失所定义的。当该数字小于0.5 g/L [1]时，它在实践中使用。根据世界卫生组织的数据，如果中性粒细胞的数量小于0.5 g/L，则感染的风险很高，如果低于0,1 g/L，则感染的风险更高[5]。病因众多，其中已被归因于某些药物。药物 - 葡萄糖细胞增多症的特征是循环血液中嗜中性粒细胞的严重和选择性降低[1]。Metamizol是一种属于Noramidopyrin家族的药物，即阿片类镇痛药的治疗类别。它因其导致致命的农业细胞增多症的潜在危险而闻名。根据WHO，Novalgin诱导的农业细胞增多症占所有农业细胞增多症病例的4.6％[6]。第一个案例在1936年在美国描述了[7]。促使其在美国和英国撤离的原因。 The reason for this withdrawal remains controversial by some authors, so that novalgin remains in use in some African countries, Germany, Asia and a parts of the United States [8-10]. According to Salama, et al., the mechanism by which navalgin induces agranulocytosis is immunological [11]. According to him, it’s characterized by its rapid onset and severity [1]. What is found in our patient, with severe agranulocytosis until disappearance of neutrophils within two weeks of appearance. In addition, some authors have suggested that the symptoms accompanied the agranulocytosis of immunological mechanism are fever, asthenia and myalgia [1]. These symptoms were found in our patient. Furthermore, our patient had oral thrush, a lung infection that is associated with sepsis. The major infectious risk was reported by WHO with less than 0,1 g/l of neutrophils, similar to our patient [5]. Therapeutically, the management consisted to stop the drug responsible, the broad-spectrum antibiotic therapy, anti-infective measures and the use of growth factors [1,3,4,12]. Generally the evolution is favorable with rapid correction of agranulocytosis [1,8]. What is seen in our patient in whom the number of neutrophils was increased rapidly in the first week. The fatal development in our series would be the fact that she had consulted late, at the stage of severe sepsis and the isolation room is not performing in our department that was causing her death.

我们报告了与使用元唑在使用期间促进警惕性有关的致命农业细胞增多症的病例。

Our thanks to all team of Clinical Hematology for their contribution during the management of this patient.

Authors contributions

After the controversies over the death of this patient during a medical meeting, Danho Nanho Clotaire recommended PACKO Dieu le veut Saint-cyr Sylvestre to write this manuscript. Camengo Police SM, Diakite M, Mbelesso P were in charge of bibliographic research. Boidy Kouakou, N’dhatz Comoe Emmeraude, contributed to the care of the patient during her hospitalization. Professor Koffi Kouassi Gustave participated in the correction of the article and its scientific orientation.

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