[Etiology and clinical characteristics of fever of unknown origin in 357 pediatric patients].

Objective: To explore the etiologies and clinical characteristics of fever of unknown origin (FUO) and to provide clues for early diagnosis of FUO. Methods: The data about etiology, age, sex, clinical course, length of hospital stays and the expression levels of inflammatory factors in fever phase of 357 pediatric inpatients who were diagnosed with FUO in Children's Hospital of Fudan University from 1 January 2016 to 31 December 2020 were collected and retrospectively analyzed. Participants were grouped into infectious disease, inflammatory disease, malignancy and others and according to the classification of diseases and also grouped into those aged<1 year, 1-<3 years,3-<6 years, 6-<12 years and 12-<18 years. Comparisons between groups were performed using the Mann-Whitney U test, Kruskal-Wallis H test and χ² test. Results: Among the 357 patients (217 males and 140 females). The age of onset was 3.9 (1.3, 9.2) years and visiting age was 5.1 (2.0, 9.3) years. The time-consuming of diagnosis was 94 (66, 213) days. The hospital stay was 8 (6, 14) days. The most frequently identified cause of FUO was infectious diseases (163 cases, 45.7%), followed by non-infectious inflammatory diseases (133 cases, 37.2%), malignancy (21 cases, 5.9%) and others (40 cases, 11.2%). The patients at younger age were more likely to be attacked by malignancy, oncologic diagnoses, and others, nevertheless patients at older age were more likely to be attacked by non-infectious inflammatory diseases oppositely (9.8 (3.6, 11.5) vs. 3.0 (1.2, 7.0), 2.3 (1.0, 5.2), 0.9 (0.5, 1.8) years, U=41.30, 15.94, 37.08, all P<0.01);106 (65%) patients were male, and 57 (35%) patients were female. This result indicated that boys were more susceptible to infectious diseases (χ²=14.73, P<0.01). Analysis of inflammatory factors in serum among 103 patients, interleukin (IL)-6 level in 40 infectious diseases patients (9 (2, 38) ng/L) was significantly lower than those of 6 tumor patients (89 (64, 599) ng/L) and 57 non-infectious inflammatory diseases patients (25 (8, 78) ng/L, U=51.05, 15.70, both P<0.05), no significant difference was observed in IL-2, IL-4, IL-10, tumor necrosis factor α and interferon among the groups (all P>0.05). The patients grouped into those aged 1-<3 years and 3-<6 years were more likely to be attacked by infectious diseases (51.3% (59/115) and 57.1% (40/70)), while patients grouped into those aged 6-<12 years and 12-<18 years were more likely to be attacked by non-infectious inflammatory diseases (55.6% (65/117) and 72.4% (21/29)). Conclusions: Infectious disease is still the main cause of FUO in children and the boys are more susceptible to infectious diseases. However, the morbidity of non-infectious inflammatory diseases increases to number 1 in FUO of children over 6 years of age.目的： 探讨儿童不明原因发热的病因分布及临床特征，为儿童不明原因发热的早期诊断提供线索。 方法： 收集2016年1月1日至2020年12月31日复旦大学附属儿科医院357例不明原因发热患儿的病因构成、年龄、性别、病程、住院时间、确诊时间及急性期的炎症因子水平等临床资料行病例对照分析。依据疾病种类分为感染性疾病组（简称感染组）、非感染性炎症性疾病组（简称非感染组）、肿瘤性疾病组（简称肿瘤组）和其他疾病组（简称其他组）。依据年龄分为<1岁组，1~<3岁组、3~<6岁组、6~<12岁组及12~<18岁组，组间比较采用Mann-Whitney U检验、Kruskal-Wallis H检验和χ²检验。 结果： 357例患儿中男217例、女140例，就诊年龄5.1（2.0，9.3）岁，起病年龄3.9（1.3，9.2）岁，确诊时间94（66，213）d，住院时间8（6，14）d。感染组163例（45.7%）、非感染组133例（37.2%）、肿瘤组21例（5.9%），其他组40例（11.2%），4组间起病年龄差异有统计意义（H=94.01，P<0.01），非感染组起病年龄均分别大于感染组、肿瘤组、其他组［9.8（3.6，11.5）比3.0（1.2，7.0）、2.3（1.0，5.2）、0.9（0.5，1.8）岁，U=41.30、15.94、37.08，均P<0.01］，感染组起病年龄大于其他组（U=17.64，P<0.01）。感染组男童多于女童［106例（65.0%）比57例（35.0%），χ²=14.73，P<0.01］。对103例血清炎症因子水平进行对比分析，感染组（40例）白细胞介素6水平均分别低于肿瘤组（6例）和非感组（57例）［9（2，38）比89（64，599）、25（8，78）ng/L，U=51.05、15.70，均 P<0.05］，而白细胞介素2、4、10、肿瘤坏死因子α及干扰素在各组之间差异均无统计学意义（均P>0.05）。1~<3岁组和3~<6岁组感染性疾病分别占同年龄层的51.3%（59/115）和57.1%（40/70），6~<12岁组和12~<18岁组非感染性炎症性疾病分别占同年龄层的55.6%（65/117）和72.4%（21/29）。 结论： 感染性疾病是儿童不明原因发热的主要病因，且男童较女童更易患感染性疾病。随着年龄增长，非感染性炎症性疾病比例逐渐上升，成为6岁以上儿童不明原因发热的首要病因。.