继发于恙虫病的噬血细胞综合征19例临床特征分析

Clinical analysis of scrub typhus-associated hemophagocytic syndrome

目的 总结19例恙虫病并发噬血细胞综合征的临床特征.方法 分析2007年6月至2013年7月温州医科大学附属育英儿童医院19例恙虫病并发噬血细胞综合征的时间、临床表现、影像学和实验室检查、抗生素选择及预后情况.19例患儿中男9例,其中2008年前发病5例,2009年后发病14例.发病年龄11个月～ 10岁,平均（44±32）个月.发病时间：6月份3例,7月份7例,8月份5例,9月份1例,10月份2例,12月份1例.患儿发病前均有到草地上行走、玩耍史.结果 临床诊断恙虫病4例,实验室诊断恙虫病15例,19例均并发噬血细胞综合征.其中皮肤焦痂12例,溃疡7例,6至9月份发病15例.所有患儿门诊均误诊,9例入院诊断恙虫病,10例入院诊断误诊,其中5例入院3d内修正为恙虫病,另5例出院时仍误诊.恙虫病并发噬血细胞综合征时间点为恙虫病起病发热后平均（9±4）d.19例患儿实验室检查：丙氨酸转氨酶（149±37）U/L,白蛋白（23±4）g/L,C反应蛋白（103±51）mg/L,血小板（48±41）×109/L.15例患儿进行了外斐试验阳性6例,14例间接免疫荧光试验IgM抗体均阳性.16例骨髓涂片均可见噬血细胞.19例患儿胸部X线检查17例两肺可见小片状阴影,其中14例胸腔积液.5例误诊者均联合或先后应用多种高级抗生素,但均未选择针对立克次体抗生素;而14例诊断恙虫病者8例选择氯霉素,3例选择阿奇霉素,2例先后应用阿奇霉素和氯霉素,1例先后应用红霉素和氯霉素.19例恙虫病合并噬血细胞综合征,其中应用甲泼尼龙静脉点滴4例,选择地塞米松静脉点滴10例.5例误诊者入院后病情迅速恶化,均进展为多脏器功能不全综合征（MODS）,其中死亡4例;而14例诊断恙虫病者,入院后未发生MODS,均治愈.结论 恙虫病极易误诊,常早期并发噬血细胞综合征,若未选择有效抗生素,容易持续进展为MODS,甚至死亡.患儿如来自疫区,夏季发病,有发热、C反应蛋白升高,血小板降低,低蛋白血症,脾肿大,或胸部X线检查有片状阴影伴胸腔积液,应高度怀疑该患儿为恙虫病并发噬血细胞综合征.

Objective To analyze the clinical manifestations and intervention against fulminant scrub typhus-associated hemophagocytic syndrome.Method The medical records for the onset time of hemophagocytic syndrome,the clinical course,the chest radiographic findings,laboratory data,antibiotic therapy,clinical outcome and its prognosis were retrospectively reviewed.Result （1） Four patients were diagnosed as scrub typhus based on clinical manifestations only,while 15 patients met the criteria of laboratory diagnosis.All 19 patients with scrub typhus had hemophagocytic syndrome.Eschar lesion was identified in 12 patients,7 patients were described as an ulcer.A seasonal pattern （78.9％ from June through September in 15 patients） was observed.Clinical misdiagnosis was common （all 19 cases）.There were 9 patients with admitting diagnosis of scrub typhus,10 patients were not diagnosed as scrub typhus after admission.In 5 cases within 3 days after admission diagnosis was corrected as scrub typhus.Until discharge from the hospital,5 cases were not diagnosed with scrub typhus.In this study,the length of time from the illness onset （beginning of fever） to the occurrence of clinical symptoms was （9 ± 4） days.（2） All 19 patients had changed AST levels （149 ±37） U/L,albumin levels （23 ±4） g/L,C-reactive protein levels （103 ±51） mg/L,and platelet count （48 ±41） × 109/L; bone marrow aspiration revealed in 16 patients marked hemophagocytosis.Weil-Felix agglutination test revealed positive results in 6 of 15 cases.Diagnostic IFA results were positive for 14 patients; 19 patients had interstitial pneumonitis and 17 patients had pleural effusion.（3） Five cases with failure to diagnose the disease had ineffective antibiotics treatment （imipenem or β-lactam-based regimens）.These patients did not receive appropriate treatment with antibiotics against scrub typhus.Fourteen patients with admitting diagnosis of scrub typhus were successfully treated with appropriate antibiotics,8 cases with chloramphenicol,3 cases with azithromycin,and in 3 patients （2 cases of azithromycin and one case of erythromycin）,therapy was then switched to chloramphenicol.Four patients were treated with methylprednisolone and 10 patients with dexamethasone.（4） During their hospitalization,the clinical course in five cases with failure to diagnose the disease rapidly developed and progressed to the life-threatening MODS,four of five cases died.However,the course in 14 patients were relieved and did not progress to MODS.Conclusion The diagnosis of scrub typhus was frequently delayed,the early course of scrub typhus could be associated with hemophagocytic syndrome.Serious complications of MODS generally occur without antibiotic treatment.Scrub typhus-associated hemophagocytic syndrome should be taken into consideration among patients with acute systemic febrile illness,significant increases in levels of CRP,hypoalbuminemia,thrombocytopenia,splenomegaly,pneumonitis with pleural effusion,especially those with suspected exposure history.It was not easily recognized without careful observation and was present for a few days in each patient.