治疗GAS感染儿童不会增高发生PANDAS症状风险


  Sept. 8, 2004 - 一项发表于9月号儿童与青少年医学学志的前瞻性世代研究结果显示,治疗A群链球菌(GAS)感染儿童不会增高发生儿童免疫神经精神异常(PANDAS)的风险。
  
  美国北卡罗来纳大学教堂山分校小儿科Eliana Miller Perrin医师与其同事指出,PANDAS被理论化以描述一群在GAS感染后几个星期内发生突发性强迫症(OCD)与面部痉挛的儿童;也已证实罹患PANDAS的儿童,同时患有神经精神问题的机率很高。
  
  根据研究人员表示,虽然PANDAS在生物学上看起来有理的,而且流行病学试验暗示与GAS有关,但事实上,相互冲突的试验结果,使得PANDAS仍有争议存在。
  
  由于符合所有标准的诊断可能是很罕见的,因此研究人员假设在一项大型、前瞻性门诊病患试验中可以捕捉到变异比较轻微的、短暂症状的PANDAS患者;轻微变异定义为最近发生的(小于2个星期)发生2个以上PANDAS症状。
  
  4至11岁的儿童(共814位)及在小儿科门诊接受检查的(共196位),被认为是病毒引起的喉咙痛(共207位),或是因为GAS感染引起的喉咙痛(共399位)被收纳进入试验中;有症状GAS感染的儿童接受抗生素治疗,12位儿童被发现只是GAS带原者,而被排除在分析外。
  
  试验开始前、开始后2星期、3个月时,病患完成一份共有20项关于有或没有PANDAS症状的问卷,症状包括原发性神经精神异常症状(OCD症状、面部痉挛)与合并注意力相关问题(单独焦虑、一般性的担心或恐惧、消极、强迫性擦面纸以及异常的浴室习惯、新发作的夜尿症及频尿);共有682位儿童完成一份共有10项有关内在或焦虑思想及OCD症状问卷。
  
  试验开始时,病童的父母相较于健康儿童的父母提供较多最近发生的PANDAS症状,而GAS感染与病毒感染的族群中,盛行率是相当的,而GAS、病毒与健康族群中的盛行率也是相似的。
  
  从试验开始到2及12个星期后,PANDAS症状或变异型的盛行率在GAS、病毒与健康族群中是相似的(P<.01);这是由父母与儿童本身提供的信息。
  
  多变项分析显示,感染GAS群体的父母指出行为恶化速度相较于没有得到GAS感染儿童的父母提供的相似,GAS感染群体儿童短暂产生行为恶化相较于健康儿童,校正后的风险为1.76(95%信赖区间为0.47-6351),而病毒感染群体的是0.92(95%信赖区间为0.50-8.02)。
  
  GAS感染群体相较于健康儿童产生持续行为恶化的校正后相对风险为1.67(95%信赖区间为0.71-3.93),病毒感染的是0.92(95%信赖区间为0.33-2.55)。
  
  该项试验的局限,包括无法有效地侦测到罕见事件、由父母与儿童自行报提供信息有关的误差、GAS病菌株随著季节的变异、以及排除没有症状的GAS感染儿童。
  
  研究人员指出,我们并没有发现支持有症状的、治疗GAS引起的咽喉炎可以降低发生大部分神经精神症状或轻微的PANDAS变异症状风险的证据,这可能是因为GAS感染与OCD及面部痉挛之间没有关联性;研究人员进一步指出,抗生素在预防或治疗PANDAS的角色、没有症状但是受到感染的宿主发生PANDAS的盛行率与仍然需要进一步研究。
  
  这项试验由Robert Wood Johnson临床奖学金计划与来自国家健康研究机构的资金赞助。
  
  在研究伴随的评论中,北卡罗来纳州杜克大学医学中心儿童情感与焦虑异常计画的John S March医师、公共卫生硕士表示,为了要寻找这个问题的答案,需要建立一套确效的及可靠的PANDAS诊断标准,这个标准需要从与这个症状群相关的很广泛的精神与神经症状中建立。
  
  March医师表示,目前诊断PANDAS的圣杯是可靠的生物标记,在缺乏更新的方法之下,利用经典的精神学上的方法来划分PANDAS症候群,建立假设性生物标记的操作型特征是可能会失败的,因为缺乏以诊断为基础的可靠、确效的标准。

Children Treated for GAS Infec

By Yael Waknine
Medscape Medical News

Sept. 8, 2004 — Children treated for group A streptococcal (GAS) infection are not at increased risk for developing symptoms of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) compared with virally infected and healthy children, according to the results of a prospective cohort study published in the September issue of the Archives of Pediatric and Adolescent Medicine.

"PANDAS is hypothesized to describe a subset of children with sudden onset obsessive-compulsive disorder (OCD) and tic disorders that occur in the weeks following a [GAS] infection," writes Eliana Miller Perrin, MD, from the Department of Pediatrics at the University of North Carolina at Chapel Hill, and colleagues. "The children in the PANDAS subgroup...also have been documented to have a high frequency of comorbid neuropsychiatric problems."

Although PANDAS are biologically plausible, and epidemiological studies suggest a link with GAS, conflicting research results have rendered the entity of PANDAS controversial, according to the authors.

Acknowledging that a diagnosis that meets all criteria may be rare, the investigators postulated that milder variants of PANDAS with more transient symptoms could be captured in a large, prospective outpatient study. A mild variant was defined recent onset (< two weeks) of two or more PANDAS symptoms.

Children aged four to 11 years (n = 814) and examined in pediatric practice for well-child care (n = 196), sore throat of presumed viral origin (n = 207), or sore throat due to GAS infection (n = 399) were enrolled in the study. Children with symptomatic GAS infection were treated with antibiotics. Twelve children found to be GAS carriers only were excluded from analysis.

At baseline, two weeks, and three months, parents completed a 20-item questionnaire regarding the presence/absence of PANDAS, including symptoms of primary neuropsychiatric disorders (OCD symptoms, tics) and comorbid attention-related problems (separation anxiety, generalized worries and fears, negativity, obsessive toilet paper wiping and unusual bathroom routines, new-onset enuresis, and urinary urgency). Children who were able (n = 682) completed a 10-item questionnaire concerning internalizing or anxious thoughts and OCD symptoms.

At baseline, recent onset of several PANDAS symptoms was reported more frequently by parents of ill children compared with parents of well children, with similar incidence between the GAS and viral cohorts. Children reported similar incidence rates among GAS, viral, and healthy cohorts.

From baseline to two and 12 weeks, incidence of PANDAS symptoms or variants was similar among the GAS, viral, and healthy cohorts (P < .01), as reported by both parents and children.

Multivariate analysis showed that parents of the GAS-infected cohort reported worsened behavior at rates similar to those of parents of children without GAS infection. Adjusted relative risks for transiently worsened behavior were 1.76 (95% confidence interval [CI], 0.47 - 6.51) for children in the GAS cohort and 2.00 (95% CI, 0.50 - 8.02) for those in the viral cohort compared with healthy children.

The adjusted relative risks for persistent worsened behavior were 1.67 (95% CI, 0.71 - 3.93) among children in the GAS cohort and 0.92 (95% CI, 0.33 - 2.55) for those in the viral cohort compared with healthy children.

Study limitations include low power for rare events, errors associated with self-reporting by parents and children, seasonal variations in GAS strains, and the exclusion of asymptomatic children with GAS infection.

"We found no evidence to support the notion that symptomatic, treated GAS tonsillopharyngitis confers significant risk toward the development of most neuropsychiatric symptoms or mild PANDAS variants.... [I]t is possible that there is no relationship between GAS and OCD and tic disorders," the authors write, adding that the role of antibiotics in the prevention or treatment of PANDAS deserves further research, as does the incidence of PANDAS in asymptomatic, infectious hosts.

The study was funded by the Robert Wood Johnson Clinical Scholars Program and a grant from the National Institutes of Health.

In an accompanying editorial, John S. March, MD, MPH, from the Program for Child Affective and Anxiety Disorders at Duke University Medical Center in Durham, North Carolina, suggests that in order to "ask the right questions" in research, a valid and reliable diagnostic standard for PANDAS needs to be established from the wide variety of psychiatric and neurologic comorbidities associated with the syndrome.

"The holy grail for PANDAS is a reliable biomarker with mixed results so far," Dr. March writes. "[A]bsent a renewed commitment to delimit the PANDAS syndrome using state-of-the-art psychometric methods, it is likely that establishing the operating characteristic of a putative biomarker will founder on the lack of a reliable and valid standard on which to base the diagnosis."

Arch Pediatr Adolesc Med. 2004;158:848-856, 927-929

Reviewed by Gary D. Vogin, MD

    
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