Rectal bleeding in infancy:: Clinical, allergological, and microbiological examination
Rectal bleeding in infancy:: Clinical, allergological, and microbiological examination
复制标题
DOI：
10.1542/peds.2005-1069
复制
发表时间：
2006-04-01
期刊：
影响因子：
8
通讯作者：
Isolauri, E
中科院分区：
文献类型：
--
作者：
Arvola, T;Ruuska, T;Isolauri, E
OBJECTIVE.直肠出血是一个令人担忧的症状，需要额外的调查。在婴儿中，它主要被解释为过敏。除了饮食抗原外，管腔内微生物因子也会挑战未成熟的肠粘膜。虽然在成熟的肠道中受到控制，但这些抗原可能在发育中的胃肠道中诱导炎症。本研究的目的是前瞻性地评估直肠出血的临床过程，并评估牛奶过敏和异常肠道微生物群对病情的影响。由于从婴儿饮食中去除牛奶抗原被用作第一种治疗方法，没有证据表明其有效性，我们还旨在评估牛奶去除饮食对直肠出血持续时间的影响。该研究涉及坦佩雷大学医院儿科2年期间连续40名可见直肠出血的婴儿（平均年龄：2.7个月）。大多数婴儿（68%）完全母乳喂养。在登记时，婴儿被随机分配接受牛奶消除饮食（n = 19）或继续他们以前的饮食（n = 21）1个月。对结肠镜检查、粪便细菌培养、选定肠道属的荧光原位杂交、粪便肠道病毒、轮状病毒和腺病毒的特异性检测、粪便病毒电子显微镜检查和粘膜病毒电子显微镜检查的结果进行了评估。在每次访视期间，根据SCORAD方法评估特应性湿疹（如果有的话）的严重程度。在评价致敏程度时，研究了牛奶、鸡蛋和小麦的血清总免疫球蛋白E（IgE）和特异性IgE以及皮肤点刺试验。牛奶过敏是通过消除和激发试验诊断的。5名患者住院治疗;所有其他患者均在门诊接受治疗。随访访视安排在1个月后和1岁时进行。根据以下标准选择64名健康参考婴儿作为对照：年龄和粪便采样时间在1个月内相同。总共有32例（80%）婴儿在随访期间出现血便（平均值[范围]：每天2.1 [1-15]）。随访时直肠出血的平均天数为6天。通常情况下，血便发生不规则，因此，最后一次发生直肠出血的平均时间为入院后24天（范围：1-85）。38%的婴儿在就诊时或随访期间被诊断为特应性湿疹。特异性IgE浓度升高或皮肤点刺试验阳性并不常见。婴儿在入院时和随访期间的生长正常。结肠镜检查显示典型的局灶性粘膜红斑和口疮性溃疡。不到一半的患者粘膜正常。光镜下未见肛门直肠裂及结肠息肉，黏膜结构完整。急性炎症或炎症后状态和固有层嗜酸性粒细胞局灶性浸润是最常见的异常。奶牛的排奶饮食不影响直肠出血的持续时间。牛奶过敏被诊断为7例（18%）患者。8例结肠上皮微绒毛层内可见病毒颗粒聚集。病毒阳性结肠活检标本的表面上皮细胞在微绒毛层和上皮细胞中有规律地表现出退行性变化。结肠活检的电子显微镜研究揭示了上皮细胞表面上的病毒颗粒（直径30 nm）。只有少数患者的粪便中存在病毒颗粒或RNA。所有粪便培养物均为沙门氏菌、志贺氏菌和耶尔森氏菌阴性。在1例患者的粪便中发现空肠弯曲菌，4例患者粪便培养为艰难梭菌阳性，8例患者为金黄色葡萄球菌阳性，2例患者为酵母菌阳性。荧光原位杂交显示，在入院时的细菌总数和双歧杆菌和乳酸杆菌在粪便中的数量较低的患者与对照组相比。本研究中表征的微生物（拟杆菌、双歧杆菌、梭菌、乳杆菌和肠球菌）的粪便浓度在患者或对照组入院时和第二次访视时之间没有显著差异。1岁时，7名患者仍患有牛奶过敏，其中5名患者还患有多种食物过敏。特应性湿疹和组织病理学证实的结肠粘膜炎症表现与1岁时牛奶过敏的持续性有关。无患者出现胃肠道不适或可见便血。婴儿直肠出血通常是一种良性和自限性疾病。在接下来的几个月里，只有几天不规则地出现血便。与前一份报告一样，大多数婴儿都是纯母乳喂养。大多数患者的病因尚不清楚。在一些患者中可以看到与病毒的相关性。通常导致较大儿童和成人出血性腹泻的微生物，沙门氏菌，志贺氏菌和耶尔森氏菌，在本材料中不存在。粪便样品中的低生物量细菌数量可能表明显著的变异，这可能为益生菌干预提供目标，以使肠道微生物群正常化。肠道微生物群总体上似乎是稳定的，因为测试的主要微生物群的数量在入院时和1个月后没有显著变化。在这些患者中，牛奶过敏比以前认为的更不常见。因此，牛奶挑战对于在无牛奶饮食期间变得无过敏的婴儿至关重要，以减少假阳性牛奶过敏诊断的数量。
OBJECTIVE. Rectal bleeding is an alarming symptom and requires additional investigation. In infants it has been explained mainly by hypersensitivity. In addition to dietary antigens, intraluminal microbial agents challenge the immature gut mucosa. Although controlled in the mature gut, these antigens may induce inflammation in the developing gastrointestinal tract. The objectives of this study were to evaluate prospectively the clinical course of rectal bleeding and evaluate the impact of cow's milk allergy and aberrant gut microbiota on the condition. Because withdrawal of cow's milk antigens from the infants' diet is used as a first treatment without evidence of its efficacy, we also aimed to asses the effect of a cow's milk-elimination diet on the duration of rectal bleeding.METHODS. The study involved 40 consecutive infants (mean age: 2.7 months) with visible rectal bleeding during a 2-year period at the Tampere University Hospital Department of Pediatrics. Most of the infants (68%) were fully breastfed. At enrollment the infants were randomly allocated to receive a cow's milk-elimination diet (n = 19) or continue their previous diet (n = 21) for 1 month. Findings of colonoscopy, fecal bacterial culture, fluorescence in situ hybridization of selected gut genera, specific detection of fecal enteroviruses, rotaviruses, and adenoviruses, fecal electron microscopy for viruses, and mucosal electron microscopy for viruses were assessed. During each visit the severity of atopic eczema, if any, was assessed according to the SCORAD method. In evaluating the extent of sensitization, serum total immunoglobulin E (IgE) and specific IgE and skin-prick tests for cow's milk, egg, and wheat were studied. Cow's milk allergy was diagnosed by elimination and provocation testing. Five patients were hospitalized; all others were treated on an outpatient basis. The follow-up visits were scheduled 1 month later and at the age of 1 year. Sixty-four healthy reference infants were selected as controls according to the following criteria: age and timing of fecal sampling being identical to within 1 month.RESULTS. Altogether, 32 (80%) infants manifested bloody stools during follow-up (mean [range]: 2.1 [1-15] per day). The mean number of days with rectal bleeding on follow-up was 6. Typically, bloody stools occurred irregularly, for which reason the mean time to the last occurrence of rectal bleeding was 24 (range: 1-85) days from admission. Atopic eczema at presentation or during follow-up was diagnosed in 38% of the infants. Increased specific IgE concentrations or a positive skin-prick test were uncommon. The growth of the infants was normal on admission and during follow-up. Colonoscopy revealed typically focal mucosal erythema and aphthous ulcerations. The mucosa appeared normal in less than half of the patients. No anorectal fissures or colonic polyps were found. Light microscopy revealed that the overall architecture of the mucosa was well maintained. Acute inflammation or postinflammatory state and focal infiltration of eosinophils in the lamina propria were the most common abnormalities. A cow's milk-elimination diet did not affect the duration of rectal bleeding. Cow's milk allergy was diagnosed in 7 (18%) patients. Virus-particle aggregates were found in the microvillus layer of the colon epithelium in 8 cases. The surface epithelium of the virus-positive colon biopsy specimens regularly showed degenerative changes in the microvillus layer and epithelial cells. Electron microscopy study of the colon biopsies disclosed virus particles (30 nm in diameter) on the surface of epithelial cells. Virus particles or RNA were present in feces in only a minority of the patients. All fecal cultures were negative for Salmonella, Shigella, and Yersinia. Campylobacter jejuni was found in the feces of 1 patient, and fecal cultures were positive for Clostridium difficile in 4 patients, Staphylococcus aureus in 8 patients, and yeast in 2 patients. Fluorescence in situ hybridization revealed that at the time of admission the total numbers of bacteria and the numbers of bifidobacteria and lactobacilli in feces were lower in the patients compared with controls. The fecal concentrations of microbes characterized in this study (Bacteroides, bifidobacteria, Clostridium, lactobacilli, and enterococci) did not differ significantly between the time of admission and the second visit in the patients or controls. At the age of 1 year, 7 patients still suffered from cow's milk allergy, 5 of whom also suffered from multiple food allergies. Atopic eczema and histopathologically confirmed inflammation of the colonic mucosa at presentation were associated with persistence of cow's milk allergy at the age of 1 year. No patients exhibited gastrointestinal complaints or visible blood in stools.CONCLUSIONS. Rectal bleeding in infants is generally a benign and self-limiting disorder. Bloody stools occurred irregularly for only a few days during the following months. As in a previous report, most infants were exclusively breastfed. In the majority of the patients the cause of the condition remains unknown. An association with viruses can be seen in some patients. The microbes that commonly lead to bloody diarrhea in older children and adults, Salmonella, Shigella, and Yersinia, were absent in the present material. The low bifidobacterial numbers in fecal samples may indicate a significant aberrance that may provide a target for probiotic intervention to normalize gut microbiota. The gut microbiota overall seemed stable, because the numbers of major groups of microbiota tested did not change significantly between the time of admission and after 1 month. Cow's milk allergy among these patients is more uncommon than previously believed. Cow's milk challenge is thus essential in infants who become symptom-free during a cow's milk-free diet to reduce the number of false-positive cow's milk-allergy diagnoses.