pdf oldie: Rectal bleeding in infancy: an autism subgroup (by parental reports & medical histories)

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*Rectal bleeding in infancy: clinical, allergological, and

microbiological examination*

Arvola T, Ruuska T, Keränen J, Hyöty H, Salminen S, Isolauri E.

Tampere University Hospital

Pediatrics. 2006 Apr;117(4):e760-8.

http://pediatrics.aappublications.org/cgi/reprint/117/4/e760

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.