F. Cavataio

Intolerance of Cow's Milk and Chronic Constipation in Children

Background: Chronic diarrhea is the most common gastrointestinal symptom of intolerance of cows milk among children. On the basis of a prior open study, we hypothesized that intolerance of cows milk can also cause severe perianal lesions with pain on defecation and consequent constipation in young children. Methods: We performed a double-blind, crossover study comparing cows milk with soy milk in 65 children (age range, 11 to 72 months) with chronic constipation (defined as having one bowel movement every 3 to 15 days). All had been referred to a pediatric gastroenterology clinic and had previously been treated with laxatives without success; 49 had anal fissures and perianal erythoma or edema. After 15 days of observation, the patients received cows milk or soy milk for 2 weeks. After a one week washout period, the feedings were reversed. A response was defined as eight or more bowel movements during a treatment period. Results: Forty-four of the 65 children (68 percent) had a response while receiving soy milk. Anal fissures and pain with defecation resolved. None of the children who received cows milk had a response. In all 44 children with a response, the response was confirmed with a double blind challenge with cows milk. Children with a response had a higher frequency of coexistent rhinitis, dermatitis, or bronchospasm than those with no response (11 of 44 children vs. 1 of 21, P = 0.05); they were also more likely to have anal fissures and erythema or edema at base line (40 of 44 vs. 9 of 21, P < 0.001), evidence of inflammation of the rectal mucosa on biopsy (26 of 44 vs. 5 of 21, P = 0.008), and signs of hypersensitivity, such as specific IgE antibodies to cows-milk antigens (31 of 44 vs. 4 of 21, p < 0.001). Conclusions: In young children, chronic constipation can be a manifestation of intolerance of cows milk.

Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: exploring a new clinical entity.

OBJECTIVES:Non-celiac wheat sensitivity (WS) is considered a new clinical entity. An increasing percentage of the general population avoids gluten ingestion. However, the real existence of this condition is debated and specific markers are lacking. Our aim was thus to demonstrate the existence of WS and define its clinical, serologic, and histological markers.METHODS:We reviewed the clinical charts of all subjects with an irritable bowel syndrome (IBS)-like presentation who had been diagnosed with WS using a double-blind placebo-controlled (DBPC) challenge in the years 2001–2011. One hundred celiac disease (CD) patients and fifty IBS patients served as controls.RESULTS:Two hundred and seventy-six patients with WS, as diagnosed by DBPC challenge, were included. Two groups showing distinct clinical characteristics were identified: WS alone (group 1) and WS associated with multiple food hypersensitivity (group 2). As a whole group, the WS patients showed a higher frequency of anemia, weight loss, self-reported wheat intolerance, coexistent atopy, and food allergy in infancy than the IBS controls. There was also a higher frequency of positive serum assays for IgG/IgA anti-gliadin and cytometric basophil activation in “in vitro” assay. The main histology characteristic of WS patients was eosinophil infiltration of the duodenal and colon mucosa. Patients with WS alone were characterized by clinical features very similar to those found in CD patients. Patients with multiple food sensitivity were characterized by clinical features similar to those found in allergic patients.CONCLUSIONS:Our data confirm the existence of non-celiac WS as a distinct clinical condition. We also suggest the existence of two distinct populations of subjects with WS: one with characteristics more similar to CD and the other with characteristics pointing to food allergy.

Gastroesophageal reflux and cow's milk allergy in infants : A prospective study

BACKGROUND Recent reports have suggested that gastroesophageal reflux in pediatric patients may be caused by food allergy. OBJECTIVE The aim of our study was to determine the frequency of the association of gastroesophageal reflux with cows milk protein allergy in patients win the first year of life. METHODS We studied 204 consecutive patients (median age, 6.3 months) who had been diagnosed as having gastroesophageal reflux on the basis of 24-hour continuous pH monitoring and histologic examination of the esophageal mucosa. RESULTS Clinical history suggested diagnosis of cows milk allergy in 19 infants, and 93 others had positive test results (serum IgE anti-lactoglobulin, prick tests, circulating or fecal or nasal mucus eosinophils) but did not have symptoms indicating cows milk allergy. The cows milk-free diet and two successive blind challenges confirmed the diagnosis of cows milk allergy in 85 of the 204 patients with gastroesophageal reflux. The clinical presentations of the infants with gastroesophageal reflux alone were different, in view of the greater frequency of diarrhea (p less than 0.0001) and atopic dermatitis (p less than 0.0002). In all, gastroesophageal reflux was associated with, and probably caused by cows milk allergy, in 85 of 204 cases (41.8%). CONCLUSIONS Considering the frequency of this association, patients younger than 12 months old with symptoms of gastroesophageal reflux should be carefully examined to determine whether this disorder is primary or caused by cows milk allergy.

Intolerance to hydrolysed cow's milk proteins in infants: clinical characteristics and dietary treatment

Multiple food intolerance in infants, including intolerance to extensively hydrolysed proteins (HP), is often difficult to treat. However, few data have been reported on clinical outcome and dietary treatment of these patients.

Sideropenic anemia and celiac disease: one study, two points of view.

Recent studies have pointed to the relationshipbetween iron deficiency anemia and celiac disease,although data on the prevalence of celiac disease inanemic patients have been conflicting, and there is no agreement on the best screening procedurefor CD in these patients. Our aims were to evaluate therelationship between anemia and celiac disease (CD) fromtwo different points of view — the hematology clinic and the pediatric gastroenterologydepartment — and to evaluate the utility ofanti-endomysial antibody determination in screeninganemic patients for CD using human umbilical cord assubstrate. We studied 130 patients with CD (58 males, 72females; median age 18 months) diagnosed at a departmentof Pediatric Gastroenterology, and 85 patients with irondeficiency anemia (38 males, 47 females; median age 48 years) observed at a hematologyoutpatient clinic. From the 85 adult patients with irondeficiency anemia, we selected a subgroup of 25 subjectswith no improvement in Hb after two months of iron therapy (80 mg/day orally). Routinehematochemical tests were performed in all 215 patients.All pediatric and adult subjects underwent immunologicalscreening for celiac disease (AGA and EmA assay);intestinal biopsy was also performed on patients testingpositive. In the adult anemic patients a serum samplewas stored at –20°C on first observation, andafter 6-18 months EmA on human umbilical cord wereassayed. In the pediatric patients with CD, anemia wasobserved in 91/130 patients (70% of cases, the mostfrequent symptom after poor growth); however, this wasthe only presenting symptom of CD in 2/130 patients (1.5% of cases). Anemia was sideropenic in41/91 patients (iron <45 μg/dl, ferritin <15mug/liter). In the adult patients with iron deficiencyanemia, immunological screening (AGA and EmA) showed suspected CD in 5/85 cases (5.8%), withdiagnosis confirmed on intestinal biopsy. These fivepatients were in the subgroup of iron supplementationtherapy nonresponders. CD prevalence in the refractory anemia subgroup was, therefore, 5/25 (20%). Ondiagnosis the hematological indices of the anemia + CDpatients were not different than those of the refractoryanemia patients without CD. The median age of the CD + anemia patients was significantlylower than that of the whole group of anemic subjects,and there was also a prevalence of females (4/5 cases).The results of the EmA determination on human umbilical cord in the adult anemic patientsshowed a perfect concordance with those using atraditional kit that uses monkey esophagus as substrate.In the pediatric age group many cases of CD with anemia as the only sign of the disease are probablynot diagnosed. In our adult patients with sideropenicanemia, CD prevalence was 5-6%; however, the observationof anemic patients not responding to oral iron therapy makes a diagnosis of CD much moreprobable. EmA determination on human umbilical cord isthe most logical approach to screen anemic patients forsuspected CD.

Exocrine pancreatic function in children with coeliac disease before and after a gluten free diet.

This study was designed to determine the extent of pancreatic insufficiency in untreated coeliac disease and whether pancreatic secretion is impaired after a prolonged gluten free period. Three groups of patients were studied: group A comprised 44 patients, mean (SD) age 4.0 (3.1) years, with coeliac disease and total or subtotal atrophy of the intestinal mucosa; group B comprised 67 patients, mean age 4.4 (3.0) years, with coeliac disease but with normal morphology of the intestinal villi (after 12.9 months of a gluten free diet); group C comprised 49 control subjects, mean age 3.2 (3.0) years, with normal jejunal histology. In all subjects exocrine pancreatic function was determined by the secretin-caerulein test; bicarbonate concentration and lipase, phospholipase, and chymotrypsin activity were measured after an intravenous injection of secretin 1 clinical unit (CU) + caerulein 75 ng/kg body weight. Faecal chymotrypsin concentration was also assayed. No significant difference was found between values of the duodenal output of pancreatic enzymes and bicarbonate obtained in the three groups; however, 10 of 44 untreated coeliac patients showed tryptic or lipolytic activity, or both, below the normal limit for our laboratory. The mean value of the faecal chymotrypsin concentration was significantly lower in untreated than in treated coeliac patients (p less than 0.0001) or in control subjects (p less than 0.0001). It is concluded that untreated coeliac patients may have pancreatic deficiency independent of a decrease in enterohormone release. No primary or secondary pancreatic insufficiency was found in coeliac patients where the intestinal mucosa had returned to normal.

Diagnostic accuracy of fecal elastase 1 assay in patients with pancreatic maldigestion or intestinal malabsorption: A collaborative study of the Italian society of pediatric gastroenterology and hepatology

Several reports have indicated that fecal elastase-1 (EL-1) determination is a new, sensitive, and specific noninvasive pancreatic function test; however, very few patients with malabsorption due to small intestine diseases have been included in the previous studies. The aim of the study was to compare the diagnostic accuracy of fecal EL-1 and fecal chymotrypsin (FCT) in distinguishing between pancreatic maldigestion and intestinal malabsorption. Three groups of subjects were studied: group A included 49 patients with known cystic fibrosis (25 males, median age 5 years); group B included 43 subjects with various small intestine diseases (17 males, median age 6 years); and group C included 45 children without any history of gastrointestinal disease (22 males, median age 5 years). In all patients, stools were collected for 72 h on a standard diet and fecal EL-1, FCT, and steatocrit tests were performed. Both EL-1 and FCT were below normal limits in all CF patients with pancreatic maldigestion not treated with pancreatic enzyme (100% sensitivity for both assays); El-1, but not FCT, was also below normal in all the CF patients with pancreatic maldigestion treated with pancreatic extracts. Both EL-1 and FCT values in the CF group were significantly lower than in subjects with various small intestinal diseases and in children without any history of gastrointestinal disease (P < 0.0001). FCT, but not EL-1, values showed an inverse statistically significant correlation with steatocrit values in the whole CF group (P < 0.001); FCT was below normal in three of four CF patients with steatorrhea on pancreatic enzyme therapy. Both EL-1 and FCT had 100% specificity when calculated in children without any history of gastrointestinal disease; in contrast, specificity was 86% for EL-1 and 76% for FCT if we considered the control group with small intestinal diseases: low EL-1 was observed in two cases of intestinal giardiasis, two cases of short bowel syndrome, one case of celiac disease, and one case of intestinal pseudobstruction; FCT was abnormal in four cases of intestinal giardiasis, three cases of celiac disease, one case of short bowel syndrome, one case of Crohns disease, and one case of intestinal pseudobstruction. Diagnostic accuracy was 92% for fecal EL-1 and 82% for FCT. Steatocrit values were over the normal limit in 11 patients with small intestine diseases; in 7/11 of these patients at least one of the pancreatic test results was below the normal limit. In conclusions, in patients with CF, fecal EL-1 determination is not more sensitive than FCT in identifying pancreatic maldigestion; however, fecal EL-1 assay is more specific than FCT determination in distinguishing pancreatic maldigestion from intestinal malabsorption.

Gastric emptying in infants with gastroesophageal reflux. Ultrasound evaluation before and after cisapride administration.

The present study aimed to evaluate gastric emptying in children with gastroesophageal reflux (GER) by means of real-time ultrasonography, on the basis of measurements of the cross-sectional area of the gastric antrum. Twelve children with GER were studied (seven males, five females; age range, 3-13 months) and compared with 12 normal control children (six males, six females; age range, 3-13 months). The diagnosis of GER was confirmed by 24-h esophageal pH-monitoring. The GER patients had a significantly greater antral area than the controls at 90, 105, and 120 min after eating a standard meal (cows milk formula, 300 ml/m2 body surface area); in addition, final gastric emptying time was significantly greater in the patients than in the controls (145 +/- 36.9 versus 78.7 +/- 19.3 min; p less than 0.0025). After 8 weeks of treatment with cisapride (0.3 ml/kg, three times a day) 24-h esophageal pH-monitoring and ultrasonography studies were repeated in the patients. The total percentage reflux time was significantly lower (p less than 0.038), and ultrasonography showed a decreased antral area at all the various study times, with no significant difference between patients and controls; final gastric emptying time was also significantly lower than before treatment (p less than 0.009). Furthermore, in the GER patients there was a significant correlation between gastric emptying time and the sum of the various reflux times recorded in the 2 h after all meals over the 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Persistent cow's milk protein intolerance in infants : the changing faces of the same disease

Recent research has shown that cows milk protein intolerance (CMPI) often persists beyond 4 years of age.

Milk-induced reflux in infants less than one year of age.

Cows milk allergy (CMA) and gastroesophageal reflux are considered to be among the most common disturbances in infants less than 1 year of age. In recent years, the relationship existing between these two entities has been investigated and some important conclusions have been reached: In just under half the cases of GER in infants less than 1 year of age there is an association with CMA; in a high proportion of cases, GER is not only CMA-associated but also CMA-induced; the frequency of this association should induce pediatricians to screen for possible concomitant CMA in all infants with GER less than 1 year old; with the exception of some patients with mild typical CMA manifestations (diarrhea, dermatitis, or rhinitis), the symptoms of GER associated with CMA are the same as those observed in primary GER; immunologic tests are useful in a suspected association between GER and CMA; and subjects with GER secondary to CMA show a typical pH-monitoring tracing pattern, characterized by a progressive, slow decrease in esophageal pH between feedings. This article reviews the main features of the two diseases, stressing the aspects in common between them and comments on all the listed points.