Gastrointestinal symptoms in infancy: a population-based prospective study.

BACKGROUND: During the first months of life, infants can suffer from many 'minor' gastroenterological disturbances. However, little is known about the frequency of these problems and the factors which predispose or facilitate their onset. AIMS: (a) To ascertain the frequency of the most common gastrointestinal symptoms in infants during the first 6 months after birth; (b) to evaluate the influence of some variables on the onset of the symptoms. STUDY DESIGN AND PATIENTS: Each of the 150 paediatricians distributed throughout Italy followed 20 consecutive infants from birth to 6 months. 2879 infants (1422 f, 1457 m) concluded the study. The presence of the following symptoms was evaluated: constipation, diarrhoea, vomiting, regurgitation, failure to thrive and prolonged crying fits (colic). Symptoms were recorded whenever the parents requested a clinical check-up or during a set monthly examination. RESULTS: 1582/2879 (54.9%) infants suffered from one of the gastrointestinal symptoms. Regurgitation was the most common disturbance (present in 23.1% of infants), followed by colic (20.5%), constipation (17.6%), failure to thrive (15.2%), vomiting (6%) and diarrhoea (4.1%). Low birth weight was the factor most frequently associated with the onset of gastrointestinal symptoms, followed by low gestational age. Feeding habits did not influence the onset of symptoms, with the exception of constipation, which was linked to a low frequency of breast-feeding. Ninety-three infants (3.2%) were hospitalised for one or more of the gastrointestinal symptoms which were considered. During the whole study period the type of formula-milk was changed in 60% of the infants with one or more gastrointestinal symptoms, and in 15.5% of the infants who did not suffer from any gastrointestinal troubles. CONCLUSIONS: Gastrointestinal symptoms are very common in infants during the first 6 months after birth. These symptoms required hospitalisation only in a small percentage of cases, but led to the prescription of a 'dietary' milk formula in approximately 60% of the cases. Low birth weight and low gestational age were the main factors influencing the onset of the symptoms.

Production of anti-endomysial antibodies in cultured duodenal mucosa: usefulness in coeliac disease diagnosis.

BACKGROUND: Although anti-endomysial antibodies (EmA) have been found in the supernatants of cultured intestinal mucosa from patients with coeliac disease (CD), in no study has the clinical reliability of this new diagnostic tool been investigated. Our aims were to evaluate the clinical usefulness of the in vitro production of EmA in CD diagnosis in consecutive patients with suspected CD, and to evaluate the reliability of the in vitro challenge in CD patients on a gluten-free diet (GFD). METHODS: For the former aim, consecutive patients who were due to undergo intestinal biopsy for suspected diagnosis of CD were enrolled: according to the final diagnosis, these patients were divided into two groups: Group 1 comprised 91 newly diagnosed CD patients (40 males; age range 7 months to 84 years), Group 2 included 100 subjects with diseases other than CD (44 males; age range 9 months to 76 years). For the latter aim, we also studied 21 CD patients on a gluten-free diet after 16-123 months (8 males; age range 3-51 years), with normal intestinal architecture (Group 3) and 22 patients who served as controls (12 males; age range 4-60 years) with gastroesophageal reflux disease-like symptoms (Group 4). All patients underwent determination of serum anti-gliadin (AGA) and EmA antibodies, histology evaluation of the intestinal biopsies and EmA assay in the supernatants of in vitro gliadin-challenged duodenal mucosa. RESULTS: EmA assay in the supernatants showed a sensitivity and specificity of 96% and 100%, respectively; these were not significantly different from those observed for serum EmA (88% and 99%, respectively). However, EmA assay in the supernatants was useful in CD patients with mild intestinal histology lesions (infiltrative/hyperplastic type): in this subgroup it was positive in 9/12 of cases, but serum EmA was positive in only 2/12. As regards the reliability of the in vitro gliadin challenge, EmA production in supernatants was recorded only in 10/21 CD patients on a gluten-free diet. The patients with a positive in vitro challenge had a higher number of intra-epithelial lymphocytes than patients with a negative challenge. CONCLUSIONS: 1) EmA assay in the medium of cultured intestinal biopsy can detect gluten-sensitive enteropathy, characterized by an infiltrative/hyperplastic histological pattern, which is often associated with negative serum EmA. 2) The in vitro challenge in CD patients on a gluten-free diet detects EmA production in the culture medium only in half of the cases and other studies must be performed to evaluate whether EmA production after in vitro challenge can be considered a reliable test for confirming CD diagnosis.

Treatment of giardiasis reverses "active" coeliac disease to "latent" coeliac disease.

In patients with coeliac disease, a regression of intestinal damage without a gluten-free diet is a very rare event. We describe a young child with diarrhoea, intestinal mucosa atrophy and positive serum anti-endomysial and anti-tissue transglutaminase (anti-tTG) antibodies during intestinal giardiasis infection. He showed normal intestinal mucosa architecture and negative anti-endomysial and anti-tTG antibodies after his giardiasis was cured, although he continued to assume a normal diet. Re-evaluations on a 6-monthly basis showed that he was symptom free, and all haemato-chemical parameters were within normal limits. Three years after the initial diagnosis, a third intestinal biopsy showed: normal mucosa architecture; an increase in the intra-epithelial CD3+ and gamma/delta+ lymphocyte counts; and immunoglobulin-A anti-endomysial antibody detection in the supernatant of the intestinal mucosa culture incubated with gliadin. An active coeliac disease status, with intestinal mucosa atrophy, may regress to a latent coeliac disease status with normal intestinal mucosa histology after removal of the environmental factors that have presumably precipitated mucosa damage. Serum anti-endomysial and anti-tTG antibody behaviour is not a permanent, life-long feature and this must recommend the repetition of anti-endomysial or anti-tTG antibody assays in the same patient whenever coeliac disease diagnosis is again suspected, irrespective of previous negativity.

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 Crohn's 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.

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

BACKGROUND: 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. AIMS: To evaluate the clinical characteristics of patients with HP-intolerance and the long-term outcome of treatment with ass' milk. PATIENTS AND METHODS: This study included 21 HP-intolerant infants (15 males, median age at diagnosis 2 months) treated with an ass' milk-based diet and 70 cow's milk (CM) intolerant infants (40 males, median age at diagnosis 3 months) treated with casein hydrolysate milk-based diet. All patients were followed-up for a median period of 4 years. Both HP-intolerance and intolerance to other foods were diagnosed according to the double-blind placebo-controlled procedure. Formal CM-challenges were conducted at yearly intervals until tolerance was demonstrated. At diagnosis and after one year of the respective diets, the following growth parameters were determined: relative weight for sex and age, relative weight for height and height z-score. RESULTS: During the study period, multiple food intolerance was documented in 21/21 HP-intolerant infants (ass' milk group) and in 20/70 infants with CM-intolerance but tolerating HP (casein hydrolysate group) (P < 0.0001). In the ass' milk group, the more frequent food intolerances were toward soya, oranges, tomatoes and fish; goat's milk intolerance was demonstrated in five out of six patients receiving this food, and sheep's milk derivatives intolerance in four out of seven; these patients tolerated ass' milk. During the study period 3/21 patients in the ass' milk group became ass' milk intolerant; they showed vomiting (one cases) or diarrhoea (two cases). A lower percentage (52%) of patients in the ass' milk group became CM-tolerant during the study period than in the casein hydrolysate group (78%) (P < 0.01) and the age of the children at CM-tolerance was higher in the ass' milk than in the casein hydrolysate-treated children (P < 0.05). At diagnosis, a higher frequency of cases with elevated serum total IgE and specific IgE to CM antigens (P < 0.01) was observed in the ass' milk group. No difference was recorded between the two treatment groups in any of the growth parameters considered either at diagnosis or during the follow-up. CONCLUSIONS: HP-intolerant patients showed a higher frequency of persistent food intolerance and of multiple food intolerance than patients tolerating casein hydrolysate. Ass' milk feeding was confirmed as a safe and valid treatment of the most complicated cases of multiple food intolerance.

Evidence of very delayed clinical reactions to cow's milk in cow's milk-intolerant patients.

BACKGROUND: In patients with cow's milk protein intolerance (CMPI), delayed clinical reactions to cow's milk (CM) ingestion may be misdiagnosed if the clinical symptoms are not "classical" and there is a long time lapse between ingestion of CM and the clinical reaction. The aim was to evaluate the clinical outcome of CMPI in a cohort of CM-intolerant children, with particular attention to the occurrence of clinical manifestations beyond 72 h after CM challenge. METHODS: Eighty-six consecutive patients (44 boys, 42 girls) with new CMPI diagnoses were enrolled; median age at diagnosis was 4 months. Patients were followed up for a mean period of 40 months. In all patients, CMPI diagnosis was made on the observation of symptoms, their disappearance after elimination diet, and their reappearance on double-blind CM challenge. At CMPI diagnosis, immunologic tests to demonstrate IgE-mediated hypersensitivity were performed. After 12 months of CM-free diet, CM tolerance was re-evaluated with a CM challenge continued at home for up to 30 days, according to a double-blind, placebo-controlled method. Patients who did not achieve CM tolerance continued a CM-free diet and subsequently underwent yearly CM challenge. RESULTS: The percentages of CMPI patients who became CM-tolerant after 1, 2, and 3 years of CM-free diet were 30%, 54.5%, and 70%, respectively. At the end of the follow-up period, 26/86 subjects showed persistent CMPI; these patients had a higher percentage of positivity of total serum IgE (P<0.05), RAST (P<0.01), and cutaneous prick tests for CM antigens (P<0.001) than all the others. At CMPI diagnosis, all patients had a clinical reaction within 72 h from the beginning of the CM challenge; at the subsequent "cure" challenges, we observed patients who first reacted to CM more than 72 h after ingestion. In total, 10 out of 86 patients showed "very delayed reactions"; in these patients, the mean time between the beginning of CM challenge and the onset of a clinical symptom was 13.3 days (range 4-26 days). The number of "very late reactors" increased from the first to the third of the "cure" CM challenges, performed at yearly intervals. The "very delayed" CMPI manifestations in these subjects were constipation (five cases), wheezing (two cases), dermatitis plus constipation (two cases), and dermatitis alone (one case); in 6/10 patients, the symptoms observed at the "cure challenge" were different from those at CMPI onset. CONCLUSIONS: Very delayed clinical reactions to reintroduction of CM in the diet can occur in CMPI patients; thus, accurate follow-up and frequent outpatient observation in patients with a long history of CMPI are probably more useful and safer than prolonged CM challenge.

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

Cow's 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.

Usefulness of faecal elastase-1 assay in monitoring pancreatic function in childhood coeliac disease.

BACKGROUND: In coeliac disease it has been demonstrated that the indirect pancreatic function tests detect a greater percentage of subjects with exocrine pancreatic insufficiency than the secretin-caerulein test. AIMS: To evaluate faecal pancreatic elastase-1 assay in monitoring patients with coeliac disease. PATIENTS: Thirty patients with coeliac disease (11 m; age range 1-7 years) completed a 2-month follow-up. As controls, we studied two sex-, age-matched patient groups: a) 15 patients with cystic fibrosis, b) 40 surgical patients without gastroenterological disease. METHODS: In all coeliac subjects, stools were collected over 24 hours at diagnosis and then 30 and 60 days after commencement of the gluten-free diet; on a sample of the faeces we assayed elastase-1 activity. In the control patients, faeces were collected over 24 hours for elastase-1 assay only once. The coeliac patients only underwent the secretin-caerulein test, at diagnosis. RESULTS: Ten out of 30 coeliac patients (33%) had subnormal faecal elastase-1 values at diagnosis, while all the surgical controls had values within the normal range; median values in coeliac patients were significantly lower than those of the surgical controls (median 287 mcg/g, 95% CI 271-430, versus 487 mcg/g, 95% CI 426-538, p < 0.007). Cystic fibrosis patient values (median 10 mcg/g, 95% CI 7-155) were significantly lower than both those of coeliac patients and those of the surgical controls (p < 0.0001). The secretin-caerulein test showed that 7/30 coeliac patients (23%) had a deficiency in one or more pancreatic enzymes; all these subjects had below normal faecal elastase-1 values. During the follow-up, we observed a progressive reduction in the number of coeliacs with pancreatic impairment; however, after 2 months of gluten-free diet, faecal elastase-1 deficiency persisted in 2/30 coeliacs. CONCLUSIONS: Faecal elastase-1 determination in coeliac patients reveals a similar frequency and duration of pancreatic impairment to those observed in studies performed using the faecal chymotrypsin assay; a reduction in faecal elastase-1 values can be linked to "non-typical pancreatic diseases".

Intolerance of cow's milk and chronic constipation in children.

BACKGROUND: Chronic diarrhea is the most common gastrointestinal symptom of intolerance of cow's milk among children. On the basis of a prior open study, we hypothesized that intolerance of cow's 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 cow's 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 erythema or edema. After 15 days of observation, the patients received cow's milk or soy milk for two 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 cow's milk had a response. In all 44 children with a response, the response was confirmed with a double-blind challenge with cow's 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 cow's-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 cow's milk.

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

BACKGROUND: Recent research has shown that cow's milk protein intolerance (CMPI) often persists beyond 4 years of age. AIMS: To evaluate the clinical and immunological characteristics of a group of infants with persistent CMPI. PATIENTS AND METHODS: Twelve infants (6 m, 6f) with persistent CMPI were followed up from birth until a median age of 5 years. The patients underwent CMP challenge each year to evaluate CMP-tolerance. As controls we followed 26 infants (12 m, 14 f) with CMPI that resolved within 1-2 years. RESULTS: A family history of atopic disease was found in 10/12 patients with persistent CMPI and in 10/26 controls (P<0.01). Clinical presentation changed over time: at onset symptoms were prevalently gastrointestinal, while at the end of the study there was an increased frequency of wheezing and constipation and a higher frequency of delayed reactions to CMP-challenge than at study commencement (9/12 vs 2/12; P<0.007). 11/12 infants with persistent CMPI and 3/26 controls (P<0.0001) presented multiple food intolerance. During the observation period 9/12 infants with persistent CMPI and 2/26 controls showed atopic disease: asthma, rhinitis, eczema (P < 0.0001). CONCLUSIONS: Persistent CMPI forms are characterized by: (a) considerable importance of familial atopic disease; (b) change in CMPI manifestations over time and more prolonged delay between CMP consumption and manifestation of symptoms; (c) very high frequency of multiple food intolerance and allergic diseases.

Gluten stimulation induces an in vitro expansion of peripheral blood T gamma delta cells from HLA-DQ2-positive subjects of families of patients with celiac disease.

The intestinal gluten sensitivity formally known as celiac disease (CD) is characterized by an evident involvement of local immune response and it is associated with the expression of HLA-DQ2 allele. The major role in the disease seems to be played by the T lymphocyte population bearing gamma delta T cell receptor (T gamma delta cells) which are increased both in peripheral blood and intestinal mucosae of celiac patients. In this paper data on the effects of in vitro gluten stimulation on lymphocytes expressing the T gamma delta phenotype are reported. Gluten seems to be able to induce the expansion of the T gamma delta cell population both in CD patients and their HLA-DQ2-positive asymptomatic relatives, in spite of the absence of clinical evidence of the disease. In addition, the evaluation of gluten-induced cytokine production shows that interleukin-4 could be implied in the early phases of pathogenesis of CD.

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

Recent studies have pointed to the relationship between iron deficiency anemia and celiac disease, although data on the prevalence of celiac disease in anemic patients have been conflicting, and there is no agreement on the best screening procedure for CD in these patients. Our aims were to evaluate the relationship between anemia and celiac disease (CD) from two different points of view--the hematology clinic and the pediatric gastroenterology department--and to evaluate the utility of anti-endomysial antibody determination in screening anemic patients for CD using human umbilical cord as substrate. We studied 130 patients with CD (58 males, 72 females; median age 18 months) diagnosed at a department of Pediatric Gastroenterology, and 85 patients with iron deficiency anemia (38 males, 47 females; median age 48 years) observed at a hematology outpatient clinic. From the 85 adult patients with iron deficiency anemia, we selected a subgroup of 25 subjects with no improvement in Hb after two months of iron therapy (80 mg/day orally). Routine hematochemical tests were performed in all 215 patients. All pediatric and adult subjects underwent immunological screening for celiac disease (AGA and EmA assay); intestinal biopsy was also performed on patients testing positive. In the adult anemic patients a serum sample was stored at -20 degrees C on first observation, and after 6-18 months EmA on human umbilical cord were assayed. In the pediatric patients with CD, anemia was observed in 91/130 patients (70% of cases, the most frequent symptom after poor growth); however, this was the only presenting symptom of CD in 2/130 patients (1.5% of cases). Anemia was sideropenic in 41/91 patients (iron <45 microg/dl, ferritin <15 microg/liter). In the adult patients with iron deficiency anemia, immunological screening (AGA and EmA) showed suspected CD in 5/85 cases (5.8%), with diagnosis confirmed on intestinal biopsy. These five patients were in the subgroup of iron supplementation therapy nonresponders. CD prevalence in the refractory anemia subgroup was, therefore, 5/25 (20%). On diagnosis the hematological indices of the anemia + CD patients were not different than those of the refractory anemia patients without CD. The median age of the CD + anemia patients was significantly lower 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 patients showed a perfect concordance with those using a traditional 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 probably not diagnosed. In our adult patients with sideropenic anemia, CD prevalence was 5-6%; however, the observation of anemic patients not responding to oral iron therapy makes a diagnosis of CD much more probable. EmA determination on human umbilical cord is the most logical approach to screen anemic patients for suspected CD.

Use of 24-hour oesophageal pH-metry for the detection of gastro-oesophageal reflux in infants: what is the ideal score and the optimal threshold? A receiver-operating-characteristic analysis.

BACKGROUND: The search for the ideal score and best cut-off value to interpret the data from 24-hour continuous pH-monitoring interests both gastroenterologists with adult patients and paediatric gastroenterologists. AIMS: To evaluate 24-hour continuous pH monitoring as a discriminatory test in the diagnosis of gastro-oesophageal reflux disease in a paediatric population, using various pH-metry scores and cut-off values. PATIENTS: One hundred and one patients presenting gastro-oesophageal reflux disease (endoscopic diagnosis of oesophagitis or coincidence between apnoea and reflux episodes observed during pH-metry), median age 10 months, were studied, together with a control group of 84 subjects, median age 11 months. RESULTS: After plotting the receiver operating characteristic curves and calculating the area below them, the evaluation of the total percentage reflux time proved to have a higher capacity for distinguishing between the patients and controls than the Euler score (p < 0.05). The cut-off value of 5.2% for the total percentage reflux time had a sensitivity of 75% and was 88% specific. Using higher cut-off values according to age, a 95% specificity and a 49% sensitivity were obtained. The most sensitive score was the Jolley score: 96% with a cut-off of 64 and 90% with a cut-off of 100 (a value determining the maximum diagnostic accuracy); specificity, however, was low: 39-61%. In addition, the Jolley score was the most useful parameter in detecting patients with apnoeic episodes secondary to gastro-oesophageal reflux disease and allowed a correct diagnosis in 12/13 cases. CONCLUSIONS: a) The simple determination of total percentage reflux time, according to the methodology used, has a higher predictive capacity than the more complex pH-monitoring scores; b) the best cut-off value for total percentage reflux time is 5.2% as it combines a good specificity and sensitivity which are necessary for this test; c) age-dependent cut-off values are highly specific but sensitivity is much too low; d) the Jolley score is very sensitive and this was maintained even when the cut-off was raised to a value of 100; it is the best predictive score for episodes of gastro-oesophageal reflux-dependent apparent life-threatening events.

Role of pancreatic impairment in growth recovery during gluten-free diet in childhood celiac disease.

BACKGROUND & AIMS: Clinical significance and duration of insufficient release of pancreatic enzymes in childhood celiac disease have not been clarified. The aim of this study was to evaluate the role that pancreatic impairment plays in growth recovery and the duration of this impairment. METHODS: Forty-six patients with celiac disease who had a median age of 2.5 years were enrolled. Fecal chymotrypsin level was determined at diagnosis and then every 15 days after the beginning of a gluten-free diet in all patients. RESULTS: At diagnosis, 17 of 46 patients with celiac disease had subnormal fecal chymotrypsin values. During the gluten-free diet, a progressive reduction in the percentage of patients with subnormal fecal chymotrypsin values was observed: 12 of 46 patients after 30 days and 2 of 46 patients after 60 days. Weight increase after 2 months of gluten-free diet was significantly greater in patients with normal fecal chymotrypsin values at diagnosis than in patients with subnormal values, and a positive correlation was found between fecal chymotrypsin at diagnosis and weight increase (r = 0.56). CONCLUSIONS: A small percentage of patients with celiac disease still had subnormal chymotrypsin concentrations after 60 days of gluten-free diet. Fecal chymotrypsin is a predictive index of weight recovery in the first months after diagnosis of celiac disease; it could be used to select patients for enzyme supplementation therapy.

Evaluation of pancreatic function development after hydrolyzed protein-based and soy-based formulas in unweaned infants.

AIMS: Different protein sources could determine differences in the maturation of the exocrine pancreas in humans during the first months after birth; however, no studies have been carried out in man to evaluate the effect of a hydrolyzed protein diet on exopancreatic function. Our aim was therefore to determine the effect of two different milk formulas on pancreatic secretion in patients with cow's milk protein allergy (CMPA). METHODS: We selected 12 infants (median age, 3.0 months), fed for 6 weeks with a hydrolyzed casein-based formula, and 14 infants (median age, 3.0 months) who received a soy-protein based formula over the same period. As controls, two groups of age-matched infants with no gastrointestinal disease and receiving a free diet were studied. In the patients with CMPA a secretin-cerulein test was performed at the commencement of the diet and after 6 weeks; in the controls the same test was performed only once. Enzyme concentrations and outputs of trypsin, chymotrypsin, lipase, and phospholipase were assayed. RESULTS: No significant difference was observed between the two groups of patients with CMPA for any of the enzymes studied, either at base line or after 6 weeks of diet. No difference was recorded between CMPA patients and age-matched controls on a free diet either. In both CMPA groups there was a significant increase over basal values in trypsin, chymotrypsin, and lipase concentrations after 6 weeks. Furthermore, there was a significant positive correlation between the age of the patients and enzyme concentrations. Mean daily weight gain was 27.4 +/- 3.9 g with hydrolyzed casein and 27.2 +/- 3.5 g in soyfed patients. CONCLUSIONS: It is suggested that the diets with different protein content used in subjects with CMPA did not determine any difference in the stimulation of proteolytic and lipolytic pancreatic enzymes.

Pancreatitis-associated protein in patients with celiac disease: serum levels and immunocytochemical localization in small intestine.

Since PAP is a stress protein expressed in human pancreas during pancreatitis but also constitutively synthesized in the small intestine, we looked whether its expression would be altered in patients with celiac disease. Serum PAP concentrations were determined consecutively in 54 patients with celiac disease on a free diet (group A), in 47 patients with celiac disease on a gluten-free diet (group B), in 22 patients with other intestinal pathologies but with normal intestinal mucosa (group C), in 14 patients with retarded growth, no gastrointestinal disease and normal intestinal mucosa (group D), and in 17 controls (group E). Serum PAP levels (ng/ml) were significantly higher in group A (127.3 +/- 56.8) than in the other groups (B: 47.2 +/- 20.5; C: 51.5 +/- 32.2; D: 47 +/- 22.8; E: 27.6 +/- 9.0), which were not different from each other. In group A, a positive correlation was observed between serum PAP values and antigluten antibody levels (vs. AGA IgG r = 0.58, p < 0.001; vs. AGA IgA r = 0.66, p < 0.001). Furthermore, 12 patients from group A were evaluated after 10-12 months of gluten-free diet and in all of them PAP serum concentration had decreased (mean +/- SE before the diet 122.5 +/- 36.4, after the diet 48.7 +/- 13.7, p < 0.0001). In addition, we performed an immunocytochemical study to localize PAP in the intestinal mucosa of patients from all groups except E. PAP was localized to the Paneth cells and to some globet cells, in patients with mucosal atrophy as well as in those with normal mucosa with no obvious quantitative difference. We concluded that in patients with celiac disease the active phase of the disease was accompanied by an increased serum concentration of PAP. Further studies are necessary to understand the mechanism leading to PAP elevation in the serum of patients with celiac disease.