A cytologic assay for diagnosis of food hypersensitivity in patients with irritable bowel syndrome.

BACKGROUND & AIMS: A percentage of patients with symptoms of irritable bowel syndrome (IBS) suffer from food hypersensitivity (FH) and improve on a food-elimination diet. No assays have satisfactory levels of sensitivity for identifying patients with FH. We evaluated the efficacy of an in vitro basophil activation assay in the diagnosis of FH in IBS-like patients. METHODS: Blood samples were collected from 120 consecutive patients diagnosed with IBS according to Rome II criteria. We analyzed in vitro activation of basophils by food allergens (based on levels of CD63 expression), as well as total and food-specific immunoglobulin (Ig)E levels in serum. Effects of elimination diets and double-blind food challenges were used as standards for FH diagnosis. RESULTS: Twenty-four of the patients (20%) had FH (cow's milk and/or wheat hypersensitivity); their symptom scores improved significantly when they were placed on an elimination diet. Patients with FH differed from other IBS patients in that they had a longer duration of clinical history, a history of FH as children, and an increased frequency of self-reported FH; they also had hypersensitivities to other antigens (eg, egg or soy). The basophil activation assay diagnosed FH with 86% sensitivity, 88% specificity, and 87% accuracy; this level of sensitivity was significantly higher than that of serum total IgE or food-specific IgE assays. CONCLUSIONS: A cytometric assay that quantifies basophils after stimulation with food antigens based on cell-surface expression of CD63 had high levels of sensitivity, specificity, and accuracy in diagnosing FH. This assay might be used to diagnose FH in patients with IBS-like symptoms.

Food hypersensitivity as a cause of rectal bleeding in adults.

BACKGROUND & AIMS: Rectal bleeding and lymphonodular hyperplasia (LNH) in children can be caused by food hypersensitivity (FH). Our aim was to verify whether similar clinical and endoscopy presentations in adults can be due to FH. METHODS: Consecutive adult patients with rectal bleeding were enrolled. All underwent routine assays, colonoscopy, and histology study. RESULTS: Ten of 64 (15%) patients showed LNH as the unique sign at colonoscopy. An oligoantigenic diet resolved the rectal bleeding in 9 patients, and the reintroduction of several foods caused symptom reappearance. Double-blind placebo-controlled challenges with cow's milk and wheat protein confirmed the FH; symptoms reappeared 1-96 hours after the challenge. None of the patients were positive for IgE-mediated assays. In patients with LNH and FH, histology of the ileum and colon mucosa showed a higher number of lymphoid follicles and intraepithelial and lamina propria eosinophils compared with the other patients with rectal bleeding. CONCLUSIONS: Recurrent rectal bleeding can be caused by FH in adult patients. Endoscopic evidence of LNH characterizes these cases.

Clinical symptoms in celiac patients on a gluten-free diet.

OBJECTIVE: Persistent villous atrophy in patients with celiac disease (CD) on a gluten-free diet (GFD) is reported with increasing frequency. The aim of this study was to evaluate a possible association between persistent damage of the villi and "atypical" gastrointestinal symptoms in CD patients on a GFD. MATERIAL AND METHODS: Sixty-nine CD patients on a GFD were divided into two groups: Group A included 42 patients (6 M, 36 F, age range 17-62 years) undergoing esophagogastroduodenoscopies (EGDs) due to the presence of symptoms; Group B included 27 control patients (6 M, 21 F, age range 24-71 years) who were asymptomatic at the time of the study. Both groups underwent EGDs and a duodenal histologic study. RESULTS: Persistent endoscopic lesions were more frequent in Group A (30/42) than in Group B (12/27; p=0.01). Villous atrophy was significantly more frequent in Group A than in Group B: 85% versus 33% (p<0.0001; odds ratio (OR)=12; 95% CI 3.7-38.9). Gastrointestinal symptoms in the Group A patients were different from those present at CD diagnosis: anemia/diarrhea/weight loss in 6 cases; gastroesophageal reflux disease (GERD)-like symptoms in 12 cases; abdominal pain/constipation in 24 cases. In Group A there was no difference in gender distribution, age and duration of GFD between subjects with normal villi and those with persistent partial villous atrophy. Patients with persistent symptoms showed a higher intraepithelial eosinophil count (p=0.005) than the asymptomatic patients (p=0.01). CONCLUSIONS: Persistent intestinal villous atrophy in CD patients on a GFD is associated with gastrointestinal symptoms considered "atypical" for CD and not present at CD diagnosis.

Colonic lymphoid nodular hyperplasia in children: relationship to food hypersensitivity.

BACKGROUND & AIMS: The clinical significance of lymphoid nodular hyperplasia (LNH) of the lower gastrointestinal tract is unclear. The aim of this study was to define the frequency and clinical significance of LNH in pediatric patients undergoing colonoscopy. METHODS: Two hundred forty-five children (101 male, 144 female; median age, 8.5 years) for whom colonoscopy had been indicated were evaluated during a 3-year period. Apart from ileocolonoscopy with biopsy, all patients underwent routine biochemistry, serum total and specific IgE, and/or skin prick tests for food allergens. Patients with LNH underwent elimination diet and subsequent food challenges. RESULTS: LNH was observed in 73 of 245 (30%) consecutive colonoscopies. LNH was the only abnormal finding in 52 of the 73 cases (71%). In 43 of these 52 patients a diagnosis of cow's milk or multiple food hypersensitivity was made. Food allergy was significantly more common than in patients without LNH (83% vs 31%; P < .0001). The patients with LNH and food hypersensitivity presented hematochezia (P < .0001), elevated serum anti-beta-lactoglobulin IgG (P < .0001), anemia (P < .005), and failure to thrive (P < .03) more frequently than those without LNH. In the LNH patients histologic examination showed a higher number of lymphoid follicles throughout the colon and the terminal ileum and an increased number of lamina propria and intraepithelial eosinophils. CONCLUSIONS: The presence of LNH in the colon and/or terminal ileum is a frequent finding in symptomatic children undergoing colonoscopy. Unless associated with other specific endoscopic or histologic lesions, LNH is related to a condition of delayed-type food hypersensitivity.

Food intolerance and chronic constipation: manometry and histology study.

BACKGROUND: Chronic constipation in children can be caused by cows' milk intolerance (CMI), but its pathogenesis is unknown. AIMS: To evaluate the histology and manometry pattern in patients with food intolerance-related constipation. PATIENTS AND METHODS: Thirty-six consecutive children with chronic constipation were enrolled. All underwent an elimination diet and successive double-blind food challenge. All underwent rectal biopsy and anorectal manometry. RESULTS: A total of 14 patients were found to be suffering from CMI and three from multiple food intolerance. They had a normal stool frequency on elimination diet, whereas constipation recurred on food challenge. The patients with food intolerance showed a significantly higher frequency of erosions of the mucosa, and the number of intra-epithelial lymphocytes and eosinophils. The rectal mucous gel layer showed that the food-intolerant patients had a significantly lower thickness of mucus than the other subjects studied. Manometry showed a higher anal sphincter resting pressure and a lower critical volume in food intolerance patients than in the others suffering from constipation unrelated to food intolerance. Both histology and manometry abnormalities disappeared on the elimination diet. CONCLUSIONS: Food intolerance-related constipation is characterized by proctitis. Increased anal resting pressure and a reduced mucous gel layer can be considered to be contributory factors in the pathogenesis of constipation.

The "red umbilicus": a diagnostic sign of cow's milk protein intolerance.

INTRODUCTION: Red umbilicus is considered to be an infectious disease typical of neonates. In our experience, umbilical erythema could be due to cow's milk protein intolerance (CMPI). AIMS: To evaluate the frequency and clinical significance of umbilical erythema in a series of consecutive children referred for suspected CMPI. PATIENTS AND METHODS: Seven hundred ninety-six consecutive patients (median age, 18 months) referred for suspected CMPI diagnosis were studied. CMPI diagnosis was based on the disappearance of symptoms on elimination diet and their subsequent reappearance on double-blind placebo-controlled cow's milk challenge. RESULTS: CMPI was diagnosed in 384 patients: 120 with respiratory, 75 dermatologic and 198 gastroenterological symptoms. Although some patients showed more than 1 type of symptom, whether gastroenterological, dermatologic or respiratory, they were classified in 1 category only according to the main reason for referral to the outpatients clinic. Umbilical erythema was observed in 36 patients (median age, 10 months): 16 (8%) with gastroenterological symptoms, 9 (7.5%) with recurrent asthma and 11 (15%) with atopic dermatitis. None of the symptomatic controls without CMPI had umbilical erythema. On elimination diet, the erythema disappeared within the second week. On CMPI challenge, it reappeared within 24 hours. CONCLUSIONS: Umbilical erythema can be a sign of food intolerance and can be a useful diagnostic tool for CMPI.

[Anti-TNF (infliximab) treatment in Crohn disease: safety profile]. / Terapia biologica con infliximab (anti-TNF) nella malattia di Crohn: analisi delle complicanze.

Anti-tumor necrosis factor (anti-TNF) therapy is an important therapeutic addition in the treatment of active Crohn's disease. Although controlled trials have confirmed the efficacy of anti-TNF (infliximab) treatment, serious toxicities related to the therapies have emerged. The purpose of this article was to review the safety profile of infliximab, and in particular analyse the infectious complications, the autoimmune disorders and the theoretical risk of cancer and lymphoma.

[Osteoporotic risk in Crohn's disease]. / Il rischio osteoporotico nella malattia di Crohn. Epidemiologia, patogenesi e trattamento.

The pathogenetic mechanisms, risk factors and relationship between densitometric data and risk of fractures have been examined. The results of treatment trials and prevention measures have been showed.

Extreme thrombocytosis as a sign of coeliac disease in the elderly: case report.

Increase in the number of blood platelets to over 1,000,000/mm3 in elderly patients is generally considered secondary to a myeloproliferative or neoplastic disease. To report the case of an elderly woman hospitalized for extreme thrombocytosis associated with severe anaemia, who was found to be suffering from coeliac disease. The patient, aged 83 years, was hospitalized presenting with fatigue. Laboratory tests showed microcytic hypochromic anaemia (haemoglobin 4 g/dl) and extreme thrombocytosis (platelet count 1,400,000/mm3). Physical examination was normal, with the exception of marked thinness. There was no evidence of macroscopic bleeding from the gastrointestinal or genitourinary tracts. She had never suffered from gastrointestinal problems and had no family history of gastroenterological diseases. Oesophagogastroduodenoscopy and histology of the gastric and duodenal mucosa evidenced atrophic gastritis and an adenomatous polyp. The duodenal mucosa showed total villous atrophy, suggesting the diagnosis of coeliac disease. Antiendomysial IgA and anti-transglutaminase IgA antibodies were also positive. Colonoscopy was negative. An ultrasound examination of the abdomen was normal, and the spleen was within the normal range. A peripheral blood smear showed no alterations in erythrocyte morphology typical of hyposplenism due to coeliac disease. The platelet count decreased rapidly after blood transfusions, when both serum iron and ferritin levels were still below normal limits. Furthermore, we observed a significant inverse correlation between the platelet count and haemoglobin concentration (r = -0.94, P < 0.003). Platelet count and red blood cell count normalized after 2 months of a gluten-free diet; the haemoglobin concentration was also normal at this time. After 1 year of following a gluten-free diet, the patient remained well and had no complaints. There were no gastrointestinal disturbances. All haematological parameters were within normal limits. Intestinal biopsies showed normal villi and crypts without inflammatory infiltration of the lamina propria. This case shows that the association of haematological signs--extreme thrombocytosis and severe anaemia--considered in an elderly patient to be typical of myeloproliferative disorders or neoplastic conditions can be due to coeliac disease; thus, coeliac disease must also be considered among the possible diagnoses.

[Predictive value of serological tests in the diagnosis of celiac disease]. / Valore predittivo dei test sierologici nella diagnosi di malattia celiaca.

In the diagnostic work-up of celiac disease (CD) the simpler enzyme-linked immunosorbent assay (ELISA) for the identification of serum anti-transglutaminase (tTG) autoantibodies could substitute the immunofluorescence technique used for the detection of anti-endomysial antibodies (EmA). However, most of the studies on anti-tTG assay have considered pre-selected groups of patients and not consecutive subjects with suspected CD. The aim of this study was to compare the sensitivity, specificity and predictive value of anti-gliadin antibodies (AGA), EmA and two anti-tTG ELISAs, one based on guinea pig (gp)-tTG and the other on human (h)-tTG as antigens, in consecutive patients investigated for suspected CD. The study included 130 consecutive patients (age range 16-84 years), who underwent intestinal biopsy for suspected CD. They presented with one or more of the following symptoms: weight loss, anemia, chronic diarrhea, abdominal pain, dyspepsia, alternating bowel habits and constipation. At the time of admission in the study, an intestinal biopsy was performed and a serum sample was taken for immunoglobulin (Ig) G and IgA AGA, IgA EmA, anti-gp-tTG and anti-h-TG determination. Intestinal histology revealed that 15 patients had partial or total villous atrophy. In these patients the diagnosis of CD was confirmed at subsequent follow-up. The remaining 115 patients included in the study had an intestinal histology characterized by a normal villi/crypts ratio and were considered as controls. Serum EmA, anti-gp-tTG, and anti-h-tTG were positive in all the 15 CD subjects, whereas IgG and IgA AGA were positive in 10/15; in the control group, none were positive for serum EmA, but 11/115 (10%) were positive for anti-gp-tTG and 6/115 (5%) were positive for anti-h-tTG. The sensitivity was 100% for EmA, gp-tTG and h-tTG and 66% for IgA and IgG AGA. The specificity was 100% for EmA, 90% for anti-gp-tTG, 95% for anti-h-tTG, 74% for IgG AGA and 87% for IgA AGA. The negative predictive value was 100% for EmA, anti-h-tTG and anti-gp-tTG, 94% for IgG AGA and 95% for IgA AGA. The positive predictive value was 100% for EmA, 71% for anti-h-tTG (p = 0.03 vs EmA) and 58% for anti-gp-tTG (p = 0.003 vs EmA). Most of the patients who were false positive for anti-tTG had Crohn's disease or chronic liver disease. In conclusion, although both the anti-tTG ELISAs evaluated in the present study showed an optimum sensitivity, their low specificity determined positive predictive values which were significantly lower than those of EmA assay. Besides, the positive predictive value of gp-tTG was too low to warrant submitting a patient to intestinal biopsy for suspected CD.

Searching for wheat plants with low toxicity in celiac disease: Between direct toxicity and immunologic activation.

BACKGROUND: Natural or induced variations in the noxiousness of gluten proteins for celiac disease (CD) patients are currently being investigated for their potential in breeding wheat crops with reduced toxicity. AIMS: We evaluated the bread wheat line C173 for its effects on the in vitro-grown duodenal mucosa of CD patients. METHODS: In vitro-grown duodenal mucosa biopsies of 19 CD patients on a gluten-free diet were exposed to peptic/tryptic-digested prolamins from bread wheat line C173 lacking gliadin-glutenin subunits, analyzed for morphology, cytokine and anti-tTG antibody production, and compared with mucosa biopsies exposed to prolamins from wild-type cv. San Pastore. RESULTS: Duodenal mucosa biopsies exposed to prolamins from C173 and San Pastore released higher amounts of IFN-γ, IL-2, IL-10 and anti-tTG antibodies in the culture medium than untreated controls. The line C173 differed from cv. San Pastore as it did not produce negative effects on enterocyte height, suggesting that manipulating prolamin composition can affect innate immune responses of CD mucosa to wheat gluten. CONCLUSIONS: Our data demonstrated that this gliadin-deficient wheat has a lower direct toxicity but activates an immunologic reaction of the duodenal mucosa like that of the common wheat species.

Antiendomysium antibodies assay in the culture medium of intestinal mucosa: an accurate method for celiac disease diagnosis.

BACKGROUND: Celiac disease (CD) diagnosis is becoming more difficult as patients with no intestinal histology lesions may also be suffering from CD. AIM: To evaluate the diagnostic accuracy of antiendomysium (EmA) assay in the culture medium of intestinal biopsies for CD diagnosis. PATIENTS AND METHODS: The clinical charts of 418 patients with CD and 705 non-CD controls who had all undergone EmA assay in the culture medium were reviewed. RESULTS: EmA assay in the culture medium had a higher sensitivity (98 vs. 80%) and specificity (99 vs. 95%) than serum EmA/antibodies to tissue transglutaminase (anti-tTG) assay. All patients with CD who were tested as false-negatives for serum EmA and/or anti-tTG (32 adults and 39 children) carried the human leukocyte antigen alleles associated to CD. Furthermore, during the follow-up, four patients with negative-serum EmA/anti-tTG, normal villi architecture, and positive-EmAs in the culture medium, developed villous atrophy and underwent gluten-free diet with consequent resolution of the symptoms and complete intestinal histology recovery. CONCLUSION: EmA assay in the culture medium should be included in the diagnostic criteria for CD diagnosis in 'seronegative' patients.

Chronic urticaria as a presenting symptom of Crohn's disease.

Clinical presentation of Crohn's disease (CD) may be variable according to the location and the intensity of the inflammation. Some patients may have atypical symptoms which could delay the diagnosis. We report the first case of chronic urticaria related to a subclinical, complicated CD. Although the pathologic mechanism of this association was unclear in our patient, this case suggests that in patients with unexplained chronic urticaria it is opportune to investigate for a possible CD, even if there are no or few specific symptoms of intestinal inflammatory disease.

Plasma calprotectin levels in patients suffering from acute pancreatitis.

Calprotectin (Cal) concentration is elevated in acute inflammatory reactions and its increase in the plasma suggests a diagnostic potential for Cal assay. This study aimed (a) to evaluate the Cal plasma levels in patients suffering from acute pancreatitis (AP) and (b) to assess whether early assay of Cal plasma levels can be helpful in assessment of the severity of AP. Forty-six consecutive patients, median age 45 years, suffering from a first attack of AP were recruited at two medical centers. Data collected on admission included age, sex, delay between pain onset and admission, and Glasgow score. A severe outcome was defined according to the Atlanta criteria. AP was defined as edematous or necrotic according to the CT findings. Plasma Cal and serum C reactive protein (CRP) were assayed in all patients within the first 24 hr after hospitalization. Sixty subjects suffering from blood hypertension were recruited as controls. Plasma Cal was measured by a commercial ELISA system. In all AP patients and in none of the controls, plasma Cal concentration was higher than the normal limit. Cal values in AP patients were significantly higher than in controls (P < 0.0001). There was not a statistically significant difference in Cal values between patients with severe and patients with mild AP. Plasma Cal values did not differ in necrotizing and edematous AP. During the follow-up plasma Cal was reassayed in six of the patients with abdominal fluid collection and the values were higher in the two patients with infected necrosis. We conclude that plasma Cal is elevated in patients with AP but it is not a useful marker for early prediction of pancreatitis severity. Further studies could evaluate its usefulness in pancreatic infected necrosis.

Multiple food hypersensitivity as a cause of refractory chronic constipation in adults.

Chronic constipation that is unresponsive to laxative treatment is a severe illness, but children unresponsive to laxatives have been successfully treated with an elimination diet. We report the first cases of refractory chronic constipation caused by food hypersensitivity in adults. Four patients with refractory constipation who were unresponsive to high doses of laxatives were put on an oligo-antigenic diet and underwent successive double-blind, placebo-controlled, food challenges (DBPFC). Routine laboratory tests, immunological assays, colonoscopy, esophago-gastroduodenoscopy and rectal and duodenal histology were performed. While on an elimination diet, bowel habits normalized in all patients and a DBPFC challenge triggered the reappearance of constipation. In comparison with another 13 patients with refractory constipation unresponsive to the elimination diet, observed over the same period, the patients with food-hypersensitivity-related constipation had the following characteristics: longer duration of illness (p < 0.03), lower body mass index (p < 0.03), higher frequency of self-reported food intolerance (p < 0.01), higher frequency of nocturnal abdominal pain and anal itching (p < 0.01). In patients with food hypersensitivity, hemoglobin concentrations and peripheral leukocytes were lower than those in controls (p < 0.03). The duodenal and rectal mucosa histology showed lymphocyte and eosinophil infiltration, and the duodenal villi were flattened in two cases. In adult patients, refractory chronic constipation may be caused by food hypersensitivity and an elimination diet is effective in these subjects.

Anti-transglutaminase antibody assay of the culture medium of intestinal biopsy specimens can improve the accuracy of celiac disease diagnosis.

BACKGROUND: We measured anti-transglutaminase (anti-tTG) antibody in the culture medium of intestinal biopsy specimens from patients with suspected celiac disease (CD) and evaluated the relationship between antibody production and severity of intestinal mucosal damage. METHODS: We performed diagnostic testing for CD on 273 consecutive patients. In addition to routine histologic evaluation of duodenal biopsy specimens, we assayed anti-tTG antibodies in serum and in the culture medium of duodenal biopsy specimens. RESULTS: CD was diagnosed in 191 of the 273 patients. Sensitivity and specificity of the serum anti-endomysium (EmA) and anti-tTG assays were 83% and 85% and 99% and 95%, respectively, and both had 88% diagnostic accuracy. EmA and anti-tTG assayed in the culture medium had 98% sensitivity, 100% specificity, and 98% diagnostic accuracy (vs serum assays; P <0.0001). Twenty-nine CD patient specimens (16%) were negative for serum anti-tTG and EmA; for 24 of these patients, anti-tTG assay of the culture medium was positive. The CD patients whose biopsy specimens were positive for serum antibodies showed the following intestinal histologies: total villous atrophy, 35%; severe villous atrophy, 25%; mild atrophy, 25%; villi with no atrophy but with increased intraepithelial lymphocytes, 15%. None of the CD patients whose specimens were negative for serum antibodies showed total or severe villous atrophy; 77% had mild villous atrophy, and 23% had no villous atrophy but had increased intraepithelial lymphocyte counts. Mild villous atrophy was also seen in specimens from approximately 15% of patients without CD. CONCLUSION: Anti-tTG assay of the culture medium of biopsy specimens can improve the accuracy of CD diagnosis in patients negative for serum antibodies.

Unexplained elevated serum pancreatic enzymes: a reason to suspect celiac disease.

BACKGROUND & AIMS: The frequency of elevated serum pancreatic enzymes in patients with celiac disease (CD) is unknown. The aim of this study was to evaluate the serum levels of pancreatic enzymes in CD patients. METHODS: Serum pancreatic isoamylase and lipase levels were assayed in 90 adult and 112 pediatric consecutive CD patients at diagnosis and after 12 months of gluten-free diet (GFD). Serum elastase and trypsin levels were assayed in a subgroup of adult CD patients. Pancreatic ultrasonography was also performed. RESULTS: Twenty-six adult (29%) and 29 pediatric (26%) CD patients exhibited elevated values of serum pancreatic amylase and/or lipase; trypsin was elevated in 69% and elastase in 19%. The frequency of elevated serum pancreatic enzymes observed was identical in the patients with "typical" and "atypical" CD symptoms and in the asymptomatic patients. Most of the elevated values were lower than 2-fold the threshold limits. Elevated pancreatic enzymes were not associated with alcohol consumption, drug use, presence of abdominal pain, or diabetes mellitus. Abdominal ultrasound scan showed no abnormal findings in the pancreatic region in any of the CD patients. After 12 months of GFD, pancreatic amylase was elevated in 3 cases and lipase in 2 cases; these patients had not strictly adhered to the GFD. CONCLUSIONS: We demonstrated a frequency of about 25% of elevated pancreatic enzymes values in CD patients, including subjects without gastrointestinal manifestations and apparently asymptomatic subjects. The finding of elevated serum amylase or lipase level, in the absence of signs of pancreatic disease, would appear to suggest a need to screen for celiac disease.

Usefulness of the organ culture system in the in vitro diagnosis of coeliac disease: a multicentre study.

OBJECTIVE: Diagnosis of coeliac disease is based on the presence of villous atrophy which recovers following a gluten-free diet. The presence of circulating antiendomysial antibodies as well as their disappearance after a gluten-free diet supports the diagnosis. It has also been demonstrated that antiendomysial antibodies are detectable in supernatants of cultured intestinal biopsies from patients with coeliac disease. The objective of this study was to compare the histology and antiendomysial antibodies in culture supernatants of intestinal biopsies to validate the in vitro organ culture system as a future diagnostic tool for coeliac disease. MATERIAL AND METHODS: Seventy-five antiendomysial serum-positive patients on a gluten-containing diet were evaluated. Patients underwent endoscopy with 5 biopsy fragments: 3 for histology, 1 cultured with and the other without gliadin-peptide activator. Antiendomysial antibodies were evaluated in all culture supernatants. RESULTS: Sixty-eight patients had evidence of villous atrophy, while 73 out of 75 were positive to the organ culture system. The agreement rate between organ culture and histology results was 94%. CONCLUSIONS: As all the centres participating in the study obtained good agreement between organ culture and histology results, the new system could be considered a reliable tool for the diagnosis of coeliac disease. Nevertheless, it is possible to highlight cases with an organ culture-positive and -negative histology. This feature could be of considerable interest because, as the sensitivity of organ culture seems to be greater than the initial histology, the new system might be useful in uncertain cases where the risk of missing the diagnosis of coeliac disease is high.

Chronic constipation and food intolerance: a model of proctitis causing constipation.

OBJECTIVE: Chronic constipation in children can be linked to cow's milk intolerance (CMI) but the existence of a food intolerance-dependent proctitis is still debated. The aim of this study was to evaluate the histologic data in patients with food intolerance-related constipation. MATERIAL AND METHODS: Fifty-two consecutive patients (22 M, median age 4 years) with chronic constipation unresponsive to common treatment were enrolled. All patients were put on a cow's milk-free diet for 4 weeks and those uncured on this diet underwent a subsequent 4-week period of oligoantigenic diet. In the patients cured on elimination diet, a subsequent double-blind food challenge was performed to confirm the diagnosis of food intolerance. At entry to the study, routine hemato-chemical and immunologic assays, rectoscopy, and histologic study of the rectal mucosa were performed. In the patients cured on elimination diet, rectal histology was repeated when they were cured. RESULTS: Twenty-four patients were found to be suffering from CMI and 6 from multiple food intolerance. These patients had a normal stool frequency on elimination diet, while constipation reappeared on food challenge. The condition of the remaining 22 patients did not improve on elimination diet. The patients with food intolerance showed a significantly higher frequency of erosions of the mucosa, number of intraepithelial lymphocytes and eosinophils, and number of eosinophils in the lamina propria. Study of the rectal mucus gel layer showed that the food-intolerant patients had a significantly lower thickness than the other subjects studied. In the food intolerant patients, histologic abnormalities disappeared on elimination diet, when the patients were well. CONCLUSIONS: Food intolerance-related constipation is characterized by proctitis with eosinophil infiltrate of the rectal mucosa. A reduced mucus gel layer can be considered a contributory factor in the pathogenesis of the constipation.