Autoimmune enteropathy and rheumatoid arthritis: a new association in the field of autoimmunity.

We report the case of a 35-year-old woman with a diagnosis of coeliac disease at the age of 32 due to a severe malabsorption and flat mucosa without endomysial and tissue transglutaminase antibodies. The lack of clinical and histological improvement after 1 year of a gluten-free diet led to a diagnosis of refractory sprue. She had a good clinical response to steroids that were stopped after 3 months when she became pregnant. After delivery, she again started to complain of malabsorption with arthritis. Positivity for enterocyte autoantibodies together with a flat mucosa persistence allowed to identify a condition of autoimmune enteropathy; moreover, a rheumatological assessment gave evidence of an associated rheumatoid arthritis. Treatment by steroids and methotrexate brought to the remission of intestinal and articular symptoms together with an improvement of duodenal histology. This is the first description of an autoimmune enteropathy associated with rheumatoid arthritis. Autoimmune enteropathy should be always ruled out in patients with a villous atrophy unresponsive to a gluten-free diet, autoimmune manifestations and negativity of coeliac disease markers.

Response to infliximab is related to disease duration in paediatric Crohn's disease.

BACKGROUND: Infliximab is an effective therapy in adult patients with refractory and fistulizing Crohn's disease. Experience in children is still limited. AIM: : To evaluate the experience in 22 children and adolescents treated with infliximab with refractory and/or fistulizing Crohn's disease, and to compare duration of response in children between early Crohn's disease and late Crohn's disease. METHODS: The experience in 22 children and adolescents treated with a total of 73 infusions was evaluated retrospectively. Treatment indication was refractory Crohn's disease in 9/22 patients, fistulizing Crohn's disease in 7/22 patients and both these conditions in 6/22. All patients with refractory Crohn's disease had late Crohn's disease (> 1 year), whereas 6/13 patients with fistulas had early disease (< 1 year). RESULTS: Mean Paediatric Crohn's Disease Activity Index (PCDAI) decreased from 41.2 to 16.2 at 4 weeks (P < 0.01), and to 15.4 at 18 weeks (P < 0.01). Mean PCDAI at 18 weeks in children with early Crohn's disease and late Crohn's disease was 5.5 and 18.1, respectively (P < 0.05). Complete closure of fistulas was obtained in 5/6 children with early Crohn's disease and in 2/7 children with late Crohn's disease. Immediate adverse reactions were observed in two children. CONCLUSIONS: Infliximab is a highly effective treatment in children and adolescents with both severe refractory or fistulizing Crohn's disease. Children with early Crohn's disease have a higher chance of prolonged response to infliximab than children with late Crohn's disease.

Gastric pepsin and acid secretion during total parenteral nutrition and constant-rate enteral nutrition in infancy.

Total Parenteral Nutrition (TPN) and constant rate enteral nutrition (CREN) are widely used: their effects on gastric function, especially pepsin secretion, are unknown. Basal and pentagastrin-stimulated pepsin (BPO, MPO) and acid (BAO, MAO) secretions were measured in three groups of infants: controls (14 infants fed normally), TPN groups (seven infants on TPN), CREN groups (14 infants on CREN). The MAO and MPO of the TPN group were significantly lower than controls (p less than 0.02), and the ratio of pentagastrin-stimulated PO/AO did not change, suggesting a large decrease of acid gastric function in the TPN group. BPO was not different from controls and BAO was significantly higher because of amino acids perfusion. The data for CREN group were not different from those of the control group, despite the fact that 11 infants were on TPN before CREN. These results demonstrate that TPN causes decreases in both acid and pepsin secretions in human infants. When TPN children are placed on CREN, these secretions return to normal.

Comparison of two non-absorbable antibiotics for treatment of bacterial enteritis in children.

Thirty-one children with bacterial diarrhoea were administered an oral suspension of rifaximin (14 children, mean age: 4.3 yrs; dosage: 5 ml, equal to 100 mg, x 4/day for 3 days on average) or of neomycin + bacitracin (17 children, mean age: 3.6 yrs; dosage: 5 ml x 4/ day for 4 days on average). Etiologic agents were: minor Salmonella spp in 9 and 7 cases respectively; enteropathogenic E. coli in 5 and 10 cases. Rifaximin yielded bacteriological cure in 12/14 children; the reference drug in 13/17. With both antibiotics, stool number/day fell, after one day, from 6 on average, to normality (2-3 stools); within two days stool consistency and characteristics shifted to normal. Symptomatology was quickly eliminated in all of the cured children. Both treatments showed excellent systemic tolerability; rifaximin was completely tolerated also locally, while two cases of stomach ache were reported with the reference drug.

Food and pentagastrin stimulation of gastrin, pepsinogen I and acid in children with primary duodenal ulcer.

Six cases of duodenal ulcer were studied in male children (mean age 8.8 yrs., range 6-12 yrs., mean weight 29.8 kg). All were submitted to X-ray examination and/or digestive endoscopy. Ten healthy children, matched by weight, age and sex were chosen as controls. All children underwent a standardized protein meal to evaluate serum gastrin and pepsinogen I response and the pentagastrin test for acid secretion. The serum gastrin level was found to be similar in the two groups (normal children and duodenal ulcer) both in the fasting state and after food stimulation, whereas the basal and after-meal serum pepsinogen I values were statistically higher in the duodenal ulcer group (p less than 0.01). The pentagastrin test showed a basal, maximal and peak acid output significantly lower in controls than in the subjects with primary duodenal ulcer. The results confirm that elevated gastric acid response is already present in duodenal ulcer of childhood and seems to be its cause rather than its consequence. Our finding of an already elevated pepsinogen I level, coupled with the already reported family histories of the disease, further support an inherited basis for duodenal ulcer in childhood.

[Endoscopic study in the diagnosis of nodular lymphoid hyperplasia of the colon in childhood]. / L'indagine endoscopica nella diagnosi di iperplasia nodulare linfoide del colon in età pediatrica.

Colonic lymphoid hyperplasia has been diagnosed in 10 children, aged from 11 months to 12 years, with heterogeneous clinical symptoms such as rectal bleeding, abdominal pain, chronic diarrhea and constipation. The Authors underline the value of endoscopy in the diagnosis of colonic lymphoid hyperplasia which also permitted to exclude other colonic diseases often misdiagnosed by double contrast barium enema (familial polyposis, lymphoid polyps, Crohn's disease, Ulcerative colitis). In This study the Authors discuss the probable etiopathogenetic mechanisms and the prognosis of colonic lymphoid hyperplasia: it should be considered as a benign conditions reflecting a non-specific response to different stimuli.

[Detection of coeliac disease in the late childhood. Discussion on clinical presentation and diagnostic criteria. (Preliminary results) (author's transl)]. / Malattia celiaca a riscontro tardivo. Discussione sulla presentazione clinica ed i criteri diagnostici. (Risultati preliminari).

In this study 9 children ranging from 8 to 15 years of age affected by "short stature" not due to endocrine diseases underwent intestinal biopsy. In 5 of then a subtotal villous athrophy (STVA) has been shown and coeliac disease then diagnosed. The AA. underline the fact that in children with short stature, anamnestic and laboratoristic criteria are unreliable in suspecting the disease and stress the importance of jejunal biopsy as part of the diagnostic work-up in all cases of short stature which find any other clearcut explanations. The possibility monosymptomatic coeliac disease in the late childhood is in fact by now supported by documentary evidence.

[Yersinia enterocolitica infection in thalassemia. Report of one case (author's transl)]. / L'infezione da Yersinia enterocolitica in corso di talassemia mayor. Descrizione di un caso.

The Authors describe a rare case of Yersinia Enterocolitica (Y.E.) infection in a child affected by thalassemia. The onset of the disease was that of an acute enteritis with diarrhea, fever, vomiting and abdominal pain which subsequently evolved in a picture consistent with an acute appendicitis. Laparotomy was then performed and showed a marked suppurative mesenterial lymphadenitis with mild appendicular inflammation and Y.E. infection was suspected. Culture from lymphonodes confirmed the presence of Y.E. sensitive to tobramicin and CTM. The use of these chemiotherapic agents has been followed by a rapid clinical improvement. Our recent experience could suggest some practical considerations: 1) Culture of Y.E. should be routinely performed in all children affected by acute gastroenteritis and particularly in those, above 5 years of age, in which the infection can simulate acute appendicitis. 2) Special attention should be carried out in children affected by thalassemia who can easily present more serious disease often complicated by septicemia. 3) Therapy depends on the form and severity of the disease and should be always guided by in vitro sensitivity test because of the possibility of resistence of Y.E. against the most frequently used antibiotics in septicemia.

[Home-coming diarrhea. Presentation of a clinical case]. / Diarrea di ritorno. Presentazione di un caso clinico.

The Homing Diarrhea, described by Duhamel and Rey in 1980, represents a gastrointestinal disease which affects children of emigrants coming back from a trip to their country of origin and may become so serious to cause death secondary to dehydration or septicemia. The poor nutritional conditions at the beginning of the trip (secondary to low socioeconomic situation) and the onset of acute enteritis during the travel, caused by Salmonella or Shigella, E. Coli, Campylobacter, Myceti, Giardia Lamblia, Rotavirus, are considered the main and triggering factors of the homing diarrhea. Intensive care can be necessary to interrupt the sequence constituted by diarrhea-malnutrition-dehydration. Therefore prophylaxis, including good basal nutritional conditions and the use of p.o. glucose-electrolyte solutions at the beginning of the acute enteric episode appears to be the most effective measure to prevent the onset of the disease. A case of homing diarrhea is reported.

[Exogenous and endogenous gastric secretion in children with primary duodenal ulcer]. / Secrezione gastrica esogena ed endogena in bambini con ulcera duodenale primaria.

Twelve cases of duodenal ulcer were studied in children, 11 male and 1 female (mean age 10 +/- 2.7 years) (mean weight 30 +/- 3.7 Kg.) (Group 1). All were submitted to x-ray examination and/or digestive endoscopy. Twenty healty children, matched by weight, age and sex were chosen as controls (Group 2). All children underwent a standardizet protein meal to evaluate serum gastrin and pepsinogen I response and the pentagastrin test for gastric acid secretion. The serum gastrin levels were found to be without significative differences in the two groups, both in the fasting state (Group 1: 77 +/- 16 pg/ml vs. Group 2: 58 +/- 12 pg/ml) and after food stimulation (Group 1: 110 +/- 22 pg/ml vs. Group 2: 88 +/- 47 pg/ml), whereas the basal serum pepsinogen I (Group 1: 74 +/- 10 ng/ml vs. Group 2: 43 +/- 1.8 ng/ml) and after meal (Group 1: 83 +/- 14 ng/ml vs. Group 2: 49 +/- 2.1 ng/ml) values were statistically higher in the duodenal ulcer group (p less than 0.01). The pentagastrin test showed a statistically difference in MAO (Group 1: 0.370 +/- 0.10 mmol/H+/hr./Kg. vs. Group 2: 0.210 +/- 0.11 mmol/H+/hr./Kg. - p less than 0.001) and PAO (Group 1: 0.480 +/- 0.13 mmol/H+/hr./Kg. vs. Group 2: 0.351 +/- 0.12 mmol/H+/hr./Kg. - p less than 0.005) between the groups. The results confirm that elevated gastric acid response is already present in duodenal ulcer of children and seems to be its cause rather than its consequence. Our finding of an already reported family histories of the disease, further support an inherited basis for duodenal ulcer in children.

[Dermatitis herpetiformis and latent celiac disease in two siblings]. / Dermatite erpetiforme e malattia celiaca silente in due fratelli.

The association between coeliac disease (CD) and dermatitis herpetiformis (DH) is well known. Moreover, this cutaneous disease may be the only sign of an otherwise asymptomatic CD. Subjects presenting with both CD and DH generally show an HLA pattern in which A1, B8, DR2, DR7, DQw2 are the most frequent antigens one can find. We report about 2 brothers presenting with DH, clinically asymptomatic, without antigliadin serum antibodies (AGA), but positive to the research of antiendomysial (EMA) ones. The biopsy performed by digestive endoscopy showed a complete atrophy of duodenal villi and the diagnosis of CD was confirmed according to the European Society for Pediatric Gastroenterology and Nutrition (ESPGAN) criteria. The diet without gluten caused the DH to recovery and the duodenal villi microscopic aspect to normalize as well. Both the brothers had the same HLA pattern: A1, B8, DR3-DR2, DQw2. Our clinical study suggests that it is very important, especially for the general practitioner, to recognize a DH and in every child presenting with a dermatitis like that it will be mandatory to perform a laboratory research of both AGA and EMA.

[Clinical approach to constipation: proposal of a diagnostic and therapeutic protocol]. / Contributo all'inquadramento clinico della stipsi: proposta di protocollo diagnostico e terapeutico.

A study concerning constipation in children has been carried out in the University Department of Pediatrics and in the Division of Pediatric Surgery of Parma with the aim of reaching an homogeneus approach: it has been applied to 20 children up to now observed for such a problem. According to clinical and anamnestic criteria, children were divided into 3 groups on the basis of different degree of constipation: 1) moderate, 2) mild, 3) severe. Children belonging to the 2nd and 3rd group underwent barium enema and rectal manometry; two cases of ultrashort Hirschprung's disease and 7 cases of functional megarectum were diagnosed. Different treatment have been employed for each group and good results were observed in 18 cases. The AA. briefly discuss the different aspects concerning constipation and its therapy in childhood including diet, drugs, psychotherapy and surgical treatment.

Relationship between baseline impedance levels and esophageal mucosal integrity in children with erosive and non-erosive reflux disease.

BACKGROUND: Baseline impedance measurement has been reported to be related to esophageal acid exposure and hypothesized to be a marker of microscopic changes of the esophageal mucosa. Aims of the study were to establish whether any relationship existed between the magnitude of intercellular space diameter (ISD) of esophageal mucosa and baseline impedance levels in children with gastro-esophageal reflux disease (GERD), and to compare baseline impedance levels between children with non erosive (NERD) and erosive (ERD) reflux disease. METHODS: Fifteen children (median age: 11.2 years) with NERD, and 11 with ERD (median age: 9.6 years) were prospectively studied. All patients underwent upper endoscopy. Biopsies were taken 2-3cm above the Z-line, and ISD was measured using transmission electron microscopy. All patients underwent impedance pH-monitoring, and baseline impedance levels were assessed in the most distal impedance channel. KEY RESULTS: Mean (±SD) ISD did not differ between NERD (1.0±0.3µm) and ERD (1.1 ± 0.3 µm, ns). Considering all patients together, no correlation was found between distal baseline impedance and ISD (r: -0.15; ns). Conversely, negative correlations were found between distal baseline impedance and acid exposure time (r: -0.76; P<0.001), long-lasting reflux episodes (r: -0.78; P<0.001), acid reflux episodes (r: -0.62; P<0.001), and acid clearance time (r: -0.79; P<0.001). Distal baseline impedance was significantly lower in ERD [1455 (947-2338) Ω] than in NERD children [3065 (2253-3771) Ω; P<0.01]. CONCLUSIONS & INFERENCES: In children with GERD baseline impedance levels are not useful in predicting reflux-induced ultrastructural changes in the esophageal mucosa, despite their ability to discriminate between NERD and ERD.

Infliximab for pediatric ulcerative colitis: a retrospective Italian multicenter study.

BACKGROUND: Infliximab (IFX), the chimeric anti TNFalpha antibody, an established treatment for Crohn's disease in adults and in children, is used less frequently in ulcerative colitis (UC). AIM OF THE STUDY: To report the clinical course of pediatric patients with active UC receiving IFX. PATIENTS AND METHODS: Charts of 22 patients were reviewed (13 male, 9 female): 4 with a severe UC attack refractory to systemic corticosteroids (CS); 18 with a protracted course, of which 16 CS-dependent and 2 CS-resistant. The baseline therapeutic program consisted of 3 consecutive intravenous infusions (0, 2, 6 weeks) of IFX (5 mg/kg), followed by a retreatment schedule (infusion every 8 weeks); azathioprine (AZA) was administered chronically in all. Clinical evaluation was done with the Lichtiger Colitis Activity Index (LCAI). Follow-up was performed until week 54. LCAI >/= 9 was considered treatment failure; a LCAI 9: 12 had a full response and were on remission at week 54 and did not receive CS (8 on IFX re-treatment and AZA, 4 on AZA alone); 6 had a partial response; 4 were non responders. Colectomy was performed in 7 patients, beyond the period of the acute attack in all but one. CONCLUSIONS: In children with severe ulcerative colitis IFX is a valuable treatment for inducing remission, avoiding emergency colectomy; retreatment may be offered to maintain remission.

Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996-2003).

BACKGROUND: The purpose was to assess in Italy the clinical features at diagnosis of inflammatory bowel disease (IBD) in children. METHODS: In 1996 an IBD register of disease onset was established on a national scale. RESULTS: Up to the end of 2003, 1576 cases of pediatric IBD were recorded: 810 (52%) ulcerative colitis (UC), 635 (40%) Crohn's disease (CD), and 131 (8%) indeterminate colitis (IC). In the period 1996-2003 an increase of IBD incidence from 0.89 to 1.39/10(5) inhabitants aged <18 years was observed. IBD was more frequent among children aged between 6 and 12 years (57%) but 20% of patients had onset of the disease under 6 years of age; 28 patients were <1 year of age. Overall, 11% had 1 or more family members with IBD. The mean interval between onset of symptoms and diagnosis was higher in CD (10.1 months) and IC (9 months) versus UC (5.8 months). Extended colitis was the most frequent form in UC and ileocolic involvement the most frequent in CD. Upper intestinal tract involvement was present in 11% of CD patients. IC locations were similar to those of UC. Bloody diarrhea and abdominal pain were the most frequent symptoms in UC and IC, and abdominal pain and diarrhea in CD. Extraintestinal symptoms were more frequent in CD than in UC. CONCLUSIONS: The IBD incidence in children and adolescents in Italy shows an increasing trend for all 3 pathologies. UC diagnoses exceeded CD.