Thalidomide as rescue therapy for acute severe ulcerative colitis.

INTRODUCTION: Acute severe exacerbations of Ulcerative Colitis (UC) represent a medical emergency in children and adults. Intravenous steroids remain the first line therapy for this condition, although the steroid refractoriness is common. Second-line therapy, based on the infliximab or thiopurines should be started if no response to corticosteroids is noted. The use of infliximab in children with acute severe UC, nevertheless, does not avoid the colectomy in all cases. METHODS: We present a case of severe acute UC in a paediatric patient successfully treated with thalidomide following the failed treatment with infliximab and a review of the literature. CONCLUSIONS: This is the first case of a patient presenting with acute severe UC who was treated with thalidomide, with favorable evolution. In our case the use of this drug was able to avoid the colectomy that represent the conventional but very invasive recommended therapeutic option of this condition. Therefore, thalidomide may be considered as rescue therapy in selected and carefully monitored cases of acute severe CU.

Autoimmune liver diseases.

Autoimmune liver diseases are characterized histologically by a dense mononuclear cell infiltrate in the portal tract and serologically by high levels of transaminases and immunoglobulin G (IgG) and positive autoantibodies, in the absence of a known etiology. In pediatrics, there are three liver disorders in which liver damage is likely to arise from an autoimmune attack: autoimmune hepatitis (AIH); autoimmune sclerosing cholangitis (ASC); and de novo autoimmune hepatitis after liver transplantation. The exact pathogenesis of AIH is still unknown, but it is known that unidentified environmental factors, and occasionally drugs, might trigger disease in genetically-susceptible individuals. The clinical spectrum of disease is very wide, ranging from asymptomatic individual with abnormal liver function test to fulminant liver failure. The diagnosis is based on the combination of biochemical and histological parameters, and exclusion of other liver diseases. It is a relatively rare but devastating disease, which progresses rapidly unless immunosuppressive treatment is started promptly. Standard therapy consists of a combination of corticosteroids and azathioprine, which is efficacious in 80% of patients. Alternative therapies are increasingly being explored in patients who do not respond to the standard treatment and/or have intolerable side effects. The purpose of this review was to provide an overview of the current knowledge on pediatric autoimmune liver disease.

Diagnostic work-up of inflammatory bowel disease in children: the role of calprotectin assay.

BACKGROUND: Some reports highlight the potential application of fecal calprotectin as a direct biomarker of intestinal inflammation and, therefore, as support in choosing candidates for endoscopy. The value of 100 µg/g was recently assumed as the best cutoff for this assay. The purpose of this study was to assess the diagnostic precision of the fecal calprotectin assay, compared to histology, as a stool-screening biomarker for inflammatory bowel disease (IBD) among a group of prospectively identified patients referred for recurrent abdominal pain and altered bowel habits. METHODS: Between 1999 and 2007 we prospectively evaluated the calprotectin assay in a cohort of patients with recurrent abdominal pain and altered bowel habits associated or not with other symptoms suggestive of IBD. All patients suspected of IBD, according to Rome and Porto criteria, provided stool specimens for the calprotectin assay and subsequently underwent endoscopic procedures. RESULTS: Compared to histology, the cutoff of 100 µg/g reached a sensitivity and specificity of 100% and 68%, respectively, and a likelihood ratio (LR) of 3.1. The cutoff value of 160 µg/g, however, in our series produced the best joint estimate of sensitivity and specificity: 100% and 80%, respectively, with an LR of 5. CONCLUSIONS: In pediatric patients with recurrent abdominal pain and changes in stool habits, a positive calprotectin assay is closely associated with IBD; its systematic employment, therefore, seems to improve the process of endoscopy referral. This test, simple and inexpensive, could be included in the first noninvasive phase of an IBD diagnostic work-up.

Positive impact of blocking tumor necrosis factor alpha on the nutritional status in pediatric Crohn's disease patients.

BACKGROUND: TNFalpha seems to contribute to inflammation and malnutrition in Crohn's disease (CD) patients. In CD patients, the comparative effects on nutritional status of infliximab and traditional therapy have not yet been determined. The aim of our study was to assess the effects of infliximab as compared with those of standard therapy on nutritional status, disease activity, resting energy expenditure (REE), and food intake in CD children and adolescents. METHODS: From September 1999 to September 2005, all CD patients treated with infliximab (group A) were reviewed and matched with CD patients treated with traditional therapy (mesalazine and azathioprine) (group B). RESULTS: Fourteen CD patients from group A and 14 from group B were included; median interval before follow-up investigation was 10 months. Baseline and final values of weight, height, body mass index (BMI), pediatric CD activity index (pCDAI), REE, and food intake were studied. In treated patients, but not in control group, mean baseline weight (kg) and BMI values, 39.7 +/- 13.1 and 17.9 +/- 3.3, respectively, were significantly lower than their final values 42.6 +/- 13.2 and 18.9 +/- 3.1, and median pCDAI values 23.5 were significantly higher than their final values 10 (P < 0.05). Significant changes in height, REE, and food intake were not found in either group. CONCLUSIONS: In pediatric CD patients, infliximab seems to impact positively on the nutritional status as demonstrated by the improvement in weight and BMI, but not in linear growth; effects on nutritional status seem to be due to amelioration of disease activity, rather than to REE reduction or food intake increase.

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.

Clinical role of calprotectin assay in determining histological relapses in children affected by inflammatory bowel diseases.

BACKGROUND: Inflammatory bowel diseases (IBD) are characterized by periods of remission with recurrent episodes of symptom exacerbation because of acute intestinal inflammation, which is correctly evaluated by endoscopy with biopsy sampling. However, many surrogate markers of intestinal inflammation, including fecal calprotectin (FC), are detected as potential predictors of mucosal inflammation in IBD patients. The aim of our study was to retrospectively assess the clinical efficacy of the calprotectin assay in determining histological relapses of pediatric IBD patients. METHODS: We retrospectively reviewed the histological examinations, clinical records, and FC values of patients who had undergone colonoscopy at our hospital over an 8-year period, from December 31, 1998, to December 31, 2006. Only patients with a first histological examination showing a quiescent IBD who submitted to a second histological examination during the next 3 years were selected. RESULTS: Seventy-three IBD patients, all with a first biopsy showing a quiescent IBD, were studied; at the second histological examination, 32 presented with relapse and 41 presented with remission. Relapsed patients showed significantly increased FC levels compared with nonrelapsed patients. A FC value of 275 mug/g achieved sensitivity and negative predictive value of 97% and specificity and positive predictive value of 85% in predicting histological relapse. CONCLUSIONS: FC seems to be a direct measure of intestinal inflammation and therefore a good marker of the risk of histological relapse in pediatric IBD patients. The application of this test in clinical practice may enable the avoidance of invasive tests as well as targeting treatment.

Long-term treatment with autologous red blood cells loaded with dexamethasone 21-phosphate in pediatric patients affected by steroid-dependent Crohn disease.

BACKGROUND: Inflammatory bowel disease (IBD) present in childhood in 15% to 25% of cases. The aim of therapy in children is not only to guarantee normal growth but also to prevent relapse and to maintain remission. Steroids are effective to induce remission; however, resistance, dependency, and irreversible side effects can develop. The aim of this study was to determine whether treatment with repeated infusions of autologous red blood cells (RBCs) loaded with dexamethasone 21-phosphate (Dex 21-P) is safe and allows maintenance of long-term remission in children with steroid-dependent Crohn disease (CD). PATIENTS AND METHODS: Eighteen consecutive pediatric patients who met the inclusion criteria were admitted to the study. Infusions of autologous RBCs loaded with Dex 21-P were performed every 4 weeks; the mean duration of treatment was 24 months. At the beginning of treatment and after 6, 12, and 24 months, we performed clinical evaluation according to the Pediatric Crohn Disease Activity Index (pCDAI). Assessment of body mass in dexamethasone and bone mineral density by means of computerized bone mineralometry-dual energy x-ray absorptiometry, endoscopic evaluation, and hematic morning cortisol determination were also performed. RESULTS: During treatment, the mean pCDAI significantly decreased (P < 0.05); 78% of patients discontinued steroids. Determination of morning cortisol showed suppression only on the first day after infusion, followed by normalization of values. Endoscopic findings showed remission in 44% of patients. None of the patients experienced serious side effects. CONCLUSIONS: These data suggest that repeated infusions of RBCs loaded with Dex 21-P can be safe and useful to maintain long-term remission in pediatric patients with moderately active CD.

Role of cyclosporin in preventing or delaying colectomy in children with severe ulcerative colitis.

BACKGROUND: Oral cyclosporin (CyA) has been widely and successfully used in adult patients with severe ulcerative colitis (UC) to delay or avoid colectomy. AIM: To determine if treatment with oral CyA is similarly effective in pediatric patients MATERIALS AND METHODS: Data on all patients with severe UC treated with oral CyA in our unit were collected retrospectively. Patients were treated with CyA if dependent on or resistant to steroids, and therefore, candidates for colectomy. RESULTS: Thirty-two patients with severe UC were treated with CyA administered orally at a dose needed to obtain therapeutic blood levels (150-250 ng/ml). Twenty-eight of 32 patients (87%) had an immediate response within 11 days. Four (13%) did not respond and underwent colectomy. One patient had two cycles of treatment and is in remission. Two patients underwent three cycles of treatment because of relapse, but both eventually underwent elective colectomy. Three other patients underwent elective colectomy. A total of nine colectomies were performed. CONCLUSIONS: Treatment with oral CyA altered the course of UC in 28/32 (87%) of patients; 4/32 (13%) did not respond to oral CyA and underwent colectomy. Of the 28 patients that responded to CyA, five underwent later elective colectomy. Overall, in 72% of patients, colectomy was avoided. We, therefore, suggest a trial of oral CyA in all children with severe UC who are dependent or resistant to corticosteroids.

Prevalence of liver complications in pediatric patients on home parenteral nutrition: indications for intestinal or combined liver-intestinal transplantation.

Parenteral nutrition (PN) is the only treatment for patients affected by chronic intestinal failure (CIF). Home parenteral nutrition (HPN) programs are started when patients need prolonged PN. Unfortunately, many patients on prolonged PN develop liver disease (LD). The aim of our study was to assess the prevalence of LD in our series of patients on HPN. We reviewed our records of patients discharged from the hospital on HPN for CIF. HPN was started when one parent was fully trained in the use of this treatment and if the social and familial home environment was reliable. All patients received total PN by a central venous catheter. All patients with abnormal AST, ALT, ALK, gammaGT, and bilirubin values for more than 3 months were considered affected by PN-related LD. Thirty-six patients (23 of whom were boys and 13 girls) were discharged on HPN. During the study period, for CIF, 16 were affected by short bowel syndrome (SBS), of whom 6 had ultra-short bowel; 16 with functional intestinal failure, and 4 with chronic intestinal pseudobstruction (CIPO). Mean duration of HPN was 2.1 years/patient. Nine of 36 patients (25%) on HPN for CIF showed LD. Seven of the 16 patients (43%) with LD were affected by SBS and 2 (12.5%) patients by functional intestinal failure. No patients with CIPO developed LD. In patients affected by SBS, the onset of LD was very earlier than in patients with ID.

Complications of home parenteral nutrition in a large pediatric series.

When adequate nutrition cannot be provided by enteral route as a consequence of failure of intestinal functions, parenteral nutrition (PN) become the only way to maintain adequate nutrition; however, prolonged periods of PN can lead to severe complications. Furthermore, long hospital admissions for this form of nutrition can be detrimental for the child and the family. In the past 20 years, home parenteral nutrition (HPN) programs have been developed. The aim of our study was to retrospectively evaluate the kind and the frequency of complications in a HPN pediatric case series. We had 61 patients on HPN. Total duration of the program was 27,740 days (76 total years, mean 1.2 years per patient). We observed a total of 58 complications; mean 0.79 per patient per year with a prevalence of central venous catheter-related complications (mechanical, 52%; infective, 26%). We had a very low incidence of metabolic complications (3%) and a low incidence of PN-related hepatic complications (19%). None of the complications described was the cause of death. Half of our patients have been able to stop the program. We had a low incidence (0.20 per patient per year) of septic episodes, lower than we had in patients on hospital PN in the same period (0.38 per patient per year). We had to replace 20 catheters, 18 of them for mechanical problems. Our study shows that HPN still can be a valid alternative to small intestinal transplantation in patients affected by intestinal failure and that only patients with PN-related liver disease must be considered early candidates for combined liver-small bowel transplant.

Intractable diarrhea of infancy with congenital intestinal mucosa abnormalities: outcome of four cases.

Microvillous inclusion disease (MID) and epithelial dysplasia (ED) or tufting enteropathy are the most frequent causes of intractable diarrhea with persistent villous atrophy and indefinite dependence on total parenteral nutrition (PN) from early infancy. Since these are intractable diseases, they have been proposed to be elective indication for early bowel transplantation in order to avoid complications, such as PN-related liver disease, that would require a combined small bowel-liver transplant. We describe four cases of intractable diarrhea, two with MID and two with ED, seeking to discover whether these diseases are really elective, early indications for bowel transplant. Among our four patients, only one with ED underwent transplantation. The prognosis of small bowel transplant is still poor and worse than that of prolonged HPN. Further study is necessary to achieve a safe HPN program. Referral for transplant (small bowel only or combined with liver) should be considered when there is a venous access reduction and/or severe and irreversible liver disease.

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.

Role of electrogastrography in detecting motility disorders in children affected by chronic intestinal pseudo-obstruction and Crohn's disease.

Gastrointestinal motility disorders are frequently found in several pathologies. The aim of this study was to assess, by means of electrogastrography, the presence of gastrointestinal motility abnormalities in children affected by Crohn's disease (CD) or Chronic Intestinal Pseudo-Obstruction (CIPO). Patients and Methods. We studied 34 subjects; 20 control subjects (M = 15, mean age = 10 +/- 3.5 yrs), 8 patients (M = 4, mean age = 18 +/- 7 yrs) with Crohn's disease in a quiescent phase and 6 patients (M = 6, mean age = 10 +/- 3.5 yrs) with Chronic Intestinal Pseudo-Obstruction. Results. Analysis of gastric electrical activity (GEA) parameters demonstrated that in the control group physiological post-prandial changes are represented by an increase of 3 Cycles Per Minute (3 CPM) activity, Period Dominant Power (PDP) and Period Dominant Frequency (PDF) and by the reduction of bradygastria. Crohn patients showed an insignificant increase of 3 CPM and PDP; CIPO patients showed an abnormal variation of 3 CPM, PDP and post-prandial bradygastria. Moreover, CD patients showed a significant difference in post-prandial values of PDP compared to normal subjects. CIPO patients revealed a significant difference in the values of either preprandial PDF with tachygastria or the post-prandial value of 3 CPM, compared to normal subjects. Conclusions. EEG is a non-invasive method to study gut motility related to GEA alterations present in CIPO as well as in CD patients.

Resting energy expenditure in young patients with cystic fibrosis receiving antibiotic therapy for acute respiratory exacerbations.

BACKGROUND: patients with cystic fibrosis commonly have severe malnutrition and growth retardation. Among possible causes of these manifestations are low caloric intake, loss of nutrients and increased resting energy expenditure. This study was designed to assess the influence of antibiotic therapy for infectious exacerbations on resting energy expenditure in young patients with cystic fibrosis. METHODS: We studied 17 patients with cystic fibrosis (mean age, 13.6 years). All were hospitalized to receive intravenous antibiotic therapy (mean duration, 2 weeks) for acute respiratory exacerbations. At the beginning of therapy and after it ended, all patients underwent blood chemical tests, anthropometrical measures, determination of body composition by bioelectrical impedance, spirometry, and indirect calorimetry. RESULTS: Antibiotic therapy led to a significant improvement in biochemical, spirometric variables and in estimated calorimetry measurements expressed in relation to fat-free mass. These findings suggest that infective exacerbations are among the causes of increased resting energy expenditure in young patients with cystic fibrosis. CONCLUSIONS: Indirect calorimetry may prove useful in the diagnosis of infective exacerbations and in monitoring the effect of antibiotic therapy in patients with cystic fibrosis.