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.

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.

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.

Gender-stratified analysis of DLG5 R30Q in 4707 patients with Crohn disease and 4973 controls from 12 Caucasian cohorts.

BACKGROUND: DLG5 p.R30Q has been reported to be associated with Crohn disease (CD), but this association has not been replicated in most studies. A recent analysis of gender-stratified data from two case-control studies and two population cohorts found an association of DLG5 30Q with increased risk of CD in men but not in women and found differences between 30Q population frequencies for males and females. Male-female differences in population allele frequencies and male-specific risk could explain the difficulty in replicating the association with CD. METHODS: DLG5 R30Q genotype data were collected for patients with CD and controls from 11 studies that did not include gender-stratified allele counts in their published reports and tested for male-female frequency differences in controls and for case-control frequency differences in men and in women. RESULTS: The data showed no male-female allele frequency differences in controls. An exact conditional test gave marginal evidence that 30Q is associated with decreased risk of CD in women (p = 0.049, OR = 0.87, 95% CI 0.77 to 1.00). There was also a trend towards reduced 30Q frequencies in male patients with CD compared with male controls, but this was not significant at the 0.05 level (p = 0.058, OR = 0.87, 95% CI 0.74 to 1.01). When data from this study were combined with previously published, gender-stratified data, the 30Q allele was found to be associated with decreased risk of CD in women (p = 0.010, OR = 0.86, 95% CI 0.76 to 0.97), but not in men. CONCLUSION: DLG5 30Q is associated with a small reduction in risk of CD in women.

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.

Long-term parenteral nutrition in pediatric autoimmune enteropathies.

Severe and protracted or persistent diarrhea (SPD) is the most severe form of diarrhea in infancy and has also been defined as intractable diarrhea when it leads to dependence on total parenteral nutrition (TPN). One of the rare causes of SPD is represented by autoimmune enteropathy that is characterized by life-threatening diarrhea mainly occurring within the first years of life, persistent villous atrophy in consecutive biopsies, resistance to bowel rest, and evidence of antigut autoantibodies. We evaluated 10 patients (seven boys, mean age at diagnosis 18 months; range: 0 to 160 months) fulfilling criteria of autoimmune enteropathy to assess dependence on TPN. TPN was first required in all patients to avoid dehydration and electrolytic imbalance. All patients were dependent on immunosuppressive therapy (steroid, azothioprine, cyclosporine, tacrolimus). Three patients died of sepsis: two during TPN while in the hospital, and one at home after he was weaned off TPN. Five patients are weaned off TPN after a mean period of 18 months; they are actually on oral alimentation with a cow milk-free diet after a period of enteral nutrition with elemental formula. One underwent total colectomy and bone marrow transplantation and one developed an IPEX syndrome. One patient is still dependent on TPN for 24 months. She is on home parenteral nutrition. Patients with diagnosis of IPEX syndrome require parenteral support with three or four infusion per week. TPN represents a fixed step in the management of autoimmune enteropathy, but it may be considered as an interim treatment while waiting for intestinal adaptation, at least in some selectioned case of autoimmune enteropathy. Bone marrow transplantation should be considered and reserved for those patients with severe complications due to home parenteral nutrition, or in those that are really dependent on parenteral nutrition.

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.

Ocular changes associated with Giardia lamblia infection in children.

BACKGROUND: The protozoan disease giardiasis can cause ocular complications, including "salt and pepper" retinal changes. METHODS: Ophthalmic examinations were performed in 141 children (mean age 4.7 (SD 2.0) years) with active or past giardiasis diagnosed on the basis of microscopic examination of stool specimens or duodenal secretions--53 were newly diagnosed and untreated (group A), 50 had active infections in spite of metronidazole therapy (group B), and 38 had been successfully treated, with negative stool specimens for 1-3 years (group C). 300 children with no evidence of giardiasis were used as controls. RESULTS: Salt and pepper retinal changes (with normal electroretinographic findings) were diagnosed in 28 (19.9%) of the patients with giardiasis (11 from group A, 10 from group B, and seven from group C), including five pairs of siblings. In all subgroups, the children with retinal changes were consistently younger than those with normal retinas. In eight cases, the lesions could be visualised only with direct ophthalmoscopy. CONCLUSION: Our findings indicate that asymptomatic, non-progressive retinal lesions are particularly common in younger children with giardiasis. This risk does not seem to be related to the severity of the infection, its duration, or the use of metronidazole but may reflect a genetic predisposition.

[Clinical comparison of different replacement milk formulas in children with allergies to cow's milk proteins. 24-month follow-up study]. / Comparazione clinica di differenti formule di latte sostitutivo in bambini con allergia alle proteine del latte vaccino. Follow-up a 24 mesi.

The elective treatment for allergy to cow's milk protein is the elimination of these proteins from the diet. The present study with a follow-up of over two years took the form of a comparison between different replacement formulas based on soya (group A), hydrolysate of soya and bovine collagen (group B), and hydrolysate of casein (group C), randomly administered to 55 children (30 males and 25 females, aged between 2-48 months) with documented allergy to cow's milk proteins, but with different clinical symptoms. Tests to evaluate the acquisition of clinical tolerance to cow's milk proteins were performed using a day-hospital regime every 6 months. Sensitivity reactions were observed in 22% of cases in group A, 8% in group B and 37.5% in group C. It is worth underlining that 5 of the 6 children with reactions to soya protein then showed an excellent tolerance to hydrolysate of soya when it was administered subsequently until tolerance was achieved. Weight and statutory growth was uniformly good in all three groups. A high percentage of children achieved tolerance after 24 months (72%); the mean time taken to acquire clinical tolerance was 11.6 +/- 4.8 in group A, 11.6 +/- 6.02 in group B, and 14 +/- 5.6 in group C. No correlation was found between the type of initial symptoms, age at onset, method of response to first challenge and the time taken to acquire tolerance.