Fabio Panetta

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 &mgr;g/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 &mgr;g/g reached a sensitivity and specificity of 100% and 68%, respectively, and a likelihood ratio (LR) of 3.1. The cutoff value of 160 &mgr;g/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. (Inflamm Bowel Dis 2010)

Long-term outcome of home parenteral nutrition in patients with ultra-short bowel syndrome.

Objective: The patients with ultra-short bowel syndrome (U-SBS) have been considered potential candidates for a preemptive/rehabilitative intestinal transplantation owing to the high risk of death from the underlying disease. We hypothesized that children with U-SBS, in the absence of intestinal failure-associated liver disease (IFALD), could also have a good rate of survival on home parenteral nutrition (HPN). Methods: A prospective database from the “Bambino Gesù” Artificial Nutrition and Intestinal Failure Program was used to evaluate outcomes and morbidities of consecutive patients with ⩽10 cm of small bowel enrolled since 2000. Results: Eleven patients were identified with a median bowel length of 7.5 (3–9) cm. Eight patients developed IFALD, which reversed in 7 of them; the IFALD progressively worsened in 1 patient until death. One patient underwent isolated intestinal transplantation and 1 patient is no longer receiving parenteral nutrition (PN) and both are fully enterally fed. The other patients remained at least partially dependent on HPN. The number of days of inpatient care decreased in all of the patients except for the 1 who had repeated episodes of central line infections. Conclusions: The survival of patients with U-SBS receiving HPN was good. Although IFALD was frequent, it had been manageable in most of the patients, but in a single complex case, it led to death. The multidisciplinary management warranted to these patients to approach the school age, to grow, and to maintain the oral intake. Patients with U-SBS are rare, and to better understand their long-term survival, further studies, including more large patient populations, are required.

Celiac Disease and Overweight in Children: An Update

The clinical presentation of celiac disease in children is very variable and differs with age. The prevalence of atypical presentations of celiac disease has increased over the past 2 decades. Several studies in adults and children with celiac disease indicate that obesity/overweight at disease onset is not unusual. In addition, there is a trend towards the development of overweight/obesity in celiac patients who strictly comply with a gluten-free diet. However, the pathogenesis and clinical implications of the coexistence of classic malabsorption (e.g., celiac disease) and overweight/obesity remain unclear. This review investigated the causes and main clinical factors associated with overweight/obesity at the diagnosis of celiac disease and clarified whether gluten withdrawal affects the current trends of the nutritional status of celiac disease patients.

Thyroid autoimmunity in children with coeliac disease: a prospective survey.

Background Thyroid autoimmunity (TA) is often associated with coeliac disease (CD). Objective To evaluate, in children and adolescents with CD on a gluten-free diet (GFD): (1) the prevalence of TA; (2) the impact of TA on growth and the need for L-thyroxine (L-T4) treatment, during a longitudinal survey. Method Between January and December 2005, 545 patients with CD, prospectively followed up until December 2007, and 622 controls were screened for TA. Antithyroperoxidase and antithyroglobulin antibodies were assayed and, if positive, serum free tri-iodothyronine, free thyroxine and thyroid-stimulating hormone (TSH) assays and thyroid ultrasound were performed. L-T4 was started if TSH was >5.5 mU/ml at two successive measurements. Results There was no significant difference in TA prevalence between patients with CD on a GFD (10%) and controls (8.2%). Duration of GFD differed significantly in coeliac patients with TA in comparison with those without TA (7.9±0.9 and 10.2±0.3 years, p<0.001), but no significant difference was found for weight and height gain (1.8±1.0 vs 3.7±1.5 and 2.1±1.2 kg/year vs 4.0±1.1 cm/year, respectively). At the end of the follow-up an increase of 7% in the prevalence of patients with CD with TA requiring L-T4 was found. Conclusions TA seems no more common in paediatric and adolescent patients with CD on a GFD than in controls; its clinical evolution does not seem to impact on growth. Therefore, a long-term regular screening programme for thyroid disease may not be necessary for all patients with CD on a GFD, but only for those who are suspected of having thyroid diseases.

Celiac disease in pediatric patients with autoimmune hepatitis: etiology, diagnosis, and management.

Celiac disease (CD) is defined as a permanent intolerance to ingested wheat gliadins and other cereal prolamins, occurring in genetically susceptible people. Persistent elevation of serum aminotransferase activity is expression of liver damage related to CD, which occurs in two distinctive forms. The most frequent is a mild asymptomatic liver injury, with a moderate increase of serum aminotransferase activities and a mild inflammatory portal and lobular infiltrate on liver biopsy (celiac hepatitis), reversible on a gluten-free diet (GFD). More rarely, severe and progressive inflammatory liver damage, induced by an autoimmune process and identified as autoimmune hepatitis (AIH), can develop and it is generally unaffected by gluten withdrawal.Surveys that included only pediatric patients report a wide range of prevalence of CD in AIH of 11.5–46% (mean 21.5%). CD and AIH share selected combinations of genes coding for class II human leukocyte antigens, which could explain their coexistence. Increased intestinal permeability and circulation of anti-tissue transglutaminase (tTG) have also been considered as further potential causes of liver damage in CD patients. tTG in the liver and in other extraintestinal tissues could modify other external- or self-antigens and generate different neo-antigens, which are responsible for liver injury in patients with CD.Patients with AIH represent a population at high risk for developing CD; screening for CD should be integrated into the diagnostic routine of all patients with AIH, with or without gastrointestinal manifestations, before starting immunosuppressive treatments. The only currently available treatment for CD is the GFD and the supportive nutritional care for iron, calcium, and vitamin deficiencies. Due to the difficulties of a GFD, in the past decade researchers have become increasingly interested in therapeutic alternatives to continuous or intermittent use of a GFD in patients with CD. Interventions addressed to correct the defect in the intestinal barrier are currently at the most advanced stage of clinical trials. The impact of a GFD on the outcome of AIH is not clear but it seems to be ineffective in the treatment of AIH. The early detection and treatment of CD, however, may prevent progression to end-stage liver failure.

Is the screening for celiac disease useful in anorexia nervosa

The main objective of the study was to prospectively assess if the prevalence of celiac disease (CD) in patients with anorexia nervosa (AN) is higher than that reported in the general population to require a regular screening program. The study was conducted at the Neuropsychiatry Unit of “Bambino Gesù” Children’s Hospital in Rome from January 2005 to December 2010. All patients with diagnosis of AN according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria were screened for CD. One hundred and seventy-seven patients (33 males and 144 females) were enrolled. Only one patient was found to be affected with CD as confirmed by intestinal biopsy. The overall prevalence of CD in AN patients was 0.6 % which is similar to that observed in the general population. In conclusion, AN patients do not seem to require a regular screening program for CD. The screening for CD may be useful in selected AN patients in which the symptoms are only partially responding to psychiatric interventions.

Chronic pancreatitis as presentation of Crohn's disease in a child.

It is reported that a pancreatic disease may precede the diagnosis of inflammatory bowel disease (IBD) both in children and in adults. Idiopathic chronic pancreatitis, however, occasionally co-exists with the IBD, mainly at pediatric age. We report a case of a patient who progressively developed the features of a chronic pancreatitis, before the diagnosis of Crohns Disease (CD). Ten months after the onset of the first episode of pancreatitis the patient developed bloody diarrhea, mucus stools and biochemical findings of inflammation. The colonoscopy revealed a diffuse colitis without involvement of the last loop and the gastroscopy showed inflammation of the iuxta-papillary area. The histological findings confirmed the diagnosis of CD that involved the colon and the duodenum. In conclusion, in children the idiopathic chronic pancreatitis may be an unusual presentation of CD. Thus, if other known cause of chronic pancreatitis are not found, a not invasive work up to exclude the IBD should be warranted. An early coincidental diagnosis of the IBD may delay the progression of the pancreatic disease.

Celiac disease and endocrine autoimmune disorders in children: an update

Celiac disease (CD) is a life-long inflammatory condition of the gut that occurs in genetically susceptible individuals. Several autoimmune diseases (AI) are associated with CD. To date, no conclusive evidence is available that proves if the relationship between CD and AI is mediated by gluten exposure, or if CD and AI could co-occur due to other causes, in particular the loss of the intestinal barrier function and the common genetic background. Furthermore, it is not clear yet if CD needs a regular screening program for AI. This review will cover the key studies on both the pathogenetic and clinical evidence explaining this association. We will review the reports including patients aged <18 years with CD and endocrine AI.

Clinical accuracy of anti-tissue transglutaminase as screening test for celiac disease under 2 years

Aim:  To investigate, in patients with suspected celiac disease (CD) younger than 2 years, the clinical value of anti‐tissue transglutaminase (tTG) in diagnostic work‐up of CD.

Plasma citrulline in Crohn's disease as a marker of inflammation or disease localization

acute uncomplicated diverticulitis within 7 days after exclusion of complication, which is considered the only parameter avoiding early colonoscopy,12 and after a course of antibiotic therapy, without any early or late complication.13 Thus, an early endoscopic approach to acute diverticulitis (within 7 to 10d after an episode of uncomplicated diverticulitis) seems to be more effective than classic approach (4 to 6wk after hospital discharge). In this way, Schmilovitz-Weiss and colleagues did not perform an “early” colonoscopy, because they performed colonoscopy 4 to 6 weeks after hospital discharge—this is not an “early” timing but the “standard” timing in performing colonoscopy after an episode of acute diverticulitis.11 In my opinion, early colonoscopy is the only way to have a yield on the outcome of the patients. This is particularly true in patients with persistent diverticulitis. We know that diverticulitis, especially when uncomplicated, generally resolves within 3 days14,15: whether 7 to 10 days have passed without resolution (or whether significant improvement of symptoms is lacking), colonoscopy should be mandatory in order to explain why symptoms are still present. This is another point that should be taken into account in clinical practice. In fact Lahat et al16 found that colonoscopy detected other significant pathology in patients with persistent diverticulitis, which accounted for the clinical presentation in 17% of patients with persisting disease. 1. In conclusion, I mean that: colonoscopy is still mandatory in acute diverticulitis because: