Viviana Granata

Issues related to gluten-free diet in coeliac disease.

Purpose of reviewIn the last few years, knowledge about coeliac disease has significantly improved, resulting in a better understanding of disease pathogenesis, diagnosis and therapy. This review describes the latest progress in research concerning treatment with gluten-free diet in patients with coeliac disease. Recent findingsGluten-free diet is generally admitted as effective therapy in symptomatic patients, but a life-long dietary treatment in some challenging cases such as ‘silent’ and ‘latent’ patients is under discussion. Tolerance to gluten may be acquired later in life, but, as latency may be transient, a strict follow-up is necessary in these patients. The composition of gluten-free diet needs a better definition; latest evidence demonstrates that oats are tolerated by most patients with coeliac disease. Finally, the amount of gluten permitted in gluten-free products is still a matter of debate; significant progress has been made in the sensitivity of techniques for gluten detection, but the daily amount of gluten that can be safely consumed is not yet defined. SummaryGluten-free diet remains the cornerstone of therapy of coeliac disease. More studies addressing the need of gluten-free diet for cases of ‘potential’ coeliac disease are necessary, as well as studies linking the best available analytical detection of gluten to the clinical threshold of tolerance.

Serum and intestinal celiac disease-associated antibodies in children with celiac disease younger than 2 years of age.

Objectives: In children younger than 2 years of age, a diagnosis of celiac disease (CD) is difficult to make because anti-endomysium (anti-EMA)/anti-tissue transglutaminase 2 (anti-TG2) antibodies are less sensitive than in older children. The aim of our study was to evaluate how many children younger than 2 years of age and diagnosed with CD, were negative for serum anti-TG2 antibodies and to test the hypothesis that in these patients, TG2-specific IgA deposits could instead be present at mucosal level. Patients and Methods: A total of 104 children younger than 2 years of age and 179 children older than 2 years, all of whom had been diagnosed with CD, were investigated for serum CD-associated antibodies (anti-gliadin [AGA] IgA and IgG, EMA-IgA, anti-TG2–IgA). The presence of intestinal anti-TG2 extracellular IgA deposits was searched by using double immunofluorescence in 56 of the patients younger than 2 years of age and in 40 of those who were older than 2 years. Results: In children with CD who were younger than 2 years of age, high levels of AGA-IgA were found in 93/104 (89%) and 98/104 (94%) were found of have high levels of AGA-IgG. In children older than the age of 2 years with CD, 120/179 (67%) had high levels of AGA-IgA and 151/179 (84%) had high levels of AGA-IgG. Serum EMA were present in 92/104 (88%) in the younger group and in 176/179 (98%) of the older group. Ninety-one of 104 children (87%) younger and 172/179 (96%) older than 2 years showed high serum levels of anti-TG2. Finally, 41/56 (73%) children younger than 2 years and all of the 40 children (100%) older than 2 years of age showed mucosal anti-TG2–IgA deposits. Conclusions: EMA and anti-TG2–antibody measurements show higher sensitivity for the diagnosis of CD in children older than 2 years compared with younger children. The search for mucosal deposits of anti-TG2–IgA does not improve the diagnostic performance.

Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG reduces the occurrence of other allergic manifestations in children with cow's milk allergy: 3-year randomized controlled trial

Background Children with cows milk allergy (CMA) have an increased risk of other allergic manifestations (AMs). Objective We performed a parallel‐arm randomized controlled trial to test whether administration of an extensively hydrolyzed casein formula (EHCF) containing the probiotic Lactobacillus rhamnosus GG (LGG) can reduce the occurrence of other AMs in children with CMA. Methods Children with IgE‐mediated CMA were randomly allocated to the EHCF or EHCF+LGG groups and followed for 36 months. The main outcome was occurrence of at least 1 AM (eczema, urticaria, asthma, and rhinoconjunctivitis). The secondary outcome was tolerance acquisition, which was defined as the negativization of a double‐blind food challenge results at 12, 24, and 36 months. AMs were diagnosed according to standardized criteria. Tolerance acquisition was evaluated every 12 months. Results A total of 220 children (147 boys [67%]) with a median age of 5.0 months (interquartile range, 3.0‐8.0 months) were randomized; 110 children were placed in the EHCF group, and 110 children were placed in the EHCF+LGG group. In the complete case analysis the absolute risk difference for the occurrence of at least 1 AM over 36 months was −0.23 (95% CI, −0.36 to −0.10; P < .001), and the absolute risk difference for the acquisition of cows milk tolerance was 0.20 (95% CI, 0.05‐0.35; P < .01) at 12 months, 0.24 (95% CI, 0.08‐0.41; P < .01) at 24 months, and 0.27 (95% CI, 0.11‐0.43; P < .001) at 36 months. In the sensitivity analysis the effect size of the main outcome was virtually unchanged when the occurrence of AMs was assigned to all 27 missing children. Conclusions EHCF+LGG reduces the incidence of other AMs and hastens the development of oral tolerance in children with IgE‐mediated CMA.

Italian paediatricians' approach to coeliac disease diagnosis.

The aim of this study was to investigate the current implementation of the 1990 ESPGHAN criteria for the diagnosis of celiac disease (CD) in Italy to form a foundation for their revision.From September 2006 to March 2007 a nationwide questionnaire concerning current diagnostic methods was sent by mail to 54 Italian centres for the diagnosis of CD, which were distributed across the entire national territory. The questionnaire investigated the tests performed, diagnostic criteria currently used, and the management of some special cases in each centre.Eighty percent of the centres use anti-tissue transglutaminase to diagnose CD and anti-endomysium antibodies to confirm the results. Fifty-five percent still use anti-gliadin antibodies. A total of 87.5% of centres perform HLA typing, especially in first-degree relatives and in unclear diagnosis. Regarding histology, 67.5% of centres consider an infiltrative lesion consistent with diagnosis of CD. The majority of centres (85%) use the 1990 ESPGHAN criteria for both symptomatic and asymptomatic patients, but 80% do not perform a second biopsy in asymptomatic cases or a gluten challenge in children younger than 2 years of age. Furthermore, most centres (72.5%) do not prescribe a gluten-free diet to asymptomatic patients with positive serology and normal bowel architecture (ie, potential cases), but they do program a careful follow-up.In conclusion, ESPGHAN criteria are widely followed by Italian CD centres. However, their revision may be useful, but it should be evidence based. Large, multicentre studies are greatly needed.

Atopy patch tests are useful to predict oral tolerance in children with gastrointestinal symptoms related to non-IgE-mediated cow's milk allergy.

Atopy patch tests (APTs) have been proposed for the diagnostic approach in children with non‐IgE‐mediated cows milk allergy and gastrointestinal symptoms. We aimed to investigate the benefit of APTs in predicting oral tolerance in these patients. We prospectively evaluated 172 subjects with a sure diagnosis of non‐IgE‐mediated CMA and gastrointestinal symptoms (97 boys, 56.4%; age, 6.37 m; range, 2–12 m). At diagnosis, 113/172 (65.7%) children had positive APTs to cows milk proteins (CMP). After 12 months of exclusion, diet APTs were repeated immediately before OFC. APTs significantly correlated (P < 0.001) with the OFC outcome (r 0.579). Diagnostic accuracy was sensitivity of 67.95%, specificity of 88.3%, PPV of 82.81%, NPV of 76.85%, and a +LR of 5.80. APTs are a valuable tool in the follow‐up of children with non‐IgE‐mediated CMA‐related gastrointestinal symptoms by contributing in determining whether an OFC can safely be undertaken.

Gut Microbiota as a Target for Preventive and Therapeutic Intervention against Food Allergy

The gut microbiota plays a pivotal role in immune system development and function. Modification in the gut microbiota composition (dysbiosis) early in life is a critical factor affecting the development of food allergy. Many environmental factors including caesarean delivery, lack of breast milk, drugs, antiseptic agents, and a low-fiber/high-fat diet can induce gut microbiota dysbiosis, and have been associated with the occurrence of food allergy. New technologies and experimental tools have provided information regarding the importance of select bacteria on immune tolerance mechanisms. Short-chain fatty acids are crucial metabolic products of gut microbiota responsible for many protective effects against food allergy. These compounds are involved in epigenetic regulation of the immune system. These evidences provide a foundation for developing innovative strategies to prevent and treat food allergy. Here, we present an overview on the potential role of gut microbiota as the target of intervention against food allergy.

The Potential Therapeutic Efficacy of Lactobacillus GG in Children with Food Allergies

Food allergy (FA) continues to be a growing health concern for infants living in Western countries. The long-term prognosis for the majority of affected infants is good, with 80–90% naturally acquiring tolerance by the age of five years. However, recent studies suggest that the natural history of FA is changing, with an increasing persistence until later ages. The pathogenesis of FA as well as oral tolerance is complex and not completely known, although numerous studies implicate gut-associated immunity and enteric microflora, and it has been suggested that an altered composition of intestinal microflora results in an unbalanced local and systemic immune response to food allergens. In addition, there are qualitative and quantitative differences in the composition of gut microbiota between patients affected by FA and healthy infants. These findings prompted the concept that specific beneficial bacteria from the human intestinal microflora, designated probiotics, could restore intestinal homeostasis and prevent or alleviate allergy, at least in part by interacting with the intestinal immune cells.

Role of Probiotics in Allergies

Allergies continue to be a growing health concern for children living in Western countries. Over the past few years several studies have assessed the relationship between alterations in gut microbiota and allergies in humans. It is known that the gut microbiota of atopic subjects is different in quality and quantity from that of healthy controls. These findings prompted the concept that specific beneficial bacteria from the human intestinal microflora, designated probiotics, which may restore the intestinal ecosystem could be considered as a potential alternative strategy for the prevention and treatment of allergies with promising results.

Anti-gliadin, anti-endomysium and anti-tissue transglutaminase antibodies in the serum of celiac children younger than two years

The aim of this study was to assess the impact of two differnt therapeutic interventions on own perception of HRQOL n IBD patient. Methods and materials. Children and adolescents ffected by IBD were divided in two groups: first group in tandard therapy (5ASA and azathioprine); second group in tandard therapy plus monthly infusions of autologous red lood cell loaded with dexametasone -21P, because of their ependence. Quality of life was assessed by a self-administered quesionnaire, Short Form 36 Health Survey (SF-36), that all ubjects completed. The SF-36 is divided in two major roups physical and mental, which include 7 domains. ann–Whitney U-test was performed to compare the RQOL between the 2 groups of IBD patients. Results. A total of 76 IBD patients followed at our Gasroenterology Unit aged 8-18 years were included. Among hem 35 were affected by CD and 41 by UC (42 boys, 34 irls). 56 patients were treated with the standard therapy and 0 with standard therapy plus the infusions of autologous BC loaded with DEX 21-P (11 CD and 9 CU). No sigificant differences were found between the two groups for hysical and mental indexes (median 77, IQR 63–81 versus 5, IQR 70–94 p= 0.07, and 71, IQR 52–82 versus 74, IQR 0–89 p= 0.5 respectively). Regarding the different domains, perception of general ealth was significantly lower in the group of patients treated ith the infusions of autologous RBC loaded with DEX-21P n comparison to the group treated with standard therapy. o other significant differences were found in other domains Physical Functioning, Body Pain, Vitality, Social Function, motional and Mental Health). Conclusion. Perception of general health seems to be ower in the group of patients treated with the infusions of utologous RBC loaded with DEX-21P. We can hypothesize hat these group of patients had more severe or active disase, and the monthly hospitalization impacts on their general ealth. Future research should investigate to correlate their isease activity with HRQOL.