scholarly journals Celiac disease in children - modern diagnostic approach

2008 ◽  
Vol 136 (Suppl. 2) ◽  
pp. 152-157
Author(s):  
Nedeljko Radlovic

Celiac disease presents a hereditary disorder of gluten tolerance, i.e. of gliadin and related prolamins of wheat, rye and barley. It primarily occurs in Caucasians (1:100-300), while it is considerably or exceptionally rare in colored races. It is particularly frequent in close relatives of the patient, as well as in persons with congenital IgA deficiency and in patients with autoimmune and some chromosomal diseases. The basis of the disease, as well as the key finding in its diagnostics, lies in small bowel inflammation, which withdraws on gluten free diet. Beside clinically manifest or non-manifest enteropathy, changes involving other organs and systems are also frequently seen. The diagnosis of the manifest form of the disease is based on characteristic pathohistological finding detected by the examination of small bowel mucosa in patients on standard diets and their clinical improvement after the introduction of gluten free diet. However, in the diagnosis of the asymptomatic form of the disease, it is necessary to perform enterobiopsy, which confirms the normalization of the appearance of small bowel mucosa in patients on the elimination diet. In children with gluten sensitive enteropathy detected in the first two years of life, as well as in cases in which mucosa samples taken on the first enterobiopsy do not have typical appearance or are inadequate for a reliable interpretation, a definite diagnosis is made based on biopsy finding during the provocation of gluten tolerance. As the quality of permanent teeth can be disturbed, this procedure is not suggested to be done before the completed age of 6 years, and due to adverse effects on the growth and development of the child, it should not be done during puberty. Due to incomplete sensitivity and specificity, the serological indicators of the disease do not have diagnostic value. Therefore, they are primarily used in the disclosure of asymptomatic and atypical forms of celiac disease, as well as in the assessment of the consistency of elimination diet in cases with already verified disease. In addition, the application of these tests makes easier passing the decision to perform pathohistological examination of small bowel mucosa in patients with provoked gluten tolerance, which also gives a more complete understanding into the remission of the disease during the initial phase of treatment.

2009 ◽  
Vol 137 (11-12) ◽  
pp. 632-637 ◽  
Author(s):  
Nedeljko Radlovic ◽  
Marija Mladenovic ◽  
Zoran Lekovic ◽  
Dragana Zivanovic ◽  
Radivoj Brdar ◽  
...  

Introduction. Gluten-free diet (GFD) presents the basis of coeliac disease (CD) treatment. If strictly applied, the disorders of the small bowel mucosa and other disease signs rapidly resolve. Objective. The goal of the study was to evaluate the effect of GFD on the growth and nutritional status of children with the classical form of CD. In addition, we analyzed the differences between these parameters with the duration and the patients' compliance with GFD. Methods. The study goals were achieved on a sample of 90 children, 56 female and 34 male, aged 0.5-7.5 (1.53?1.05) years, with the classic CD diagnosed on the basis of typical pathohistological findings of the small bowel mucosa and clinical recovery of patients on GFD. The duration of the patients' follow-up was 1.08-8.75 (3.03?1.14) years, i.e. until the age of 2.5-15 (4.59?1.78) years. The initial and control values of body height (BH) in relation to matched values for age and gender were expressed in percentiles, while the deviation in body weight (BW) for the matched values of height and gender was expressed in percentages. The referent haemoglobin (Hb) rate in blood, as a laboratory indicator of nutritional status in children aged up to 5 years was ?110 g/L, and for those aged above 5 years it was ?115 g/L. Compliance with GFD was based on the pathohistological findings of the small bowel mucosa or determination of tissue transglutaminase. Results. Over the studied period, the effect of GFD was highly significant, both on the increase of BH percentiles (37.62?26.26 vs. 57.22?25.29; p<0.001), and on the decrease of BW deficit 11.58?10.80 vs. 0.89?8.194; p<0.001). After the treatment period, none of the children showed slowed growth rate or BW deficit above 20%, while BW deviation ranging between 10-20% in relation to the referent values was registered in 17 (18.19%) and the excess of over 20% in 2 patients. In 86 (95.56%) patients, control Hb values in blood were normal, while mild anaemia was registered in 4 patients, all compliant with GFD. The difference between the compliant and non-compliant patients with GFD was not detected either in BH percentiles (p=0.586) or in BW percentage deviation as compared to standard values (p=0.516) or in blood Hb values (p=0.445). In addition, differences between the children on GFD lasting over and below 3 years were not detected either in BH percentiles (p=0.915) or in BW deviation percentages in relation to the ideal rate (p=0.476). Conclusion. GFD applied for 1-3 years has a highly significant effect on the growth rate and nutritional status of children with the classical form of CD. Significant differences in these parameters of the disease were not detected between strictly compliant and non-compliant patients on GFD.


2009 ◽  
Vol 55 (1) ◽  
pp. 150-157 ◽  
Author(s):  
Daniela Basso ◽  
Graziella Guariso ◽  
Paola Fogar ◽  
Alessandra Meneghel ◽  
Carlo-Federico Zambon ◽  
...  

AbstractBackground: AGA IgA II and AGA IgG II have recently been suggested as reliable tools for celiac disease (CD) diagnosis. We compared their utility for diagnosis and monitoring CD in children with that of tTG IgA, an established CD marker.Methods: We studied a cohort of 161 CD and 129 control children in whom CD was histologically confirmed or ruled out. We followed 37 children with CD on a gluten-free diet for 12–84 months. In fasting sera, we measured AGA IgA II, AGA IgG II, and tTG IgA using ELISAs.Results: The best sensitivity (92.5%), specificity (97.6%), positive predictive value (98%), and negative predictive value (91.2%) were obtained using tTG IgA. AGA IgG II correctly identified 3 of 3 children with CD with total IgA deficiency who had negative AGA IgA II and tTG IgA results. In children &lt;2 years old without total IgA deficiency, AGA IgG II and tTG IgA performed equally well (sensitivity 96.4% and specificity 100%). AGA IgA II, AGA IgG II, and tTG IgA concentrations diminished significantly (P &lt; 0.0001) after 1 year of a gluten-free diet, reaching values below the cutoff in 87%, 70%, and 51% of cases, respectively.Conclusions: The best available index for diagnosing CD in children was tTG IgA. In infants &lt;2 years old, AGA IgG II performed as well as tTG IgA in cases without total IgA deficiency and allowed detection of CD when total IgA was &lt;0.06 g/L. Gluten-free diet monitoring can be achieved using any of the studied serum markers.


2015 ◽  
Vol 33 (2) ◽  
pp. 244-251 ◽  
Author(s):  
Emanuele Rondonotti ◽  
Silvia Paggi

Background: Because of its technical characteristics (i.e. 8-fold magnification, capability to inspect the entire small bowel) and minimal invasiveness, videocapsule endoscopy (VCE) has been proposed as a useful tool for managing patients with celiac disease (CD). Key Messages: Although VCE has been found to be highly sensitive and specific in identifying CD endoscopic markers, it is still inadequate to replace esophagogastroduodenoscopy (EGD) with biopsies in the diagnosis of CD. Nevertheless, it represents a reliable alternative in patients unable or unwilling to undergo EGD. Up to now, available studies have failed to identify any correlation between the length of small bowel involvement and the severity of symptoms. The available evidence on the use of VCE in diagnosing CD in equivocal cases (patients with positive serology and negative or nonspecific histology or those with negative serology and histologically proven villous atrophy) is limited, and its role is still under discussion. In CD patients not improving on gluten-free diet, a complete workup is necessary. In patients with nonresponsive (NRCD) or refractory CD (RCD), VCE has been shown to be able not only to detect significant findings, driving further management, but also to rule out major complications. Nevertheless, in this setting, the inability of VCE to take tissue samples and the risk of capsule retention can represent major limitations. Conclusions: At the present time, for diagnostic purposes, VCE can be proposed only in patients unable or unwilling to undergo EGD, whereas it could be useful in some equivocal cases. Conversely, there is no room for VCE either to estimate the length of the small bowel affected by villous atrophy or to follow up patients improving on gluten-free diet. In patients with NRCD or RCD, VCE can play a role, but it should be combined with other diagnostic techniques.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1665-1665
Author(s):  
R.K. Marwaha ◽  
Deepak Bansal ◽  
Amita Trehan ◽  
Akash Patel

Abstract Celiac disease (CD) is a malabsorptive disorder wherein the proximal small bowel mucosa is damaged as a result of dietary exposure to gluten. Children with intractable diarrhea and failure to thrive are diagnosed with relative ease. Diagnosis can however be challenging and is often delayed when children present with ‘difficult to treat anemia’, without overt gastrointestinal manifestations. The case records of 77 patients with CD were scrutinized retrospectively. Diagnosis was established with serology (tissue transglutaminase-IgA assay) in 46 (59.7%), serology along with small bowel mucosal biopsy in 23 (29.9%) and with biopsy alone in the remaining 8 (10.4%). All children belonged to the predominantly wheat consuming northern Indian states. The mean age at presentation was 99.1±34.8 months (median: 102, range: 22–168). Males outnumbered females in a ratio of 1.96:1. The mean duration of symptoms was 41±31.2 months (median: 36, range: 1–132). The overwhelming majority, i.e., 75 (97.4%) children had anemia (Hemoglobin <11 g/dL). Mean hemoglobin (Hb) was 7.0±2.2 g/dL (median: 7.2, range: 2.3–12.5). 52 (67.5%) had received iron supplements for sufficient lengths, without benefit. The red cell morphology was microcytic hypochromic in 37 (48%) and dimorphic in 33 (42.9%). A history of diarrhea was not forthcoming in 32 (41.6%) cases. 59 (76.6%) were malnourished, with a weight less than 80 % of expected for the age and 30 (39 %) were stunted, with a height falling below the 90% of expected. Two children had skin bleeds secondary to coagulopathy, due to Vitamin K malabsorption. In another 2, recurrent anemia was attributed to pulmonary hemosiderosis; further investigations for secondary causes unearthed CD. All children were initiated on an austere gluten free diet, along with iron and folic acid supplements for the initial 6–9 months. Mean duration of follow was 17.7±20.9 months. Improvement was perceptible within days of initiating gluten free diet. Of the 38 (49.4%) children who had a follow up of a year or longer, the mean Hb at the last visit had risen to 12.9±1.2 g/dL. Conclusions: Hematologists need to be aware of the mono-symptomatic presentation of CD with anemia. The typical period of presentation of CD is described to be between 6 mo and 2 yr of age. Prolonged duration of symptoms and a diagnosis at a relatively older age is striking in the index study. In a suggestive clinical background, identification of CD with serodiagnosis alone, without resorting to small bowel biopsy is increasingly gaining acceptance, as the specificity of newer serological assays is 95–98%. This is particularly true in tropical countries, where some degree of flattening of villi may be attributed to malnutrition and or infections, such as rotavirus enteritis, Giardia lamblia, or tropical sprue. A biopsy may be misleading in such cases. Heightened awareness is essential to identify CD at an early age, especially, in children in whom anemia is the dominant manifestation. The benefits of gluten free diet are apparent with the rise in hemoglobin and the improvement in growth parameters are gratifying both for physicians and the caretakers.


2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Tamara Vorobjova ◽  
Aili Tagoma ◽  
Astrid Oras ◽  
Kristi Alnek ◽  
Kalle Kisand ◽  
...  

Cytokines play a pivotal role in the maintenance of intestinal homeostasis inducing pro- or anti-inflammatory response and mucosal barrier function in celiac disease (CD) and type 1 diabetes (T1D). We aimed to compare the levels of pro- and anti-inflammatory cytokines in CD patients without and with coexisting T1D, as well as to evaluate its association with the presence of enteroviruses (EV), regulatory T cells (Tregs), and dendritic cells (DCs) in small bowel mucosa. Altogether, 72 patients (median age 10.1 years) who had undergone small bowel biopsy were studied. The study group consisted of 24 patients with CD (median age 6.5 years), 9 patients with CD and concomitant T1D (median age 7.0 years), two patients with T1D (median age 8.5 years), and 37 patients (median age 14.0 years) with functional gastrointestinal disorders (FGD) and a normal small bowel mucosa as controls. The levels of 33 cytokines in serum were measured by multiple analysis using the Milliplex® MAP Magnetic Bead assay. The densities of FOXP3+ Tregs, CD11c+ DC, indoleamine 2,3-dioxygenase+ (IDO+) DC, langerin+ (CD207+) DCs, and EV were evaluated by immunohistochemistry as described in our previous studies. Circulating anti-EV IgA and IgG were evaluated using ELISA. The most important finding of the study is the significant increase of the serum levels of IL-5, IL-8, IL-13, IL-15, IL-17F, IL-22, IL-27, IP-10, MIP-1β, sIL-2Rα, sTNFRII, and TNFαin CD patients compared to controls and its correlation with the degree of small bowel mucosa damage graded according to the Marsh classification. The leptin level was higher in females in all study groups. The levels of IL-2, IL-6, IL-12 (P70), IL-15, IP-10, and IFNγcorrelated significantly with the density of FOXP3+ Tregs inlamina propriaof the small bowel mucosa, which supports the evidence about the signaling role of these cytokines in the peripheral maintenance of FOXP3+ Tregs. At the same time, a significant negative correlation occurred between the level of IL-4 and density of FOXP3+ Tregs in controls. Another important finding of our study was the correlation of IL-17F, IP-10, sTNFRII, MCP-1, and GM-CSF with the density of EV-positive cells in thelamina propriaof the small bowel mucosa. Correlation of MIP-1 (CCL-4) with CD103+ DC and langerin+ DC densities may point to their significance in the recruitment of immune cells into thelamina propriaand in driving the inflammatory response in CD patients. Our results suggest the predominance of Th1 and Th17 immune responses over EV VP1 protein in CD and T1D patients. The significant elevation of Th2 cytokines, like IL-5 and IL-13, but not IL-4, in CD patients and its correlation with the degree of small bowel mucosa damage could reflect the role of these cytokines in gut defense and inflammation.


2017 ◽  
Vol 49 (4) ◽  
pp. 412-416 ◽  
Author(s):  
Konstantinos Efthymakis ◽  
Angelo Milano ◽  
Francesco Laterza ◽  
Mariaelena Serio ◽  
Matteo Neri

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