乳糜泻在中国慢性腹泻患儿中的发病情况

目的 研究乳糜泻在中国慢性腹泻患儿中的发病情况.方法 收集2005年1月至2008年12月上海、济南、武汉、成都等地的慢性腹泻住院患儿进行临床多中心研究.详细记录所有患儿的病史、营养发育情况及相关辅助检查.数据处理采用SPSS11.5统计软件统计.结果共收集慢性腹泻患儿199例,纳入研究者118例,疑似乳糜泻的患儿14例(12%),其中1例确诊.去麸质饮食治疗有效.疑似病例男女比为12∶2.年龄6个月～12岁.14例疑似患儿中6例伴随营养不良,4例伴有贫血.内镜诊断十二指肠黏膜绒毛萎缩4例,病理分期Ⅰ期1例,Ⅱ期2例,Ⅲa期7例,Ⅲb期3例,Ⅲc期1例.结论本研究第一次在中国慢性腹泻儿童中进行乳糜泻的筛查,研究发现疑似乳糜泻患儿14例,占慢性腹泻儿童的12%,确诊1例.乳糜泻确实在中国儿童中存在,应该引起中国儿科医师的重视.     

Factors affecting adherence to a gluten-free diet in children with celiac disease

BACKGROUND:

The treatment of celiac disease is a strict, life-long gluten-free (GF) diet. This diet is complex and can be challenging. Factors affecting adherence to the GF diet are important to identify for improving adherence.

OBJECTIVE:

To identify factors that inhibit or improve adherence to a GF diet in children with celiac disease.

METHODS:

Patients (<18 years of age) with biopsy-confirmed celiac disease followed by the gastroenterology service at a tertiary care paediatric institution were surveyed using a mailed questionnaire. Factors influencing adherence to a GF diet were scored from 1 to 10 based on how often they were problematic (1 = never, 10 = always). Parents of patients <13 years of age were instructed to complete the survey with their child. Adolescents ≥13 years of age were asked to complete the survey themselves.

RESULTS:

Of 253 subjects, 126 completed the survey; the median age was 12 years (range two to 18 years). Forty percent were adolescents. Overall, participants reported good adherence at home and school, but lower adherence at social events. Adolescents reported lower adherence compared with parents. Availability of GF foods and cost were the most significant barriers. Other factors identified to help with a GF diet included education for schools/restaurants and improved government support.

CONCLUSIONS:

Availability, cost and product labelling are major barriers to adherence to a GF diet. Better awareness, improved labelling and income support are needed to help patients.     

The changing face of celiac disease

The face of celiac disease has changed significantly over the past 50 years. With the advent of new noninvasive and more sensitive screening tools, it has become increasingly apparent that this disease presents in a heterogeneous fashion, with symptomatic disease only occurring in a small number of patients. Furthermore, great insights have been made into the disease''s genetic and immunological components, thus increasing the medical community''s understanding of the disease. The current gold standard for diagnosis is histological confirmation, and the cornerstone of therapy is lifelong elimination of gluten. Further advances in immunobiological techniques will most likely aid in earlier detection and commencement of the appropriate diet, thus preventing the development of associated complications.     

Diagnosis of celiac disease

Celiac disease is an immune mediated enteropathy initiated by ingestion of gluten, in genetically susceptible individuals. With changing epidemiology, celiac disease initially thought to affect only Europeans, has been increasingly reported from other parts of the world including India. However, its true prevalence in India is still not known, as the diagnosis is being missed. The gold standards for diagnosis have been characteristic small intestinal mucosal changes on gluten and a full clinical remission on its removal from the diet. Presence of serological antibodies, which disappear on gluten free diet further confirms the diagnosis. The understanding of the histopathology of celiac disease has changed over the years. The small bowel mucosal lesion of celiac disease is an evolutionary process with normal mucosal architecture and an increase in intraepithelial lymphocytes at one end of the spectrum and classical flat mucosa at the other. In the Indian subcontinent celiac disease has a heterogeneous histological presentation and the diagnosis may be missed if it is based only on severe mucosal changes or the serology is not considered when moderate or mild mucosal changes are present. The last two decades have shown that antiendomysical (Anti EMA) and anti tissue transglutaminase antibodies (anti-tTGA) have a sensitivity and specificity of more than 95% to diagnose celiac disease. Anti EMA tests being operator dependent are more liable to errors and anti- tTGA may be preferred for large scale screening. However, the different source of tTGA antigen, varied techniques of production and the use of arbitrary units by different commercial kits can influence the diagnostic accuracy of the anti-tTGA assay. There is a strong genetic association of celiac disease with HLA-DQ2 or DQ8. The presence of HLA-DQ2 hetrodimer in more than 97% of a group of North Indian patients with celiac disease indicates that this population has a similar genetic risk for the disease. HLA DQ2 typing can be used for ruling out celiac disease where the diagnosis is equivocal as it has a negative predictive value of greater than 95%. Given the protean clinical manifestation and the heterogeneous histology a standard algorithm for diagnosis of celiac disease is important.     

Unusual manifestations of celiac disease

Celiac disease in multifaced autoimmune disorder with several extraintestinal manifestations and connections to other autoimmune diseases and other conditions. The recognition of the complex clinical picture of the disease helps doctors to search and diagnose celiac disease even if the gastrointestinal symptoms are lacking. Individuals at risk for celiac disease should be thoroughly investigated and individuals with unusual manifestations of the disease should be screened actively.     

Gastric function and absorption of vitamin B12 in children with celiac disease

Gastric acid secretion in nineteen children with celiac disease remained almost unchanged and the level of fasting serum gastrin was comparable with that of a control group of the same age. The absorption of vitamin B₁₂ was significantly decreased, most clearly in the infants with celiac disease as compared with their controls. The serum B₁₂ level, however, was decreased only in the oldest children. The results suggest that the mucosal lesion in the small intestine is most extensive in the youngest children, but the absorption defect of vitamin B₁₂ becomes clinically significant only after a long duration of the disease and not in childhood.     

Liver involvement in celiac disease

Celiac disease may present as a cryptogenic liver disorder being found in 5–10% of patients with a persistent and cryptogenetic elevation of serum aminotransferase activity. In fact, a wide spectrum of liver injuries in children and adults may be related to CD and in particular: (1) a mild parenchymal damage characterised by absence of any clinical sign or symptom suggesting a chronic liver disease and by non-specific histological changes reversible on a gluten-free diet; (2) a chronic inflammatory liver injury of autoimmune mechanism, including autoimmune hepatitis, primary sclerosing cholangitis and primary biliary cirrhosis, that may lead to fibrosis and cirrhosis, generally unaffected by gluten withdrawal and necessitating an immunosuppressive treatment; (3) a severe liver failure potentially treatable by a gluten-free diet. Such different types of liver injuries may represent a spectrum of a same disorder where individual factors, such as genetic predisposition, precocity and duration of exposure to gluten may influence the reversibility of liver damage. A rigorous cross-checking for a asymptomatic liver damage in CD individuals and conversely, for CD in any cryptogenic liver disorder including end-stage liver failure is recommended.     

Increasing age at diagnosis of celiac disease in Malta

Objective : Recent studies have shown that celiac disease is being diagnosed at a progressively later age. This paper analyses trends in age at diagnosis in a closed island population.Methods : Patient case notes of all known patients with celiac disease were retrieved and demographic information, mode of presentation including symptomatology and diagnostic criteria were obtained. Over the period 1985 to 2000, information was available on 42 patients with celiac disease. All were aged ≤14 years.Result : The mean age at diagnosis showed an increasing age, with a constant disease incidence. A highly significant positive correlation was found for age at diagnosis with time (rho=0.4, p=0.009).Conclusion : It is thought that breast feeding, with later introduction of gluten containing products in the diet, leads to a later presentation of celiac disease. In Malta, over the period under study, the breast feeding rate rose from 20% to 60%. Our findings support the hypothesis that breast feeding offers a degree of protection against the early development of celiac disease, without actually reducing the incidence of the disease     

Practical considerations for the identification and follow-up of children with celiac disease

Celiac disease is an immune-mediated enteropathy affecting 0.5% to 1% of children and is induced by dietary gluten in susceptible individuals carrying the human leukocyte antigen DQ2 or DQ8 heterodimer. If serological screening is positive or if a patient displays suggestive symptoms, an endoscopic biopsy of the distal duodenum is required to confirm the diagnosis. Symptoms of celiac disease are often mild or absent. Overt malabsorption occurs in only 2% to 10% of children. Individuals with a higher risk of developing celiac disease, including first-degree relatives of affected patients and children with type I diabetes, Turner syndrome, Williams syndrome or Down syndrome, should be offered screening for celiac disease along with a discussion of the implications. If serological testing is negative, a high index of suspicion should remain if malabsorption, iron deficiency or osteopenia is present. Also, immunoglobulin A deficiency should be excluded. At-risk individuals should undergo serial serological screening. Lifelong adherence to a gluten-free diet is the only treatment. If left untreated, symptomatic children with celiac disease carry an increased risk of developing osteoporosis and have a greater lifetime risk of cancer. The long-term outcome of undiagnosed or untreated asymptomatic individuals is less clear.     

IgA endomysium antibodies – an early predictor for celiac disease in children without villous atrophy

Aim: To evaluate possible differences between children with anti-endomysium antibodies (EMA) positivity and normal small bowel mucosa and children with positive EMA and an enteropathy diagnosed as celiac disease (CD).
Methods: Children with suspected CD and positive EMA (≥1/10) undergoing small bowel biopsy during 1996 to 2002, were investigated (n = 133). Data registered were: year and month of birth, timing of the first biopsy, sex, heredity for CD, dermatitis herpetiformis and diabetes mellitus and outcome of the anti-gliadin antibody test (AGA). The case group, with EMA positivity and normal histology (n = 39; 59% female, mean age at the first biopsy 7.3 years, range 1.4–16), was compared with the disease control group, with positive EMA and a biopsy suggestive and further on diagnosed as CD (n = 94; 56% female; mean age 7.6 years at the first biopsy, range 0.70–17).
Results: AGA positivity and heredity for CD were found to predict the outcome of a pathological jejunal mucosa. Nineteen of the 39 children in the case group were rebiopsied of whom 11 had developed an enteropathy during a follow-up period of 2–7 years (median 4.5 years).
Conclusions: EMA positivity in the absence of small bowel enteropathy could be a very early predictor for later overt CD, and necessitates further follow-up, especially if the child is AGA positive and there is a family history of CD.     

Clinical presentation of celiac disease and the diagnostic accuracy of serologic markers in children

There has been growing recognition of a changing clinical presentation of celiac disease (CD), with the manifestation of milder symptoms. Serologic testing is widely used to screen patients with suspected CD and populations at risk. The aim of this retrospective analysis was to evaluate the clinical presentation of CD in childhood, assess the diagnostic value of serologic tests, and investigate the impact of IgA deficiency on diagnostic accuracy. We evaluated 206 consecutive children with suspected CD on the basis of clinical symptoms and positive serology results. Ninety-four (46%) had biopsy-proven CD. The median age at diagnosis of CD was 6.8 years; 15% of the children were <2 years of age. There was a higher incidence of CD in girls (p = 0.003). Iron deficiency and intestinal complaints were more frequent in children with CD than those without CD (61% vs. 33%, p = 0.0001 and 71% vs. 55%, p = 0.02, respectively), while failure to thrive was less common (35% vs. 53%, p = 0.02). The sensitivity of IgA tissue transglutaminase (IgA-tTG) was 0.98 when including all children and 1.00 after excluding children with selective IgA deficiency. The specificity of IgA-tTG was 0.73 using the recommended cut-off value of 20 IU, and this improved to 0.94 when using a higher cut-off value of 100 IU. All children with CD and relative IgA deficiency (IgA levels that are measurable but below the age reference [n = 8]) had elevated IgA-tTG. In conclusion, CD is frequently diagnosed in school-age children with relatively mild symptoms. The absence of intestinal symptoms does not preclude the diagnosis of CD; many children with CD do not report intestinal symptoms. While the sensitivity of IgA-tTG is excellent, its specificity is insufficient for the diagnostic confirmation of a disease requiring life-long dietary restrictions. Children with negative IgA-tTG and decreased but measurable IgA values are unlikely to have CD.     

Increasing incidence of childhood celiac disease in Sicily: results of a multicenter study

By screening the patient list of four Sicilian centers of gastroenterology and those with gluten-free product consumption, 1074 patients (607 females and 467 males) with celiac disease, diagnosed between 1975 and 1989, were identified. A maximum cumulative incidence rate by birth cohort was reached in 1986 (1.65/1000). When the incidence rate was adjusted for the years of follow-up, the actual standardized rate was 3 cases per 1000 live births. Growth failure and chronic diarrhea were the most common symptoms, but a diminishing trend for chronic diarrhea was observed when symptoms were distributed by year of diagnosis. Even though 61.1% of all cases were diagnosed within six months from the onset of symptoms, mean age at diagnosis showed an increasing trend, from less than two years to approximately four years of age. The results of our study showed an increasing incidence of celiac disease due to diagnosis of less typical cases at an older age and also to a steady increase in the rate of diagnosis of cases with a classic clinical picture.     

Celiac disease in children with short staure

Objective  The aim of the present study was to determine the prevalence of celiac disease in children with short stature. Methods  In all children with short stature (height more than 2 SD below the mean for age and sex) and normal physical examination, attending Motahary pediatric clinic in Shiraz, Iran, from 2003 till 2005, work-ups were made to find a cause for their short stature and of course their serum was assayed for IgG anti-tissue transglutaminase (TTG) antibody by ELISA test, as a marker for CD. Results  There were 26 girls and 46 boys with mean age of 9.8 years. Routine work-up showed microcytic hypochromic anemia in four children (5.6%) and giardiasis in five (6.9%). GH stimulation test revealed GH deficiency in five children (6.9%). Elevated IgG anti-TTG antibody level was detected in two children (2.8%). Duodenal biopsies of these children were in favor of celiac disease. Conclusion  Although, the prevalence of CD in this study was not significantly different (P value = 0.14) from the prevalence rate in healthy blood donors in Iran, the findings emphasize the fact that CD must be considered in a child with short stature, especially if the height is more than 3 SD below the mean for sex and age, even in the absence of gastrointestinal symptoms. In conclusion, the measurement of anti-TTG antibody should be included in the diagnostic evaluation of children with short stature.     

Knowledge and opinions of asymptomatic adolescents and their caregivers on celiac disease screening

ObjectivesCeliac disease (CD) is an immune enteropathy caused by sensitivity to gluten affecting one per cent of the general population. Most people with CD are asymptomatic and some may be affected from childhood. Despite the latest recommendations of paediatric gastroenterology societies, targeted screening is still uncommon in clinical paediatric settings. A poor understanding of the asymptomatic population’s opinions creates obstacles for broader implementation of CD screening. This study aims to fill this gap by reporting on the knowledge and opinions of adolescents and caregivers of children on CD screening.MethodsAdolescents with absence of classical symptoms of CD and caregivers of presumably asymptomatic children were asked about their knowledge and opinions of CD through a self-administered questionnaire.ResultsThere were 227 respondents including 76 adolescents and 151 caregivers. A minority of respondents (8% of caregivers and 23% of adolescents) were identified as having a CD-associated condition (such as hypothyroidism, type 1 diabetes, Down syndrome, etc.). A majority of caregivers (84%) and half of adolescents (49%) already knew about CD. Half of the respondents (46%) were in favour of screening asymptomatic paediatric populations and this agreement increased to 81.7% when they were confronted with hypothetical risks of 10%.ConclusionThis study reveals an increased willingness to screen when participants were faced with increasing hypothetical risks. This suggests that screening recommendations targeting high-risk populations, such as those of paediatric and non-paediatric gastroenterology societies, may be more widely accepted.     

Need for quantitative assessment of transglutaminase autoantibodies for celiac disease in screening-identified children

OBJECTIVES: To assess several transglutaminase autoantibody (TGAA) assays in their ability to distinguish celiac disease (CD) in screening-identified children with abnormal intestine biopsy specimens from those with normal biopsy specimens. STUDY DESIGN: Children at risk for CD (n = 54) composed of type 1 diabetics, first-degree relatives of type 1 diabetics or CD, and HLA-DQ2+ individuals followed from birth received intestine biopsy. Sera obtained at the time of biopsy were tested for TGAA, using the radioimmunoassay and 5 other commercially available enzyme-linked immunosorbent assays. RESULTS: False-positive rates ranged from 28% to 80%. The positive predictive value (PPV) of the tests ranged from 63% to 84% (lower than reported for symptomatic children). Setting a higher cutoff for each assay maximized PPV. CONCLUSIONS: There are significant quantitative differences among all TGAA assays that could affect interpretation of a positive test for CD. The overall false-positive rate for all assays was high in this population. Using the assay as a quantitative rather than qualitative tool by increasing the cutoff of positivity to indicate biopsy increases PPV. Multicenter workshops are needed to identify critical differences and to standardize TGAA assays among laboratories.     

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??Coeliac disease is an immune-mediated systematic disorder induced by ingestion of gluten. The typical clinical manifestations are gastrointestinal signs including diarrhea??bloating??weight loss and abdominal pain. It can also be manifested as extra-intestinal symptoms??such as iron-deficiency anemia??growth retardation??delayed puberty and recurrent mouth ulcers. Some children are considered to be at high risk of developing coeliac disease??such as those with a family history??who carry a susceptibility gene or have other autoimmune diseases. If the child is suspected with coeliac disease??serological screening with anti-tissue transglutaminase titers should be carried out first??and then the diagnosis may be confirmed by small bowel biopsy with a normal diet. For the treatment of celiac disease lifelong adherence to a gluten-free diet is needed??which can effectively relieve the clinical symptoms and prevent long-term complications. Therefore??clinicians should beware of the different clinical manifestations to ensure early diagnosis and timely application of gluten-free diet therapy.     

Occurrence of secondary cystathioninuria in children with inherited metabolic disorders,liver diseases,neoplasms, cystic fibrosis and celiac disease

Secondary cystathioninuria was found in two of 46 children suffering from tumors, leukemia, liver diseases, inherited metabolic disorders, cystic fibrosis and celiac disease. Of these two patients, one had congenital biliary atresia and the other cytomegalovirus infection. Seven further children had only moderately elevated excretion of cystathionine. It is suggested that secondary cystathioninuria is uncommon in the diseases investigated.Dedicated to Professor Dr. A. Wiskott on the occasion of his 80th birthday