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Guidelines for the Diagnosis and Treatment of Celiac Disease in Children

Posted on: Tuesday, 11 January 2005, 03:00 CST

Case Studies

Jennifer, age 2 years, is being seen for her regular 2-year well child visit. You note her weight is only at the 5% and has been dropping percentiles over the past year. When you ask her mother about Jennifer's diet, she reports Jennifer is a "picky eater" and often complains of a "stomach ache. " Her mother reports her stomach looks "bloated."

Steven, age 7 years, is brought into the clinic because of recurrent abdominal pain with occasional constipation or diarrhea. Steven's mother had been told in the past that he probably had "irritable bowel syndrome" but changes in his diet, occasional use of a laxative, and relaxation techniques have not improved his symptoms.

Rebecca, age 12 years, is brought into your clinic because her mother has recently learned that two first cousins have been diagnosed with celiac disease. She is wondering if Rebecca should be screened for this condition since she has heard it runs in families.

Incidence

Celiac disease is an immune-mediated enteropathy caused by a permanent sensitivity to the gliadin protein fraction of gluten found in cereal grains including wheat, rye, and barley. Celiac disease was previously thought to be rare and a disease of childhood but is now recognized as a common condition that can present at any age (American Gastroenterological Association, 2001; National Institute of Health [NIH], 2004). The prevalence is greater than previously thought with current estimates to be 3-13 per 1000 children, or approximately 1:300 to 1:80 children (North American Society for Pediatric Gastroenterolgy, Hepatology and Nutrition [NASPGHAN], 2004). Celiac disease may be the most common predetermined condition in humans, affecting roughly 1% of the U.S. population (Hill, 2003; NIH, 2004).

Celiac disease is found throughout the world but few prevalence studies have been performed. Studies find a frequency of 1 in 77 Swedish children, 1 in 230 school-age Italian children, and 1 in 100 five-year old children in Denver, Colorado (Carlsson, Axelsson, Borulf, Bredberg, & Ivarsson, 2001; Catassi, Fabiani, Ratsch, Coppa, Giorgi, Pierdomenico, et al, 1996; Catassi, Ratsch, Fabiani, Ricci, Bordicchia, Pierdomenico, et al, 1995; Hoffenberg, MacKenzie, Barriga, Eisenbarth, Bao, Haas, et al, 2003). The recent improvement in serologic screening techniques will enable future studies to determine prevalence in different ethnic/racial groups and people of different ages. It is currently believed to be rare in black Africans, and people of Chinese or Japanese origin (Hill, Bhatnagar, Cameron, Rosa, Maki, Russell, et al, 2002).

Although it is believed that many people with celiac disease may be undiagnosed, at this time there is insufficient evidence to support screening of the general population (NIH, 2004).

Etiology

Celiac disease occurs in genetically susceptible individuals and a family history of celiac disease is a key indicator for diagnostic testing in young children with gastrointestinal (GI) symptoms. Over 99% of people with celiac disease are positive for human leukocyte antigen (HLA)-DQ2 or DQ8 (NASPGHN, 2004; Pietzak & Thomas, 2003). The genetic predisposition to gluten sensitivity is also apparent in the list of genetic conditions associated with a higher incidence of celiac disease. Children with type 1 diabetes, IgA deficiency, Down syndrome, Turner syndrome, and Williams syndrome have a significantly higher incidence of celiac disease than the general population (NASPGHAN, 2004). Children with autoimmune disorders such as type 1 diabetes, autoimmune thyroiditis, and rheumatoid arthritis have a higher incidence of celiac disease with the incidence reported as high as 1 in 12 children with type 1 diabetes also having gluten intolerance (Pietzak & Thomas, 2003).

The autoimmune reaction to the toxic gliadin protein fraction of gluten is variable between individuals, with some individuals having more severe mucosal damage to the small intestine than others. Proinflammatory cytokines have also been found to be increased in children with celiac disease and may play a role in mucosal damage (Hoffenberg, Emery, Barriga, Baos, Taylor, Eisenbarth, et al., 2004). Celiac disease results in villous atrophy of the duodenal mucosa, lymphocytic infiltrates, and marked crypt hyperplasia (NASPGHAN, 2004; Pietzak & Thomas, 2003). These changes are found in the small intestine most often in the proximal duodenum. Histological changes in the mucosa may be intermittent so multiple biopsies are recommended to fully assess for changes consistent with celiac disease (NIH, 2004). These changes in duodenal mucosa result in malabsorption of nutrients resulting in failure to thrive, and complex anemia from iron, folate, and/or vitamin B12 deficiencies. In children with severe mucosal damage absorption of fat-soluble vitamins, zinc, and protein are also affected. The mucosal damage can increase over time so an initial negative small bowel biopsy does not rule out future positive findings.

Clinical Manifestations

Symptoms of celiac disease are highly variable often resulting in prolonged delays in diagnosis. As many as 50% of newly diagnosed individuals with celiac disease do not have gastrointestinal symptoms at the time of diagnosis (Hill, 2003). Gastrointestinal symptoms of celiac disease vary from severe diarrhea leading to malnutrition and failure to thrive with anemia and abdominal distention, to chronic intermittent, mild gastrointestinal complaints of abdominal pain/bloating, diarrhea or constipation, nausea and vomiting. Some children with small bowel biopsies consistent with celiac disease have no signs and symptoms of the condition (silent celiac disease). The classic presentation of celiac disease, the infant who initially does well but after the introduction of cereal become irritable with a potbelly, wasted extremities, bulky loose stools, and weight loss or failure to gain weight, may be less common than the older child with milder disease who has less dramatic or variable symptoms (NASPOHN, 2004) (see Table 1). This variability in symptoms leads to delay in diagnosis and treatment and frequently frustrated parents. A recent survey of children diagnosed with celiac disease found children had symptoms for over a year prior to diagnosis (Johnson, 2004).

Table 1. Symptoms of Celiac Disease in Children

Table 2. Conditions Associated with Celiac Disease

Table 3. Common Foods and Food Additives to Avoid in a Gluten- Free Diet

There is growing recognition that celiac disease is really a multi-system autoimmune disorder with many associated conditions (see Table 2). There is a distinct neurological component to celiac disease that includes ataxia, epilepsy, chronic neuropathies and dementia in adults and may be associated with softer neurological signs, such as headaches, learning disorders, depression, developmental delay and hypotonia in children (Farrell & Kelly, 2002; Zelnik, Pacht, Obeid, & Lerner, 2004). Additional non- gastrointestinal symptoms associated with celiac disease, possibly secondary to chronic malnutrition, include dental enamel hypoplasia of the permanent teeth, osteoporosis, short stature, delayed puberty, anemia, folate and vitamin K deficiency, arthralgia, alopecia, infertility, and recurrent spontaneous abortions (Farrell & Kelly, 2002; NASPGHAN, 2004). Dermatitis herpetiformis, an autoimmune blistering skin condition, is also found more frequently in people with celiac disease and, when present, should increase the suspicion of celiac disease in a symptomatic child (NASPGHN, 2004).

Long-term Effects of Celiac Disease

The natural history of untreated, treated, and partially treated celiac disease is not known (Hill, 2003). In those individuals with significant gastrointestinal symptoms, malnutrition due to poor absorption of nutrients from the small intestine can be significant. Permanent stunting of growth can occur when the disease presents during childhood. The neurological associated manifestation can have profound impact on school performance and quality of life. It is unknown if children with untreated celiac disease have increased incidence of other autoimmune diseases. Identified long-term complications of untreated celiac disease include increased risk of gastrointestinal malignancies, dental enamel defects, and osteoporosis (Hill, Bhatnagar, Cameron, De Rosa, Maki, & Russell et al., 2002).

Table 4. Internet Sites for Celiac Disease Information

Screening and Diagnosis

The North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (2004) recommends that primary care providers consider celiac disease early in children with a combination of persistent diarrhea and poor weight gain, weight loss or failure to thrive. Children with recurrent gastrointestinal symptoms, including abdominal pain, anorexia, constipation, vomiting or other global symptoms found in celiac disease (see Table 1) should also be evaluated, as part of a differential diagnosis, for the presence of celiac disease. In addition, all children who are first degree relatives of an individual with confirmed celiac disease, have type 1 diabetes, Down syndrome, Turner syndrome, Williams syndrome, selective IgA deficiency or autoimmune thyroiditis should be screened even if they are without gastrointestinal s\ymptoms (NASPGHN, 2004).

Although small bowel biopsy to determine histological changes in the mucosa is the definitive diagnostic test for celiac disease, there are screening tests to help determine those children with high probability of the disease from those with low probability. The currently recommended screening test is a measurement of IgA antibody to human recombinant tissue transglutaminase (tTG IgA) (NASPGHN, 2004). The tissue transglutaminase antibody test (tTG) has replaced the anti-gliadin (GAG IgA and AGA IgG) and the anti- endomysium (BMA IgA) as the screening test of choice because of its accuracy. The sensitivity of tTG IgA in both children and adults ranges from 0.92-1.00 and specificity from 0.91-1.00 (NASPGHAN, 2004). The IgA endomysial antibody immunofluorescence (EMA) test is also recommended as an equivalent screening test by the National Institute of Health (2004). Elevation in tTG IgA level or IgA-EMA level is indicative of celiac disease, but in approximately 2% of symptomatic children a concurrent IgA deficiency can mask elevations. Therefore, measurement of quantitative serum IgA should be taken concurrently.

If the child has normal IgA serum levels and an elevated IgA antibody to human recombinant tissue transglutaminase an intestinal biopsy should be scheduled to confirm the diagnosis and determine the level of involvement in the small intestine. Intestinal biopsy should also be done in children with negative serological tests but with failure to thrive, chronic diarrhea, or a diagnosis with high incidence of celiac disease (NASPGHN, 2004). A positive serology test and a negative small bowel biopsy may represent a false positive serology test or milder disease without current changes in the small bowel (latent celiac disease). Children must be ingesting gluten for the small intestine to have the characteristic histological changes so clinicians should not prescribe a gluten- free diet prior to testing being completed. As genetic markers for celiac disease become more defined, they will also be used to screen people for this condition.

The diagnosis of celiac disease is made when a child over 2 years of age, who has symptoms suggestive of celiac disease, is found to have histological changes in the small bowel and resolution of symptoms when put on a glutenfree diet (NASPGHN, 2004). A positive serology test that reverts to negative after compliance with a gluten-free diet is considered supportive evidence. In situations where the diagnosis is uncertain in a symptomatic child, HLA typing can be done, repeat small bowel biopsy may be scheduled, or a trial on a gluten-free diet (GFD) can be instituted.

Treatment

The only treatment currently available for celiac disease is strict adherence to a gluten-free diet (GFD). Even small amounts of gluten regularly can result in villi damage. The National Food Authority defines gluten-free foods as food with no gluten and foods with less than 200 ppm as low gluten (NASPGHN, 2004). Gluten detection techniques are not always accurate and there is lack of solid scientific evidence for a threshold of gluten consumption that causes harm (NASPGHN, 2004). The American Dietetic Association has published guidelines for dietary treatment of celiac disease that are supported and used by most professionals treating children with celiac disease (American Dietetic Association, 2002).

Gluten is found in wheat, barley, and rye. Other forms of wheat include semolina (durum wheat), farina, einkorn, bulgur, and couscous. Malt is also harmful because it is a partial hydrolysate of barley. Any ingredient with barley malt, malt syrup, malt extract, or malt flavoring should be avoided. Oats, buckwheat, amaranth, and quinoa do not contain gluten as grown but are often milled in facilities that also mill wheat, barley, or rye and therefore can be contaminated with gluten (see Table 3 for common gluten-containing foods).

Children who adhere to a GFD generally have resolution of their gastrointestinal symptoms, regain weight and stature if diagnosed early, regain normal amounts of red blood cells, and have improvement in their sense of physical and psychological well being (NASPGHN, 2004). If GFD is initiated during the toddler/preschool years, the dental enamel defects may be averted. In addition, the histological changes in the small intestines return to normal several months after diet change in younger people but may take years to resolve in older people. The tTG IgA also returns to normal as healing of the villi occurs. Accidental ingestion of gluten will cause abdominal discomfort in many affected people but even if symptoms do not occur, damage to the small intestine does, so gluten should be avoided.

Although many food groups are not eliminated by a gluten-free- diet, i.e., fresh meats and fish, most dairy products, fruits, and vegetables, the inability to eat breads, cereals, pasta, cookies, cakes, processed meats, gravies and many sauces made with wheat, barley, or rye make adherence to a GFD difficult. Cross contamination of foods can occur via cooking or eating utensils so many families resort to a GFD for the entire household. Parents and children trying to maintain a GFD must learn to read all food labels for ingredients containing gluten, such as malt flavoring, food starches, and additives for bulk such as used in sausages or hot dogs. Medications can also contain gluten as a binding agent, and even some lipsticks have been found to have gluten. All families with the diagnosis of celiac disease should meet with a dietitian to learn about reading food labels, common food additives to avoid, and use of rice, soy, corn, or potato flour for cooking in the home.

Table 5. Key Elements in the Management of Children and Adolescents with Celiac Disease

Adolescents and children need to be educated about the foods they should avoid when eating outside the home. This can be particularly difficult for adolescents who want to conform to their peer group eating habits. Fortunately, the current focus on eating low carbohydrate foods to control weight has made not eating breads, pasta, and pastries more acceptable. Parents and providers can help children identify common foods in restaurants that are gluten free or even call ahead to restaurants to talk with the food preparers to identify food choices that are acceptable so adolescents do not need to do this in front of their peers.

Referring families to a celiac support group is an excellent way of providing information regarding the condition and on maintaining a GFD. The internet also provides access to valuable information from professional organizations developed to help support individuals and families with celiac disease and commercial companies supplying gluten-free foods and recipes (see Table 4).

The NIH identified six key elements in the management of celiac disease (NIH, 2004) (see Table 5). These six elements provide the pediatric nurse and the pediatric primary care provider with a framework for providing condition-specific health care.

Followup on Case Studies

All three children presented earlier are prime candidates for screening with tTG IgA. If this screening test is positive and there is no underlying IgA deficiency then they should be referred to a pediatric gastroenterologist to be evaluated and scheduled for small bowel biopsy. No change in diet should be instituted until the testing has been completed. If the diagnosis of celiac disease is made, their families should be referred for counseling to a pediatric dietician and to a local celiac support group. Follow-up in the primary care clinic should occur shortly after the diagnosis to answer questions about the diagnosis and then approximately every 6 months to monitor growth and resolution of symptoms. Siblings should also be screened for celiac disease and other close family members informed of the diagnosis.

The Primary Care Approaches section focuses on physical and developmental assessment and other topics specific to children and their families. If you are interested in author guidelines and/or assistance, contact Patricia L. Jackson Allen at pat.jacksonallen@yale.edu.

References

American Dietetic Association. (2002). American Dietetic Association complete food and nutrition guide (2nd edition). New York: Wiley, Inc.

American Gastroenterological Association. (2001). American Gastroenterological Association medical position statement: Celiac sprue. Gastroenterology, 120(6), 1522-1525.

Carlsson, A., Axelsson, I., Borulf, S., Bredberg, A., & Ivarsson, S.A. (2001 ). Serological screening for celiac disease in healthy 2.5-year-old children in Sweden. Pediatrics, 107(1), 42-45.

Catassi, C., Fabiani, E., Ratsch, I., Coppa, G., Giorgi, P., & Pierdomenico, R., et al. (1996). The celiac iceberg in Italy. A multicentre antigliaden antibodies screening for celiac disease in school- age subjects. Acta Paediatr, 472(1), 29-35.

Catassi, C., Ratsch, L, Fabiani, E., Ricci, S., Bordicchia, F., & Pierdomenico, R., et al. (1995). High prevalence of undiagnosed celiac disease in 5280 Italian students screened by antigliadin antibodies. Acta Paediatr, 84(6), 672-676.

Farrell, R.J., & Kelly, C. (2002). Current concepts: Celiac sprue. New England Journal of Medicine, 346(3), 180-188.

Hill, I.D. (2003). Celiac disease: A never-ending story. Journal of Pediatrics, 143(3), 289-291.

Hill, I.D., Bhatnagar, S., Cameron, D.J., De Rosa, S., Maki, M., & Russell, G.J., et al. (2002). Celiac disease: Working group report of the first world congress of pediatric gastroenterology, hepatology, and nutrition. Journal of Pediatric Gastroenterology and Nutrition, 35(S2), S78- S88.

Hoffenberg, E.J., Emery, L.M., Barriga, K.J., Baos, F., Taylor, J., & Eisenbarth, G.S., et al. (2004). Clinical features of children with screening-identified evidence of celiac disease. Pediatrics, 113(5), 1254-1259.

Hoffenberg, E.J., MacKenzie, T., Barriga, K.J., Eisen\barth, G.S., Bao, & Haas, J.F, et al. (2003). A prospective study of the incidence of childhood celiac disease. Journal of Pediatrics, 143(3), 308-314.

Johnson, K. (2004, March). Celiac disease has new, subtle atypical forum. Pediatric News, p. 30.

National Institute of Health, (2004, September 11). National Institute of Health Consensus Development Conference Statement: Celiac disease http://consensus.hih.gov/cons/118/118cdc_intro.htm.

North American Society for Pediatric Gastroenterology, Hepatology and Nutrition [NASPGHN] (2004). Guidelines for the diagnosis and treatment of Celiac Disease in children.

Pietzak, M.M., & Thomas, D.W. (2003). Childhood malabsorption. Pediatrics in Review, 24(6), 195-204.

Zelnik, N., Pacht, A., Obeid, R., & Lerner, A. (2004). Range of neurologic disorders in patients with celiac disease. Pediatrics, 113(61, 1672-1676.

Patricia L. Jackson Allen, MS, RN, PNP, FAAN

Patricia L. Jackson Allen, MS, RN, PNP, FAAN, is Professor, Yale University School of Nursing, New Haven, CT; and Clinical Professor Emeritus at the university of California, San Francisco, CA.

Copyright Anthony J. Jannetti, Inc. Nov/Dec 2004

Source: Pediatric Nursing

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