CeliacDiseaseStefano Guandalini, MD, Director, University of Chicago Celiac Disease Program, Section Chief of Gastroenterology, Hepatology and Nutrition; Professor, Department of Pediatrics, University of Chicago Comer Children's Hospital Phyllis A Vallee, MD, Associate Program Director, Department of Emergency Medicine, Henry Ford Hospital Updated: May 4, 2010

Introduction

BackgroundCeliac disease (CD) is a multifactorial, autoimmune disorder that occurs in genetically susceptible individuals.[1 ]It is triggered by a well-identified environmental factor (gluten and related prolamins), and the autoantigen is also well known (ie, the ubiquitous enzyme tissue transglutaminase). The disease primarily affects the small intestine, where it progressively leads to flattening of the small intestinal mucosa. Three cereals contain gluten and are toxic for patients with celiac disease: wheat, rye, and barley. The genetic susceptibility to celiac disease is conferred by well-identified haplotypes in the human leukocyte antigen (HLA) class II region (ie, DR3 or DR5/DR7 or HLA DR4). Such haplotypes are expressed on the antigen-presenting cells of the mucosa (mostly dendritic cells); approximately 90% of patients express the DQ2 heterodimer, and approximately 7% of patients express the DQ8 heterodimer. The remaining 3% of patients possess only half of the DQ2 heterodimer. Celiac disease can occur at any stage in life; a diagnosis is not unusual in people older than 60 years. Because the historical prevalence and long-term outcome of undiagnosed celiac disease were unknown, Rubio-Tapia et al collected serological information on 3 cohorts.[2 ]These included 9,133 healthy young adults from whom sera were collected between 1948-1954 and 12,768 gender-matched subjects from 2 recent cohorts, one whose years of birth were similar to those of members of the first cohort, and one in which age at sampling was similar. Sera was tested for tissue transglutaminase and, if abnormal, for endomysial antibodies. In the older cohort, during 45 years of follow-up, all-cause mortality was nearly 4-fold greater in persons with undiagnosed celiac disease than among those who were seronegative (hazard ratio = 3.9; 95% confidence interval, 2-7.5; P 1 wk) in children without checking growth parameters and adrenal function; caution in hyperthyroidism, osteoporosis, peptic ulcer, cirrhosis, nonspecific ulcerative colitis, diabetes, and myasthenia gravis

Follow-upFurther Outpatient CareAfter the diagnosis of celiac disease (CD) has been established and a strict diet has been initiated, the first follow-up requirement is to monitor the patient's response to the diet. Depending on the severity of the clinical situation and the type of symptoms, the first outpatient appointment is typically scheduled for 4-8 weeks after the diagnosis. At this time, serologic tests for celiac disease are not needed because antibody levels still have not declined. Further follow-up appointments are dedicated to assessing the patient's dietetic compliance and the adequacy of growth and well-being. Anti-tTG and the newer deamidated antigliadin antibodies should be periodically monitored for regression; their levels usually return to normal within 4-6 months after the beginning of a rigorous diet. However, the best indicator of dietary compliance is attainable by a careful review of the diet, and simple survey questionnaires have been developed for use in adults.[23 ]For patients whose initial levels of anti-tTG were particularly elevated, normalization can take up to 12-18 months. For asymptomatic patients and for those who are clinically responding well to diet, follow-up appointments are usually scheduled annually. Celiac disease can be associated with numerous autoimmune disorders. If any are present (eg, type I diabetes mellitus, thyroiditis), follow-up care must include an adequate assessment of these conditions, which most often do not respond to the diet, and referral to other specialists is required (see Consultations). A dietitian must be present at each of the follow-up appointments because the questions that most interest the patient's family are, by far, those concerning the diet. In patients who had obvious malabsorption at diagnosis, assessment of the status of specific nutritional deficiencies (eg, iron deficiency, folate deficiency, zinc deficiency) is appropriate.

Deterrence/PreventionThe only way to prevent recurrences is to closely monitor the patient's diet. Because celiac disease is more common in relatives of patients, first-degree relatives should at least be serologically screened (see Causes). Concerned parents usually accept this simple procedure, which often reveals previously undetected celiac disease, even in asymptomatic individuals. This effective preventive strategy must be encouraged. Also, prevention of complications by early diagnosis (secondary prevention) may be achieved by applying a protocol of blood screening to all patients who belong to other at-risk categories (eg, type 1 diabetes mellitus, Down syndrome). With elucidation of the role that infant feeding practices and rotavirus infections play, primary prevention of celiac disease no longer seems impossible. Primary prevention (at least in some cases) may be achieved through the expected reduction of rotavirus infections after the introduction of the vaccine and through proper breast feeding and gluten introduction in infants born to at-risk families.

ComplicationsCeliac disease is fully reversible if trigger foods are avoided. However, when compliance is suboptimal, complications may occur. The level of gluten that is safe to consume widely varies among people with celiac disease; hence, a zero-tolerance policy must be enforced. Available evidence suggests that although almost no individuals with celiac disease show signs or symptoms of relapse while ingesting as much as 10-20 mg of gliadin per day, most react to ingestion of more than 100 mg/d.[22 ] Complications in noncompliant patients include the following: Osteopenia/osteoporosis Adverse effects during pregnancy, including miscarriages Anemia Ulcerative jejunitis, colitis, refractory celiac disease (thought to be a low-grade intestinal lymphoma) GI malignancies, most commonly an enteropathy-associated T-cell lymphoma (EATL)

PrognosisThe prognosis is excellent; the disorder is fully reversible if trigger foods are avoided.

Patient EducationIn modern society, living a life without gluten is not easy. Educating patients and their families about how to select and properly maintain such a diet is a major, ongoing task. The role of support groups can never be overestimated. The physician has a duty to care for patients with celiac disease and to adequately inform the family about how to connect with such groups. Several university-associated centers that provide excellent materials for patient education are now available in the United States (eg, the University of Chicago Celiac Disease Center[24 ]) and in Europe. In the United States, the American Celiac Disease Alliance (ACDA) offers patient education as well as links to other centers. For excellent patient education resources, visit also eMedicine's Esophagus, Stomach, and Intestine Center and Teeth and Mouth Center. Also, see eMedicine's patient education articles Celiac Sprue, Anatomy of the Digestive System, and Canker Sores.

MiscellaneousMedicolegal PitfallsFailure to perform a sweat test on children with any type of malabsorption syndrome to exclude cystic fibrosis

(CF), a more serious condition that may present similarly at onset, is a pitfall. If the patient's condition fails to respond to dietary changes after the initial diagnosis (remember that the diagnosis depends not only on biopsy results but also a clear response to diet), failure to consider alternative diagnoses is a pitfall. Such diagnoses include food allergies; other GI diseases; immunodeficiency disorders; and viral, bacterial, parasitic, and fungal infections.

Multimedia

Media file 1: Potbelly and muscle wasting in a child with celiac disease.

Media file 2: The celiac iceberg.

Media file 3: The different presentations of celiac disease.

Media file 4: Extraintestinal manifestations of celiac disease.

Media file 5: GI signs and symptoms of celiac disease.

Media file 6: Approximate prevalence of celiac disease in other autoimmune disorders.

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Keywordsceliac sprue, celiac disease, wheat, osteopenia, osteoporosis, short stature, delayed puberty, anemia, diarrhea, abdominal distension, malnutrition, celiac crisis, explosive watery diarrhea, dehydration, constipation, treatment, symptoms

Contributor Information and DisclosuresAuthor

Stefano Guandalini, MD, Director, University of Chicago Celiac Disease Program, Section Chief of Gastroenterology, Hepatology and Nutrition; Professor, Department of Pediatrics, University of Chicago Comer Children's Hospital Stefano Guandalini, MD is a member of the following medical societies: American Gastroenterological Association, European Society for Paediatric Gastroenterology, Hepatology & Nutrition, and North American Society for Pediatric Gastroenterology and Nutrition Disclosure: Nothing to disclose.Coauthor(s)

Phyllis A Vallee, MD, Associate Program Director, Department of Emergency Medicine, Henry Ford Hospital Phyllis A Vallee, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Medical Association, and Michigan State Medical Society

Disclosure: Nothing to disclose.Medical Editor

Jorge H Vargas, MD, Professor of Pediatrics and Clinical Professor of Pediatric Gastroenterology, David Geffen School of Medicine, University of California at Los Angeles; Consulting Physician, Department of Pediatrics, University of California at Los Angeles Health System Jorge H Vargas, MD is a member of the following medical societies: American Liver Foundation, American Society for Gastrointestinal Endoscopy, American Society for Parenteral and Enteral Nutrition, Latin American Society of Pediatric Gastroenterology, Hepatology & Nutrition, and North American Society for Pediatric Gastroenterology and Nutrition Disclosure: Nothing to disclose.Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine Disclosure: Nothing to disclose.Managing Editor

Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada Disclosure: Nothing to disclose.CME Editor

Steven M Schwarz, MD, FAAP, FACN, AGAF, Professor of Pediatrics, Children's Hospital at Downstate, SUNYDownstate Medical Center Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research Disclosure: TAP Pharmaceuticals Honoraria Speaking and teaching; Curemark, LLC Consulting fee Board membership; Centocor, Inc. Grant/research funds Independent contractor; Johnson & Johnson, Inc. Grant/research funds Independent contractorChief Editor

Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada Disclosure: Nothing to disclose. Acknowledgments The authors and editors of eMedicine gratefully acknowledge the contributions of previous author Ginette V Busschots, MD, to the writing and development of this article. Further Reading

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