Overview

Celiac disease and gluten intolerance are misunderstood and often overlooked in the medical community. Celiac disease is defined as a multisystem autoimmune disorder and can present with a variety of symptoms that may result in many complications, including death. Healthcare professionals should be alert to differentiate this condition from many others and provide adequate follow-up treatment in order to maintain a quality standard of health for the patient. This course will outline the clinical presentation, diagnosis, pathophysiology, associated complications, and psychosocial impact of celiac disease.

Education Category: Infection Control / Internal Medicine
Release Date: 12/01/2013
Expiration Date: 11/30/2016

Audience

This course is designed for nurses, dieticians, and allied health professionals who may have a patient with celiac disease primary or secondary to their presenting diagnosis.

Accreditations & Approvals

NetCE is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. NetCE is approved to offer continuing education through the Florida Board of Nursing Home Administrators, Provider #50-2405. NetCE is approved by the California Nursing Home Administrator Program as a provider of continuing education. Provider number 1622. NetCE is accredited by the International Association for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU. This program has been pre-approved by The Commission for Case Manager Certification to provide continuing education credit to CCM® board certified case managers. The course is approved for 2 CE contact hour(s). Activity code: H00021169. Approval Number: 160001962. To claim these CEs, log into your CE Center account at www.ccmcertification.org.

Designations of Credit

NetCE designates this continuing education activity for 2 ANCC contact hour(s). NetCE designates this continuing education activity for 4 ANCC contact hour(s). NetCE designates this continuing education activity for 4.8 hours for Alabama nurses. This home study course is approved by the Florida Board of Nursing Home Administrators for 4 credit hour(s). This course is approved by the California Nursing Home Administrator Program for 4 hour(s) of continuing education credit - NHAP#1622004-5381/P. California NHAs may only obtain a maximum of 10 hours per course. AACN Synergy CERP Category A. NetCE is authorized by IACET to offer 0.4 CEU(s) for this program.

Individual State Nursing Approvals

In addition to states that accept ANCC, NetCE is approved as a provider of continuing education in nursing by: Alabama, Provider #ABNP0353, (valid through December 12, 2017); California, BRN Provider #CEP9784; California, LVN Provider #V10662; California, PT Provider #V10842; Florida, Provider #50-2405; Iowa, Provider #295; Kentucky, Provider #7-0054 through 12/31/2017.

Course Objective

The purpose of this course is to provide healthcare professionals with the information necessary to identify and provide adequate care for those with celiac disease.

Learning Objectives

Upon completion of this course, you should be able to:

  1. Discuss the history and epidemiology of celiac disease in the United States.
  2. Explain the pathophysiology of celiac disease and risk factors for development.
  3. Discuss the clinical signs and symptoms of celiac disease.
  4. Describe the methods used for the diagnosis of celiac disease.
  5. Identify comorbidities and complications commonly associated with celiac disease.
  6. Describe recommended treatment of celiac disease and discuss therapeutic alternatives.
  7. Explain the importance of ongoing education and support for the individual and family with celiac disease.

Faculty

Diane Thompson, RN, MSN, CDE, CLNC, has an extensive history in nursing and nursing education. She possesses a strong background in diabetes and cardiac care, starting her professional career at the cardiac care area of the Cleveland Clinic in Cleveland, Ohio. Ms. Thompson took the knowledge and experience she learned from the Cleveland Clinic and transferred it into the home health arena in rural Ohio, after which she moved to Florida and obtained further knowledge while working as a PRN nurse in all areas, including medical/surgical, intensive care, emergency, critical care, and cardiology. With a desire to have a specific area to concentrate her profession, Ms. Thompson accepted a position as a pneumonia case manager, which led into a diabetes case manager career.

Ms. Thompson has been employed in diabetes care since 2001, when she was hired as a diabetes case manager. After the completion of 1000 hours of education to diabetes patients, Ms. Thompson earned her certification as a diabetes educator in 2003. Since 2006, Ms. Thompson has been the Director of Diabetes Healthways at Munroe Regional Medical Center in Ocala, Florida. As the director of the diabetes center, Ms. Thompson is responsible for the hospital diabetes clinicians, hospital wound care clinicians, and out-patient education program. Ms. Thompson has also lectured at the local, state, and national level regarding diabetes and the hospital management of hyperglycemia. Ms. Thompson is a member of the ADA, AADE, Florida Nurses Association, and the National Alliance of Certified Legal Nurse Consultants.

Ms. Thompson acknowledges her family as her greatest accomplishment. She is a wife of 26 years and a mother of a daughter and son, of which she is very proud. Ms. Thompson credits her husband for the support needed to see a goal and achieve it. He has been by her side through nursing school and completion of her Bachelor's degree and Master's degree, which she was awarded in 2015 from Jacksonville University in Florida.

Sylvia A Llewelyn Bower, RN, has been practicing as a nurse for more than 50 years. She received her nursing diploma from Grant Hospital School of Nursing in Columbus, Ohio, and attended St. Joseph's College in Windham, Maine, and Franklin University in Columbus, Ohio. Ms. Llewelyn Bower has worked in a variety of settings, including home care, public health, staff education, ambulatory care, discharge planning, and hospice. Since being diagnosed with celiac disease in 2000, Ms. Llewelyn Bower has made educating healthcare professionals and the lay public about the disease her main profession. She has published two books on the subject.

Faculty Disclosure

Contributing faculty, Diane Thompson, RN, MSN, CDE, CLNC, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Contributing faculty, Sylvia A Llewelyn Bower, RN, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

Division Planner

Jane C. Norman, RN, MSN, CNE, PhD

Division Planner Disclosure

The division planner has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.

About the Sponsor

The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.

Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.

Disclosure Statement

It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.

Table of Contents

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#38560: Celiac Disease

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INTRODUCTION

Celiac disease (CD) is a global health concern, impacting 1% to 3% of the global population and requiring a multidisciplinary approach to care and treatment [1,2]. Research estimates that as many as 1 in 141 Americans, or approximately 1% of the U.S. population, have celiac disease [3]. Celiac disease is a burden to the U.S. healthcare system, costing approximately $4,019 per female patient and $14,191 per male patient over a four-year period [3].

Until the 1970s, the estimated global prevalence of celiac disease was only 0.03%. A Finnish population-based study demonstrated an almost doubled prevalence of celiac disease observed between 1980 (1.03%) and 2001 (1.99%). This overall increase is due to improved awareness, screening, and diagnostics and may also be attributed to environmental changes worldwide [4]. With increased awareness of this disease among adult and pediatric primary care providers, there will undoubtedly be an increase in the number of individuals being evaluated for CD in outpatient diagnostic centers and gastroenterology practices [5].

HISTORY

The term celiac is derived from the Greek word koiliakos, meaning "suffering of the bowel." It was first introduced in 250 C.E. by Aretaeus of Cappadocia. Allergies, food intolerances, and sensitivities began when humans learned to cultivate crops, generating a new battery of food antigens, including cereal grains, bird's eggs, and the milk of cows, goats, and donkeys [6]. The first century C.E. provides the earliest documented evidence of CD. The case was a young woman of short stature (140 cm) with a history of anemia and a decreased bone mass with evidence of osteoporosis and bone fragility. The archeological artifacts from the tomb, and the quality of the burial architecture, suggest that the tomb was built for a wealthy person in an area with an extensive culture of wheat consumption. Clinical presentation and the possible continuous exposure to wheat suggest CD [7].

There have been numerous documented cases of CD since this first observation. In 1888, a British physician, Dr. Samuel Gee, presented clinical studies of CD that included both children and adults. Dr. Gee felt that the regulation of food was the principle component of treatment, and he documented a case of a patient improving after introduction to a gluten-free diet [8]. In 1953, a Dutch pediatrician, Dr. Willem Karel Dicke, wrote his doctoral dissertation based on observations that the ingestion of wheat proteins, not carbohydrates, was the cause of CD. In the mid-1960s, an enteropathy similar to CD was identified in patients with dermatitis herpetiformis. This skin condition was shown to be a manifestation of gluten-sensitive enteropathy. Around that time, adult CD was also noted to be associated with numerous neurological disorders, including epilepsy, cerebral calcifications, and peripheral neuropathy [9].

In the 1970s, gastrointestinal (GI) endoscopic techniques were introduced. This provided the opportunity to obtain routine biopsy samples, which in turn provided improved opportunities in CD case finding and diagnosis. In the 1980s and 1990s, two human leukocyte antigen molecules (HLA-DQ2 and HLA-DQ8) typically associated with CD were identified, which led to more specific diagnosis [4]. In 1990, the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) published guidelines to achieve higher diagnostic accuracy of CD. A panel of experts established that CD is an autoimmune disease associated with specific genes (DQ2 and DQ8) and identified the autoantigen in CD as the enzyme tissue transglutaminase [2]. In 2012, a working group within ESPGHAN established new guidelines as well as a new definition of CD based on scientific and technical developments [2].

EPIDEMIOLOGY

The updated ESPGHAN guidelines define CD as "an immune-mediated systemic disorder elicited by gluten and related prolamins in genetically susceptible individuals and characterized by the presence of a variable combination of gluten-dependent clinical manifestations and CD-specific antibodies" [2]. CD, also known as gluten intolerance, gluten-sensitive enteropathy, nontropical sprue, and celiac sprue, is an immune-mediated response to gluten (e.g., wheat, rye, barley) in genetically predisposed individuals [5]. When an individual with CD consumes gluten, it damages the small intestines and results in difficulty absorbing nutrients from foods. As previously noted, approximately 1 in 141 individuals in the United States (or about 1%) have celiac disease. The risk is greater (i.e., 1 in 22) in individuals with a first-degree relative with CD [10].

Until the 1990s, celiac disease was considered rare among non-European and developing nation populations. Prevalence rates are now thought to be similar, due in part to increased awareness of the disease and the introduction of serologic screening tests in the Middle East, India, and North Africa. However, CD is still rarely reported in sub-Saharan African, African American, and East Asian populations [11,12]. This immune-mediated disorder is more common in individuals with other such disorders (e.g., type 1 diabetes). The individual with type 1 diabetes has a prevalence of 1% to 16% of comorbid CD [13]. Although CD is most often recognized as an illness affecting the pediatric population, for adult individuals, the diagnosis is often made between the fourth and sixth decade of life [14].

Individuals with CD often have an inherited predisposition influenced by environmental factors [15]. An estimated 5% to 22% of individuals with CD have an immediate family member (i.e., first-degree relative) who also has the disease [3]. CD affects twice as many women as men and is most commonly seen among relatives, especially siblings [16].

There is often a delay in diagnosis due in part to the varied clinical manifestations of CD. The average time to diagnosis from initial presentation of symptoms ranges from 6 to 10 years [3]. In 2004, public awareness of CD was brought to the forefront by the National Institute of Health Consensus Development Conference and its statement on CD. This statement was instrumental in addressing issues of protein manifestations, epidemiology, diagnostic testing, and therapy for CD and resulted in an increase in reported incidence [14].

PATHOPHYSIOLOGY

Gluten is the general term used for storage proteins considered antigenic in CD. Gluten is a complex macromolecule that is largely indigestible and, under normal circumstances, left partly unabsorbed by the GI tract [17]. The gluten in wheat, rye, and barley is toxic to the intestinal epithelial cells of genetically susceptible individuals [18]. Specifically, the alcohol-soluble protein fraction (prolamins) of gliadin in wheat (secalin in rye, hordein in barley) is responsible for initiating the intestinal damage typical of CD [19]. Exactly how gliadin is able to cross the intestinal epithelial barrier is not clear.

Celiac disease originates as a result of a combined action that involves both adaptive and innate immunity [17,20]. Four presentations are recognized (Table 1) [17,20]:

  • Typical: GI signs and symptoms

  • Atypical (extraintestinal): Minimal or absent GI signs/symptoms, but a number of other manifestations

  • Silent: Damaged small intestinal mucosa and no symptoms, but disease can be detected by serology

  • Latent: Individual possesses genetic compatibility and may show positive autoimmune serology but normal mucosa, with or without symptoms

CLASSIFICATION OF CELIAC DISEASEa

Type

Serology

(tTG and/or EMA)

Age Most Often AffectedSymptomsPathology
TypicalPositiveToddler, young childAbdominal pain, distention, diarrhea, vomiting, anorexia, constipationMarsh 2–3
AtypicalPositiveOlder child, adultMostly extraintestinalMarsh 1–3
SilentPositiveAdultNoneMarsh 1–3
LatentPositive or negativeAdultNone, gastrointestinal, extraintestinal
Marsh 0–1
(previous or future gluten enteropathy)
PotentialPositiveAny ageNone, gastrointestinal, extraintestinalMarsh 0–1
aIn all cases, genetic asset is HLA-DQ2 and/or HLA-DQ8. EMA = endomysial antibody, tTG = tissue transglutaminase.

CD primarily affects the mucosal layer of the small intestine, where a cascade of immune events leads to changes that can be documented by histology [17]. Three distinctive histological stages, termed the Marsh classification, have been described [17,21]:

  • Type 0 or preinfiltrative stage (normal)

  • Type 1 or infiltrative lesion (increased intraepithelial lymphocytes)

  • Type 2 or hyperplastic lesion (type 1 plus hyperplastic crypts)

  • Type 3 or destructive lesion (type 2 plus villous atrophy of progressively more severe degrees)

Destruction of mucosal cells instigates inflammation. Water and electrolytes are secreted, causing diarrhea. Potassium loss leads to muscle weakness. Magnesium and calcium malabsorption can cause seizures or tetany [18]. Unabsorbed fatty acids combine with calcium, and secondary hyperparathyroidism increases phosphorus excretion, resulting in bone reabsorption. Calcium is no longer available to bind oxalate in the intestine and is absorbed, producing hyperoxaluria [22]. The function of the gallbladder may be abnormal, and bile salt conjugation may be decreased [18]. Vitamin K malabsorption leads to hypoprothrombinemia. In one-third of cases, iron and folic acid malabsorption is manifested as cheilosis, anemia, and a smooth, red tongue. Vitamin B12 absorption is impaired in those with extensive ileal disease, and folate and iron deficiencies are common [18]. Failure to thrive is noted, and hypotonia is common [23]. Extraintestinal manifestations of CD include dermatitis herpetiformis, dental enamel hypoplasia, aphthous ulcers, delayed tooth eruption, and arthritis/arthralgia [17].

RISK FACTORS

As noted, the single most important risk factor for CD is having a first- or second-degree relative (particularly a sibling) in whom the disease is already defined. An incidence of up to 20% has been noted in this population. The risk is greater in families in whom two siblings are affected, especially if one is a man who carries HLA-DQ2 [24]. The presence of another autoimmune disorder (e.g., thyroid disease, type 1 diabetes) may also increase the risk of developing CD [3]. Women appear to be at greater risk than men [25]. Other environmental factors include a high number of gastrointestinal infections before 6 months of age and frequent rotavirus infections in children younger than 4 years of age [100].

Evidence is emerging that early (<3 months of age) or late (>7 months of age) first exposure to gluten may favor the onset of CD in infants predisposed to the disease [26]. Some studies show a protective effect of breastfeeding, while other studies show no effect [27]. Although no studies have shown a long-term preventive effect, researchers agree that it is reasonable to recommend introducing gluten in small amounts between 4 and 6 months of age, while breastfeeding, and that breastfeeding be continued for a minimum of an additional 2 to 3 months [27]. Future studies, such as the European multicenter study Prevent CD, may help clarify the association between infant nutrition and the risk of developing CD [28].

DIAGNOSIS

The American Gastroenterological Association recommends diagnostic testing for CD only for symptomatic patients at high risk, with high risk defined as a premature onset of osteoporosis or unexplained elevations in liver transaminase levels or iron-deficient anemia [101]. In addition, the Association notes that testing should be selectively considered for individuals with another autoimmune disease known to be associated with celiac disease or who have a family history of the disease [102].

The differential diagnosis of celiac disease involves the exclusion of several conditions with similar characteristics, including anorexia nervosa, bacterial overgrowth, Crohn's disease, and intestinal lymphoma [103]. Irritable bowel syndrome has been diagnosed before the detection of celiac disease in as many as 36% of individuals [103].

There is no one universally accepted diagnostic standard, and the diagnosis of celiac disease should be made on the basis of several factors, including the findings of the history and physical examination, serologic testing, and biopsy of the small intestine [104]. Diagnostic testing should be done while the patient's diet includes foods that contain gluten.

CLINICAL SIGNS AND SYMPTOMS

Adults with CD commonly present with weight loss, diarrhea, lassitude, and anemia. Very young children (9 to 24 months of age) often present with failure to thrive, vomiting, chronic diarrhea, muscle wasting, anorexia, abdominal distension, and irritability. Symptoms may begin at various times after the introduction of gluten-containing foods. Older children present with nausea, recurrent abdominal pain, bloating, constipation, and intermittent diarrhea [17]. Other symptoms in both children and adults may include itchy skin rash, headache, depression, and bone and/or joint pain [3,29]. Symptoms may vary widely from patient to patient; some patients are asymptomatic or minimally symptomatic, especially older children and adults [17]. Many symptoms of CD mimic those of other diseases, leading to a high rate of misdiagnosis [30]. Dermatitis herpetiformis may be an extraintestinal manifestation of gluten-sensitive enteropathy, manifesting as a pruritic, blistering rash [29]. The reversible nature of CD makes prompt diagnosis important [31].

SEROLOGIC MARKERS

Three antibodies commonly appear in patients with CD: antibodies to tissue transglutaminase (tTG), antiendomysial antibodies, and antigliadin antibodies. The American Gastroenterological Association and the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommend using serologic markers to screen patients with either nonspecific symptoms of CD or medical conditions that increase the risk of CD; small intestinal biopsy should be performed to confirm the diagnosis [31]. The ESPGHAN recommends foregoing the confirmatory duodenal biopsy in selected cases of children and adolescents to reduce the burden on patients and their families [32].

Four serum antibody assays can help to identify candidates for biopsy [31]:

  • Immunoglobulin A anti-tissue transglutaminase (IgA anti-tTG)

  • IgA endomysial antibody (IgA EMA)

  • IgA antigliadin antibody (IgA AGA)

  • IgG antigliadin antibody (IgG AGA)

The IgA EMA assay is the best serologic test for CD, with a sensitivity of 97% to 100% and a specificity of 98% to 99%. Because 2% to 3% of individuals with CD have selective IgA deficiency, IgA levels should be measured. The IgA tTG assay has a sensitivity and specificity of 95% and 94%, respectively [29]. No statistically significant difference has been found between IgA EMA and IgA tTG. The IgA AGA assay has a reported sensitivity of 80% to 90% and a specificity of 85% to 95%. The IgG AGA has a reported sensitivity and specificity of 80% [31].

Routine full blood count, urea and electrolytes, liver function tests, serum iron or ferritin, folate or red blood cell folate, and vitamin B12 should also be measured at initial diagnosis [29].

INTESTINAL BIOPSY

Esophagogastroduodenoscopy (EGD) with duodenal biopsy is considered the gold standard for the diagnosis of CD. During EGD, a small flexible endoscope is introduced through the mouth or nose and advanced through the pharynx, esophagus, stomach, and duodenum. Most endoscopes use a video chip, which provides the best imaging. Moderate sedation and topical anesthesia are used in the United States to ensure patient comfort and cooperation. Benzodiazepines (e.g., midazolam, diazepam) and opioids (e.g., meperidine, fentanyl) are the most commonly used sedative agents. EGD is contraindicated in patients who are medically unstable or unwilling. Possible complications (occurring in 1 in 1000 procedures) include bleeding, infection, perforation, and cardiopulmonary problems caused by the sedation agent [33,34]. Diagnostic criteria include abnormal small intestinal mucosa, usually accompanied by increased intraepithelial lymphocytosis, followed by objective clinical response and unequivocal improvement in villous architecture on a gluten-free diet [29,35]. Experts recommend that six biopsy samples be obtained from the distal and proximal areas of the small intestine to protect against missed diagnoses. In the past, repeat biopsy was the standard of care, but this is now often avoided [29].

The histological lesions characteristic of CD may be missed in some cases, even with multiple duodenal biopsies [36,37]. Also, some patients with clinical presentation highly suggestive of CD may have a normal EGD and nondiagnostic biopsy [33]. These patients may benefit from video capsule endoscopy (VCE). VCE, also referred to as physiologic endoscopy, is a noninvasive procedure that provides high-resolution magnified views of the small intestinal mucosa, with a reported sensitivity of 76% to 99% and specificity of 56% to 100% [38]. It is mainly used to evaluate patients with CD in whom the disease course after diagnosis has been unfavorable and a diagnosis of adenocarcinoma, lymphoma, or refractory CD is suspected [29,35]. Other indications for the use of VCE include iron-deficiency anemia, chronic diarrhea, and abdominal pain due to suspected Crohn's disease [35]. No well-designed trial has tested for noninferiority or equivalence between VCE and EGD with biopsy [35].

OTHER TESTING

Some argue that small intestine biopsy can, under certain circumstances, be replaced by serology testing. Positive CD serology has been linked to an increase in mortality rates; however, the predictive value and long-term consequences of CD serology in individuals with normal mucosa are unknown [39]. Additional tests to confirm the diagnosis of CD may include [16]:

  • Malabsorption studies

  • Glucose tolerance test: Demonstrates poor absorption of glucose

  • D-xylose tolerance test: Demonstrates low urine and blood levels of xylose (<3 grams over 5-hour period); the presence of renal failure may contribute to a false-positive result

  • Serum carotene levels: Measure absorption; low levels indicate malabsorption

  • Stool analysis: Analyzed for fat and pancreatic function; done to rule out cystic fibrosis

  • Barium studies of the small bowel: Show protracted barium passage; barium shows up in a segmented, coarse, scattered, clumped pattern; jejunum shows generalized dilatation

  • Hemoglobin, hematocrit, leukocyte, and platelet counts: Low levels indicative of possible CD

  • Albumin, sodium, potassium, cholesterol, and phospholipid levels: May be reduced with CD

  • Prothrombin (PT) times: Diminished in patients with CD

SCREENING

Screening for CD is not routinely performed in the United States; however, it is recommended for first-degree relatives of individuals with the disease. Four to twelve percent of an affected individual's first-degree relatives will also have the disease [40].

COMORBIDITIES AND COMPLICATIONS OF CELIAC DISEASE

Two theories have been proposed to explain the association between CD and other autoimmune disorders [41]. The first suggests that untreated CD leads to the onset of another disorder in genetically susceptible individuals. This theory is supported by the prevalence of autoimmune disorders in patients with CD in relation to the duration of gluten exposure and by an increased prevalence of comorbid autoimmune disorders in first-degree relatives of individuals with CD [42,43,44]. The second theory suggests that the association is secondary to a more frequent than expected, simultaneous occurrence of genes that predispose individuals for both the autoimmune disorder and CD [41]. Authors of one study screened for the presence of autoimmune disorders in 605 healthy controls and 422 patients with CD. Both groups included individuals 16 to 84 years of age who had been on a gluten-free diet for at least one year. A three-fold higher prevalence of autoimmunity was found in patients with CD as compared to the controls [45]. The autoimmune disorders associated with CD were both organ-specific (e.g., type 1 diabetes, thyroid disease) and nonorgan-specific (e.g., rheumatoid arthritis) [41].

TYPE 1 DIABETES

CD is one of the most frequent autoimmune disorders co-occurring in patients with type 1 diabetes. The prevalence of CD is 8 times higher in patients with type 1 diabetes than in the general population. The prevalence varies from 3% to 16%, with a mean prevalence of 8% worldwide, as confirmed by duodenal biopsy [17,46].

The close association between CD and type 1 diabetes may be due to the same HLA pattern, specifically HLA-DQ2 and/or HLA-DQ8, which predisposes individuals to both disorders. Consumption of gluten may also be a causative factor, and undiagnosed CD may favor the onset of type 1 diabetes [46]. Because symptoms (e.g., bloating, diarrhea) of the two disorders are similar, diagnosis of CD may be missed unless screening is performed [17].

THYROID DISEASE

Hashimoto thyroiditis is the most common type of thyroid disease and involves inflammation and eventual destruction and fibrosis of the thyroid gland, resulting in hypothyroidism [3,47]. The prevalence of CD in individuals with Hashimoto thyroiditis is estimated to be 3% to 7% [3,45].

Graves' disease, though rare, is the most common cause of hyperthyroidism in the United States. One large study confirmed the presence of CD in 4.5% of adults with Graves' disease [3].

The prevalence of CD has invariably been higher in patients with autoimmune thyroid diseases than in controls [48,49,50,51]. Adherence to a gluten-free diet has occasionally been reported to result in improvement in thyroid disease management after the detection and treatment of comorbid CD [52]. Therefore, individuals with autoimmune thyroid disorders should be screened and tested for CD [3].

DOWN SYNDROME

Approximately 8% to 12% of individuals with Down syndrome also suffer from CD [17]. This is largely because individuals with Down syndrome are at higher risk of developing autoimmune diseases than the general population [3,53]. Two-thirds of individuals with Down syndrome who have CD have some GI symptoms (e.g., abdominal bloating, anorexia) [17]. Children with Down syndrome should be screened for CD, as prompt treatment can improve quality of life [54].

DERMATITIS HERPETIFORMIS

Dermatitis herpetiformis is a severe, itchy, blistering skin manifestation of CD. It affects men more frequently than women and generally presents in adults 20 to 55 years of age. It may occur in children, although this is uncommon. Approximately 80% of individuals with dermatitis herpetiformis have some degree of villous atrophy, and approximately 20% have intestinal symptoms of CD. A small percentage of patients with CD will develop dermatitis herpetiformis despite adherence to a gluten-free diet [3].

DEPRESSION

Depression is present in a higher percentage of patients with CD than in the general population. A combination of factors (e.g., genetic, psychological, environmental) can cause depression in patients with CD. Some studies have suggested that depression in individuals with CD is the result of a connection between brain functions and the malabsorption of vitamins, minerals, and other essential nutrients [3]. Other studies attribute the association between depression and CD to the real and perceived social, emotional, and physical demands of adhering to a gluten-free diet and living with a chronic illness [55,56]. One year of adherence to a gluten-free diet fails to significantly affect depressive symptoms, suggesting that these patients need psychological support [57,58].

AUTISM

Autism is a developmental neurological disorder that impacts the functioning and development of the brain [3]. The causes of autism remain unclear but are thought to include psychological, physiological, and sociological factors [16]. Studies have found that the opiates in gluten and casein are released even when the gluten and casein are only partially digested [3]. When the GI tract is not functioning properly, as with CD, the opiates are released into the bloodstream, where they impair brain function (worsening autism symptoms) and produce cravings for gluten- and casein-containing foods, perpetuating the problem. Although trial periods on diets that are gluten- and casein-free have demonstrated improvements in behavior and functioning in children with autism, no direct link between CD and autism has been established [3].

INFERTILITY

Several studies have examined the link between CD and infertility and found that women suffering from unexplained infertility may have silent CD with minimal or no symptoms [59,60]. The prevalence of CD in women reporting infertility is estimated to be 2.5% to 3.5% higher than in the general population [59]. Celiac disease also represents a risk for recurrent spontaneous abortion, low-birth-weight infants, and short breastfeeding duration. The malabsorption of folic acid and other nutrients resulting from CD may explain the unfavorable outcomes of pregnancy; however, additional research is required [59,60]. Men with CD have demonstrated gonadal dysfunction, which may contribute to fertility complications. Patients presenting with unexplained infertility or recurrent spontaneous abortion should be screened for CD [3].

INTESTINAL CANCER

Celiac disease is associated with intestinal lymphoma and other forms of cancer, especially adenocarcinoma of the small intestine, pharynx, and esophagus. Enteropathy-associated T-cell lymphoma is a rare form of high-grade non-Hodgkin lymphoma of the upper small intestine that is specifically associated with CD [61]. A significant increase in the incidence of enteropathy-associated T-cell lymphoma has been noted in the United States that correlates to the increase in CD diagnoses [62]. Long duration or undiagnosed or silent CD appears to increase the risk of cancer of the small intestine. Adherence to a gluten-free diet for several years can lower the risk of lymphoma for patients with CD, especially when started early [61].

MIGRAINE

An association between migraine and CD has been reported. A 2003 study found that migraine sufferers have a higher risk of CD than the general population [63]. Of the 90 migraine patients included in the study, 4.4% were found to have CD compared with 0.4% of the controls. During a six-month gluten-free diet, those with CD experienced an improvement in frequency, duration, and intensity of migraine.

A study published in 2011 included 100 children with migraine headache (classified according to criteria of the International Headache Society) [64]. Serum total IgA and anti-tTGA antibodies were measured. Duodenal biopsy was performed to confirm CD in children with positive serologic results. Researchers found the same prevalence (2%) of positive serologic results for CD in both groups.

A study published in 2013 included 502 subjects: 188 with CD, 111 with inflammatory bowel disease, 25 with gluten sensitivity, and 178 controls [64]. Thirty percent of the subjects with CD reported chronic headaches; 72% of these patients graded their migraines as severe in impact. The study authors recommend screening migraine patients for CD.

OSTEOPOROSIS/OSTEOPENIA

Osteoporosis can be a complication of untreated CD [65]. A variety of factors contribute to the risk of osteoporosis in the individual with CD, including individual body composition (e.g., thinness, small frame), vitamin D deficiency, malabsorption of calcium and magnesium (leading to low bone density and fracture risk), and inflammation.

Calcium metabolism defects are common in children with untreated CD and return to normal after initiation of a gluten-free diet [66]. Studies have described a 35% to 85% prevalence of osteoporosis among children with untreated CD.

A study published in 2012 measured bone mineral density (BMD) in 35 adult CD patients (19 receiving a gluten-free diet, 16 not) and 36 controls [67]. The CD patients also received calcium and a vitamin D analog daily for one year. Reduced BMD was diagnosed in 57% to 77% of the patients with CD. Patients on the gluten-free diet had higher BMD than those not on the diet but lower BMD than the controls. In this study, a gluten-free diet increased BMD in patients with CD.

TURNER SYNDROME

Turner syndrome is a chromosomal condition that affects only girls and commonly results in short stature and lack of sexual development at puberty [3]. The prevalence of CD in girls with Turner syndrome is estimated to be 2% to 8%, much higher than in the general population [3,68]. The National Foundation for Celiac Awareness recommends that girls with Turner syndrome be tested for CD [3].

JUVENILE IDIOPATHIC ARTHRITIS

Juvenile idiopathic arthritis is the most common form of arthritis in children. The cause is poorly understood but is believed to be related to both genetic and environmental factors. Symptoms include joint inflammation, contracture, and alteration or change in growth. The estimated prevalence of CD in children with juvenile idiopathic arthritis is 1.5% to 6.6%. As with CD and other autoimmune diseases, the onset of juvenile idiopathic arthritis usually occurs before CD is diagnosed [3].

PERIPHERAL NEUROPATHY

Peripheral neuropathy is one of the most frequently reported neurologic manifestations of CD. An estimated 5% of patients with peripheral neuropathy have CD. Common symptoms include severe burning, stinging, and electric shock-type pain. Adherence to a gluten-free diet is the recommended treatment, but there is data that indicates that neurologic manifestations may persist independent of gluten exposure [69,70].

LIVER DISEASE

The disease-causing mechanism of liver damage in celiac patients is poorly understood, and the spectrum of liver abnormalities associated with CD is wide [71]. The most frequent occurrence, present in approximately 50% of untreated CD patients, expresses as mild liver impairment (i.e., celiac hepatitis), which reverts to normal after a few months of gluten withdrawal [71,72]. More severe liver injury (chronic hepatitis or liver cirrhosis) presents in only a few cases of patients with CD and may improve after gluten withdrawal. Autoimmune liver dysfunction is rare and usually does not improve after gluten withdrawal [71].

SJÖGREN SYNDROME

Sjögren syndrome is a slowly progressing autoimmune disease characterized by dry eyes and dry mouth [73]. Although the pathogenesis of the disease is poorly understood, environmental, genetic, and hormonal factors appear to be involved. Sjögren syndrome has been reported in up to 15% of patients with biopsy proven CD [74].

WILLIAMS SYNDROME

Williams syndrome is a rare congenital disorder occurring in 1 in 20,000 live births [3]. The prevalence of Williams syndrome in patients with CD is comparable to that reported in Down syndrome and Turner syndrome [75]. The association between Williams syndrome and CD is poorly understood.

MANAGEMENT

THE GLUTEN-FREE DIET

A strict, lifelong gluten-free diet and supportive nutritional care (for iron, calcium, and vitamin deficiencies) is the only recommended treatment for CD [85,86,87]. Adherence to a gluten-free diet improves health and quality of life in the majority of patients. However, an estimated 2% to 5% of patients with CD develop refractory disease, a serious complication associated with a 50% risk of developing lymphoma. The gluten-free diet does help prevent malignant complications such as lymphoma and small bowel adenocarcinoma in these patients [85,87,88].

Medical nutrition therapy provided by a registered dietitian as part of a team-based approach is strongly recommended for the individual with CD. The dietitian can assess the individual's food- and nutrition-related history (e.g., intake, medication/supplement use, patient knowledge/willingness to change behaviors) to effectively determine nutritional needs and appropriate dietary interventions [89]. Research on individuals with CD reports that long-term compliance with a gluten-free diet improves outcomes related to bone density, iron-deficiency anemia, villous atrophy, GI and neurological symptoms, pregnancy outcomes, and quality of life [89].

Adherence to a gluten-free dietary pattern involves all foods containing or derived from wheat, barley, and rye (Table 2). This may result in a diet that is low in carbohydrates, iron, folate, niacin, zinc, and fiber. Individuals with CD often suffer from malabsorption and can develop vitamin and mineral deficiencies despite adequate intake. Age-specific gluten-free vitamin and mineral supplements are an important addition to the diets of persons with CD [89]. Iron supplements are recommended for iron-deficiency anemia, and folic acid and vitamin B12 should be taken to avoid anemia due to folate or B12 deficiencies. Vitamin K is necessary for individuals with abnormal PT times. Calcium and vitamin D supplements should be encouraged for individuals with low blood calcium levels or osteoporosis.

GLUTEN IN FOODS

Acceptable

Use Caution (May Contain Gluten)

Avoid
Brown rice, corn, flax, Montina, millet, sorghum, teff, wild rice, amaranth, buckwheat, quinoa, arrowroot, bean flours, black-eyed peas, legumes, lentils, lima beans, mesquite, Northern beans, nuts, pinto beans, potato flour/starch, soy, tapioca, gluten-free oatsaImitation seafood, marinades, processed meats, sauces and gravies, broth, candy, coating mixes, meat substitutes, soy sauce, thickeners, imitation bacon, croutonsBarley, einkorn, malt vinegar, bulgar, farina, malt/malt flavoring, couscous, faro, cracked wheat, graham, matzo, durum, Khorasan wheat (Kamut), seitan, semolina, spelt, triticale, wheat, wheat germ, wheat starch
aIndividuals who can tolerate may gradually include in the diet (approximately 50 g dry oats/daily).

The treatment of celiac disease also includes the management of complications. Dapsone can be used to treat dermatitis herpetiformis until the gluten-free diet has had effect; the drug typically relieves symptoms within 1 to 3 days [110]. Because of the potential for dapsone to cause hemolysis in some individuals, a baseline blood count and periodic follow-up testing are recommended [110]. The use of bisphosphonates for osteoporosis may be appropriate, although their use for osteoporosis related to celiac disease has not been studied extensively [104].

THERAPEUTIC ALTERNATIVES

Adherence to a gluten-free diet can be difficult to sustain due to gluten cross-contamination in food products, higher costs and limited availability of gluten-free products, lower palatability (resulting in low compliance), and cultural practices [85,87,90]. Therapeutic alternatives have been developed to reduce the need for a gluten-free diet based on available insights into the pathogenesis of the disease (Table 3). Clinical trials for some of these alternative therapies are ongoing, and none are widely recommended as of 2013 [85,91].

POTENTIAL ALTERNATIVE THERAPIES FOR PATIENTS WITH CELIAC DISEASE

Therapeutic Aim Therapies
Decrease Gluten Exposure
Manipulation or selection of dietary components
Engineer gluten-free grains
Polymeric gliadin binders and neutralizers
Enzymatic degradation of gluten
Aspergillus niger-derived prolyl endopeptidase
ALV003 enzyme cocktail
Probiotics
Inhibit Intestinal Permeability
Zonulin inhibitionLarazotide acetate
Modulate the Immune Response
Decrease adaptive immune activity
Block transglutaminase 2 (TG2) antibodies
Block antigen presentation by HLA-DQ2 and HLA-DQ8
Induce oral tolerance to glutenGluten peptide vaccine

REFRACTORY CELIAC DISEASE

Refractory CD is a malabsorption syndrome defined by villous atrophy and usually an increase of intraepithelial lymphocytes in the small bowel despite strict adherence to a gluten-free diet [76]. The real prevalence of refractory CD is unknown but likely rare; however, it may be the cause of underlying persistent or recurrent symptoms in 10% to 18% of patients treated for CD. It affects two to three times more women than men [77]. Common symptoms include persistent diarrhea, abdominal pain, and involuntary weight loss. Vitamin deficiencies, anemia, fatigue, and malaise are also frequent. Refractory CD is most often diagnosed following development of new symptoms or recurrence of diarrhea after initial clinical response to a gluten-free diet for years.

Aggressive nutritional support is an important component of the treatment of refractory CD. Total parenteral nutrition is frequently necessary [76,78,79]. Correction of trace element deficiencies (e.g., zinc, copper) should also be included. Strict adherence to a gluten-free diet is widely recommended [78,79,80]. Depending on the severity of refractory CD, alternative therapies may include prednisone, budesonide, or a combination of prednisone and azathioprine to induce clinical remission and recovery of mucosa [78,80,81,82,83,84].

FOLLOW-UP

The American Dietetic Association recommends that nutrition therapy be coordinated with a team of clinical professionals (e.g., gastroenterologists, endocrinologists, allergists), depending on the coexisting condition(s) of the individual with CD. Follow-up measures should include: monitoring and evaluation of patient compliance with the gluten-free dietary pattern, evaluation of any persistent GI symptoms, and evaluation of factors affecting the individual's quality of life (e.g., social/medical support, daily stress level) [89]. A survey to assess dietary compliance has been proposed for use in adults [92]. Follow-up measures for the child with CD should also include an assessment of the adequacy of growth and well-being [17].

Healthcare professionals should ensure that patients and their families have the resources, education, motivation, and support to comply with a gluten-free diet. Serologic testing should be done to monitor compliance with a gluten-free diet; strict adherence usually leads to antibody levels becoming normal within 3 to 12 months after starting the diet [104]. A lack of response according to serologic testing may indicate continued exposure to gluten; if the patient has been adhering to the gluten-free diet, the clinician should explore other diagnoses. Among other diseases that appear similar to celiac disease are microscopic colitis, pancreatic insufficiency, inflammatory bowel disease, ulcerative jejunoileitis, collagenous sprue, and T-cell lymphoma [104].

CD is associated with a risk of non-Hodgkin's lymphoma that is three to six times higher than for the general population, and the risk for lymphoma is higher for individuals in whom CD is diagnosed later in adulthood [105,106]. Data have suggested that the risk of lymphoma decreases over time on a strict gluten-free diet [107]. New GI symptoms or other signs of lymphoma should prompt further evaluation. Studies have indicated that the risk of other gastrointestinal malignancies, such as esophageal, gastric, and colorectal cancer, is not increased among individuals with CD [105,108,109].

EDUCATION AND SUPPORT

Healthcare practitioners who treat the individual with CD should be knowledgeable about the importance of a gluten-free diet and should understand the factors (e.g., cost concerns, social stress, feelings of isolation) that contribute to patient noncompliance [93]. Individuals with CD require ongoing education and support that address the physical and psychological concerns associated with the disease [94]. Sources of gluten may be difficult to detect. Dining at a restaurant or friend's home, attending social gatherings at which food is served, and routine grocery shopping can be stressful events if the individual is not equipped with appropriate management strategies. Patient education should include information about how to create and maintain a gluten-free lifestyle for both adults and children with CD (Table 4).

TIPS FOR MAINTAINING A GLUTEN-FREE LIFESTYLE

Location Possible Gluten Source Action Comments
Kitchen,
market/grocery store
Foods (e.g., butter, margarine, mayonnaise, mustards, jams, jellies, peanut butter)
Utensils
Appliances
Dedicate storage for bulk items.
Dedicate freezer space.
Label foods or ensure kitchen is gluten free.
Purchase dedicated cooking appliances, utensils.
Learn to read labels.
Look for products labeled as "gluten free."
Avoid foods made with wheat, rye, and barley.
Avoid oats; long-term safety is unknown.
Avoid processed foods, beer, milk/dairy products with lactose.
Use caution when purchasing products labeled "gluten free."a
Bathroom
Cabinets
Medications
Shampoos, soaps, cosmetics
Toothpaste, mouthwash
Call or check website of product manufacturer.
Check with pharmacist and/or pharmaceutical company to ensure medications are gluten free.
Tablets, capsules and vitamins may contain gluten; wheat starch is commonly employed as binding agent.
Gluten is used in some cosmetics, but this is generally an issue only if the product is ingested (e.g., lipstick).
Office
Postage stamps
Envelopes
Stickers
Use wet sponges or self-stick stamps and envelopes.
PlayroomPlay dough, glue, paint, stickers, paper mâchéCall or check website of product manufacturer.
School, daycare, play dates
Cafeteria
Sharing lunches
Birthday parties
Art supplies
Meet with teacher and school nurse.
Provide child with bag lunch.
Work with cafeteria staff to develop gluten-free options.
Provide child with gluten-free treats.
Many schools accommodate children under 504 plans (part of the Rehabilitation Act and the Americans with Disabilities Act).
Restaurants
Difficulty finding gluten-free items on the menu
Possible cross-contamination during meal preparation (e.g., the deep fryer)
Call or visit restaurant ahead of time.
Avoid busy times.
Plan ahead when traveling.
Many restaurants offer gluten-free menu options.
Church
Communion wafers
Church socials
Discuss with minister, priest, or church leader.
aEffective August 2014, the U.S. Food and Drug Administration requires that any food labeled "gluten free" contain less than 20 ppm of gluten.

Individuals with CD and their families should be encouraged to participate in CD support and advocacy groups. They also should be encouraged to seek healthcare practitioners who provide supportive patient-centered care and who understand the daily stresses associated with maintaining a gluten-free lifestyle [96]. Healthcare practitioners should be knowledgeable about the coping strategies used by the patient with CD and should assess the impact of these strategies on the individual's quality of life [95,94,99].

CASE STUDY

T is a girl, 7 years of age, who presents to her pediatrician, Dr. G, with complaints of fatigue, abdominal cramping, and diarrhea. T weighed eight pounds, three ounces at birth, and her growth and development have been consistent and appropriate. She has no pre-existing conditions and is current on all of her immunizations.

T is afebrile and her vital signs are within normal limits. A diagnosis of viral gastritis is made. Dr. G advises T's mother (Mrs. H) to limit her daughter's diet to bland foods and give the symptoms time to run their course. Mrs. H is advised to call if symptoms do not improve.

At home, T rests and consumes chicken broth and gelatin. After three days, she is feeling better and ready to return to school. At school the next day, T lunches at 11:30 a.m. on tomato soup, a grilled cheese sandwich, and mixed fruit. T is feeling tired but otherwise well. She consumes all of her soup and fruit, but only a few bites of the sandwich. Around 1:00 p.m., T complains to her teacher of stomach cramping and asks to go to the restroom.

Mrs. H picks T up from school at 3:00 p.m.; T continues to experience stomach cramping and tells her mother that she has had three episodes of diarrhea that day. When she arrives home, T consumes nothing but gelatin and ginger ale and spends the rest of the day in bed. Although T feels better the next morning, Mrs. H keeps her at home and in bed and continues to give T only gelatin, chicken broth, and ginger ale. For the next two weeks, Mrs. H keeps T on a diet of soups and liquids to allow her stomach time to recover. When T appears to be improving, Mrs. H decides to slowly introduce other foods back into her diet.

Within two days, T relapses and experiences diarrhea, bloating, and stomach cramping. Mrs. H schedules a follow-up appointment with Dr. G, who re-evaluates T and discovers that she has lost one pound in body weight and that her stomach is tender to palpation. Dr. G orders additional workup, including blood work, with the following results:

  • Hemoglobin: 10.8 g/dL (Normal range: 11.5–14.5 g/dL)

  • Hematocrit: 34% (Normal range: 35%–42%)

  • Platelets: 225 (Normal range: 250–500)

  • Sodium: 127 mEq/L (Normal range: 136–145 mEq/L)

  • Potassium: 3.3 mEq/L (Normal range: 3.5–5.0 mEq/L)

  • Calcium: 6.9 mg/dL (Normal range: 9.0–11.0 mg/dL)

  • Albumin: 2.6 g/dL (Normal range: 3.5–5.5 g/dL)

Mrs. H and T return to Dr. G's office to review the results of the blood work. T has continued to have spells of diarrhea and stomach pains, and she has lost an additional six ounces. Dr. G suspects that T has CD. He schedules further evaluation and an EGD.

Two weeks later, Mrs. H and T return to Dr. G's office for a consultation. Dr. G explains the study results, which revealed atrophy of intestinal villi. He explains that T is experiencing malabsorption of important nutrients, likely due to an intolerance to wheat, rye, or barley products in the foods she is eating. T is referred to a dietitian, Ms. D, who specializes in pediatric nutrition and CD.

T and her parents meet with Ms. D, who explains that CD is an immunological response to wheat, rye, or barley products that causes destruction of the lining of the small intestine, which in turn causes malabsorption of important nutrients. Ms. D further explains that destruction of the lining leads to diarrhea, fatty stools, weight loss, foul-smelling gas, and iron-deficiency anemia. She reassures the family that, although it sounds frightening, CD is easily controlled with dietary changes and provides the family with a list of foods to avoid as well as sources of "hidden" gluten (e.g., school supplies).

Ms. D works with the family to develop one week's worth of gluten-free meals that T will be willing to eat. They openly and at length discuss challenges that the family may encounter. Ms. D recommends that the family explore a nearby CD support group, which can help them with the adjustments they need to make.

T and her mother return to Dr. G's office for a one-year check-up. T's laboratory tests are normal, and she is slowly gaining weight. Mrs. H reports that T has had some minor episodes of bloating and diarrhea after eating something on the forbidden list when at a friend's house. Dr. G states that T is progressing well and indicates that a few slips in the diet are to be expected, but reminds them that these should not be frequent.

One month later, Mrs. H finds T lying on her bed, crying. Mrs. H asks what is wrong, but T responds that she does not want to talk about it. When Mrs. H persists, T tells her that she was not invited to V's sleepover because V's mother is afraid that T will eat something she should not and get sick. She also reports taunting and feeling left out at school.

Mrs. H calls one of the mothers from the support group to discuss what is happening to T, and the mother provides Mrs. H with some helpful tips. Mrs. H then schedules a meeting with T's teacher to educate him about T's CD and to discuss ways to help lessen the alienation T is feeling. Mrs. H asks him to telephone her if another student's parent plans a celebration so that she can send in a special treat for T. He agrees and promises to be more aware of the way that T is being treated by her classmates.

Later in the week, Mrs. H calls V's mother and invites her to meet for coffee. When they met the next day, Mrs. H explains what celiac disease is and how it is controlled. She tells V's mother that she is not trying to force her to invite T to her home; she simply wants her to know that CD is nothing to fear. V's mother explains that she was not sure she wanted to take the risk of T becoming ill at her home if she ate something she was not supposed to have. Mrs. H responds that T is very knowledgeable about what she can and cannot eat and explains that small amounts of forbidden foods do not cause a severe reaction in T. That evening, V calls and invites T to the sleepover and apologizes for not having invited her sooner.

After the telephone call, Mr. and Mrs. H discussed some of the misconceptions that the school and their community had about CD. They decide to develop an educational program to present to area schools to increase awareness about celiac disease. Six months later, they have presented the program to local schools and received positive responses and many questions. The next year, prior to the start of the school year, the couple is asked to return and present the information again.

T states that her school days improved greatly after the educational programs were presented.

CONCLUSION

Celiac disease is an immune-mediated systemic disorder elicited by gluten in genetically susceptible individuals. It is a costly burden to the U.S. healthcare system and a global health concern, impacting 1% to 3% of the global population and requiring a multidisciplinary approach to care and treatment. The symptoms of CD can mimic those of other autoimmune diseases and may vary widely from one individual to another, making diagnosis difficult. However, because CD is reversible, early diagnosis is important in the management of the disease. Strict adherence to a lifelong gluten-free diet is the only recommended treatment for CD. Ongoing education and support are vital to helping the patient (and family) comply with the dietary pattern.

RESOURCES

Academy of Nutrition and Dietetics
http://www.eatright.org
American Celiac Disease Alliance
http://www.americanceliac.org
Canadian Celiac Association
http://www.celiac.ca
Celiac.com/R.O.C.K. (Raising Our Celiac Kids)
http://www.celiac.com
Celiac Disease Foundation
http://www.celiac.org
Celiac-Disease (Celiac News and Gluten-Free Diet Resources)
http://www.celiac-disease.com
Celiac Sprue Association
http://www.csaceliacs.info
Center for Celiac Research and Treatment
http://www.celiaccenter.org
Gluten-Free Drugs
http://www.glutenfreedrugs.com
Gluten-Free Registry
http://www.glutenfreeregistry.com
Gluten Intolerance Group
http://www.gluten.net
National Digestive Diseases Information Clearinghouse (NDDIC)
http://www.digestive.niddk.nih.gov
National Foundation for Celiac Awareness
http://www.celiaccentral.org
PreventCD
http://www.preventcd.com

Works Cited

1. Rubio-Tapia A, Murray JA. Celiac disease. Curr Opin Gastroenterol. 2010;26(2):116-122.

2. Husby S, Koletzko S, Korponay-Szabo IR, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54(1):136-160.

3. National Foundation for Celiac Awareness. Celiac Disease Facts and Figures. Available at http://www.celiaccentral.org/celiac-disease/facts-and-figures. Last accessed November 7, 2013.

4. Tack GJ, Verbeek WH, Schreurs MW, Mulder CJ. The spectrum of celiac disease: epidemiology, clinical aspects and treatment.Nat Rev Gastroenterol Hepatol. 2010;7(4):204-213.

5. Meize-Grochowski R. Celiac disease: a multisystem autoimmune disorder. Gastroenterol Nurs. 2005;28(5):394-402.

6. Guandalini S. History of celiac disease. Impact Magazine. 2007.

7. Gasbarrini G, Miele L, Corazza GR, Gasbarrini A. When was celiac disease born? The Italian case from the archeologic site of Cosa. J Clin Gastroenterol. 2010;44(7):502-503.

8. Silberberg B. The Autism and ADHD Diet: A Step-by-Step Guide to Hope and Healing by Living Gluten Free and Casein Free (GFCF) and Other Interventions. Naperville, IL: Sourcebooks, Inc.; 2009.

9. Bower SA. What Nurses Know…Gluten-Free Lifestyle. New York, NY: Demos Health; 2011.

10. Chang HJ, Burke AE, Golub RM. Celiac disease. JAMA. 2011;306(14):1614.

11. Fenster C. Food safety in the kitchen. Gluten-Free Living. 2010;(2).

12. Mahadov S, Green PH. Celiac disease: a challenge for all physicians. Gastroenterol Hepatol. 2011;7(8):554-556.

13. Banion C, Valentine V. Type 1 diabetes through the life span. In: Mensing C (ed). The Art and Science of Diabetes Self-Management Education: A Desk Reference for Healthcare Professionals. Chicago, IL: American Association of Diabetes Educators; 2006: 309-340.

14. Smith MM, Goodfellow L. The relationship between quality of life and coping strategies of adults with celiac disease adhering to a gluten-free diet. Gastroenterol Nurs. 2011;34(6):460-468.

15. Muscari ME. Pediatric Nursing. Philadelphia, PA: Lippincott, Williams and Wilkins; 2005.

16. Kowalak JP. Professional Guide to Diseases. 10th ed. Ambler, PA: Lippincott Williams and Wilkins; 2013.

17. Guandalini S. Pediatric Celiac Disease. Available at http://emedicine.medscape.com/article/932104-overview. Last accessed November 7, 2013.

18. Evers DB. Alterations of digestive function in children. In: Huether SE, McCance KL (eds). Understanding Pathophysiology. 3rd ed. St Louis, MO: Mosby; 2007: 1027-1045.

19. McManus R, Kelleher D. Celiac disease: the villain unmasked? N Engl J Med. 2003;348(25):2573-2574.

20. Setty M, Hormaza L, Guandalini S. Celiac disease: risk assessment, diagnosis, and monitoring. Mol Diagn Ther. 2008;12(5):289-298.

21. Marsh MN, Hinde J. Inflammatory component of celiac sprue mucosa. I: mast cells, basophils, and eosinophils. Gastroenterology. 1985;89(1):92-101.

22. Lyn S. Lange Smart Charts Physiology. New York, NY: McGraw-Hill Medical; 2004.

23. Westerfield J, Holcomb S, Jensen S (eds). Current Trends in Diabetes Management: A Guide for the Health Care Professional. 7th ed. Nashville, TN: Healthways; 2008.

24. Freeman HJ. Risk factors in familial forms of celiac disease. World J Gastroenterol. 2010;16(15):1828-1831.

25. MedlinePlus. Celiac Disease: Sprue. Available at http://www.nlm.nih.gov/medlineplus/ency/article/000233.htm. Last accessed November 7, 2013.

26. Guandalini S. The influence of gluten: weaning recommendations for healthy children and children at risk for celiac disease.Nestle Nutr Workshop Ser Pediatr Program. 2007;60:139-151.

27. Szajewska H, Chmielewska A, Piescik-Lech M, et al. Systematic review: early infant feeding and the prevention of coeliac disease. Aliment Pharmacol Ther. 2012;36(7):607-618.

28. Hogen Esch CE, Rosen A, Auricchio R, et al. The PreventCD Study design: towards new strategies for the prevention of coeliac disease. Eur J Gastroenterol Hepatol. 2010;22(12):1424-1430.

29. American Gastroenterological Association. American Gastroenterological Association medical position statement: celiac sprue. Gastroenterology. 2001;120(6):1522-1525.

30. National Digestive Diseases Information Clearinghouse. Celiac Disease. Available at http://digestive.niddk.nih.gov/ddiseases/pubs/celiac/. Last accessed November 7, 2013.

31. Reddick, BK, Crowell K. What blood tests help diagnose celiac disease? J Fam Pract. 2006;55(12):1090, 1093.

32. Husby S, Koletzko S, Korponay-Szabó IR, et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54(1):136-60.

33. Chang MS, Rubin M, Lewis SK, Green PH. Diagnosing celiac disease by video capsule endoscopy (VCE) when esophagogastroduodenoscopy (EGD) and biopsy is unable to provide a diagnosis. BMC Gastroenterol. 2012;12(90).

34. Yusuf TE. Esophagogastroduodenoscopy. Available at http://emedicine.medscape.com/article/1851864-overview. Last accessed November 7, 2013.

35. Cellier C, Green PH, Collin P, Murray J. ICCE consensus for celiac disease. Endoscopy. 2005;37(10):1055-1059.

36. Bonamico M, Thanasi E, Mariani P, et al. Duodenal bulb biopsies in celiac disease: a multicenter study. J Pediatr Gastroenterol Nutr. 2008;47(5):618-622.

37. Lebwohl B, Kapel RC, Neugut AI, Green PH, Genta RM. Adherence to biopsy guidelines increases celiac disease diagnosis. Gastrointest Endosc. 2011;74(1):103-109.

38. Rondonotti E, Spada C, Cave D, et al. Video capsule enteroscopy in the diagnosis of celiac disease: a multicenter study.Am J Gastroenterol. 2007;102(8):1624-1631.

39. Ludvigsson JF, Montgomery SM, Ekhom A, Brandt L, Granath F. Small intestinal histopathology and mortality risk in celiac disease. JAMA. 2009;302(11):1171-1178.

40. Rodrigo L. Celiac disease. World J Gastroenterol. 2006;12(4):6585-6593.

41. Fasano A. Systemic autoimmune disorders in celiac disease. Curr Opin Gastroenterol. 2006;22(6):674-679.

42. Ventura A, Magazzu G, Greco L. Duration of exposure to gluten and risk for autoimmune disorders in patients with celiac disease. SIGEP Study Group for Autoimmune Disorders in Celiac Disease. Gastroenterology. 1999;117:297-303.

43. Not T, Tommasini A, Tonini G, et al. Undiagnosed coeliac disease and risk of autoimmune disorders in subjects with type 1 diabetes mellitus. Diabetologia. 2001;44:151-155.

44. Cataldo F, Marino V. Increased prevalence of autoimmune diseases in first-degree relatives of patients with celiac disease.J Pediatr Gastroenterol Nutr. 2003;36:470-473.

45. Ch'ng CL, Jones MK, Kingham JG. Celiac disease and autoimmune thyroid disease. Clin Med Res. 2007;5(3):184-192.

46. Volta U, Tovoli F, Caio G. Clinical and immunological features of celiac disease in patients with type 1 diabetes mellitus.Expert Rev Gastroenterol Hepatol. 2011;5(4):479-487.

47. Venes D (ed). Taber's Cyclopedic Medical Dictionary. 21st ed. Philadelphia, PA: FA Davis Company; 2009.

48. Kumar V, Rajadhyaksha M, Wortsman J. Celiac disease-associated autoimmune endocrinopathies. Clin Diagn Lab Immunol. 2001;8:678-685.

49. Meloni GF, Tomasi PA, Bertoncelli A, Fanciulli G, Delitala G, Meloni T. Prevalence of silent celiac disease in patients with autoimmune thyroiditis from Northern Sardinia. J Endocrinol Invest. 2001;24:298-302.

50. Volta U, Ravaglia G, Granito A, et al. Coeliac disease in patients with autoimmune thyroiditis. Digestion. 2001;64:61-65.

51. Larizza D, Calcaterra V, De Giacomo C, et al. Celiac disease in children with autoimmune thyroid disease. J Pediatr. 2001;139: 738-740.

52. Collin P, Kaukinen K, Valimaki M, Salmi J. Endocrinological disorders and celiac disease. Endocrine Rev. 2002;23(4):464-483.

53. Carnicer J, Farre C, Varea V, Vilar P, Moreno J, Artigas J. Prevalence of coeliac disease in Down's syndrome. Eur J Gastroenterol Hepatol. 2001;13(3):263-267.

54. Adams S. Down syndrome: celiac disease prevalent in children with Down syndrome. Am J Med Gen. 2001;98:70-74.

55. Fera T, Cascio B, Angelini G, Martini S, Guidetti CS. Affective disorders and quality of life in adult coeliac disease patients on a gluten-free diet. Eur J Gastroenterol Hepatol. 2003;15(12):1287-1292.

56. Hauser W, Gold J, Stein J, Caspary WF, Stallmach A. Health-related quality of life in adult coeliac disease in Germany: results of a national survey. Eur J Gastroenterol Hepatol. 2006;18(7):747-754.

57. Addolorato G, Capristo E, Ghittoni G, et al. Anxiety but not depression decreases in coeliac patients after one-year gluten-free diet: a longitudinal study. Scand J Gastroenterol. 2001;36(5):502-506.

58. Edwards George JB, Leffler DA, Dennis MD, Franko DL, Blom-Hoffman J, Kelly CP. Psychological correlates of gluten-free diet adherence in adults with celiac disease. J Clin Gastroenterol. 2009;43(4):301-306.

59. Pellicano R, Astegiano M, Bruno M, Fagoonee S, Rizzetto M. Women and celiac disease: association with unexplained infertility. Minerva Med. 2007;98(3):217-219.

60. Stazi AV, Trinti B. Reproductive aspects of celiac disease. Ann Ital Med Int. 2005;20(3):143-157.

61. Kumar P. Coeliac disease and lymphoma. Eur J Gastroenterol Heptaol. 2006;18:131-132.

62. Sharaiha RZ, Lebwohl B, Reimers L, Bhagat G, Green PH, Neugut AI. Increasing incidence of enteropathy-associated T-cell lymphoma in the United States, 1973–2008. Cancer. 2012;118(15):3786-3792.

63. Gabrielli M, Cremonini F, Fiore G, et al. Association between migraine and celiac disease: results from a preliminary case-control and therapeutic study. Am J Gastroenterol. 2003;98(3):625-629.

64. Dimitrova AK, Ungaro RC, Lebwohl B, et al. Prevalence of migraine in patients with celiac disease and inflammatory bowel disease. Headache. 2013;53(2):344-355.

65. NIH Osteoporosis and Related Bone Diseases National Resource Center. What People with Celiac Disease Need to Know about Osteoporosis. Available at http://www.niams.nih.gov/Health_Info/Bone/Osteoporosis/Conditions_Behaviors/celiac.asp. Last accessed November 7, 2013.

66. Zanchi C, Di Leo G, Ronfani L, Martelossi S, Not T, Ventura A. Bone metabolism in celiac disease. J Pediatr. 2008;153(2): 262-265.

67. Szymczak J, Bohdanowicz-Pawlak A, Waszczuk E, Jakubowska J. Low bone mineral density in adult patients with coeliac disease. Endokrynol Pol. 2012;63(4):270-276.

68. Bonamica M, Pasquino AM, Mariani P, et al. Prevalence and clinical picture of celiac disease in Turner syndrome. J Clin Endocrinol Metab. 2002;87(12):5495-5498.

69. Chin RL, Latov N. Peripheral neuropathy and celiac disease. Curr Treat Options Neurol. 2005;7(1):43-48.

70. Brannagan TH 3rd, Hays AP, Chin SS, et al. Small-fiber neuropathy/neuronopathy associated with celiac disease: skin biopsy findings. Arch Neurol. 2005;62(10):1574-1578.

71. Volta U. Liver dysfunction in celiac disease. Minerva Med. 2008;99(6):619-629.

72. Rubio-Tapia A, Murray JA. Liver involvement in celiac disease. Minerva Med. 2008;99(6):595-604.

73. Mavragani CP, Moutsopoulos HM. The geoepidemiology of Sjögren's syndrome. Autoimmun Rev. 2010;9(5):A305-A310.

74. Luft LM, Barr SG, Martin LO, Chan EK, Fritzler MJ. Autoantibodies to tissue transglutaminase in Sjögren's syndrome and related rheumatic diseases. J Rheumatol. 2003;30(12):2613-2619.

75. Giannotti A, Tiberio G, Castro M, et al. Coeliac disease in Williams syndrome. J Med Genet. 2001;38(11):767-768.

76. Daum S, Cellier C, Mulder CJ. Refractory coeliac disease. Best Pract Res Clin Gastroenterol. 2005;19(3):413-424.

77. Rubio-Tapia A, Murray JA. Classification and management of refractory celiac disease. Gut. 2010;59(4):547-557.

78. Malamut G, Afchain P, Verkarre V, et al. Presentation and long-term follow-up of refractory celiac disease: comparison of type I with type II. Gastroenterology. 2009;136(1):81-90.

79. Rubio-Tapia A, Kelly DG, Lahr BD, Dogan A, Wu TT, Murray JA. Clinical staging and survival in refractory celiac disease: a single center experience. Gastroenterology. 2009;136(1):99-107.

80. Al-Toma A, Verbeek WH, Hadithi M, von Blomberg BM, Mulder CJ. Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: retrospective evaluation of single-centre experience. Gut. 2007;56(10):1373-1378.

81. Brar P, Lee S, Lewis S, et al. Budesonide in the treatment of refractory celiac disease. Am J Gastroenterol. 2007;102(10): 2265-2269.

82. Cellier C, Cerf-Bensussan N. Treatment of clonal refractory celiac disease or cryptic intraepithelial lymphoma: a long road from bench to bedside. Clin Gastroenterol Hepatol. 2006;4(11):1320-1321.

83. Goerres MS, Meijer JW, Whaab PJ, et al. Azathioprine and prednisone combination therapy in refractory coeliac disease.Aliment Pharmacol Ther. 2003;18(5):487-494.

84. Daum S, Ipczynski R, Heine B, Schulzke JD, Zeitz M, Ulrich R. Therapy with budesonide in patients with refractory sprue. Digestion. 2006;73(1):60-68.

85. Tack GJ, Verbeek, WHM, Schreurs MWJ, Mulder CJJ. The spectrum of celiac disease: epidemiology, clinical aspects and treatment. Nat Rev Gastroenterol Hepatol. 2010;(4):204-213.

86. Bakshi A, Stephen S, Borum ML, Doman DB. Emerging therapeutic options for celiac disease: potential alternatives to a gluten-free diet. Gastroenterol Heptaol (NY). 2012;8(9):528-588.

87. McAllister CS, Kagnoff MF. The immunopathogenesis of celiac disease reveals possible therapies beyond the gluten-free diet.Semin Immunopathol. 2012;34(4):581-600.

88. Malamut G, Cellier C. Celiac disease. Rev Med Interne. 2010;(6):428-433.

89. American Dietetic Association. Celiac Disease (CD): Evidence-Based Nutrition Practice Guideline. Chicago, IL: American Dietetic Association; 2009.

90. Lerner A. New therapeutic strategies for celiac disease. Autoimmun Rev. 2010;(3):144-147.

91. Schuppan D, Junker Y, Barisani D. Celiac disease: from pathogenesis to novel therapies. Gastroenterology. 2009;137(6):1912-1933.

92. Leffler DA, Dennis M, Edwards GJ, et al. A simple validated gluten-free diet adherence survey for adults with celiac disease.Clin Gastroenterol Hepatol. 2009;7(5):530-536.

93. Holms S. Coeliac disease: symptoms, complications and patient support. Nurs Stand. 2010;24(35):50-56.

94. Gainer CL. Celiac disease: helping patients live gluten-free. Nurse Pract. 2011:36(9):14-19.

95. Greenberg L. Case management implications of celiac disease. Prof Case Manag. 2008;13(4):211-217.

96. Tully MA. Pediatric celiac disease. Gastroenterol Nurs. 2008;31(2):132-140.

97. Gainer CL. The great gluten escape: a camp for children with celiac disease. Gastroenterol Nurs. 2007;30(5):380-381.

98. Primary Ciliary Dyskinesia Foundation. What is a 504 Plan? Available at http://www.pcdfoundation.org/pcd-at-work-and-school/what-is-a-504-plan. Last accessed November 7, 2013.

99. Leffler D. Celiac disease diagnosis and management: a 46-year-old woman with anemia. JAMA. 2011;306(14):1582-1592.

100. Barton SH, Murray JA. Celiac disease and autoimmunity in the gut and elsewhere. Gastroenterol Clin North Am. 2008;37(2):411-428.

101. American Gastroenterological Association Institute. American Gastroenterological Association Institute medical position statement on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology. 2006;130(3):935-939.

102. Rostom A, Murray JA, Kagnoff MF. American Gastroenterological Association (AGA) Institute technical review on the diagnosis and management of celiac disease. Gastroenterology. 2006;131(6):1981-2002.

103. Dewar DH, Ciclitira PJ. Clinical features and diagnosis of celiac disease. Gastroenterology. 2005;128(4 suppl 1):S19-S24.

104. Presutti RJ, Cangemi JR, Cassidy HD, Hill DA. Celiac disease. Am Fam Physician. 2007;76(12):1795-1802.

105. Freeman HJ. Lymphoproliferative and intestinal malignancies in 214 patients with biopsy-defined celiac disease. J Clin Gastroenterol. 2004;38(5):429-434.

106. Catassi C, Bearzi I, Holmes GK. Association of celiac disease and intestinal lymphomas and other cancers. Gastroenterology. 2005;128(4 suppl 1):S79-S86.

107. Rostom A, Dubé C, Cranney A, et al. Celiac Disease. Evidence Report/Technology Assessment No. 104. (Prepared by the University of Ottawa Evidence-based Practice Center, under Contract No. 290-02-0021.) AHRQ Publication No. 04-E029-2. Rockville, MD: Agency for Healthcare Research and Quality; 2004.

108. Freeman HJ. Adult celiac disease and its malignant complications. Gut Liver. 2009;3(4):237-246.

109. Lebwohl B, Stavsky E, Neugut AI, Green PH. Risk of colorectal adenomas in patients with coeliac disease. Aliment Pharmacol Ther. 2010;32(8):1037-1043.

110. Porter RS, Kaplan JL (eds). Merck Manual of Diagnosis and Therapy. 18th ed (online version). Available at http://www.merckmanuals.com/professional/index.html. Last accessed November 8, 2013.

Evidence-Based Practice Recommendations Citation

1. Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray JA. ACG clinical guidelines: diagnosis and management of celiac disease.Am J Gastroenterol. 2013;108(5):656-676. Summary retrieved from National Guideline Clearinghouse at http://www.guideline.gov/content.aspx?id=45327. Last accessed November 8, 2013.


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