|
| A) | 1950s. | ||
| B) | 1960s. | ||
| C) | 1970s. | ||
| D) | 1990s. |
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 Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) published guidelines to achieve higher diagnostic accuracy of CD among children. A panel of experts established that CD is an autoimmune disease associated with specific genes (HLA-DQ2 and HLA-DQ8) and identified the autoantigen in CD as the enzyme tissue transglutaminase [12]. In 2012, a working group within ESPGHAN established new guidelines as well as a new definition of CD based on scientific and technical developments; these evidence-based guidelines were further updated and expanded in 2020 [12]. In 2019, the European Society for the Study of Coeliac Disease (ESsCD) published their first guidelines for CD in adults, updating them in 2025 to refine diagnostic strategies and enhance overall quality of care [10]. Additionally, the American College of Gastroenterology (ACG) updated their 2013 guidelines in 2023 with current clinical recommendations [11].
| A) | fat. | ||
| B) | gluten. | ||
| C) | protein. | ||
| D) | carbohydrates. |
The EssCD guidelines define CD as "an inflammatory disorder in genetically predisposed persons triggered by an immune response to gluten, proteins present in wheat, barley, and rye. CD is a chronic small-bowel enteropathy in which specific antibodies are systemically detectable" [10]. When an individual with CD consumes gluten, it damages the small intestine and results in difficulty absorbing nutrients from foods. As previously noted, approximately 1 in 133 individuals in the United States (or about 1%) have CD. While overall occurrence of CD is similar between men/boys and women/girls, women/girls are diagnosed twice as often as men/boys [10]. In addition, the risk of CD in individuals with a sibling with CD has ranged between 5% to 20%, and between 5% to 10% in other first-degree relatives [10,11].
| A) | 1% | ||
| B) | 5% | ||
| C) | 10% | ||
| D) | 15% |
The EssCD guidelines define CD as "an inflammatory disorder in genetically predisposed persons triggered by an immune response to gluten, proteins present in wheat, barley, and rye. CD is a chronic small-bowel enteropathy in which specific antibodies are systemically detectable" [10]. When an individual with CD consumes gluten, it damages the small intestine and results in difficulty absorbing nutrients from foods. As previously noted, approximately 1 in 133 individuals in the United States (or about 1%) have CD. While overall occurrence of CD is similar between men/boys and women/girls, women/girls are diagnosed twice as often as men/boys [10]. In addition, the risk of CD in individuals with a sibling with CD has ranged between 5% to 20%, and between 5% to 10% in other first-degree relatives [10,11].
| A) | 1% and 5%. | ||
| B) | 5% and 20%. | ||
| C) | 25% and 35%. | ||
| D) | 50% and 70%. |
The EssCD guidelines define CD as "an inflammatory disorder in genetically predisposed persons triggered by an immune response to gluten, proteins present in wheat, barley, and rye. CD is a chronic small-bowel enteropathy in which specific antibodies are systemically detectable" [10]. When an individual with CD consumes gluten, it damages the small intestine and results in difficulty absorbing nutrients from foods. As previously noted, approximately 1 in 133 individuals in the United States (or about 1%) have CD. While overall occurrence of CD is similar between men/boys and women/girls, women/girls are diagnosed twice as often as men/boys [10]. In addition, the risk of CD in individuals with a sibling with CD has ranged between 5% to 20%, and between 5% to 10% in other first-degree relatives [10,11].
| A) | twice as often. | ||
| B) | three to four times as often. | ||
| C) | five times as often. | ||
| D) | at the same rate as men. |
The EssCD guidelines define CD as "an inflammatory disorder in genetically predisposed persons triggered by an immune response to gluten, proteins present in wheat, barley, and rye. CD is a chronic small-bowel enteropathy in which specific antibodies are systemically detectable" [10]. When an individual with CD consumes gluten, it damages the small intestine and results in difficulty absorbing nutrients from foods. As previously noted, approximately 1 in 133 individuals in the United States (or about 1%) have CD. While overall occurrence of CD is similar between men/boys and women/girls, women/girls are diagnosed twice as often as men/boys [10]. In addition, the risk of CD in individuals with a sibling with CD has ranged between 5% to 20%, and between 5% to 10% in other first-degree relatives [10,11].
| A) | causes diarrhea. | ||
| B) | instigates inflammation. | ||
| C) | leads to malabsorption of essential nutrients. | ||
| D) | All of the above |
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. 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. The function of the gallbladder may be abnormal, and bile salt conjugation may be decreased. 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. Failure to thrive is noted, and hypotonia is common. Extraintestinal manifestations of CD include dermatitis herpetiformis, dental enamel hypoplasia, aphthous ulcers, delayed tooth eruption, and arthritis/arthralgia [14,15].
| A) | age and diet. | ||
| B) | age and weight. | ||
| C) | heredity and age. | ||
| D) | adaptive and innate immunity. |
Celiac disease originates as a result of a combined action that involves both adaptive and innate immunity. Various subtypes of CD are recognized, including (Table 1) [14,15]:
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; often associated with other autoimmune (e.g., type 1 diabetes) or genetic disorders (e.g., Down syndrome)
Latent: Individual possesses genetic compatibility and may show positive autoimmune serology but normal mucosa, with or without symptoms
Potential: Individual has not been diagnosed with CD but shows appropriate genetic background and positive serology, with normal or mildly abnormal histology
Refractory: Defined by presence of malabsorptive symptoms and villous atrophy that persist after six months to one year of a strict gluten-free diet; some individuals may not respond to the diet at all, while some may initially respond but have recurrence of symptoms even with a strict diet
| A) | a preinfiltrative stage. | ||
| B) | an infiltrative lesion. | ||
| C) | crypt hyperplasia. | ||
| D) | partial atrophy of villi. |
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. Classification of distinctive histologic stages can be made using the modified Marsh-Oberhüber histological classification, or the simplified Corazza-Villanacci classification. The Marsh-Oberhüber classification is categorized in the following types [11,14,15,16]:
Type 0: Preinfiltrative stage (normal)
Type 1: Infiltrative lesion (increased intraepithelial lymphocytes)
Type 2: Crypt hyperplasia + type 1
Type 3: Atrophy of villi + type 2
Type 3A: Partial atrophy of villi
Type 3B: Subtotal atrophy of villi
Type 3C: Total atrophy of villi
| A) | Gastrointestinal symptoms are rare. | ||
| B) | Symptoms vary little from patient to patient. | ||
| C) | Many of the symptoms of celiac disease mimic those of other diseases. | ||
| D) | Symptoms always begin immediately after the introduction of gluten-containing foods. |
Adults with CD commonly present with weight loss, diarrhea, lethargy, 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. Other symptoms in both children and adults may include itchy skin rash, headache, depression, and bone and/or joint pain. Symptoms may vary widely from patient to patient; some patients are asymptomatic or minimally symptomatic, especially older children and adults. Many symptoms of CD mimic those of other diseases, leading to a high rate of misdiagnosis. Dermatitis herpetiformis may be an extraintestinal manifestation of gluten-sensitive enteropathy, manifesting as a pruritic, blistering rash. The reversible nature of CD makes prompt diagnosis important [11,15].
| A) | Antigliadin antibodies | ||
| B) | Antiendomysial antibodies | ||
| C) | Tissue transglutaminase (tTG) | ||
| D) | All of the above |
Three antibodies commonly appear in patients with CD: antibodies to tissue transglutaminase (tTG), antiendomysial antibodies (EMAs), and antigliadin antibodies (AGAs). The ACG recommends using serologic markers to screen patients with either nonspecific symptoms of CD or medical conditions that increase the risk of CD; intestinal biopsy should be performed to confirm the diagnosis in adults. While biopsy is preferred for confirmation of diagnosis, a nonbiopsy strategy may be used in children and adults unable to tolerate biopsy; this strategy consists of a combination of high-level tTG IgA (>10 times upper limit of normal) with a positive EMA in a second blood sample as reliable tests for diagnosis of CD [11]. Additionally, the ESPGHAN recommends foregoing the confirmatory duodenal biopsy in selected cases of children and adolescents to reduce the burden on patients and their families [10,12].
| A) | Chest x-ray | ||
| B) | Serum antibody assay | ||
| C) | Video capsule endoscopy (VCE) | ||
| D) | Esophagogastroduodenoscopy (EGD) with duodenal biopsy |
Esophagogastroduodenoscopy (EGD) with duodenal biopsy is considered the criterion standard to confirm 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 1,000 procedures) include bleeding, infection, perforation, and cardiopulmonary problems caused by the sedation agent. 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. Experts recommend that six biopsy samples be obtained from the distal and proximal areas of the small intestine to protect against missed diagnoses [11,15,19]. In the past, repeat biopsy was the standard of care, but this is now often avoided.
| A) | Repeat biopsy is unnecessary. | ||
| B) | There are no contraindications for the use of EGD. | ||
| C) | VCE has been shown to be superior to EGD for diagnosis of celiac disease. | ||
| D) | The histologic lesions characteristic of celiac disease may sometimes be missed. |
Esophagogastroduodenoscopy (EGD) with duodenal biopsy is considered the criterion standard to confirm 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 1,000 procedures) include bleeding, infection, perforation, and cardiopulmonary problems caused by the sedation agent. 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. Experts recommend that six biopsy samples be obtained from the distal and proximal areas of the small intestine to protect against missed diagnoses [11,15,19]. In the past, repeat biopsy was the standard of care, but this is now often avoided.
The histologic lesions characteristic of CD may be missed in some cases, even with multiple duodenal biopsies. Also, some patients with clinical presentation highly suggestive of CD may have a normal EGD and nondiagnostic biopsy. 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 89% and specificity of 95%. 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. Other indications for the use of VCE include iron-deficiency anemia, chronic diarrhea, and abdominal pain due to suspected Crohn disease [15].
| A) | Type 1 diabetes | ||
| B) | Thyroid disease | ||
| C) | Rheumatoid arthritis | ||
| D) | All of the above |
Two theories have been proposed to explain the association between CD and other autoimmune disorders [21]. 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 [22,23,24]. 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 [21]. 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 [25]. The autoimmune disorders associated with CD were both organ-specific (e.g., type 1 diabetes, thyroid disease) and nonorgan-specific (e.g., rheumatoid arthritis) [21].
| A) | divergent symptom profiles. | ||
| B) | the same human leukocyte antigen (HLA) pattern. | ||
| C) | undiagnosed diabetes leading to onset of celiac disease. | ||
| D) | a connection between brain functions and malabsorption. |
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. Because symptoms (e.g., bloating, diarrhea) of the two disorders are similar, diagnosis of CD may be missed unless screening is performed [26,27].
| A) | is usually asymptomatic. | ||
| B) | occurs most often in children. | ||
| C) | affects women more frequently than men. | ||
| D) | usually presents in individuals with some degree of villous atrophy. |
Dermatitis herpetiformis is a severe, itchy, blistering skin manifestation of CD. It occurs in approximately 10% of people with CD, affecting men more frequently than women and generally presenting 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 [1,28].
| A) | cirrhosis. | ||
| B) | celiac hepatitis. | ||
| C) | chronic hepatitis. | ||
| D) | autoimmune liver dysfunction. |
The disease-causing mechanism of liver damage in patients with CD is poorly understood, and the spectrum of liver abnormalities associated with CD is wide. The most frequent occurrence, present in approximately 50% of patients with untreated CD, expresses as mild liver impairment (i.e., celiac hepatitis or autoimmune hepatitis), which typically reverts to normal levels within 12 months of a gluten-free diet. 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 [26,27].
| A) | Management of complications and related symptoms | ||
| B) | Age-specific gluten-free vitamin and mineral supplements | ||
| C) | Medical nutrition therapy provided by a registered dietitian | ||
| D) | All of the above |
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. The dietitian can also help monitor the patient's compliance with the diet and can identify dietary nutrient deficiencies, inadequate fiber intake, and excess weight gain, each of which may be associated with adherence to the gluten-free diet. 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 neurologic symptoms, pregnancy outcomes, and quality of life [11,14].
The treatment of CD also includes the management of complications. Dapsone is a sulfone antibiotic that can be used for short-term relief of a skin manifestation of CD, dermatitis herpetiformis, until management through a gluten-free diet is achieved; the drug typically relieves symptoms within one to three days. Because of the potential for dapsone to cause hemolysis in some individuals, a baseline blood count and periodic follow-up testing are recommended. The use of bisphosphonates for osteoporosis may be appropriate, although their use for osteoporosis related to CD has not been studied extensively [39].
| A) | Refractory celiac disease occurs when a patient with celiac disease stops following a gluten-free diet. | ||
| B) | The real prevalence of refractory celiac disease is estimated to occur in less than 1% of patients with celiac disease. | ||
| C) | Aggressive nutritional support is an important component of the treatment of refractory celiac disease. | ||
| D) | Strict adherence to a gluten-free diet for treatment of refractory celiac disease is widely recommended. |
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. The real prevalence of refractory CD is unknown, but it is believed to occur in less than 1% of individuals with CD. Common symptoms include persistent diarrhea, abdominal pain, involuntary weight loss, gastrointestinal bleeding, fever, night sweats, and bowel obstruction. 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 long-term gluten-free diet [40].
Refractory CD can be subdivided into types 1 and 2, with phenotypically normal and aberrant intraepithelial T lymphocytes in the small intestinal mucosa, respectively. Type 2 can be complicated by ulcerative jejunitis or enteropathy-associated lymphoma. The five-year survival rates are 80% to 96% for type I and 44% to 58% for type 2, which carries a higher risk of developing lymphoma [40,41].
Aggressive nutritional support is an important component of the treatment of refractory CD. Total parenteral nutrition is frequently necessary. Correction of trace element deficiencies (e.g., zinc, copper) should also be included. Strict adherence to a gluten-free diet is widely recommended. Depending on the severity of refractory CD, alternative therapies may include prednisone, methylprednisolone, and budesonide. An addition of an immunosuppressant agent, such as azathioprine, mercaptopurine, or tioguanine, has been shown to be effective refractory CD type 1. Alternative therapies being investigated include cladribine, infliximab, autologous stem cell transplantation, and interleukin-15-blocking antibodies [40,41].
| A) | Social stress | ||
| B) | Feelings of isolation | ||
| C) | Concerns about the cost | ||
| D) | Excessive gluten-free food options |
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. Individuals with CD require ongoing education and support that address the physical and psychologic concerns associated with the disease. 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 3) [33,44,45,46].
| A) | Patient compliance is a concern. | ||
| B) | Sources of gluten are always easily detected. | ||
| C) | Individuals with celiac disease require ongoing education and support. | ||
| D) | Individuals with celiac disease and their families should be encouraged to participate in support and/or advocacy groups. |
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. Individuals with CD require ongoing education and support that address the physical and psychologic concerns associated with the disease. 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 3) [33,44,45,46].