Diagnosis and management of celiac disease

Celiac disease affects roughly 1% of the general population. While most physicians recognize the gluten-free diet as the treatment of choice, identification and appropriate diagnostic testing are often a challenge.

In February 2013, the American College of Gastroenterology released guidelines on the work-up of celiac disease and recommendations on management.

Celiac disease results from inflammation of the mucosa of the small intestine, causing blunting of villi, which leads to a loss of absorptive area and subsequent decreased absorption of vitamins and minerals. Symptoms typically include abdominal pain and bloating, diarrhea, and weight loss with less-common symptoms of dyspepsia, constipation, and neuropathy. Presentation can often be subtle, and the decision to embark on diagnostic testing requires an understanding that patient may present with nonspecific symptoms and signs including iron deficiency, weight loss, abnormal transaminases, irritable bowel symptoms, infertility, amenorrhea, and chronic fatigue. Celiac disease has been associated with various conditions, including diseases of the thyroid, unexplained iron-deficiency anemia, elevated transaminases, and even seizures. When celiac disease is treated the associated symptoms resolve. If left untreated, the disease can progress and cause decreased bone mineralization, increasing fatigue, gastrointestinal symptoms, anemia, weight loss, peripheral neuropathy, menstrual abnormalities, and cancer, particularly lymphoma of the small bowel and esophagus.

Celiac disease is associated with other medical conditions, particularly type 1 diabetes mellitus, and Down syndrome. Between 3% and 10% of patients with type 1 diabetes will test positive for celiac disease and approximately 10% of those with Down syndrome test positive.

In addition to its relationship to certain medical conditions, celiac disease shows a genetic predominance. There is approximately a 20% elevated risk of celiac disease in siblings and 10% in other first-degree relatives and up to 5% in second-degree relatives of patients who have been diagnosed with celiac disease. Celiac disease has a strong relation to testing positive for the HLA-DQ gene, perhaps explaining not only its genetic predominance but also its connection to certain other diseases, such as type 1 diabetes, which also has an increased prevalence in individuals with positive HLA-DQ typing.

The diagnosis of celiac disease relies on two factors: the genetic risk of a patient to develop the condition, and the symptomatology of that patient. In the past, antigliadin antibodies and antiendomysial antibodies served as diagnostic markers, although each suffered from a relatively low sensitivity and specificity for the condition. Testing for antitissue transglutaminase (anti-TTG) antibodies is now the diagnostic test of choice as it is more sensitive and specific for celiac disease than its two predecessors. Anti-TTG should be ordered in the following individuals:

• Those with a first-degree relative diagnosed with celiac disease, regardless of whether currently expressing symptoms.

• Those with symptoms suggestive of celiac disease.

• Those expressing symptoms and concurrently suffering from a predisposing condition, such as type 1 diabetes.

The correct diagnostic algorithm for ruling-in celiac disease in most situations is to first test with anti-TTG antibodies and then to confirm the positive antibody finding with a small bowel biopsy looking for villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes. A trial of a gluten-free diet is not recommended to help establish the diagnosis of celiac disease because both celiac disease and nonceliac gluten sensitivity will respond to the gluten-free diet; only the former has known associated morbidity. In addition, strict adherence of the diet will cause levels of anti-TTG antibodies to drop to within normal limits, with the time for this to occur varying from patient to patient.

If a patient is already on a gluten-free diet, HLA-DQ typing can be helpful in ruling out celiac disease as it is found in the vast majority of those suffering from that disease, with a negative predictive value of 99%. A positive finding on HLA-DQ typing is not specific though, so is not useful for ruling in the diagnosis of celiac disease, as it is found in numerous other conditions including type 1 diabetes as well as in individuals without other illness. Anti-TTG antibodies can have false-negative results in the setting of a patient with IgA deficiency. IgA deficiency is rare in the general population, with a prevalence of about 0.2%, but has about a 10-fold higher prevalence in patients with celiac disease, affecting about 2%-3% of patients. Therefore, when the suspicion of celiac disease is high, it is reasonable to check total IgA levels in addition to anti-TTG antibodies and to consider further diagnostic testing beyond anti-TTG if total IgA levels are low.

Treatment for celiac disease is a gluten-free diet, with avoidance of foods or drinks made with or containing wheat, rye, or barley. For dietary advice, monitoring, and follow-up, referral to a nutritionist is important. In addition, the patient should advise first-degree relatives on the need to get tested for the condition. Follow-up should confirm the resolution of elevated anti-TTG antibodies on a gluten-free diet. Ongoing follow-up should be done on an annual basis, providing support for compliance with a gluten-free diet and checking antibodies to confirm control of the disease.

The Bottom Line

Celiac disease affects roughly 1% of patients and often goes undiagnosed. Elevated anti-TTG with confirmatory duodenal biopsy establishes the diagnosis. Treatment consists of lifelong adherence to a gluten-free diet.

Reference

Rubio-Tapia, A., Hill, I., Ciaran, K., Calderwood, A., & Murray, J. ACG clinical guidelines: Diagnosis and management of celiac disease (Am. J. Gastroenterol. 2013;108:656-76).

Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia. Dr. Callahan is a second-year resident in the family medicine residency program at Abington.

Celiac disease affects roughly 1% of the general population. While most physicians recognize the gluten-free diet as the treatment of choice, identification and appropriate diagnostic testing are often a challenge.

In February 2013, the American College of Gastroenterology released guidelines on the work-up of celiac disease and recommendations on management.

Celiac disease results from inflammation of the mucosa of the small intestine, causing blunting of villi, which leads to a loss of absorptive area and subsequent decreased absorption of vitamins and minerals. Symptoms typically include abdominal pain and bloating, diarrhea, and weight loss with less-common symptoms of dyspepsia, constipation, and neuropathy. Presentation can often be subtle, and the decision to embark on diagnostic testing requires an understanding that patient may present with nonspecific symptoms and signs including iron deficiency, weight loss, abnormal transaminases, irritable bowel symptoms, infertility, amenorrhea, and chronic fatigue. Celiac disease has been associated with various conditions, including diseases of the thyroid, unexplained iron-deficiency anemia, elevated transaminases, and even seizures. When celiac disease is treated the associated symptoms resolve. If left untreated, the disease can progress and cause decreased bone mineralization, increasing fatigue, gastrointestinal symptoms, anemia, weight loss, peripheral neuropathy, menstrual abnormalities, and cancer, particularly lymphoma of the small bowel and esophagus.

Celiac disease is associated with other medical conditions, particularly type 1 diabetes mellitus, and Down syndrome. Between 3% and 10% of patients with type 1 diabetes will test positive for celiac disease and approximately 10% of those with Down syndrome test positive.

In addition to its relationship to certain medical conditions, celiac disease shows a genetic predominance. There is approximately a 20% elevated risk of celiac disease in siblings and 10% in other first-degree relatives and up to 5% in second-degree relatives of patients who have been diagnosed with celiac disease. Celiac disease has a strong relation to testing positive for the HLA-DQ gene, perhaps explaining not only its genetic predominance but also its connection to certain other diseases, such as type 1 diabetes, which also has an increased prevalence in individuals with positive HLA-DQ typing.

The diagnosis of celiac disease relies on two factors: the genetic risk of a patient to develop the condition, and the symptomatology of that patient. In the past, antigliadin antibodies and antiendomysial antibodies served as diagnostic markers, although each suffered from a relatively low sensitivity and specificity for the condition. Testing for antitissue transglutaminase (anti-TTG) antibodies is now the diagnostic test of choice as it is more sensitive and specific for celiac disease than its two predecessors. Anti-TTG should be ordered in the following individuals:

• Those with a first-degree relative diagnosed with celiac disease, regardless of whether currently expressing symptoms.

• Those with symptoms suggestive of celiac disease.

• Those expressing symptoms and concurrently suffering from a predisposing condition, such as type 1 diabetes.

The correct diagnostic algorithm for ruling-in celiac disease in most situations is to first test with anti-TTG antibodies and then to confirm the positive antibody finding with a small bowel biopsy looking for villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes. A trial of a gluten-free diet is not recommended to help establish the diagnosis of celiac disease because both celiac disease and nonceliac gluten sensitivity will respond to the gluten-free diet; only the former has known associated morbidity. In addition, strict adherence of the diet will cause levels of anti-TTG antibodies to drop to within normal limits, with the time for this to occur varying from patient to patient.

If a patient is already on a gluten-free diet, HLA-DQ typing can be helpful in ruling out celiac disease as it is found in the vast majority of those suffering from that disease, with a negative predictive value of 99%. A positive finding on HLA-DQ typing is not specific though, so is not useful for ruling in the diagnosis of celiac disease, as it is found in numerous other conditions including type 1 diabetes as well as in individuals without other illness. Anti-TTG antibodies can have false-negative results in the setting of a patient with IgA deficiency. IgA deficiency is rare in the general population, with a prevalence of about 0.2%, but has about a 10-fold higher prevalence in patients with celiac disease, affecting about 2%-3% of patients. Therefore, when the suspicion of celiac disease is high, it is reasonable to check total IgA levels in addition to anti-TTG antibodies and to consider further diagnostic testing beyond anti-TTG if total IgA levels are low.

Treatment for celiac disease is a gluten-free diet, with avoidance of foods or drinks made with or containing wheat, rye, or barley. For dietary advice, monitoring, and follow-up, referral to a nutritionist is important. In addition, the patient should advise first-degree relatives on the need to get tested for the condition. Follow-up should confirm the resolution of elevated anti-TTG antibodies on a gluten-free diet. Ongoing follow-up should be done on an annual basis, providing support for compliance with a gluten-free diet and checking antibodies to confirm control of the disease.

The Bottom Line

Celiac disease affects roughly 1% of patients and often goes undiagnosed. Elevated anti-TTG with confirmatory duodenal biopsy establishes the diagnosis. Treatment consists of lifelong adherence to a gluten-free diet.

Reference

Rubio-Tapia, A., Hill, I., Ciaran, K., Calderwood, A., & Murray, J. ACG clinical guidelines: Diagnosis and management of celiac disease (Am. J. Gastroenterol. 2013;108:656-76).

Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia. Dr. Callahan is a second-year resident in the family medicine residency program at Abington.

Celiac disease affects roughly 1% of the general population. While most physicians recognize the gluten-free diet as the treatment of choice, identification and appropriate diagnostic testing are often a challenge.

In February 2013, the American College of Gastroenterology released guidelines on the work-up of celiac disease and recommendations on management.

Celiac disease results from inflammation of the mucosa of the small intestine, causing blunting of villi, which leads to a loss of absorptive area and subsequent decreased absorption of vitamins and minerals. Symptoms typically include abdominal pain and bloating, diarrhea, and weight loss with less-common symptoms of dyspepsia, constipation, and neuropathy. Presentation can often be subtle, and the decision to embark on diagnostic testing requires an understanding that patient may present with nonspecific symptoms and signs including iron deficiency, weight loss, abnormal transaminases, irritable bowel symptoms, infertility, amenorrhea, and chronic fatigue. Celiac disease has been associated with various conditions, including diseases of the thyroid, unexplained iron-deficiency anemia, elevated transaminases, and even seizures. When celiac disease is treated the associated symptoms resolve. If left untreated, the disease can progress and cause decreased bone mineralization, increasing fatigue, gastrointestinal symptoms, anemia, weight loss, peripheral neuropathy, menstrual abnormalities, and cancer, particularly lymphoma of the small bowel and esophagus.

Celiac disease is associated with other medical conditions, particularly type 1 diabetes mellitus, and Down syndrome. Between 3% and 10% of patients with type 1 diabetes will test positive for celiac disease and approximately 10% of those with Down syndrome test positive.

In addition to its relationship to certain medical conditions, celiac disease shows a genetic predominance. There is approximately a 20% elevated risk of celiac disease in siblings and 10% in other first-degree relatives and up to 5% in second-degree relatives of patients who have been diagnosed with celiac disease. Celiac disease has a strong relation to testing positive for the HLA-DQ gene, perhaps explaining not only its genetic predominance but also its connection to certain other diseases, such as type 1 diabetes, which also has an increased prevalence in individuals with positive HLA-DQ typing.

The diagnosis of celiac disease relies on two factors: the genetic risk of a patient to develop the condition, and the symptomatology of that patient. In the past, antigliadin antibodies and antiendomysial antibodies served as diagnostic markers, although each suffered from a relatively low sensitivity and specificity for the condition. Testing for antitissue transglutaminase (anti-TTG) antibodies is now the diagnostic test of choice as it is more sensitive and specific for celiac disease than its two predecessors. Anti-TTG should be ordered in the following individuals:

• Those with a first-degree relative diagnosed with celiac disease, regardless of whether currently expressing symptoms.

• Those with symptoms suggestive of celiac disease.

• Those expressing symptoms and concurrently suffering from a predisposing condition, such as type 1 diabetes.

The correct diagnostic algorithm for ruling-in celiac disease in most situations is to first test with anti-TTG antibodies and then to confirm the positive antibody finding with a small bowel biopsy looking for villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes. A trial of a gluten-free diet is not recommended to help establish the diagnosis of celiac disease because both celiac disease and nonceliac gluten sensitivity will respond to the gluten-free diet; only the former has known associated morbidity. In addition, strict adherence of the diet will cause levels of anti-TTG antibodies to drop to within normal limits, with the time for this to occur varying from patient to patient.

If a patient is already on a gluten-free diet, HLA-DQ typing can be helpful in ruling out celiac disease as it is found in the vast majority of those suffering from that disease, with a negative predictive value of 99%. A positive finding on HLA-DQ typing is not specific though, so is not useful for ruling in the diagnosis of celiac disease, as it is found in numerous other conditions including type 1 diabetes as well as in individuals without other illness. Anti-TTG antibodies can have false-negative results in the setting of a patient with IgA deficiency. IgA deficiency is rare in the general population, with a prevalence of about 0.2%, but has about a 10-fold higher prevalence in patients with celiac disease, affecting about 2%-3% of patients. Therefore, when the suspicion of celiac disease is high, it is reasonable to check total IgA levels in addition to anti-TTG antibodies and to consider further diagnostic testing beyond anti-TTG if total IgA levels are low.

Treatment for celiac disease is a gluten-free diet, with avoidance of foods or drinks made with or containing wheat, rye, or barley. For dietary advice, monitoring, and follow-up, referral to a nutritionist is important. In addition, the patient should advise first-degree relatives on the need to get tested for the condition. Follow-up should confirm the resolution of elevated anti-TTG antibodies on a gluten-free diet. Ongoing follow-up should be done on an annual basis, providing support for compliance with a gluten-free diet and checking antibodies to confirm control of the disease.

The Bottom Line

Celiac disease affects roughly 1% of patients and often goes undiagnosed. Elevated anti-TTG with confirmatory duodenal biopsy establishes the diagnosis. Treatment consists of lifelong adherence to a gluten-free diet.

Reference

Rubio-Tapia, A., Hill, I., Ciaran, K., Calderwood, A., & Murray, J. ACG clinical guidelines: Diagnosis and management of celiac disease (Am. J. Gastroenterol. 2013;108:656-76).

Dr. Skolnik is associate director of the family medicine residency program at Abington (Pa.) Memorial Hospital and professor of family and community medicine at Temple University, Philadelphia. Dr. Callahan is a second-year resident in the family medicine residency program at Abington.