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Introduction In the past 25 years, clinical understanding of the pathophysiology of celiac disease has made great progress
.
However, some myths about the clinical features and treatment of the disease still exist
.
This article summarizes 10 myths and corresponding facts related to celiac disease, as detailed below
.
Myth 1: Celiac disease mainly occurs in Europeans and European descent.
For most of the 20th century, it is believed that celiac disease mainly affects Europeans and European descent
.
But now every continent except Antarctica has epidemiological data on celiac disease
.
The researchers conducted a meta-analysis of these data, and the results showed that despite some geographic differences, celiac disease is very common
.
Globally, the combined seroprevalence of celiac disease was 1.
4% (95% CI 1.
1%-1.
7%), and the prevalence of celiac disease confirmed by biopsy was 0.
7% (95% CI 0.
5%-0.
9%)
.
In China, epidemiological data is also particularly scarce, because China may have some geographical differences
.
A study in rural areas in northern China showed that the seroprevalence rate for celiac disease was 1.
27%
.
Myth 2: People with celiac disease are not obese.
In fact, many people with celiac disease are overweight or obese
.
In the Western world, an estimated 15%-31% of patients with celiac disease are overweight at diagnosis, and 6.
8%-13% are obese
.
In a study of 679 adult patients with celiac disease and an average follow-up of 39.
5 months, the researchers found that one-third of the patients had a higher body mass index (BMI) at the time of diagnosis (21% were overweight, 12% were obese)
.
Overall, the BMI of patients during the gluten-free diet (GFD) increased significantly (mean 24.
0-24.
6, P<0.
001), and 22% of patients with normal or high BMI at the time of diagnosis had a significant increase in BMI (increased> 2)
.
The degree of BMI increase is proportional to the duration of GFD, indicating that weight maintenance counseling is an important aspect of celiac disease follow-up care and diet education
.
Other research reports have shown that for some overweight or obese individuals, BMI may decrease during GFD treatment
.
This may be related to individual food choices, because processed and manufactured gluten-free foods tend to have higher calorie and fat content than natural gluten-free foods
.
Myth 3: The human anti-tissue transglutaminase antibody IgA (tTG IgA) test cannot be used to diagnose or exclude patients with celiac disease with low serum IgA.
tTG IgA is the recommended initial screening test for celiac disease in all age groups, but it may not be detected To patients with celiac disease who lack IgA
.
Therefore, it is recommended to determine the patient's total serum IgA after the serum tTG IgA test is negative
.
In IgA-deficient populations, the tTG IgG and human anti-endomysial antibody IgG (EMA IgG) tests appear to have similar sensitivity and specificity to the tTG IgA-based tests used in IgA-sufficient populations
.
Myth 4: All celiac disease patients respond well to GFD treatment.
At present, the number of patients who follow GFD after the diagnosis of celiac disease is increasing.
It is obvious that many celiac disease patients do not respond to GFD
.
Although GFD is strictly followed, more than 15% of adult patients still have persistent or frequent symptoms, also known as "non-reactive celiac disease" (NRCD)
.
It is important to evaluate such patients, because although gluten intake is the most common cause of NRCD, it is not the only cause.
Other causes require very different treatments, such as microscopic colitis and other food intolerances.
, Small intestinal bacterial overgrowth and irritable bowel syndrome (IBS)
.
In addition, after receiving GFD treatment for 2 years, only one-third of adults returned to normal villus structure (healthy, healed intestines), and after receiving GFD treatment for 5 years, only two-thirds of adults returned to normal villus structure
.
This is based only on the evaluation of the duodenum, and the proportion of patients with celiac disease who achieve complete recovery of the entire small intestinal mucosa is still unknown
.
Myth 5: GFD is mainly used to treat celiac disease.
For many reasons (such as athletes or public figures), more and more individuals are adopting gluten-free or gluten-reduced diets
.
It is estimated that in 2012, although at least 2 million people in the United States are receiving GFD, only 300,000 of them (15%) actually suffer from celiac disease
.
A recent analysis of the NHANES cohort showed that although the prevalence of people who avoid gluten in the United States is increasing, the prevalence of people diagnosed with celiac disease following GFD is also increasing (from 0.
1% in 2009-2010 to 2013- 0.
4% in 2014)
.
But in 2013-2014, at least 1.
7% of people who avoided gluten were not diagnosed with celiac disease
.
Myth 6: A clinical response to GFD suggests that being diagnosed with celiac disease has a consequence of increased awareness of GFD that it is becoming more common for patients to use GFD for self-treatment before medical consultation
.
Serological and histological test results of celiac disease returned to normal after GFD, making subsequent diagnosis more challenging
.
In addition, IBS and so-called NCGS may also respond to GFD
.
It is clinically important to distinguish celiac disease from other diseases, because only celiac disease requires strict GFD for life.
Celiac disease has a significant risk of health complications and is associated with the risk of diseases in children and other relatives
.
The diagnostic methods of celiac disease mainly include serological diagnosis, small intestinal tissue biopsy, and responsiveness to GFD
.
Serological diagnosis is currently the main clinical application of anti-EMA antibodies and anti-tTG antibodies with high specificity and sensitivity
.
The specificity of anti-EMA antibody is higher than that of anti-tTG antibody, and it is often used as the gold standard for serological diagnosis of celiac disease.
However, the detection method is tedious and time-consuming, and the detection personnel need to receive full-time training, and the results may be affected by human factors
.
The sensitivity and specificity of anti-tTG antibody detection is similar to that of anti-EMA antibody, which can reach 95%-99%.
Therefore, it has become the most commonly used serological diagnosis method for celiac disease
.
In clinical practice, anti-EMA antibodies and anti-tTG antibodies are often combined to improve the accuracy of diagnosis
.
Small bowel biopsy is the gold standard for diagnosing celiac disease
.
However, pathological changes such as villus atrophy may also be seen in other diseases, such as viral diarrhea, other protein allergies, lymphocytic enterocolitis and so on
.
At present, the gold standard for the diagnosis of celiac disease recommended by the World Gastroenterology Organization is: a positive small intestine biopsy and a positive serology test for celiac disease can be used to diagnose celiac disease
.
Suspected patients with celiac disease who are unwilling to undergo a small bowel biopsy can be treated with a gluten-free diet to observe whether the symptoms improve and whether the serum antibody indicators turn negative; whether the symptoms reappear or worsen after re-intake of gluten-containing foods To assist in the diagnosis of celiac disease
.
In addition, HLA-DQ genotyping can also be used as an auxiliary diagnostic method to diagnose celiac disease based on the results of genetic testing when the results of small intestinal tissue biopsy and serology are inconsistent
.
Myth 7: GFD has "solved" the problem of celiac disease.
GFD is an imperfect treatment with a high treatment burden
.
Among patients in the investigator’s hospital, it is reported that the burden of GFD treatment of celiac disease is heavier than the treatment burden of type 1 diabetes, IBS, inflammatory bowel disease, and congestive heart failure
.
In addition, strict GFD is difficult to maintain, especially when eating food prepared by others outside the home, such as in restaurants or cafeterias, during travel or social events
.
Myth 8: An "almost" gluten-free diet is sufficient.
Adhering to an absolutely strict 100% GFD is a huge challenge
.
Therefore, patients often ask whether a less strict GFD diet is sufficient
.
Catassi et al.
conducted a study that included patients with biopsy-confirmed celiac disease with normal duodenal villi structure after receiving strict GFD treatment for 2 years or more.
They were randomized to receive 10 mg gluten, 50 mg gluten daily Or cornstarch placebo for 3 months while maintaining its usual strict GFD
.
At baseline, the ratio of villi height to crypt depth (Vh:Cd) of the 3 groups of patients was similar, but after 3 months, the Vh:Cd of the 50 mg group was significantly lower than that of placebo
.
Importantly, individual sensitivities can be highly heterogeneous
.
Vh:Cd increased/improved in 19/39 subjects (including 2 in the 50 mg group) during the trial
.
Based on the above studies, it can be fairly concluded that individuals’ responses to gluten exposure are highly heterogeneous, but chronic gluten exposure of at least 50 mg for more than one month may cause intestinal damage
.
Myth 9: Most patients with celiac disease follow GFD.
Recently, researchers conducted a study on the grams of gluten ingested and excreted (DOGGIEBAG) in adults who consume gluten-free food
.
Eighteen adult patients with celiac disease diagnosed by biopsy who received GFD treatment for 24 months were enrolled, and food, urine, and stool samples were collected within 10 days
.
The results showed that at least one sample of two-thirds of patients tested positive for gluten immunogenic peptides
.
Eliminating gluten in all diets may be an ideal goal, even for highly motivated patients
.
This has been implicitly acknowledged for many years, because the definition of "gluten-free" is not absolute, but allows food to contain 20 parts per million gluten
.
Myth 10: GFD is sufficient to treat celiac disease.
All celiac disease management guidelines recommend that strict GFD be followed for life
.
However, as mentioned earlier, GFD has a high treatment burden and is an imperfect treatment for celiac disease
.
Therefore, it is necessary to develop drugs for the treatment of celiac disease
.
The survey shows that most patients with celiac disease are interested in medication
.
The current treatment goal is to achieve the ultimate goal-to achieve "tolerability" so that patients with celiac disease can safely consume gluten-whether in small amounts or in the amount that is ultimately in a normal diet
.
Therapeutic drugs currently under development include glutenases (latiglutenase), tight junction modulators (larazotide), and nanoparticles that can induce tolerance to gliadin (TAK-101)
.
References: [1] Silvester JA, Therrien A, Kelly CP.
Celiac Disease: Fallacies and Facts[J].
Am J Gastroenterol.
2021 Jun 1;116(6):1148-1155.
[2] Yuan Juanli, Jiang Xu, Hu Shuai, et al.
Research progress of celiac disease[J].
Journal of Food Safety and Quality Inspection, 2015, 6(11):4510-4515.
.
However, some myths about the clinical features and treatment of the disease still exist
.
This article summarizes 10 myths and corresponding facts related to celiac disease, as detailed below
.
Myth 1: Celiac disease mainly occurs in Europeans and European descent.
For most of the 20th century, it is believed that celiac disease mainly affects Europeans and European descent
.
But now every continent except Antarctica has epidemiological data on celiac disease
.
The researchers conducted a meta-analysis of these data, and the results showed that despite some geographic differences, celiac disease is very common
.
Globally, the combined seroprevalence of celiac disease was 1.
4% (95% CI 1.
1%-1.
7%), and the prevalence of celiac disease confirmed by biopsy was 0.
7% (95% CI 0.
5%-0.
9%)
.
In China, epidemiological data is also particularly scarce, because China may have some geographical differences
.
A study in rural areas in northern China showed that the seroprevalence rate for celiac disease was 1.
27%
.
Myth 2: People with celiac disease are not obese.
In fact, many people with celiac disease are overweight or obese
.
In the Western world, an estimated 15%-31% of patients with celiac disease are overweight at diagnosis, and 6.
8%-13% are obese
.
In a study of 679 adult patients with celiac disease and an average follow-up of 39.
5 months, the researchers found that one-third of the patients had a higher body mass index (BMI) at the time of diagnosis (21% were overweight, 12% were obese)
.
Overall, the BMI of patients during the gluten-free diet (GFD) increased significantly (mean 24.
0-24.
6, P<0.
001), and 22% of patients with normal or high BMI at the time of diagnosis had a significant increase in BMI (increased> 2)
.
The degree of BMI increase is proportional to the duration of GFD, indicating that weight maintenance counseling is an important aspect of celiac disease follow-up care and diet education
.
Other research reports have shown that for some overweight or obese individuals, BMI may decrease during GFD treatment
.
This may be related to individual food choices, because processed and manufactured gluten-free foods tend to have higher calorie and fat content than natural gluten-free foods
.
Myth 3: The human anti-tissue transglutaminase antibody IgA (tTG IgA) test cannot be used to diagnose or exclude patients with celiac disease with low serum IgA.
tTG IgA is the recommended initial screening test for celiac disease in all age groups, but it may not be detected To patients with celiac disease who lack IgA
.
Therefore, it is recommended to determine the patient's total serum IgA after the serum tTG IgA test is negative
.
In IgA-deficient populations, the tTG IgG and human anti-endomysial antibody IgG (EMA IgG) tests appear to have similar sensitivity and specificity to the tTG IgA-based tests used in IgA-sufficient populations
.
Myth 4: All celiac disease patients respond well to GFD treatment.
At present, the number of patients who follow GFD after the diagnosis of celiac disease is increasing.
It is obvious that many celiac disease patients do not respond to GFD
.
Although GFD is strictly followed, more than 15% of adult patients still have persistent or frequent symptoms, also known as "non-reactive celiac disease" (NRCD)
.
It is important to evaluate such patients, because although gluten intake is the most common cause of NRCD, it is not the only cause.
Other causes require very different treatments, such as microscopic colitis and other food intolerances.
, Small intestinal bacterial overgrowth and irritable bowel syndrome (IBS)
.
In addition, after receiving GFD treatment for 2 years, only one-third of adults returned to normal villus structure (healthy, healed intestines), and after receiving GFD treatment for 5 years, only two-thirds of adults returned to normal villus structure
.
This is based only on the evaluation of the duodenum, and the proportion of patients with celiac disease who achieve complete recovery of the entire small intestinal mucosa is still unknown
.
Myth 5: GFD is mainly used to treat celiac disease.
For many reasons (such as athletes or public figures), more and more individuals are adopting gluten-free or gluten-reduced diets
.
It is estimated that in 2012, although at least 2 million people in the United States are receiving GFD, only 300,000 of them (15%) actually suffer from celiac disease
.
A recent analysis of the NHANES cohort showed that although the prevalence of people who avoid gluten in the United States is increasing, the prevalence of people diagnosed with celiac disease following GFD is also increasing (from 0.
1% in 2009-2010 to 2013- 0.
4% in 2014)
.
But in 2013-2014, at least 1.
7% of people who avoided gluten were not diagnosed with celiac disease
.
Myth 6: A clinical response to GFD suggests that being diagnosed with celiac disease has a consequence of increased awareness of GFD that it is becoming more common for patients to use GFD for self-treatment before medical consultation
.
Serological and histological test results of celiac disease returned to normal after GFD, making subsequent diagnosis more challenging
.
In addition, IBS and so-called NCGS may also respond to GFD
.
It is clinically important to distinguish celiac disease from other diseases, because only celiac disease requires strict GFD for life.
Celiac disease has a significant risk of health complications and is associated with the risk of diseases in children and other relatives
.
The diagnostic methods of celiac disease mainly include serological diagnosis, small intestinal tissue biopsy, and responsiveness to GFD
.
Serological diagnosis is currently the main clinical application of anti-EMA antibodies and anti-tTG antibodies with high specificity and sensitivity
.
The specificity of anti-EMA antibody is higher than that of anti-tTG antibody, and it is often used as the gold standard for serological diagnosis of celiac disease.
However, the detection method is tedious and time-consuming, and the detection personnel need to receive full-time training, and the results may be affected by human factors
.
The sensitivity and specificity of anti-tTG antibody detection is similar to that of anti-EMA antibody, which can reach 95%-99%.
Therefore, it has become the most commonly used serological diagnosis method for celiac disease
.
In clinical practice, anti-EMA antibodies and anti-tTG antibodies are often combined to improve the accuracy of diagnosis
.
Small bowel biopsy is the gold standard for diagnosing celiac disease
.
However, pathological changes such as villus atrophy may also be seen in other diseases, such as viral diarrhea, other protein allergies, lymphocytic enterocolitis and so on
.
At present, the gold standard for the diagnosis of celiac disease recommended by the World Gastroenterology Organization is: a positive small intestine biopsy and a positive serology test for celiac disease can be used to diagnose celiac disease
.
Suspected patients with celiac disease who are unwilling to undergo a small bowel biopsy can be treated with a gluten-free diet to observe whether the symptoms improve and whether the serum antibody indicators turn negative; whether the symptoms reappear or worsen after re-intake of gluten-containing foods To assist in the diagnosis of celiac disease
.
In addition, HLA-DQ genotyping can also be used as an auxiliary diagnostic method to diagnose celiac disease based on the results of genetic testing when the results of small intestinal tissue biopsy and serology are inconsistent
.
Myth 7: GFD has "solved" the problem of celiac disease.
GFD is an imperfect treatment with a high treatment burden
.
Among patients in the investigator’s hospital, it is reported that the burden of GFD treatment of celiac disease is heavier than the treatment burden of type 1 diabetes, IBS, inflammatory bowel disease, and congestive heart failure
.
In addition, strict GFD is difficult to maintain, especially when eating food prepared by others outside the home, such as in restaurants or cafeterias, during travel or social events
.
Myth 8: An "almost" gluten-free diet is sufficient.
Adhering to an absolutely strict 100% GFD is a huge challenge
.
Therefore, patients often ask whether a less strict GFD diet is sufficient
.
Catassi et al.
conducted a study that included patients with biopsy-confirmed celiac disease with normal duodenal villi structure after receiving strict GFD treatment for 2 years or more.
They were randomized to receive 10 mg gluten, 50 mg gluten daily Or cornstarch placebo for 3 months while maintaining its usual strict GFD
.
At baseline, the ratio of villi height to crypt depth (Vh:Cd) of the 3 groups of patients was similar, but after 3 months, the Vh:Cd of the 50 mg group was significantly lower than that of placebo
.
Importantly, individual sensitivities can be highly heterogeneous
.
Vh:Cd increased/improved in 19/39 subjects (including 2 in the 50 mg group) during the trial
.
Based on the above studies, it can be fairly concluded that individuals’ responses to gluten exposure are highly heterogeneous, but chronic gluten exposure of at least 50 mg for more than one month may cause intestinal damage
.
Myth 9: Most patients with celiac disease follow GFD.
Recently, researchers conducted a study on the grams of gluten ingested and excreted (DOGGIEBAG) in adults who consume gluten-free food
.
Eighteen adult patients with celiac disease diagnosed by biopsy who received GFD treatment for 24 months were enrolled, and food, urine, and stool samples were collected within 10 days
.
The results showed that at least one sample of two-thirds of patients tested positive for gluten immunogenic peptides
.
Eliminating gluten in all diets may be an ideal goal, even for highly motivated patients
.
This has been implicitly acknowledged for many years, because the definition of "gluten-free" is not absolute, but allows food to contain 20 parts per million gluten
.
Myth 10: GFD is sufficient to treat celiac disease.
All celiac disease management guidelines recommend that strict GFD be followed for life
.
However, as mentioned earlier, GFD has a high treatment burden and is an imperfect treatment for celiac disease
.
Therefore, it is necessary to develop drugs for the treatment of celiac disease
.
The survey shows that most patients with celiac disease are interested in medication
.
The current treatment goal is to achieve the ultimate goal-to achieve "tolerability" so that patients with celiac disease can safely consume gluten-whether in small amounts or in the amount that is ultimately in a normal diet
.
Therapeutic drugs currently under development include glutenases (latiglutenase), tight junction modulators (larazotide), and nanoparticles that can induce tolerance to gliadin (TAK-101)
.
References: [1] Silvester JA, Therrien A, Kelly CP.
Celiac Disease: Fallacies and Facts[J].
Am J Gastroenterol.
2021 Jun 1;116(6):1148-1155.
[2] Yuan Juanli, Jiang Xu, Hu Shuai, et al.
Research progress of celiac disease[J].
Journal of Food Safety and Quality Inspection, 2015, 6(11):4510-4515.
