How does celiac disease impact mortality rates. What are the potentially fatal complications of untreated celiac disease. Can celiac disease lead to an increased risk of cancer, heart disease, and other serious conditions. Is there a higher mortality rate for people with long-term celiac disease.

The Hidden Dangers of Untreated Celiac Disease

Celiac disease, while not immediately life-threatening, can have severe long-term consequences if left untreated. Many individuals with celiac disease may experience few or no classic symptoms, making it easy to continue consuming gluten without realizing the potential risks. However, ignoring the condition can lead to numerous health complications, some of which can be fatal.

A recent study has shed light on the mortality rates associated with celiac disease. The research, conducted in Sweden between 1969 and 2017, revealed a small but significant increase in mortality among celiac patients compared to the general population. Dr. Benjamin Lebwohl, Director of Clinical Research at the Celiac Disease Center at Columbia University, explains the findings: “If you take a hundred people without celiac disease and follow them for 10 years, 91.4 of them will still be alive, as opposed to a hundred people with celiac disease over 10 years, 90.3 of them will still be alive.”

This comprehensive study, which included 49,829 celiac patients, underscores the importance of proper diagnosis and treatment. With this in mind, let’s explore six potentially fatal complications that can arise from untreated celiac disease.

Cancer: The Silent Threat for Celiac Patients

One of the most serious risks associated with untreated celiac disease is an increased likelihood of developing certain types of cancer. The gut damage caused by prolonged gluten consumption in celiac patients can significantly elevate their cancer risk.

Gastrointestinal Cancer and Lymphoma

Individuals with untreated celiac disease face a staggering 40 to 100 times higher risk of developing gastrointestinal cancer compared to the general population. Among these, Enteropathy-Associated T-cell Lymphoma (EATL) is particularly concerning. EATL is a rare but aggressive form of gut cancer that often proves fatal.

Additionally, celiac patients need to be vigilant about non-Hodgkin’s lymphoma, another type of cancer that occurs more frequently in this population.

Thyroid Cancer Risk

Celiac disease also increases the risk of thyroid-related issues, including cancer. Research indicates a 2.5-fold higher risk of papillary thyroid cancer in celiac patients. While the prognosis for this type of cancer is generally good, with 10-year survival rates between 80% and 90%, it’s important to note that 10-20% of patients do not survive.

Heart Health: The Cardiovascular Impact of Celiac Disease

The connection between celiac disease and heart health is a crucial aspect that often goes overlooked. Untreated celiac disease can have significant implications for cardiovascular well-being.

Increased Risk of Coronary Artery Disease

Studies have shown that celiac disease doubles the risk of coronary artery disease. This condition, characterized by the narrowing or blockage of the coronary arteries, can lead to heart attacks and, in severe cases, prove fatal. The inflammation and nutritional deficiencies associated with untreated celiac disease may contribute to this increased cardiovascular risk.

Regular cardiovascular check-ups and maintaining a strict gluten-free diet are essential for celiac patients to mitigate these risks. Addressing any nutritional deficiencies, particularly in vitamins and minerals crucial for heart health, is also vital.

Neurological Complications: Epilepsy and Celiac Disease

While less common, the neurological manifestations of celiac disease can be severe and potentially life-threatening. One such complication is epilepsy, which occurs more frequently in individuals with autoimmune disorders like celiac disease.

Epilepsy and Sudden Unexpected Death

Patients with autoimmune diseases face a nearly four-fold higher risk of developing epilepsy. In some cases, people with epilepsy can experience sudden unexpected death in epilepsy (SUDEP). While the mechanisms of SUDEP are not fully understood, it is believed to be the most common cause of death related to epilepsy complications, accounting for 7.5% to 17% of all epilepsy-related deaths and 50% of deaths in refractory epilepsy cases.

For celiac patients experiencing neurological symptoms, it’s crucial to consult with both a gastroenterologist and a neurologist to ensure comprehensive care and minimize risks.

Diabetes and Celiac Disease: A Dangerous Duo

The relationship between celiac disease and diabetes is complex and potentially dangerous. Both conditions affect the body’s ability to process nutrients, and their coexistence can lead to severe complications.

Increased Risk and Mortality

People with celiac disease have higher rates of diabetes compared to the general population. More alarmingly, long-term celiac disease increases death rates in individuals with diabetes. A study found that having a celiac disease diagnosis for at least 15 years was associated with a 2.80 times greater risk of death in people with Type 1 diabetes.

Potential Benefits of a Gluten-Free Diet

Interestingly, some evidence suggests that adhering to a gluten-free diet may lower the rates of Type 1 diabetes. This underscores the importance of early diagnosis and strict dietary management for celiac patients, especially those at risk of or already diagnosed with diabetes.

Regular monitoring of blood sugar levels, careful dietary planning, and close collaboration between endocrinologists and gastroenterologists are essential for managing this dual diagnosis effectively.

Respiratory Complications in Celiac Disease

While not as widely recognized, the impact of celiac disease on respiratory health can be significant and, in some cases, life-threatening. The recent study on celiac disease mortality highlighted an increased risk of death from respiratory diseases such as influenza and pneumonia among celiac patients.

Increased Susceptibility to Respiratory Infections

The compromised immune function associated with celiac disease may make individuals more susceptible to severe respiratory infections. This heightened vulnerability underscores the importance of preventive measures such as vaccinations and prompt medical attention for respiratory symptoms in celiac patients.

Potential Lung Complications

Some research suggests a possible link between celiac disease and certain lung conditions, including interstitial lung diseases. While rare, these conditions can significantly impact respiratory function and overall health.

Celiac patients experiencing persistent respiratory symptoms should consult with their healthcare providers to ensure proper evaluation and management of potential lung-related complications.

Obesity and Celiac Disease: An Unexpected Connection

Contrary to the common perception of celiac disease causing weight loss, recent studies have revealed a surprising link between celiac disease and obesity. This connection highlights the complex nature of the disease and its potential long-term health implications.

Prevalence of Overweight and Obesity in Celiac Patients

Research indicates that nearly 40% of people diagnosed with celiac disease are overweight, not underweight as traditionally assumed. Even more striking, 30% of celiac disease patients are obese at the time of their diagnosis. These findings challenge the stereotypical image of a thin, malnourished celiac patient and underscore the importance of considering celiac disease even in overweight individuals presenting with relevant symptoms.

Long-Term Health Risks

Long-term obesity can increase the likelihood of fatality in numerous health categories, including cardiovascular disease, diabetes, and certain cancers. For celiac patients, the combination of obesity and the underlying autoimmune condition can compound these risks.

Interestingly, studies show that people treating celiac disease with a strict gluten-free diet are more likely to achieve and maintain a healthier weight. This highlights the importance of proper diagnosis and dietary management in mitigating the long-term health risks associated with both celiac disease and obesity.

Managing Celiac Disease: Keys to Longevity and Health

While the potential complications of untreated celiac disease can be severe, it’s important to emphasize that proper management can significantly reduce these risks. Early diagnosis, strict adherence to a gluten-free diet, and regular medical follow-ups are crucial for maintaining health and longevity in celiac patients.

Importance of Early Diagnosis

Given the wide-ranging and potentially serious complications of untreated celiac disease, early diagnosis is paramount. Healthcare providers should be aware of the diverse presentations of celiac disease, including atypical symptoms and the possibility of overweight or obese patients.

Strict Gluten-Free Diet Adherence

A lifelong, strict gluten-free diet remains the cornerstone of celiac disease management. This dietary approach not only alleviates symptoms but also helps prevent many of the long-term complications discussed earlier. Nutritional counseling can be beneficial in ensuring a balanced and healthy gluten-free diet.

Regular Medical Follow-Ups

Regular check-ups with a gastroenterologist and other relevant specialists are essential for monitoring disease progression and catching any potential complications early. These visits may include blood tests to check for nutritional deficiencies, antibody levels, and other health markers.

Addressing Comorbidities

Given the increased risk of various health conditions, celiac patients should be vigilant about managing any comorbidities. This may include regular cancer screenings, cardiovascular check-ups, and monitoring for diabetes and thyroid function.

While celiac disease can have serious long-term consequences if left untreated, with proper management, individuals with celiac disease can lead healthy, fulfilling lives. The key lies in awareness, early diagnosis, and committed adherence to treatment plans. As research continues to unveil more about this complex condition, we can hope for even better management strategies and potentially curative treatments in the future.

Six Ways Celiac Disease Can Kill You

Celiac.com 08/13/2014 – Even though some folks suffering from symptoms of celiac disease will claim they would welcome death, most people will not actually die from the immediate symptoms of celiac disease; no matter how bad those symptoms get.

However, left untreated, celiac disease can lead to numerous other conditions, several of which are potentially fatal. Remember, many people experience few, or no classic symptoms of celiac disease. These folks may find it easy to keep eating gluten with relatively few noticeable consequences; at least for a time.

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So, for people with celiac disease who ignore either their doctors, or their bodies, the risks can be huge. They can even lead to death by one of the following:

1) Cancer—Nobody wants cancer, and especially nobody wants the type of cancer that can strike people with gut damage that comes with long-untreated celiac disease.

People with untreated celiac disease are at risk of developing any number of associated conditions, including gastrointestinal cancer at rates of 40 to 100 times those of the general population. Chief among these types of cancer are a type known as Enteropathy-Associated T-cell Lymphoma (EATL). EATL is a gut cancer that often ends in death. People with celiac disease also need to watch out for non-Hodgkins lymphoma.

2) Thyroid Disease – There is a 2.5-fold increased risk of papillary cancer of thyroid for celiac patients.

The good news is that papillary cancer of the thyroid has a high cure rate, with 10-year survival rates estimated at 80% to 90% for any given patient. Still, the dark side is that 10-20% of patients with papillary cancer of the thyroid don’t survive.

3) Epilepsy – Rare form of celiac disease.

Patients with an autoimmune disease faced a nearly four-fold higher risk for epilepsy. In some cases, people with epilepsy can suffer from sudden unexpected death (SUDEP).

SUDEP are still poorly understood, it is possibly the most common cause of death as a result of complications from epilepsy, accounting for between 7.5 to 17% of all epilepsy related deaths and 50% of all deaths in refractory epilepsy.

4) Heart Failure – Celiac disease doubles the risk of coronary artery disease, which can, in many cases prove fatal.

5) Diabetes – Diabetes can cause numerous complications, some of which can be fatal. People with celiac disease have higher rates of diabetes than people without celiac disease. Moreover, long-term celiac disease increases death rates in people with diabetes.

There is also some evidence that a gluten-free diet can lower rates of Type 1 diabetes.

In the end, for people with T1D, having a celiac disease diagnosis for at least 15 years was associated with a 2.80 times greater risk of death

6) Obesity – Recent studies suggest that people with celiac disease are likely to be overweight or obese at the time of presentation.

Studies show that nearly 40% of people diagnosed with celiac disease are actually overweight, not underweight. Also, a full 30% of celiac disease patients are obese at the time of their diagnosis.

Of course, long term obesity can increase the likelihood of fatality in numerous categories. People treating celiac disease with a gluten-free diet are more likely to have a healthier weight. 

So, while celiac disease won’t kill anyone in the short term, it can have devastating consequences if it remains untreated for a long period of time. Share your thoughts on these ways to die from untreated celiac disease, or add additional insights in the comments section.

Study Shows Slightly Increased Mortality in Celiac Disease

By Van Waffle

People with celiac disease have a small but significantly increased mortality rate. The finding comes from the largest study of its kind, which used long-term health records of celiac patients in Sweden between 1969 and 2017.

“Another way of thinking about that is, if you take a hundred people without celiac disease and follow them for 10 years, 91.4 of them will still be alive, as opposed to a hundred people with celiac disease over 10 years, 90.3 of them will still be alive,” says lead researcher Benjamin Lebwohl, MD, Director of Clinical Research at the Celiac Disease Center at Columbia University, New York. Lebwohl’s work on the new study was funded in part by a Young Investigator Award from the Celiac Disease Foundation.

The study included 49,829 celiac patients of whom 6,596 died during a median follow-up of 12.5 years. They were compared with nearly 250,000 people from the general population. A higher risk was seen in all causes of death combined. With causes separated, celiac patients also showed a slightly but significantly higher risk of dying from cardiovascular disease, cancer or respiratory diseases such as flu and pneumonia.

“The great majority of people with celiac disease live long, healthy lives. And yet, the fact that we’re still seeing the signal, even in the most modern era, says that despite the improvement of awareness, increased diagnosis rates and easier access to gluten-free options, there is still a measurable impact on the ultimate outcome, which is mortality in people with celiac disease.”

“What that tells me is that celiac disease is a multi-system condition, and it can impact health in many different ways. There was no one predominant way in which celiac disease caused people to have any shortened lifespan,” says Lebwohl.

To follow up this research, he adds, “We would like to investigate the specific conditions that may contribute to mortality risk. That will involve studying individual cancer types, for example.”

Mortality risk affected all age groups but was most elevated among adults between 18 and 39 years of age. It was highest during the first year after diagnosis yet remained significant even after 10 years of following a gluten-free diet.

A study of this kind could not occur in the United States, which does not have a centralized health system like Sweden, says Lebwohl. While caution is needed in applying data to different populations, lessons from this study about celiac disease management can be adapted to American patients.

“For example, we know from this study and other studies that a substantial minority of people with celiac disease do not have intestinal healing and that’s also the case in the United States. That is likely a consequence of accidental gluten exposure,” Lebwohl says.

Previous smaller studies found no effect on mortality, while a study of 30,000 patients found slightly higher mortality. However, this latest research used data from the largest number of deaths and allowed comparison of patients over decades of gluten-free diet management. It added weight to the finding of a UK study of 1,000 patients showing that mortality risk had not decreased over time. In the Swedish data, increased mortality rate was still seen among those who entered treatment from 2010 to 2017.

“The great majority of people with celiac disease live long, healthy lives. And yet, the fact that we’re still seeing the signal, even in the most modern era, says that despite the improvement of awareness, increased diagnosis rates and easier access to gluten-free options, there is still a measurable impact on the ultimate outcome, which is mortality in people with celiac disease.”

The study was published in JAMA: The Journal of the American Medical Association. More details can be found here.

Celiac disease – symptoms and causes

Contents of the article

1. What is celiac disease and how to treat it? Prevention and causes of disease
2. Causes
3. Classification
4. Symptoms
5. Complications, risk of disease
6. Diagnostics
7. Treatment
8. Diagnosis and treatment of celiac disease in Moscow
9. FAQ

What is celiac disease and how is it treated? Prevention and causes of disease

Celiac disease is a disorder in the small intestine, in which it does not accept gluten. Disease
genetically determined and requires a lifelong gluten-free diet. If you don’t stick to your diet, you can
cause serious complications, even death. And a strict diet gives a complete restoration of the work of the thin
intestines in 85% of cases. This requires 3 to 6 months of treatment.

Celiac disease is twice as common in women as in men.

Causes

As already mentioned, causes of celiac disease lie in a genetic predisposition. Disease
10-15% of first-degree relatives are passed on. But the immune status also matters, so the disease can
appear against the background of diabetes mellitus, connective tissue diseases, dermatitis, arthritis and other diseases,
which greatly weaken the body.

Classification

Taking into account the classification according to the forms of the flow, a typical variety of celiac disease is distinguished, erased and latent.
Typical manifests itself in the first years of life and its clinical manifestations are quite obvious and understandable. Erased form
has extraintestinal symptoms. For example, the patient has anemia, osteoporosis, iron deficiency.

The latent form is most often found in elderly people, while they do not have clear complaints that
would indicate this disease.⁠

Symptoms

symptoms of celiac disease in adults include:

• diarrhea
• unstable stool, which is characterized by either constipation or diarrhea
• signs of dehydration due to frequent diarrhea
• flatulence
• pain and aches in muscles, bones (more typical for older patients)
• steatorrhea – excess fat in the stool
• strong weight loss
• lack of large amounts of vitamins
• the inability to “take away” individual nutrients from food.

Symptoms in children include:

• sudden weight loss
• loose stools with fat
• growth retardation.

Symptoms of celiac disease in children make themselves felt at 9-18 months, and in adults they may first manifest themselves
at the age of 30-40 years for women and 40-50 years for men. Moreover, at this age there is often a provoking factor,
for example, pregnancy in women, a severe infection, or, for example, the consequences of a major operation.

Complications, risk of disease

If you ignore clinical guidelines for celiac disease and do not treat the disease, then the following are possible
complications:

• development of bowel cancer. This happens in 6-8% of people suffering from pathology. The disease usually manifests itself after
  50 years.
• Ulcerative jejunoileitis (one of the varieties of intestinal inflammation). Against this background, there may be
  subsequent complications in the form of internal bleeding, perforation of the small intestine (its wall), peritonitis and
  etc.
• Iron-deficiency anemia.
• Infertility, impaired fertility (against the background of the fact that many useful substances are not absorbed).
• Reduced bone density, their fragility (also due to the fact that there is a lack of essential substances).
• Reducing the size of the spleen.
• Arterial hypotension. It occurs in 70-75% of people who have celiac disease .

Obviously, the problem entails many undesirable consequences, including fatal risks, so
you can’t leave her unattended.

Diagnostics

To carry out diagnosis of celiac disease , it is necessary to resort to a whole range of measures:

• Analysis for antibodies (AgG, AgA, AgE, AgG4), which is done on the basis of venous blood. Now used very
  precise and efficient technique that produces results more precisely 95%.
• Endoscopic biopsy of the intestine. With its help, the presence of atrophy of the villi and the accumulation of lymphocytes in
  mucous membrane.
• Instrumental methods, including ultrasound of the abdominal cavity, CT, MRI of individual vessels, fluoroscopy of the intestine.
• Functional tests, such as vitamin D absorption.

A comprehensive and varied examination allows for a thorough diagnosis of celiac disease , delete
or to confirm the presence of additional related diseases.

Treatment

In order for treatment of celiac disease to give the desired result, you need to act in several directions.
The first is the restoration of all intestinal functions. The second is the correction of body weight to a healthy state, and the third is
elimination of deficiency of vital and necessary for health substances.

The basis of treatment in this case is a gluten-free diet. It is necessary to exclude the damaging factor. Such a diet
appointed for life and must be strictly observed. The exact menu will be given by the attending physician – a gastroenterologist.
It excludes:

• Products from wheat, barley, rye, oatmeal.
• Macaroni, semolina.
• Sausages, frankfurters, canned goods and other foods that are supposed to be gluten-free but may contain it
  leftovers.
• Beer, kvass, vodka and other drinks that use grain raw materials.

This is only a general list, usually patients are given a more detailed one, which requires careful study from patients.
And often celiac disease develops along with lactose intolerance, which is why such patients
You can not eat more and dairy products.

It is very important to stick to a diet even when the body has recovered and temporary relief has come.

Along with diet , the treatment of celiac disease also involves drug therapy. As a rule, her
prescribed if simply giving up inappropriate products does not help. It is also relevant when the patient
associated diseases are observed. Then hormone therapy is possible.

Diagnosis and treatment of celiac disease in Moscow

JSC “Medicina” (clinic of Academician Roitberg) has all the necessary equipment for diagnosis and treatment
celiac disease. If you suspect celiac disease , you should immediately contact a gastroenterologist. Reception
patients in JSC “Medicina” (clinic of Academician Roitberg) is carried out in a modern diagnostic complex,
built with the latest advances in medicine. At your service are the best specialists in this field with 30 years
experience in a clinic with international recognition in the very center of Moscow. We always have reception and diagnostics on the day
treatment, no queues, excellent service and medical care in full accordance with Russian
and international standards.

FAQ

Is it possible to completely cure celiac disease and return to a normal diet?

Now this is impossible. Gluten-free nutrition is prescribed for life and requires strict adherence to all
rules.

What happens if you do not follow a diet with celiac disease?

According to various sources, 10-30% of people who constantly break the diet with celiac disease , due to different
complications die much sooner.

How does celiac disease affect pregnancy?

This disease increases the risk of developing heart defects in the fetus. Women who are ill should
be examined more carefully and strictly follow the recommendations of doctors.

What preventive measures help to avoid the disease?

Primary prevention of the disease does not exist. When 9 occurs0027 symptoms of celiac disease makes sense
only secondary prevention, which consists in strict adherence to the diet.

Celiac disease: outcomes and new approaches to diagnosis | #08/12

Celiac disease is a congenital immunologically mediated intolerance to the protein cereal gluten, leading to atrophy of the villi of the small intestine mucosa and the syndrome of impaired intestinal absorption. Against the background of the disease, in the absence of treatment, severe multiple organ failure develops, which can cause not only a serious condition, but also the death of the patient. At the same time, timely therapy, based on a gluten-free diet, in most cases leads to the restoration of impaired functions and remission of the disease. In this case, strict lifelong adherence to a gluten-free diet is a prerequisite not only for maintaining remission, but also ensures a high quality of life for the patient, adequate physical and intellectual development. The danger of the disease lies in the fact that often in patients who have strictly observed a diet for many years, an illusion of complete recovery is created. At the same time, minor deviations from the diet may not cause significant changes in the state of health, which in some cases leads to the abandonment of the diet. At the same time, despite the imaginary well-being, these patients are at high risk of oncological pathology [1].

In general, celiac disease should not be the cause of death of the patient. Mortality in celiac disease is determined both by the disease itself and by developing complications. Timely diagnosed celiac disease in modern conditions should not pose a threat to the patient’s life, subject to adequate treatment. Unfortunately, it is impossible to determine the frequency of deaths in cases where the diagnosis was not made at all and the cause of death is considered to be intestinal infection, malnutrition of unknown origin, etc. Another aspect associated with mortality in celiac disease is determined by complications of celiac disease, usually developing at a later age, among which special attention is drawn to oncological diseases.

J. West et al., who conducted a large-scale study, following the fate of 4732 patients with celiac disease from 1987 to 2002, identified 134 cases (5%) of oncological diseases (in total, 237 patients died from various causes during this period). The overall probability of developing any cancer, compared with the general population, according to the data obtained in this study was 1.29, gastrointestinal cancer – 1.85, breast cancer – 0.35, lung cancer – 0.34, lymphoproliferative disease – 4.80. Mortality among patients with celiac disease was 1.31, compared with the general population [2]. The results of the work indicate a moderately increased risk of gastrointestinal cancer and a significantly increased risk of lymphoproliferative diseases with a decrease in the risk of breast and lung cancer. The authors attribute the latter feature to the fact that patients with celiac disease smoke less.

An in-depth analysis of the spectrum of oncological diseases over the same period of time [3], which included more than 5,000 patients with celiac disease, showed that the risk of this pathology in individuals diagnosed (more than two years ago) and receiving adequate therapy does not differ from that in the general population. population, amounting to 1.02. At the same time, the high relative risk of developing non-Hodgkin’s lymphoma (5.8) and lymphoma of the small intestine (40.51) attracts attention, but the actual frequency of these diseases is very low (4 cases and 1 case, respectively). The risk of gastrointestinal cancer, according to the results of this study, was 1.58, lung cancer – 1.51 and breast cancer – 0.59. Interestingly, among patients in the process of examination and during the first two years of treatment (i.e., among those who diet for a relatively short time), the risks of these diseases are significantly higher: the overall risk of oncological pathology is 2.00; 358.8, non-Hodgkin’s lymphoma – 20.94, gastrointestinal cancer – 4.24, lung cancer – 1.48, breast cancer – 1.59. Although we are talking about a relatively small number of diseases in absolute terms, nevertheless, this observation points to the preventive role of a gluten-free diet.

This pattern was noted earlier in the course of shorter observations. So, G. K. T. Holmes et al. revealed a 2-fold risk of cancer in patients with celiac disease, but a risk comparable to that in the general population in patients strictly adhering to a gluten-free diet for five or more years [4].

It is also interesting that according to P. D. Howdle and G. K. T. Holmes, out of 175 cases of adenocarcinoma of the small intestine (1998–2000), in 13% of cases it was diagnosed in patients with celiac disease. At the same time, the diagnosis of “celiac disease” was made simultaneously with the diagnosis of “adenocarcinoma” in about 1/3 of cases. In the remaining patients, the diagnosis of celiac disease was made on average 8 years before the detection of a tumor of the small intestine, and the course of the disease was characterized by a good response to a gluten-free diet in most patients [5].

Italian investigators published similar data by following up 1072 adult celiac patients from 1962 to 1994. According to their data, the relative risk of death from oncological diseases (the main cause is non-Hodgkin’s lymphoma) among patients with celiac disease was approximately 2 times higher than that in the general population, and the most dangerous in this regard were the first three years from the moment of diagnosis, and significant risk factors were non-compliance with a gluten-free diet, persistent malabsorption syndrome and late diagnosis of celiac disease [6].

Comparing the group of patients with celiac disease who were diagnosed in childhood with those who received it at an older age, it was found that in the long term, the risk of death during the observation period was significantly higher in the first group (3.32 compared with 1 .58, respectively). It is important, however, that the high mortality rate among patients since childhood was higher due to causes not related at first glance to the underlying disease, primarily accidents, but the authors of the study consider this a natural result of a chronic disease and insufficient life adaptation of patients [7 ].

Thus, celiac disease without adequate treatment, in addition to the problems associated with trophic and metabolic disorders, poses a serious threat to the life of patients who do not follow a gluten-free diet, significantly increasing the risk of oncological pathology. At the same time, strict adherence to a gluten-free diet significantly reduces this risk, making it comparable to that in the general population. Timely diagnosis and proper treatment make the life of a patient with celiac disease full and safe in terms of the development of life-threatening complications.

The severity of celiac disease outcomes without treatment determines the need to improve diagnostic algorithms for its early and reliable diagnosis. Today, the diagnosis of celiac disease is made on the basis of a combination of clinical data, the results of a histological examination of the small intestine mucosa, and serological markers in accordance with previously adopted international and domestic protocols [8–10]. Characteristic histological signs of the disease are atrophy of the villi of the mucous membrane of the small intestine, deepening of the crypts, lymphoplasmacytic infiltration of the lamina propria, and increased mitotic activity of the epithelium. Among serological markers, the most widely used is the determination of antibodies to tissue transglutaminase (ATTG), an increased titer of which indicates celiac disease with a high degree of probability. However, there are no unambiguous pathognomonic tests for celiac disease, and in the case of atypical forms of the disease, serious diagnostic difficulties may arise. In this regard, algorithms for diagnosing celiac disease are constantly being discussed among specialists in this field. One of the constant topics of these discussions is whether it is possible to refuse biopsy of the small intestine mucosa in at least some patients, replacing it, for example, with reliable serological tests.

So, in their study H. Clouzeau-Girard et al. showed that the combination of positive typing results for HLA DQ2/DQ8 haplotypes characteristic of celiac disease and serological markers (in particular, ATTG) is characterized by high sensitivity (98.8%) and specificity (96.2%) for celiac disease. Therefore, according to the authors, in those patients in whom this combination is detected, biopsy can be abandoned [11].

This idea formed the basis of a new algorithm for diagnosing celiac disease, proposed in January 2012 by a working group of experts of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition, ESPGHAN) [12].

The essence of the new algorithm is as follows. Assuming the possibility of celiac disease on the basis of clinical data, the doctor prescribes to the patient the determination of the IgA class ATTG in the blood, as well as the total content of IgA in the blood. The latter is necessary to exclude false-negative results in patients with selective IgA deficiency. If the indicated immunodeficiency occurs (i.e., a low content of total IgA and ATTG is detected), it is necessary to determine the ATTG of the IgG class or other reliable serological markers of the disease (IgG antibodies to deamidated gliadin peptides (ADPG) or anti-endomysial (AEMA) antibodies). The low content of these antibodies in patients without immunodeficiency makes it possible to exclude celiac disease with a high degree of probability. At the same time, in the presence of distinct clinical symptoms, it is still recommended to conduct a biopsy of the small intestine mucosa and HLA typing in order to determine the DQ2 or DQ8 haplotypes characteristic of celiac disease.

High titers (more than 10 times the norm) of serological markers indicate a high probability of celiac disease, and the next step is the determination of AEMA in the blood and HLA typing. Positive results of these tests confirm the diagnosis of celiac disease. In this case, a biopsy of the small intestine mucosa is not required. In the case of low titers of serological markers determined at the first stage of the examination, as well as with ambiguous results obtained at the second stage, a biopsy is indicated, which allows a final judgment to be made whether the patient has celiac disease or not.

For persons with suspected celiac disease, but without its obvious clinical manifestations, HLA typing is recommended at the first stage of the examination, and in the absence of DQ2 or DQ8 haplotypes, celiac disease seems unlikely. On the contrary, if they are detected, the determination of serological markers (ATTG) is shown, and in case of exceeding the norm by 3 or more times, a study on AEMA should be carried out. A positive result of the latter is an indication for a biopsy of the small intestine mucosa.

Discussing the algorithm presented by experts, one cannot fail to note its relative complexity, especially from the point of view of its implementation in domestic conditions. On the other hand, not all gastroenterologists are ready to refuse a biopsy of the small intestine mucosa, even in some cases for fear of missing the disease. Currently, the algorithm is not only widely discussed, but its effectiveness is being tested in multicenter studies. Time will give answers to the questions that have arisen, but today a biopsy and the determination of both classes of ATTG (IgA and IgG) in most cases can be considered the optimal diagnostic choice.

Simultaneously with the development of algorithms, a search is underway for fundamentally new diagnostic markers of celiac disease, and previously known diagnostic methods are being improved. As an additional (and sometimes alternative to the definition of ATTH) serological method of research, the determination of BPPG in the blood, which has recently entered wide clinical practice, can be recommended.

According to W. Sakly et al., who examined a large group of children and adults with celiac disease, the sensitivity of IgG and IgA to ADPG is 94% and 97%, respectively, compared with 96% for AEMA and ATTG. The specificity of ADPG is 93.6% for IgG and 92% for IgA. The specificity of AEMA and ATTG according to the results of this study is 100%. Positive results of the determination of IgG and IgA BPPG were observed significantly more often in patients with celiac disease, compared with persons in the control group (94%, compared with 4.4%, p < 10 ^-7 and 97%, compared with 8%, p < 10 ^-7 ), the same in both children and adults (94% and 95.5% for IgG and IgA, respectively) [13].

According to the results of a meta-analysis, during which the results of a survey of 3110 patients (1876 with celiac disease and 1234 without celiac disease) were analyzed, the informativeness of serological methods to date is as follows. The sensitivity and specificity of the determination of IgA-AEMA, as well as IgA-ATTG, exceeds 90% in most studies. When determining IgA-ADPG, the sensitivity in various studies ranges from 80.7% to 95.1%, and specificity – from 86.3% to 93.1%. In the case of determining IgG-ADPG, the sensitivity ranged from 80.1% to 98.6%, and specificity from 86% to 96.9% [14].

The results of numerous studies aimed at determining the place in the diagnostic algorithm of celiac disease of various serological tests are somewhat contradictory, although in general one can speak of a similar diagnostic significance of the determination of ATTH and APPG [15–18].

Traditional serological tests are known to be less effective in diagnosing celiac disease in children younger than 2 years of age. So, according to M. Maglio et al. in children under 2 years of age, high levels of antigliadin antibodies (AGA) of the IgA class (AGA-IgA) can be detected in 89% of cases, and AGA-IgG – 94%, and in children older than 2 years – 67% and 84%, respectively. As for AEMA and ATTG, these values ​​are 88% and 87%, respectively, for children of the younger group, but 88% and 96%, respectively, for the older group [19]. The presented data indicate that AGA, previously excluded from the algorithms for diagnosing celiac disease, may find a “new life” for diagnosing this disease in young children.

In this regard, of interest is the work of A. Mubarak et al., who included 212 children with suspected celiac disease in their study. The authors found that the positive and negative predictive values ​​for IgA-ADPG are 85–89% and 74-85%, respectively, and for IgG-ADPG – 85% and 89-91%. For AEMA, these values ​​are 77% and 97%, and for ATTG, 87% and 96%, respectively. Thus, in general, the serological tests used in the work presented similar results with some advantage of the determination of ATTG. A different picture was observed in the group of children under 2 years of age (41 children): 100% positive and 94% negative predictive level was established for both ADPH and ATTH. For AEMA, these figures were 96% and 93% respectively. Based on these results, it can be concluded that for children under 2 years of age, the determination of APPG has an advantage over AEMA [20].

The high informativeness of the determination of APPG was also demonstrated in dermatitis herpetiformis [21]. Moreover, the determination of BPPG is also effective for assessing the degree of dietary compliance in patients with celiac disease [22, 23]. Serological markers of celiac disease are detected in 20% of first-line relatives who do not present complaints characteristic of the disease [24], which allows them to be used to determine risk groups.

In addition to the traditional enzyme-linked immunosorbent assay (ELISA) method for detecting antibodies, a new fast magneto-electrochemical immunosensor for CD diagnosis has attracted serious interest in recent years. This system uses magnetic beads coated with tissue transglutaminase antigens that bind ATTH in serum samples and are conjugated with IgA alkaline phosphatase as a label [25]. The method allows you to get results within 30 minutes with a minimum concentration of antibodies 390 ng/mL using relatively affordable equipment outside a specialized laboratory. The results of the study are comparable to those obtained with the traditional ELISA test [26–28]. We can assume interesting prospects for the application of this method after its introduction into wide clinical practice.

The results of studies evaluating the value of video capsule endoscopy for the diagnosis of celiac disease are mixed. According to the results of the meta-analysis, it may be an alternative method for examining these patients, although its accuracy leaves much to be desired. The main disadvantage of the method, of course, remains the impossibility of taking a biopsy and a targeted study of one or another part of the intestine. On average (according to meta-analysis), its sensitivity is 89% (95% confidence interval: 82-94%) and specificity – 95% (95% confidence interval: 89-98%). The method can currently be used in cases where conventional endoscopy is not possible, but further work in this direction is certainly needed [29].

It also seems promising to determine the deposits of IgA antibodies to tissue transglutaminase (anti-TSH-IgA) in the small intestine mucosa. According to M. Maglio et al., who examined a significant group of children, these deposits can be detected in 96% of children with celiac disease, as well as in 68% of children with high titers of ATTH, but without atrophy of the small intestinal mucosa, but in 12% of children with low levels of ATTH. The authors calculated the sensitivity of this test at the level of 96%, and the specificity – 88%, and the concordance for detecting deposits and high levels of ATTH is 85% [30]. At the same time, the determination of anti-TSH-IgA deposits does not increase the efficiency of diagnosing celiac disease under the age of 2 years, since they are found in 73% of children in the younger age group, but in 100% in the older one [31].

Thus, today the diagnostic process in celiac disease is still based on three key positions: clinical data, histological picture and serological markers. It should be recognized that an attempt to modify this algorithm, supplementing it, for example, with HLA typing, makes it possible in some cases to avoid a biopsy, but leads to some complication of the procedure. At the same time, it is promising to introduce the determination of APPG in the blood, first of all, in children of the first two years of life, although the diagnostic significance of this approach still requires further clarification. Undoubtedly, a new magneto-electrochemical immunosensor method for detecting antibodies in the blood is of interest, which significantly simplifies and speeds up diagnostics without a significant (according to the authors) increase in its cost. Finally, the high diagnostic value of determining anti-TSH-IgA deposits in the small intestine mucosa is recognized, but in this case it seems impossible to refuse a biopsy. And this will be a completely different path than the one that EPSGHAN experts are aiming for. Celiac disease still leaves a lot of room for thought and research.

Although the lack of clear understanding of the pathogenesis of celiac disease complicates the development of highly effective methods for its diagnosis, the existing possibilities allow timely diagnosis and adequate treatment, preventing severe life-threatening consequences of both impaired intestinal absorption and the immunopathological process itself. The same methods allow monitoring throughout the patient’s life and timely corrective therapy. The development of the diagnostic base for celiac disease continues. The emergence of new methods and algorithms will ensure a high quality of life for patients with this difficult disease.

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