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Coeliac Disease

Disease Details

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Description: Coeliac disease is an autoimmune disorder where ingestion of gluten leads to damage in the small intestine.
Type: Coeliac disease is an autoimmune disorder. The genetic transmission is primarily associated with specific human leukocyte antigen (HLA) genes, particularly HLA-DQ2 and HLA-DQ8.
Signs And Symptoms: The classic symptoms of untreated coeliac disease include pale, loose, or greasy stools (steatorrhoea), and weight loss or failure to gain weight. Other common symptoms may be subtle or primarily occur in organs other than the bowel itself. It is also possible to have coeliac disease without any of the classic symptoms at all. This has been shown to comprise at least 43% of presentations in children. Further, many adults with subtle disease may only present with fatigue, anaemia or low bone mass. Many undiagnosed individuals who consider themselves asymptomatic are in fact not, but rather have become accustomed to living in a state of chronically compromised health. Indeed, after starting a gluten-free diet and subsequent improvement becomes evident, such individuals are often able to retrospectively recall and recognise prior symptoms of their untreated disease that they had mistakenly ignored.
Prognosis: Coeliac disease, a chronic autoimmune disorder triggered by the ingestion of gluten, has a generally favorable prognosis when managed appropriately. Adhering to a strict gluten-free diet can lead to symptom resolution, intestinal healing, and the prevention of complications. However, vigilance is crucial, as even small amounts of gluten can cause significant issues. Lifelong dietary management is essential, but with proper adherence, individuals with coeliac disease can lead healthy lives.
Onset: Coeliac disease can develop at any age after gluten is introduced into the diet. While it often manifests in early childhood or between the ages of 30 and 50, symptoms can appear at any time in genetically predisposed individuals.
Prevalence: Coeliac disease has an estimated prevalence of about 1% of the global population. This can vary depending on the specific region and the population studied.
Epidemiology: Globally coeliac disease affects between 1 in 100 and 1 in 170 people. Rates, however, vary between different regions of the world from as few as 1 in 300 to as many as 1 in 40. In the United States it is thought to affect between 1 in 1750 (defined as clinical disease including dermatitis herpetiformis with limited digestive tract symptoms) to 1 in 105 (defined by presence of IgA TG in blood donors). Due to variable signs and symptoms it is believed that about 85% of people affected are undiagnosed. The percentage of people with clinically diagnosed disease (symptoms prompting diagnostic testing) is 0.05–0.27% in various studies. However, population studies from parts of Europe, India, South America, Australasia and the USA (using serology and biopsy) indicate that the percentage of people with the disease may be between 0.33 and 1.06% in children (but 5.66% in one study of children of the predisposed Sahrawi people) and 0.18–1.2% in adults. Among those in primary care populations who report gastrointestinal symptoms, the rate of coeliac disease is about 3%. In Australia, approximately 1 in 70 people have the disease. The rate amongst adult blood donors in Iran, Israel, Syria and Turkey is 0.60%, 0.64%, 1.61% and 1.15%, respectively.People of African, Japanese and Chinese descent are rarely diagnosed; this reflects a much lower prevalence of the genetic risk factors, such as HLA-B8. People of Indian ancestry seem to have a similar risk to those of Western Caucasian ancestry. Population studies also indicate that a large proportion of coeliacs remain undiagnosed; this is due, in part, to many clinicians being unfamiliar with the condition and also due to the fact it can be asymptomatic. Coeliac disease is slightly more common in women than in men. A large multicentre study in the U.S. found a prevalence of 0.75% in not-at-risk groups, rising to 1.8% in symptomatic people, 2.6% in second-degree relatives (like grandparents, aunt or uncle, grandchildren, etc.) of a person with coeliac disease and 4.5% in first-degree relatives (siblings, parents or children). This profile is similar to the prevalence in Europe. Other populations at increased risk for coeliac disease, with prevalence rates ranging from 5% to 10%, include individuals with Down and Turner syndromes, type 1 diabetes, and autoimmune thyroid disease, including both hyperthyroidism (overactive thyroid) and hypothyroidism (underactive thyroid).Historically, coeliac disease was thought to be rare, with a prevalence of about 0.02%. The reason for the recent increases in the number of reported cases is unclear. It may be at least in part due to changes in diagnostic practice. There also appears to be an approximately 4.5 fold true increase that may be due to less exposure to bacteria and other pathogens in Western environments. In the United States, the median age at diagnosis is 38 years. Roughly 20 percent of individuals with coeliac disease are diagnosed after 60 years of age.
Intractability: Coeliac disease is not considered intractable. It can be effectively managed through a strict, lifelong gluten-free diet, which helps to alleviate symptoms and promote intestinal healing. While there is no cure, adhering to dietary restrictions allows individuals to lead normal, healthy lives.
Disease Severity: Coeliac disease severity can vary widely among individuals. Some people may experience mild symptoms, while others can have severe symptoms and complications. The disease primarily affects the small intestine, causing malabsorption of nutrients due to an immune reaction to gluten. Symptoms can range from digestive issues like diarrhea, constipation, and abdominal pain to extraintestinal symptoms such as anemia, osteoporosis, and neurological issues. In severe cases, untreated coeliac disease can lead to significant nutritional deficiencies and an increased risk of certain cancers.
Healthcare Professionals: Disease Ontology ID - DOID:10608
Pathophysiology: Coeliac disease appears to be multifactorial, both in that more than one genetic factor can cause the disease and in that more than one factor is necessary for the disease to manifest in a person. Almost all people (95%) with coeliac disease have either the variant HLA-DQ2 allele or (less commonly) the HLA-DQ8 allele. However, about 20–30% of people without coeliac disease have also inherited either of these alleles. This suggests that additional factors are needed for coeliac disease to develop; that is, the predisposing HLA risk allele is necessary but not sufficient to develop coeliac disease. Furthermore, around 5% of those people who do develop coeliac disease do not have typical HLA-DQ2 or HLA-DQ8 alleles (see below).
Carrier Status: Coeliac disease is an autoimmune disorder triggered by the ingestion of gluten in genetically predisposed individuals. Carrier status for coeliac disease is not typically used in the same way as for some other genetic conditions, as having the gene does not guarantee the development of the disease. However, certain genetic markers, specifically the HLA-DQ2 and HLA-DQ8 haplotypes, are strongly associated with an increased risk of developing coeliac disease. Approximately 95% of individuals with coeliac disease have the HLA-DQ2 gene variant, while most of the remaining cases have HLA-DQ8. It's important to note that having these genetic markers does not mean a person will definitely develop the disease, but their absence makes the disease highly unlikely.

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Mechanism: Coeliac disease is an autoimmune disorder where the ingestion of gluten leads to damage in the small intestine. This condition is characterized by an immune response to gluten, a protein found in wheat, barley, and rye.

**Mechanism:**
When individuals with coeliac disease consume gluten, their immune system reacts abnormally. This response involves the production of antibodies that target the enzyme tissue transglutaminase (tTG) when gluten is present. The immune reaction results in inflammation and damage to the villi in the small intestine. The villi are small, finger-like projections that help absorb nutrients from food. Damage to the villi impairs nutrient absorption, leading to various gastrointestinal and systemic symptoms.

**Molecular Mechanisms:**
1. **Genetic Predisposition:** Coeliac disease has a strong genetic component. The majority of affected individuals carry specific HLA-DQ2 or HLA-DQ8 alleles. These genes encode MHC class II proteins, which present gluten-derived peptides to T cells, initiating an inappropriate immune response.

2. **Gluten Processing and Presentation:** During digestion, gluten is broken down into peptides, one of which is gliadin. Tissue transglutaminase modifies gliadin into a more immunogenic form. The modified gliadin peptides are then presented by HLA-DQ2 or HLA-DQ8 molecules on antigen-presenting cells.

3. **Immune Activation:**
- **T Cell Activation:** The presentation of modified gliadin peptides to CD4+ T cells in the intestinal mucosa triggers an inflammatory response. Activated T cells produce pro-inflammatory cytokines, which contribute to the tissue damage.
- **B Cell Activation:** B cells are stimulated to produce antibodies against tTG, deamidated gliadin peptides, and other related antigens. The presence of these antibodies is used in diagnosing coeliac disease.

4. **Intestinal Damage:** The inflammation caused by the immune response leads to villous atrophy, crypt hyperplasia, and increased intestinal permeability. This morphological change in the small intestine results in malabsorption of nutrients.

Understanding these mechanisms is crucial for diagnosing and managing coeliac disease, typically involving a strict gluten-free diet to mitigate symptoms and prevent intestinal damage.
Treatment: The treatment for coeliac disease primarily involves a strict, lifelong gluten-free diet. This means avoiding all foods that contain gluten, a protein found in wheat, barley, and rye. By eliminating gluten from the diet, individuals with coeliac disease can manage their symptoms and promote intestinal healing. Regular monitoring and consultations with a healthcare provider or dietitian may also be necessary to ensure nutritional balance and address any complications.
Compassionate Use Treatment: Coeliac disease is an autoimmune disorder where ingestion of gluten leads to damage in the small intestine. While the primary and most effective treatment is a strict lifetime gluten-free diet, there have been various experimental and off-label treatments explored.

1. **Compassionate Use Treatments**:
- These typically involve therapies that are still in clinical trials but may be available to patients who have not responded to conventional treatments. For coeliac disease, these might include enzyme therapies designed to break down gluten peptides before they can trigger an immune response.

2. **Off-Label Treatments**:
- Certain medications approved for other conditions may be used off-label. For example, immunosuppressive drugs (like azathioprine) are sometimes used in cases of refractory coeliac disease, where the immune system continues to attack the intestine despite a gluten-free diet.

3. **Experimental Treatments**:
- Several experimental therapies are under investigation. One approach involves transglutaminase 2 inhibitors, which aim to prevent the enzyme from modifying gluten peptides in a way that triggers the immune system.
- Another experimental treatment is the use of monoclonal antibodies targeting interleukin-15, which plays a role in the inflammation and damage seen in coeliac disease.

Research is ongoing, and these treatments are not yet widely available, but they offer potential avenues for those who do not respond to a gluten-free diet alone.
Lifestyle Recommendations: For coeliac disease, the primary lifestyle recommendation is the strict adherence to a gluten-free diet. This means avoiding all foods and products that contain gluten, a protein found in wheat, barley, and rye. Key recommendations include:

1. **Read Food Labels**: Always check food labels for gluten-containing ingredients.
2. **Avoid Cross-Contamination**: Ensure food is prepared and stored in a gluten-free environment to prevent cross-contamination.
3. **Use Gluten-Free Alternatives**: Opt for grains and flours that do not contain gluten, such as rice, corn, quinoa, and buckwheat.
4. **Consult a Dietitian**: Seek guidance from a registered dietitian familiar with coeliac disease to ensure nutritional needs are met.
5. **Eat Naturally Gluten-Free Foods**: Focus on fresh fruits, vegetables, meat, fish, and dairy, which are naturally gluten-free.
6. **Educate Yourself and Others**: Learn about gluten-free living and educate family and friends to support your dietary needs.

Following these lifestyle changes can help manage symptoms and promote overall health for individuals with coeliac disease.
Medication: Coeliac disease is primarily managed through a strict gluten-free diet. This involves avoiding all foods that contain gluten, which is found in wheat, barley, and rye. Currently, there is no medication available that cures coeliac disease or prevents its symptoms directly; instead, the focus is on dietary management to prevent symptoms and complications.
Repurposable Drugs: Currently, there is no specific drug treatment available for coeliac disease. However, some drugs used for other conditions are being investigated for their potential use in managing coeliac disease. These repurposable drugs include:

1. **Larazotide Acetate**: Originally developed as a tight junction regulator, it may reduce intestinal permeability and lessen autoimmune reactions in coeliac patients.
2. **Aless-9523**: An investigational drug aimed at targeting specific pathways involved in the immune response.
3. **Anti-TNF agents (e.g., Infliximab, Adalimumab)**: Used in inflammatory disorders like rheumatoid arthritis and Crohn's disease, these drugs are being studied for their efficacy in refractory coeliac disease.

Note that these are investigational and not yet approved specifically for treating coeliac disease. As of now, the primary management for coeliac disease remains a strict, lifelong gluten-free diet.
Metabolites: Coeliac disease is an autoimmune disorder triggered by the ingestion of gluten. The primary metabolites associated with this condition include:

1. Elevated levels of specific autoantibodies (e.g., anti-tissue transglutaminase antibodies).
2. Gliadin-derived peptides.
3. Deaminated gliadin peptides.
4. Changes in amino acid profiles, particularly a reduction in essential amino acids due to malabsorption.
5. Alterations in gut microbiota metabolites, such as short-chain fatty acids.

Nan (not a number) is not applicable to the context of metabolites in coeliac disease.
Nutraceuticals: Currently, there are no specific nutraceuticals approved for the treatment of coeliac disease. The primary treatment remains adherence to a strict gluten-free diet. While research is ongoing into alternative treatments and supportive therapies, including the potential use of nanotechnology, no conclusive evidence or approved nanomedicine treatments exist for coeliac disease at this time. It is important for patients to consult healthcare professionals for appropriate management strategies.
Peptides: Coeliac disease is an autoimmune disorder where ingestion of gluten leads to damage in the small intestine. Peptides from gluten, specifically gliadin peptides, trigger an immune response in susceptible individuals. The immune system reacts to these peptides, leading to inflammation and damage to the villi of the small intestine. This affects nutrient absorption and can cause various gastrointestinal and systemic symptoms.