Coeliac disease

Overview

Celiac disease, also known as celiac sprue or gluten-sensitive enteropathy, is a chronic digestive ailment characterized by an inability to tolerate gliadin, the alcohol-soluble part of gluten. Gluten is a protein present in grains such as wheat, rye, and barley.

When celiac disease patients consume gliadin, an immunologically driven inflammatory reaction develops, causing damage to the mucosa of their intestines and leading in maldigestion and nutritional malabsorption.

 

What is coeliac disease?

Celiac disease is a small intestine enteropathy. It is caused by gluten intake in vulnerable people's diets. Susceptibility is determined by genetics. The illness is persistent, and the only therapy available at the moment is to avoid gluten completely.

Gliadin, the alcohol-soluble portion of gluten, is intolerable to celiac patients. Gluten is a protein present in grains such as wheat, rye, and barley. Most celiac disease patients tolerate oats, but they should be continuously watched. When persons with celiac disease consume gliadin, an immunologically driven inflammatory reaction damages the mucosa of their intestines, resulting in maldigestion and malabsorption.

Patients with celiac disease may have failure to thrive as well as diarrhea. Some people, however, have just minor symptoms or are asymptomatic.

 

Epidemiology

The prevalence of celiac disease in the general population is between 0.5 and 1 percent. Over the last 10 to 20 years, both real prevalence and detection and diagnosis have grown. People with autoimmune diseases, such as type 1 diabetes, are more likely to be affected. The risk is one in ten in first-degree relatives of celiac disease patients.

The prevalence of celiac disease in the United States is quite low, with around one case per 3000 people. According to estimates, around 1% of the Western population is afflicted, yet celiac disease is underdiagnosed in the majority of affected persons.

Celiac disease is most common in Western Europe and the United States, although it is becoming more common in Africa and Asia. Females are somewhat more impacted than males. The age distribution of celiac disease patients is bimodal, with the first peaking at 8-12 months and the second peaking in the third to fourth decades. The average age at the time of diagnosis is 8.4 years (range, 1-17 y)

When gluten consumption begins in infancy, Celiac disease may become obvious. Celiac disease symptoms might last throughout infancy if left untreated, although they normally fade by puberty. Symptoms frequently return in early adulthood, between the third and fourth decades of life.

Approximately 20% of celiac disease patients are above the age of 60. Extraintestinal symptoms of celiac disease, such as short stature, behavioral issues, exhaustion, and skin problems, are common in adolescents. Celiac disease is frequently not diagnosed until the patient is in their forties or older.

 

Etiology

Celiac disease symptoms are caused by damage to enterocytes in the small intestine. Chronic inflammation and villi loss are common hallmarks of the small intestine in the entire clinical picture.

A person must have HLA dominant DQ2 or DQ8 genes. The condition is caused by the immune system's negative reaction to gluten, and one of the key proteins involved is an antibody to tissue transglutaminase. However, several suggested routes that contribute to the illness have been postulated. The glycoprotein gliadin (found in gluten) has a direct harmful impact on enterocytes via increasing IL-15 production. 

Some research suggests that gastrointestinal infections in childhood may play a role in the development of celiac disease later in life. This is not surprising given the organ involved, but it is also likely to be directly related to the fact that celiac disease is caused by an immune function issue.

Celiac disease is frequently diagnosed using IgA antibodies to smooth muscle endomysium and tissue transglutaminase. However, only around 5% of celiac disease individuals are deficient in this immunoglobulin.

 

Pathophysiology

Celiac disease is highly hereditary. In first-degree relatives, the disease affects around 10% of the population.

There is a substantial link between celiac disease and two human leukocyte antigen (HLA) haplotypes (DQ2 and DQ8). The presentation of the gluten-derived peptide gliadin, which consists of 33 amino acids, to helper T lymphocytes via HLA molecules causes damage to the small intestine mucosa. The inflammatory response is mediated by helper T cells. Endogenous tissue transglutaminase deamidates gliadin, converting it into a negatively charged protein with increased immunogenicity. Celiac disease is characterized by autoantibodies against type 2 transglutaminase (TG2).

The small intestine is damaged by gliadin, a protein generated from gluten. Local inflammation occurs, and the process results in the destruction of the tiny intestinal villi. This damage, in turn, leads to diminished gut surface functioning and malabsorption. 

The lack of nutritional absorption has an immediate influence on the digestive system, but it also has an indirect impact on all of the body's systems. This has a negative influence on overall health, which is why celiac disease can have signs and symptoms in practically every system of the body, not only the gastrointestinal tract.

 

Coeliac disease symptoms

Lethargy and diarrhea are typical symptoms, thus the term celiac sprue. Abdominal distension, discomfort or pain, vomiting, and constipation are some other gastrointestinal symptoms. Failure to thrive is a significant feature of the history in childhood, but unexplained weight loss is the comparable symptom in maturity.

Recurrent aphthous ulcers in the mouth, iron deficiency anemia, ataxia, persistent headaches, and delayed menarche are symptoms from systems other than the gastrointestinal system. Some obstetric issues, including as premature labor, growth limitation, and stillbirth, are more common in women with untreated celiac disease.

Dermatitis herpetiformis is a skin disorder characterized by gluten intolerance that, like enteropathy, normally responds to gluten elimination from the diet.

Extraintestinal symptoms are common and may include:

  • Anemia caused by a lack of vitamin B12, folate, or iron absorption
  • Coagulopathy is caused by a lack of vitamin K absorption.
  • Osteoporosis
  • Muscle weakness, paresthesias, seizures, and ataxia are examples of neurological symptoms.

Physical examination

A physical exam may reveal the following:

  • A protuberant and tympanic abdomen
  • Evidence of weight loss
  • Orthostatic hypotension
  • Peripheral edema
  • Ecchymoses
  • Hyperkeratosis or dermatitis herpetiformis
  • Cheilosis and glossitis
  • Evidence of peripheral neuropathy
  • Chvostek or Trousseau sign (seen in calcium deficiency)

 

CD can be associated with different autoimmune and idiopathic diseases, including: 

  • Dermatitis herpetiformis (which, as a single manifestation, should prompt testing for CD), 
  • Type 1 diabetes mellitus, 
  • Hashimoto’s thyroiditis, 
  • Selective IgA deficiency, 
  • Alopecia areata, 
  • Addison’s disease, 
  • Connective tissue diseases (mainly Sjogren’s syndrome),
  • Chromosomal diseases (Down, Turner, and William’s syndromes), 
  • Neurological diseases (cerebellar ataxia, peripheral neuropathy, epilepsy with and without occipital calcifications),
  • Hepatic autoimmune diseases (primary biliary cholangitis, 
  • Autoimmune hepatitis, primary sclerosing cholangitis), and 
  • Idiopathic dilated cardiomyopathy

 

Coeliac disease test

The combination of mucosal alterations revealed by duodenal biopsy and serological test positive (anti-tTG antibodies, anti-endomysium antibodies (EmA), and deamidated gliadin peptide (DGP) antibodies) is the gold standard for CD diagnosis. Despite advances in serology, no antibody test currently available gives 100 percent sensitivity and specificity.

Serological tests are often used to begin a diagnostic workup. The two antibodies tested are anti-tissue transglutaminase antibodies (measured quantitatively by enzyme-linked immunosorbent assay or ELISA) and anti-endomysial antibodies, which are often reported as negative, mildly positive, or positive.

The following step, and the gold standard for diagnosis, is a duodenal mucosal biopsy; in celiac disease, this reveals villous atrophy. It is critical that these tests be conducted while the patient is on a gluten-free diet.

Human leukocyte antigen is another valuable test (HLA). Celiac disease has been significantly linked to specific HLA genotypes. HLA testing might be utilized to aid in the diagnosis. According to the 2013 Joint BSPGHAN and Celiac UK recommendations, positive serological testing with positive HLA typing in the context of typical symptoms can be regarded as confirmative of diagnosis without the necessity for biopsy.

The American College of Gastroenterology (ACG) recommends that antibody testing, particularly immunoglobulin testing, be performed. Although biopsies are required for confirmation, an anti-tissue transglutaminase antibody (IgA TTG) test is the best initial test for suspected celiac disease; in children less than 2 years, the IgA TTG test should be paired with testing for IgG-deamidated gliadin peptides.

 

Laboratory studies:

  • Because celiac disease is common among type 1 diabetics and those with Down syndrome, a proper workup is essential.
  • Hypocalcemia, hypokalemia, and metabolic acidosis may be shown by electrolytes.
  • Anemia caused by a lack of folate, iron, or vitamin B12
  • Prothrombin time may be extended.
  • The feces are oily and have a foul odor.

Patients with celiac disease should be tested for a variety of impairments, including reduced bone density. Patients who are currently on a gluten-free diet without prior testing should be assessed to determine the possibility of celiac disease; genetic testing and a gluten challenge are especially beneficial.


Radiology

Small intestine follow-up may indicate obliteration of the intestinal mucosa, bowel dilatation, and barium flocculation.

 

Upper endoscopy is often used to confirm the diagnosis

Endoscopy and biopsy

Upper endoscopy with at least 6 duodenal biopsies is regarded the gold standard for diagnosing celiac disease. Histologically, duodenal biopsies are classified into five stages:

  • Stage 0 - Normal
  • Stage 1 - Increased percentage of intraepithelial lymphocytes (>30%)
  • Stage 2 - Increased presence of inflammatory cells and crypt cell proliferation with preserved villous architecture
  • Stage 3 - Mild (A), moderate (B), and subtotal to total (C) villous atrophy
  • Stage 4 - Total mucosal hypoplasia

 

Duodenal biopsy

The morphological assessment of the duodenal biopsy is still crucial for validating the CD diagnosis. Histology is still considered the "gold standard" for CD diagnosis. However, in recent years, the histological criteria for CD have shifted dramatically, with the addition of modest villous atrophy and minor lesions (defined by an isolated increase in IELs) as probable manifestations of gluten-related intestinal damage.

Four biopsies on the second duodenum and two biopsies at the bulb are now recommended. The orientation of biopsy samples using cellulose acetate Millipore filters is a basic component for accurate assessment. According to the Marsh classification, which is presently used in all reference centers for the diagnosis of CD, the various forms of CD-related lesions of the intestinal mucosa may be classified into five phases.

Type 1 and type 2 lesions, defined by an increase in IELs (with or without crypt hyperplasia) and normal villi, are consistent with but not specific for CD. Minimal intestinal lesions, in conjunction with positive anti-tTG and EmA, indicate the possibility of CD.

In most cases, minimal lesions are caused by other factors such as food allergies (e.g., cow milk proteins), Crohn's disease, lymphocytic colitis, bacterial and parasitic intestinal infections such as Giardia, common variable immunodeficiency, small intestinal bacterial overgrowth, nonsteroidal anti-inflammatory drugs, and Helicobacter pylori infection.

 

Management

It is suggested that all celiac disease patients adhere to a gluten-free diet. This adherence is best accomplished with the assistance of professionals, such as a dietitian. In typically, symptoms improve within days to weeks after starting a gluten-free diet. Unresponsive individuals require a re-evaluation of their diagnosis as well as an assessment of their adherence to the diet. Serology testing can be used to determine compliance. Noncompliance might be inadvertent in someone who is still consuming gluten without recognizing it.

The US Food and Drug Administration (FDA) has issued standards that provide standardized food-label definitions of "gluten-free" to aid in the removal of gluten from the diet. According to these regulations, items branded "no gluten," "free of gluten," or "without gluten" must contain fewer than 20 parts gluten per million. The European Union and Canada have adopted similar criteria.

Oats may be reintroduced into the diet of celiac disease patients after an initial period of abstention. These individuals should be closely watched for recurrence symptoms. To ensure full compliance, the physician and dietician must frequently carefully and thoroughly indoctrinate the patient.

Other testing include examining the effect of malabsorption (due to celiac disease). Full blood count, iron reserves, folate, ferritin, vitamin D and other fat-soluble vitamin levels, and bone mineral density can all be examined.

The management of individuals with positive serology but no abnormal results on duodenal biopsy is debatable. There are several instances where the diagnosis is ambiguous. Despite the fact that no alterations were found on a tiny intestinal biopsy, some individuals suffer relevant symptoms. There is also celiac disease that is seronegative.

This name refers to the circumstance in which, despite typical symptoms, there is no serological evidence of the illness but considerable villous atrophy on duodenal biopsy.

The gluten-free diet is now the sole approved therapy for celiac disease. This has a tremendous influence on the lives of those impacted and can be difficult to sustain. There is ongoing research on non-dietary therapy that may allow patients with celiac disease to tolerate gluten.

Immune modulators are one of the key areas of study in this field. Other treatments, such as vaccinations or consuming drugs that alter gluten toxicity, are also being investigated. However, none have progressed to the point of being suggested or authorized for such treatment.


Corticosteroids

A small percentage of celiac disease patients do not respond to a gluten-free diet. Corticosteroids may be beneficial in certain resistant individuals. Other concomitant illnesses, such as lymphomas of the small intestine, must be checked out in individuals who do not respond to corticosteroids.

 

Differential Diagnosis

  • Bacterial gastroenteritis
  • Crohn disease
  • Giardia
  • Irritable Bowel syndrome
  • Malabsorption
  • Viral gastroenteritis

 

Prognosis

Patients who receive the proper diagnosis and therapy have an excellent prognosis. Unfortunately, adhering to a gluten-free diet is extremely tough, and relapses are common. Some individuals may not react to a gluten-free diet or corticosteroids, and their quality of life suffers as a result.

 

Morbidity/mortality

Although celiac disease is seldom fatal, it is a severe and frequently debilitating maldigestive and malabsorption illness affecting several organ systems.

Patients with celiac disease are more likely to develop problems such as lymphomas and adenocarcinomas of the gastrointestinal tract. Untreated pregnant women are more likely to miscarry and have a kid with a congenital abnormality.

When celiac disease limits food absorption throughout childhood, when nutrition is important to growth and development, short height is commonly the outcome. Celiac disease malabsorption symptoms can include one or more of the following:

  • Chronic diarrhea
  • Steatorrhea
  • Abdominal bloating or cramps
  • Flatulence
  • Weight loss
  • Fatigue
  • Anemia
  • Bleeding diathesis
  • Osteopenia
  • Seizure disorders
  • Stunted growth

 

Complications

In the long run, there is a risk of lymphomas and small bowel adenocarcinomas.

Pregnant mothers may miscarry or have a child with congenital birth abnormalities. Children can be born with short height and a failure to thrive.

Failure to absorb the nutrients can lead to the following:

  • Osteopenia
  • Bleeding diathesis
  • Stunted growth
  • Anemia
  • Lack of exercise endurance
  • Seizures
  • Hyposplenism

 

Refractory CD

RCD accounts for around 10% of all OACD cases and 1–1.5 percent of total CD cases. After at least a year on a rigorous GFD, this syndrome is characterized by symptoms of malabsorption, weight loss, and diarrhea, as well as chronic villous atrophy, which is validated by negative CD serology. Before considering RCD, clinicians should rule out other, more common explanations of persistent CD signs and symptoms, as previously documented.

Refractory CD is further classified into two categories: primary and secondary, based on whether the patients experienced a symptomatic response from the start of GFD or a return of symptoms after a more or less extended time of recovery.

 

Follow-up for CD in adults

Once CD has been identified, clinicians and patients should agree on a well-defined follow-up approach. The first follow-up visit is usually scheduled within 6 months of diagnosis, and then every 12–24 months (every 3–6 months if complications occur) is sufficient to confirm GFD compliance, rule out the onset of autoimmune diseases and metabolic changes, and, most importantly, allow for the early diagnosis of any complications.

Follow-up blood tests should include a complete blood count, anti-tTG IgA (or IgG in the event of IgA deficiency), thyroid stimulating hormone, anti-thyroidperoxidase, anti-thyroglobulin, ferritin, folate, vitamin D3, transaminases, and a metabolic profile. To rule out the existence of indicators predictive of autoimmune disorders linked with CD, the initial follow-up should include a test for antinuclear antibodies and non-organ-specific autoantibodies.

If the antinuclear antibodies test reveals a high titer as well as extractable nuclear antigen antibody positive, this information might be used to look into other autoimmune CD-related illnesses, such as primary biliary cholangitis and Sjogren syndrome.

A bone density scan in adults should be conducted after 12–18 months of a GFD and repeated on a regular basis only if abnormal or if there are other indications. Subjects with osteopenia should be treated with calcium and vitamin D supplements, whereas subjects with osteoporosis should be treated with bisphosphonates if necessary.

Excessive intake of dietary items high in vegetable fats (colza, palm, and coconut oil), which are typically found in GFD, may result in a rise in body weight. As a result, dietary counseling is recommended throughout follow-up to avoid metabolic problems such as hepatic steatosis. Patients initiating GFD, on the other hand, should be examined with an abdominal ultrasound to rule out spleen abnormalities.

 

Conclusion 

The number of celiac disease cases has increased during the previous three decades. In fact, the condition is frequently misdiagnosed as irritable bowel syndrome, causing the diagnosis to be delayed for months or years. Celiac disease can lead to serious problems if left untreated, necessitating an interdisciplinary team approach to diagnosis and treatment. The majority of patients first see a nurse practitioner, pediatrician, or primary care physician with symptoms of diarrhea and stomach discomfort.

A gastroenterologist should be consulted if the disease is suspected. Patients are normally handled as outpatients once the condition has been established. Nurses are critical in monitoring these patients for problems and adherence to the diet. A nutritional consultation is strongly advised since these patients must understand the significance of a gluten-free diet.

In addition, children must be checked for stunted development and failure to thrive.

Because celiac disease may affect multiple organs in the body, some national recommendations have advised an interprofessional approach to treating it. According to new findings, these individuals may be prone to a high prevalence of fractures, hence bone scans should be conducted.

A multidisciplinary approach to therapy is essential for comprehensive nutritional management. The nurse should keep an eye on patients who are resistant to therapy since they may require corticosteroids. Furthermore, all healthcare staff who care for celiac patients should be informed that the illness might eventually lead to lymphomas and adenocarcinomas of the gut. Furthermore, celiac disease has been linked to mental disorder, sadness, and infertility.