While Celiac Disease is considered common in Europe, there is a general lack of recognition and diagnosis of Celiac Disease in the United States. Recent studies from Columbia University have indicated that it takes an average of nine years from onset of symptoms to diagnosis in the U.S.
Celiac Disease can have varied modes of presentation, or can even be asymptomatic, making diagnosis more elusive. A timely diagnosis of CD is essential to treating or preventing its complications.
It is unclear whether celiac disease is an autoimmune disease or an inflammatory condition with autoimmune aspects. The clinical classification of celiac disease is based on the presence of gastrointestinal symptoms. Symptomatic, active or classical celiac disease refers to presentations with diarrhea, with or without malabsorption, whereas in asymptomatic or silent celiac disease gastrointestinal symptoms are lacking or not prominent even though extra-intestinal symptoms may be present. The majority of individuals with celiac disease are considered to have the silent form.
Symptomatic celiac disease is associated with considerable morbidity due to chronic gastrointestinal symptoms and malabsorption of nutrients, weight loss, metabolic bone disease, anemia and general debility. The significance of the disease in the majority of individuals with silent celiac disease is less clear. However, most patients with silent celiac disease have occult manifestations of the disease, including reduced bone density, iron or folate deficiency and associated autoimmune diseases that are frequently more clinically significant. Celiac disease results in an increased risk of the development of various malignancies including lymphoma at any site, not only the small intestine. There is also an increased mortality rate in celiac disease, exceeding that of the general population by a factor of 1.9 to 3.8. The increased mortality is mainly due to malignancies. The excess mortality is reduced after 1 to 5 years on a gluten free diet, demonstrating protection by the gluten-free diet.
Infants and young children present with diarrhea, abdominal distension and failure to thrive. However, vomiting, irritability, anorexia and constipation are also common. Older children often present with extra-intestinal manifestations, such as short stature, neurologic symptoms or anemia.
DIAGNOSIS OF CELIAC DISEASE DEPENDS ON AN ABNORMAL SMALL INTESTINAL BIOPSY TOGETHER WITH CLINICAL RESPONSE TO A GLUTEN-FREE DIET. These criteria were established by the European Society of Pediatric Gastroenterology and Nutrition [14] and have been extrapolated to adults. Of note the criteria require an initial biopsy and not a follow up biopsy, though this is commonly performed especially in adults to document healing when the classical, diarrhea predominant presentation is lacking. Serologic testing facilitates the diagnosis of celiac disease but is not part of the diagnostic criteria.
Celiac disease is more common in the United States than previously thought, and there is evidence that it is underdiagnosed. Identification of patients with celiac disease requires awareness of the gastrointestinal and systemic manifestations of this disease. Although no single serologic test is ideal, using several tests in concert can provide effective screening in patients with suspected celiac disease. When clinical suspicion is high, negative serologies does not exclude the diagnosis, and the clinician should proceed with a duodenal biopsy. Positive serologies also require biopsy confirmation of the presence of celiac disease. Prompt diagnosis and treatment with a lifelong gluten-free diet mitigates and even reverses the gastrointestinal and systemic effects of celiac disease, and reduces the risks of subsequent development of malignancy.
Associated Conditions/Indications for Screening for Celiac Disease
Failure to thrive
Short stature
Down syndrome
First degree relatives of patients with celiac disease
Chronic fatigue
Diabetes Mellitus (Type I)
Gastrointestinal complaints
Dyspepsia, Esophageal reflux
Diarrhea, Constipation
Abdominal Pain
Reduced Bone Density
Osteopenia, osteoporosis
Hypocalcemia
Secondary hyperparathyroidism
Neurological Problems
Ataxia, peripheral neuropathy,
Epilepsy (with and without occipital calcifications)
Anemia
Iron, folate or vitamin B12 deficiency
Dermatitis herpetiformis
Apthous stomatitis
Dental enamel defects
Gynecologic problems
Delayed menarche, premature menopause
Infertility, spontaneous abortion
Liver disease
Primary biliary cirrhosis
Autoimmune hepatitis
Elevated transaminases
Sjogren's syndrome
Biopsy Diagnosis of Celiac Disease
The features in a duodenal biopsy suggesting celiac disease include an intraepithelial lymphocytosis, villous atrophy, crypt hypertrophy, abnormal epithelial cells and increased chronic inflammatory cells in the lamina propria. Other features that may be present include gastric metaplasia. Jejunal biopsies are not necessary for the diagnosis of celiac disease, duodenal biopsies are sufficient.
The normal small intestinal or duodenal biopsy (FIGURE 1) consists of long finger like villi and small crypts, forming a crypt to villous ratio of 1 to 3 or 4. The epithelial cells have basal nuclei and a normal surface microvillous structure.
Normally there should be fewer than 30 lymphocytes per 100 epithelial cells. This change is followed by the development of crypt hyperplasia. Partial villous atrophy (FIGURE 2), subtotal villous atrophy and total villous atrophy are the subsequent changes. This final highpower view of a villous tip demonstrates marked intraepithelial lymphocytosis (FIGURE 3).
These changes are usually reversible once the patient adheres to a gluten-free diet.
Biopsy Pitfalls:
1. Inadequate number of biopsy pieces. The disease is patchy, this combined with the fact that all biopsy pieces may not be oriented sufficiently to assess the crypt to villous ratio means that at least 4 to 6 biopsy pieces need to be taken. Biopsy of the descending duodenum is sufficient.
2. Over-interpretation of villous atrophy because of poor orientation of the biopsies. If the pieces are not sufficiently oriented to assess the presence of, or degree of villous atrophy deeper cuts of the tissue block need to be ordered.
3. If the biopsy interpretation does not match either the clinical impression or serologic results the biopsy should be re-interpreted by a pathologist expert in the interpretation of gastrointestinal pathology.
Serologic and Genetic Testing
Of the commercially available serologic tests that aid in the diagnosis of celiac disease, no one test is ideal. Using multiple serologies increases the diagnostic yield. Therefore, in the United States, screening in patients with possible celiac disease should consist of a panel of the following serologic tests:
Anti-gliadin antibodies (AGA) both IgA and IgG
Anti-endomysial antibodies (EMA) - IgA
Anti-tissue transglutaminase antibodies (tTG) - IgA
Total IgA level.
The reason for the use of the panel to detect celiac disease is several fold. They include selective IgA deficiency (SIgA deficiency), lack of concordance of endomysial antibody and tTG, and the occurrence of seronegative celiac disease.
Endoscopic Appearance in Celiac Disease
Characteristic changes in the appearance of the duodenum on endoscopy are suggestive of celiac disease.
1. Reduced or absent duodenal folds
2. Scalloping of folds
3. Mosaic pattern to the mucosa
4. Mucosal fissures or cracks
5. Visible vessels
Management After The Diagnosis of CD
1. A strict gluten-free diet is advised for life. Learn the intricacies of the diet.
2. Assess nutritional deficiencies.
3. Check that medications are gluten-free.
4. Obtain bone density determination.
5. Pneumovax administration.
6. Screen family members.
7. Monitor serum antibody levels.
8. Refer patient to an experienced nutritionist or dietitian that is familiar with the gluten-free diet.
9. Referral to National and Local Celiac Support groups.
10. There are currently no recommended guidelines for screening individuals with celiac disease for malignancies. It would seem prudent for patients to at least have an annual thorough physical examination and to have the stool examined for occult blood.
