Celiac disease is an autoimmune condition affecting the small intestine, triggered by consuming gluten, a protein found in wheat, barley, and rye. This immune response damages the lining of the small intestine, hindering the body’s ability to absorb nutrients. An accurate diagnosis requires specific testing to confirm both the immune reaction and the resulting intestinal damage. Endoscopy is a central procedure used to confirm the presence of this damage.
The Screening Process Before Endoscopy
Before an endoscopy is recommended, the diagnostic process begins with highly sensitive blood tests to screen for a gluten-triggered immune response. These serological tests look for specific antibodies, primarily tissue transglutaminase immunoglobulin A (tTG-IgA), endomysial antibodies (EMA), and deamidated gliadin peptides (DGP). A positive result on these tests suggests that the patient’s immune system is reacting to gluten.
The patient must remain on a gluten-containing diet while these tests are performed. Removing gluten prematurely lowers antibody levels and allows the intestinal lining to heal, potentially causing a false-negative result on both the blood test and endoscopy. Genetic testing for the human leukocyte antigen (HLA) genes, specifically HLA-DQ2 and HLA-DQ8, is also sometimes used in the initial evaluation. Nearly all people with celiac disease carry one or both of these genes, but a negative result can effectively rule out the condition.
The Procedure and Purpose of Upper Endoscopy
When blood tests suggest the presence of celiac disease, an upper gastrointestinal endoscopy is typically the next step to confirm the diagnosis. This procedure involves a gastroenterologist guiding a thin, flexible tube, known as an endoscope, through the mouth, down the esophagus, and into the stomach and the first part of the small intestine, called the duodenum. The endoscope is equipped with a light and a small camera, which allows the physician to visually examine the lining of the upper gastrointestinal tract.
While the endoscope allows for visual inspection, its primary purpose is to obtain tissue samples (biopsies) from the small intestine. A tiny tool passed through the endoscope is used to collect multiple tissue pieces, typically four to six, from the duodenum. It is recommended that samples be taken from both the descending duodenum and the duodenal bulb, as the intestinal damage can be patchy. Collecting these samples is a brief step during the procedure and is considered the definitive method for confirming celiac disease in adults.
Recognizing Intestinal Damage
Tissue samples collected during endoscopy are sent to a laboratory, where a pathologist examines them under a microscope. This microscopic examination, not the visual inspection, formally confirms the diagnosis. The most recognizable sign of celiac disease is villous atrophy: the flattening or shortening of the villi, the small, finger-like projections responsible for nutrient absorption.
Two other specific histological markers confirm the damage pattern characteristic of celiac disease. The pathologist also looks for crypt hyperplasia, which is the elongation and enlargement of the intestinal crypts located at the base of the villi. In addition, there is typically an increased number of intraepithelial lymphocytes (IELs), which are immune cells found within the epithelial lining of the intestine.
The severity of intestinal damage is standardized using the Marsh classification system. This system grades microscopic changes from Marsh I (increased IELs with normal villous architecture) up to Marsh III (varying degrees of villous atrophy). Celiac disease is typically confirmed when positive serology is combined with villous atrophy.
What Happens When Results Are Unclear
Sometimes, endoscopy and biopsy results are not definitive, presenting a diagnostic challenge. One common cause of an unclear result is partial or complete gluten avoidance by the patient before testing, which can lead to mucosal healing and a false-negative biopsy. Because the disease can be patchy, another reason for inconclusive results is that the biopsy samples missed the affected areas.
If the biopsy shows only minor changes, such as a Marsh I or Marsh II classification, the diagnosis may be considered probable rather than definite, and other conditions must be considered. Villous atrophy can also be caused by differential diagnoses, including certain medications, infections like Giardia, or other autoimmune conditions. In these ambiguous situations, a doctor may recommend genetic testing if it has not already been performed, as a negative result for HLA-DQ2/DQ8 can definitively rule out celiac disease. If a patient follows a strict gluten-free diet but still experiences symptoms, they may be diagnosed with non-responsive celiac disease, requiring further follow-up with a specialist.