Many conditions share symptoms with celiac disease, and an estimated 83% of Americans with celiac are either undiagnosed or initially misdiagnosed with something else. The overlap is so significant that 5 to 15% of people eventually diagnosed with celiac were first told they had irritable bowel syndrome. Understanding what mimics celiac, and how these conditions differ, can help you have a more productive conversation with your doctor and avoid years of delayed diagnosis.
Irritable Bowel Syndrome (IBS)
IBS is the most common misdiagnosis for celiac disease. Both cause bloating, abdominal pain, diarrhea, and general digestive distress. The overlap is so deep that more than one-third of people with celiac have altered gut motility or “IBS-like” symptoms even after diagnosis. And because a gluten-free diet sometimes improves IBS symptoms too, people can end up managing the wrong condition and feeling just well enough to stop investigating.
The prevalence of celiac disease in people who also have IBS is about four times greater than in the general population. The key difference is that celiac causes measurable intestinal damage and nutrient deficiencies over time, while IBS does not. If you’ve been diagnosed with IBS but also deal with unexplained iron deficiency, weight loss, or bone thinning, celiac testing is worth pursuing. A blood test for tissue transglutaminase antibodies (tTG-IgA) has over 95% sensitivity and specificity, making it a reliable first step.
Non-Celiac Gluten Sensitivity
Non-celiac gluten sensitivity (sometimes called non-celiac wheat intolerance) causes diarrhea, bloating, abdominal pain, and fatigue that worsen when you eat gluten. It looks a lot like celiac from the outside. The critical difference is that people with gluten sensitivity have no antibodies on blood tests and no intestinal damage on biopsy. They’re also less likely to develop nutrient deficiencies, weak bones, or neurological symptoms.
There is no test to confirm gluten sensitivity. It’s diagnosed by exclusion: celiac blood tests come back negative, a biopsy shows no damage, and symptoms improve on a gluten-free diet. This means celiac must be thoroughly ruled out first. If you go gluten-free before testing, celiac antibodies can drop to normal levels, making diagnosis nearly impossible without a gluten challenge of at least 3 grams of gluten daily for 8 weeks.
Wheat Allergy
Wheat allergy and celiac disease both involve an immune reaction to something in wheat, but the mechanisms are completely different. A wheat allergy is an immediate immune overreaction to a wheat protein, driven by the same type of antibodies (IgE) responsible for peanut or shellfish allergies. Symptoms can include hives, itching, wheezing, difficulty breathing, and in severe cases, anaphylaxis.
Celiac disease is an autoimmune condition where gluten triggers the immune system to attack the lining of the small intestine over time. People with celiac do not get anaphylaxis from eating gluten. The digestive symptoms can overlap, especially milder ones like bloating and stomach pain, but the skin reactions, breathing problems, and rapid onset of wheat allergy are distinct. A wheat allergy is typically diagnosed through skin prick testing or IgE blood panels, neither of which is used for celiac.
Small Intestinal Bacterial Overgrowth (SIBO)
SIBO occurs when excessive bacteria colonize the small intestine, fermenting sugars and carbohydrates before your body can absorb them. This produces gas, bloating, abdominal pain, diarrhea, and weight loss. The symptom list is nearly identical to celiac disease. What makes SIBO particularly tricky is that it can also cause mild damage to the intestinal lining, including the same type of villous blunting and increased immune cells seen in celiac biopsies.
Left untreated, SIBO can even cause elevations in celiac antibody levels, which could lead to a false trail during testing. SIBO is typically diagnosed through a breath test that detects gases produced by the overgrown bacteria. It can also coexist with celiac disease, so treating one doesn’t necessarily rule out the other.
Drug-Induced Enteropathy
Certain medications can damage the small intestine in ways that look almost identical to celiac disease on biopsy, complete with villous atrophy and chronic diarrhea. The blood pressure medication olmesartan is the most well-known culprit, but other drugs linked to this type of intestinal damage include methotrexate (used for autoimmune conditions and cancer), azathioprine (an immune suppressant), colchicine (used for gout), and some nonsteroidal anti-inflammatory drugs.
If your biopsy shows villous atrophy but celiac antibodies are negative, your doctor should review your medication list carefully. The intestinal damage from these drugs typically reverses after the medication is stopped, which is another distinguishing feature from celiac, where the trigger is dietary gluten rather than a prescription.
Tropical Sprue
Tropical sprue is an infection-related condition that affects the small intestine and shares overlapping biopsy findings with celiac, including villous atrophy and crypt hyperplasia. It occurs primarily in people who live in or have traveled to tropical regions in Asia, the Caribbean, or Central America. Symptoms include chronic diarrhea, malabsorption, and nutritional deficiencies, particularly of folate and vitamin B12.
The geographic history is often the biggest clue. Tropical sprue responds to antibiotics rather than a gluten-free diet, so if someone’s intestinal damage doesn’t improve after removing gluten, travel history becomes an important part of the diagnostic picture.
Giardiasis and Other Infections
Giardia, a waterborne parasite, can cause total villous atrophy in the small intestine even in the absence of celiac disease or immune deficiency. This was first documented in a case published in Gastroenterology where a patient’s biopsy showed complete flattening of the intestinal villi, a hallmark of severe celiac, but the damage was caused entirely by the parasite. After a single course of antiparasitic treatment, the biopsy returned to normal despite continued gluten exposure.
Giardiasis causes watery diarrhea, cramping, bloating, and nausea, all of which overlap with celiac. It’s diagnosed through stool testing rather than biopsy, so it’s important to check for infections before jumping to a celiac diagnosis based on intestinal damage alone.
Crohn’s Disease and Autoimmune Enteropathy
Crohn’s disease can involve any part of the digestive tract, including the small intestine, and when it affects the duodenum it can mimic celiac histologically. Both conditions cause inflammation and can result in malabsorption, diarrhea, and weight loss. Crohn’s tends to cause deeper, patchy inflammation (affecting some areas while skipping others), while celiac damage is more uniform across the upper small intestine. Crohn’s may also involve symptoms outside the gut, like joint pain, skin lesions, and mouth sores.
Autoimmune enteropathy is rarer but can also present with villous atrophy, malabsorption, and chronic diarrhea. It involves the immune system attacking the intestinal lining through a different pathway than celiac. It’s more common in children and in people with other autoimmune conditions. Both conditions require careful immunological testing to distinguish from celiac.
Microscopic Colitis
Microscopic colitis causes chronic watery diarrhea, and there’s a known overlap with celiac disease. Both conditions involve an increase in immune cells called intraepithelial lymphocytes, but in different parts of the gut. Celiac damages the small intestine (specifically the duodenum), while microscopic colitis affects the colon. The colon looks normal during a standard colonoscopy, so diagnosis requires biopsies examined under a microscope.
The two conditions can coexist. Some people diagnosed with celiac who continue to have diarrhea despite a strict gluten-free diet may actually have microscopic colitis as well. About 20% of people with celiac continue to experience symptoms on a gluten-free diet, and microscopic colitis is one of several explanations worth investigating.
Common Variable Immunodeficiency
Common variable immunodeficiency (CVID) is an immune disorder that can manifest with villous atrophy, malabsorption, and chronic diarrhea. On biopsy, the intestinal changes can look remarkably similar to celiac. The difference is that CVID involves a broader immune deficiency, so patients typically have a history of recurrent infections, particularly respiratory and sinus infections, alongside their digestive symptoms. CVID is identified through blood tests showing low immunoglobulin levels, which also makes celiac antibody testing unreliable in these patients since their bodies may not produce enough antibodies to trigger a positive result.
How Celiac Is Confirmed
Because so many conditions mimic celiac, the diagnostic process involves multiple steps. The standard approach starts with a tTG-IgA blood test. If positive, an upper endoscopy with biopsies confirms the diagnosis. Current guidelines recommend taking at least six biopsy samples: two from the duodenal bulb and four from further down the duodenum. This approach reaches up to 96% sensitivity.
Biopsy findings are graded by the degree of villous atrophy, crypt hyperplasia, and increased intraepithelial lymphocytes. An important caveat from the American College of Gastroenterology: increased lymphocytes without villous atrophy is not enough to diagnose celiac and should prompt investigation of other causes. Genetic testing for HLA-DQ2 or DQ8 markers can be useful for ruling celiac out, since nearly all people with celiac carry one of these markers, but having the gene alone doesn’t confirm the disease.
If you’ve already started a gluten-free diet before testing, results may be falsely negative. In that case, a gluten challenge (eating at least 3 grams of gluten daily for 8 weeks) is needed before testing can be reliable. Three grams is roughly the amount in two slices of standard wheat bread.