The Stages of Celiac Disease Explained

Whether you’re newly diagnosed or suspect you may have celiac disease, understanding the stages of celiac disease can help you navigate diagnosis and treatment.  Here, we explain how celiac disease develops over time, how it’s diagnosed and when the Marsh classification system comes into play, and how to manage celiac disease with a gluten-free diet. 

What Is Celiac Disease?

Celiac disease is a complex, long-term autoimmune condition that primarily affects the small intestine. Celiac disease is triggered when a person with celiac eats gluten, a protein found in wheat, barley, and rye. Celiac disease is more serious than gluten intolerance and is different from a food allergy. 

In people with celiac disease, the immune system causes inflammation and sends antibodies to destroy the gluten molecules, but they mistakenly attack the small intestine in the process. This immune reaction damages the lining of the intestine, which is covered in tiny finger-like projections called villi. These villi are essential for the absorption of nutrients, so when they’re damaged, malabsorption of nutrients can occur and a range of related health issues can develop.

Unlike a food allergy, which can cause an immediate, life-threatening response in the body, celiac disease is a long-term autoimmune response that can cause digestive issues in the short term. Left untreated, it may lead to complications such as osteoporosis, infertility, neurological disorders, and cancer of the small intestine.

How Celiac Disease Develops Over Time

The progression of celiac disease typically begins when consumption of foods containing gluten initiates an immune response. When the immune system reacts, it produces antibodies that attack the tissue in the small intestines, creating inflammation. Chronic inflammation damages the villi, impairing nutrient absorption. Initial symptoms typically include digestive issues like diarrhea, bloating, and abdominal pain, or, in children, failure to thrive and delayed growth.

If left undiagnosed or untreated, celiac disease can lead to more severe symptoms and health consequences over time, including malnutrition, osteoporosis, an increased risk of certain cancers and other non-digestive symptoms such as fatigue, joint pain, and skin rashes.

It is important to note that some people with celiac disease may remain asymptomatic for years even while damage is happening inside their body.

The Marsh Classification System: Grading Intestinal Damage

The modified Marsh classification system is used for determining the severity of celiac-related intestinal damage and stage of celiac disease, as examined under a microscope. Originally ranging from 0 to 4, with a type of 3 indicating celiac disease, the Marsh Types have since been changed to a range of 0-3, with stage 3 consisting of 3 substages.

To determine the stage of celiac disease using the Marsh classification system, an intestinal biopsy is performed, where a small tissue sample is taken from the lining of the small intestine and examined under a microscope. The intestinal biopsy shows various aspects of intestinal damage, including:

• The density of intraepithelial lymphocytes (IELS), which are white blood cells that are found in the immune system
• Crypt hyperplasia – when the crypts (the grooves between the villi that line the small intestine and promote nutrient absorption) are elongated compared to a normal intestinal lining
• Blunted or atrophic villi
• Changes to epithelial cells, which line the intestines and act as a barrier between the inside and outside of the body

The Marsh system categorizes the stages of intestinal damage on a scale from 0 to 3, grading the severity as follows:

• Marsh Type 0: Normal intestine, with no visible damage. Also known as the “pre-infiltrative stage”, it is unlikely the individual has celiac disease. 
• Marsh Type 1: Increased intraepithelial lymphocytes (IELS), a type of white blood cell found in the immune system. Normal villi and normal crypt hyperplasia. Type 1 is seen in patients on a gluten free diet, patients with dermatitis herpetiformis, and family members of celiac disease patients. Type 1 may also indicate other health conditions such as gastroduodenitis, hypersensitivity to food infections, bacterial overgrowth, use of pharmacological drugs, IgA deficit, or Crohn’s disease.  
• Marsh Type 2: Inflammation plus increased crypt hyperplasia/damage to the crypts. Normal villi. This type is rare, but seen occasionally in patients with dermatitis herpetiformis.
• Marsh Type 3: Indicates symptomatic celiac disease. Changes from Type 2 plus progressive atrophy (flattening) of the villi. Type 3 has three substages:
• Marsh Type 3A: Mild villous atrophy
• Marsh Type 3B: Marked villous atrophy
• Marsh Type 3C: Complete villous atrophy

The Marsh score is considered the gold standard for celiac diagnosis. However, because other conditions can cause some of these same changes, blood tests and the patient’s response to a gluten-free diet can also help with diagnosis of celiac disease. 

Clinical Stages of Celiac Disease: Beyond the Marsh Score

Your doctor may describe celiac disease in clinical stages that describe the severity of symptoms and disease activity:

• Latent Celiac Disease: The person carries the celiac genes and may have positive blood tests but has no intestinal damage. Symptoms are very mild or not present at all.
• Silent Celiac Disease: Intestinal damage has been confirmed on biopsy, but the patient doesn’t experience any noticeable symptoms. This is often found through screening or after a related diagnosis (e.g., dermatitis herpetiformis).
• Active Celiac Disease: The person experiences symptoms and shows clear signs of damage and inflammation in the small intestine.
• Refractory Celiac Disease: Symptoms persist even after strictly avoiding gluten for 6–12 months. This rare form may require additional treatments beyond a gluten-free diet.
• Classic Celiac Disease: Patients experience classic gastrointestinal symptoms. 
• Nonclassic Celiac Disease: Patients experience non-gastrointestinal symptoms such as anaemia, migraines, fatigue, anxiety, or vitamin deficiency. 

Symptoms of Celiac Disease by Life Stage

Symptoms of celiac disease can manifest differently depending on the patient’s age. 

• Infants and Young Children: Failure to thrive, chronic diarrhea or constipation, abdominal pain or bloating, irritability, sadness, dental enamel defects or delayed growth
• Teens: Delayed puberty, weight loss, fatigue, skin rashes, headaches/migraines, depression, dermatitis herpetiformis, or dental enamel defects

• Adults: Digestive issues (bloating, gas, diarrhea), anemia, bone or joint pain, infertility or miscarriage, neurological symptoms (tingling, migraines, brain fog), dental enamel defects, or dermatitis herpetiformis 

Diagnostic Testing at Different Stages

Diagnosing celiac disease involves several steps and tests, which vary based on disease stage and symptom severity. Your doctor will begin by evaluating symptoms, reviewing family and medical history, and conducting blood tests, including antibody and genetic tests. Blood tests detect immune responses that suggest celiac disease or identify genes that increase the risk of developing celiac disease.

These blood tests detect immune responses that may be celiac disease, but they aren’t enough to confirm a celiac diagnosis alone. If the results of the antibody or genetic screening tests are positive, your doctor may suggest an endoscopic biopsy of your small intestine. 

It’s important not to start a gluten-free diet before testing, as removing gluten can normalize results.

Managing Celiac Disease at Any Stage

The only treatment for celiac disease is strict adherence to a gluten-free diet. This means avoiding all foods containing wheat, barley, and rye, including hidden sources in processed foods, medications, supplements, and cosmetics. Exposure to even trace amounts of gluten can trigger symptoms and stall recovery. 

Helpful tips for avoiding gluten include:

• Familiarize yourself with hidden sources of gluten and read ingredient labels thoroughly
• Avoid cross-contamination that can occur in shared kitchens and processing facilities
• Choose certified gluten-free products when available
• Work with a doctor who is experienced in celiac disease to develop an individualized gluten-free diet
• Monitor symptoms and follow up with your healthcare provider regularly

When To Talk to Your Doctor

It’s time to talk to your doctor if you: have persistent digestive symptoms or fatigue, have a family history of celiac disease or autoimmune disorders, notice signs of malnutrition or unexplained weight loss, are struggling with infertility, are experiencing delayed growth in children or delayed puberty in teens, or you have dermatitis herpetiformis or other unexplained skin issues. Early diagnosis and treatment, before extensive damage occurs, can prevent long-term complications and improve quality of life dramatically for individuals living with celiac disease. Don’t wait, contact your healthcare provider today.