Non-Responsive Celiac Disease

Non-responsive celiac disease is defined as having symptoms, elevated antibodies or small intestinal damage even after following a strict gluten-free diet for six to 12 months.

Some celiac disease patients don’t respond to the gluten-free diet because of conditions unrelated to celiac disease, including bacterial overgrowth and lactose intolerance, but even when these are excluded, a seemingly strict gluten-free diet can inadvertently include enough gluten to trigger symptoms or damage.

Who’s at Risk of Having Non-Responsive Celiac Disease?

Non-responsive celiac disease is common in both children and adults.

A 2007 study by the gastroenterology department at Beth Israel Deaconess Medical Center, Boston, found that 36% of patients with non-responsive celiac disease were inadvertently consuming gluten.

In recent years, endoscopy and biopsy studies have shown that non-responsive celiac disease includes a larger group of patients than previously thought. While current scientific literature indicates that about 30% of patients have non-responsive celiac disease, there is evidence the number is closer to 50% when those who don’t have symptoms but continue to have damage to the intestine, called mucosal atrophy, are included.

How is Non-Responsive Celiac Disease Treated?

Doctors will first want to pinpoint the cause. Potential reasons for continuing symptoms include:

• Accidental gluten consumption
• Lactose intolerance
• Cow’s milk allergy
• Bacterial overgrowth

Once the cause is known, healthcare professionals may recommend a variety of treatments, such as cutting out additional foods, further education with a dietitian or nutritionist, additional testing, or a referral to an expert. 

Enfermedad celíaca refractaria

Refractory celiac disease is marked by a lack of response to a strict gluten-free diet after six to 12 months, with symptoms, intestinal damage and a specific type of white blood cell in the gut called “abnormal intraepithelial lymphocytes.” These cells, found in the lining of the small intestine, distinguish refractory celiac disease from non-responsive celiac disease. Their presence can—but does not always—indicate the beginning of cancer.

Because refractory celiac disease is rare, doctors may also rule out autoimmune enteropathy, which can mimic RCD, as a cause.

Type I versus Type II

There are two types of refractory celiac disease, type I or type II. Doctors use a device called a flow cytometer to analyze the chemical and physical properties of your cells. Patients with less than 20% of the abnormal lymphocytes have type I refractory celiac disease, and those with more than 20% have type II. 

About 1 in 100 celiac disease patients have Type I refractory celiac disease, and 1 in 200 have Type II. Patients with Type II have a greater than 50% chance of the abnormal lymphocytes spreading outside the gut, causing a full-blown lymphoma, which has a poor prognosis and high mortality.

What Causes Refractory Celiac Disease?

It is unclear what exactly causes refractory celiac disease, although not following the gluten-free diet consistently can be a risk factor. Once refractory celiac disease has developed, a gluten-free diet does not stop the lymphocytes from increasing, so drug therapies are often needed in addition to the gluten-free diet. Anyone with celiac disease, no matter what type, must remain on a strict, gluten-free diet for the rest of their life.

Who’s at Risk of Developing Refractory Celiac Disease?

Most cases of refractory celiac disease occur in older patients who are not diagnosed until later in life. Typically, they have had symptoms for many years until severe pain develops or abnormalities such as severe anemia are discovered, and then celiac disease is pinpointed as the cause.

Refractory celiac disease only appears in patients who have not been on a gluten-free diet or have not followed the diet correctly for decades.

How is Refractory Celiac Disease Treated?

According to the American Gastroenterological Association, the first line of therapy for both type I and type II refractory celiac disease is a type of immunosuppressant called corticosteroids, specifically open-capsule budesonide or prednisone. Patients should also stay on a gluten-free diet.

Some doctors may also prescribe an elemental (and gluten-free) diet for those with refractory celiac disease. An elemental diet is a type of liquid diet that makes nutrients easier for the intestine to absorb.

If these do not work, patients may be encouraged to enroll in clinical trials.

Fortunately, drugs to treat celiac disease are currently in development.