What is Refractory Celiac Disease & How is it Treated? | Causes, Risk Factors, Symptoms, and Complications of Refractory Celiac Disease

What is Refractory Celiac Disease?

Refractory celiac disease is an autoimmune condition. It is a type of celiac disease that remains unresponsive to at least 12 months of a gluten-free diet.

Celiac disease is a very common gastrointestinal disorder that people manage with a gluten-free diet. In refractory celiac disease, people even after excluding gluten from the diet do not feel any improvement in the symptoms and continue to have symptoms of damage to the gut.

According to a review, there are several types of celiac disease identified by doctors based on their clinical presentations.(1) These include:

  • Potential
  • Subclinical
  • Intestinal or classic
  • Seronegative
  • Gluten-free diet nonresponsive
  • Refractory
  • Extraintestinal or non-classic

Refractory celiac disease is of two types i.e., type 1 and type 2. Type 2 is known to occur predominantly in adults aged 50 years.(2)

Causes and Risk Factors of Refractory Ciliary Disease

According to the National institute of diabetes and digestive and kidney diseases, celiac disease may occur in people with specific genes or if a family member is suffering from this condition.(3)

According to a multinational study done on children, it was suggested that those genetically susceptible or who eat more gluten are more at risk of developing celiac disease.(4)

There are three elements that play a role in the body’s immune system. These include:

  • Lymphocytes
  • Cytokines
  • Antigens
  • Lymphocytes

These are the white blood cells and the main cells of the body’s immune system. There are two types of lymphocytes and intraepithelial or T-cells are the type of lymphocytes.

T-cells are present in the lining of the intestine. The protein present on the surface of the T-cells is known as the T-cell receptor. In celiac disease when T-cells recognize gluten, the protein activates. By taking the gluten-free diet the T-cells remain inactive. In refractory ciliary disease, the T-cells get active even without gluten. This keeps the damage persistent despite removing gluten from the diet.

Cytokines

Cytokines are small proteins that help in regulating communication among the cells of the immune system and other tissues.

In people with refractory celiac disease, there is an increase in the proinflammatory cytokines called interleukin-15, which support inflammation.

Interleukin-15 in turn stimulates another small protein called interferon-gamma that is known to increase the toxicity of T cells in the intestinal lining. More and more damage to the cells of the lining of the intestine leads to symptoms of refractory celiac disease.

Antigens

About 2-3 % of people with celiac disease test negative for antibodies and this is termed seronegative celiac disease.(2)

Those with seronegative celiac disease are at a higher risk of developing refractory celiac disease.

Symptoms of Refractory Celiac Disease

The symptoms of refractory celiac disease in adults include:

The symptoms are due to the damage to the gut cells after 1-year strict restriction of gluten.

There may be additional symptoms and complications including:

  • Nutritional deficiencies
  • Fever
  • Night sweats
  • Gastrointestinal bleeding
  • Bowel obstruction

Diagnosis of Refractory Celiac Disease

About 2 million people in the United States have celiac disease, many do not have a diagnosis.(5)

The condition is diagnosed by assessing the symptoms of gut damage for at least a year after the beginning of a gluten-free diet. The diagnosis is confirmed by a celiac disease antibody test and checking for villous atrophy.

The diagnostic test performed by the doctor may include:

  • Endoscopy
  • PET scan
  • MRI scan
  • Enterography

Treatment of Refractory Celiac Disease

Currently, the only treatment for celiac disease is being on a gluten-free diet for lifelong. Refractory celiac disease may be treated depending on the subtype.

The treatments for type 1 refractory celiac disease may include, immunosuppressants. Type 2 refractory celiac disease treatment may include cyclosporine or chemotherapy, anti-IL-15 antibodies, or stem cell transplant.

Complications of Refractory Celiac Disease

Refractory celiac disease may lead to the following complications:

  • Ulcerative jejunoileitis, which causes ulcers and scarring in the jejunum and ileum.
  • Collagenous sprue, which affects the mucosa in the small bowel leading to collagen deposits.
  • Intestinal lymphoma, which is a type of stomach cancer.

Refractory celiac disease is a type of celiac disease in which the symptoms occur even after following a strict gluten-free diet. Its outlook depends on the subtype. The condition can lead to complications and should therefore be treated at the earliest.

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