Entanercept Successfully Treats Mouth Ulcers and Celiac Symptoms

Dentist There have been a number of studies showing an association of celiac disease with recurrent aphthous stomatitis, which means frequent, severe, painful mouth ulcers. These are usually very difficult to treat. The studies that have shown also found that the gluten-free diet sometimes, but not always, improves the symptoms of aphthous stomatitis.

A recently-published case report details a specific person with aphthous stomatitis and celiac disease, and the unusual treatment that improved the severe symptoms. There are a number of lessons to be learned from this case, most importantly that some of the new biologic agents used for other autoimmune diseases may help non- intestinal symptoms of celiac disease.

The patient was a 32-year-old woman with aphthous ulcers all over her mouth, extending to the back of throat. They were so numerous and painful that she had trouble chewing, eating and swallowing. Her ability to speak was affected and her quality of life was poor. Each bout of this problem started with an eruption of blisters. The blisters turned into ulcers. She also had other symptoms that often occurred at the same time as the ulcers, including joint pain, significant fatigue, and red irritated eyes.

New biologic agents used for other autoimmune diseases may help non- intestinal symptoms of celiac disease

Since she already had allergic rhinitis, the medical term for hay fever, she was taking antihistamines and using a steroid spray in the nose to treat this. She also took medication for migraine headaches. She had a family history of autoimmune diseases, as well as Raynaud’s phenomenon, a problem with blood vessels in the hands that may occur with autoimmune diseases.

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For all of these reasons, she was tested for celiac disease. Her antibody tests and intestinal biopsies confirmed the diagnosis of celiac disease. She was placed on a gluten-free diet, a number of vitamins to correct deficiencies, and a variety of treatments for the ulcers, from mouthwashes to medication to prevent acid from backing up into the mouth from the stomach. The ulcers continued. The only medication that helped was an oral steroid (prednisone) which improved the ulcers and some of her other symptoms. They returned when this medication was stopped. Although a repeat biopsy of her intestine showed healing of the celiac disease, her mouth ulcers did not heal.

A group of medications failed to improve the ulcers, including many that are used to treat other autoimmune diseases or excess stomach acid. Only prednisone and narcotics for pain gave her any relief. Finally, she was prescribed the injectable medication etanercept (Enbrel). After a short period of time on the injections, her apthous ulcers healed completely and the other symptoms of fatigue, joint pain and red eyes improved. enbrel_logo

Of course, this was a very good outcome for the patient by the time the medication was tried. It is not usually given to people with celiac disease, and the doctors taking care of her attempted to explain how this medication worked where others failed. It is known that people with CD can have abnormal white blood cells called T cells, and that they may have elevated levels of a substance called Tumor Necrosis Factor-α. TNF-α can start an inflammatory response via a number of chemical pathways, and this may be what causes recurrent aphthous stomatitis. People with recurrent aphthous stomatitis can have elevated level of this substance in saliva.

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Some of the systemic treatments given to the patient, such as prednisone, cyclosporine, azathioprine and colchicine can help change this inflammatory reaction. Small studies have shown promising results in treating recurrent aphthous stomatitis with biologic agents like etanercept (and others), although not specifically in patients with celiac disease as well. Etanercept does affect the immune system, increasing the risk of certain infections and possibly cancer. Although it is usually well tolerated, there are possible side effects and patients have to be followed carefully, which includes checking blood counts and blood chemistries. It is also expensive.

If you suffer with mouth ulcers discuss with your doctor if etanercept can help

The FDA has approved etanercept for a variety of inflammatory arthritis conditions. These include psoriatic arthritis (and severe psoriasis), ankylosing spondylitis, rheumatoid arthritis, and juvenile rheumatoid arthritis. It will almost certainly be approved to treat other conditions, but is already being used “off label” for a number of disorders.

In this case, the patient’s severe stomatitis affected her ability to work and her quality of life so significantly that the use of the medication was justified. It improved her fatigue and joint pain as well as her stomatitis, suggesting that these symptoms were all related.

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The case study published about this patient means that other doctors treating this condition may consider etanercept or other similar medications to treat recurrent aphthous stomatitis associated with celiac disease that does not respond to a gluten-free diet. If you suffer with mouth ulcers, discuss this with your doctor.


Adey Hasan, Hiren Patel, Hana Saleh, George Youngberg, John Litchfield, Guha Krishnaswamy.
Remission of severe aphthous stomatitis of celiac disease with etanercept. Clinical and Molecular Allergy 2013, 11:6.
Shakeri R., Zamani F., Sotoudehmanesh R., et al. Gluten sensitivity enteropathy in patients with recurrent aphthous stomatitis. BMC Gastroenterology 2009, 9:44.

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  1. I have the same problem, severe aphthous ulcers which seem to get a little better if I avoid all dairy. I currently take plaquenil which helps a little with RA symptoms but not much. I will be asking my doctor about enbrel. Thank you so much for all the info.

  2. Hi. I used to get these mouth ulcers, and found that eliminating toothpaste with sodium
    laurel sulfate took care of the problem.

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