How Does Mucositis Develop?

Our mucous membranes are very sensitive to the inflammatory effects of radiation therapy and various chemotherapy drugs. When interacting with mucous membranes, these anti-cancer therapies create free radicals in the affected tissues. A key inflammatory ‘switch’ (a protein called, NF-kB) becomes activated after sensing these highly reactive chemicals, and turns on a cascade of inflammatory cells and proteins which cause the development of painful sores and ulcers in the mouth and throat; a condition commonly referred to as “mucositis.” Harmful bacteria and fungi are able to colonize these inflamed tissues, which can make the condition worse. Not infrequently, patients can get yeast infections of the mouth and throat (i.e. thrush or candidiasis.)

Time Course of Mucositis:

During Chemotherapy: Mucositis can develop within a 5-10 days after starting certain chemotherapy drugs, and this can last for 2-4 weeks after completing chemotherapy (particularly, after recovery of white blood cell counts.) It is not uncommon for these drugs to cause mucositis throughout the entire gastrointestinal system, which can cause symptoms related to the affected sites.

During Radiation Therapy: Mucositis of the mouth and throat only develops when radiation is directed at cancers within these tissues (unless it is due to a chemotherapy drug.) Typically, the first signs of mucositis begin about 3 weeks into treatment and peak a few days after the final treatment session. Radiation-induce mucositis can last for several weeks to months after completing treatment. 

How Does It Heal?

Once the inciting chemotherapy agents and/or radiation therapy have been discontinued and are no longer stimulating the inflammatory process, the mucous membranes are able to begin healing. Over days-to-weeks, wound healing cells (i.e. fibroblasts), proteins, nutrients and oxygen flow into the damaged tissues through newly formed blood vessels. Quickly thereafter, the painful sores resolve, the inflammatory process deactivates and the natural flora of oral microorganisms returns to normal.

Prevention Reduces Mucositis Risks and Severity

Research has shown that by optimizing oral hygiene, one can reduce the risk and severity of mucositis. If possible, it is important to involve your dentist in your cancer care before starting chemotherapy or radiation therapy (when the cancer involves the head and neck.) They play an essential role in helping to identify and address any pre-existing tooth and gum issues. If you have a dental appliance, they will assess whether they are fitting properly. Appliances (i.e. dentures) that don’t fit well can apply friction or too much pressure on the surrounding tissues, which can exacerbate mucositis symptoms. Untreated gingivitis can also increase the risk and severity of mucositis.

To reduce the build-up of the bacteria that can cause plaque and gingivitis, it is important to brush (after meals) and floss your teeth, daily. Proper technique will help to prevent injuring your gums. (Learn how to brush and floss.) Use a soft brush and change it regularly. To reduce the risk of oral or systemic infections, American Dental Associate recommends:

• Changing your toothbrush every 3-4 months
• Do not share toothbrushes
• Thoroughly rinse toothbrushes with water after brushing to remove any remaining toothpaste and debris
• Do not routinely cover toothbrushes or store them in closed containers

Use a non-alcoholic oral rinse to further help reduce the amount of plaque-causing bacteria. These rinses are not a replacement for brushing and flossing. We recommend making your own oral rinse with salt and water (the addition of baking soda is also frequently added to help break up the thick salivary secretions):

• Mix 1/2 to 1 teaspoon of salt (with or without 1 to 2 teaspoons of baking soda) with 1 cup of warm water. Rinse several times each day for 1 minute (swish, gargle and spit.) Make a fresh mouth rinse each time.
• Tom’s of Maine makes a quality alcohol-free baking soda mouth rinse, as well.

Anectdotally, these salt-based rinses seem to help speed the healing of established mouth sores.

• Ice chips have also been shown to help reduce mucositis when sucked on during the administration of certain chemotherapy drugs (i.e. 5-FU, malphalan). Ice (cryotherapy) helps to reduce the blood flow and perfusion of drug into the oral mucosa during the bolus administration.

Laser therapy (using a “cold” laser or “low-level light therapy”) has been shown to reduce the severity of chemotherapy-induced mucositis. By shining a non-thermal (no heat) laser on the tissues of the mouth (tongue, lips, gums, cheeks, roof and floor of mouth), the underlying mucous membrane cells speed up their rate of repair.  This works best is started before beginning cancer chemotherapy (although not a proven contraindication, to avoid any possibility of tumor protection we don’t recommend using laser therapy for those with cancers of the mouth.)

What to do Once You Have Mucositis:

It is important to continue to maintain oral hygiene to minimize the inflammatory effects of plaque causing bacteria. The use of salt rinses (with or without baking soda) should be continued. Mucosal protectants, topical anti-inflammatories, topical anesthetics and various complementary therapies (chamomile tea, honey, licorice extract, L-glutamine) are among the first-line approaches to managing mucositis. Second and third-line approaches (beyond the scope of this blog post) involve non-opioid, opioid pain medications, and a numerous other pain management approaches.

Mucosal protectants are compounds that coat and form a protective mucosal barrier to help reduce the severity of mucositis. Although they are quite effective when started at any during the mucositis course, there are data that suggest that they may work even better if started prior to the onset of mucositis.

Prescription options:

• Gelclair
• MuGard

Non-prescription options:

• Honey (1 to 2 tablespoons, swish and swallow) or add to chamomile tea, both of which have been reported to protect against mucositis. Chamomile tea should be steeped for 15 minutes, covered and then swished and swallowed as a cool/warm (not hot) tea.
• Canker Goo (licorice solid extract and peppermint essential oil): apply to sores and ulcers 6 times daily, as needed. Licorice extracts are reported to protect against mucositis.
• Deglycyrrhizinated Licorice tablets (chew one every two hours, as needed)

Supports mucosal barrier health:

• L-Glutamine powder (2-5 grams in 4 ounces of water every 2 hours, as needed). Orally administered L-glutamine, an essential amino acid, has been reported to protect against mucositis by supporting cellular repair.

Pain medications and anti-inflammatories:

• Benezydamine hydrochloride oral rinse (a topical anti-inflammatory)
• Liquid lidocaine oral solutions (topical anesthetic)
• “Magic mouthwash” is a commonly prescribed formulation of liquid lidocaine, diphenhydramine (anti-inflammatory), maalox (mucosal protectant). There are many formulations for magic mouthwash, which may include: anti-fungals, corticosteroids and/or antibiotics. **Although commonly prescribed, there is no evidence that this is more effective than a salt/baking soda solution.

Dietary Factors:

• Maintaining a healthful nutritional status is essential in reduce the risk and severity of mucositis, as wound healing is impaired in those who are nutritionally depleted. We often recommend a referral to a nutritionist or dietician prior to starting cancer treatment.
• Spicy, acidic or hot foods and liquids, and alcoholic beverages can irritate and further inflame sensitive mucous membrane tissues.

Other factors:

• Use of tobacco products can irritate mucous membrane tissues.
• Dry air can further exacerbate mucositis symptoms. Use of oral moisturizers (glycerin-based oral rinses), salt/baking soda oral rinses and breathing humidified air (particularly when sleeping at night) may be of help. 

Late Effects of Mucositis:

Patients who have been treated with radiation therapy to the head and neck, may develop permanent thinning of the mucous membrane tissues, thickened salivary secretions and/or dry mouth. Late effects can include an increased risk of:

• dental carries (cavities)
• gingivitis
• mucosal sensitivity and pain
• diminished taste sensation

It is important to continue to follow-up with your dentist regularly after cancer treatment is over. If you have dental appliances, they may need to be adjusted due to changes in tissue thickness and sensitivity. Additionally, your dentist may prescribe a fluouride mouth rinse for prevention of dental carries.