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Mucositis - Oral Problems and Solutions
Ernest H Rosenbaum, MD, Sol Silverman, MA, DDS, Bernadette Festa, MS, RD, Isadora R. Rosenbaum, MA, Julie Matel, MS, RD, Rosemary Elliott-Snow, RDH, and Robert J. Ignoffo, PharmD

Surgery To the Head And Neck Area
Radiation Effects

Mucocutaneous Changes and Mucositis
Loss of Taste

Salivary Function
Dental Caries
Candidiasis

Osteonecrosis
Osteoradionecrosis

Soft Tissue Necrosis
Dental Treatment Planning

Mucositis Table of Contents


Surgery To the Head And Neck Area
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Surgery to the head and neck area often affects the ability to eat. Proper planning before surgery should include a visit to a dentist to insure optimal oral/dental health, whether that involves tooth decay, gum disease or dentures. If necessary, special dental appliance can be made to replace any teeth or tissues to be removed for cancer control. These appliances will help drinking, speech, chewing and swallowing.

Your diet may have to be modified because of a change in your ability to chew some foods. Adapting to surgery involving the tongue or other oral structures often takes time, and may require swallowing rehabilitation with a speech pathologist or occupational therapist specifically trained in head and neck swallowing disorders.


Radiation Effects
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Ionizing radiation delivered in doses that kill cancer cells induces unavoidable changes in the surrounding normal tissues, causing compromises in function and host defenses and severe complications.


Mucocutaneous Changes and Mucositis
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Unless intraoral or interstitial treatment is used, most patients will develop some erythema (redness) and moderate tanning of the skin in the treatment portal. Hair follicles are quite radiosensitive, therefore if hair is in the radiation treatment beam field, it will cease to grow and will fall out. This is often transient.

The acute oral mucosal reaction (mucositis) is secondary to radiation-induced cell division (mitotic) death of the basal cells in the oral mucosa. If the radiation is delivered at a rate equivalent to the ability of the oral mucosa to regenerate, then only mild mucositis will be seen. Oral microorganisms probably play a role in aggravating the impaired epithelium. Smoking is also a factor. Clinically observed late or post radiation-induced atrophy (tissue damage) and telangiectasis (blood vessel, spider-like red spots) of the mucosa often increase the risk for pain and/or necrosis.

Management of acute mucositis may sometimes require a one-week interruption of therapy See Mucositis - Chemotherapy Problems and Solutions for more information. Topical anesthetics (Viscous Xylocaine ®) may be of some value, but the pain usually requires systemic analgesic drugs. Since infections may be associated, appropriate diagnosis and antimicrobial agents must be considered for either fungal or bacterial organisms. Viral infections are rarely a complication of radiation-induced mucositis. A short course of systemic prednisone (40 to 80 mg daily for not more than one week) has been helpful in reducing inflammation and discomfort.


Loss of Taste
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Taste buds, which occur primarily in the tongue papillae (circumvallate and fungiform), are very sensitive to radiation. Because of their location in the tongue, they are included in the beam of radiation for most oral cancers. Therefore, patients will develop a partial (hypogeusia) or, most usually, complete (ageusia) loss of taste during treatment. The cells comprising taste buds usually will regenerate within four months after treatment. However, the degree of long-term impairment of taste is quite variable from patient to patient.

Dietary consultations regarding recipes with pleasing texture and perceptible and pleasing tastes are essential to improve intake of food. However, there are tremendous patient to patient differences, which preclude standard recommendations. Failure in taste perception, in addition to pain, dysphagia, hyposalivation and depression, is associated with the loss of pleasure in eating, thus, a loss of appetite. Weight loss, weakness, malaise and dehydration often follow. This is further complicated when prior surgery has caused problems in mastication and swallowing. Trials with zinc supplements such as zinc sulfate (ZnSO4) exceeding the usual recommended daily doses (RDA) appear to be helpful. We have prescribed 50 to 100 mg elemental zinc daily with success in some patients (220-440 mg ZnSO4). While zinc serves as a critical enzyme in many biochemical reactions, its role in taste and saliva remains unknown. Saliva probably has a modulating effect on the acuity of some tastes (sour, bitter, salt, sweet) through biochemical interactions, as well as providing an ionic environment in signal transduction for taste cells.


Salivary Function
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Exposure of the major salivary glands to the field of ionizing radiation induces fibrosis, fatty degeneration, glands (acinar) atrophy, and cellular necrosis within glands. A critical dose level has not been identified. The serous glands (acini) appear to be more sensitive than the mucinous. During irradiation, the glandular secretions are usually diminished, thick, sticky, and very bothersome to the patient. Some patients are unable to produce more than 1 ml (15 drops) of pooled saliva in 10 minutes. The duration of this depressed salivary function varies from patient to patient. Some regeneration can occur several months after treatment, and the undesirable signs and symptoms of xerostomia (dry mouth with discomfort, difficulty in speech and swallowing) may be modified. However, recovery of adequate saliva for oral comfort and function may take up to 12 months; in others the saliva remains inadequate indefinitely and is the source of major post-treatment complaints. When both of the parotid glands are exposed to the treatment beam, saliva diminution is most marked, and the prognosis for recovery is the worst. Obviously, the higher the dosage of irradiation, the worse the prognosis for mouth dryness.

Frequent sips of water and water rinses are essential for partial control of radiation-induced xeroxtomia. Sugarless chewing gum and tart candy may be helpful. In some patients, pilocarpine hydrochloride as a solution or tablets (Salagen®) has been effective in stimulating saliva production (5 mg 3 or 4 times daily). Side effects can include sweating and stomach discomfort. Another salivary gland stimulant, cevimeline (Evoxac®), administered as 30 mg capsules 3 times daily, has been helpful in many xerostomic patients. These agents are contraindicated in patients with asthma, gastrointestinal ulcers and narrow angle glaucoma.

Synthetic saliva solutions and saliva substitute lubricants have been of limited help in the majority of patients with dry mouth, although some favorable reports have been published. Oral Balance®, an over-the-counter gel, is a good example. In some patients in whom the salivary complaint is related to the "thickness" (excess mucous-type secretions), guaifenesin (Organidin NR®) as a liquid or tablet may help as a mucolytic agent (200-400 mg, 3 to 4 times daily).

Because of the painful mucositis, loss of taste, and xerostomia, the lack of desire or frank inability to eat is a common and almost universal complaint in patients receiving external irradiation to the oral cavity. A resultant weight loss tends to weakness, inactivity, discouragement, further anorexia, and susceptibility to infection. Therefore, close attention is given to food intake and weight maintenance during treatment and follow-up. Anemia, bleeding, or immune deficiencies have not been complications of head and neck radiation.


Dental Caries
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Patients who have not shown any degree of caries activity for years may develop dental decay and varying degrees of disintegration after irradiation. This condition appears to be due to the lack of saliva as well as to changes in its chemical composition.

To prevent or at least minimize radiation caries, oral hygiene must be maximal, including intensive home care and frequent office visits for examination and prophylaxis. Mouth rinsing is essential. Antiseptic mouth rinses, for example, chlorhexidine (Peridex®, Periogard®), if tolerated, are helpful in eliminating debris and controlling microbial flora. Daily topical fluoride applications, either as a solution for mouth rinsing, a gel delivered by means of a tray, or brushed on as a paste or gel, are all effective (as examples, Prevident® and Gel Kam®). Prevident is a sodium fluoride paste, and Gel Kam is a stannous fluoride gel. Attempts should be made to increase salivary flow either by local or systemic means. Foods and beverages containing sucrose should be avoided as much as possible. If carious lesions develop, removal and restoration should take place immediately. Appropriate use of dental x-ray imaging is in order when indicated to monitor caries activity.


Candidiasis
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Infections of the mouth by Candida albicans are commonly seen in irradiated patients, and are related to alterations in the saliva. Clinically, the signs may be confused with radiation mucositis or other sources of infection. Candidiasis is usually painful. Management is primarily with the use of antifungal drugs. Systemic administration (200 mg ketoconazole daily with food, or fluconazole 100 mg daily) is usually more effective for both response and compliance. Duration of treatment depends upon control of signs and recurrences, since complete elimination of Candida from the oral flora usually does not occur. Topical administration entails the use of nystatin or clotrimazole tablets dissolved orally. Because of pain and dryness from mucositis, patients may experience difficulty in dissolving tablets topically. Suspensions are another alternative form of treatment, but often this is not as effective because of limited contact time between drug and fungus. Antiseptic mouth rinses similar to those used for caries control may be helpful, if tolerated. In addition, topical (Viscous Xylocaine®) or systemic analgesics may be required. Keeping the mouth moist is essential. There is always the possibility of developing fungal resistance, or the need of higher dosages, when these agents are used for prolonged periods of time. (See table on antifungal drugs) Removable dental appliances (prostheses) can be treated with various soaks for the dentures: chlorhexidine (Peridex, Periogard), Listerine, dilute Clorox (1 tsp. in 8 oz. water).


Osteonecrosis
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Avascular necrosis (osteonecrosis) is a disease resulting from the temporary or permanent loss of the blood supply to the bones. Without blood, the bone tissue dies and causes the bone to collapse. Osteonecrosis of the jaws (ONJ) is a condition whereby there is loss or destruction of the bone underneath the teeth. This loss of bone appears to be caused by a combination of poor blood supply and impaired bone remodeling or healing. Osteonecrosis has been reported in patients with cancer receiving treatment for metastatic disease and multiple myeloma including bisphosphonates such as: Aredia® and Zometa®, chemotherapy, and/or corticosteroids. Bisphosphonates remain a critical element of care to reduce bone destruction in cancer patients See Elevated blood calcium level (Hypercalcemia) , Osteoporosis - Prevention, Diagnosis and Therapy, Osteoporosis - Diagnosis and Consequences , Osteoporosis - Evaluation, Prevention and Therapy. Patients should continue to use bisphosphonates as recommended by their physicians. The majority of reported cases have been associated with dental procedures such as tooth extraction and poor dentition. A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with concomitant risk factors with recommendations for preventive dentistry. Once bisphosphonate therapy has begun, invasive dental procedures must be undertaken with due caution. Be alert and aware that bisphosphonate use can be associated with jaw or dental problems, including pain, bone loss, and poor healing. Problems are more likely with longer periods of bisphosphonate use. No data are available as to whether discontinuation of bisphosphonate therapy reduces the risk of ONJ in patients requiring dental procedures.

If the osteonecrosis is severe, if at all feasible, steroids such as prednisone or dexamethasone should be discontinued or reduced. Major surgical intervention irradiation therapy involving the head/neck should be avoided if at all possible.

Conservative measures such as antibiotic treatment and mouth rinses would seem to be quite helpful and safe. Intravenous antibiotics may be required for more severe or acute secondary infections. Ongoing use of an antibiotic such as penicillin has also been recommended if problems persist.


Osteoradionecrosis
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Osteoradionecrosis is one of the more serious complications of head and neck irradiation for cancer. Bone cells and vascularity may be irreversibly injured. Fortunately, in many cases devitalized bone fragments will sequestrate, and lesions will spontaneously heal. However, when radiation osteonecrosis is progressive, it can lead to intolerable pain or fracture and may necessitate jaw resection.

The risk for developing spontaneous osteoradionecrosis is somewhat unpredictable, but it is related to the dose of radiation delivered (usually more than 6000 cGy) and bone volume. The mandible is at higher risk than the maxilla. The risk is increased in patients without dentures and even more if teeth within the treatment field are removed after therapy. Spontaneous bone exposure usually occurs more than one year after radiation is completed. The risk for osteonecrosis continues indefinitely following radiation therapy.

If osteonecrosis does not progress clinically or radiographically, the usual management involves periodic observation. If flares (swelling, suppuration, pain) only occur occasionally, antibiotics are usually effective. If pain and/or flares occur too frequently or present other difficulties for the patient, surgery must be considered. Hyperbaric oxygen treatments along with surgery and antibiotics may be helpful in healing based upon angiogenesis induced by increased oxygen.


Soft Tissue Necrosis
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Soft tissue necrosis may be defined as the occurrence of a mucosal ulcer in irradiated tissue that has no residual cancer. The incidence of soft tissue necrosis is related to dose, time, and volume irradiated. The risk is far greater with interstitial implantation and intraoral techniques because of the higher irradiation doses used.

Soft tissue necrosis is usually quite painful. Optimal hygiene is required and analgesics are usually helpful, but antiobiotics are generally of little help in relieving pain and promoting healing. Since these ulcerations are often at the site of the primary tumor, periodic assessment for recurrence is essential until the necrosis heals.


Dental Treatment Planning
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In view of the risk that accompanies high-dose irradiation, special attention to preradiation dental planning appears critical.

Factors important in the dental management of these patients include the following:

  1. anticipated bone dose,
  2. pretreatment dental status, dental hygiene, and retention of teeth that will be exposed to high-dose irradiation,
  3. extraction techniques,
  4. allowance of adequate healing time for teeth extracted before radiotherapy, and (5) patient motivation and capability of compliance to preventive measures.

Since many infections occur months or years after treatment, it is evident that the tissue changes induced by radiation persist for long periods of time and may be irreversible. Therefore, extreme care must be taken in evaluating the status of the teeth, and periodontal hygiene must be maintained because of the lowered biologic potential for healing in response to physical irritation, chemical agents, and microbial organisms. Such attention is critical because of the potentially progressive nature of radiation osteonecrosis, which may involve large segments of bone and present a major therapeutic problem, possibly requiring extensive resection.

It is impossible to establish precise formulas for managing preradiation and postradiation dental problems. Extractions are considered primarily for teeth with a poor prognosis due to such conditions as advanced periodontal disease, extensive caries activity, and periapical lesions. Other considerations are sources of chronic soft-tissue irritation (trauma), and the degree of patient cooperation and compliance in preventive home care and dental office programs. The decision is modified further for each patient on the basis of prognosis, age, desires, economic aspects, and radiation delivery. Patient orientation to pros, cons and risks is essential.

Reported studies and personal experience don't substantiate the advisability of extracting all teeth before treatment as a good preventive measure. When teeth are extracted before or after radiation, the alveolar bone must be evenly trimmed and carefully smoothed so that a primary tissue closure is possible. This is necessary because suppression of bone cell viability diminishes remodeling, and if a suitable alveolectomy is not performed, the resulting alveolar ridge will be irregular and may increase the risk of subsquent bone exposure and discomfort. It may also compromise effective wearing of dentures. A minimum of one week to ten days is arbitrarily allowed for initial healing before radiation is instituted. However, if the situation permits, more time is preferable, up to 14 or even 21 days. Since dosages are fractionated, healing can usually continue before damaging levels of radiation are delivered to a surgical area. Obviously, teeth completely out of the treatment field are not affected similarly.

The use of antibiotics during the healing period is important to minimize infection. Whenever possible, an attempt is made to retain teeth to support tooth-borne appliances for the tentatively planned rehabilitation of these patients.

The periodontium is maintained in optimal condition by periodic routine periodontal procedures. When areas exposed to radiation are treated, extreme care is exercised and antibiotics may be selectively administered. Fluoride applications (daily, in the form of fluoride trays or prescription toothpaste or gels) appear to aid in minimizing tooth decalcification and caries in these patients. There are no unusual contraindications for endodontic procedures.



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First appeared February 2, 2002; updated October 31, 2007; reviewed August 7, 2011