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Managing Oral Mucositis
By Frank P Whyte
Last edited: Tuesday, August 19, 2008
Posted: Tuesday, August 19, 2008



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Oral Mucositis is a troubling disorder for cancer patients receiving chemotherapy or radiation therapy, primarily for head and neck cancers. This article gives disease pathogenesis, etiology, and tips for managing this disorder.

 

 
With the diagnosis of cancer comes the reality of an unforgiving disease process, one that never sleeps or takes a respite, but rather remains hard at work invading our body’s tissues, and changing our cells from what they once were into some unrecognizable mutation. The disease process is one that cleverly disguises itself, rendering our natural defenses impotent. While this causes great anguish in and of itself, it is often what comes next, beyond the fear, beyond the life changes, beyond the realization that nothing will ever be the same which proves to be more terrifying. It is the cancer treatment itself that challenges patients. It is chemotherapy-induced neutropenia, persistent nausea and vomiting, alopecia, neuropathies and myalgias, and on, and on, and on.
 
Among these, perhaps, there is none as demoralizing as chemotherapy and radiation therapy-induced oral mucositis. Oral mucositis is a term used to describe a constellation of symptoms causing inflammation and infection of the oral mucosa that is different from oral lesions with other pathogenic origins which are generally referred to as stomatitis, (1) and is an expression that became popular in the late nineteen eighties. It is a treatment-induced condition that leads to a reduced ability to consume food and fluids at a time when nutrition and hydration is critical to the prospect of treatment success. Oral mucositis is also painful and often requires significant daily doses of opiates; this after inpatient admission to the hospital, usually through emergency rooms, all leading to a significant increase in overall treatment related expenses. Once admitted, these patients are at an increased risk for nosocomial infection, experience a serious disruption of their daily activities, and face the very real possibility that their treatment protocols will be delayed or even discontinued.
 
Epidemiology:

Oral mucositis is a term used to describe a group of symptoms affecting the oral mucosa which results from chemotherapy or radiation therapy for the treatment of cancer. Symptoms may be mild or severe and can vary from vague discomfort to severe pain and an inability to tolerate food and fluids. There are approximately 400,000 new cases annually in the United States, (2) and these include cases of mucositis (stomatitis), xerostomia (dry mouth syndrome), bacterial, viral, fungal infections, dental caries, disruption of taste, and osteoradionecrosis. (2)
 
From an epidemiological perspective, 5% to 40% of patients who are treated with standard chemotherapy regimens will develop some form of mucositis. (3) For those patients receiving more aggressive regimens with agents such as fluorouracil, methotrexate, cyclophosphamide, and cisplatin, the incidence can be much higher and the symptoms much more debilitating. (4) For those patients who receive high-dose chemotherapy in advance of bone marrow transplantation, the incidence can be as high as 75% to 100%. (3) More than 80% of patients who receive high-dose radiation for head and neck cancers will be affected. (3), (4)
 
Research has likewise shown that the incidence of oral mucositis will be higher for patients receiving both chemotherapy and radiation. (5) It has also been determined that the degree and duration of symptoms is related to radiation source, cumulative dose, intensity, and the total volume of irradiated mucosa. (6)
 
Of particular note, with regard to patient related factors, is the fact that a full 75% of the population suffers from some degree of periodontal disease. This, coupled with the reality that many patients will suffer from acute bacterial super-infections following chemotherapy, suggests that clinical vigilance for signs and symptoms of oral mucositis is well-justified. (5)
 
Pathogenesis:
 
Stephen Sonis DMD, the preeminent authority on oral mucositis, has suggested a four-stage developmental process for this disorder. According to Sonis, et al, there is an initial or vascular stage of development, when exposed cells in the buccal mucosa release free radicals, modified proteins, and pro-inflammatory cytokines. The net effect of this process is that vascular permeability of mucosal cells is greatly increased, and this leads to an increased uptake of cytotoxic drugs into these cells. (7) (8)
 
This vascular phase then gives way to the epithelial phase when cell division is retarded and there is a reduced epithelial turnover, resulting in subsequent epithelial breakdown. Erythema and epithelial atrophy can be expected four to five days following chemotherapy, and patients will suffer microtrauma of the tissue resulting from speech, swallowing, and chewing. (7) (8)
 
Approximately one week after treatment, this degenerative process proceeds and enters the ulcerative or bacteriologic phase where there will be a loss of epithelial cells, exudate formation, and the production of pseudo-membranes and ulcers. It is at this time of complete cellular breakdown that cells become colonized by gram negative organisms and yeast. (7) (8)
 
The fourth and final phase in the Sonis paradigm is the healing phase, and this can be expected to last for twelve to sixteen days, and will be dependent upon several factors including epithelial proliferation rate, hematopoetic recovery, and a reestablishment of normal local microbial flora. Healing will occur as long as there is no persistent infection or mechanical irritation. (7) (8)
 
Risk:
 
Individuals at an increased risk for developing oral mucositis are the young, given their rapid mitotic rate, patients with poor nutritional status and decreased neutrophil counts prior to beginning treatment, and those persons with pre-existing xerostomia. The type of malignancy being treated also plays a role secondary to the prolonged and intense myelosuppression associated with hematological cancers.
 
Increased epidermal growth factor receptors, poor hygiene, ill-fitting dental prostheses, and medications with anti-cholinergic effect, such as tricyclic antidepressants all predispose patients to develop oral mucositis. (6)
 
Prevention and Treatment:
 
From a treatment perspective, there is sadly nothing available that is completely successful at preventing oral mucositis. (9) A thorough dental evaluation, with an eye to problem areas, should be conducted on every patient prior to beginning treatment. (6) Patients should also be encouraged to use a soft toothbrush with fluoridated toothpaste, and toothbrushes should be replaced monthly. If financial hardship is an issue, advise patients to run their existing toothbrush through the dishwasher monthly instead. (5) A balanced and nutritious diet is also key. (9)
 
Even though oral mucositis cannot be totally prevented, there are a number of interventions that oncology nurses can undertake to alleviate it when possible, and to treat it if it develops. Clinical studies evaluating the benefit of cryotherapy, which refers to the near-constant usage of ice chips during the at-risk period in the days immediately following the administration of chemotherapy, has shown some benefit. It is felt that the vasoconstriction caused by the cold temperatures reduces uptake of cytotoxic materials at a time when mucosal cells would be otherwise at an increased risk, secondary to permeability changes previously described by the Sonis paradigm.(9), (10), (11)
 
There have also been numerous studies evaluating the benefit of certain mouthwash preparations. Amifostine, associated with significant tolerability issues, (9) (12) Palifermin (13) and Gelclair, (14) have all shown similar limited benefit, as have fluoride tray treatments in the advance of chemotherapy administration. A study published by Athena Pappas DMD of the Tufts University School of Dental Medicine in Boston in 2003, however, has suggested significant decreases in morbidity with the use of an aqueous oral rinse, commercially available as Caphasol (15). In the Tufts study, Pappas, who originally formulated Caphasol, a supersaturated aqueous solution of calcium and phosphate, that was designed to restore the normal ionic and pH balance of the oral cavity, discovered that when it was utilized in conjunction with four fluoride tray treatments, that it was successful in decreasing total days of mucositis, peak level of mucositis, and days requiring treatment with morphine for the discomfort associated with mucositis. The conclusion of the Tufts study also suggested that Caphasol was particularly beneficial in the treatment of those patients who were intensely myelosuppressed in advance of hematopoetic stem cell transplantation, and those patients beset with xerostomia. (16)
 
In addition to commercially available products, oncology nurses can do much in their daily practices to assist their chemotherapy and radiation therapy patients suffering from oral mucositis. As much as possible, patients should be positioned sitting up at a ninety degree angle with their heads tilted slightly forward. Ice chips are also beneficial when used frequently in the days immediately following treatment.
 
Patients should be encouraged to eat small frequent meals, and both food and drinks should be warm, and not hot so as to avoid scalding mucosal tissues. Soft foods should be encouraged and crunchy foods discouraged, secondary to their propensity to abrade tissues. If appetite is an issue or if oral mucositis has decreased a patient’s desire to eat, suggest baby food or high protein milkshakes as an alternative. Commercially available products such as Ensure or Boost may also help to provide an adequate caloric intake. Alcohol and tobacco should also be avoided, as should spicy foods, and patients should be discouraged from talking while they have food in their mouths. The mouth should also be rinsed thoroughly before and after meals. (3), (6), (9)
 
Conclusions:
 
While oral mucositis has been historically dismissed for its clinical significance, in recent decades it has been recognized as a significant disorder capable of severely impacting treatment for cancer patients by causing potentially severe discomfort, reducing their intake of food and fluids, and leading to depression and potential non-compliance during a critical period in their treatment during initial and subsequent cycles. Oral mucositis can also lead to long term destruction of the teeth and bony structures of the oral cavity.
 
New research has led to the development of products that are yielding positive results. Nurses should be aware of the potentially catastrophic results of severe mucositis and should promote within their practices those interventions, and those products, which will lead to the prevention or control of this disorder.
 
Bibliography:
 
1.)     Dose AM, et al. Semin Oncol Nurs. 1995; 11: 248-55
2.)     Naidu MUR, et al. Neoplasia 2004; 6: 423-31.
3.)     Peterson DE. J Support Oncol 2007 ; 4 (suppl 1) : 9-13
4.)     Silverman S. J Support Oncol. 2007 ; 5 (suppl 1) : 13-21
5.)     Wilkes JD. Semin Oncol. 1998 ; 25 : 538-51
6.)     Berger AM, Kilroy TJ. In : Principles and Practice of Oncology. 5th ed. 1997:2714.
7.)     Sonis ST. Oral Oncol. 1998;34:39-43
8.)     Sonis ST, et al. Cancer. 2004;100(9 suppl):1995-2025
9.)     Rubenstein EB, et al. Cancer. 2004;100(9 suppl):2026-46
10.)Rocke LK. Cancer. 1993 ; 72 :2234-8
11.)Mahood DJ, et al. J Clin Oncol. 1991 ;9 :449-52
12.)Kostler WJ, et al. CA Cancer J Clin. 2001 ;51 :290-315
13.)Spielberger R, et al. N Engl J Med. 2004;351:2590-8
14.)Gelclair (bioadherent oral gel) prescribing information. October 2006
15.)Caphosol Prescribing Information, Cytogen Corporation, Princeton, NJ.
16.)Pappas AS, Clark RE, et al. Bone Marrow Transplantation. 2003 ; 31 :705-712
 

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