Stomatitis: An Overview

Protecting the oral cavity during cancer treatment.

By Carlton G. Brown, MSN, RN, AOCN, and Linda H. Yoder, PhD, RN, AOCN

ames Bryant, 70 years old, was diagnosed

three months ago with stage III colon cancer.
He had surgery to remove the tumor and
began chemotherapy treatment of fluorouracil (5-FU) given by bolus for five days
every four weeks. Mr. Bryant was admitted for neutropenic fever one week prior to his last 5-FU treatment and complained of mouth sores so severe that
he could hardly eat, drink or speak. Assessment of
his oral cavity revealed bilateral ulcerated inner portion of upper lip, thick, ropy saliva and his tongue
was shiny with redness. He also had generalized
ulceration without bleeding of the mucosal membrane of the inner cheek area.
Mr. Bryant is likely suffering from stage III or IV
stomatitis; 5-FU, a chemotherapy commonly used
in the treatment of colon cancer, is the likely cause.
He is immediately assessed and treated for pain and
infection prevention, and given nutritional support.
Before Mr. Bryant receives his next cycle of 5-FU, he
and his support group of family and friends are provided oral hygiene education, which includes information on brushing, flossing, rinsing, and
moisturizing the oral cavity. Mr. Bryant is also educated about adverse conditions of the mouth that he
should report to the health care team.

tumors also are affected.1 Seventy-five percent of

those with stomatitis complain of acute oral pain.2
The pain is sometimes so severe that patients receive
narcotics to relieve it or they prematurely withdraw
from their cancer therapy.
Ablating chemotherapy and intensive radiation
therapy kill not only cancer cells, but also all fastgrowing cells, particularly those mucosal cells lining
the inside of the mouth and throat. Damage to oral
mucosal cells can leave patients with extremely
painful open oral and esophageal sores, which make
eating, drinking, and talking difficult. Stomatitis
negatively affects patients quality of life, especially
those who suffer this painful side effect every time
they receive a cycle of chemotherapy or several
cycles of radiation treatments. The immunosuppressed patient with stomatitis is at severe risk for
life-threatening septicemia.
Stomatitis morbidity continues to be a significant
problem for cancer patients and their health care
team. Its important that nurses understand the etiology of stomatitis to prevent or reduce distressing
side effects. This article discusses the pathophysiology, specific causes, and prevention measures for
stomatitis.

PATHOPHYSIOLOGY
STOMATITIS
Mucositis and stomatitis are often used synonymously but each has a distinct meaning. Mucositis
is a toxic inflammatory consequence of chemotherapy or radiation treatment that disturbs the entire
gastrointestinal tract from the mouth to the anus.
Stomatitis is a form of mucositis that is specific to
the oral or oropharyngeal mucosus membranes.
Stomatitis is perhaps one of the most debilitating
and painful side effects of cancer therapy.
Approximately 40% of all patients receiving
chemotherapy endure stomatitis; 80% of all
patients receiving radiation for head and neck
Captain Carlton G. Brown is the oncology clinical nurse specialist at
Walter Reed Army Medical Center in Washington, DC. His mentor,
Colonel Linda H. Yoder, is a senior nurse scientist, also at Walter Reed.
The opinions or assertions contained herein are the private views of the
authors and are not to be construed as official or as reflecting the views
of the Department of the Army or the Department of Defense.

20

AJN April 2002

Supplement

The oral mucosa consists of nonkeratinized squamous epithelium cells that rapidly rejuvenate every
10 to 14 days. Unfortunately, chemotherapy and
radiation treatments meant to obliterate rapidly
replicating cancer cells also destroy epithelial cells
from the gastrointestinal tract, bone marrow, hair
follicles, and oral mucosa.
The intact oral mucosal lining serves as a first line
of protection against bacterial, viral, and fungal
infections. Every human being has normal flora
within the mouth consisting of gram-positive and
gram-negative bacteria, fungi, and viruses. This normal flora is kept in check by an intact immune system and undamaged oral mucosal lining. If the oral
mucosa becomes compromised by damage caused
by the effects of chemotherapy or radiation, the protective lining is broken, giving microorganisms,
especially those from the patients own normal
flora, a portal of entry into the body and eventually
http://www.nursingcenter.com

Four Phases in the Development of Stomatitis

PHASE

NAME

DAY
0

ETIOLOGY

Inflammatory/Vascular

Cytokine release. Tissue damage.

II

Epithelial

45

Decreased renewal of epithelial cells. Increased

atrophy and vascularity.

III

Ulcerative/Bacteriologic

612

Areas of erosion develop fibrinous

pseudomembrane. Bacterial colonization.
Most symptomatic phase for patients.

IV

Healing

1216

Renewal in epithelial proliferation. Reestablishment of

local microbial flora.

Source: Sonis ST. Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatotoxicity.
Oral Oncol 1998;34(1):39-43.

the blood stream. A pinpoint break in the tissue of

the lower lip, for example, could be an open door
for infection, particularly in the immunocompromised patient. The mortality rate of all patients
who become septic is 40% to 60%.3 Thus, its
important that nurses and other health care
providers know the early signs and symptoms of
infection. And if the patient with cancer experiences nutritional deficit coupled with a poorly
functioning immune system, septicemia can occur
quickly.
Stomatitis usually begins with asymptomatic
redness and erythema that progresses to minimally
painful white patches to large, contiguous, acutely
painful lesions. Sonis hypothesized that there are
four major phases related to stomatitis.4 In phase I
(inflammatory or vascular phase), shortly after a
chemotherapy or radiation treatment (day zero),
cytokines are released into the oral cavity that
cause damage to local tissue. Additionally, continued chemotherapy causes increased vascularity and
submucosal vascularity. During phase II (epithelial
phase), around days four to five, theres a marked
reduction in the renewal of epithelial cells; thus, no
new cells are available for repair or replacement.
Increased atrophy and ulceration are significant
confounders to tissue recovery. Phase III (ulcerative
or bacteriologic phase) occurs around days 6
through 12 and is the most complicated and symptomatic time for the patient suffering from stomatitis. During this phase, localized areas of erosion
develop a fibrinous pseudomembrane and colonization of bacteria occurs. This bacterial colonization releases damaging cytokines, further depleting
healthy levels of epithelial cells. The final phase,
phase IV (healing phase), usually takes place
around days 12 through 16, after chemotherapy or
radiation is completed. During this phase, theres
an eventual renewal in epithelial proliferation and
differentiation, leading to healing, along with
reestablishment of local microbial flora.
http://www.nursingcenter.com

RISK FACTORS
The most important risk factor associated with the
development of stomatitis is preexisting oral or dental disease.5 A dentist should evaluate patients
before chemotherapy or radiation therapy is initiated.6 Children and young adults younger than 20
years have a propensity to develop stomatitis more
frequently7, 8 but their lesions heal quickly.4 Sloan
and colleagues showed that women report both the
presence of stomatitis more frequently and at a
higher severity when compared to men.9 Other risk
factors associated with the development of oral
complications include: type of malignancy,
chemotherapeutic drugs used (including dose and
administration schedule), presence and severity of
myelosuppression, and location of radiation field.10

CHEMOTHERAPY-INDUCED COMPLICATIONS
Chemotherapy has both a direct and indirect stomatotoxic outcome. Direct stomatotoxicity is the
direct result of the chemotherapeutic drug on the
oral mucosa, which can cause atrophy, diffuse or
localized ulceration, and inflammation.6 Indirect
stomatotoxicity occurs when chemotherapy suppresses bone marrow cells during the nadir (the
point following treatment when a patients leukocytes (white blood cells), red blood cells, and
platelets are at their lowest point due to the cytotoxic effect of chemotherapy).11 Because leukocytes
and oral mucosal cells have similar rates of restoration, alterations in the oral cavity correlate with the
onset of myelosuppression.6 Thus, stomatitis is
linked with infection caused by decreased leukocytes during nadir.
Not every chemotherapy drug induces stomatitis.
Specific antineoplastic agents that cause stomatitis
include bleomycin, dactinomycin, doxorubicin,
floxuridine, 5-FU, hydroxyurea, methotrexate, mitomycin, vinblastine, vincristine, and vinorelbine.10
The danger of stomatitis is also exacerbated when
agents are given in high doses and frequent repetiAJN April 2002

Supplement

21

Grading of Stomatitis by the World Health

Organization
Grade

Symptom

0 . . . . . . . . . . . . None
I . . . . . . . . . . . . . Painful ulcers, erythema, or mild soreness
II . . . . . . . . . . . . . Painful erythema, edema, or ulcers, but able to eat
III . . . . . . . . . . . . Painful erythema, edema, or ulcers, but unable to eat
IV . . . . . . . . . . . . Requires parenteral or enteral support

tive schedules, or in combinations with other

chemotherapeutic agents or ionizing irradiation.10

RADIATION-INDUCED COMPLICATIONS
Radiation-induced stomatitis is considered one of
the most troublesome acute reactions for the patient
being treated for head and neck cancers, as well as
other oral cancers.12 As previously discussed, the
oral mucosa is highly populated with epithelial cells
that are sensitive to radiation and chemotherapy.
With radiation treatment, patients receive a specific
amount of radiation for a given number of days,
often for a prolonged regimen for weeks at a time.
Because of the prolonged radiation treatment to a
specific region of the head and neck, there is an
accumulation of damage to the oral cavity, resulting
in the formation of chronic oral ulcers.13 An infection can worsen the severity of stomatitis. For
patients undergoing radiation therapy, stomatitis is
considered a dose-limiting side effect; the damage
lasts as long as a patient is treated with radiation.

ASSESSMENT
Before a patient receives chemotherapy or radiation,
it is important to perform a thorough assessment of
the oral cavity to establish a baseline from which to
measure change throughout the treatment regimen.14 Numerous grading and assessment tools are
available to the nurse caring for the patient with
stomatitis, including Becks Oral Examination
Guide,14 Eilers Oral Assessment Guide,15 and the
World Health Organization (WHO) Grading for
Mucositis/Stomatitis (see Grading of Stomatitis by
the World Health Organization, above). The WHO
grading system encompasses considerations for the
overall appearance of the oral cavity coupled with
the general physical and nutritional status of the
patient.

PROPHYLACTIC INTERVENTIONS
While the management of stomatitis is well documented in nursing, medical, and dental literature,
no specific agent or educational technique has been
22

AJN April 2002

Supplement

shown to be more efficacious than the other. Nurses

should design an intervention plan for the patient
that is specific to both potential and actual problems related to stomatitis. Additionally, a stomatitis
care plan should be simple and realistic for the
patient and family members to ensure proper
implementation.

ORAL HYGIENE
Some clinicians believe that regular oral care is
equally or more important than use of a particular
agent or device in preventing stomatitis.5, 14 Oral
hygiene is often overlooked in the plan of care for
the prevention and treatment of stomatitis. Quality,
frequency, and consistency of oral care are important factors in stomatitis prevention.5
The intensity of the oral care plan is determined
by the condition of the patients oral cavity.14, 16 For
patients with mild stomatitis, oral care should be
performed every two to three hours and patients
with moderate to severe stomatitis should perform
oral care every one to two hours.16 Oral care completed before meals helps freshen the mouth and
stimulate the appetite.14
The accumulation of plaque causes significant,
caustic gingival inflammation, which further
impedes the oral health of a patient with stomatitis.7 A simple regimen of oral care involving brushing, flossing, rinsing, and moisturizing are
imperative to minimize the risk of developing oral
complications.7, 11 The American Dental Association (ADA) recommends brushing the teeth with a
soft-bristled brush that fits the patient appropriately.17 The ADA also suggests that patients place
their toothbrush at a 45-degree angle against the
gums and move it back and forth gently in short
strokes. Patients should also brush their tongue to
remove bacteria and freshen their breath.17 If a
patient has a platelet count less than 50,000/mm3,
its controversial whether toothbrushing might be
contraindicated because of the increased risk of
bleeding.10 While the toothbrush is most efficient in
removing plaque buildup, some patients may not
tolerate it because it causes excessive pain. Specially
made toothbrushes, designed for care of sensitive
or diseased tissue, are available.
When a toothbrush is contraindicated, the nurse
can recommend a toothette (a foam swab affixed to
an applicator), which is softer and less abrasive to
the gingiva and other soft tissues of the oral cavity.
The toothette was found to be not as effective as a
toothbrush, but does remove some plaque while
stimulating the production of saliva and improving
vascularity of the oral cavity.18 Toothettes previously soaked in glycerin or flavorings should be
avoided because the substances can burn and dry
http://www.nursingcenter.com

the mouth. For the patient who cannot tolerate

either a toothbrush or a toothette, a piece of gauze
wrapped around a finger can be used to remove
plaque and debris.16
Daily flossing is beneficial because it effectively
cleans the areas between the teeth. The ADA recommends that a patient use approximately 18
inches of floss wound mostly around one of the
middle fingers and guide the floss between the teeth
using a gentle rubbing up-and-down motion.17 By
rubbing each side of each tooth with floss, plaque
buildup is removed. Sometimes waxed floss is easier to use but patients may also use unwaxed and
mint-flavored floss.
Once brushing and flossing are complete, the
oral cavity should be rinsed to remove loose debris
and to irrigate healthy tissue. Madeya recommends
that the patient rinse for one to two minutes using
the ballooning and sucking cheek motion, which
forces the mouthwash between the teeth.7 Numerous agents can be used as a mouthwash for the
prevention and treatment of stomatitis, including
tap water, normal saline, sodium bicarbonate,
hydrogen peroxide, commercial mouthwashes, and
chlorhexidine.19 However, normal saline (one-half
teaspoon of salt in 8 ounces of water) mouthwash
is thought to aid the healing process and appears to
be safe, economical, and readily available.5,19
Because some commercial mouthwashes contain
alcohol, oil, astringents, and antiseptics, they
should be avoided. Alcohol in mouthwash can irritate the mucosal tissue, causing pain and drying of
the mucous membrane.7
A final step in oral hygiene of the patient with
the potential or actual problem of stomatitis is
moisturizing the oral cavity. Perhaps the easiest
way to ensure proper moisturization of the oral
cavity and lips is through hydration. Frequent
intake of water or any other drink that is tolerable
is essential for the patient enduring stomatitis.
However, acidic oral fluids that may burn the damaged tissue, such as orange, cranberry, and grapefruit juice, should be avoided. Moisturizers to
protect the lips, such as petroleum jelly, lipstick
balms, and water-based lubrications can be used,
especially at night, to keep the tissue moist and
soft.11

PATIENT EDUCATION
Patient education may very well be one of the most
important interventions in the campaign to eliminate or lessen the severity of stomatitis. In part, a
patients health is his responsibility. Most patients
have a strong desire to do whatever it takes to get
better, but they cant help themselves unless they
are properly educated.
http://www.nursingcenter.com

Patients need to be taught how to perform their

own oral care, including the proper time interval,
equipment (toothbrush, floss), and technique.
Additionally, patients should be taught which conditions of the mouth should be brought to the attention of the health care team. Its vital that a patients
family and friends are educated along with the
patient so that if the patient becomes too debilitated
to complete mouth care, his support team can assist
with the task.
REFERENCES
1. Sonis ST, et al. Validation of a new scoring system for the
assessment of clinical trial research of oral mucositis induced
by radiation or chemotherapy. Mucositis Study Group. Cancer
1999;85(10):2103-13.
2. McGuire DB, et al. Patterns of mucositis and pain in patients
receiving preparative chemotherapy and bone marrow transplantation. Oncol Nurs Forum 1993;20(10):1493-502.
3. Astiz ME, Rackow EC. Septic shock. Lancet
1998;351(9114):1501-5.
4. Sonis ST. Mucositis as a biological process: a new hypothesis
for the development of chemotherapy-induced stomatotoxicity.
Oral Oncol 1998;34(1):39-43.
5. Dodd MJ, et al. Randomized clinical trial of chlorhexidine versus placebo for prevention of oral mucositis in patients receiving chemotherapy. Oncol Nurs Forum 1996;23(6):921-7.
6. Madeya ML. Oral complications from cancer therapy: Part
2Nursing implications for assessment and treatment. Oncol
Nurs Forum 1996;23(5):808-19.
7. Madeya ML. Oral complications from cancer therapy: Part
1Pathophysiology and secondary complications. Oncol Nurs
Forum 1996;23(5):801-7.
8. Wilkes JD. Prevention and treatment of oral mucositis following cancer chemotherapy. Semin Oncol 1998;25(5):538-51.
9. Sloan JA, et al. Sex differences in fluorouracil-induced stomatitis. J Clin Oncol 2000;18(2):412-20.
10. National Cancer Institute. Oral complications of cancer and
cancer therapy. Updated 2000. http://www.graylab.ac.uk/
cancernet/302904.html.
11. Beck SA. Mucositis. In: Yarbro CH, et al., editors. Cancer
symptom management. 2nd ed. Sudbury (MA): Jones and
Bartlett; 1999. p. 328-38
12. Loprinzi CL, et al. Oral complications. In: Abeloff MD, et al,
editors. Clinical oncology. 2nd ed. New York: Churchill
Livingstone; 2000. p. 965-79
13. Iwamoto RR. Cancers of the head and neck. In: Dow KH, et
al, editors. Nursing care in radiation oncology. 2nd ed.
Philadelphia: Saunders; 1997. p. 239-60
14. Beck S. Impact of a systematic oral care protocol on stomatitis
after chemotherapy. Cancer Nurs 1979;2(3):185-99.
15. Eilers J, et al. Development, testing, and application of the oral
assessment guide. Oncol Nurs Forum 1988;15(3):325-30.
16. Iwamoto RR. Alterations in oral status. In: McCorkle R, et al,
editors. Cancer nursing: a comprehensive textbook. 2nd ed.
Philadelphia: Saunders; 1996. p. 944-62
17. American Dental Association. Frequently asked questions:
cleaning your teeth and gums (oral hygiene). 1998.
http://www.ada.org/public/faq/cleaning.html.
18. Pearson LS. A comparison of the ability of foam swabs and
toothbrushes to remove dental plaque: implications for nursing
practice. J Adv Nurs 1996;23(1):62-9.
19. Miller M, Kearney N. Oral care for patients with cancer: a
review of the literature. Cancer Nurs 2001;24(4):241-54.

AJN April 2002

Supplement

23