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SOURCE: Dept. of Otolaryngology,
UTMB, Grand Rounds
DATE: November 29, 1995
RESIDENT PHYSICIAN: Carl Schreiner,
FACULTY: Francis B. Quinn,
SERIES EDITOR: Francis B.
Quinn, Jr., M.D.
"This material was prepared by resident
physicians in partial fulfillment of educational requirements established for
the Postgraduate Training Program of the UTMB Department of Otolaryngology/Head
and Neck Surgery and was not intended for clinical use in its present form. It
was prepared for the purpose of stimulating group discussion in a conference setting.
No warranties, either express or implied, are made with respect to its accuracy,
completeness, or timeliness. The material does not necessarily reflect the current
or past opinions of members of the UTMB faculty and should not be used for purposes
of diagnosis or treatment without consulting appropriate literature sources and
informed professional opinion."
Otolaryngologists examine the oral
cavity on a daily basis and require a broad understanding of oral pathology. Stomatitis
is inflammation of the oral mucosa and may be secondary to infection, trauma,
systemic diseases or autoimmune mechanisms. This presentation is a brief summary
of common benign conditions of the oral mucosa. For organization, the lesions
will be categorized as vesiculobullous, ulcerative, red, or white lesions, although
considerable overlap exists. Several common tongue lesions will also be discussed.
Herpes simplex virus Type I (HSV I)
manifests as a primary or secondary infection which principally involves the lips
and oral mucosa but may also involve the skin,eyes and rarely the central nervous
system. The incubation period is around 7 days and the route of spread is by direct
contact with infected fluids.
Primary herpetic gingivostomatitis
is rare in adults and is usually seen in children from 1 to 3 years of age.
Small vesicles appear on any mucosal surface of the oral cavity and are usually
accompanied by fever, malaise, headache and cervical adenopathy. The primary
infection is often not diagnosed as the symptoms can be mild and the vesicles
rupture rapidly and may go unnoticed. The most common sites of involvement include
the palate, buccal mucosa, and gingiva. Healing without scarring usually occurs
within 2 week sand the virus migrates along the periaxonal sheath of the trigeminal
nerve to the trigeminal ganglion and lies dormant until reactivation.
Recurrent lesions affect 30% -
40% of the population and are usually localized to the mucocutaneous junction
of the lips and attached gingiva. They represent reactivation of the latent
virus in the trigeminal ganglion and are often precipitated by ultraviolet light,
stress, fever, or immunosuppression. Painful vesicles appear after a prodrome
of tingling or burning and rapidly coalesce to form a superficial ulcer that
crusts and heals without scarring in a week to 10 days.
Microscopically, the lesions show
ballooning degeneration of basal cell and the formation of intraepithelial vesicles.
Infected cells show a glassy, homogenous nucleus, or appear as multinucleated
giant cells that are indistinguishable from herpes zoster or chicken pox.
Vesicle formation is the key to
differential diagnosis as aphthous ulcers and acute necrotizing gingivitis are
not preceded by vesicles.
Treatment is mainly supportive
in the nonimmunocompromized and consists of hydration and analgesics. Oral acyclovir
may be beneficial if given frequently (100 - 200 mg 5 x day) early in the course
of the disease. In immunocompromized patients intravenous acyclovir may be required
but prophylactic oral acyclovir has been shown to be more beneficial in these
Herpes zoster represents a reactivation
of prior infection of the varicella zoster (chicken pox) virus which travel to
sensory ganglia during the primary infection. Fever, pain and tenderness over
the involved nerve occurs often several days before the vesicular rash appears
and associated lymphadenopathy is common even without secondary infection. The
lesions heal spontaneously in several weeks and postherpetic neuralgia is a common
complication. The ophthalmic nerve is the most commonly affected branch of the
trigeminal nerve and ophthalmological consultation is indicated.
Histologically, the lesions are
essentially identical to herpes simplex and treatment is supportive.
Herpangina is a febrile illness of
children and young adults characterized by fever, malaise, sore throat and gastrointestinal
symptoms followed by the formation of several small vesicles in the oropharynx.
The lesions are often limited to the soft palate and usually do not appear until
several days after the systemic symptoms begin. The causative agent is a Caxsackie
virus and it usually resolves quickly without complications.
The differential diagnosis includes
strep throat, measles, and herpetic gingivitis, although herpangina usually
does not involve the gingiva. Treatment is supportive and infection provides
immunity to reinfection.
Pemphigoid is characterized by the
formation of tense, subepithelial bullae of the skin and mucous membranes. Two
separate entities, benign mucous membrane pemphigoid and bullous pemphigoid, are
often described but many think they represent variants of the same disease.
Benign mucous membrane pemphigoid
occurs in the 40 to 50 year old age group and affects women twice as often as
men. Tense oral bullae form and may persist for days before rupturing, forming
large erosions that usually scar with healing. Gentle rubbing of adjacent uninvolved
skin may denude the epithelium, producing an ulcer or vesicle (positive Nikolsky's
sign). Involvement of the conjunctivae is relatively common and may lead to
Bullous pemphigoid affects older
patients and cutaneous lesions are more common than mucosal lesion. The lesions
are similar but may heal with less scarring.
Both lesions are histologically
similar and show direct immunofluorescence to lgG in the basement membrane,
supporting an autoimmune etiology. Biopsy shows subepithelial clefting with
autoimmune etiology. Biopsy shows subepithelial clefting with dissolution of
the basement membrane but no degenerative intraepithelial changes.
Treatment is often difficult if
multiple sites are involved but potent topical steroids or intralesional steroids
can be effective. Systemic steroids may be required for severe cases or ocular
involvement. Steroids combined with immunosuppressants (cyclophosphamide, methotrexate)
may be needed in refractory cases.
Pemphigus is a more severe group of
potentially fatal diseases characterized by intraepithelial bullae and acantholysis.
The disease is more common in Jewish and Italian people and males are more often
affected than females. The lesions almost invariably initially involve the oral
mucosa and the bullae are so easily ruptured that painful irregular ulcers are
often the presenting lesions. The most common sites include the buccal mucosa,
palate and gingiva.
Microscopically, the lesions show
early intercellular edema and los of intercellular bridges. The lack of cohesion
allows cell separation and rounding (acantholysis), and intraepithelial clefting
(as opposed to subepithelial in bullous pemphigoid) occurs. The basal cells
remain attached to the lamina propria creating a "tombstone" effect and free
acantholytic cells assume a spherical form ("Tzanc cells") which are considered
pathognomonic for pemphigus vulgaris. Direct immunofluorescence shows antibodies
against intercellular bridges. Serum levels of intercellular antibodies have
been shown to correlate with the severity of the disease.
Treatment with high dose steroids
has greatly reduced the mortality and morbidity of pemphigus but significantly
morbidity from steroids has been reported as doses of 100 mg/day are often required
for initial control. The dose can be tapered down to 20 mg/day over three months.
Intramuscular gold has been with some success and plasmaphoresis is currently
Erythema multiforme is a rapidly progressive,
vesiculobullous eruption of unknown etiology that most commonly affects young
adults. An allergic reaction to drugs, infection, food or alcohol is suspected
resulting in antigen-antibody complex deposition in the vessels of the subdermis.
Characteristic ring-like "target lesions" appear on the skin but are rarely seen
on the oral mucosa. Diffuse ulceration and crusting of the lips, tongue, and buccal
mucosa are more common oral manifestations. The lesions are usually self-limited
and heal without scarring in a few weeks.
The histopathology in erythema
multiforme is nonspecific and its explosive onset after a precipitating infection
or drug is key in differentiating it from other vesiculobullous diseases.
Stevens-Johnson syndrome is a severe
from of erythema multiforme with systemic symptoms and involvement of the eyes,
gastrointestinal tract, and genitalia. Treatment of severe cases of erythema
multiforme and Stevens-Johnson syndrome requires systemic steroids. The prognosis
if erythema multiforme is generally good but blindness or death can occur with
Stevens- Johnson syndrome.
Recurrent Aphthous Ulcers
Aphthous ulcers are extremely common
and seem to be more prevalent in upper socioeconomic classes and professionals.
The cause is unknown but the best evidence points to an autoimmune mechanism.
The "L" form of streptococci in ulcers have been shown to produce a skin hypersensitivity
response in guinea pigs. Other theories include HSV or bacterial infections, stress,
hormonal alterations, and food allergies. Histologically, aphthous ulcers have
no distinguishing features. Clinically, the disease has been divided into three
groups based on size, distribution, and severity.
Minor aphthae (cancer sores) measure
less than 1 cm and are located on freely-mobile gingiva or mucosa. The lesions
are well-demarcated white ulcers with an erythematous halo. They heal without
scarring in 7 to 10 days. Treatment is often sought as pain is often in excess
of the appearance of the lesion.
Major aphthous ulcers are less
common, larger, and more severe. They range from 1 to 3 cm and may persist for
up to 6 months. The tongue, soft palate, and anterior facial pillar are often
involved. In contrast to minor aphthae, they heal with scarring.
Herpetiform ulcers present as an
extremely painful crop of 20 to 200 small ulcers 1 to 3 mm in diameter. They
appear similar to herpetic lesions but lack a vesicular stage.
Treatment attempts over the years
have been imaginative and largely unsuccessful. Medical treatment has ranged
from antibiotics, immunosuppressants and yogurt, to Lactobacillus capsules.
An oral suspension of tetracycline taken every 6 hours has shown good results
and topical steroids (Lidex, Celestone) may shorten the duration significantly
if started early. Systemic steroids are often needed to control mayor aphthae.
Peridex and retinoids have also been tried empirically but controlled studies
Acute Necrotizing Ulcerative Gingivitis
Also known as "trench mouth" (after
World War II) or Vincent's stomatitis, the incidence of ANUG is now increasing
with the appearance of AIDS. Ulceration of the interdental papillae with bleeding
and pseudomembrane formation occurs with a characteristic fetid odor. Systemic
symptoms of fever, malaise and lymphadenopathy may occur. Juveniles and young
adults are often affected. The disease is noncommunicable and cultures contain
large numbers of fusiform bacilli and spirochetes. The course is often chronic
and may lead to bone loss and periodontitis. Treatment consists of superficial
scaling, debridement and the aggressive use of mouthwashes and antibiotics. Close
dental follow up is needed.
Lichen planus is a chronic disease
of the skin and mucous membranes which is felt to be due to basal cell layer destruction
by activated lymphocytes. Characteristic skin lesions include violaceous, pruritic
papules of ever the flexor surfaces of the extremities and several types of oral
lesions have been described, including reticular, plaque and atrophic (erosive)
Reticular lichen planus shows fine,
slightly raised, white or violaceous threadlike lesions in a ringlike pattern
(Wickham's striae). These lesions are often located on the buccal mucosa. The
hypertrophic form resembles leukoplakia as homogenous white plaques. Atrophic
or erosive lichen planus present as erythematous shallow ulcers that, in contrast
to most forms of lichen planus, may be painful.
Histologically, lichen planus shows
hyperkeratosis, "saw- tooth" rete ridges, liquefactive degeneration of the basal
cell layer, and a "band-like" subepithelial inflammatory infiltrate. Discrete
eosinophilic ovoid bodies (Civatte bodies) are occasionally seen in the basal
Treatment is symptomatic and mild
cases usually do not require therapy. Topical steroids may be useful in controlling
local symptoms and topical retinoids, with antikeratinizing effects, can be
used for the plaque form. Dapsone has also been used for severe forms with some
Candida albicans is an oral commensal
that can be found in the mouth of 40% - 60% of healthy individuals. Oral candidal
infections almost always involve a compromised host. Local factors include decreased
salivation (medications, radiation, or Sjogren syndrome) or dentures. Systemic
factors include diabetes, antibiotic or systemic steroid use, AIDS, or pernicious
anemia. Many clinical forms of candidiasis have been described, including: pseudomembranous,
hyperplastic, and denture stomatitis.
Pseudomembranous candidiasis presents
as tiny, soft, yellow- white plaques that consist of fungi, bacteria, desquamated
cells and food debris. The lesions are readily scraped off and an underlying
erythema is key to the diagnosis.
The hyperplastic variant (Candida
leukoplakia) are white, firm, plaques that often involves the buccal mucosa,
tongue or lips. The lesions are truly leukoplakic, as the overlying keratotic
mucosa does not easily scrape away. These lesions are often resistant to standard
Denture stomatitis lesions occur
in older patients and are most common with a complete maxillary denture. The
lesions are red, flat plaques that extend right up to but not beyond the denture
border. The patients often wear their dentures for extended periods of time
and during sleep.
Diagnosis of candida infections
is usually clinical and is confirmed by resolution of the lesions after 2 weeks
of antifungal therapy. Cultures or smears are usually reserved to cases that
fail treatment. Cultures are often unreliable and may take up to 2 weeks for
growth. Fungal smears with PAS staining is faster and less expensive. The slides
show hyphae and polymorphonuclear leukocytes in the superficial layers of the
The three most commonly used antifungals
include nystatin, clotrimazole, and ketoconazole. Nystatin has the advantage
of being effective and safe for long term use, but is less potent that the latter
two and may cause burning when swished orally. Patient compliance is also a
problem with a regiment of swishing for two minutes and then expectorating four
times a day. Clotrimazole is more potent and comes in a lozenge, which increases
patient compliance. It has the disadvantage of causing occasional liver enzyme
elevation and should not be used in patients with known liver disease. Ketoconazole
is prescribed in 200 mg tablets taken once daily but also can cause liver enzyme
Leukoedema is a benign condition in
which the oral mucosa takes on an opaque, grey, film that may appear to hang like
a "veil" on the mucosa, creating a "mother of pearl" appearance. It is more common
in dark-skinned patients and is likely aa variant of normal in which there is
incomplete shedding of parakeratotic cells, although some studies have shown as
association with tobacco use. Histologically, leukoedema is characterized by marked
intracellular edema and vacuoles. Its significance is important only in differentiating
leukoedema from leukoplakia or white sponge nevus.
White Sponge Nevus
White sponge nevus is an autosomal
dominantly inherited condition of the oral mucosa. The buccal mucosa is commonly
affected and appears as white or grey, thickened, deeply folded lesions often
described as "scrotal" in appearance. The lesions are asymptomatic and the rectal
or vaginal mucosa is often involved. A defect causing faulty epithelial migration
with impaired desquamation is suspected. Histology shows parakeratosis, acanthosis
and prickle cell vacuolated cells giving a "washed out" appearance. The differential
diagnosis includes lichen planus and candidiasis. No treatment is necessary.
Leukoplakia is defined as a white patch
or plaque of the mucosa that cannot be rubbed off the mucosa and cannot be classified
as any other disease entity. The term "leukoplakia" is strictly a clinical condition
and lacks any histologic connotation. Although most leukoplakia are histologically
benign, some may progress to dysplasia or eventually squamous cell carcinoma.
Leukoplakia presents as an irregular, slightly raised white lesion that is sharply
demarcated from surrounding tissue. The majority of cases occur between the ages
of 40 and 60 and men are affected more than women. The most common sites include
the buccal mucosa, alveolar mucosa and hard palate and these locations rarely
malignantly transform. In contrast, leukoplakia of the floor of the mouth and
tongue are less common, but much more frequently progress to malignancy. Multiple
classifications of leukoplakia have been described based on the macroscopic appearance
of the lesions, including planar, verruciform, and speckled forms, the latter
two forms reported as associated with a higher rate of malignant transformation.
Ten per cent transformation of dysplastic leukoplakias is a commonly quoted figure
but the literature does not closely correlate with histology and biopsy with close
follow up is mandatory.
Histologically, the majority of
leukoplakias show combinations of hyperorthokeratosis, hyperkaratosis and acanthosis.
Dysplasia is characterized by increased mitotic figures, abnormal mitosis in
the upper strata, nuclear pleomorphism, individual cell keratinization, and
loss of polarity and is generally considered to represent a shift toward malignant
Although the etiology of leukoplakia
is unknown, it is widely believed that tobacco plays a major role. Other possible
factors include chronic irradiation, dietary deficiencies, chronic candidiasis,
and alcoholism. Many nondysplastic lesions disappear with removal of the irritating
stimulus and those that do not respond usually can be cured by surgical excision.
Dysplastic leukoplakias, on the other hand, are less likely to respond to nonsurgical
treatment. They are also more likely to recur after excision. In general, the
more severe the dysplasia, the higher potential for malignant transformation
and dysplastic lesions of the ventral surface of the tongue or floor of the
mouth should be approached with particular caution. <3>Red Lesions
Erythroplakia is the red counterpart
to leukoplakia and represents a red plaque of the mucosa not attributable to a
specific pathologic condition. Once again, "erythroplakia" implies no histologic
connotation although virtually all erythroplakias show microscopic dysplasia.
Several studies have shown an impressive 80% - 90% of lesions containing severe
dysplasia, carcinoma-in-situ, or squamous cell carcinoma.
The lesions are often asymptomatic,
homogenous, velvety-red flat plaques that are well circumscribed from normal
mucosa. Erythroplakia and leukoplakia may be mixed, giving the so called "speckled"
pattern. Like leukoplakia, the clinical appearance is unreliable with regard
to histology and biopsy is mandatory.
Histologically, the lesions differ
from erythroplakia by showing a lack of orthokeratin or parakeratin and an intense
inflammatory infiltrate is often seen. A thinned epithelium with absent rete
ridges and congested superficial capillaries give the lesions their red color.
The differential diagnosis of erythroplakia
includes candidiasis, denture stomatitis, tuberculosis. Treatment usually requires
complete surgical excision with frozen section margins and close follow up.
Radiation mucositis is a painful inflammatory
reaction of the oral mucosa to radiation therapy. The degree of injury varies,
depending on the dose, portal of the beam, age, and general health of the patient.
The first reaction is usually noted during the second week of a 5 or 6 week treatment
and consists of diffuse erythema, followed by desquamation and ulceration. Xerostomia
adds to the discomfort and usually persists indefinitely to some degree. An alteration
in taste often precedes the mucosal reaction and may persist, depending on the
dose. Hydrogen peroxide and water (4:1 solution) and sodium bicarbonate solutions
may improve symptoms. Numerous anesthetic mucosal coating agents are available,
including combinations of benadryl, viscous lidocaine, and Dyclone.
Geographic Tongue (Benign migratory
Geographic tongue is a common condition
of the tongue characterized by alternating areas of red desquamated zones bordered
by sharp raised margins. Over a period of days to weeks, the "bald" areas migrate
across the surface of the tongue by haling on one border and extending onto another
border. The desquamated areas represent areas devoid of filiform papillae but
intact red fungiform papillae. Psychological factors have been shown to correlate
with the severity of involvement but the etiology is unknown. The course of the
disease is variable but often persists for months to years. It is reported to
exist in 1 - 2% of the general population and is usually asymptomatic, although
patients may complain of mild burning with spicy foods or citrus fruits. Topical
steroids may help with burning, but reassurance is usually the only required treatment.
Median Rhomboid Glossitis
Median rhomboid glossitis is a well-circumscribed
red area devoid of papillae in the midline dorsum of the tongue. Once felt to
be a developmental abnormality due to failure of withdrawal of the tuberculum
impar, recent evidence has implicated candida albicans as a causative agent. The
lesion is asymptomatic and usually picked up on routine examination. No treatment
is necessary unless candida is cultured.
Hairy tongue is a striking condition
caused by hypertrophy of the filiform papillae. The individual "hairlike" papillae
(sometimes reaching 15-20 mm in length) always occur anterior to the terminal
sulcus and tend to migrate laterally and anteriorly. The pathogenesis is unknown
but antibiotic therapy, steroids, radiation therapy, and smoking have been implicated.
Most cases are considered idiopathic. In the cases of hairy tongue after antibiotics,
it has been postulated that antibiotics alter the normal flora of the mouth, leading
to the overgrowth of fungi. Attempts to culture these fungi have been inconsistent.
The color of the filiform fibers may be black ("black hairy tongue") or yellow
and is felt to be due to overgrowth of chromogenic organisms or smoking. Treatment
consists of withdrawing antibiotics if applicable and meticulous oral hygiene,
including brushing the tongue with a soft bristle brush.
This new clinical entity has recently
been described in association with HIV infection. Thee lesion presents as a white,
corrugated patch on the lateral surface of the tongue and is often bilateral.
The lesions may be present in as many as 20% of HIV patients and is often confused
with candidiasis. Histologically, the lesions show epithelial projections in a
"hairlike" configuration and marked hyperkaratosis. Recent immunohistochemical
studies have shown Epstein-Barr virus DNA in the epithelium. The patients often
complain of a "cotton-wool" feeling in the mouth and the lesions may become superinfected
with candida. Treatment is symptomatic.
Bailey, Byron J, ed. Head and Neck
Surgery-Otolaryngology. Philadelphia, PA: J.B. Lippencott 1993.
Lee, K.W. Color Atlas of Oral Pathology.
Lea and Febiger - Philadelphia, 1985.
Pindborg, J.J. Atlas of Diseases
of the Oral Mucosa. W. B. Saunders. Munksgaard-Copenhagen 1993.
Smith, R.M. et al. Atlas of Oral
Pathology. C.V. Mosby Co. Toronto. 1981.
Rondu, B., Mattingly, B.S. Oral
Mucosal Ulcers: Diagnosis and Management. JADA, Vol 123, Oct 1992:883-86.
Rogers, R. Common Lesions of the
Oral Mucosa. Postgraduate Medicine. May 1992:141-53.
Zegarreli, D.J. Fungal Infections
of the Oral Cavity. Otolaryngologic Clinics of North America. Dec 1993, Vol
26, No3 1069-88.
Discussion by Dr. Quinn:
( Outline of discussant's remarks)
GLOSSODYNIA: (glossopyrosis, glossalgia,
orofacial dysesthesia, "burning tongue syndrome")
Incidence: middle aged females
(73% in one study)
Physical findings: occasionally
xerostomia, usually completely normal mouth, pharynx, gums & tongue.
Lab: occasionally anemia (one case
of large intestine tumor - glossodynia subsided after removal of tumor; two
cases of pernicious anemia) possible manifestation of diabetic neuropathy?
Psychiatric concommitants: Many
patients score high on somatization, depression, anxiety scales More common
in patients who are living alone Correlated positively with psychological stress
but not related to recent life changes (Recent Life Changes questionnaire) In
one study, 60% showed a psychiatrically relevant disorder, usually depression.
Treatment: Reassurance by carful
history ("homework"*) with thorough physical examination of upper aerodigestive
passages; screening labs (RPR, ?HIV)
Then referral for:
- a: Dental exam
- b: ?Psychiatric evaluation?
- c: Nutritional consultation
(unsuspected nutritional deficiencies?)
- d: OB/GYN or PCP for ?Sex hormone
supplementation (possibly a manifestation of menopause?)
Caution: Don't forget to look for
a cylindroma (adenoid cystic carcinoma, psuedoadenomatous basal cell carcinoma)
(Sometimes the presenting symptom of this rare tumor is sometimes burning pain
about the mouth & jaws.)
* "Homework:" assign to patient
the task of writing out in exhaustive detail the entire history of her/his complaint,
including its waxing and waning, any associated symptoms/disorders/treatments,
or stressful events or conditions. Assignment to be delivered to the physician
BEFORE the next visit, to enable thoughtful perusal of the patient's account
and interpretation of the problem. This assures that all pertinent historical
information is in the hands of the physician.
Quinn's rule for stomatitis: "Call
it aphthous stomatitis. Treat it for two weeks. If it's still there, biopsy