104 C H A P T E R 3   White Lesions
• BOX 3-13 Candidiasis
• Figure 3-56  ​Oral discoid lupus erythematosus showing interface
and perivascular lymphocytic infiltrate.
keratinocytes are a primary target in mucous membranes.
Because this is also the case for lichen planus, the two dis-
eases may be difficult, on occasion, to separate by routine
microscopic studies. Demonstration of CD123+ plasmacy-
toid dendritic cells may aid in differentiation.
In SLE, oral lesions are microscopically similar to lesions
of DLE, although inflammatory cell infiltrates are less intense
and more diffuse. The epithelial lesions are hyperproliferative
in nature and are positive for cytokeratin markers CK 5/6
and CK 14. Other organs, when involved in SLE, show vas-
culitis, mononuclear infiltrates, and fibrinoid necrosis. Direct
immunofluorescent testing of skin and mucosal lesions shows
granular-linear deposits of immunoglobulins (IgG, IgM,
IgA), complement (C3), and fibrinogen along the basement
membrane zone in a majority of patients.
Differential Diagnosis
Clinically, lesions of oral LE most often resemble erosive lichen
planus but tend to be less symmetrically distributed. The kera-
totic striae of LE are more delicate and subtle than Wickham’s
striae of lichen planus and show characteristic radiation from a
central focus. Erythematous gingival lupus may be confused
with mucous membrane pemphigoid, erythematous lichen
planus, erythematous candidiasis, and contact hypersensitivity.
Treatment
DLE is usually treated with topical corticosteroids. High-
potency corticosteroid ointments can be used intraorally. In
refractory cases, antimalarials or sulfones may be used.
Systemic steroids may be used in the treatment of
SLE. The prednisone dose is generally dependent on the
severity of the disease, and prednisone may be combined
with immunosuppressive agents for their therapeutic and
steroid-sparing effects. Antimalarials and nonsteroidal anti-
inflammatory drugs may help control this disease.
Nonepithelial White-Yellow Lesions
Candidiasis
Candidiasis is a common opportunistic oral mycotic
infection that develops in the presence of one of several
Synonyms
Thrush, angular cheilitis, median rhomboid glossitis, denture sore
mouth, yeast infection, candidal leukoplakia, antibiotic stoma-
titis, moniliasis
Cause
Candida albicans and other Candida species in oral flora
Predisposing factors required
Opportunistic overgrowth
Types
Acute, chronic, mucocutaneous
predisposing conditions. Clinical presentation is variable
and is dependent on whether the condition is acute or
chronic (Box 3-13).
Etiology and Pathogenesis
Candidiasis is caused by C. albicans and much less
commonly by other species of Candida: C. parapsilosis,
C. tropicalis, C. glabrata, C. krusei, C. pseudotropicalis, and
C. guilliermondii. C. albicans is a commensal organism re-
siding in the oral cavity in a majority of healthy persons.
Transformation, or escape from a state of commensalism to
that of a pathogen, relates to local and systemic factors. The
organism is a unicellular yeast of the Saccharomycetaceae
family and may exist in three distinct biological and mor-
phologic forms: (1) the vegetative or yeast form of oval cells
(blastospores), measuring 1.5 to 5 mm in diameter; (2) the
elongated cellular form (pseudohyphae); and (3) the chla-
mydospore form, which consists of cell bodies measuring
7 to 17 mm in diameter, with a thick, refractile enclosing
wall. As evidenced by its frequency in the general popula-
tion, C. albicans is of weak pathogenicity, thereby reflecting
the necessity for local or systemic predisposing factors to
produce a disease state (Box 3-14).
Infection with this organism is usually superficial, affect-
ing the outer aspects of the involved oral mucosa or skin. In
• BOX 3-14 Candidiasis: Predisposing Factors
Immunodeficiency
Immunologic immaturity of infancy
Acquired immunosuppression
Endocrine disturbances
Diabetes mellitus
Hypoparathyroidism
Pregnancy
Hypoadrenalism
Corticosteroid therapy, topical or systemic
Systemic antibiotic therapy
Malignancies and their therapies
Xerostomia
Poor oral hygiene
 CHAPTER 3  White Lesions 105

• BOX 3-15 Candidiasis: Classification

Acute
Pseudomembranous (white colonies)
Erythematous (red mucosa)

Chronic
Erythematous (red mucosa)
Hyperplastic (white keratotic plaque)

Mucocutaneous
Localized (oral, face, scalp, nails)
Familial
Syndrome associated

• Figure 3-58  ​Candidiasis, pseudomembranous type.

severely debilitated and immunocompromised patients,

such as patients with AIDS, infection may extend into the
alimentary tract (candidal esophagitis), the bronchopulmo-
nary tract, or other organ systems. The opportunistic nature
of this organism is observed in the frequency of mild forms
of the disease resulting from short-term use of systemic
antibiotic therapy for minor bacterial infections.

Clinical Features
The most common clinical type of candidiasis is the acute
pseudomembranous form, also known as thrush (Box 3-15).
Young infants and the elderly are commonly affected. Esti-
mates of disease frequency range up to 5% of neonates; 5%
of patients with cancer; and 10% of institutionalized, • Figure 3-59  ​Candidiasis, pseudomembranous type.
debilitated elderly patients. This infection is common in
patients being treated with radiation or chemotherapy for
leukemia and solid tumors, with up to half of those in the
former group and 70% in the latter group affected. Recalci-
trant candidiasis has been recognized in patients who have
HIV infection and AIDS.
Oral lesions of acute candidiasis (thrush) are characteristi-
cally white, soft plaques that sometimes grow centrifugally
and merge (Figures 3-57 to 3-63). Plaques are composed of
fungal organisms, keratotic debris, inflammatory cells, des-
quamated epithelial cells, bacteria, and fibrin. Wiping away

• Figure 3-60  ​Candidiasis, erythematous type.

the plaques or pseudomembranes with a gauze sponge leaves

• Figure 3-57  ​Candidiasis, pseudomembranous type.
a painful erythematous, eroded, or ulcerated surface. Al-
though lesions of thrush may develop at any location, favored
sites include the buccal mucosa and mucobuccal folds, the
oropharynx, and the lateral aspects of the tongue. In most
instances in which the pseudomembrane has not been dis-
turbed, associated symptoms are minimal. In severe cases,
patients may complain of tenderness, burning, and dysphagia.
Persistence of acute pseudomembranous candidiasis
may eventually result in loss of the pseudomembrane, with
106 C H A P T E R 3   White Lesions
• Figure 3-61  ​Candidiasis, angular cheilitis form.
• Figure 3-62  ​Candidiasis, hyperplastic type or median rhomboid
glossitis.
• Figure 3-63  ​Candidiasis, hyperplastic type.
presentation as a more generalized red lesion, known as
acute erythematous candidiasis. Along the dorsum of the
tongue, patches of depapillation and dekeratinization may
be noted. In the past, this particular form of candidiasis was
known as antibiotic stomatitis or antibiotic glossitis because
of its common relationship to antibiotic treatment of acute
infection. Broad-spectrum antibiotics or concurrent admin-
istration of multiple narrow-spectrum antibiotics may pro-
duce this secondary infection to a much greater degree than
do single narrow-spectrum antibiotics. Withdrawal of the
offending antibiotic, if possible, and institution of appro-
priate oral hygiene lead to improvement. In contrast to the
acute pseudomembranous form, oral symptoms of the
acute atrophic form are marked because of numerous ero-
sions and intense inflammation.
Chronic erythematous candidiasis is a commonly seen
form, occurring in as many as 65% of geriatric individuals
who wear complete maxillary dentures (denture sore mouth).
Expression of this form of candidiasis depends on condition-
ing of the oral mucosa by a covering prosthesis. A distinct
predilection for the palatal mucosa compared with the man-
dibular alveolar arch has been noted. Chronic low-grade
trauma resulting from poor prosthesis fit, less than ideal oc-
clusal relationships, and failure to remove the appliance at
night all contribute to the development of this condition.
The clinical appearance is that of a bright red, somewhat
velvety to pebbly surface, with relatively little keratinization.
Also seen in individuals with denture-related chronic
atrophic candidiasis is angular cheilitis. This condition is
especially prevalent in individuals who have deep folds at
the commissures as a result of mandibular overclosure. In
such circumstances, small accumulations of saliva gather in
the skin folds at the commissural angles and are subse-
quently colonized by yeast organisms (and often by Staphy-
lococcus aureus). Clinically, the lesions are moderately pain-
ful, fissured, eroded, and encrusted. Angular cheilitis may
also occur in individuals who habitually lick their lips and
deposit small amounts of saliva in the commissural angles.
A circumoral type of atrophic candidiasis may be noted
in those with severe lip-licking habits with extension of the
process onto surrounding skin. The skin is fissured and
demonstrates a degree of brown discoloration on a slightly
erythematous base. This condition is to be distinguished
from perioral dermatitis, which characteristically shows less
crusting and a circumferential zone of uninvolved skin im-
mediately adjacent to the cutaneous-vermilion junction.
Chronic candidal infections are capable of producing a
hyperplastic tissue response (chronic hyperplastic candidiasis).
When occurring in the retrocommissural area, the lesion re-
sembles speckled leukoplakia and, in some classifications, is
known as candidal leukoplakia. It occurs in adults with no
apparent predisposition to infection by C. albicans, and it is
believed by some clinicians to represent a premalignant lesion.
Hyperplastic candidiasis may involve the dorsum of the
tongue in a pattern referred to as median rhomboid glossitis.
It is usually asymptomatic and is generally discovered on rou-
tine oral examination. The lesion is found anterior to the cir-
cumvallate papillae and has an oval or rhomboid outline with
a paramedian distribution. It may have a smooth, nodular, or
fissured surface and may range in color from white to a more
characteristic red. A similar-appearing red lesion may also be
present on the adjacent hard palate (“kissing lesion”). Whether
on the tongue or on the palate, the condition may occasion-
ally be mildly painful, although most cases are asymptomatic.
In the past, this particular condition was believed to be a de-
velopmental anomaly, presumably resulting from persistence

of the tuberculum impar of the developing tongue. Because it
is never seen in children, it is more likely a hyperplastic form
of candidiasis. Microscopically, epithelial hyperplasia is evi-
dent in the form of bulbous rete ridges. C. albicans hyphae
usually can be found in the upper levels of the epithelium. A
thick band of hyalinized connective tissue separates the epi-
thelium from deeper structures.
Nodular papillary lesions of the hard palatal mucosa
predominantly seen beneath maxillary complete dentures
are thought to represent, at least in part, a response to
chronic fungus infection. The papillary hyperplasia is com-
posed of individual nodules that are ovoid to spherical and
form excrescences measuring 2 to 3 mm in diameter on an
erythematous background.
Mucocutaneous candidiasis is a diverse group of condi-
tions. The localized form of mucocutaneous candidiasis is
characterized by long-standing and persistent candidiasis of
the oral mucosa, nails, skin, and vaginal mucosa. This form
of candidiasis is often resistant to treatment, with only tem-
porary remission following the use of standard antifungal
therapy. This form begins early in life, usually within the
first two decades. The disease begins as a pseudomembra-
nous type of candidiasis and soon is followed by nail and
cutaneous involvement.
A familial form of mucocutaneous candidiasis, believed
to be transmitted in an autosomal-recessive fashion, occurs
in nearly 50% of patients with an associated endocrinopa-
thy. The endocrinopathy usually consists of hypoparathy-
roidism, Addison’s disease, and occasionally hypothyroidism
or diabetes mellitus. Other forms of familial mucocutaneous
candidiasis have associated defects in iron metabolism and
cell-mediated immunity.
A rare triad of chronic mucocutaneous candidiasis, myo-
sitis, and thymoma has been described. The role of the
thymus relates to a deficiency in T cell–mediated immuno-
logic function, hence providing an opportunity for the
proliferation of Candida.
A final form of candidiasis, both acute and chronic, is
evident within the immunosuppressed population of pa-
tients, in particular those infected with HIV. This form of
candidiasis was originally described in 1981 and is now well
A B
• Figure 3-64  Oral candidiasis. A, Psoriasiform pattern. B, High magnification of fungal pseudohyphae
in keratin layer.
CHAPTER 3  White Lesions 107
recognized as being one of the more important opportunis-
tic infections that afflict this group of patients. The signifi-
cantly depleted cell-mediated arm of the immune system is
believed to be responsible for allowing the development of
severe candidiasis in these patients.
So-called denture stomatitis, a chronic form of erythem-
atous candidiasis, is in large measure associated with the
prosthesis-related surface biofilm that becomes colonized
with candidal organisms. The relationship between dura-
tion of denture use and development of this form of candi-
diasis has been established.
Histopathology
In acute candidiasis, fungal hyphae are seen penetrating the
upper layers of the epithelium at acute angles (Figure 3-64).
Neutrophilic infiltration of the epithelium with superficial
microabscess formation is typically seen. Fungal forms may
be enhanced in tissue sections by staining with methena-
mine silver or periodic acid–Schiff (PAS) reagent. The pre-
dominant fungal forms growing in this particular form of
the disease are pseudohyphae.
Epithelial hyperplasia is a rather characteristic feature of
chronic candidiasis. However, organisms may be sparse,
making histologic demonstration sometimes difficult. Al-
though chronic candidiasis may give rise to oral leukopla-
kia, no clear evidence indicates that chronic candidiasis is in
and of itself a precancerous state.
Clinical laboratory tests for this organism involve re-
moval of a portion of the candidal plaque, which is smeared
on a microscope slide and macerated with 20% potassium
hydroxide (KOH) or stained with PAS. The slide is subse-
quently examined for typical hyphae. Culture identification
and quantification of organisms may be done on Sabouraud
broth, blood agar, or cornmeal agar.
Differential Diagnosis
Candidal white lesions should be differentiated from slough
associated with chemical burns, traumatic ulcerations, mu-
cous patches of syphilis, and white keratotic lesions. Red
lesions of candidiasis should be differentiated from drug
reactions, erosive lichen planus, and DLE.
108 C H A P T E R 3   White Lesions
• BOX 3-16 Candidiasis: Treatment
Topical
Nystatin—oral suspension* and pastille*; powder and ointment
for denture; vaginal tablets (dissolved in mouth)
Clotrimazole—oral troches*
Systemic
Fluconazole, ketoconazole
*Contains sugar; do not use with dentate patients with xerostomia.
Treatment and Prognosis
Attending to predisposing factors is an important compo-
nent of management of patients with candidiasis. The ma-
jority of infections may be treated simply with topical ap-
plications of nystatin suspension, although this may be
ineffective because contact time with the lesion is short
(Box 3-16). Nystatin powder, cream, or ointment is often
effective when applied directly to the affected tissue on
gauze pads and for denture-associated candidiasis when ap-
plied directly to the denture-bearing surface itself. In both
circumstances, prolonged contact time with the lesion
proves to be an effective delivery strategy. Clotrimazole can
be conveniently administered in troche form. Topical ap-
plications of nystatin, miconazole or clotrimazole should be
continued for at least 1 week beyond the disappearance of
clinical manifestations of the disease. It is important to note
that antifungals designed specifically for oral use contain
considerable amounts of sugar, making them undesirable
for the treatment of candidiasis in dentate patients with
xerostomia. Sugar-free antifungal vaginal suppositories, dis-
solved in the mouth, are an excellent treatment alternative
to avoid the complications of dental caries.
For hyperplastic candidiasis, topical and systemic antifungal
therapy may be ineffective in completely removing the lesions,
particularly those that occur on the buccal mucosa, near the
commissures. In these circumstances, surgical management
may be necessary to complement antifungal medications.
In cases of chronic mucocutaneous candidiasis or oral
candidiasis associated with immunosuppression, topical
agents may not be effective. In such instances, systemic
administration of medications such as ketoconazole, fluco-
nazole, itraconazole, or others may be necessary. All are
available in oral form. Caution must be exercised, however,
because these drugs may be hepatotoxic.
The prognosis for acute and most other forms of chronic
candidiasis is excellent. The underlying defect in most types
of persistent mucocutaneous candidiasis militates against
cure, although intermittent improvement may be noted
after the use of systemic antifungal agents.
Mucosal Burns
Etiology
The most common form of superficial burn of the oral mu-
cosa is associated with topical applications of chemicals,
such as aspirin or caustic agents. Topical abuse of drugs,
accidental placement of phosphoric acid-etching solutions
or gel by a dentist, or overly fastidious use of alcohol-
containing mouth rinses may produce similar effects.
Clinical Features
In cases of short-term exposure to agents capable of induc-
ing tissue necrosis, a localized mild erythema may occur
(Figure 3-65). As the concentration and contact time of the
offending agent increase, surface coagulative necrosis is
more likely to occur, resulting in the formation of a white
slough, or membrane. With gentle traction, the surface
slough peels from the denuded connective tissue, producing
pain.
Thermal burns are commonly noted on the hard palatal
mucosa and generally are associated with hot, sticky foods.
Hot liquids are more likely to burn the tongue or the soft
palate. Such lesions are generally erythematous rather than
white (necrosis), as is seen with chemical burns.
Another form of burn that is potentially serious is the
electrical burn. In particular, children who chew through
electrical cords receive rather characteristic initial burns that
are often symmetric. The result of these accidents is signifi-
cant tissue damage, often followed by scarring. The surface
of these lesions tends to be characterized by a thickened
slough that extends deep into the connective tissue.
Histopathology
In cases of chemical and thermal burns in which an obvious
clinical slough has developed, the epithelial component
shows coagulative necrosis through its entire thickness. A
fibrinous exudate is also evident. The underlying connective
tissue is intensely inflamed. Electrical burns are more de-
structive, showing deep extension of necrosis, often into
muscle.
Treatment
Management of chemical, thermal, or electrical burns is
varied. For patients with thermal or chemical burns, local
symptomatic therapy aimed at keeping the mouth clean,
• Figure 3-65  ​Mucosal burn (necrosis) caused by prolonged aspirin
contact.

such as sodium bicarbonate mouth rinses with or without
the use of systemic analgesics, is appropriate. Alcohol-based
commercial mouth rinses should be discouraged because of
their drying effect on the oral mucosa. For patients with
electrical burns, management may be much more difficult.
The services of a pediatric dentist or an oral and maxillofa-
cial surgeon may be necessary in more severe cases. Pressure
stents over the damaged areas may be required to prevent
early contracture of the wounds. After healing, further
definitive surgical or reconstructive treatment may be neces-
sary because of extensive scar formation.
Submucous Fibrosis
Etiology
Several factors contributing to submucous fibrosis include
general nutritional or vitamin deficiencies and hypersensi-
tivity to various dietary constituents. The primary factor
appears to be chewing of the areca (betel) nut. It appears
that this condition is due to impaired degradation of nor-
mal collagen by fibroblasts rather than excess production.
Also, chronic consumption of chili peppers or chronic and
prolonged deficiency of iron and B complex vitamins, espe-
cially folic acid, increases hypersensitivity to many potential
irritants (areca nut, dietary spices, and tobacco), with an
attendant inflammatory reaction and fibrosis. It has been
reported that a polymorphism of the promoter region of the
matrix metalloproteinase 3 (MMP 3) gene is common in
oral submucous fibrosis and may contribute to develop-
ment of the disease. Also postulated in terms of pathogen-
esis is an increased degree of collagen cross-linking through
upregulation of lysyl oxidase activity stimulated by areco-
line, an alkaloid contained in the areca nut component of
paan and gutka.
Clinical Features
Once rarely seen in North America, submucous fibrosis is
relatively common in Southeast Asia, India, and neighboring
countries. Recent patterns of immigration to the Western
hemisphere have led to an increase in the number of cases.
The condition is seen typically between the ages of 20 and
40 and is often associated with the habitual use of com-
pounds containing areca (betel) nut and tobacco in various
forms, including a quid form (paan) and a powdered form
(gutka), where these are placed in the oral cavity for extended
periods of time and often are replaced up to several times per
day. The addictive properties of this habit are well known, as
are the mucosal alterations that accompany long-term use, in
particular submucous fibrosis.
Oral submucous fibrosis presents as a whitish yellow
change that has a chronic, insidious biological course. It is
characteristically seen in the oral cavity, but on occasion it
may extend into the pharynx and the esophagus. Submu-
cous fibrosis occasionally may be preceded by or may be
associated with vesicle formation. Over time, the affected
mucosa, especially the soft palate and the buccal mucosa,
loses its resilience and shows limited vascularity and elastic-
ity. This process then progresses from the lamina propria to
CHAPTER 3  White Lesions 109
the underlying musculature. Fibrous bands are readily pal-
pable in the soft palate and the buccal mucosa. The clinical
result is significant trismus with considerable difficulty in
eating.
Histopathology
Microscopically, the principal feature is atrophy of the epithe-
lium and subjacent fibrosis (Figure 3-66). Epithelial dysplasia
occasionally may be evident. The lamina propria is poorly
vascularized and hyalinized; fibroblasts are few. A diffuse mild
to moderate inflammatory infiltrate is present. Type I collagen
predominates in the submucosa, whereas type III collagen
tends to localize at the epithelium–connective tissue interface
and around blood vessels, salivary glands, and muscle.
Treatment and Prognosis
Eliminating causative agents is part of the management
of submucous fibrosis. Therapeutic measures include local
injections of chymotrypsin, hyaluronidase, and dexametha-
sone, with surgical excision of fibrous bands and submuco-
sal placement of vascularized free flap grafts. All methods of
treatment, including surgical modalities, however, have
proved to be of only modest help in this essentially irrevers-
ible condition.
The primary importance of submucous fibrosis relates
to its premalignant nature. The development of squamous
cell carcinoma has been noted in as many as one third of
patients with submucous fibrosis.
Fordyce’s Granules
Fordyce’s granules represent ectopic sebaceous glands or
sebaceous choristomas (normal tissue in an abnormal loca-
tion). This condition is regarded as developmental and can
be considered a variation of normal.
Fordyce’s granules are multiple and often are seen in ag-
gregates or in confluent arrangements (Figures 3-67 and
3-68). Sites of predilection include the buccal mucosa and
the vermilion of the upper lip. Lesions generally are sym-
metrically distributed and tend to become obvious after
puberty, with maximal expression occurring between 20 and
• Figure 3-66  ​Submucous fibrosis showing epithelial atrophy over
fibrotic submucosa.