Red and White Lesions of the

Oral Mucosa

Ass. Prof. Dr Ameena Ryhan

Burket’s ORAL MEDICINE

12th edition 2015/2021
Oral mucosal lesions may be
classified according to different
characteristics
A white appearance of the oral mucosa may be
caused by a variety of factors:

 The oral epithelium may be stimulated to an increased

production of keratin (hyperkeratosis)
 or an abnormal but benign thickening of stratum spinosum
(acanthosis)
 Intra- and extracellular accumulation of fluid in the
epithelium may also result in clinical whitening.
 Microbes, particularly fungi, can produce whitish
pseudomembranes consisting of sloughed epithelial
cells, fungal mycelium, and neutrophils, which are loosely
attached to the oral mucosa
Mechanisms leading to a white appearance of the oral mucosa due to an
increased production of keratin (hyperkeratosis).
Mechanisms leading to a white appearance of the oral mucosa due to
an abnormal but benign thickening of stratum spinosum (acanthosis).
Mechanisms leading to a transparent white appearance of the oral mucosa
due to intra‐ and extracellular accumulation of fluid in the epithelium
(leukodema)
Mechanisms of a white appearance of the oral mucosa due to
microbes, particularly fungi, which can produce whitish
pseudomembranes consisting of sloughed epithelial cells, fungal
mycelium, and neutrophils, which are loosely attached to the oral
mucosa (plaques).
A red lesion of the oral mucosa may
develop as a result :

 of atrophic epithelium characterized by a

reduction in the number of epithelial cells

 or increased vascularization that is dilatation

of vessels and/ or proliferation of vessels
Mechanisms leading to a red appearance of the oral mucosa; a red lesion
of the oral mucosa may develop as the result of an atrophic epithelium
(atrophy).
Mechanisms leading to a red appearance of the oral mucosa characterized by a
reduction in the number of epithelial cells or increased vascularization; that is,
dilatation of vessels and/or proliferation of vessels.
Main clinical characteristics of red or white lesions.
 Is pain present?
 Are lesions single or multiple?
 Are lesions bilateral or unilateral?
 Is the distribution of lesions linked to mucosal type?
 Are lesion borders defined or indistinct?
 Date of onset
 Are lesions associated with changes of the skin?
 Duration of lesion
 Any changes in shape, size, or texture with time?
 Any previous response to therapy?
 What makes the pain or the lesions worse?
 Have lesions healed and recurred?
Infectious Diseases
Oral Candidiasis
Oral candidiasis is the most prevalent opportunistic infection affecting the oral
mucosa. In the vast majority of cases, the lesions are caused by Candida
albican.

The pathogenesis is not fully understood, but a number of predisposing factors

have been shown to convert C. albicans from the normal commensal flora
(saprophytic stage) to a pathogenic organism (parasitic stage).

C. albicans is usually a weak pathogen, affecting

the very young,
the very old,
the very sick.
Most candidal infections only affect mucosal linings, but rare systemic
manifestations may have a fatal course.
Oral candidiasis is divided into primary and secondary infections
The primary infections are restricted to the oral and perioral sites,
whereas secondary infections are accompanied by systemic
mucocutaneous manifestations

Etiology and Pathogenesis

C. albicans, C. tropicalis, and C. glabrata comprise together
over 80% of the species isolated from human candidal infections

To invade the mucosal lining, the microorganisms must adhere to the

epithelial surface; therefore, candidal strains with better adhesion
potential are more virulent than strains with poorer adhesion ability.

The yeasts’ penetration of the epithelial cells is facilitated by their

production of lipases and for the yeasts to remain within the
epithelium, they must overcome constant desquamation of
surface epithelial cells.
Predisposing Factors for Oral Candidiasis and
Ca Predisposing Factors for Oral Candidiasis
and
Candida-Associated Lesions
Local
Denture wearing
Smoking
Atopic constitution
Inhalation steroids
Topical steroids
Hyperkeratosis
Imbalance of the oral microflora
Quality and quantity of saliva
General
Immunosuppressive diseases
Impaired health status
Immunosuppressive drugs
Chemotherapy
Endocrine disorders
Hematinic deficiencies
 Primary Oral Candidiasis Secondary Oral Candidiasis
Acute Familial chronic mucocutaneous
candidiasis
Pseudomembranous Diffuse chronic mucocutaneous
candidiasis
Erythematous Candidiasis endocrinopathy
syndrome
Familial mucocutaneous candidiasis
Chronic Severe combined immunodeficiency
Pseudomembranous DiGeorge syndrome
Erythematous Chronic granulomatous disease
Plaque-like Acquired immune deficiency
syndrome (AIDS)
Nodular
Candida-associated lesions
Denture stomatitis
Angular cheilitis
Median rhomboid glossitis

2015
Classification of oral candidiasis.

Type Examples
Pseudomembranous—acute Thrush
Pseudomembranous—chronic With inhalers
Erythematous—acute atrophic After antibiotic therapy
Erythematous—chronic atrophic Denture stomatitis; in HIV
Chronic hyperplastic (nodular and Candidal leukoplakia, median
plaque‐like subtypes) rhomboid glossitis
Candida‐associated lesions Denture stomatitis; angular cheilitis
 Candidiasis affecting extraoral sites and conditions
predisposing to candidiasis.

 Familial chronic mucocutaneous candidiasis

 Diffuse chronic mucocutaneous candidiasis
 Erythematous candidiasis endocrinopathy syndrome
 Chronic severe combined immunodeficiency
 DiGeorge syndrome
 Chronic granulomatous disease
 HIV disease
Epidemiology
The prevalence of candidal strains, as part of the commensal
oral flora, shows

 Large geographic variations

 Candidal strains are more frequently isolated from women.
 A seasonal variation has been observed, with an increase
during summer months.
 Hospitalized patients have a higher prevalence of the yeasts.
 In healthy individuals, blood group O and non-secretion of
blood group antigens are separate and cumulative risk
factors for oral carriage of C. albicans.
 In complete denture-wearers, the prevalence of denture
stomatitis has been reported variously from 11–67%.
Clinical Findings
Pseudomembranous Candidiasis
Acute form of pseudomembranous candidiasis (thrush) is
grouped with the primary oral candidiasis and is
recognized as the classic candidal infection.

The infection predominantly affects patients taking

antibiotics, immunosuppressant drugs, or having a
disease that suppresses the immune system.
Erythematous Candidiasis

Was previously referred to as atrophic oral candidiasis erythematous

surface may not just reflect atrophy but can also be explained by
increased vascularization. The lesion has a diffuse border which helps
distinguish it from erythroplakia which usually has a sharper demarcation

The infection is predominantly seen in the palate and the dorsum of the
tongue of patients who are using inhalation steroids.
Other predisposing factors that can cause erythematous candidiasis are
smoking and treatment with broad-spectrum antibiotics.
Chronic Plaque-Type and Nodular Candidiasis

Replaces the older term, candidal leukoplakia.

o A white irremovable plaque
o Characterizes the typical clinical presentation, which may
be indistinguishable from oral leukoplakia
o A positive correlation between oral candidiasis and
moderate to severe epithelial dysplasia
o Both the chronic plaque-type and the nodular type of oral
candidiasis have been associated with malignant
transformation, but the possible role of yeasts in oral
carcinogenesis is unclear.
o It has been hypothesized that it may act through its
capacity to catalyze nitrosamin production

.
Denture Stomatitis

Denture stomatitis is classified into three different types.

Type I is limited to minor erythematous sites caused by
trauma from the denture.
Type II affects a major part of the denture-covered mucosa
In addition to the features of type II, type III has a granular
mucosa.
The denture serves as a vehicle that accumulates
sloughed epithelial cells and protects the microorganisms
from physical influences such as salivary flow.
The microflora is complex and may, in addition to C.
albicans contain bacteria from several genera, such as
streptococcus-, Veillonella-, Lactobacillus-, Prevotella-
Actinomyces-strains.
It is not known to what extent these bacteria participate in
the pathogenesis of denture stomatitis
Denture stomatitis is classified into three different types:

●● Type I is limited to erythematous sites caused by trauma

from the denture.
●● Type II affects a major part of the denture‐covered
mucosa.
●● Type III has a granular mucosa (reactive proliferation
of underlying fibrous tissue) in addition to the features
of type II..
 Chronic atrophic candidiasis (denture stomatitis)
type III with a granular mucosa in the central part of the palate
Angular Cheilitis

Angular cheilitis presents as infected fissures of the commissures

of the mouth, often surrounded by erythema

The lesions are frequently infected with both Candida albicans

and Staphylococcus aureus.
Vitamin B12 deficiency, iron deficiencies, and loss of vertical
dimension have been associated with this disorder.

Dry skin may promote the development of fissures in the

commissures, allowing invasion by the microorganisms.
30% of patients with denture stomatitis also have angular cheilitis,
but this infection is only seen in 10% of denture-wearing
 Candida‐induced bilateral angular cheilitis.
Treatment must include the intraoral Candida reservoir.
Median Rhomboid Glossitis
 Clinically characterized by an erythematous lesion in the
center of the posterior part of the dorsum of the tongue;
 an oval configuration. This area of erythema results from
atrophy of the filiform papillae and the surface may be
lobulated.
 The etiology is not fully clarified, but the lesion frequently
shows a mixed bacterial/fungal microflora.
 Biopsies yield candidal hyphae in more than 85% of the
lesions.
 Smokers and denture-wearers have an increase risk of
developing median rhomboid glossitis
 Patients using inhalation steroids.
 Sometimes a concurrent erythematous lesion may be
observed in the palatal mucosa (kissing lesions).
 Median rhomboid glossitis is asymptomatic, and
management is restricted to a reduction of predisposing
factors.
 The lesion does not entail any increased risk for malignant
transformation
 Median rhomboid glossitis apparently arising from
the junction of the posterior third and anterior two‐thirds of the
tongue. Histology confirmed chronic hyperplastic candidiasis.
Oral Candidiasis Associated with HIV

More than 90% of acquired immune deficiency syndrome (AIDS)

patients have had oral candidiasis during the course of their HIV
infection, and the infection is considered a portent of AIDS
development

The most common types of oral candidiasis in conjunction with HIV

are
Pseudomembranous candidiasis,
Erythematous candidiasis,
Angular cheilitis,
and chronic plaque-like candidiasis.

As a result of the highly active antiretroviral therapy (HAART), the

prevalence of oral candidiasis has decreased substantially.
Chronic mucocutaneous candidiasis (CMC)
 Involves a heterogeneous group of disorders, which, in
addition to oral candidiasis, also affect the skin, typically the
nail and other mucosal linings, such as the genital mucosa.
 The face and scalp may be involved.
 Approximately 90% of the patients with CMC also present with
oral candidiasis.
 The oral manifestations may involve the tongue, and lesions
are seen in conjunction with fissures.
 CMC can occur as part of endocrine disorders, including
hyperparathyroidism and Addison’s disease.
 Recent studies revealed that an impairment of interleukin‐
17 (IL‐17) immunity underlies the development of CMC
 T-helper 17 cells produce IL‐17 and play an important role in
host mucosal immunity to Candida.
 Impaired phagocytic function by neutrophilic granulocytes
and macrophages caused by myeloperoxidase (MPO) deficiency
(oxidative stress plays a key role in the release of MPO from these
cells)

 Severe combined immunodeficiency (SCID) syndrome

is characterized by a defect in the function of the cell-mediated arm
of the immune system.
 Patients with this disorder frequently contract disseminated
candidal infections.

 Thymoma is a neoplasm of thymic epithelial cells that also

entails systemic candidiasis. Thus, both the native and adaptive
immune systems are critical to prevent development of systemic
mucocutaneous candidiasis
Chronic candidiasis of (A) dorsum of
tongue and (B) fingernails of a patient
with chronic mucocutaneous candidiasis
Diagnosis and Laboratory Findings
The presence of candidal microorganisms as a member of the commensal
flora complicates the discrimination of the normal state from infection.
The detection of yeast organisms in the form of hyphae- or pseudohyphae-like
structures is usually considered a sign of infection although these structures
have also been identified in normal oral mucosa.

To increase the sensitivity, a second scrape can be transferred to a transport

medium followed by cultivation on Sabouraud agar. To discriminate between
different candidal species, an additional examination can be performed on
Pagano-Levin agar
The result is expressed as colony forming units per cubic millimeter
(CFU/mm2).
This method is a valuable adjunct in the diagnostic process of erythematous
candidiasis and denture stomatitis as these infections consist of fairly
homogeneous erythematous lesions.
Salivary culture techniques are primarily used in parallel with other
diagnostic methods to obtain an adequate quantification of candidal
organisms. Patients who display clinical signs of oral candidiasis usually
have more than 500 CFU/mL.
Candida cells can be found in 60% of people in numbers of up to 500 cfu/mL
as normal commensals.
In chronic plaque-type and nodular candidiasis, cultivation techniques
have to be supplemented by a histopathologic examination.
This examination is primarily performed to identify the presence of
epithelial dysplasia and to identify invading candidal organisms by
PAS staining.
Management
Treatment for fungal infections, which usually include antifungal
regimens, will not always be successful unless the clinician
addresses predisposing factors that may cause recurrence.
Local factors are often easy to identify but sometimes not possible to
reduce or eradicate
 In smokers, cessation of the habit may result in disappearance
of the infection even without antifungal treatment
 Antifungal drugs belong to the groups of polyenes or azoles
Polyenes such as nystatin and amphotericin B are usually the
first choices in treatment of primary oral candidiasis and are both
well tolerated.
 Elimination or reduction of predisposing factors should always be
the first goal for treatment
 This involves improved denture hygiene, not to use the denture
while sleeping.
 The denture hygiene is important to remove nutrients, including
desquamated epithelial cells, which may serve as a source of
nitrogen essential for the growth of the yeasts
 Denture cleaning also disturbs the maturity of a microbial
environment established under the denture.
 Porosities in the denture can harbor microorganisms, which may
not be removed by physical cleaning, the denture should be
stored in antimicrobial solutions during the night

Different solutions,including
alkaline peroxides, alkaline hypochlorites,acids, disinfectants, and
enzymes, have been suggested.
The latter seems to be most effective against candidal strains.
Chlorhexidine may also be used but can discolor the denture
and also counteracts the effect of nystatin.
  Type III denture stomatitis may be treated with surgical excision
in an attempt to eradicate microorganisms present in the deeper
fissures of the granular tissue. If this is not sufficient, continuous
treatment with topical antifungal drugs should be considered.

 Topical treatment with azoles such as miconazole is the treatment of

choice for angular cheilitis often infected by both S. aureus and
candidal strains. (biostatic effect on S. aureus in and fungistatic effect).

 If angular cheilitis comprises an erythema surrounding the fissure, a

mild steroid ointment may be required to suppress the inflammation.
 To prevent recurrences, patients have to apply a moisturizing cream,
which may prevent new fissure formation.
 Systemic azoles may be used for deeply seated primary
candidiasis, such as chronic hyperplastic candidiasis,
denture stomatitis, and median rhomboid glossitis with a granular
appearance,

There are several disadvantages with the use of azoles.

 They are known to interact with warfarin, leading to an increased
bleeding propensity.
 Topical application as the azoles are fully or partly resorbed from
the GIT.
 Development of resistance is particularly compelling for
fluconazole in individuals with HIV disease. In such cases,
ketoconazole and itraconazole have been recommended as
alternatives.
 The azoles are also used in the treatment of secondary oral
candidiasis associated with systemic predisposing factors and for
systemic candidiasis.
Prognosis of oral candidiasis is good when predisposing
factors are reduced or eliminated.
Persistent chronic plaque-type and nodular candidiasis have
been suggested to be associated with an increased risk for
malignant transformation compared with leukoplakia, not infected by
candidal strains.
Oral Hairy Leukoplakia
 Is the second most common HIV-associated oral mucosal lesion. HL
has been used as a marker of disease activity since the lesion is
associated with low CD4+ T-lymphocyte counts.
 The lesion is not pathognomonic for HIV disease since other states of
immune deficiencies, such as caused by immunosuppressive drugs
and cancer chemotherapy

 Is strongly associated with Epstein-Barr virus (EBV) and with low

levels of CD4+ T lymphocytes.
 Antiviral medication, which prevents EBV replication, is curative

 In AIDS, the prevalence may be as high as 80%.

 In children the prevalence is lower compared with adults (2%).
 Is more frequently in men, but the reason for this predisposition.
 A correlation between smoking and OHL has also been observed
Hairy leukoplakia at the left lateral border of tongue in an AIDS
patient showing vertical keratotic corrugations.
Clinical Findings
 Is frequently encountered on the lateral borders of the tongue but may
also be observed on the dorsum and in the buccal mucosa
 is asymptomatic,although symptoms may be present when the lesion is
superinfected with candidal strains
 it is important to always consider mucosal lesion whenever the
border of the tongue is affected by white lesions, particularly in
immunocompromised patients

Diagnosis
A diagnosis of OHL is usually based on clinical characteristics, but
histopathologic examination and detection of EBV can be performed to
confirm the clinical diagnosis

Management
 It can be treated successfully with antiviral medication, but this is
not often indicated as this disorder is not associated with adverse
symptoms.
 the disorder may show spontaneous regression.