Red and white lesions of the Red and white lesions of the oral mucosaoral mucosa

Hereditary white lesionsHereditary white lesions..

LeukodemaLeukodema

White sponge nevusWhite sponge nevus

Hereditary benign intraepithelial Hereditary benign intraepithelial dyskeratosisdyskeratosis

Darrier’s diseaseDarrier’s disease

Reactive/inflammatory white Reactive/inflammatory white lesionslesions

Frictional (Traumatic) keratosisFrictional (Traumatic) keratosis Chemical injuries of the oral mucosaChemical injuries of the oral mucosa Actinic keratosis (cheilitis)Actinic keratosis (cheilitis) Smokeless tobacco-induced keratosisSmokeless tobacco-induced keratosis Nicotine stomatitisNicotine stomatitis

Infectious white lesions and white Infectious white lesions and white and red lesionsand red lesions::

Oral hairy leukoplakia Oral hairy leukoplakia CandidiasisCandidiasis Mucous patchesMucous patches

Idiopathic "TRUE" leukoplakiaIdiopathic "TRUE" leukoplakia

ErythroplakiaErythroplakia

Oral lichen planusOral lichen planus Lichenoid reactionsLichenoid reactions

Lupus erythematosus (systemic Lupus erythematosus (systemic and discoid)and discoid)

Miscellaneous lesionsMiscellaneous lesions::

Oral submucous fibrosis.Oral submucous fibrosis. Skin graft.Skin graft.

Hereditary White LesionsHereditary White Lesions::

Leukoedema:Leukoedema:

Leukoedema is a common mucosal Leukoedema is a common mucosal alteration that represents a variation of the alteration that represents a variation of the normal condition rather than a true normal condition rather than a true pathologic change.pathologic change.

FeaturesFeatures : : Faint, white, diffuse, and filmy appearanceFaint, white, diffuse, and filmy appearance Numerous surface folds resulting in wrinkling Numerous surface folds resulting in wrinkling

of the mucosa.of the mucosa. It cannot be scraped offIt cannot be scraped off It disappears or fades upon stretching It disappears or fades upon stretching

the mucosathe mucosa. . Microscopic examination reveals thickening Microscopic examination reveals thickening

of the epithelium, with significant intracellular of the epithelium, with significant intracellular edema of the stratum spinosum. The surface edema of the stratum spinosum. The surface of the epithelium may demonstrate a of the epithelium may demonstrate a thickened layer of parakeratinthickened layer of parakeratin..

LeukoedemaLeukoedema

TreatmentTreatment

No treatment is indicated, no malignant No treatment is indicated, no malignant change has been reported.change has been reported.

White Sponge NevusWhite Sponge Nevus::

The disease usually involves the oral The disease usually involves the oral mucosa and (less frequently) the mucous mucosa and (less frequently) the mucous membranes of the nose, esophagus, membranes of the nose, esophagus, genitalia, and rectum.genitalia, and rectum.

The lesions may be present at birth or may The lesions may be present at birth or may first manifest or become more intense at first manifest or become more intense at puberty.puberty.

FeaturesFeatures:: Bilateral symmetric white, soft, “spongy”, or velvety Bilateral symmetric white, soft, “spongy”, or velvety

thick plaques of the buccal mucosa. thick plaques of the buccal mucosa. Other sites in the oral cavity may be involved, Other sites in the oral cavity may be involved,

including the ventral surface of the tongue, floor of including the ventral surface of the tongue, floor of the mouth, labial mucosa, soft palate, and alveolar the mouth, labial mucosa, soft palate, and alveolar mucosa. mucosa.

Asymptomatic and does not exhibit tendencies Asymptomatic and does not exhibit tendencies toward malignant change. toward malignant change.

Histopathologic features are epithelial thickening, Histopathologic features are epithelial thickening, parakeratosis, a peculiar perinuclear condensation parakeratosis, a peculiar perinuclear condensation of the cytoplasm, and vacuolization of the of the cytoplasm, and vacuolization of the suprabasal layer of keratinocytes suprabasal layer of keratinocytes

White Sponge NevusWhite Sponge Nevus::

TreatmentTreatment::

No treatment is indicated for this benign and No treatment is indicated for this benign and asymptomatic condition.asymptomatic condition.

Hereditary Benign Intraepithelial Hereditary Benign Intraepithelial DyskeratosisDyskeratosis::

1- Oral Lesions:1- Oral Lesions: Thick, corrugated, asymptomatic, white Thick, corrugated, asymptomatic, white

“spongy” plaques involving the buccal and “spongy” plaques involving the buccal and labial mucosa.labial mucosa.

Other intraoral sites include the floor of the Other intraoral sites include the floor of the mouth, the lateral tongue, the gingiva, and mouth, the lateral tongue, the gingiva, and the palate. the palate.

Detected in the first year of life and gradually Detected in the first year of life and gradually increase in intensity until the teens. increase in intensity until the teens.

2- Eye Lesions 2- Eye Lesions Thick, gelatinous, foamy, and opaque Thick, gelatinous, foamy, and opaque

plaques form adjacent to the cornea.plaques form adjacent to the cornea. The plaques may exhibit seasonal The plaques may exhibit seasonal

prominence, with many patients reporting prominence, with many patients reporting more-pronounced lesions in the Spring and more-pronounced lesions in the Spring and regression during the Summer months.regression during the Summer months.

Blindness due to corneal vascularization Blindness due to corneal vascularization may occur.may occur.

Histopathologic Features:Histopathologic Features: Epithelium exhibits marked parakeratin Epithelium exhibits marked parakeratin

production with thickening of the stratum production with thickening of the stratum spinosum and the presence of numerous spinosum and the presence of numerous dyskeratotic cells (eosinophilic cells that dyskeratotic cells (eosinophilic cells that resemble epithelial pearls).resemble epithelial pearls).

Treatment:Treatment: No treatment is required for the oral lesions. No treatment is required for the oral lesions.

For evaluation and treatment of the ocular For evaluation and treatment of the ocular lesions, the patient should be referred to an lesions, the patient should be referred to an ophthalmologist. ophthalmologist.

Darrier’s Disease: (Keratosis Darrier’s Disease: (Keratosis Follicularis)Follicularis)

A genetic disorder characterized by a A genetic disorder characterized by a persistent eruption of hyperkeratotic persistent eruption of hyperkeratotic papules.papules.

PathologyPathology:: Fissures (lacunae) appear due to acantholysis Fissures (lacunae) appear due to acantholysis

above the basal layer. They later extend above the basal layer. They later extend irregularly. irregularly.

Small groups of cells around the lacunae become Small groups of cells around the lacunae become separated from their neighbours, enlarge and separated from their neighbours, enlarge and present a darkly staining nucleus surrounded by present a darkly staining nucleus surrounded by clear cytoplasm and a glistening ring simulating a clear cytoplasm and a glistening ring simulating a membrane. These membrane. These corpscorps rondsronds are cells showing are cells showing premature partial keratinization (dyskeratosis); premature partial keratinization (dyskeratosis); they give rise to the they give rise to the grainsgrains, small cells with , small cells with shrunken cytoplasm, seen in the upper layers of shrunken cytoplasm, seen in the upper layers of the epidermis.the epidermis.

Skin Lesions: Skin Lesions:

A firm, rather greasy, harsh papule, which A firm, rather greasy, harsh papule, which is skin coloured, yellow-brown or brown. is skin coloured, yellow-brown or brown. Coalescence of the papules produces Coalescence of the papules produces irregular warty plaques or papillomatous irregular warty plaques or papillomatous masses, which in the flexures, become masses, which in the flexures, become vegetating and malodorous. vegetating and malodorous.

Oral Lesions:Oral Lesions: White umbilicate or cobblestone papules White umbilicate or cobblestone papules

on the palate, tongue, buccal mucosa, on the palate, tongue, buccal mucosa, epiglottis, pharyngeal wall, vulva, epiglottis, pharyngeal wall, vulva, oesophagus or rectum may occur, as may oesophagus or rectum may occur, as may hypertrophy of gums. hypertrophy of gums.

Confluence of the papules may form patches Confluence of the papules may form patches simulating leukoplakia. Blockage of the simulating leukoplakia. Blockage of the salivary glands may be associated salivary glands may be associated

Nail Lesions:Nail Lesions:

Characteristic nail changes are seen:Characteristic nail changes are seen: Broad, white, longitudinal bands;Broad, white, longitudinal bands; Broad, slightly translucent, red, longitudinal Broad, slightly translucent, red, longitudinal

bands;bands; A sandwich of red and white longitudinal A sandwich of red and white longitudinal

bands, often with a V-shaped nick at the bands, often with a V-shaped nick at the free margin of the nail. free margin of the nail.

Ear LesionsEar Lesions::

The external auditory meatus may be The external auditory meatus may be blocked by accumulated keratotic debris blocked by accumulated keratotic debris

Reactive and Inflammatory White Reactive and Inflammatory White Lesions:Lesions:

Frictional KeratosisFrictional Keratosis

Cheek ChewingCheek Chewing::

Chemical Injuries of the Oral Chemical Injuries of the Oral MucosaMucosa::

Actinic Keratosis (Cheilitis)Actinic Keratosis (Cheilitis)::

Smokeless Tobacco-lnduced Smokeless Tobacco-lnduced KeratosisKeratosis::

Nicotine StomatitisNicotine Stomatitis::

Infectious White Lesions and Infectious White Lesions and White and Red LesionsWhite and Red Lesions

Oral Hairy Leukoplakia:Oral Hairy Leukoplakia: Corrugated white lesion Corrugated white lesion Usually occurs on the Usually occurs on the

lateral or ventral lateral or ventral surfaces of the tongue surfaces of the tongue

In patients with severe In patients with severe immunodeficiency. The immunodeficiency. The most common disease most common disease associated with oral associated with oral hairy leukoplakia is HIV hairy leukoplakia is HIV infection.infection.

Epstein-Barr virus (EBV) Epstein-Barr virus (EBV) is the causative agent is the causative agent

HistopathologyHistopathology::

Hyperparakeratosis with an irregular surface,Hyperparakeratosis with an irregular surface, Acanthosis with superficial edema,Acanthosis with superficial edema, Koilocytic cells (virally affected "balloon" cells) in Koilocytic cells (virally affected "balloon" cells) in

the spinous layer. The characteristic microscopic the spinous layer. The characteristic microscopic feature is the presence of homogeneous viral feature is the presence of homogeneous viral nuclear inclusions with a residual rim of normal nuclear inclusions with a residual rim of normal chromatin.chromatin.

Demonstrating the presence of EBV through in Demonstrating the presence of EBV through in situ hybridization, electron microscopy, or situ hybridization, electron microscopy, or polymerase chain reaction polymerase chain reaction

Treatment and PrognosisTreatment and Prognosis::

The condition usually disappears when The condition usually disappears when antiviral medications such as zidovudine, or antiviral medications such as zidovudine, or acyclovir are used in the treatment of the acyclovir are used in the treatment of the HIV infection .HIV infection .

Oral CandidosisOral Candidosis

Because Candida are normal oral Because Candida are normal oral inhabitants, thrush and other forms of oral inhabitants, thrush and other forms of oral candidiasis may be classified as specific candidiasis may be classified as specific endogenous infections. endogenous infections.

Important predisposing factors for Important predisposing factors for oral candidosisoral candidosis

– Immunodeficiency (e.g. diabetes mellitus or AIDS) or Immunodeficiency (e.g. diabetes mellitus or AIDS) or immunosuppression (including steroid inhalers, cancer immunosuppression (including steroid inhalers, cancer chemotherapy, and radiotherapy). chemotherapy, and radiotherapy).

– Poor oral hygienePoor oral hygiene– PregnancyPregnancy– AnaemiaAnaemia– Suppression of the normal oral flora by antibacterial Suppression of the normal oral flora by antibacterial

drugs drugs – Xerostomia Xerostomia

– Haematologic malignanciesHaematologic malignancies

Spectrum of oral candidosisSpectrum of oral candidosis::

Acute candidosis Acute candidosis Thrush (acute pseudomembranous candidosis).Thrush (acute pseudomembranous candidosis). Acute antibiotic stomatitis (acute atrophic or erythematous)Acute antibiotic stomatitis (acute atrophic or erythematous)

Chronic candidosisChronic candidosis Denture-induced stomatitisDenture-induced stomatitis Chronic hyperplastic candidosis (candidal leukoplakia)Chronic hyperplastic candidosis (candidal leukoplakia) Median rhomboid glossitisMedian rhomboid glossitis Chronic mucocutaneous candidosis Chronic mucocutaneous candidosis Erythematous candidosisErythematous candidosis

Angular stomatitisAngular stomatitis (common to all types of oral candidosis). (common to all types of oral candidosis).

Acute Pseudomembranous Acute Pseudomembranous Candidosis (Thrush)Candidosis (Thrush)

Clinical Features:Clinical Features:

Painless, soft, friable, and creamy plaques on the Painless, soft, friable, and creamy plaques on the mucosa. mucosa.

Can be easily wiped off, to expose an Can be easily wiped off, to expose an erythematous mucosa or shallow ulceration.erythematous mucosa or shallow ulceration.

Their extent varies from isolated small flecks to Their extent varies from isolated small flecks to widespread confluent plaques.widespread confluent plaques.

Angular stomatitis is frequently associated as it is Angular stomatitis is frequently associated as it is with any form of intra-oral candidosis.with any form of intra-oral candidosis.

Sometimes a prodrome of bad taste or loss of taste Sometimes a prodrome of bad taste or loss of taste sensation precedes the appearance of the lesions.sensation precedes the appearance of the lesions.

PathologyPathology

A Gram-stained smear shows large masses of A Gram-stained smear shows large masses of tangled hyphae, detached epithelial cells and tangled hyphae, detached epithelial cells and leucocytes.leucocytes.

Biopsy shows hyperplastic epithelium infiltrated by Biopsy shows hyperplastic epithelium infiltrated by inflammatory oedema and cells, predominantly inflammatory oedema and cells, predominantly neutrophils. neutrophils.

Staining with PAS shows many candidal hyphae Staining with PAS shows many candidal hyphae growing down through the epithelial cells to the growing down through the epithelial cells to the junction of the plaque with the spinous cell layer.junction of the plaque with the spinous cell layer.

ManagementManagement

Control of any local cause such as topical Control of any local cause such as topical antibiotic treatment . antibiotic treatment .

Nystatin or amphotericin lozenges (topical Nystatin or amphotericin lozenges (topical antifungals) should allow the oral microflora antifungals) should allow the oral microflora to return to normal.to return to normal.

Failure of response to topical antifungals Failure of response to topical antifungals suggests immune deficiency. suggests immune deficiency.

In immunodeficient patients as in HIV In immunodeficient patients as in HIV infection, candidosis may respond to infection, candidosis may respond to fluoconazole or itraconazole.fluoconazole or itraconazole.

Acute Antibiotic StomatitisAcute Antibiotic Stomatitis::

Overuse or topical oral use of antibiotics, Overuse or topical oral use of antibiotics, especially tetracycline, suppressing normal especially tetracycline, suppressing normal competing oral flora. competing oral flora.

Clinically, the whole mucosa is red and sore. Clinically, the whole mucosa is red and sore. Flecks of thrush may be present. Flecks of thrush may be present.

Resolution may follow withdrawal of the Resolution may follow withdrawal of the antibiotic but is accelerated by topical antibiotic but is accelerated by topical antifungal treatment.antifungal treatment.

Generalized candidal erythema which is Generalized candidal erythema which is clinically similar, can also be a consequence clinically similar, can also be a consequence of xerostomia which promotes candidal of xerostomia which promotes candidal infection. infection.

It is a typical complication of Sjogren's It is a typical complication of Sjogren's syndrome. syndrome.

Nystatin suspension or miconazole gel held Nystatin suspension or miconazole gel held in the mouth is usually effective.in the mouth is usually effective.

Denture-induced StomatitisDenture-induced Stomatitis::

Asymptomatic erythema sharply limited to Asymptomatic erythema sharply limited to the area of mucosa occluded by a well-fitting the area of mucosa occluded by a well-fitting upper denture or even an orthodontic plate.upper denture or even an orthodontic plate.

Similar inflammation is not seen under the Similar inflammation is not seen under the more mobile lower denture which allows a more mobile lower denture which allows a relatively free flow of saliva beneath it.relatively free flow of saliva beneath it.

Angular stomatitis is frequently associated Angular stomatitis is frequently associated and may form the chief complaint.and may form the chief complaint.

PathologyPathology::

Gram-stained smears show candidal hyphae and Gram-stained smears show candidal hyphae and some yeast forms which have proliferated in the some yeast forms which have proliferated in the interface between denture base and mucosa.interface between denture base and mucosa.

Histologically, there is typically mild acanthosis Histologically, there is typically mild acanthosis with prominent blood vessels superficially and a with prominent blood vessels superficially and a mild chronic inflammatory infiltrate. The mild chronic inflammatory infiltrate. The inflammation is probably a response to enzymes inflammation is probably a response to enzymes such as phospholipases produced by the fungus such as phospholipases produced by the fungus

TreatmentTreatment:: Denture cleansing .Cleansers can be divided into groups according to Denture cleansing .Cleansers can be divided into groups according to

their primary components: their primary components: alkaline peroxides, hypochlorites, acids, alkaline peroxides, hypochlorites, acids, disinfectants, and enzymesdisinfectants, and enzymes .Yeast lytic enzymes and proteolytic .Yeast lytic enzymes and proteolytic enzymes are the most effective against the infectionenzymes are the most effective against the infection. .

Denture soak solution containing benzoic acid completely eradicates C Denture soak solution containing benzoic acid completely eradicates C albicans from the denture surface as it is taken up into the acrylic resin albicans from the denture surface as it is taken up into the acrylic resin and eliminates the organism from the internal surface of the prosthesis.and eliminates the organism from the internal surface of the prosthesis.

A protease-containing denture soak also effectively removes denture A protease-containing denture soak also effectively removes denture plaque, especially when combined with brushingplaque, especially when combined with brushing..

An oral rinse containing 0.12% chlorhexidine gluconate results in An oral rinse containing 0.12% chlorhexidine gluconate results in complete elimination of the presence of C albicans on the acrylic resin complete elimination of the presence of C albicans on the acrylic resin surface of the denture and in reduction of palatal inflammationsurface of the denture and in reduction of palatal inflammation. .

Diet: High-sucrose diets should be avoided.Diet: High-sucrose diets should be avoided.

Median Rhomboid GlossitisMedian Rhomboid Glossitis . .

Erythematous patches Erythematous patches of atrophic papillae of atrophic papillae located in the central located in the central area of the dorsum of area of the dorsum of the tongue are the tongue are considered a form of considered a form of chronic atrophic chronic atrophic candidiasis.candidiasis.

Chronic Hyperplastic CandidiasisChronic Hyperplastic Candidiasis:: Candidal leukoplakia is considered a chronic form Candidal leukoplakia is considered a chronic form

of oral candidiasis in which firm white leathery of oral candidiasis in which firm white leathery plaques are detected on the cheeks, lips, palate, plaques are detected on the cheeks, lips, palate, and tongue. and tongue.

Mycelial invasion of the deeper layers of the Mycelial invasion of the deeper layers of the mucosa and skin occurs, causing a prolifertive mucosa and skin occurs, causing a prolifertive response of host tissue.response of host tissue.

The differentiation of candidal leukoplakia from The differentiation of candidal leukoplakia from other forms of leukoplakia is based on finding other forms of leukoplakia is based on finding periodic acid-Schiff (PAS)-positive hyphae in periodic acid-Schiff (PAS)-positive hyphae in leukoplakic lesions.leukoplakic lesions.

Chronic Mucocutaneous Chronic Mucocutaneous CandidiasisCandidiasis::

Persistent infection with Candida usually Persistent infection with Candida usually occurs as a result of a defect in cell-occurs as a result of a defect in cell-mediated immunity or may be associated mediated immunity or may be associated with iron deficiency. Hyperplastic with iron deficiency. Hyperplastic mucocutaneous lesions, localized mucocutaneous lesions, localized granulomas, and adherent white plaques on granulomas, and adherent white plaques on affected mucous membranes are the affected mucous membranes are the prominent lesions that identify chronic prominent lesions that identify chronic mucocutaneous candidiasis (CMC).mucocutaneous candidiasis (CMC).

Two categories of CMC have been Two categories of CMC have been described: described:

(1)(1) Syndrome-associated CMCSyndrome-associated CMC (further (further categorized as either familial or chronic). categorized as either familial or chronic).

(2) Localized and diffuse CMC. (2) Localized and diffuse CMC.

Candidiasis endocrinopathy Candidiasis endocrinopathy syndrome (CES)syndrome (CES)

A rare autosomal recessive disorder A rare autosomal recessive disorder characterized by an onset of CMC during characterized by an onset of CMC during infancy or early childhood, associated with infancy or early childhood, associated with the appearance of hypoparathyroidism, the appearance of hypoparathyroidism, hypoadrenocorticism and other endocrine hypoadrenocorticism and other endocrine anomalies anomalies

Patients develop persistent oral candidiasis Patients develop persistent oral candidiasis and hyperplastic infections of the nail folds and hyperplastic infections of the nail folds at an early age.at an early age.

Chronic candidiasis associated with Chronic candidiasis associated with thymomathymoma

The other syndrome-associated form , The other syndrome-associated form , which appears with other autoimmune which appears with other autoimmune abnormalities such as myasthenia gravis. abnormalities such as myasthenia gravis.

Localized and diffuse CMCLocalized and diffuse CMC

Localized CMCLocalized CMC is a variant associated with is a variant associated with chronic oral candidiasis and lesions of the chronic oral candidiasis and lesions of the skin and nails. skin and nails.

The The diffusediffuse variant is characterized by variant is characterized by randomly occurring cases of severe randomly occurring cases of severe mucocutaneous candidiasis with mucocutaneous candidiasis with widespread skin involvement and widespread skin involvement and development of Candida granulomas.development of Candida granulomas.

ManagementManagement

Both oral and cutaneous lesions of CMC Both oral and cutaneous lesions of CMC can be controlled by the continuous use of can be controlled by the continuous use of systemic antifungal drugs.systemic antifungal drugs.

Once treatment is discontinued, the Once treatment is discontinued, the lesions rapidly reappear. lesions rapidly reappear.

Erythematous CandidosisErythematous Candidosis::

This term applies to red mucosal macules This term applies to red mucosal macules due to Candida albicans infection in HIV –due to Candida albicans infection in HIV –positive patients. Favoured sites, in order of positive patients. Favoured sites, in order of frequency, are the hard palate, dorsum of frequency, are the hard palate, dorsum of the tongue and soft palate. Treatment with the tongue and soft palate. Treatment with intraconazole is usually effective.intraconazole is usually effective.

Angular StomatitisAngular Stomatitis::

Angular stomatitis is typically caused by Angular stomatitis is typically caused by leakage of Candida- infected saliva at the leakage of Candida- infected saliva at the angles of the mouth. It can be seen in angles of the mouth. It can be seen in infantile thrush ,in denture wearers or in infantile thrush ,in denture wearers or in association with chronic hyperplastic association with chronic hyperplastic candidosis. It is a characteristic sign of candidosis. It is a characteristic sign of candidal infection.candidal infection.

Treatment of Oral CandidiasisTreatment of Oral Candidiasis::

Treatment of underlying predisposing factors Treatment of underlying predisposing factors (if possible)(if possible)

Antifungal DrugsAntifungal Drugs Antifungal antibiotics nystatin and amphotericin B.Antifungal antibiotics nystatin and amphotericin B. Imidazole derivatives (clotrimazole, miconazole) are Imidazole derivatives (clotrimazole, miconazole) are

available for topical use (cream, oral gel).available for topical use (cream, oral gel). Systemic therapy includes the use of any one of these Systemic therapy includes the use of any one of these

three: ketoconazole, itraconazole, and fluconazole.three: ketoconazole, itraconazole, and fluconazole. Fluconazole and amphotericin B may be used Fluconazole and amphotericin B may be used

intravenously for the treatment of the resistant lesions intravenously for the treatment of the resistant lesions of CMC and systemic candidiasis.of CMC and systemic candidiasis.

Patients for whom predisposing factors such Patients for whom predisposing factors such as xerostomia and immunodeficiency cannot as xerostomia and immunodeficiency cannot be eliminated may need either continuous or be eliminated may need either continuous or repeated treatment to prevent recurrences.repeated treatment to prevent recurrences.

The consumption of yogurt two to three The consumption of yogurt two to three times per week and improved oral hygiene times per week and improved oral hygiene can also help.can also help.

Idiopathic “TRUE” Leukoplakia:

Leukoplakia is a white oral precancerous lesion with a recognizable risk for malignant transformation.

Leukoplakia is currently defined as “a white patch or plaque that cannot be characterized clinically or pathologically as any other disease”.

EtiologyEtiology

A number of locally acting etiologic agentsA number of locally acting etiologic agents, , including including tobaccotobacco, , alcoholalcohol, , candidiasiscandidiasis, , electrogalvanicelectrogalvanic reactionsreactions, , sunlightsunlight and and (possibly) (possibly) herpesherpes simplexsimplex and and papilloma papilloma virusesviruses, have been implicated as causative , have been implicated as causative factors for leukoplakia.factors for leukoplakia.

Alcohol consumptionAlcohol consumption alone is not associated alone is not associated with an increased risk of developing leukoplakia, with an increased risk of developing leukoplakia, but alcohol is thought to serve as a promoter that but alcohol is thought to serve as a promoter that exhibits a strong synergistic effect with exhibits a strong synergistic effect with tobaccotobacco..

Clinical FeaturesClinical Features:: More frequently found in menMore frequently found in men Can occur on any mucosal surfaceCan occur on any mucosal surface Infrequently causes discomfort or pain.Infrequently causes discomfort or pain. Causes change in physical characteristics of Causes change in physical characteristics of

tissues.tissues. Prevalence increases rapidly with age.Prevalence increases rapidly with age. Approximately 70% of oral leukoplakia lesions Approximately 70% of oral leukoplakia lesions

are found on the buccal mucosa, vermilion border are found on the buccal mucosa, vermilion border of the lower lip, and gingiva.of the lower lip, and gingiva.

Lesions of the tongue and the floor of the mouth Lesions of the tongue and the floor of the mouth account for more than 90% of cases that show account for more than 90% of cases that show dysplasia or carcinoma.dysplasia or carcinoma.

SubtypesSubtypes

Homogeneous Homogeneous leukoplakialeukoplakia well- well-defined white patch, defined white patch, that is slightly elevated that is slightly elevated and that has a and that has a fissured, wrinkled, or fissured, wrinkled, or corrugated surface. corrugated surface. On palpation, these On palpation, these lesions may feel lesions may feel leathery to “dry, or leathery to “dry, or cracked mud-like”.cracked mud-like”.

Nodular (speckled) Nodular (speckled) leukoplakialeukoplakia the name the name refers to a mixed red-and–refers to a mixed red-and–white lesion in which white lesion in which keratotic white nodules or keratotic white nodules or patches are distributed over patches are distributed over an atrophic erythematous an atrophic erythematous background. This type of background. This type of leukoplakia is associated leukoplakia is associated with a higher malignant with a higher malignant transformation rate. transformation rate.

Nodular (speckled) leukoplakiaNodular (speckled) leukoplakia

Verrucous leukoplakiaVerrucous leukoplakia Thick white lesions with Thick white lesions with

papillary surfaces .papillary surfaces . Usually heavily keratinized Usually heavily keratinized Most often seen in older Most often seen in older

adults in the sixth to eighth adults in the sixth to eighth decades of life. decades of life.

Some of these lesions may Some of these lesions may exhibit an exophytic exhibit an exophytic growth pattern. growth pattern.

Proliferative verrucous leukoplakiaProliferative verrucous leukoplakia

Extensive papillary or verrucoid white Extensive papillary or verrucoid white plaques that tend to slowly involve multiple plaques that tend to slowly involve multiple mucosal sites in the oral cavity and to mucosal sites in the oral cavity and to transform into squamous cell carcinomas transform into squamous cell carcinomas over a period of many years.over a period of many years.

Histopathologic FeaturesHistopathologic Features::

Parakeratosis or orthokeratosis or both, alternately.Parakeratosis or orthokeratosis or both, alternately. The epithelium ranges from thinner than normal The epithelium ranges from thinner than normal

(atrophic) to much thicker (acanthotic)(atrophic) to much thicker (acanthotic) Most leukoplakias show no dysplastic changes Most leukoplakias show no dysplastic changes A minority display a range of dysplasia from mild to A minority display a range of dysplasia from mild to

severe and treatment is planned partly on this severe and treatment is planned partly on this basis.basis.

An inflammatory reaction of lymphocytes and An inflammatory reaction of lymphocytes and plasma cells is often present in the underlying plasma cells is often present in the underlying connective tissue.connective tissue.

Diagnosis and ManagementDiagnosis and Management::

If a leukoplakia lesion disappears If a leukoplakia lesion disappears spontaneously or through the elimination of spontaneously or through the elimination of an irritant, no further testing is indicated.an irritant, no further testing is indicated.

For For the persistent lesion, the persistent lesion, the definitive the definitive diagnosis is established by tissue diagnosis is established by tissue biopsybiopsy. .

Adjunctive methods as vital staining with Adjunctive methods as vital staining with toluidine bluetoluidine blue and and cytobrushcytobrush are helpful in are helpful in selecting the most appropriate spot for selecting the most appropriate spot for biopsy .biopsy .

Toluidine blueToluidine blue staining uses a 1% aqueous staining uses a 1% aqueous solution of the dye which stains dysplastic solution of the dye which stains dysplastic and malignant cells and resists washing and malignant cells and resists washing away by rinsing with 1% acetic acid .away by rinsing with 1% acetic acid .

Cytobrush techniqueCytobrush technique utilizes a brush with utilizes a brush with firm bristles that obtains individual cells from firm bristles that obtains individual cells from the full thickness of epithelium for cytologic the full thickness of epithelium for cytologic examination .examination .

Definitive treatment involves Definitive treatment involves surgical surgical excisionexcision although cryosurgery and laser although cryosurgery and laser ablation are often preferred because of their ablation are often preferred because of their precision and rapid healing.precision and rapid healing.

PrognosisPrognosis::

Clinical signs of malignant transformation of Clinical signs of malignant transformation of leukoplakia include :leukoplakia include :

Ulceration , erythroplasia , bleeding , Ulceration , erythroplasia , bleeding , induration and lymphadenopathy induration and lymphadenopathy

After surgical removal long-term monitoring After surgical removal long-term monitoring of the lesion site is important since of the lesion site is important since recurrences are frequent and because recurrences are frequent and because additional leukoplakias may develop.additional leukoplakias may develop.

ErythroplakiaErythroplakia

““Bright red velvety Bright red velvety plaque or patch which plaque or patch which cannot be characterized cannot be characterized clinically or histo- clinically or histo- pathologically as being pathologically as being due to any other due to any other condition”. condition”.

ErythroplakiaErythroplakia

Clinical FeaturesClinical Features:: Erythroplakia occurs predominantly in older Erythroplakia occurs predominantly in older

men, in the sixth and seventh decades of men, in the sixth and seventh decades of life. life.

Erythroplakias are more commonly seen on Erythroplakias are more commonly seen on the floor of the mouth, the ventral tongue, the floor of the mouth, the ventral tongue, the soft palate, and the tonsillar fauces, all the soft palate, and the tonsillar fauces, all prime areas for the development of prime areas for the development of carcinoma. Multiple lesions may be present. carcinoma. Multiple lesions may be present.

Almost all of the lesions are asymptomatic.Almost all of the lesions are asymptomatic.

Histopathologic FeaturesHistopathologic Features::

80 to 90% of cases of erythroplakia are 80 to 90% of cases of erythroplakia are histopathologically severe epithelial histopathologically severe epithelial dysplasia, carcinoma in situ, or invasive dysplasia, carcinoma in situ, or invasive carcinoma.carcinoma.

Differential DiagnosisDifferential Diagnosis:: In view of the clinical significance of In view of the clinical significance of

erythroplakia, its differentiation from erythroplakia, its differentiation from other red inflammatory lesions of the oral other red inflammatory lesions of the oral mucosa is critical. mucosa is critical.

Clinically similar lesions may include Clinically similar lesions may include erythematous candidiasiserythematous candidiasis, areas of , areas of mechanical irritationmechanical irritation, , denture stomatitis,denture stomatitis, vascular lesionsvascular lesions,, and a variety of and a variety of nonspecific nonspecific inflammatory lesionsinflammatory lesions

Lichen PlanusLichen Planus::

Lichen planus is a common chronic Lichen planus is a common chronic inflammatory disease of skin and mucous inflammatory disease of skin and mucous membranes. It mainly affects patients of membranes. It mainly affects patients of middle age or over. Oral lesions have middle age or over. Oral lesions have characteristic appearances and distribution characteristic appearances and distribution

AetiologyAetiology::

The predominantly T-lymphocyte infiltrate The predominantly T-lymphocyte infiltrate suggests cell-mediated immunological suggests cell-mediated immunological damage to the epitheliumdamage to the epithelium

Clinical FeaturesClinical Features::

Skin Lesions:Skin Lesions: Pruritic, polyangular, planar papules and plaques , 2 to 4 Pruritic, polyangular, planar papules and plaques , 2 to 4

mm in diameter, with angular borders, a violaceous color, mm in diameter, with angular borders, a violaceous color, and a distinct sheen in cross-lighting. and a distinct sheen in cross-lighting.

Usually symmetrically distributed most commonly on the Usually symmetrically distributed most commonly on the flexor surfaces of the wrists, legs, trunk. The face is rarely flexor surfaces of the wrists, legs, trunk. The face is rarely involved during the acute phase.involved during the acute phase.

New papules may appear at sites of minor skin injury New papules may appear at sites of minor skin injury (Koebner’s phenomenon).(Koebner’s phenomenon).

Lesions may coalesce or change over time becoming Lesions may coalesce or change over time becoming hyperpigmented, atrophic hyperkeratotic (hypertrophic LP) hyperpigmented, atrophic hyperkeratotic (hypertrophic LP) or vesiculobullous. or vesiculobullous.

If the scalp is affected,there is patchy scarring alopecia If the scalp is affected,there is patchy scarring alopecia

Nail Lesions:Nail Lesions: Nails are involved in up to 10% of cases. Nails are involved in up to 10% of cases.

Findings vary in intensity with nail bed Findings vary in intensity with nail bed discoloration ,longitudinal ridging and lateral discoloration ,longitudinal ridging and lateral thinning and complete loss of the nail matrix thinning and complete loss of the nail matrix and nail with scarring of the proximal nail and nail with scarring of the proximal nail fold onto the nail bed.fold onto the nail bed.

Oral LesionsOral Lesions::

The reticular formThe reticular form Atrophic lichen planusAtrophic lichen planus Erosive lesionsErosive lesions Bullous lesionsBullous lesions

Atrophic or erosive lichen planus involving Atrophic or erosive lichen planus involving the gingivae results in the gingivae results in desquamative desquamative gingivitisgingivitis

Histopathologic FeaturesHistopathologic Features::

Three featuresThree features are considered essential for the are considered essential for the histopathologic diagnosis of lichen planus: histopathologic diagnosis of lichen planus:

(1)(1) Areas of hyperparakeratosis or Areas of hyperparakeratosis or hyperorthokeratosis. hyperorthokeratosis.

(2)(2) “liquefaction degeneration” or necrosis of the “liquefaction degeneration” or necrosis of the basal cell layer which is often replaced by an basal cell layer which is often replaced by an eosinophilic band. eosinophilic band.

(3)(3) A dense subepithelial band of lymphocytes. A dense subepithelial band of lymphocytes. This linear sub-basilar lymphocytic infiltration is This linear sub-basilar lymphocytic infiltration is composed largely of T cells composed largely of T cells

Isolated epithelial cells, shrunken with Isolated epithelial cells, shrunken with eosinophilic cytoplasm and one or more eosinophilic cytoplasm and one or more pyknotic nuclear fragments (Civatte bodies), pyknotic nuclear fragments (Civatte bodies), are often scattered within the epithelium and are often scattered within the epithelium and superficial lamina propria. These represent superficial lamina propria. These represent cells that have undergone apoptosis.cells that have undergone apoptosis.

TreatmentTreatment:: Asymptomatic lesions require no treatment. Asymptomatic lesions require no treatment. TopicalTopical high-potency high-potency corticosteroidscorticosteroids, as pastes or as gels., as pastes or as gels. Erosive lesions may respond to oral dapsone or Erosive lesions may respond to oral dapsone or

cyclosporine rinses.cyclosporine rinses. Systemic steroidsSystemic steroids : Prednisone tablets with dosages : Prednisone tablets with dosages

varying between 40 and 80 mg dailyvarying between 40 and 80 mg daily IntralesionalIntralesional injection of injection of corticosteroidcorticosteroid may be used in may be used in

lesions resistant to topical and systemic therapy lesions resistant to topical and systemic therapy triamcinolone acetonide ampules are used (weekly triamcinolone acetonide ampules are used (weekly regimen).regimen).

Systemically administered dapsone, hydroxychloroquine, Systemically administered dapsone, hydroxychloroquine, azathioprine and cyclosporine may help in cases resistant azathioprine and cyclosporine may help in cases resistant to corticosteroids to corticosteroids

Drug combinations could also be used.Drug combinations could also be used.

Lichenoid ReactionsLichenoid Reactions

This term is given to lichen planus-like lesions This term is given to lichen planus-like lesions caused by either systemic drug treatment or those caused by either systemic drug treatment or those where the histological picture is not completely where the histological picture is not completely diagnostic.diagnostic.

Oral lichenoid reactions are most frequently Oral lichenoid reactions are most frequently responses to restorative materials, either amalgam responses to restorative materials, either amalgam or polymeric. Lesions are localized to mucosa in or polymeric. Lesions are localized to mucosa in contact, not just close to, restorations.contact, not just close to, restorations.

Lichenoid reactions are treated in exactly the Lichenoid reactions are treated in exactly the same way as lichen planus with withdrawal of same way as lichen planus with withdrawal of drug(s) if possible or removal of restoration. drug(s) if possible or removal of restoration.

Lupus ErythematosusLupus Erythematosus::

Lupus erythematosus is an Lupus erythematosus is an autoimmuneautoimmune connective tissueconnective tissue disease which has two disease which has two main forms namely systemic and discoid. main forms namely systemic and discoid. Either can give rise to oral lesions which Either can give rise to oral lesions which may appear similar to those of oral lichen may appear similar to those of oral lichen planus planus

Systemic Lupus ErythematosusSystemic Lupus Erythematosus

Has varied effects. Any organ system can be affected. A Has varied effects. Any organ system can be affected. A great variety of autoantibodies, particularly antinuclear, is great variety of autoantibodies, particularly antinuclear, is produced. produced.

Pathological features of systemic lupus erythematosus:Pathological features of systemic lupus erythematosus:Macroscopic:Macroscopic: Pleurisy.Pleurisy. Pericarditis.Pericarditis. Libman-sacks endocarditis.Libman-sacks endocarditis. Lymphadenopathy.Lymphadenopathy. Splenomegaly.Splenomegaly. May be none.May be none.

Microscopic:Microscopic: Immunoglobulins and complement at the Immunoglobulins and complement at the

dermo-epidermal junction in skin lesions dermo-epidermal junction in skin lesions (90%) and uninvolved skin (60%).(90%) and uninvolved skin (60%).

Haematoxylin bodies in the endocardium, Haematoxylin bodies in the endocardium, renal glomeruli and elsewhere.renal glomeruli and elsewhere.

Periarterial fibrosis of the spleen.Periarterial fibrosis of the spleen. Wire loop lesions in the kidneys.Wire loop lesions in the kidneys.

immunoglobulin & complement immunoglobulin & complement deposits at basement membrane deposits at basement membrane zone & nuclei of epithelial cellszone & nuclei of epithelial cells::

Discoid LupusDiscoid Lupus::

A skin disease with mucocutaneous lesions A skin disease with mucocutaneous lesions indistinguishable clinically from those of indistinguishable clinically from those of systemic lupus. These may be associated systemic lupus. These may be associated with arthralgias but rarely, significant with arthralgias but rarely, significant autoantibody production autoantibody production

Clinical Features:Clinical Features:A) Skin LesionsA) Skin Lesions::

Cutaneous features of systemic lupus erythematosus.Cutaneous features of systemic lupus erythematosus. Butterfly rash.Butterfly rash. Facial oedema.Facial oedema. Subacute cutaneous LE.Subacute cutaneous LE. Chronic discoid LE.Chronic discoid LE. Scarring DLE alopecia Scarring DLE alopecia Non-scarring alopeciaNon-scarring alopecia PhotosensitivityPhotosensitivity Raynaud’s phenomenonRaynaud’s phenomenon Chronic urticariaChronic urticaria Cutaneous vasculitis Cutaneous vasculitis

Histopathologic FeaturesHistopathologic Features::

Liquefaction degeneration of basal cell layer.Liquefaction degeneration of basal cell layer. Degenerative changes in the connective tissue Degenerative changes in the connective tissue

(hyalinization, oedema,..).(hyalinization, oedema,..). Lupus erythematosus shows more irregular Lupus erythematosus shows more irregular

patterns of acanthosis and lacks the band-like patterns of acanthosis and lacks the band-like distribution of lymphocytes in the papillary corium distribution of lymphocytes in the papillary corium of lichen planus.of lichen planus.

The inflammatory infiltrate may have a The inflammatory infiltrate may have a perivascular distribution.perivascular distribution.

ManagementManagement : :

Oral lesions of discoid lupus erythematosus Oral lesions of discoid lupus erythematosus may respond in some degree to topical may respond in some degree to topical corticosteroids. corticosteroids.

Oral lesions in acute systemic lupus Oral lesions in acute systemic lupus erythematosus may not respond to doses of erythematosus may not respond to doses of corticosteroids adequate to control systemic corticosteroids adequate to control systemic effects of the disease. Under such effects of the disease. Under such circumstances, palliative treatment is circumstances, palliative treatment is needed until disease activity decreases.needed until disease activity decreases.

Miscellaneous Lesions:Miscellaneous Lesions:Oral Submucous FibrosisOral Submucous Fibrosis

A slowly progressive chronic fibrotic disease A slowly progressive chronic fibrotic disease of the oral cavity and oropharynx, of the oral cavity and oropharynx, characterized by fibroelastic change and characterized by fibroelastic change and inflammation of the mucosa, leading to a inflammation of the mucosa, leading to a progressive inability to open the mouth, progressive inability to open the mouth, swallow, or speak. swallow, or speak.

These reactions may be the result of either direct These reactions may be the result of either direct stimulation from exogenous antigens like Areca stimulation from exogenous antigens like Areca alkaloids or changes in tissue antigenicity that may alkaloids or changes in tissue antigenicity that may lead to an autoimmune response.lead to an autoimmune response.

It occurs almost exclusively in the Indian It occurs almost exclusively in the Indian subcontinent. subcontinent.

The inflammatory response releases cytokines and The inflammatory response releases cytokines and growth factorsthat promote fibrosis by inducing the growth factorsthat promote fibrosis by inducing the proliferation of fibroblasts, up-regulating collagen proliferation of fibroblasts, up-regulating collagen synthesis and down-regulating collagenase synthesis and down-regulating collagenase production.production.

EtiologyEtiology::

General nutritional and vitamin deficiencies General nutritional and vitamin deficiencies and hypersensitivity to certain dietary and hypersensitivity to certain dietary constituents such as chili peppers, chewing constituents such as chili peppers, chewing tobacco, habitual use of betel and its tobacco, habitual use of betel and its constituents (Areca catechu).constituents (Areca catechu).

Clinical FeaturesClinical Features:: The disease first presents with a burning sensation The disease first presents with a burning sensation

of the mouth, particularly during consumption of of the mouth, particularly during consumption of spicy foods.spicy foods.

Often accompanied by the formation of vesicles or Often accompanied by the formation of vesicles or ulcerations and by excessive salivation or ulcerations and by excessive salivation or xerostomia and altered taste sensations. xerostomia and altered taste sensations.

Gradually, patients develop a stiffening of the Gradually, patients develop a stiffening of the mucosa, with a dramatic reduction in mouth opening mucosa, with a dramatic reduction in mouth opening and with difficulty in swallowing and speaking. and with difficulty in swallowing and speaking.

The mucosa appears blanched and opaque with the The mucosa appears blanched and opaque with the appearance of fibrotic bands that can easily be appearance of fibrotic bands that can easily be palpated. palpated.

Usually involves the buccal mucosa, soft palate, Usually involves the buccal mucosa, soft palate, posterior pharynx, lips, and tongue.posterior pharynx, lips, and tongue.

Histologic FeaturesHistologic Features::

Severely atrophic epithelium with complete Severely atrophic epithelium with complete loss of rete ridges. loss of rete ridges.

Varying degrees of epithelial atypia may be Varying degrees of epithelial atypia may be present. present.

The underlying lamina propria exhibits The underlying lamina propria exhibits severe hyalinization, with homogenization of severe hyalinization, with homogenization of collagen. Cellular elements and blood collagen. Cellular elements and blood vessels are greatly reduced.vessels are greatly reduced.

Treatment and PrognosisTreatment and Prognosis::

Oral submucous fibrosis is regarded as a Oral submucous fibrosis is regarded as a premalignant condition.premalignant condition.

Oral submucous fibrosis is very resistant to Oral submucous fibrosis is very resistant to treatmenttreatment. .

Submucosal injected steroids and hyaluronidase, Submucosal injected steroids and hyaluronidase, are some of the agents that have been used. are some of the agents that have been used.

In severe cases surgical intervention is the only In severe cases surgical intervention is the only treatment but the fibrous bands and other symptoms treatment but the fibrous bands and other symptoms often recur within a few months to a few years.often recur within a few months to a few years.

Skin GraftsSkin Grafts::

A skin graft may be placed in the mouth to cover a A skin graft may be placed in the mouth to cover a raw area left after excision of a lesion.raw area left after excision of a lesion.

Skin grafts typically appear sharply demarcated Skin grafts typically appear sharply demarcated smooth and paler than the surrounding mucosa smooth and paler than the surrounding mucosa and occasionally contain hairs . Grafts on the and occasionally contain hairs . Grafts on the dorsum of the tongue may become corrugated and dorsum of the tongue may become corrugated and less easy to differentiate from leukoplakia.less easy to differentiate from leukoplakia.