Ulcerative lesions of Oral cavity Definitions: Ulcer: Break in the continuity of epithelium with resultant exposure of underlying connective

tissue Erosion: Break in the epithelium extending to but not involving the basal cell layer Vesicle: Small well circumscribed, fluid filled lesion less than 5 mm in diameter Bulla: Well circumscribed fluid filled lesion larger than 5 mm in diameter Classification of oral ulcers: A. Based on mode of onset Acute Chronic B. Based on number of ulcers Single Multiple C. Based on whether preceded by other lesions (vesicles/ bullae) Primary Secondary D. Based on Etiology (cause) Traumatic Infectious Drug induced Ulcers associated with blood dyscrasias Immune mediated Oral ulcers associated with dermatological disorders Oral ulcers associated with GI disorders Neoplastic oral ulcers Ulcers of uncertain etiology I.Traumatic Ulcers: Types of trauma: o o o o Mechanical ( sharp tooth, over extended denture, orthodontic brackets, toothbrush etc) Chemical ( aspirin, concentrated clove oil, sodium hypochlorite etc) Thermal ( extremely hot or cold insults eg: hot cheese, hot beverages, popsicle) Radiation ( used in treatment of head and neck cancer)

Diagnosis: Based on h/o trauma or insult ( hot/ cold or radiation therapy) prior to onset of ulcer Mechanical trauma induced ulcers often have linear configuration Depth of ulcer depends on nature of trauma Surrounding area is inflamed Traumatic factor will often be evident in the vicinity of the ulcer ( eg: sharp edge of tooth) Treatment: Removal of traumatic factor Topical application of antiseptic and analgesic/anesthetic medication In case of multiple ulcers- analgesic/ antiseptic mouthwash Prognosis: Good on removal of traumatic factor Page 1 of 12 Dr Keerthilatha M Pai, Prof and Head, OMR

Ulcerative lesions of Oral cavity If the ulcer fails to heal even two weeks after removal of traumatic factor, biopsy may be required to r/o malignancy II. Ulcers associated with infections:

Viral

Bacterial

Fungal

Specific Herpes simplex virus: Primary herpetic gingivostomatitis Recurrent herpes labialis Recurrent intraoral herpes Varicella zoster virus: Chicken pox Herpes zoster Borrelia vincenti and Fusobaterium: ANUG Cancrum oris/ Noma Mycobacterium tuberculosis: Tuberculous ulcer Tuberculosis cutis orificialis Treponema pallidum: Chancre Snail track ulcer Gumma Gonococci: Gonococcal stomatitis

Nonspecific Infected traumatic ulcer Ruptured Odontogenic abscess presenting as ulcer Histoplasmosis Mucormycosis Blastomycosis Cryptococcosis Coccidiodomycosis

Coxsackie virus: Herpangina Hand, foot and mouth disease Epstein barr virus: Infectious mononucleosis Human immunodeficiency virus: AIDS

Primary Herpetic Gingivostomatitis Acute Onset Children below six years/ immunocompromised adults M=F 95% cases sub clinical infection 5% manifest symptoms Infection confers resistance against another primary infection for lifetime Typical onset Prodromal systemic symptoms precede oral lesions by 2-3 days ( flu like) Explosive onset of multiple oral ulcers in all parts of mouth Generalized marginal gingivitis Cervical lymphadenopathy occurs as a rule No skin lesions Self limiting condition in normal children May become disseminated in immunocompromised children/ adults Food intake is very difficult Dehydration may ensue

Diagnosis Based on history and clinical findings Cytological (PAP/ Tzanck) smears of intact or recently broken vesicles may demonstrate epithelial giant cells containing intranuclear eosinophilic viral inclusions typical of herpes viral infections D/D: Leukemia Page 2 of 12 Dr Keerthilatha M Pai, Prof and Head, OMR

Ulcerative lesions of Oral cavity Erythema multiforme Stomatitis medicamentosa

Treatment Symptomatic Antipyretic and Analgesics Soothening mouthwashes (consider Magic mouthwash- a combination of diphenhydramine hcl and magnesium hydroxide) Ensure adequate hydration Antiviral therapy in immunocompromised Prognosis Good in healthy individuals Complications may occur in immunocompromised Virus remains dormant in nerve ganglion and may get reactivated later in life causing secondary infection Manifestations of secondary infection are different

Recurrent Herpes Infection

Two types of manifestations: Intraoral Herpes ( Occurs on highly keratinized mucosa of hard palate/ gingiva) Herpes labialis ( Occurs along external vermilion border of lips )

Precipitating factors: Exposure to UV light ( sunlight) Menstruation Fever Stress Decreased immunity

Clinical presentation: Recurrent eruption of cluster of tiny fluid filled vesicles which rupture to form pin point ulcers. These ulcers may coalesce to form larger areas of ulceration Lesions may be preceded by tingling sensation or pain in the region Frequency of recurrence varies The lesions last for 5-7 days and subside Herpes labialis lesions are unsightly and may be bothersome for patient

Diagnosis: By their typical location and presentation Tzanck smear

Treatment: Symptomatic When recurrence is bothersome, acyclovir therapy for one year

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Dr Keerthilatha M Pai, Prof and Head, OMR

Ulcerative lesions of Oral cavity

Varicella zoster infection Primary infection: Chicken pox Secondary infection: Herpes zoster Chicken Pox Usually affects children Sudden onset of skin rashes and oral ulcers Skin rashes are associated with itching Systemic symptoms like fever, malaise, headache etc Skin lesions heal leaving scar which slowly fade away Herpes zoster Caused by reactivation of Varicella zoster virus that is inactive in nerve ganglion Manifests in middle age Clinical features depend on the dermatome involved When trigeminal ganglion is involved, lesions along the course of nerve. More commonly maxillary and mandibular division of the nerve Ulcers seen both inside and outside the oral cavity They stop abruptly at the midline ( ie lesions do not cross midline) Bilateral lesions may indicate severely immunocompromised state James Ramsay Hunt syndrome is a symptom complex associated with Herpes zoster Herpangina Caused by Coxsackie virus Occurs in epidemics Predominantly affects posterior parts of oral cavity No marginal gingivitis Mild systemic symptoms Self limiting condition Hand, Foot and mouth disease Caused by Coxsackie virus Occurs in epidemics Lesions on hands and feet in addition to oral ulcers Mild systemic symptoms Self limiting condition Acute Necrotizing ulcerative Gingivitis(ANUG) (Trench mouth, Vincents Gingivitis) Acute onset Fusospirochetal infection Predisposing factors are a must Marginal and Papillary gingival involvement: crater like defects Pseudo membrane formation Spontaneous or easy bleeding Foul odour Concomitant systemic symptoms Regional lymphadenopathy Indefinite course;complications: Vincents angina;noma

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Dr Keerthilatha M Pai, Prof and Head, OMR

Ulcerative lesions of Oral cavity

Comparison of ANUG and AHGS ANUG AHGS

Complex bacterial etiology Ulcers confined to gingiva Indefinite clinical course and duration Non contagious No viral antibodies Treatment with antibacterial agents

Viral etiology Ulcers all over mouth Self limiting lasts for 7-10 days Contagious in those with depressed immunity Convalescent sera shows viral antibodies No role for antibacterial agents

Management of ANUG Look for underlying factors Hematological investigations to r/o systemic diseases Well balanced diet and regular meals 3% Hydrogen peroxide diluted with equal amount of water used to rinse mouth every two hours on first day; 3-4 times/day for next 4 days Gently remove necrotic material with swab Penicillin V (oral) : 400,000 units / day for 5 days/ Amoxicillin 250-500 mg TID for 5-7 days Metronidazole 400 mg TID for 5 days Oral prophylaxis after acute symptoms subside Tuberculosis Caused by Mycobacterium tuberculosis Oral manifestations rare Most common oral manifestation is ulcer Usually single and involving tongue Irregular with ragged, undermined edges, minimal induration and yellowish granular base Sentinel tubercles in surrounding area Pain is present

D/D of TB Ulcer Infected traumatic ulcer Major aphthous ulcer Syphilitic ulcer Sarcoidosis Lymphogranuloma venereum Foreign body granuloma Histoplasmosis Malignant ulcer Treatment Symptomatic treatment of ulcer ATT for 18-24 months Syphilitic Ulcer STD caused by Treponema Pallidum All stages of acquired syphilis can present as oral ulcers (Chancre, mucous patch and Gumma) Chancre and mucous patch are self limiting and pass on to next stage Gumma is highly destructive (oronasal communication) Diagnosis: VDRL test ( Sensitive test) FTA-ABS Test / TPI assay/ELISA ( specific test) Treatment: Antibiotic ( penicillin/ Tetracycline) Page 5 of 12 Dr Keerthilatha M Pai, Prof and Head, OMR

Ulcerative lesions of Oral cavity

III.

Drug induced oral ulcers

Stomatitis medicamentosa : induced by systemically administered drugs Stomatitis venenata : induced by topical application of drugs or due to contact ( contact stomatitis) Erythema Multiforme Reactive pattern or symptom complex rather than disease Causes : Drugs Infections Auto immune diseases Internal malignancy Psychosomatic Cl.features : Sudden Onset Rapid progression Symmetric lesions Target /Bulls eye/Iris lesions on skin Lips and anterior parts of mouth more commonly involved with crusting of lips Concomitant systemic symptoms( fever, malaise, headache, nausea, vomiting) H/P features : Liquefaction degeneration of superficial layers of epithelium Sub epithelial vesicle Dense infiltration of underlying con. tissue by lymphocytes, plasma cells, neutrophils and eosinophils Treatment : In severe cases hospitalization IV fluids Soothening mouth washes Corticosteroids are the mainstay in tmt Immunosuppressants

IV. RBC disorders Anemia Iron deficiency Sickle cell anemia Thalassemia

Blood disorders causing oral ulcers WBC disorders Qualitative disorders Lazy leukocyte syndrome

Quantitative disorders Leukemia Agranulocytosis Cyclic neutropenia Multiple myeloma

These blood disorders are associated with increased risk of oral ulcers Neutropenic ulcers are characterized by lack of inflammatory halo Necrosis is a prominent feature of these ulcers Cyclic neutropenia is associated with recurring oral ulcers Other clinical symptoms and hemogram will aid in diagnosis Treatment is directed at the cause Dr Keerthilatha M Pai, Prof and Head, OMR

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Ulcerative lesions of Oral cavity

V.

Immunologic disorders Aphthous Stomatitis

Disorder characterized by recurring ulcers confined to oral mucosa in patients with NO other signs of disease Etiology Unknown Stress Allergies Nutritional Deficiency Hormonal imbalance Immunological abnormality Types Minor Major Herpetiform Location of ulcers: Mobile, less keratinized mucosa ( Buccal mucosa, labial mucosa, FOM, Tongue, Soft palate) Minor Aphthous Ulcer

Small Shallow Well defined Single or multiple Painful Inflammatory halo Heal in 7- 10 days with no scar

Major Aphthous ulcer Large Deep Ill defined Usually Single Very Painful Inflammatory halo Last for long ( 4-6 wks) and heal with scar Scar may reduce mobility

Herpetiform Aphthous Ulcer Crops of pinpoint ulcers Coalesce to form large area of ulceration Extremely painful Dr Keerthilatha M Pai, Prof and Head, OMR

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Ulcerative lesions of Oral cavity

Heal in 7-10 days

No Scar formation Cl. Features First episodes usually begin in second decade of life No systemic signs and symptoms Clinical appearance of ulcers depends on the type of ulcer (minor/major/ herpetiform) Recurrent episodes of oral ulcers with no defined frequency

Diagnosis By excluding all other diseases causing oral ulcers Hematological examination to r/o blood dyscrasias Ocular, genital, skin or rectal lesions should not be present to make a diagnosis of aphthous Stomatitis

Comparison of Recurrent Aphthous ulcer and Recurrent Intraoral Herpes Stomatitis: RAU Nonspecific etiology Wide range of age group Freely movable mucosa involved Single or 2-3 ulcers at a time except in herpetiform where crops of pinpoint ulcers occur Nonspecific findings on H/P No antibody titers Corticosteroids used RIHS Viral etiology Middle age Attached mucosa Multiple pinpoint ulcers Tzanck cells on smear Convalescent sera shows viral antibodies Corticosteroids contraindicated

Treatment of RAU The primary goals of therapy for RAU are relief of pain, reduction of ulcer duration, and restoration of normal oral function. Secondary goals include reduction in the frequency and severity of recurrences and maintenance of remission. Topical medications, such as antimicrobial mouth- washes and topical corticosteroids, can achieve the primary goals but have not been shown to alter recurrence or remission rates. Systemic medications can be tried if topical therapy is ineffective. Levamisole has shown variable efficacy in reducing ulcer frequency and duration in patients with minor RAU Dose : 150 mg per day for 3 consecutive days followed by a gap of 2 weeks Then repeat for three days. This is to be done 6 times (total therapy time: 3 months ; Total number of tablets: 18) Oral corticosteroids should be reserved for severe cases of major RAU that do not respond to topical agents. Thalidomide is effective but, because of its toxicity and cost, should be used only as an alternative to oral corticosteroids. Behcets Syndrome International Study Group Criteria for diagnosis of BS Oral ulcers ( Major/minor/herpetiform aphthous) occurring atleast thrice in a year PLUS two of the following Recurrent genital ulcerations Recurrent eye lesions( uveitis, Retinal vasculitis) Skin lesions( erythema nodosum/papulopustular lesions/acneiform nodules) Dr Keerthilatha M Pai, Prof and Head, OMR

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Ulcerative lesions of Oral cavity Positive pathergy test

VI.

Dermatological disorders Pemphigus

Chronic, Autoimmune skin disorder Term derived from Greek word for Blister Most dreaded, dramatic and devastating of all skin disorders Four types based on H/P findings Vulgaris, Vegetans, Foliaceous and Erythematoses P. Vulgaris is most severe form Rare; Jews are affected more Predominantly affects adults with no sex predilection Cl. Features Bullae of varying sizes on skin and mucosal surfaces On skin tense and round but in oral cavity rupture easily Positive Nikolskys sign (lateral pressure applied over apparently normal skin or mucosa causes sliding of the skin) Positive Asboe Hansen sign (aka Bulla spreading sign; Pressure applied over a bulla makes it spread) Oral lesions are irregular, more of erosive type with peripheral tissue tags Desquamative Gingivitis Diagnosis Demonstration of Clinical signs Histopathological examination (Intraepithelial Bulla) Direct Immunofluorescence Indirect Immunofluorescence Raised ESR Hypoalbuminemia Treatment: Systemic corticosteroids remain the mainstay of therapy for Pemphigus. Their use has transformed what was almost invariably a fatal illness into one whose mortality is now below 10%. Unfortunately, the high doses and prolonged administration of corticosteroids that are often needed to control the disease result in numerous side effects, many of which are serious or even life-threatening Systemic therapy: Prednisolone ( Wysolone) 0.5mg - 1 mg /kg/day or about 40-80 mg per day Cyclophosphamide given at an initial dose of 50mg/day and the dose escalated to 100mg/day

Topical therapy: PV is largely managed with systemic therapy but adjuvant topical therapy may be of additional benefit, although there are no controlled studies to confirm this. Rarely, patients with mild disease, particularly if confined to the mucosal surfaces, can be managed on topical therapy alone. Measures such as soft diets and soft toothbrushes help minimize local trauma. Topical analgesics or anesthetics, for example benzydamine hydrochloride 0.15% (Tantum Oral Rinse), are useful in alleviating oral pain, particularly prior to eating or tooth brushing. Oral hygiene is crucial. Otherwise PV may be complicated by dental decay; tooth brushing should be encouraged Antiseptic mouthwashes may be used, such as Chlorhexidine gluconate 0.2% Hexidinel), Clohex 0.1% or 1:4 hydrogen peroxide solutions. Patients are susceptible to oral Candidiasis, which should be treated. Topical CS therapy may help reduce the requirement for systemic agents. For multiple oral erosions, mouthwashes are most practical, for example, soluble Betamethasone sodium phosphate 0.5 mg tablet

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Dr Keerthilatha M Pai, Prof and Head, OMR

Ulcerative lesions of Oral cavity dissolved in 10 mL water may be used up to four times daily, holding the solution in the mouth for about 5 minutes Isolated oral erosions could be treated with application of triamcinolone acetonide 0.1% in adhesive paste (Kenacort in Orabase), 2.5 mg hydrocortisone lozenges or sprayed directly with an asthma aerosol inhaler, for example beclomethasone dipropionate 50-200 micrograms or budesonide 50-200 micrograms. Topical cyclosporine (100 mg/mL) in oral pemphigus has been described and may be of some benefit but is expensive.

Pemphigoid Types: Bullous Pemphigoid (Rare) Benign Mucous membrane Pemphigoid/ Cicatricial Pemphigoid Benign mucous membrane Pemphigoid Chronic, Benign course Mucous membrane involvement with no skin lesions. Ocular involvement is common Sub epithelial bulla Desquamative gingivitis Scar ( Cicatrix) formation

Diagnosis Clinical signs Histopathologic examination demonstrating sub epithelial split Direct immunoflorescence

VII. Gastrointestinal disorders associated with oral ulcers Crohns disease Coeliac disease Ulcerative Colitis

Patients have symptoms of gastrointestinal discomfort along with oral ulcers Barium meal and gastroscopic examination confirm GI involvement VIII.Neoplastic ulcers Squamous cell carcinoma Adenocarcinoma Mucoepidermoid carcinoma Metastatic carcinoma

Cl. Features: Ulcers last for longer Induration is a prominent feature Biopsy is diagnostic Treatment is surgery/ radiation or combination of both Prognosis depends upon stage of diagnosis IX. Ulcers of unknown etiology Necrotizing sialometaplasia Chronic nonhealing ulcer usually seen on posterior part of palate May be mistaken for malignant ulcer both clinically and histologically Self limiting condition. Generally heals after the area is manipulated ( Biopsy/ curettage etc)

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Dr Keerthilatha M Pai, Prof and Head, OMR

Ulcerative lesions of Oral cavity

How to diagnose oral ulcer? Ist step: Determine whether ulcers are acute or chronic, single or multiple or recurrent ( By history) Acute Single Multiple Traumatic ulcer Herpetic Aphthous ulcer gingivostomatitis Recurrent intraoral herpes Herpangina Hand, foot and mouth disease Chicken pox Herpes zoster Inf.mononucleosis HIV infection ANUG Stomatitis medicamentosa Stomatitis venenata Herpetiform aphthous ulcers Minor aphthous ulcers Leukemia Cyclic neutropenia
nd

Chronic Single Infected traumatic ulcer Major aphthous ulcer Necrotizing sialometaplasia Tuberculous ulcer Syphilitic ulcer Cancrum oris Fungal ulcer Malignant ulcer

Multiple Multiple major aphthous ulcers Behcets syndrome Reiters syndrome Pemphigus vulgaris Benign mucous membrane Pemphigoid Erosive lichen planus Lichenoid reactions

Recurrent Aphthous ulcers Cyclic neutropenia Behcets syndrome Reiters syndrome Lichen planus Pemphigus Pemphigoid

step: Note the features of the ulcer/s and associated symptoms I. Size, shape, location, surrounding area, tissue tags at periphery, tenderness, foul smell, bleeding, induration of base , edges, margins, floor II. Presence of skin lesions ( eg: Lichen planus, Pemphigus, Pemphigoid, E.multiforme, Steven Johnson syndrome etc) III. Systemic symptoms ( fever ,malaise etc) seen in viral infections, ANUG,TB, E.multiforme etc

3 step: Correlate the history and clinical findings and draw a differential diagnosis 4 step: Investigations to establish the diagnosis: Acute Chronic Single Multiple Single Multiple Generally no need Hemogram to r/o Biopsy Biopsy for of investigations hematological In case of TB, Histopathologic Routine hemogram malignancies Mantoux test, examination and may be performed Tzanck smear ESR, DIF Antibody titres in Lymphocyte Indirect IF recurrent viral inf count, Chest X Routine Paul Bunnell test ray, PCR hemogram with for Infectious In case of ESR mononucleosis syphilis, VDRL Serum protein Bone marrow test, FTA-ABS level study for test or TPI assay Patch test in case leukemia Special stains in of suspected case of Lichenoid Page 11 of 12
th

rd

Recurrent For Cyclic neutropenia, TC and DC thrice in a week for 6-8 weeks Hemogram Pathergy test in Behcets

Dr Keerthilatha M Pai, Prof and Head, OMR

Ulcerative lesions of Oral cavity suspected fungal infections reactions

Treatment: Directed at the cause In Viral ulcers, rest is important and adequate hydration to be ensured Symptomatic relief with topical anesthetic/ analgesic preparations Antiseptic ointments/ gel to prevent secondary infection Topical steroids in ulcers taking longer to heal (triamcinolone acetonide in orabase) Systemic steroids in case of Erythema multiforme, Pemphigus, Pemphigoid, erosive or Vesiculobullous lichen planus and allergic Stomatitis Avoidance of oral habits ( smoking/ pan chewing/alcohol )

Syndromes associated with Oral ulcers PFAPA syndrome( Periodic fever, aphthae, pharyngitis, adenopathy) MAGIC syndrome ( Mouth Aphthae, Genital lesions and Interstitial Chondritis) Behcets syndrome Reiters syndrome Steven Johnson syndrome James, Ramsay, Hunt syndrome

Classification of Vesiculobullous lesions: I. Hereditary: Epidermolysis bullosa II. Viral: a) HSV ( PHGS and recurrent herpes) b) Varicella zoster ( Chicken pox and Herpes zoster) c) Measles III. Allergic: a) Erythema multiforme b) Steven Johnson syndrome IV. Autoimmune: a) Pemphigus vulgaris b) Benign mucous membrane Pemphigoid c) Vesiculobullous Lichen planus V. Thermal burns may cause blistering lesions

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Dr Keerthilatha M Pai, Prof and Head, OMR