ULCERATIVE CONDITIONS

ULCER Loss of epithelium due to any cause May be preceded by vesicles or bullae that are generally short-lived intraorally The ulcer is probably the most common oral soft tissue lesion EROSION Implies a superficial defect producing some loss of epithelium ULCERATIVE CONDITIONS 1. Reactive lesions 2. Bacterial conditions 3. Fungal conditions 4. Conditions associated with immunologic dysfunction 5. Neoplasms REACTIVE LESIONS ETIOLOGY Simple mechanical trauma 1. Patient-induced Lower lip, tongue, buccal mucosa Riga-Fede disease- a traumatic ulcer in the anterior tongue of infants with natal teeth Dental prosthesis may cause a traumatic ulcer (acute or chronic) Abnormal habits (factitial injuries) 2. Iatrogenic ( dental in nature) 3. Removal of adherent cotton rolls 4. Negative pressure of a saliva ejector 5. Accidental striking of mucosa with rotating & hand instruments 6. Chemicals such as etching agents (phosphoric acid), phenol, hydrogen peroxide 30% Heat burns Pizza burns- hot cheese Hot waxes, hydrocolloid & modeling compound (iatrogenic) Radiation therapy In the head & neck : squamous cell carcinoma Large doses of radiation ( 60-70- Gy)

Lesions are covered by yellow-white exudate & are surrounded by an erythematous halo Varying degrees of pain & tenderness are associated with acute leisons Chronic ulcers may cause little or no pain Covered by yellow membrane & surrounded by elevated margins that may show hyperkeratosis Induration is due to scar & chronic inflammatory cell infiltration Traumatic granuloma Chronic ulcer associated with deep soft tissue injury Crateriform ulcer 1-2 cm in diameter Usually found in the tongue, lip or buccal mucosa Healing may take several weeks Necrotizing Sialometaplasia Chronic ulcer seen in the hard palate Associated with ischemic necrosis of a minor salivary gland Heals spontaneously in several weeks REACTIVE LESIONS HISTOPATHOLOGY Acute Ulcers Loss of surface epithelium that is replaced by a fibrin network containing neutrophils, degenerating cells & debris Ulcer base contains dilated capillaries & granulation tissue Regeneration of the epithelium begins at the ulcer margins Proliferating cells coursing over the granulation tissue & under the fibrin clot Chronic ulcers Exhibit a granulation tissue base, with scar found deeper in the tissue Epithelial regeneration may not occur because of continued trauma or unfavorable local factors ( inadequate blood supply) REACTIVE LESIONS DIAGNOSIS Acute reactive lesions Cause & effect relationship is usually apparent from the clinical examination & history Chronic reactive lesions More difficult diagnosis Differentiated with an infectious disease & malignant lesions

If after 2 weeks the ulcers did not resolved, or the lesion increase in size, a biopsy examination is in order REACTIVE LESIONS TREATMENT Observation If pain is considerable, symptomatic treatment may be of benefit Tetracyclin-nystatindiphenhydramine hydrochloride rinse Topical corticosteroids

BACTERIAL CONDITIONS

SYPHILIS A venereal disease that has been traced as far as the time of Christopher Columbus Considered fatal until the introduction of penicillin in the forties Caused by the spirochete Treponema Pallidum Mode of Transmission 1. Acquired by sexual contact with a partner with active lesions 2. By transfusion of infected blood 3. Transplacental inoculation from an infected mother SYPHILIS SYPHILIS PATHOGENESIS Disease is spread through contact Incubation period of 12-30 days Three stages: Primary stage Secondary stage Tertiary stage SYPHILIS PRIMARY STAGE

Manifested with the presence of chancre, an induration of soft tissue Lesion usually located in the genitalia Lip, oral and finger lesion occur occasionally Primary lesion heals without scarring after 3-12 days, even without treatment

REACTIVE LESIONS
CLINICAL FEATURES Acute reactive ulcers exhibit clinical signs & symptoms of acute inflammation

SYPHILIS SECONDARY STAGE After a latent period of several weeks, secondary syphilis develops (2-10 weeks if untreated) Fever, flu-like symptoms and mucocutaneous lesions with spirochetemia

Reddish-brown maculopapular cutaneous rash Condylomata lata elevated broad based plaques in skin & mucosa Lymphadenopathy is typical Lesion may persist for 8 weeks Resolves spontaneously Patients enters into another latency period Relapses to secondary syphilis may occur in some patients

Other antibiotic can be given to patient sensitive to penicillin, such as tetracycline and erythromycin.

May be supplemented by oral tetracycline

TUBERCULOSIS

GONORRHEA ETIOLOGY Most prevalent bacterial diseases in human

SYPHILIS TERTIARY STAGE Late stage syphilis May involve CNS, cardiovascular lesions or focal necrotic inflammatory lesions (gummas) of any organ Develops in about 1/3 of latent syphilitics

CNS involvement: tabes dorsalis & locomotor ataxia Cardiovascular lesions: aneurysms Gummas: intraorally occur in the palate and tongue ( syphilitic glossitis

Caused by the gram-negative diplococcus Neisseria gonorrhoeae Transmitted by direct sexual contact with an infected partner Incubation period: less than 7 days Absence of symptoms especially in females Genital infections may be transmitted to the oral and pharyngeal mucous membrane through orogenital contact Pharyngeal mucosa is more commonly affected because oral mucosa is more resistant Transmission from an infected patient to dental personnel is regarded as highly unlikely because the organism is very sensitive to drying and requires a break in the skin or mucosa to establish an infection Gloves and mask should provide adequate protection from accidental infection

Caused by the aerobic bacillus Mycobacterium tuberculosis Factors that favor spread of communicable diseases: Poor living conditions Low socio-economic status Low native resistance Compromised immunity Of particular concern is the sharp rise of this disease within the acquired immunodeficiency syndrome (AIDS)affected population The emergence of multiple drug-resistant forms of tuberculosis

SYPHILIS Patients infected via transfusion of contaminated blood bypass the primary stage and begin with the secondary syphilis Congenital Syphilis Occurs during the latter half of pregnancy, when treponema pallidum organism crosses the placenta from the infected mother. Spirochetemia may develop fetal abortion, or it may produce numerous inflammatory and destructive lesions in various fetal organs Mucocutaneous rash may been early When infectious process involves the vomer, saddle nose develops When periotitis of the tibia occurs, excessive anterior bone growth results in a deformity known as saber shin Hutchinsons Triad 1. Interstitial keratitis- inflammatory reaction in the cornea 2. Eighth nerve deafness 3. Dental abnormalities consisting of notched or screwdriver-shaped incisors (hutchinsons incisors) and mulberry molars SYPHILIS TREATMENT Drug of choice is penicillin

GONORRHEA CLINICAL FEATURES Oral lesions No specific clinical signs occur in oral region Multiple ulcerations and generalized erythema have been described Pharyngeal lesions more common general erythema with associated ulcers an cervical lymphadenpathy Chief complaint may be sore throat, although many patients are asymptomatic GONORRHEA DIFFERENTIAL DIAGNOSIS Aphthous ulcers, herpetic ulcers, erythema multiforme, pemphigus, pemphigoid, drug eruptions and streptococcal infections Bacterial culture is done for diagnosis GONORRHEA TREATMENT Drug of choice is Penicillin G Spectinomycin and third generation cephalosporins ( deftriaxone and cefoxatime) also used for treatment

TUBERCULOSIS PATHOGENESIS Spread of infection is through small airborne droplets, which carry the organism to pulmonary air spaces. Phagocytosis by alveolar macrophages follows, and the battle between bacterial virulence and host resistance begins Oral mucosa may become infected through implantation of organisms found in sputum or, less likely, through hematogenous deposition TUBERCULOSIS DIAGNOSIS Mantoux test and tine test skin tests utilizing a tubercle bacillus antigen called purified protein dervative (PPD) A positive inflammatory skin reaction indicates that the individuals cell-mediated immune system has been sensitized and signifies previous exposure TUBERCULOSIS Latent organisms may become reactivated at a later date The disease may progress through airborne, hematogenous or lymphatic spread, so called miliary spread TUBERCULOSIS CLINICAL FEATURES

Unless the primary infection becomes progressive, the infected patient will probably exhibit no symptoms Skin testing and radiographs may provide the only indicators of infection In reactivated disease: Low grade signs & symptoms of fever Night sweats Malaise Weight loss Progressive stage Cough Hemoptysis Chest pain Oral manifestations Favored location: tongue & palate Typical lesion is an indurated, chronic, non-healing ulcer Bony involvement of the maxilla & mandible may produce tuberculous osteomyelitis Pharyngeal involvement results in painful ulcers Laryngeal lesions may cause dysphagia and voice changes

Skin and peripheral nerves are affected Erythematous plaques or nodules that represent a granulomatous response to the organism In time, severe maxillofacial deformities can appear Nerve dysfunction and anesthesia, the patients extremities may suffer fro trauma, ulceration, and bone resorption

ACTINOMYCOSIS PATHOGENESIS The ff. predispose to the development of this condition Tooth extraction Gingival surgery Oral infections ACTINOMYCOSIS CLINICAL FEATURES Most infections are seen in the thorax, abdomen and head and neck region Usually preceded by trauma or direct extension of a contagious infection When occur in the head & neck , it is designated as cervicofacial actinomycosis Head and Neck Typically presents as a swelling of the mandible that may stimulate pyogenic infection The lesion may become indurated and eventually form one or more draining sinuses, leading from the medullary spaces of the mandible to the skin of the neck

LEPROSY DIAGNOSIS History either of contact with a known infected patient or of living in a known endemic area Signs & symptoms associated with skin and nerves should provide additional clues to the nature of the disease The appearance of oral lesions without skin lesions seems highly improbable Biopsy must be done to confirm the diagnosis LEPROSY TREATMENT Anti-leprosy drugs Dapsone Rifampin Clofazimine thalidomide ACTINOMYCOSIS ETIOLOGY & PATHOGENESIS A chronic bacterial disease that exhibits some clinical & microscopic features that are fungus-like

TUBERCULOSIS TREATMENT Chemotherapeutic regimen of the ff drugs: Isoniazid Rifampicin Streptomycin Ethambutol LEPROSY Also known as Hansens disease Caused by an acid-fast bacillus, Mycobacterium leprae Only moderately contagious Requires frequent direct contact with an infected individual over a long period of time Can be transmitted through inoculation via the respiratory tract LEPROSY CLINICAL FEATURES

The pus draining from the chronic lesion may contain small yellow granules, known as sulfur granules Radiographically, it presents as a radioluscency with irregular and ill-defined margins

Caused by Actinomyces israelii A. israelii is a normal inhabitant of the oral cavity in majority of health individuals Usually found in tonsillar crypts, gingival crevices, carious lesions, & non-vital root canals Not regarded as a contagious disease Infection cannot be transmitted from one individual to another Infections usually appear after the ff. Trauma Surgery Previous infection

Tuberculoid leprosy- limited form of lesion Lepromatous leprosy- generalized form Has a more seriously damaging course

ACTINOMYCOSIS DIFFERENTIAL DIAGNOSIS Definitive diagnosis is dependent upon the identification of the actinomycotic organism This is done by: Direct examination of the exudate Microscopic evaluation of the tissue sections Microbiologic culture of pathologic materials ACTINOMYCOSIS TREATMENT Long term, high dose penicillin is the required antibiotic regimen Intravenous penicillin (10 to 20 million units per day for 4 to 6 weeks) followed by oral penicillin (4 to 6 gm per day for a period of weeks or months) is a standard regimen Tetracycline and erythromycin can also be effective Drainage of abscesses Surgical excision of scar tissue & sinus tract

NOMA ETIOLOGY & PATHOGENESIS Cancrum oris Gangrenous stomatitis A rare disease of childhood Characterized by a destructive process of orofacial tissues Necrosis of tissue occurs as a consequence of invasion by anaerobic bacteria Fusiform bacilli & Vincents spirochetes NOMA PATHOGENESIS Predisposing factors Malnutrition- most frequent Debilitation from systemic disease Pneumonia or sepsis NOMA PATHOGENESIS Shares many features with the more limited and more benign acute necrotizing ulcerative gingivitis (ANUG or Vincents infection) Caused by the same organism Require compromised hosts Both result in tissue necrosis NOMA CLINICAL FEATURES Initial lesion is a painful ulceration Usually occur in the gingiva & buccal mucosa Spreads rapidly & eventually necrotizes Denudation of the involved bone may follow, leading to necrosis & sequestration Teeth may become loose & may exfoliate Penetration of organisms into the cheek, lip or palate may occur resulting in fetid necrosis lesions Before antibiotics were developed, fatalities from this disease were common NOMA TREATMENT Therapy involves treating the underlying predisposing condition as well as the infection itself Fluids, electrolytes & general nutrition are restored Introduction of antibiotics ( penicillin) Debridement of necrotic tissue may be beneficial if there is extensive destruction

FUNGAL CONDITIONS
FUNGAL DISEASES 1. Deep Fungal Diseases 2. Subcutaneous Fungal Diseases a. Sporotrichosis 3. Opportunistic Fungal Infection a. Pycomycosis DEEP FUNGAL DISEASES ETIOLOGY & PATHOGENESIS This group of fungal diseases is characterized by primary involvement of the lung May potentially disseminate from this primary focus to involve other organ system Clinically, often mimic TB, relative to primary & secondary or reactivated lesion Deep Fungal diseases with significant incidence of oral expression: 1. Histoplasmosis 2. Coccidioidomycosis 3. Blastomycosis 4. Cryptococcosis Oral infections will typically follow implantation of oral mucous membranes by infected sputum Oral infections may also follow the hematogenous spread of fungus from a lung focus Primary site is the lung DEEP FUNGAL DISEASES CLINICAL FEATURES Initial signs & symptoms are usually related to lung involvement: Cough Fever Night sweats Weight loss Chest pain Hemoptysis Oral lesions are usually preceded by pulmonary infection Swallowed infected sputum may potentially cause oral or GIT lesions The usual oral lesions is ulcerative in nature Lesions are always painful, non-healing, & indurated DEEP FUNGAL DISEASES Histoplasmosis

Symptoms include cough, fever, night sweats & weight loss Oral lesions include non-healing ulcers, secondary to lung disease Treatment : Amphotericin B , ketoconazole

DEEP FUNGAL DISEASES Coccidioidomycosis Caused by Coccidioides immitis Contracted by inhalation of spores Endemic in western US Symptoms include cough, fever, weight loss, chest pain & erythema multiforme Oral lesions include chronic non-healing ulcers secondary to lung disease Treatment: Amphotericin B & ketoconazole DEEP FUNGAL DISEASES Blastomycosis Caused by Blastomyces dematitidis Transmitted through inhalation of spores North American distribution Symptoms include fever, weight loss, night sweats Oral lesions include chronic, non-healing ulcers, draining sinus, secondary to lung infection Treatment : Amphotericin B, ketoconazole DEEP FUNGAL DISEASES Cryptococcosis Caused by Cryptococcus neoformans Transmitted through inhalation of spores, pigeons are carriers Symptoms include cough, hemoptysis, & headache Oral lesions include chronic non-healing ulcers secondary to lung infection Treatment: Amphotericin B & flucytosine DEEP FUNGAL DISEASES DIFFERENTIAL DIAGNOSIS Clinically, chronic, non-healing ulcers may be similar to the ff: Oral squamous cell carcinoma Chronic trauma Oral TB Primary syphilis

Caused by Histoplasma capsulatum Infected thru inhalation of spores in dust of bird excrement Endemic in midwestern US

To establish definitive diagnosis: Culture of organisms from lesions Microscopic identification of organisms in biopsy tissue

DEEP FUNGAL DISEASES TREATMENT Generally chemotherapeutic Surgical resection or incision and drainage used to enhance drug effect Drug of choice: Amphotericin B Ketoconazol Fluconazole SUBCUTANEOUS FUNGAL INFECTION Sporotrichosis Affect primarily subcutaneous tissues Of significance, because of the presence of oral manifestations Caused by Sporothrix schenckii Results from inoculation of the skin or mucosa by contaminated soil or thorny plants Incubation period : several weeks Subcutaneous nodules frequently become ulcerated Systemic involvement is rare, but seen in patient with defective or suppressed immune response SPOROTRICHOSIS clinical features Lesions appear at the site of inoculation and spread along lymphatic channels Red nodules appear on the skin with subsequent breakdown, exudate production and ulceration Oral lesions: non-specific chronic ulcers Presence of lymphadenopathy SPOROTRICHOSIS histopathology Central abscesses may be found in some of the granulomas Overlying epithelium may exhibit psudoepitheliomatous hyperplasia Relatively small, round to oval fungus may be seen in tissue section SPOROTRICHOSIS diagnosis Definitive diagnosis is based on culture of infected tissue on Sabouraud agar Special silver stains may also be used to identify the organism in tissue biopsies SPOROTRICHOSIS treatment

Solution of potassium iodide Ketoconazole is used in cases of toxicity or allergy with limited success Patients respond well to treatment , with little morbidity

OPPORTUNISTIC FUNGAL INFECTIONS PHYCOMYCOSIS etiology & pathogenesis Also known as mucormycosis Includes fungal infections caused by genera Mucor & Rhizopus Organisms of this family are normally found in bread mold or decaying fruits & vegetables Organisms are opportunistic, infecting humans when systemic health is compromised Infections typically occur : Poorly controlled ketoacidotic diabetics Immunosuppressed transplant patients Patients with advanced malignancies Patients being treated with steroids or radiation Immunodepressed patients Pathogenesis Route of infection : Gastrointestinal tract Respiratory tract May potentially occur anywhere along the above routes PHYCOMYCOSIS clinical features Head and neck: Nasal cavity Paranasal sinuses Oropharynx Pain & swelling precede ulceration Tissue necrosis may result in perforation of the palate PHYCOMYCOSIS clinical features Extension into the orbit or brain is a common complication The fungus has a propensity for arterial walls where invasion may lead to : Hematogenous spread Thrombosis infarction PHYCOMCOSIS histopathology

Microscopically, fungus appears as lare, pale-staining, non-septate hyphae that tend to branch at right angles Fungus in necrotic vessels walls in which thrombi may be evident is characteristic PHYCOMYCOSIS differential diagnosis Confirmation must be made by identification of the fungus in biopsy tissue exudates or cultures Because of the severity of underlying disease & the often rapid course, diagnosis may not be made until after death PHYCOMYCOSIS treatment Drug of choice is Amphotericin B Surgical debridement of the upper respiratory lesions is often required Prognosis is dependent upon the severity of the underlying disease & the institution of appropriate therapy Death is a relatively frequent consequence

CONDITIONS ASSOCIATED WITH IMMUNOLOGIC DYSFUNCTIONS

APHTHOUS ULCERS The most common of all types of nontraumatic ulceration that affects the mucous membranes Incidence ranges from 20-60% Prevalence tends to be higher in professional persons and those in upper socio-economic groups Also known as canker sores & recurrent aphthous stomatitis APHTHOUS ULCERS etiology & pathogenesis Cause is unknown Etiologic factors: Immunologic factors Microbiologic factors Nutritional factors Other factors: hormonal alterations, stress, trauma & food allergies APHTHOUS ULCERS etiologic factors: immunologic The most promising avenue of investigation Aphthous ulcers result from a focal immune dysfunction in which T lymphocytes play a significant role

Causative agent Endogenous antigen autoimmune Exogenous antigen hyperimmune etiologic factors: microbiologic After several studies, this theory has been discarded

etiologic factors: nutritional Deficiencies of vitamin B12, folic acid & iron Correction of the above deficiencies has produced improvement or cures etiologic factors: others Hormonal alterations Stress Trauma Food allergies: nuts, chocolate & gluten None of these is seriously regarded as being important in the primary causation But can have triggering role APHTHOUS ULCERS clinical features Three forms of aphthous ulcers Minor aphthous ulcers Major aphthous ulcers Herpetiform aphthous ulcers All are believed to be part of the same disease spectrum with a common etiology Differences are essentially clinical & correspond to degree of severity All forms present as painful recurrent ulcers Occasionally, patient have prodromal symptoms: tingling or burning prior to the appearance of the lesions Ulcers are not preceded by vesicles Rarely appear: gingiva & hard palate Appear on : Vestibular & buccal mucosa Tongue Soft palate Fauces Floor of the mouth MINOR APHTHOUS ULCERS clinical features Most commonly encountered form Appear as single, painful, oval ulcers Less than 0.5 cm in size Covered by a yellow fibrinous membrane Surrounded by an erythematous halo Lesion lasts 7-10 days Heals without scar formation

When the lateral or ventral surfaces of the tongue are affected, pain tends to be out of proportion to the size of the lesion Multiple oral aphthae may occasionally be seen Recurrences vary from one person to another Periods of freedom from this disease may range from a matter of weeks to as long as years

MAJOR APHTHOUS ULCERS clinical features Was referred to as periadenitis mucosa necrotica recurrens (PMNR) or Suttons disease Regarded as the most severe expression of aphthous stomatitis Lesions are larger & more painful Persist longer than minor aphthae Appear crateriform because of the depth of inflammation Heal with scar Lesions may take as long as 6 weeks to heal as soon as one lesion disappears, another one starts In patients who experience an unremitting course with significant pain and discomfort, systemic health may be compromised because of difficulty in eating and psychologic stress HERPETIFORM APHTHOUS ULCERS clinical features Unlike herpetic infection, this form are not preceded by vesicles Exhibit no virus-infected cells APHTHOUS ULCERS histopathology It is generally accepted that important clues to the etiology and pathogenesis may be found during the early stages , therefore biopsies are unnecessary and rarely done APHTHOUS ULCERS differential diagnosis Diagnosis is generally based on history & clinical appearance Secondary recurrent oral herpes is often confused with aphthous ulcers but can be distinguished from it, because the latter is not precede by a vesicle APHTHOUS ULCERS treatment

In patients with occasional or few minor aphthous ulcers usually no treatment is needed because of minor discomfort For patients who are affected severely, some form of treatment can provide significant control but not necessarily cure Because of its immunologic defect related factor, treatment includes drugs that can regulate the immune response Chemotherapeutic agents used: Systemic steroids Topical steroids antibiotics Other drugs APHTHOUS ULCERS treatment / systemic steroids Appropriate for severe disease Should not be use unless the clinician as experience in this treatment area/ working with a knowledgeable consultant Should know the effects & side effects of systemic steroids therapy APHTHOUS ULCERS treatment / systemic steroids Effects & Side Effects:

Anti-inflammation - Therapeutic Immunosuppression - Aggravation of Tb & other infections, delayed wound healing Gluconeogenesis from protein & fat - Aggravation of diabetes, muscle weakness & osteoporosis Altered fat metabolism - Buffalo hump, hyperlipidemia Fluid retention from Na resorption & K excretion - Moon face, weight gain Potentiation of vasopressors Blood pressure elevation, aggravation of congestion, heart failure Increased gastric secretions Aggravation of peptic ulcer Suppression of pituitary-adrenal axis - Adrenal atrophy CNS effects - Psychologic changes

Ocular effects - Cataracts, glaucoma For immediate control of severe case, a lo to moderate dose of prednisone over a short period of time is recommended

A typical regimen: 20-40 mg daily for 1 week Followed by another week at half the initial dose Prednisone should be taken in one bolus in the morning A slow steroid taper is not necessary if the treatment lasts for less than 4 weeks In patients requiring higher dosage prolonged, or maintenance therapy, an alternate-day regimen may be used after initial daily therapy APHTHOUS ULCERS treatment / topical steroids If used judiciously, can be effective and safe in mild to moderate condition Creams & gels: Orabase Side effects : Systemic Suppression of pituitaryadrenal axis Iatrogenic Cushings syndrome Local (skin) Striae Atrophy Hypopigmentation Telangiectasia Induced acne Folliculitis candidiasis APHTHOUS ULCERS treatment / antibiotics Tetracycline oral suspension Used to eliminate secondary bacterial infection of the ulcers Combination of tetracycline oral suspension, nystatin oral suspension anddephenhydramine hydrchloride ( Benadryl) provides more clinical benefits Oral rinse containing chlorhexidine gluconate .12% ( Peridex, Orahex) APHTHOUS ULCERS treatment / other drugs Vitamin A derivatives Anti-inflammatory drugs Sulfones sulfonamides BEHCETS SYNDROME A multisystem disease in which recurrent oral aphthae are a consistent feature System involve are: GIT, cardiovascular, ocular, CNS, articular, pulmonary, dermal

Oral manifestations are relatively minor, involvement of other sites , esp. the eyes & CNS can be quite serious

Biopsy & laboratory tests will produce nonspecific results

BEHCETS SYNDROME etiology Cause is basically unknown Underlying disease mechanism may likely be immuno-dysfunction in which vasculitis has a part Genetic predisposition to the frequent presence of HLA-B15 within the group BEHCETS SYNDROME clinical features Typically affect the oral cavity, eyes & genitalia Recurrent arthritis of the wrists, ankles and knees Cardiovascular manifestations results fro vasculitis and thrombosis CNS manifestations are in the form of headaches, but infarcts have been reported Presence of pustular erythema nodosum-like skin lesions Relapsing polychondritis ( e.g. auricular cartilage & nasal cartilage) in association with Bechets stigmata

BEHCETS SYNDROME treatment Systemic steroids Immunosuppressive drugs Chlorambucil Azathioprine Dapsone, cyclosporine & interferon REITERS SYNDROME etiology Cause is unknown Abnormal immune response to microbial antigen regarded as a likely mechanism for the multiple manifestations of this syndrome REITERS SYNDROME clinical features Major components are: Arthritis Non-gonococcal urethritis Conjuctivitis or uveitis Urethritis precedes the appearance of other lesions Mucocutaneous lesions seen in 50% of patients with this syndrome Maculopapular lesions may occur on the genitalia Oral lesions are relatively painless aphthous-like ulcers occurring anywhere in the oral cavity Tongue lesions is similar to that of georaphic tongue Occur predominantly in white males in their third decade Duration of the disease varies from weeks to months Recurrences are not uncommon REITERS SYNDROME diagnosis Upon the recognition of various signs and symptoms No specific laboratory tests REITERS SYNDROME treatment Non-steroidal anti-inflammatory agents Antibiotics can be added to the treatment regimen

Behcets stigmata known as MAGIC syndrome Mouth & genital ulcers with Inflamed Cartilage Oral manifestations are identical to the ulcers of aphthous stomatitis, minor, and with the same distribution Ocular changes such as uveitis, conunctivitis and retinitis Genital lesions are ulcerative in nature & may cause significant pain & discomfort Painful ulcerative lesions may also occur around the anus Inflammatory bowel disease & neurological problems

BEHCETS SYNDROME histopathology T-lymphocytes are very prominent Infiltration of neutrophils appear within the vessel representing leukocytoclastic vasculitis BEHCETS SYNDROME diagnosis Diagnosis is based on clinical signs & symptoms described above

ERYTHEMA MULTIFORME etiology & pathogenesis Basic cause is unknown Hypersensitivity reaction is suspected Evidence shows that the disease mechanism may be related to antigenantibody complexes that are targeted for small vessels of the upper dermis & submucosa Precipitating factors can be identified in 50% of the cases Infections drugs Other factors which trigger EM Malignancy Vaccination Autoimmune disease Radiotherapy Infections frequently reported include Herpes simples ( HSV types I & II) TB Histoplasmosis Various types of drugs that precipitate EM: Barbiturates sulfonamides ERYTHEMA MULTIFORME clinical features Usually an acute self-limiting process that affects the skin &/or mucous membranes 25-50% of the patients with cutaneous EM will have oral manifestations May be chronic in nature or recurrent acute type In recurrent cases, prodromal symptoms are experienced prior to any eruptions Young adults are mostly affected Often develop in the spring or fall & may have recurrence seasonally Include multiple & varied clinical appearances that are associated with cutaneous manifestations ( multiforme) Target or iris lesion is the classic skin lesion of EM It is consists of concentric erythematous rings separated by rings of near-normal color The skin in the center of these lesions may be erythematous or tan, representing resolution Typically, the extremities are involved Usually in symmetric distribution Other types of skin manifestations include: Macules

Papules Vesicles Bullae Urticarial plaques Orally, EM characteristically presents as an ulcerative disease Varying from a few aphthous-type lesions to multiple, superficial, widespread ulcers Areas involved are the lips, buccal mucosa, palate & tongue Recurrent oral lesions may appear as multiple painful ulcers similar to the initial episode As less asymptomatic erythematous patches with limited ulceration Symptoms range from mild discomfort to severe pain Patient experience considerable apprehension because of occasional explotive onset Systemic signs & symptoms are: Headache Slightly elevated temperature lymphadenopathy Stevens-Johnson syndrome- a major variant of EM Intense involvement of the mouth, eyes, skin, genitalia & occasionally the esophagus & respiratory tract may be seen Systemic signs & symptoms are more pronounced Cutaneous & mucosal lesions are more extensive

ERYTHEMA MULTIFORME differential diagnosis Target or iris skin lesion is present, clinical diagnosis is straightforward If skin lesion is absent, it has to be compared with primary HSV infections, aphthous ulcers, pemphigus vulgaris, bullous pemphigoid & erosive lichen planus ERYTHEMA MULTIFORME diagnosis To diagnose EM, the ff. should be present: General lack of systemic symptoms Favored oral location of lips, buccal mucosa, tongue, & palate Larger sized ulcers- not precede by vesicles Presence of target skin lesions History of recent drug ingestion or infection ERYTHEMA MULTIFORME treatment Symptomatic treatment for mild affected patients Topical corticosteroids with antifungals In severe cases, moderate dose of systemic corticosteroids may be used to shorten the course of the disease & abort recurrences or reduce its intensity Supportive measures to provide patients with substantial benefits: Oral irrigation Adequate fluid intake Use of antipyretics LUPUS ERYTHEMATOSUS Encompasses three (3) recognized subsets: Systemic (acute) LE Subacute cutaneous LE Discoid (chronic) LE- which may have oral manifestations 1. Systemic lupus erythematosus (SLE) is of greatest importance because of profound impact it has on many organ system 2. Discoid lupus erythematosus (DLE) is the least aggressive form, affecting predominantly the skin and rarely progressing to a more severe form It may be of great cosmetic significance because of its predilection for the face

ERYTHEMA MULTIFORME clinical features: stevens-johnson Lips my become encrusted Oral lesions may cause exquisite pain Superficial ulceration, often preceded by a bullae is common to all affected sites Ocular inflammation ( conjunctivitis & uveitis) may lead to scarring & blindness in some patients

ERYTHEMA MULTIFORME histopathology No specific or consistent microscopic pattern Dermal vessels shown to have IgM complement and fibrin in their walls- this support an immune-complex vasculitis cause of EM

3.

Subacute cutaneous lupus erythematosus (SCLE) lies intermediate between SLE and DLE Skin lesions of mild to moderate severity Mild systemic involvement Appearance of some abnormal autoantibodies

Oral lesions are those similar to DLE Mild systemic symptoms in the form of musculoskeletal complains as well as serologic abnormalities are frequently seen

LUPUS ERYTHEMATOSUS etiology & pathogenesis Result from an autoimmune process that may be influenced by genetic or viral factors Both humoral & cell-mediated arms of the immune system are involved LUPUS ERYTHEMATOSUS clinical features- DLE Characteristically seen in middle age, especially women Lesions frequently appear solely on the skin, most commonly on the face & scalp Oral & vermillion lesions are also frequently seen but usually accompany cutaneous lesions On the skin, lesions appear as disk-shaped erythematous plaques with hyperpigmented margins As the lesions expand peripherally, the center heals, with the formation of scar & formation of pigment Involvement of hair follicles results in permanent hair loss (alopecia) Mucous membrane lesions appear in 25% of the patients with cutaneous DLE Most frequently affected are: buccal mucosa, gingiva, & vermilion Lesions appear as erythematous plaques or erosions Usually present are delicate, white, keratotic striae radiating from the periphery of the lesions Diagnosis of oral lesions may not be evident on the basis on clinical appearance, but it is often suspected in the presence of skin lesions Progression to SLE is very unlikely although the potential does exist LUPUS ERYTHEMATOSUS clinical features- SCLE Skin lesions are annular or papulosquamous in nature Lesion persist for weeks to months and heal without a scar

Circulating antibodies to cytoplasmic components may be found in affected patients One is known as anti-Ro or Sjogrens syndrome A antibody (SS-A) since it may also be found in the serum of patients with Sjogrens syndrome anti-La (SS-B)- an auto-antibody Long term prognosis is believed to be good, with progressive to SLE an unlikely event

Joints Kidneys Heart lungs The inflammatory of the various involved tissues result in a wide array of signs & symptoms Kidney- glomerulopathy- most important & the most common cause of death for patient with SLE

LUPUS ERYTHEMATOSUS clinical features- SLE Skin and mucosal lesion are relatively mild Patient complaints are dominated by multiple system involvement Numerous auto-antibodies directed against nuclear & cytoplasmic antigens are found in patients with SLE These antibodies when complexed to their corresponding antigens either in serum or in the target organ resulting in a wide variety of clinical signs & symptoms Skin involvement results in an erythematous rash, seen over the malar processes and bridge of the nose resulting to butterfly appearance Other affected areas are: face, trunk and hands Disk-shaped lesions are non-scarring may flare as systemic involvement progresses Oral lesions are similar to that of DLE Ulceration Erythema Keratosis Areas frequently involved are: Vermilion Buccal mucosa Gingiva palate Systemic symptoms: initial Fever Weight loss Malaise Will progress into involving many organs:

LUPUS ERYTHEMATOSUS diagnosis Serologic tests for autoantibodies are positive in patients with SLE The ANA test is the most reliable & relatively specific for SLE Another serologic test for SLE is the LE test , but less sensitive & less specific LUPUS ERYTHEMATOSUS histopathology The most important microscopic feature diagnostically is the interface change, since it appears that the basal layer is the primary target in the skin & mucous membrane LUPUS ERYTHEMATOSUS differential diagnosis Lesions similar with erosive lichen planus, but lupus lesions are less symmetrical in distribution Keratotic striae in LE are more delicate & subtle than that of lichen planus The presence of characteristic skin lesions or systemic signs & symptoms may help diagnose LE Biopsy & direct immunofluorescent testing should help confirm the clinical impression Negative serologic tests for autoantibodies would rule out systemic involvement LUPUS ERYTHEMATOSUS treatment DLE is usually treated with topical steroids High-potency creams can be used intra-orally but should be used with caution on the facial skin because of secondary cutaneous changes Systemic steroids may be utilized in the treatment of SLE and SCLE

Prednisone combined with immunosuppressive agents

Anti-malarials, non-steroidal antiinflammatories, dapsone, & retinoids

DRUG REACTIONS etiology & pathogenesis Although the skin is more commonly involved in adverse reactions to drugs Oral mucosa ay occasionally be the target organ or maybe the sole site of involvement (or part of a skin reaction)

Do not stimulate an immune response in the patient Are not antibody-dependent Drugs directly affecting the mast cells, causing the release of chemical mediators Reactions may be overdose, toxicity or side effects

Oral manifestations Erythematous, vesicular or ulcerative May mimic lichen planus ( lichenoid drug reations) Widespread of ulcers typical or EM are often representative of a drug reaction

Drugs Known to Cause Adverse Reactions Anti-malarials Aspirins Barbiturates Chlorpromazine Cimetidine Codeine Erythromycin Gold compounds Indomethacin Ketoconazole Local anesthetics Meprobamate Methlydopa Oxyprenolol hydrochloride Penicillin Phenytoin Retinoids Streptomycin Sulfonamides Tetracycline Drug Reactions pathogenesis Immunologic mechanism Non-immunologic mechanism Drug Reaction pathogenesis Immunologic Mechanism Triggered an antigenic component on drug molecule (allergic reaction) Depend on the following factors: immunogenecity of the drug frequency of exposure the route of administration innate reactivity of the patients immune system Non-immunologic Mechanism

Drug Reaction clinical features 1. Cutaneous manifestations Varied depending upon many factors: Type of drug Drug dosage Individual patient differences Changes: (appear rapidly) Anaphylaxis Angioedema Urticaria Acquired Angioedema IgE-mediated allergic reactions Precipitated by drug or foods (nuts or shellfish) Substances act as sensitizing agent that elicit IgE production Hereditary Angioedema Produces the similar clinical changes as that of acquired type Inherited through autosomal dominant trait having deficiency of the inhibitor of the first component of compemen, C1 esterase Angioedema Either acquired or hereditary Appear soft, diffuse, painless swelling Usually affecting the lips, neck or face No color change Condition subsides after 1-2 days which may recur at a later date Emergency treatment may be required to prevent respiratory distress or glottic or laryngeal involvement 2. Other cutaneous manifestations Urticaria Maculopapular rash Erythema Vesicles Ulcers Target lesions (EM) Drug Reaction clinical features

Drug Reaction histopathology Non-specific: spongiosis, necrotic keratinocytes, lymphoid infiltrates, eosinophils Biopsy may be helpful but not diagnostic

Drug Reaction diagnosis Diagnosis requires a high index of suspicion and careful history taking Recent use of drug Withdrawal of suspected drug should result in improvement Drug Reaction treatment Important measure in management is identification & withdrawal of the causative agents Antihistamines Corticosteroids (occasionally) Contact Allergy etiology & pathogenesis Antigenic stimulation of vast array of foreign substances Immune response is cell-mediated Sensitization phase: Langerhans cell recognize the foreign antigen & present them it the T-lymphocytes Local lymphocytes secrete chemical mediators producing allergic reactions Contact Allergy clinical features Lesions directly adjacent to the causativ agent Presenting lesions ranges from erythematous to ulcerative

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Frequently seen in skin, uncommon intraorally Materials containing agents known to cause oral contact allergic reactions: Toothpaste Mouthwash, mouthrinse Candy Chewing gum Topical antimicrobials Topical steroids Iodine Essential oils Denture base materials Cinnamon white , lichenoid, red or ulcerative lesions

Contact Allergy histopathology Epithelium & connective tissue sho inflammatory changes Spongiosis & vesiculation is also seen Dilated blood vessels Eosinophils may be seen Contact Allergy diagnosis Careful history taking is essential Establish a cause & effect relationship may not be possible Biopsy may be helpful but non-conclusive Patch testing may be helpful but may give a false-positive or false-negative result Contact Allergy treatment Elimination of the offending agent or material Healing should take place in 1- 2 weeks Topical steroids may hasten the healing process Wegeners Granulomatosis Inflammatory condition of unknown origin Wegeners Granulomatosis clinical features Triad of upper respiratory tract, lung and kidney involvement Occasionally, only 2 of 3 sites are affected Lesions may present in the oral cavity & skin & other organ system Basic process common to all foci is necrotizing vasculitis with granuloma formation Rare disease of middle age

Initial presentation often occur with head & neck Sinusitis, rhinorrhea, nasal stuffiness & epistaxis seen w/ or w/o fever arthralgia & weight loss In majority of the cases, nasal or sinus ( maxillary) involvement is seen & is often seen in the course of the disease Destructive lesions are typically ulcerated Necrosis & perforation of nasal septum Perforation of hard palate is uncommon Intraorally, red granular gingival lesions Generalized & results in relatively uniform enlargement Most patients have kidney involvement Focal necrotizing glomerulitis Renal failure is the final outcome Inflammatory lung lesions Intensify from slight to severe May lead to respiratory failure

Represents an atypical or unrecognized lymphoma

Midline Granuloma etiology Unknown etiology Hyper-immune response to an unidentified antigen Lymphoid neoplasia from chronic immune stimulation has been suggested Midline Granuloma clinical features Unifocal destructive process in the midline of the oronasal region Lesions appear as aggressive necrotic ulcers that are progressive & non-healing Extension through soft tissue, cartilage & bone is typical Perforation of the nasal septum & hard palate is characteristic Without treatment, the inflammatory process eventually consumes the patient Because of continuous erosion into vital structures especially blood vessels: death has been a typical outcome Midline Granuloma histopathology Appear like acute & chronic inflammation in partially necrotic tissue Several biopsies are required to confirm the diagnosis Midline Granuloma differential diagnosis Wegeners granulomatosis Infectious disease Bacterial infection ( TB) Deep fungal diseases Neoplasm Poorly differentiated squamous cell carcinoma, sarcomas & lymphomas Midline Granulomatous treatment Treatment of choice High dose of local radiation Optimistic prognosis Corticosteroids Chronic Granulomatous Disease Inherited condition Resulting clinical defect: altered neutrophil macrophage function

Wegeners Granulomatosis histopathology Basic pathologic process is granuloatous with necrotizing vasculitis Presence of acute & chronic inflammatory cells Affected small vessels show a mononuclear infiltrate within their walls Wegeners Granulomatosis diagnosis Depend upon the finding of granulomatous vasculitis in biopsy tissue of URT, evidence of lung involvemen or kidney lesions Anti-neutrophil cytoplasmic antibodies (ANCA) Negative culture & tissue identification of microorganisms would help rule out infectious processes Immunohistochemical staining could be used to rule out neoplasm Wegeners Granulomatosis treatment Cytotoxic agent Cyclophosphamide Corticosteroids Remissions seen 75% of cases Midline Granuloma Diagnosis made exclusion of other granulomatous & necrotizing midfacial lesions

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Cells have the capacity to phagocyte microorganism but lack the ability to kill certain bacteria & fungi

Chronic Granulomatous Disease clinical features Manifestations appear during childhood Predominantly occur in males Affect different organs: lymph nodes, lung, liver, spleen, bone & skin Recurrent & persistent Oral lesions: multiple ulcers Recurrent & persistent Chronic Granulomatous Disease histopathology Granular nodular Granulomas may exhibit central lesions Chronic Granulomatous Disease diagnosis Clinical features & tissue samples Neutrophil function tests confirm the diagnosis Differential diagnosis: Crohns disease, TB, histoplasmosis, blastomycosis, tularemia Chronic Granulomatous Disease treatment Use of specific antimicrobial agents

Death due to oral & oropharyngeal cancer represent approximately 2% of total in men & 1% in women Survival rate is low Improvement of survival rate lies in dearly detection (oral cavity is readily accessible of clinical examination & biopsy)

Squamous Cell Carcinoma etiology Tobacco Alcohol Some microorganisms Iron deficiency associated with PlummerVinson syndrome Ultraviolet ray Chronic Irritation Squamous Cell Carcinoma clinical features Carcinoma of the lips Lower lip cancers are more common than upper lip lesions Ultraviolet ray & pipe smoking are common cause Growth rate is slower for lower lip cancers Prognosis for lower lip cancer is generally very good Lip cancers 20-30% of all oral cancers Appear 50-70 years of age Affect men more often than women Lesions are on the vermillion Appear as chronic non-healing ulcers or exophytic lesions ( verrucous in nature) Metastasis is uncommon Larger & poorly differentiated cells Carcinoma of the tongue Most common intra-oral malignancy (2540%)

Most common location- posterior lateral border (45%) uncommon- dorsum or tip of the tongue 25% occur in the posterior 1/3 or base of the tongue These lesions are more troublesome because of their silent progression in an area that is difficult to visualize Poorer prognosis, discover during the advanced stage Metastases from the tongue are relatively common at the time of primary treatment Found in the lymph nodes of the neck Submandibular or jugulodigastric nodes

Carcinoma of the Floor of the Mouth Second most common location of SCC -15% Seen predominantly in older men Especially those who are chronic alcoholics and smokers Lesions are painless, non-healing, indurated ulcers May appear white or red patch May infiltrate the soft tissue causing decreased moblity of the tongue Carcinoma of the Buccal Mucosa & Gingiva Account for 10% of oral SCC Men in their 7th decade are affected Smokeless tobacco is an important etiologic factor in malignant change Appearance varies from white patch to a non-healing ulcer to an exophytic lesion Verrucous carcinoma Presents as a broad-base wart-like mass Slow growing & very well-differentiated Rarely metastasizes w/ good prognosis Carcinoma of the Palate Soft palate & faucial tissues- 10-20% Hard palate- SCC relatively uncommon Adenocarcinoma are relatively common Seen in countries like India where reverse smoking is the custom Present as asymptomatic, red or white plaques in older men Metastasis to cervical nodes or large lesions Squamous Cell Carcinoma histopathology Most are moderately or well-differentiated lesions

Neutropenia Rare blood dyscrasia of unknown cause Manifests as severe cyclic depletions of neutrophils from blood and marrow, with mean cycle of periodicity of about 21 days Signs & symptoms: fever, malaise, oral ulcers, cervical lymphadenopathy & infections may appear neutropenic episodes Patients are prone to exaggeration of periodontal disease No definitive treatment

NEOPLASMS
1. 2. Squamous Cell Carcinonma Carcinoma of the Maxillary Sinus

Squamous Cell Carcinoma Oral and Oropharyngeal SCC represents 4% in men & 2% in women in all cancers

Predilection for male in their 6th, 7th, & 8th decades Lingual carcinoma is typically asymptomatic Later stages, deep invasion occurs, pain & dysphagia may be a prominent complaint Indurated, non-healing ulcer with elevated margins Small percentage of leukoplakias represent invasive SCC or eventually become SCC Most erythroplakia patches that appear on the tongue are either in situ or invasive SCC

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Keratin pearls & cell keratinization are usually evident Invasion into subjacent structures in the form of hyperchromatic cells In poorly differentiated lesions, keratin is absent

N- regional tumor size N1 no palpable nodes N2 ipsilateral palpable nodes N3 bilateral nodes N4 fixed palpable nodes M Metastasis to distant organs M0 no distant metastasis M1 clinical or radiographic evidence of metastasis TNM Staging Stage I T1N0M0 Stage II T2N0M0 Stage III T3N0M0, T1N1M0,T2N1M0, T3N1M0 Stage IV T1N2M0, T2N2M0, T3N2M0, T1N3M0, T2N3M0, T3N3M0, T4N0M0 Any patients with M1 Squamous Cell Carcinoma prognosis As clinical stage advances from I to IV, prognosis worsens Another factor influencing the prognosis is the increased risk for the development of a second primary lesion Carcinoma of the Maxillary Sinus Unknown cause Squamous metaplasia of sinus epithelium with chronic sinusitis & oral antral fistulas may be a predisposing factor Disease of older age, patients over age 40 Men are generally affected Past history frequently include symptoms of sinusitis As the neoplasm progresses, a dull ache in the area occurs, with eventual development of overt pain As neoplasm extents toward the apices of the maxillary posterior teeth, referred pain may occur as Toothache Tumor may displace teeth and cause vertical mobility of teeth Failure of a socket to heal following extraction may indicate a tumor involvement A recently acquired malocclusion may also indicate a growth Squamous cell carcinoma is the most common histologic type

Squamous Cell Carcinoma differential diagnosis Other ulcerative conditions should be considered Biopsy should be done to an undiagnosed chronic ulcer Careful history taking is important Biopsy will confirm the diagnosis Squamous Cell Carcinoma treatment Surgery &/or Radiation Smaller lesions are treated with surgery alone, with radiation as a backup in the event of recurrences Larger lesions may be treated with surgery followed by radiation Elective or prophylactic neck dissection or radiation is advocated Oral SCC are generally resistant to chemotherapeutic measures( serve as adjunct only) Squamous Cell Carcinoma prognosis Depend on both the histologic subtype (grade) and clinical extent (stage) of the tumor Other factor influencing clinical course: age, gender, general health, immune system status & mental attitude Grading of a tumor Well-differentiated lesions are less aggressive than poorly differentiated lesions Clinical stage of the disease is the most important indicator of prognosis TNM system T- primary tumor N- regional node metastasis M- distant metastasis T- tumor T1 T2 T3 T4 tumor tumor tumor tumor less than 2 cm in diameter 2-4 cm in diameter greater than 4 cm in diameter invades adjacent structures

Lesions are generally less differentiated that those occurring in the oral mucosa Dental origin must be ruled out before making the diagnosis Vitality test of teeth Palatal involvement should also cause the clinician to consider adenocarcinoma of minor salivary gland origin, lymphoma and SCC. Generally treated with surgery or radiation or both A combination of the 2 treatments are more effective Radiation completed first, with surgical resection following Chemotherapy used in conjunction with radiation is somewhat successful Cure is dependent upon the clinical stage of the disease at the time of initial treatment Sinus lesions are discovered in a more advanced stage because of delay in seeking treatment Difficult to remove surgically because it is richly vascularized 5 year survival rate- 25%

-Rosette Go 010811

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