Oral Ulcers BDS10017 Lecture PDF

BDS10017 Oral Ulceration Aims: The aim of this lecture is to detail the histopathological aspects of traumatic oral ulceration and ulceration due to infectious disease Objectives: On completion of this lecture, the student should be able to: Understand the histopathological features of traumatic...

BDS10017 Oral Ulceration Aims: The aim of this lecture is to detail the histopathological aspects of traumatic oral ulceration and ulceration due to infectious disease Objectives: On completion of this lecture, the student should be able to: Understand the histopathological features of traumatic ulceration Understand the histopathological aspects of syphilis and tuberculosis Aims: The aim of this lecture is to detail the histopathological aspects of immunologically-mediated disorders of the oral mucosa Objectives: On completion of this lecture, the student should be able to: Understand the histopathological features of immunobullous disease, erythema multiforme and granulomatous disease of the oral tissues. What is an ulcer? An ulcer is a break in the continuity of epithelium, exposing the connective tissue to the oral environment. Oral ulcer Oral mucosa An ulcer is a break in the continuity of epithelium, exposing the connective tissue to the oral environment. Oral ulcers Oral mucosa General criteria of oral ulcers Borders are either sharp well-defined OR ragged margins Most ulcers are covered by a greyyellow fibrin slough [this slough has a characteristic appearance, and can be easily distinguished] Superficial bacterial contamination by oral flora is common Most of the ulcers undergo uncomplicated rapid healing due to the rapid turnover of oral epithelium Oral Ulcers Infectious Vesiculobullous Ulceration without vesiculation Noninfectious Vesiculobullous Ulceration without vesiculation Infectious Non-infectious Vesicular and immunobullous diseases Primary herpetic stomatitis Herpes labialis Herpes zoster and chickenpox Hand-foot-and-mouth disease Herpangina Ulceration without preceding vesiculation Measles Glandular fever Tuberculosis Syphilis Pemphigus vulgaris Mucous membrane pemphigoid Linear IgA disease Dermatitis herpetiformis Bullous erythema multiforme Traumatic Aphthous stomatitis Behçet’s disease HIV-associated mucosal ulcers Lichen planus Lupus erythematosus Eosinophilic ulceration Wegener’s granulomatosis Some drug reactions Carcinoma Traumatic ulcers Common causes of traumatic ulcers (refer to lecture BDS10038_Oral ulceration – traumatic causes) Biting (common after a dental local anaesthetic) Denture trauma Chemical trauma usually accidentally self-inflicted (asprin burn may be followed by ulceration) or Iatrogenic (Etchant, hypochlorite and silver nitrate are among the caustic agents used in dentistry that can cause mucosal ulcers after quite short contact time) Traumatic ulcers Clinical features (refer to lecture BDS10038_Oral ulceration – traumatic causes) usually arise at trauma-prone sites such as lip, buccal mucosa or adjacent to a denture flange. They are tender, have: --a yellowish-grey floor of fibrin slough --red Inflamed margins Inflammation, swelling and erythema are variable, depending on the cause and time since trauma. Traumatic ulcers  Traumatic ulcers heal in days after elimination of the cause.  If they persist for more than 10 days without reduction in size and symptoms, biopsy should be carried out to exclude other diseases (mainly malignancy). Eosinophilic ulcer (or traumatic eosinophilic granuloma) Eosinophilic ulcers have a worrying presentation, often resembling carcinoma: exceeding 10 mm in diameter and enlarging rapidly before stabilizing. Believed to be due to unusual response to trauma A concerning feature is failure to heal, and may persist for many months Sometimes the inflammatory response below expands, raising the ulcer giving a nodular ulcerated appearance (called traumatic ulcerative granulomas (can mimic lymphoma histopathologically) Eosinophilic ulcer (or traumatic eosinophilic granuloma) Clinical features  Characteristic presentation is in infants in the first year of life where erupting lower incisors repeatedly traumatize the ventral tongue or lower lip on feeding (Riga-Fede disease)  In practice, lesions usually heal spontaneously within 3–10 weeks, but biopsy will often trigger more rapid resolution. Traumatic ulcers Histopathology Fibrinopurulent membrane (with variable thickness) consists of fibrin intermixed with neutrophils Adjacent surface epithelium may be normal or slightly hyperplastic with hyperkeratosis Ulcer bed consists of granulation tissue infiltrated with mixed inflammatory cells Traumatic ulcers Histopathology  In Eosinophilic ulcers the inflammatory infiltrate extends into deeper tissues and exhibit numerous eosinophils Recurrent Aphthous Stomatitis (refer to lecture BDS10036_RAS and related diseases)  Recurrent aphthous stomatitis is one of the most common oral mucosal pathoses  In which, the mucosal destruction appears to represent a T cell mediated immunologic reaction with production of tumor necrosis factor (major inflammatory cytokine) which assists in ultimate targeting of surface epithelium for destruction by cytotoxic T cells (CD8+) Antigenic stimulation of oral epithelial cells Production of inflammatory cytokines (mainly TNF) Destruction of surface epithelium by cytotoxic T cells Recurrent Aphthous Stomatitis  This reaction may arise due to any of the following Presence of highly antigenic reagent Decrease in mucosal barrier that previously masked the antigen Immuno-dysregulation resulting in abnormal response to a normally present antigen Clinical variations (refer to lecture BDS10036_RAS and related diseases) minor major herpetiform Recurrent aphthous stomatitis Histopathology Destruction of epithelium (central ulceration) covered by Fibrinopurulent membrane Adjacent surface epithelium may show spongiosis with numerous mononuclear cells in basilar one third (1/3) Ulcer bed consists of connective tissue with increased vascularity and mixed inflammatory cell infiltrate Biopsy plays no role in the diagnosis except to exclude carcinoma in case of clinically worrying major aphthae or to exclude viral infection in herpetiform aphthae. Immuno-bullous diseases (refer to lecture BDS10037_Immunologically-mediated diseases) These are autoimmune diseases in which auto-antibodies are directed against components of the skin or oral epithelium to produce blisters. These diseases are commonly called vesiculobullous diseases Most common immunobullous diseases Pemphigus with its variants Pemphigoid with its variants Linear IgA disease Lupus erythematosus Immuno-bullous diseases (refer to lecture BDS10037_Immunologically-mediated diseases) Pemphigus This condition results in patient’s death, if untreated The oral lesions are often the first sign of the disease and they are the most difficult to resolve with therapy “the first to show, and the last to go.” Pemphigoid  A group of chronic, blistering, mucocutaneous autoimmune diseases.  The term pemphigoid is used because clinically they often appear similar to pemphigus, however, prognosis and microscopic features are very different  Conjunctival mucosa may be affected, resulting in scarring and blindness unless the condition is recognized and treated early Immuno-bullous diseases (refer to lecture BDS10037_Immunologically-mediated diseases) Pemphigus Autoantibodies attach to certain desmosomal components (desmoglein 3 and desmoglein1) and inhibit the molecular interaction that is responsible for adherence. Desmosomes mainly desmoglin 3 &1 are affected Pemphigoid Autoantibodies are directed against one or more components of the basement membrane, however all of which produce similar clinical manifestations. Hemidesmosomes and other components of basement membrane are affected Immuno-bullous diseases For an accurate diagnosis of these lesions, we depend on the following Biopsy Direct immunofluorescence Indirect immunofluorescence perilesional tissue rather than the ulcerated lesion itself to detect the presence of autoantibodies in tissue of patient to detect the presence of circulating autoantibodies in serum of patient Immuno-bullous diseases Histopathology Pemphigus Intraepithelial separation, which occurs just above the basal cell layer of the epithelium. Sometimes the entire epithelial layers are stripped away leaving only the basal cells, which “row of tombstones.” Pemphigoid A split between the surface epithelium and the underlying connective tissue in the region of the basement membrane Immuno-bullous diseases Histopathology Pemphigus Epithelial cells appear to fall apart, (acantholysis), and the loose cells appear rounded (Tzanck cells) [also seen in exfoliative cytology]. A mild-to-moderate chronic inflammatory cell infiltrate is usually seen in the underlying connective tissue. Immuno-bullous diseases Histopathology Pemphigus Direct & indirect immunofluorescence Positive reaction can be demonstrated in the intercellular spaces between the epithelial cells Reaction mimics wire fence appearance Immuno-bullous diseases Histopathology Pemphigoid Direct immunofluorescence show a continuous linear band of immunoreactants at the basement membrane zone Indirect immunofluorescence is positive in only 5% to 25% of patients, indicating a relatively consistent lack of detectable circulating autoantibodies Erythema Multiforme (refer to lecture BDS10037_Immunologically-mediated diseases) It is an immunologically mediated mucocutaneous condition characterized by blistering and ulceration, its etiopathogenesis is uncertain Apparent precipitating causes: Preceding infection, such as herpes simplex Exposure to certain drugs such as antibiotics or analgesics. Erythema Multiforme (refer to lecture BDS10037_Immunologically-mediated diseases) Erythema multiforme Minor 80% Major 2 or more mucosal sites with skin lesions Erythema Multiforme Histopathologic Features perilesional mucosa shows subepithelial or intraepithelial vesiculation necrotic basal keratinocytes. A mixed inflammatory infiltrate is present. [Sometimes arranged in a perivascular orientation] Because the immunopathologic features are also nonspecific, the diagnosis is often based on the clinical presentation and the exclusion of other vesiculobullous disorders. Granulomatous diseases (refer to lecture BDS10039_ Oral ulceration other causes) Important granulomatous diseases Infections Tuberculosis Cat-scratch disease Toxoplasmosis Syphilis Reactive Foreign body reactions Unknown causes Sarcoidosis Crohn’s disease Melkersson– Rosenthal syndrome Orofacial granulomatosis Wegener’s granulomatosis [Granulomatosis with polyangiitis] Orofacial Granulomatosis (refer to lecture BDS10039_Oral ulceration other causes) This term has emerged since 1985, it is encompassing a variety of clinical presentations that, on biopsy, reveal the presence of nonspecific granulomatous inflammation. The disorder appears to represent an abnormal immune reaction to a variety of agents. Orofacial Granulomatosis (refer to lecture BDS10039_ Oral ulceration other causes) Histopathologic Features Scattered aggregates of noncaseating granulomatous inflammation, consisting of: lymphocytes epithelioid histiocytes with or without multinucleated giant cells. Tuberculosis (refer to lecture BDS10035_Oral infections Bacteria) Chronic infection caused by Mycobacterium tuberculosis [It is stained by Ziehl-Neelsen stain] Primary mode of transmission is droplet infection by inhalation Oral lesions usually represent secondary infection from initial pulmonary lesions Diagnosis is confirmed by biopsy, chest radiography and a specimen of sputum. Tuberculosis Clinical features (refer to lecture BDS10035_Oral infections Bacteria) Typical lesion is an ulcer on the middorsum of the tongue. The ulcer is irregular with overhanging edges and a pale floor Early stages are painless then may become painful in later stages Involvement of jaw bones commonly appear as a non-healing extraction socket. Regional palpable lymph nodes are seen Histological features Tuberculosis It is characterized by granuloma formation (tubercle) [due to cell mediated hypersensitivity reaction]. Granulomas are circumscribed collections of : 1. Epitholioid histiocytes [macrophages with abundant eosinophilic cytoplasm, giving them resemblance to epithelial cells], surrounded by lymphocytes and fibroblasts Histological features Tuberculosis It is characterized by granuloma formation (tubercle) [due to cell mediated hypersensitivity reaction]. Granulomas are circumscribed collections of : 2.Multinucleated giant cells [Langhan’s cells], their nuclei are distributed around the periphery of the cytoplasm in a horseshoe or ring shape Often with central caseous necrosis Syphilis  Chronic infection caused by Treponema pallidum  Primary mode of transmission is sexual contact or from mother to fetus  After the advent of penicillin therapy in 1940, the prevalence of syphilis decreased for years but often demonstrated peaks Syphilis Clinical features (refer to lecture BDS10035_Oral infections Bacteria)  Primary syphilis is characterized by the chancre that develop at site of inoculation (about 4% of lesions occur orally). It begins as papular lesion then develop central ulceration  Secondary syphilis 30% of patients show irregular thick white mucous patches, which often fuse forming snail-track pattern, superficial epithelial necrosis may occur leading to ulceration Clinical features Syphilis (refer to lecture BDS10035_Oral infections Bacteria)  Tertiary syphilis develops in about 30% of affected individuals (not in those treated effectively). Scattered foci of granulomatous inflammation known as gumma are very characteristic and usually affect palate or tongue intraorally Ulcers of the palate usually perforate to the nasal cavity tongue usually appear large and irregularly shaped Syphilis Histopathology  The histopathologic features of oral syphilitic lesions is not specific  Primary & Secondary stages Surface epithelium may be ulcerated (almost all primary lesions) or hyperplastic  Extensive exocytosis neutrophils into epithelium of  Intense chronic inflammatory cell infiltrate in underlying connective tissue Histopathology Syphilis  Special stains or immunohistochemistry may be used to detect the organism which appears as corkscrew-like spirochetes Steiner stain Immunohistochemical stain Histopathology Syphilis  Tertiary stage -surface ulceration with peripheral pseudoepitheliomatous hyperplasia. -The underlying inflammatory infiltrate usually demonstrate: endarteritis (inflammation of the inner lining of an artery) foci granulomatous inflammation with well circumscribed histiocytes and multinucleated giant cells -Organisms are hard to demonstrate In conclusion  Most of oral ulcers undergo uncomplicated rapid healing. If they persist for more than 10 days, biopsy should be carried out to exclude other diseases (mainly malignancy). T.B and syphilis are granulomatous disease, their causative organisms can be detected by special stains or immunohistochemistry. Eosinophilic ulcers have a worrying presentation, often resembling carcinoma AND biopsy will often trigger rapid resolution In conclusion  Recurrent aphthous stomatitis is one of the most common oral mucosal lesions. Biopsy plays no role in its diagnosis except to exclude carcinoma or viral infection. Pemphigus and pemphigoid are immunobullous diseases in which auto-antibodies are directed against components of the skin or oral epithelium. direct and indirect immunofluorescence play major role in their diagnosis.  Diagnosis of erythema multiforme is often based on the clinical presentation Aims: The aim of this lecture is to detail the histopathological aspects of traumatic oral ulceration and ulceration due to infectious disease Objectives: On completion of this lecture, the student should be able to: Understand the histopathological features of traumatic ulceration Understand the histopathological aspects of syphilis and tuberculosis Aims: The aim of this lecture is to detail the histopathological aspects of immunologically-mediated disorders of the oral mucosa Objectives: On completion of this lecture, the student should be able to: Understand the histopathological features of immunobullous disease, erythema multiforme and granulomatous disease of the oral tissues. Reading material: Students are advised to review any relevant teaching provided in the first year. In addition they are advised to read relevant sections of the following texts: Odell E.W. Cawson’s Essentials of Oral Pathology and Oral Medicine. 9th Edition. Elsevier, 2017 pp 235-254 Robinson M et al. Soames’ and Southam’s Oral Pathology. 5th edition. Oxford University Press, 2018 pp 26-27 Reading material: Students are advised to review any relevant teaching provided in the first year. In addition, they are advised to read relevant sections of the following texts: Odell E.W. Cawson’s Essentials of Oral Pathology and Oral Medicine. 9th Edition. Elsevier, 2017 pp 255-277 Robinson M et al. Soames’ and Southam’s Oral Pathology. 5th edition. Oxford University Press, 2018 pp 40-47 Thank you