"Other" Oral Inflammatory Conditions Flashcards
What is a granuloma?
- Focus of chronic inflammation.
- Microscopic aggregation of activated epithelioid macrophages fused to form giant cells, surrounded by lymphocytes +/- plasma cells +/- a rim of fibroblasts and connective tissue
What are orofacial granulomatosis?
- Unexplained granulomatous inflammatory lesions
* Non-specific diagnosis of exclusion
Subtypes of orofacial granulomatosis…
• Cheilitis granulomatosis - Limited to lips • Melkersson-Rosenthal Syndrome - Swells of face, oral mucosa, etc - Fissured tongue - Unilateral facial nerve paralysis
Clinical features of orofacial granulomatosis
- Lips affected more than other parts of face
- Swelling: nontender, persistent
- Rare lymphangioma-like vesicles
- Rare cervical lymphadenopathy
- Intraoral edema, ulcers, papules
- Gingival swelling, erythema, pain, erosions
- Buccal cobblestone
- Vestibular linear hyperplastic folds
Histology of orofacial granulomatosis
- Non-necrotizing granulomas
- Edema, dilated lymphatics, scattered lymphocytes
- Negative for micro-organisms and foreign substances
Diagnosis of orofacial granulomatosis
• Unexplained granulomatous inflammatory lesions
• OFG is diagnosis of exclusion - known causes of granulomatous lesions must be eliminated:
- Systemic:
• Chronic granulomatous disease
• Crohn's disease
• Sarcoidosis
• Infections (fungi, TB, etc)
- Local
• Chronic oral infection
• Foreign body reactions
• AllergyManagement for orofacial granulomatosis include…
- Special stains (for microorganisms)
- Polarize microscopy (for foreign material)
- Eliminate chronic inflammatory bowel disease
- Eliminate sarcoidosis
- Look for antigen
- Topical or intralesional corticosteroids
- Clofazimine (antileprosy agent)
- Surgical recontouring (but often recur)
Differential diagnosis for fissured tongue
- Normal variant
- Inherited condition
- Down syndrome
- Melkersson Rosenthal syndrome
- Erythema migrans-associated
- Plasma cell gingivitis
Causes of foreign body granulomas…
• Endogenous substances - Keratin - Bony sequestra • Exogenous - Usually birefringent (seen under polarized light) - Sutures - Dental materials
Clinical presentation of granulomatous gingivitis
- Solitary or multifocal lesions
- On interdental papilla or gingival margin
- Up to 2cm in diameter
- Red macules or enlargements
Diagnosis of granulomatous gingivitis…
• Rule out:
- Histologically distinctive/specific granulomatous conditions
• Foreign substances
• Deep fungal infections
• Acid fast bacilli
- Systemic granulomatous diseases
• Crohn's
• Wegener
• Sarcoid
• Diagnosis of nonspecific granulomatous gingivitis is made after r/o other diagnosesHistology of granulomatous gingivitis
• Foreign particles identified associated with:
- Granulomas = foreign body granulomatous gingivitis
- Nonspecific mucositis
- Lichenoid reaction
• Particles less than 1um may be undetected
• When there are granulomas without particles, diagnosis of nonspecific granulomatous gingivitis can be made after r/o all other diagnoses
Etiology of granulomatous gingivitis
- Trimming restorations near gingival margin
* Dental prophylaxis paste used too soon
Clinical features of Wegener granulomatosis
- Probably immune dysfunction
- Starts in upper respiratory tract
- Initially, nasal discharge or sinus pain
- Nasal septum and/or palatal destruction
- May affect lungs and kidneys
- May involve paranasal sinuses, TMJ, or gingivae
- Untreated disseminated cases survive only a few months
Treatment of Wegener’s granulomatosis
• Cytotoxic drugs
- Especially cyclophosphamide with prednisone
• can achieve long-term survival, even cure
Histology of Wegener’s granulomatosis
- Necrotizing vasculitis associated with granulomas
- Leukocytoclastic vasculitis
- Diagnosis involves identification of c-ANCA (serum antibodies against cytoplasmic components of neutrophils)
Discuss ANCAs as seen in Wegener Granulomatosis
• Circulating autoantibodies against a component of granules in cytoplasm of neutrophils
- Serum from patients with vasculities reacts with cytoplasmic antigens in neutrophils - Due to antineutrophil cytoplasmic antibodies - Cause IF patterns in ethanol-fixed neutrophils - One shows cytoplasmic localization of stain (c-ANCA) - Group of autoantibodies against enzymes mainly in azurophilic or primary granules in neutrophils - The most common target antigen is proteinase-3 (PR3), a component of a neutrophil granule
Autoantibodies present in Wegener granulomatosis…
- c-ANCA: autoantibodies against a component of granules in cytoplasm of neutrophils
- Titers correlate with disease activity
- May be important in pathogenesis
Etiology of sarcoidosis
• Abnormal immune response to unknown antigen
- Infectious agent
- Environmental factors
• Genetic predisposition
Clinical presentation of sarcoidosis
- Multisystem disease characterized by non-caseating granulomas in many organs
- Bilateral hilar lymphadenopathy or lung disease in 90% of cases
- Skin and mucous membranes (including nose and mouth)
- Eyes in 25% (blindness rare)
- Also lymph nodes, bone marrow, spleen, liver, kidneys, heart, CNS, parotid glands enlarged in 10-20% (cause of xerostomia)
Demographics of sarcoidosis
- Incidence varies wildly in countries throughout the world
* In U.S. it affects blacks more than whites, with peak incidence in the fourth decade.
Oral lesions in sarcoidosis…
• Soft tissue - Salivary gland enlargement --> xerostomia - Submucosal enlargements - Mucosal macules • Intraosseous - Radiolucencies
Histology of sarcoidosis
• Non-caseating granulomas
- Schaumann bodies (laminated calcifications in giant cells)
- Asteroid bodies in giant cells
Laboratory tests for Sarcoidosis…
• Elevated: - Angiotensin converting enzyme - Erythrocyte sedimentation rate - Serum calcium - Alkaline phosphatase - Vitamin D (Mnemonic: A SAVE) • Positive Kveim-Siltzbach skin test (but not often performed) • Transbronchial lung biopsy is often used
Pronosis for sarcoidosis
- Most patients recover
* 10-20% succumb to progressive fibrosis and cor pulmonale
Treatment for sarcoidosis
- Corticosteroids
- Steroid-sparing agents
- Antimalarial agents
Area mostly affected in Crohn’s disease
Mainly affects distal small intestine and proximal colon.
What is Crohn’s disease?
• Inflammatory GI (mainly) disease:
- Non-necrotizing granulomas
- Probably immunologically-mediated
• Abdominal cramping, nausea, diarrhea, etc.
Demographics of Crohn’s disease
Diagnosis in teens or in people over 60 years of age
Oral manifestations of Crohn’s disease…
• Initial manifestation in some cases
• Diffuse or nodular swellings
• Cobblestone
• Deep linear ulcers in vestibule
- Denture hyperplasia
• Mucogingivitis: patchy red macules and plaques
• Recurrent aphthous ulcers
• Pyostomatitis vegetans
- Manifestation of CIBD
- Multiple pustules
- Intraepithelial abscesses
• Eosinophils +++Reactions to physical & chemical agents include…
- Frictional keratosis
- Traumatic ulcers
- Eosinophilic ulcers
- Burns
- Submucosal hemorrhage
- Anticancer therapy
- Reactions to amalgam
- Tobacco
- Cervico-facial emphysema
- Hairy tongue
- Toxic metals
- Drug-related discolorations
What is frictional keratosis?
- Chronic mechanical irritation –> frictional keratosis
* Reversible
Clinical types of frictional keratosis
- Linea alba
- Morsicatio
- Toothbrush gingival abrasion
- Irritation including broken teeth, prostheses, and restorations
- Mastication on edentulous alveolar ridge
What is linea alba?
- Clinical type of frictional keratosis
- Very common
- White line on buccal mucosa (often bilateral) at level of occlusal plane
- Friction or sucking trauma
What is chronic mucosal chewing?
- “Morsicatio buccarum, linguarum, labiorum”
- White plaques with surface shedding
- +/- focal red erosions or ulcers
- Often bilateral
Histology of frictional keratosis
• Benign hyperkeratosis +/- other features:
- Ragged surface projections
- Bacterial colonies may coat surface
- Vacuolated spinous cells
Clinical features of traumatic ulcers
• Cause usually readily identified • Symmetrical or irregular • Shallow or deep • Base usually firm • Onset abrupt or gradual • Persist until cause is removed • Acute ulcers painful but chronic may be non-painful • Often exhibit a white or yellow surface - Removable, fibrinopurulent membrane
Describe an acute traumatic ulcer…
- Pain
- Yellow base, red halo
- History of trauma
- Heals in 7 to 10 days if cause eliminated
Describe a chronic traumatic ulcer…
- Little or no pain
- Yellow base, elevated margins (scar)
- History of trauma, if remembered
- Delayed healing if irritated, especially tongue lesions
- Clinical appearance mimics carcinoma and infectious ulcers
What are traumatic eosinophilic ulcer or ganuloma?
• Deep ulcer with indurated elevated border
• Clinical resemblance to SCC (or pyogenic granuloma)
• Pain and source of trauma may be lacking
• Most on tongue; may be multiple
• Traumatic eosinophilic granuloma is variant
- Discolored nodule, resembling pyogenic granuloma
Histology of traumatic eosinophilic ulcer or granuloma
- Ulcer bed: fibrin and inflamed granulation tissue
- Inflammation extends into underlying tissue
- Deeper inflammatory infiltrate eosinophils and histiocytes (some atypical)
- Inflammatory tissue replaces skeletal muscle
What is Riga-Fede disease?
- Variant of traumatic eosinophilic ulcer on anterior ventral tongue of infants
- Chronic mucosal trauma due to lower anterior teeth (natal or neonatal)
Types of burns
- Electric burns
- Thermal burns
- Chemical burns
Electric burns
• Most electric burns in oral cavity are arc type
- Saliva acts as conducting medium
- Electric arc flows between source and oral mucosa
• Heat up to 3000°C possible with resulting tissue damage
Examples of electrical burns
- Chewing on female end of extension cord or biting through live wire
- Biting through live wire
Thermal burns
- Most thermal burns in mouth are from hot food/drinks
- Zones of erythema and ulceration +/- necrotic epithelium at periphery
- If swallowed, upper airway swelling –> dyspnea
Chemical burns
• Caustic chemicals and medications
- Aspirin, phenol, H2O2, bisphosphonates
- Gasoline, turpentine, rubbing alcohol
• Brief exposure –> superficial white wrinkled appearance
• Longer exposure –> necrosis increases
- Epithelium desquamates –> bleeding connective tissue surface
- Sometimes coated by fibrinopurulent membrane
What is “Cotton roll stomatitis”?
- Caustic mat leaks into roll and damages mucosa
* When dry roll is pulled away, it strips epithelium
Histology of burns
- White slough: coagulative necrosis of stratified squamous epithelium
- Level of necrosis depends on duration of contact and concentration of agent
- Connective tissue: acute and chronic inflammatory cells
Submucosal hemorrhage
• Blood entrapped in connective tissue • Non-blanching, flat or raised - Petechiae: minute hemorrhage into mucosa - Purpura: slightly larger - Ecchymosis: more than 2 cm diameter - Hematoma: if it's a mass • Red to blue to black to green to yellow • Initial pain • R/o systemic disease
Reactions to amalgam includes…
1) Frictional keratosis
2) Pigmented macule (inert)
3) Foreign body reaction
4) Contact hypersensitivity reaction
Clinical features of amalgam tattoo
- Black, blue, or grey macules more often than papules
- Shape varies
- Local spread after implantation
- Some visible on radiograph
Histology of amalgam tattoo
• Dark-brown or black fragments • Varied tissue reaction - Inert - Stained reticular fibers - Dense fibrous connective tissue - Chronic inflammatory cells - Foreign body granulomas
Reactions to tobacco include…
1) Melanosis
2) Nicotine stomatitis
• Reverse smokers’ palate –> SCC: epithelial dysplasia
3) Hyperkeratosis
4) Epithelial dysplasia
5) Invasive SCC
Demographics of Smoker’s melanosis
- Seen more often in whites than in blacks
* More often in women than in men
What is smoker’s melanosis?
- Oral pigmentation (melanosis) is protective reaction against components of tobacco smoke.
- Cigarette smoking: anterior gingivae is most common site
- Pipe smoking: commissures and buccal mucosa
- Reverse smokers: hard palate
Etiology of cervicofacial emphysema
• Air forced into tissues
• Most linked to surgery
- Difficult extractions
- Sneezing after oral surgery
• Compressed air
- Air-driven hand piecesClinical features of cervicofacial emphysema
- Soft tissue enlargement
- Little pain
- Crepitus (crackling/grating sound)
- Swelling increases if there is 2nd inflammation and edema
- +/- pain, facial erythema, dysphagia, vision defect, mild fever
Prognosis and treatment for cervicofacial emphysema
• Usually subsides 2-5 days
- Rarely respiratory distress
• Broad-spectrum antibiotics in some cases
Appearance of hairy tongue due to…
Appearance is due to keratin accumulation on filiform papillae and/or increased keratin production or decreased keratin desquamation.
Etiology of hairy tongue
• Uncertain • Many affected people are heavy smokers • Basic problem may be altered oral flora resulting in: - Proliferation of fungi and chromogenic bacteria - Papillae overgrowth • Systemic medications - Broad-spectrum antibiotics - Corticosteroids
Clinical features of hairy tongue
• Starts on dorsal midline • Color due to: - Pigment-producing bacteria - Food - Tobacco • Asymptomatic (occasional gagging)
Treatment for hairy tongue
- Identify and eliminate initiating factor
- Brush/scrape tongue with baking soda
- Treat underlying disease
- Little significance, other than annoying to patient, cosmesis
- Bx (biopsy?) rare
Predisposing factors of hairy tongue
- Systemic or topical meds
- Heavy smoking
- Debilitation
- Poor oral hygiene
- Radiotherapy
Toxic metals include…
- Bismuth
- Lead
- Arsenic
- Cis-platinum
- Silver
Lead as a toxic metal…
• Lead solder (plumbing), paint, gas (all now banned)
• Industrial use
• Systemic effects
- Acute: abdominal colic, anemia, fatigue, etc.
- Chronic: affects nervous system, kidneys, bone marrow, bone, teeth
• 90% of lead deposits in bone
Clinical presentation of lead in oral cavity…
• Ulcerative stomatitis
• Burton’s line: gingival lead line
- Bluish line along gingival margin due to bacterial H2S acting on lead in sulcus –> precipitation of lead sulfide
Medicinal heavy metals that are toxic metals include…
Silver was the most common heavy metal employed historically. Others included arsenic, bismuth, cis-platinum.
Clinical manifestation of medicinal heavy metals (toxic metals)
• Acute and chronic manifestations
• Systemic
• Skin and oral mucosa
• Gingivae:
- Gray to black
- Linear along gingival margin
- Staining proportional to inflammation
- Metal reacts with H2S produced by bacteriaSYSTEMIC clinical manifestations of silver as a toxic metal
• Systemic:
- Acute: coma, pleural edema, bone marrow failure
- Chronic = argyria
• Subepithelial deposits in skin
• Diffuse gray discoloration especially in sun-exposed sites, nails, sclerae
ORAL clinical manifestations of silver
• Oral (may be first sign)
- Slate-blue silver line along gingival margins
• This is 2nd to deposits of Ag and Ag2S (silver sulfide)
- Diffuse blue-black mucosa
Drug-related discolorations can be caused by…
• Phenolphthalein • Minocycline • Tranquilizers - Chlorpromazine • Anti-malarials • Estrogen • Chemotherapeutic agents - Cyclophosphamide • AIDS medications - AZT
Mechanisms involved in drug-related discolorations
- Metabolite deposition
* Melanocyte stimulation
Affects of drug-related discolorations
(For minocycline?) • Bones and developing teeth • Skin and eyes • Oral mucosa: - Linear band cervical to facial attached gingiva - Broad zone on palate - Lips, tongue
What happens in immunologic reactions to local agents (stomatitis venenata)?
• Antigens presented to T-cells by Langerhans cell
• 2nd exposure:
- Lymphocytes –> cytokines –> clinical and histologic changes
• Agents: toothpaste, mouthwash, candy, chewing gum, cinnamon, amalgam
Clinical features of immunologic reactions to local agents
- Changes occur adjacent to causative agent
- Acute or chronic
- Localized – isolated allergen
- Widespread – food, drink, etc
Acute contact stomatitis
- Burning
- Red (mild to brilliant)
- +/- edema
- Superficial ulcers (like RAU)
- Vesicles rare
Chronic contact stomatitis
- Red or white-adherent
- Focal erosions within these areas
- Some allergens (in toothpastes) –> widespread erythema with desquamation of superficial epithelium
What is cinnamon contact stomatitis?
- Cinnamic aldehyde has a hyacinth odor and is often used as a fragrance in perfumes, cosmetics, detergents, and as flavoring in chewing gums, confectionary, ice cream, oral hygiene products and soft drinks.
- Concentration up to 100x normal spice.
- Reactions linked to contact time and frequency
Organic compound that gives cinnamon its flavor and odor
Cinnamaldehyde
Cinnamaldehyde
- Organic compound that gives cinnamon its flavor and odor
- Pale yelow, viscous liquid that occurs naturally in the bark of cinnamon trees and other species of the genus Cinnamomum
- The essential oil of cinnamon bark is about 90% cinnamaldehyde
Clinical features of cinnamon contact stomatitis…
• Pain and burning
• Pattern linked to mode of delivery
- Toothpaste: diffuse
• Plasma cell gingivitis
• Erythematous mucositis
- Gum and candy: localized
• White due to hyperkeratosis with ragged surface
- Like morsicatio
• Bilateral buccal mucosa
- Oblong patch
- White on red base +/- ulcer
• Lateral tongue
- Vertically corrugatedHistology of cinnamon contact stomatitis
Lichenoid and perivascular mucositis
What is plasma cell gingivitis?
• 1970s chew gum –> “plasma cell gingivostomatitis”
- Entire gingivae bright red & enlarged
- Cinnamon possible allergen
- Lips dry, atrophic, fissured
- Angular cheilitis
- Tongue red, loss of papillae, enlarged, furrowed
• Recently
- Much less common
- Allergy to specific toothpaste, food, etc (not chew gum)
- Many cases idiopathic
- Lesions often limited to gingivae
Epithelium histology of plasma cell gingivitis as caused by 1970s chew gum
- Psoriaform hyperplasia & spongiosis
* Intense exocytosis with neutrophil microabscesses
Lamina propria histology of plasma cell gingivitis as caused by 1970s chew gum
- Dilated capillaries
* Dense chronic inflammatory cell infiltrate, mainly plasma cells
Current histology of plasma cell gingivitis
- Less involvement of epithelium
* Less dense plasma cells
Mucosal allergic reaction to amalgam
- Must rule out toxic reaction, frictionless keratosis, etc.
- True lichenoid hypersensitivity reaction to amalgam (Hg) rare
- Localized
- Clinical and histology like lichen planus: “Lichenoid contact stomatitis”
- Disappears when restoration removed (as does frictional keratosis)
Drug induced gingival fibrous hyperplasia
- Numerous medications have been reported to cause this condition
- Those with the strongest association are cyclosporine, phenytoin, and nifedipine
- These agents may interfere with normal intracellular degradation of collagen
Nonimmunologic mucosal reactions to systemic medications include…
- Drug-induced gingival fibrous hyperplasia
* Anticancer therapy
Etiology of immunologic mucosal reactions to systemic medications (Stomatitis medicamentosa)
• Triggered by antigenic component (hapten) on drug molecule
• Reaction depends on:
- Immunogenecity of drug
- Frequency of use
- Route of administration
• Mechanisms
- IgE-mediated (type I)
- Cytotoxic (antibody binds to drug already on cell surface) [type II]
- Circulating antigen-antibody complexes (type III)
- CD8 cytotixic T cells and CD4 helper T cells recognize antigens (type IV)
Drug-induced allergic changes resemble the following oral mucosal diseases clinically, histologically, and immunologically…
• These drug reactions patterns resemble several oral mucosal diseases:
- Angioedema
- Erythema multiforme
- Anaphylactic stomatitis
- Pemphigus-like
- Intraoral fixed drug reaction
- Lichenoid reaction
- LE-like drug reaction
- Nonspecific vesiculo-bullous or aphthous-like lesions
• These drug reactions are often bilateral
Immunology of drug-induced allergic changes
• I.F. studies in most cases do not separate drug reactions from primary vesiculo-ulcerative diseases, with some exceptions:
- In some lichenoid cases, I.I.F. for IgG shows a “string of pearls” due to circulating basal cell cytoplasmic antibody
- LE-like reasons are dsDNA negative with most (not all) drugs [SLE itself is dsDNA positive]
Pemphigus like drug reactions
- A variety of drugs have been implicated in the onset of drug-induced pemphigus
- Some of these drugs induce antibody formation, which results in acantholysis via a mechanism identical to that found in idiopathic pemphigus
- Other drugs are postulated to induce acantholysis directly in the absence of antibody formation
Lichenoid mucositis
- Lesions with clinical and/or histological resemblance to classical lichen planus
- May exhibit some variation from classical features
- These cases are often drug-related
Histology of lichenoid mucositis
- Classical lichen planus +/- other features
- Eosinophils
- Plasma cells
- Deep and perivascular lymphocytic infiltrate
What is acquired angioedema?
- IgE-mediated allergic reaction precipitated by drugs or foods
- These antigens –> IgE production
- 2nd antigenic challenge: mast cells bound with IgE release contents
Etiology of angioedema
• IgE-mediated allergic reaction - Drugs, foods (nuts, shell fish), plants, dust • Contact allergies - Cosmetics, rubber dam, etc • AD hereditary activated complement - Type I - Type II • Acquired activated complement • ACE inhibition --> elevated bradykinin • Other
Clinical presentation of acquired angioedema
- Rapid onset of diffuse edematous connective tissue swelling
- Painless swelling of lips, face, neck
- Effect on GI or respiratory tracts rare but may be fatal
- Usually subsides in 1 to 2 days
Transient lingual papillitis etiology
- Some cases are food allergies
* Some cases due to friction
Clinical features of transient lingual papillitis
• Affects fungiform papillae • Solitary or multiple papules - Red papules with yellow (ulcerated) cap • Sensitive or pain (symptomatic) • +/- fever • Resolve in days, but may recur
What is oral reactive lymphoid hyperplasia?
- Discrete nontender submucosal swellings
- < 1cm diameter
- Color normal or yellowish
What sites are affected in oral reactive lymphoid hyperplasia?
• Foliate papillae lymphoid tissue • Buccal lymph node - Freely movable nodule • Lymphoid tissue aggregates - Floor of mouth - Posterior soft palate • Palatal follicular lymphoid hyperplasia • Waldeyer's ring lymphoid tissue
Acute graft v host disease
- Within first 100 days of transplant
- Affects 50% of bone marrow recipients
- Skin mild to severe like “TEN”
- Severe GI symptoms and liver dysfunction
Chronic graft v host disease
- Continuation of acute GVHD or starts later than 100 days
- In up to 60% of bone marrow recipients
- Mimics A-I diseases (SLE, Sjogren, etc)
- Skin changes resemble lichen planus or systemic sclerosis
Oral changes in graft v host disease occurs in how many cases?
- In 33-75% of acute GVHD
* In ~80% of chronic GVHD
Appearance and histology of oral changes in graft v host disease…
• Lichenoid appearance:
- Histology resembles lichen planus, but inflammatory response is not as intense
- With advanced cases, collagen deposition resembles systemic sclerosis
Clinical features of graft v host disease
• Lichenoid appearance
• Burning
• 2nd candidiasis
• Ulcers
• Xerostomia (immune destruction of salivary glands)
- Minor glands show periductal inflammation in early stages with gradual acinar destruction and periductal fibrosis later
