Pemphigus vulgaris	Mucous membrane pemphigoid
Etiology Target proteins	– Autoimmune reaction – Intercellular keratinocyte protein (desmoglein 3) destroyed by auto antibodies	– Autoimmune reaction to basement membrane proteins: – Lamina 5 – BP 180
Clinical	Intraepithelial blisters	Subepithelial blisters
Site	– Oral mucosa – Skin – Mucosa	– Oral mucosa – Conjunctiva – Skin rarely
Histology	– Intraepithelial clefting – Loss of desmosomal contacts therefore free floating acantholytic Tzanck cells	– Subepithelial clefting – Chronic inflammatory infiltrate
Direct immunofluorescence testing	Circulating auto IgG	No circulating auto IgG

Pemphigus vulgaris

• Autoimmune blistering disorder
• Results in loss of integrity of intercellular attachments within epidermis and mucosal epithelium

Subtypes:

• P. Vulgaris (common)
• P. Vegetans (wart like)
• P. Foliaceus (flower like)
• P. Erythematosus (reddened)

Nikolsky’s sign: Positive – stroke mucosa gently, vesicle or bulla appears

Management: Corticosteroids + Azathioprine + Cyclophosphamide

Prognosis: Good. Fatal if untreated

Mucous membrane pemphigoid

• Autoimmune blistering disorder
• Results in loss of integrity of dermal-epidermal junctions
• Affects oral tissues in 30% of cases
• More severe

Management: Corticosteroids

Prognosis: Fair

Differential diagnosis:

• Erythematous lichen planus
• Linear IgA disease
• Discoid lupus erythematous
• Contact allergy

Etiology

• Immunological disorder – T cell mediated
• Neurogenic inflammation
• Nutritional deficiency – B12, folic acid, iron
• Microbial – Viral, bacteria
• Mucosal healing defects – by cytokine inhibition

Clinical

• Burning/tingling sensation
• Painful recurrent ulceration
• Ulcer on non keratinized mucosa
  • Slightly raised erythematous margin
  • Necrotic base

Histology

• Non specific inflammation + macrophages and mast cells
• Absence of viral infected cells
• Differential diagnosis: Herpetic gingivostomatitis

Subtypes

	Minor aphthae	Major aphthae	Herpetiform aphthae
Size	0-0.5cm	>0.5cm	0-0.5cm
Shape	Oval	Ragged oval, crateriform	Oval
Number	1-10	1-5	10-100
Location	Non keratinized mucosa	Non keratinized mucosa	Any intra oral site

Management

• Corticosteroid therapy + tetracycline mouthwash

Picture

Etiology

• RNA retrovirus – Human Immunodeficiency Virus

Pathology

• HIV – specific affinity for – CD4+ T helper cells – Therefore damage cell mediated immune system
• Enters host – replicates using host DNA – stay latent – cell fusion/cell death
• Notes under Virology

Modes of spread

• Vertical transmission and breast feeding
• Sexual contact
• Parental exposure:
  • Organ transplant
  • Blood transfusion
  • Contaminated needles
  • Artificial insemination

Clinical

1. Systemic signs and symptoms

• Chronic fever
• Weight loss
• Diarrhea
• TB
• Persistent generalized lymphadenopathy
• Encephalopathy (AIDs dementia)
• Other STIs

2. Oral infections

• Fungal:
  • Candidiasis
  • Histoplasmosis
  • Cryptococcus neoformans
  • Penicilliosis

• Viral:
  • Herpes: HSV, VZV, EBV, CMV
  • EBV – Hairy leukoplakia

• Bacterial:
  • PDL disease – Linear gingival erythema, NUG, NUP, Necrotizing stomatitis
  • NOMA
  • TB – Chronic indurated non healing ulcer, TB osteomyelitis
  • Necrotizing fasciitis

• Autoimmune:
  • Recurrent aphthous ulcer
  • Salivary gland disease
  • Idiopathic thrombocytopenic purpura (ITP) – Gingival bleeding, petechia, hamartomas on mucosa, palate and tongue
  • Diffuse infiltrative lymphocytosis syndrome (DILS)

• Protozoa: Leishmania

3. Oral neoplasms

• Most common: Kaposi sarcoma
• Less common:
  • Non Hodgkin’s lymphoma
  • Squamous cell carcinoma

4. Other manifestations

• Cervical lymphadenopathy
• Neurologic:
  • Trigeminal neuropathy
  • Facial palsy
• Aphthous ulcer
• Xerostomia
• Hyperpigmentation
• Exfoliative chelitis
• Lichen planus
• Hairy leukoplakia
• Thrombocytopenia
• Opportunistic infections

Diagnosis

• ELISA
• PCR
• CD4 counts
• CD4 : CD8
• Indirect immunofluorescence – HIV specific IgM

Management

• ARVs eg. Zidovudine, Ritonavir

Clinical features of pediatric AIDs

Age of onset: Neonate to late infancy

Infections:

• Fungi – C. albicans
• Mycobacteria – M. TB, M. bovis, atypical
• Bacteria – S. pneumonia, S. aureus, Gram -ve’s
• Virus – HSV, EBV, VZV, CMV, adenovirus
• Protozoa – P. carinii (Update: Now considered a fungus by the name Pneumocystis jirovecii)

Malignancy:

• Lymphoma
• Kaposi sarcoma – rare

Nutrition:

• Diarrhea
• Failure to thrive

Systemic:

• Fever
• Lymphadenopathy
• Hepatosplenomegaly

Parotid: Diffuse, non suppurative enlargement

CNS: Developmental delays

AIDS dysmorphic syndrome: Variable teratogenicity

Etiology

• Actinomyces israelii

Subtypes

• Cervicofacial
• Abdominal
• Pulmonary
• Cutaneous

Predisposing factors

• Surgery and dental procedures
• Previous infection
• Osteoradionecrosis
• Trauma
• Systemic illness

Mnemonic: SPOTS

Clinical

• Indurated woody hard swelling + multiple discharging sinuses Picture
• Pus discharge – Yellow and granular (sulfur granules)
• Chronic low grade persistent infection

Histology

• Sulfur granules
• Filamentous rays in round colonies surrounded by pleomorphs, giant cells and macrophages

Management

• Penicillin + surgical debulking

• Primary TB
• Secondary TB
• Miliary TB – Diffuse dissemination by vascular system in immune suppressed

Etiology

• Mycobacterium tuberculosis
• Oral lesion secondary to pulmonary TB
• AIDS defining illness

Clinical

• Scrofula – lymphadenopathy on neck Picture
• Fever
• Night sweats
• Malaise
• Weight loss
• Cough
• Hemoptysis
• Intraoral lesion: Indurated chronic non healing ulcer and is painful

Diagnosis

• Mantoux test
• ZN staining for AFB (acid fast bacilli)
• HIV screening

NB: Immunocompromised patients have atypical mycobacteria infections eg. M. avium intracellulare

Histology

• Caseating necrosis/granuloma – cheesy appearance
• Langerhans giant cells
• Inflammatory response

Management

• Directly observed therapy (DOT) – multidrug therapy
• Isoniazid
• Rifampicin
• Ethambutol
• Pyrazinamide
• Streptomycin

Mnemonic: PRIESt

Clinical stages

• Non immune host exposed to TB (skin test positive)
• Primary TB of lung
• Arrested TB in immunocompetent individuals
• Progressive TB – hematogenous, lymphatic, direct spread
• Arrested TB reactivated – secondary TB – progressive TB

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Cervical TB:

• Most common in level 2 nodes
• Lymph nodes > 2cm
• With or without evidence of TB elsewhere
• Clinical: Night sweats, weight loss, fever
• Diagnosis: FNA, ZN staining with AFB, Mantoux test

1. Sexually transmitted (acquired)

Primary – Chancre (chronic ulcer) Picture

Secondary

• Oral mucosal patches
• Condyloma latum
• Maculopapular rash
• Organopathy

Tertiary

• Gumma (non cancerous growth) Picture
• Destructive ulcers
• CNS disease – Neurosyphilis:
  • Meningovascular lesions
  • Tabes dorsalis
  • General paresis
• CVS disease – Aortitis:
  • Aneurysms
  • Aortic regurgitation and gumma

NB: Can go into latency

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2. Vertically transmitted (congenital)

Early

• Spirochetosis
• Dental defects
• Deafness
• Ocular Keratitis
• Bone and joint lesion
• Organopathy

Late: Latency

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Diagnosis

• VDRL (Venereal Disease Research Laboratory)
• RPR (Rapid Plasma Reagin)
• ELISA

Management

• Penicillin
• Tetracycline

Notes under white lesions

Prenatal infection:

• Hutchinson’s incisors – tapered crown + notched incisal edge
• Mulberry molars – Lobulated occlusal surfaces

Picture

Definitions

1. Macule

• Focal area of colour change
• No elevation or depression in relation to surroundings

2. Papule

• Solid raised lesion
• Less than 5mm in diameter

3. Nodule

• Solid raised lesion
• More than 5mm in diameter

4. Sessile

• Tumor/growth
• Base is widest part of lesion

5. Pedunculated

• Tumor/growth
• Base is narrower than widest part of lesion

6. Papillary

• Tumor/growth
• Numerous warty projections

7. Verrucous

• Tumor/growth
• Rough warty surface

8. Vesicle

• Superficial blister filled with clear fluid
• Less than 5mm in diameter

9. Bulla – Blister > 5mm in diameter

10. Pustule – Blister filled with purulent exudate

11. Ulcer

• Loss of surface epithelium ± underlying CT
• Depressed/ excavated

12. Erosion

• Superficial lesion
• Partial/ total loss of surface epithelium
• After rupture of vesicle or bulla

13. Fissure – Narrow slit like ulceration/ groove

14. Plaque – Elevated and flat on surface

15. Petechia – Round pinpoint area of hemorrhage

16. Ecchymosis – Non elevated hemorrhage, larger than petechia

17. Telangiectasia

• Vascular lesion
• Dilation of small superficial blood vessel

18. Cysts

• Pathological epithelium lined cavity
• Filled with liquid or semisolid content

19. Unilocular – Radiolucent lesion – single compartment

20. Multilocular – Radiolucent lesion – several compartments

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Traumatic lesions

Clinical manifestations of trauma

1. Acute/chronic ulcers
2. Red/white lesions
3. Mucositis
4. Reactive hyperplasia
5. Bone exposure and sequestration

Etiology

Physical trauma

• Factitial injury – Self induced/psychological
  • Eg. Cheek biting – subconscious reaction to stress, emotions, boredom
• Riga-Fede disease – Traumatic ulcer on anterior tongue with natal teeth in infants, or repetitive tongue thrusting habit after eruption of 1ry lower incisors
• Frictional hyperkeratosis – white lesion, ill fitting dentures
• Iatrogenic

Chemical burns, thermal burns

Therapeutic radiation

Classification

1. Acute traumatic ulcer

• Pain
• Yellow base, red halo
• Heals in 7 to 10 days

2. Chronic traumatic lesions

• Little or no pain
• Scar formation
• Mimic carcinoma/infective ulcer

Clinical

• Single lesion
• Erythematous
• Non inverted margins
• Clean base covered in pseudomembrane
• Painful
• Disappear in 7-10 days after eliminating cause

Histology

• Loss of epithelium – replaced by fibrin network
• Granulation tissue base
• Scar formation deep in tissues
• Dense inflammatory infiltrate – macrophages and eosinophils

Management

• Observe for 2 weeks to rule out infection
• Topical corticosteroids

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Pathological lesions

Etiology

1. Neoplasm

• Squamous cell carcinoma
• Salivary gland carcinoma

2. Immunological disease

• Lichen planus
• Pemphigoid
• Pemphigus vulgaris

3. Aphthous ulcer/ Canker sore – Multifactorial

4. Infections

• Bacteria:
  • Syphilis
  • Tuberculosis
  • Actinomyces
  • NOMA

• Viral:
  • HIV
  • Herpes

• Fungi
  • Candida

Nb: Chronic infectious ulcers (TB, syphilis, fungal)

• Mimic carcinoma/traumatic ulcer
• Non healing and persistent
• Multiple
• Diagnosis – Biopsy and culture
• Management – Antimicrobial agent

Group of fibrous connective tissue (CT) lesions that occur when over exuberant repair (granulation tissue and scar) follows injury

Types of localized fibrous overgrowths:

1. Fibromatous

• Nodular fasciitis
• Gingival fibromatosis

2. Neoplastic & tumor like lesions

• Neurofibroma
• Giant cell fibroma
• Fibrous histiocytoma
• Malignant fibrous histiocytoma
• Fibrosarcoma

3. Hyperplastic lesions/ localized CT hyperplasia

• Epulides – CT tissue hyperplasia arising from gingiva
  • Fibrous epulis/ focal fibrous hyperplasia
  • Peripheral giant cell granuloma/ giant cell epulis
  • Vascular epulis/ pyogenic granuloma
• Fibroepithelial polyp – firm, painless pedunculated/ sessile polypoid swelling away from gingiva
• Papillary hyperplasia of palate
• Generalized gingival hyperplasia
• Denture induced fibrous hyperplasia

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Fibrous epulis/ focal fibrous hyperplasia

Clinical:

• Pedunculated/sessile mass
• Firm consistency
• Similar colour to gingiva
• Surface may be ulcerated

Histology:

• Cellular fibroblastic granulation tissue + interlacing bundles of collagen fibers
• Inflammatory infiltrate = mostly plasma cells
• Hyperkeratotic epithelium
• Calcification in 1/3 of cases

Management: Surgical excision + full mouth scaling

Picture

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Peripheral giant cell granuloma/ giant cell epulis

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Vascular epulis/ pyogenic granuloma

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Fibroepithelial polyp

Etiology:

• Local irritants eg. calculi
• Overhanging margins
• Restorations
• Foreign bodies
• Chronic biting
• Margins of caries and sharp spicules of bone
• Overextended borders of appliance

Clinical:

• Pedunculated/ sessile growth
• Small lesions, rarely > 1cm

• No malignant potential
• Recur only if chronic irritation persists

Picture

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Generalized gingival hyperplasia

Picture

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Denture induced fibrous hyperplasia

Etiology: Chronic trauma due to I’ll fitting denture

Site:

• Vestibular mucosa
• Mandible lingual sulcus

Clinical:

• Painless folds of fibrous tissues surrounding edge of overextended denture

Histology:

• Hyperplastic epithelium with drop rete pegs
• Connective tissue core
• Early (vascular), late (avascular)
• Leaf like shape

Management:

• Replace or reline denture
• Surgical removal of lesion

Picture

1. Oral squamous cell papilloma

Oral wart/ verruca vulgaris (autoinoculation from wart)

• Etiology: HPV 2, 6, 11, 57

• Clinical:
  • Benign growth originating from epidermis
  • Cauliflower like, corrugated surface, exophytic growth
  • Keratinized – appear white
  • Recurrence/multiple lesions in immunocompromised

• Histology:
  • Long thin finger like projections extending from stratified squamous epithelium, enclosing a central vascular CT core
  • Hyperkeratinized epithelium, contains superficial vacuolated cells

• Management: Conservative excision

Picture

2. Focal epithelial hyperplasia

• Etiology: HPV 13, 32

• Clinical: Multiple nodular soft tissue masses

• Histology:
  • Acanthosis
  • Parakeratosis
  • Enlarged ballooning cells with abnormal nuclei

• Management:
  • Spontaneous regression is common
  • Surgical removal if persistent

Picture

3. Verrucous carcinoma

Low grade variant of OSCC

• Etiology:
  • Tobacco
  • HPV 16 & 18

• Clinical:
  • Seen in elderly patient
  • Slow growing exophytic growth/ patch
  • Locally destructive but rarely metastasis

• Sites: Buccal mucosa > gingiva > tongue > palate

• Histology:
  • Well differentiated carcinoma
    • Little/no dysplasia
    • Little pleomorphism
    • Few mitotic figures
  • Bullous rete pegs with blunt pushing margins
  • Keratin plugs + parakeratosis

• Management:
  • Surgical excision
  • Excellent prognosis

Picture

HIV oral melanosis

• On buccal mucosa, gingival, palate, tongue
• Brown macules
• Multifocal, diffuse, macular brown pigmentation

Picture

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Drug induced melanosis

• Hard palate
• Grey to blue black macules
• In patient taking drug therapies for 4+ months:
  • Quinolone
  • Hydroxyquinolone
  • Amodiaquine
  • Minocycline
  • Cyclophosphamide
  • Zidovudine

Picture

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Physiological pigmentation

• Gingiva
• Brown
• Symmetric and persistent pigmentation
• Normal gingival stippling
• Darker races

• Histology: Melanin in basal keratinocytes & connective tissue macrophages

Pictures

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Oral melanotic macule

• Random
• Brown

• Types:
  • Idiopathic – intraoral freckles
  • Post inflammatory
  • Syndrome associated – Peutz-Jegher, Addison syndrome

• Histology: Excess melanin in basal keratinocytes & melanophagocytosis

Picture

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Melanoma

• Palate, gingiva
• Variable
• Neoplasm of epidermal melanocytes
• Elderly males
• Poor prognosis

• Clinical:

1. Early: Pigmented macule
2. Late:
   • A – Assymetry
   • B – Border’s irregular
   • C – Colour variable
   • D – Rapid increase in diameter
   • I – Induration
   • B – Bleeding
   • S – Satellite lesions (metastases)

• Subtypes:

1. In situ melanoma – prolonged proinvasive junction
2. Invasive melanoma – CT invasion

• Histology:
  • Dark staining intraepithelial melanocytes
  • Malignant round/spindle melanocytes with bizzare nuclei
  • Invading deep tissue

• Management:
  • Surgery
  • Chemotherapy

Picture

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Pituitary hyperfunction

• Adrenocorticotropic hormone (ACTH)
• Melanocyte-stimulating hormone (MSH)

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Other hormonal imbalance

• Pregnancy
• Contraceptive pills
• Female hormones

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Naevus

• Skin/mucosa
• Congenital tumor like malformations of skin/ mucosa – benign proliferation of melanocytes

• Subtypes:

1. Junctional: Melanocytes in – basal layer of epithelium
2. Intradermal: Melanocytes in – superficial layer of epithelium
3. Blue naevus: Melanocytes in – deep CT

Picture

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Smokers melanosis

• Anterior labial mucosa
• Abnormal melanin pigmentation:
  • Cigarette smoking
  • Females on birth control pills

• Histology: Melanin in basal keratinocytes and CT macrophages

Picture