Oral Mucosa Flashcards
Describe hard palate mucosa
Layer of keratin on surface to resist stresses of mastication. Keratinised stratified squamous epithelium, followed by lamina propria.
Small amount of adipose tissue and mucous salivary gland tissue
Difference between masticatory mucosa and lining mucosa
Masticatory - found gingivae and hard palate
Masticatory mucosa is keratinised stratified squamous epithelium
Basal cell layer only few cells thick, majority prickle cell layer. Granulayer layer beneath surface where keratin is being made.
Masticatory mucosa formly mixed to underlying mucoperiosteum, designed to resist stresses of mastication, little submucosa (as dont want flexibility)
Lining - found uvula, soft palate, buccal mucosa, ventral tongue, FOM
Non-keratinised, loose submucosa to allow flexibility, no granular layer as no keratin production
4 types of papillae:
Filiform - most numerous
Fungiform - larger than filiform
Foliate - lateral, posterior aspect of tongue
Circumvallate - posterior 3rd of tongue, V shape
Taste buds found on foliate, fungiform and circumvallate
Filiform involved in abrasion and mastication, no taste buds
Leukodema
Presents symmetrically, typically on buccal mucosa but can be found lateral portions of tongue, FOM, labial surface and lip
Opacification of buccal mucosa - milky-white translucent area, diffuse appearance
No clear border
May have association with smoking
More apparent in African ethnic backgrounds
Will disappear on stretching
Asymptomatic
Differentials for leukodema
Leukodema biopsy will show clear epithelial cells that are larger than normal but wouldnt not routinely biopsy this
Differentials:
White sponge naevus - bilateral white patches but are thickr, folded, more extensive. WSN not diappeare on stretching
Frictional keratosis (cheek biting) - patch would be in occlusal plane, see sharp cusps
Lichen planus - classic appearance, white reticulations and lace pattern, more erosive and red areas, may have skin lesions
Geographic tongue
Islands of erythema with white borders - red patches with white halo Asymptomatic or mild soreness Aggravating factors - spicy/acidic Predominantly dorsum tongue Difflam to take edge off soreness
Differentials:
Lichen planus - red and white patches usually intermingled, not discrete. Rarely only affects dorsum
Frictional keratosis - associated sharp tooth, denture e.g. - usually all white
Fordyce spots
White/yellow speckling Asymptomatic Ectopic sebaceous glands Often in elderly Histology - normal mucosa with sebaceous glands in lamina propria
White sponge naevus
AD
Family history but may skip generations
Point mutation in keratin 4 or 13 genes
Clinical: •Bilateral •Cheeks and floor of mouth •Thick , white folds, wrinkled – ‘ebbing tide’ •Life long •May affect other mucosal sites •Won’t disappear on stretching, don’t rub off •Often presents in childhood
Histology:
•Very hyperplastic epithelium
•Acanthosis – thickness in prickle cell layer
•No inflammation
•Epithelial cells have very pink cytoplasm – related to abnormal keratin they are forming
White sponge naevus differentials
Lichen planus
Lichenoid drug reaction
Chronic cheek biting
Leukodema
Causes of traumatic ulceration
Trauma from dentures/teeth
Chemical burns
Irradiation for malignancy
Frictional keratosis
White patch caused by continual trauma - usually sharp cusps/ortho wires/dentures
Histology:
Keratin on surface of buccal mucosa (unusual)
Acanthosis of epithelial layer
No inflammation
Diagnosis - must be able to demonstrate lesion caused by trauma. If remove cause, lesion should regress. If not, consider other white lesions i.e. leukoplakia
Trauma specific to oral mucosa
Frictional keratosis
Stomatitis nicotina
Papillary hyperplasia of palate
Chemical burns
Stomatitis nicotina
• Palate in pipe and cigar smokers • Not a pre-malignant lesion • Positive correlation between intensity of smoking and severity • White bumps with red centre • Mixture of chemical trauma and heat trauma Treatment: • Stop or reduce smoking • Lesions may disappear • Regular review
Paillary hyperplasia of the palate
- Caused by ill-fitting dentures
- Symptomless – erythematous overgrowth of mucosa
- Corresponds to outline of denture
Management: • New dentures • Excision of papillary projections for advanced cases • Not pre-malignant • Usual advice about denture hygiene
Factors influencing healing
- Primary or secondary intention – wounds closely opposed heal faster than those separated
- Foreign body – acts as a focus of infection and delays healing
- Vascular supply – reduced blood supply reduces healing capacity
- Nutritional deficiencies – vitamin C
- Irradiation – reduces blood supply
- Malignancy – failure to heal e.g. non healing tooth socket
- Infection – reduces healing capacity
- Poor immune response – leukaemia, diabetes, immunosuppression
Localised swellings of gingival tissue
Fibrous hyperplasia (fibro-epithlial polyp) Pyogenic granuloma Peripheral giant cell granuloma Gingival cysts Bohns nodules
Generalised swellings of gingival tissue
Chronic hyperplastic gingivitis Leukamic infiltration Endocrine related (puberty, pregnancy) Crohn's disease Gingival fibromatosis Drug induced hyperplasia
Fibrous epulis (fibrous hyperplasia/fibro-epithelial polyp)
Epulis = gingival swelling, if lesion present elsewhere of gingiva then = fibro-epithelial polyp
Pedunculated or sessile
Same colour as normal mucosa as overlying epithelium normal
Caused by trauma
Overgrowth of fibrous CT
Covered by hyperkeratinised stratified squamous epithelium
Firm (collagenous centre)
Painless unless traumatised
Magaement of fibro-epithelial polyp
Excision
Remove cause
Send for histopath to check correct diagnosis
Histopath - CT overgrowth, hyperkeratinised startiifed squamous epithelium
Pyogenic granuloma
Red/blue/purple vascular growth Sessile or pedunculated Rapid growth Bleeds easily <40 years usually Common in pregnancy and puberty Caused by trauma - e.g. plaque, calculus, denture, ortho
Histo - overgrowth of very vascular granulation tissue (endothelial cells and fibroblasts) - explains red colour clinically
Management of pyogenic granuloma
Excise, warn can recur
If pregnant - avoid surgery until 3rd trimester
Remove inducing factor e.g. plaque, calculus
Lesions can mature into dense fibrous tissue (fibrous epulis)
Peripheral giant cell granuloma
Blue-ish sessile or pedunculated swelling on anterior gingiva Anterior Mandible > maxilla <40 years May cause superficial bone resoprtion
Histo: multinucleated giant cells, vascular fibrous tissue
Histological diagnosis - giant cell lesion
Radiographic investigation needed to exclude central giant cell lesion that has eroded through buccal plate appearing as peripheral giant cell lesion. X-ray would show well-defined, corticated margins causing expasion if CGCG
CGCG histologically same as hyperparathyroidism so blood test (serum calcium and alkaline phosphatase) to exclude
Management of peripheral giant cell granuloma
Excise and currettage of bone to prevent recurrence
Determine whether lesion has arisen in gingiva or bone - x-rays
Bloods to rule out hyperparathyroidism
Bohns nodules and Epstein pearls
Epstein pearls - midline where palatal shelves fuse, seen in babies, tend to disappear
Bohns nodules - similar to above but appear on gingival crest
Gingival fibromatosis
Hereditary - AD Lifelong Pale pink, firm overgrowth May cover and submerge teeth May regrow after removal Treatment - gingivectomy, may recur
Chronic hyperplastic gingivitis
Associated with poor OH
Erythematous ginigva, bleeding on probing
Hormone related gingival hyperplasia
Exuberant response to plaque
Puberty and pregnancy
Bleeds easily on probing, red, erythematous
Gingival hyperplasia in scurvy
Lack of vitamin C Failure to synthesise collagen Loss of teeth Inflammatory type hyperplasia Very rare in UK
Gingival hyperplasia associated with leukemia
Red, swollen gingivae May exude pus Ulceration Response in excess of amount of plaque May be associated with petechial haemorrhages, tiredness
Drug induced gingival hyperplasia
Nifedipine (anti-hypertensive), cyclosporin (immunosupressant), phenytoin (anticonvulsant)
Gingiva pale. lobulated surface, little inflammation
Management - surgical excision, improve OH, change drug regime if possible
Histologically - dense fibrous tissue, little inflammation, elongated rete ridges
Squamous cell papilloma
Benign neoplasm HPV driven
Pedunculated or sessile
Commonly on palate
HPV 11 & 16 - non-oncogenic
Overgrowth of epithelium which is hyperkeratinised - white appearance
Cauliflower like appearance
Histo - surface thrown into fronds, dense vascular connective tissue core
Management - excise with margins, reassurance unlikely to recur
Heck’s disease (focal epithelial hyperplasia)
Multiple papillomas HPV 13 & 32 Multiple flat viral warts May resolve spontaneously/excise Discrete populations e.g. Inuit/central America
Fibrous hyperplasia (of oral mucosa)
Continued trauma
Common on cheeks, tongue, lip
Mucosal coloured, firm nodule
Hist - fibrous CT core with lots of collagen with stratified squamous epithelium on surface
If occured on gum - would be fibrous epulis and covered with hyperkeratinised ……………
Pyogenic granuloma (of oral mucosa)
Caused by trauma
Red/red-white
Overgrowth of vascular granulation tissue
Usually ulcerated
Traumatic neuroma
Haphazard overgrowth of nerve fibres Following trauma/traumatic extraction Mental region Painful Managament - excise
Lipoma
Benign neoplasm Composed of fat Yellow/pink Smooth surface Common cheek and tongue Management - excise
Haemangioma
Type of hamartoma
Blue/blue-purple colour
Excess blood vessels
Localised or diffuse
Apply pressure, will blanch then fill up again with blood
Management - excise but care as could be a larger vascular malformation behind what can be seen intra-orally
Sturge-Weber syndrome
Congenital
Characteristic features - port wine stain, glaucoma, seizures, varying degrees of mental retardation
Mucocele
Clinical terms to describe 2 types of swelling:
mucus extravasation - salivary duct damaged, mucin spilt out into CT forming swelling
mucus retention cyst
Mucocele will go up and down
Management - excise along with damaged duct
What is an ulcer
A full thickness loss of epithelium Exposes underlying connective tissue Ulcer covered by slough Mixed inflammatory infiltrate Painful
Differentials for ulcers
Neoplastic e.g. SCC
Traumatic e.g. sharp tooth
Idiopathic e.g. RAS
Infective e.g. syphilis
Developmental e.g. epidermolysis bullosa
Manifestation of systemic disease e.g. Crohn’s
Manifestation of dermatological disease e.g. lichen planus
Causes of single episode ulcers
Trauma - physical, chemical
Malignancy - SCC, salivary neoplasm, lymphoma
Infective - TB, syphilis, HSV
Drugs - methotrexate
Single episode ulcer management
Reassurance
Remove cause
Difflam/corsodyl if needed
Monitor - should show signs of improvement
Causes of single episodes of multiple ulcers
Herpes simples Herpes zoster Hand, foot and mouth Herpangina Iatrogenic - nicorandil, methotrexate, methyldopa, pencillamine, allopurinol, gold, cytotoxics, indomethacin
Mgt drug related - liaise with GP or Dr
Mgt of infective - normally self-limiting, may requite anti-fungals/Abs/acyclovir
Recurrent episodes of multiple ulcers
RAS Muco-cutaneous disorders Behcets disease Recurrent erythema multiforme Other systemic disorders
Types of RAS
Minor RAS
Major RAS
Herpetiform RAS
Minor RAS
80% of ulcers Usually between 10-30 years Size - 3-8mm, must be less than 10mm for minor RAS Duration ~7 days Normally non-keratinised mucosa Variable ulcer free period Front of mouth Heal without scarring
Major RAS
10% of ulcers Variable size, must be over 10mm Last longer - 3 weeks-3 months Single or multiple Heal with scarring Non-keratinised mucosa but can affect masticatory mucosa
Herpetiform RAS
<5% ulcers
Dozens of small ulcers (1-2mm)
May coalesce to form larger, irregular ulcers
Mainly FOM, margins and ventral surface of tongue
Last 7-10 days
Not associated with herpes infection (no vesicles)
Treatment - often heal themselves, symptomatic - doxycycline MW
Contributory and pedisposing factors for aphthous ulcers
Contributory:
Stress
Trauma
Hormones
Smoking
Predisposing:
Hematological deficiencies - b12, folate, Fe
Neutropenia
Immune deficiency e.g. HIV+
GI tract disease - coeliac, Crohn’s, UC
Vitamin deficiency - B1, B2, B6
Food intolerance - chocolate, benzoates, cinnamon
RAS investigations
FBC, ferritin B12 and folate
Coeliac screen
Other tests according to history e.g. food allergens
Management for RAS
Preventative: Correct haematological deficiencies Treat underlying systemic disease Remove trauma Dietary elimination OHI/diet advice
Suppressive treatment (local): Topical steroids Hydrocortisone pellets (Corlan) Beclomethasone spray Betamethasone mouthwash Flixonase nasules
Systemic:
Prednisolone
Thalidomide
Azathioprine
Behcets disease
• Named after a Turkish physician • Serious systemic disease: o Blindness o Neurological damage o Severe oro-genital ulceration o Vasculitis o Death • Mainly young adult males ~30years • Male to female ratio = 2.3:1 • Increased incidence in Japan and Turkey
International study group criteria:
• Recurrent oral aphthous ulceration
Plus two of the following:
• Recurrent genital ulcers
• Uveitis, cells in the vitreous or retinal vasculitis
• Skin lesions – erythema nodosum, acne like papulopustular lesions
• Positive pathergy test
• Other common features – arthriris, GI lesions, CNS involvement, vascular lesions etc
Management:
• Multi-disciplinary approach – oral medicine, dermatology, rheumatology, ophthalmology
Ulcer - exam qs
- What causes of ulceration do you know?
- What investigations would be appropriate? E.g. management of cancerous ulcer vs RAS ulcer
- Describe your management of a non-healing ulcer
GORD
Common
Risk factors - obesity, smoking, alcohol
Symptoms of dyspepsia (heartburn)
Risk of Barretts oesophagus - metaplasia of SSE to columnar epithelium with degrees of dyplasia - can eventually become carcinoma
Oral effects - erosion and halitosis
Treatment - proton pump inhibitors
Coeliac disease
Affects 0.5-1% population
Any age
Genetic susceptibility
Intolerance to a-gliadin peptides in gluten found in wheat, barley, rye
Pathogenesis - exposure, proliferation of lymphocytes, damage to lining of gut, crypt formation, sub-villous atrophy - affects absorbtion, in duodenum and jejunum mostly
Oral effects of coeliac
Malabsorption - iron (anaemia), calcium, vit D, B12
Clinical features:
Diarrhoea and steatorrhea (fatty poo)
Wasting, loss of apetite
Abdo discomfort/pain
Tiredness/weakness
Peripheral neuropathy and CNS disturbances
Tetany and osteomalacia
Dermatitis herpetiformis
Increased risk of intestinal neoplasms (lymphoma)
Oral manifestations: Malabsorption gives rise to anaemia resulting in... Oral ulceration Glossitis Candidiasis Angular chelitis Hypoplasia of enamel of permanent teeth
Diagnosis and treatment of coeliac
Diagnosis:
History and clinical signs
Blood tests - FBC and haematinics, anti-endomysial Abs, tissue transglutaminase, anti-gliadin Abs, anti-reticulin
Endoscopy and jejunal mucosal biopsy - gold standard
Treatment:
Exclusion diet to remove gluten
Replacement of haematinics (iron, folate)
Regular monitoring due to increased risk of T-cell lymphoma and other bowel malignancies
Crohn’s
• Young adults, western world
• Any part of GIT:
o May affect several separate areas (skip lesions)
o Mostly terminal ileum and ascending colon
o Can also affect extra-gastrointestinal sites e.g. skin
• Transmural inflammation
o Granuloma formation – cobblestone appearance
o Biopsy of bowel would show granuloma inflammation – granulomas congregate under mucosa giving cobblestone appearance
o Wall is thickened and lumen narrowed
o Aphthous-like ulceration and fissuring
o Fistulae and abscesses
• Chronic inflammation
• Lymphoid hyperplasia
• Clinical features (relapsing and remitting):
o Abdominal pain
o Diarrhoea
o Weight loss
o Malabsorption – B12, bile salts
o Variable presentation, depends on severity and site and often intermittent
Oral manifestations of Crohn’s
Ulceration Glossitis Lip swelling Cobblestone mucosa Tissue tags Fissures and ulcers Angular chelitis Mucosal inflammation esp of attached gingiva
Other diseases that show granulomatous inflammation
Crohns
Sarcoidosis
TB
OFG
Management of Crohn’s
Investigations:
Biopsy
Blood tests - FBC, haematinics, gut antibodies, ACE (exclude sarcoid)
Onward referral
Treatment: Symptomatic relief - Difflam Topical measures first for oral manifestations Immunosuppresants - methotrexate, azothioprine Replacement therapy Anti TNF Abs, infliximab etc Elemental diets Surgery
Oro-facial granulomatosis
- Oral features of Crohn’s disease with no clinical features of gut involvement
- Separate entity or Crohn’s disease?
- Cobblestone appearance of mucosa
- Lip swelling, angular cheilitis
- May have an allergic aetiology
- Responds to an exclusion diet (not all cases)
Other causes of lip swelling need excluding:
• Crohn’s
• Sarcoidosis
• Foreign-body reactions
• Melkerson-Rosenthal syndrome e.g. triad of lip swelling, fissured tongue and facial palsy
• Infections (rare) – TB, syphilis, leprosy
Management:
• Surgery in severe cases
• Topical and intralesional (inject) steroids (temporary relief)
• Systemic drugs e.g. azathioprine
• Exclusion diet: Chocolate, Crisps, Carbonated drinks, Carvone, Cinnamon, Benzoates – E210-E219 – tomatoes, fruit juices, carbonated drinks, pickles
Ulcerative colitis
- Affects large intestine and rectum only – tends to be a continuous region of variable extent
- Inflammation extends no further than lamina propria
- Inflamed, bleeds easily, later ulceration develops, chronic inflammatory infiltrate
Signs: • Bloody diarrhoea • Pain • Weight loss • Tiredness • Iritis, ankylosing spondylitis etc
Oral manifestations:
• Oral ulceration – due to deficiencies
• Pyostomatitis vegetans – affects gingiva
Gardeners
• Autosomal dominant, APC gene mutation
• Multiple colon polyps, epidermoid cysts, osteomas, thyroid cancer, fibromas
• Risk of colon cancer in these individuals age 21 is 10%, by age 50 its 95%
• Oral manifestations:
o Osteomas
o Odontomes
o Supernumerary teeth
o Osteomas develop first, often 10-30 years, identify on OPT, early referral
Peutz Jehgers syndrome
- Autosomal dominant
- Hamartomatous polyps (only small risk of developing cancer)
- But have increased risk of cancer in ovaries, pancreas and liver
- Pigmented macules on the lips and oral cavity – develop in childhood so early diagnosis
Haematological disorders
Anaemia - iron deficiency, macrocytic Angina bullosa hameorrhagica Stem cell transplants/GVHD Neutropenia/agranulocytosis Leaukaemias
Anaemia
• Decreased ability of the blood to carry O2
• Hb concentration below normal range - <13.5g/dl in males, <11.5d/dl in females
• Multifactorial – can be due to:
• Decreased numbers of RBC:
o Loss/destruction of RBC – injury, chronic diseases, infections, sickle cell anaemia, haemolytic anaemias e.g. spherocytosis, red cell auto-Abs
o Failure of production – low Fe, folate, B12, aplastic anaemia, leukaemia, thalassaemia, renal failure gives decreased erythropoietin
• Reduction of concentration of haemoglobin e.g. blood loss or hypervolaemia
• Reduced ability of RBCs to carry oxygen e.g. sickle cell anaemia and thalassemia
Anaemia by morphology of RBC:
• Normocytic anaemia e.g. blood loss – blood cells look the same
• Macrocytic anaemia e.g. B12 or folate deficiency – blood cells are larger than normal
• Microcytic anaemia e.g. iron deficiency – blood cells smaller than normal
Iron deficiency anaemia
Iron deficiency anaemia:
• Most common type world-wide
• 30% world population
o Inadequate intake – diet/malabsorption e.g. coeliac
o Increased loss e.g. GI bleed
o Increased demand e.g. pregnancy
• Hypochromic (less Hb) microcytic anaemia (small)
Systemic features – iron deficiency anaemia: • Lethargy • Dyspnoea • Skin and nail changes • Mucosal changes • Oesophageal webbing • Tachycardia/palpitations • Cardiac failure/exacerbation of cardiac disease (as heart working harder to get O2 around body)
Macrocytic anaemias
• Macrocytosis - rise in mean cell volume above normal range 80-95fl in adults, lower in children • Causes: o Dietary deficiency of B12/folate o Alcohol o Malabsorption o Liver disease o Hypothyroidism o Increased demand e.g. pregnancy o Drugs e.g. azothioprine can affect folate stores
Vitamin B12 deficiency
• Absorbed in ileum
• Dietary insufficiency – uncommon as many foods fortified
• Gastro-intestinal disease e.g. Crohns
• Pernicious anaemia:
o Auto-immune gastritis
o Lymphocytes damage parietal cells in stomach
o Parietal cells produce intrinsic factor and acid – intrinsic factor is needed in small intestine to absorb B12
o B12 not absorbed in small intestine
o Achlorhydria – low HCl
Folate deficiency
- Absorbed in upper small intestine
- Dietary insufficiency
- Malabsoprtion esp. in coeliac
- Drugs e.g. anticonvulsants, suphasalazine
Systemic features - megaloblastic anaemia
- Pallor
- Jaundice
- Neaurological changes
- Neural tube defects – e.g. spina bifida
- Gonadal dysfunction
- Mucosal changes
- Cardiovascular disease
- Risks with GA
Oral manifestations of anaemia
- None – if mild
- Pallor when Hb <8g/dl
- Oral ulceration and exacerbation of RAS
- Mucosal atrophy/stomatitis/glossitis
- Depapillated, smooth tongue
- Altered taste
- Oral candidosis
- Worsening of existing mucosal pathology
- Sometimes linked to burning mouth syndrome
- Dysphagia – oesophageal web, Plummer Vinson syndrome
Leukaemia
• Malignant diseases of blood forming cells in bone marrow
• One type of WBC produced in excess, at detriment of others
• Acute:
o Lymphoblastic – children (85%) and middle age
o Myeloid – older adults and children
• Chronic:
o Lymphocytic – adults
o Myeloid – adults
• Generally acute more in children and more aggressive, chronic more in adults and less aggressive
Acute leaukameia - symptoms:
Symptoms due to bone marrow failure or organ infiltration: o Signs and symptoms of anaemia o Bacterial infections – mouth, throat, chest, skin, peri-anal o Delayed healing o Bruising and healing o Bone pain o Lymphadenopathy o Hepatosplenomegaly
Chronic leaukaemia - clinical features and oral manifestations
clinical features: • Anaemia • Bleeding • Infection • Splenomegaly • Weight loss • Fatigue • Sweating
Oral manifestations: • Gingival inflammation and swelling • Ulceration (cytotoxic drugs/infection) • Increased susceptibility to oral infections • Bleeding
Stem cell transplant/GVHD
• Chemotherapy or chemo-radiotherapy • Transplant of own or donor stem cells • May lead to GVHD o Lichen planus o Sjogren’s like syndrome – dry mouth, dry eyes, burning mouth
Multiple myeloma
• Tumour of monoclonal plasma cells
• Plasma cells produce and secrete polyclonal Ab’s but in multiple myeloma, they only produce monoclonal protein/Ab, produced in excessive amounts
• Ig light chain of Ab congregates in urine, can test with Bence-Jones protein in urine
• Abnormal plasma cells can grow in bones – bone pain, osteoporosis, osteolytic lesions
• Recurrent infection
• Anaemia
• Renal failure
• Amyloidosis
Amyloidosis:
• Fibrillar protein Ig light chain building up in tissues
• Amyloid deposits
Leucopenia
- Reduction in white cell population
- Primary – reduction in haemopoiesis
- Secondary – auto-immune disease, infection, drug therapy (e.g. carbamazepine), HIV
- Increased risk of opportunistic infections
Cyclical neutropenia
- Rare
- Unknown aetiology
- Most common in childhood
- Neutropenia
- Average cycles of 21 days
- Prone to infections in period of neutropenia
Oral manifestations:
• Ulcerations – irregular, any surface, may heal with scarring within 2/52
• Gingivitis
• Periodontitis
• Susceptibility to infection e.g. candidiasis
• Management – supportive, self-limiting
Angina Bullosa Haemorrhagica (ABH)
- Idiopathic
- Can occur in thrombocytopenia
- Diagnosis – history and clinical signs
- FBC and clotting screen
- Reassure
- What are the oral effects of Crohn’s disease?
- What other conditions can share similar features?
- Describe how you would manage the oral effects of anaemia.
Allergy
Autoimmunity
Hypersensitivity
When the immune system responds in an exaggerated or inappropriate way to an extrinsic antigen
Autoimmunity - when the immune system responds in an exaggerated or inappropriate way to an intrinsic antigen
Hypersensitivity - when the immune system responds in an exaggerated or inappropriate way resulting in harm i.e. allergy and autoimmunity both forms of hypersensitivity
Hypersensitivity
On exposure SECOND time to antigen Is a characteristic of individual Split into: type I - immediate/anaphylaxis type II - cytotoxic type III - immune complex type IV - delayed
I - III antibody mediated, IV - cell mediated
Type I hypersensitivity
Acute hypersensitivity/anaphylaxis
IgE mediated
On 1st exposure - Ag bind to B cell, B cell turns into plasma cell which releases Abs into blood stream. IgE Abs bind to receptors on surface mast cells
On 2nd exposure - Ag binds to receptors, receptors cluster and transmit intracellular signal, causing mast cells to degranulate, stimulating histamine release.
Histamine release causes: Vasodilation Bronchospasm Increased vascular permeability i.e. oedema Urticarial rash Increased nasal and lacrimal secretions
Dgx: wheel and flare skin test.
Type II hypersensitivity
Ab mediated hypersensitivity - cytotoxic
Abs target self-Ags - usually IgG/IgM which induce cell damage or inflammation
Activate either:
ADCC
Complement
Type II hypersensitivity important in acute transplant rejection (GvH) and autoimmune diseases e.g pemphigus/pemphigoid
Type III hypersensitivity
Immune complex mediated hypersensitivity
Immune complexes form between Ag and Abs - bind to RBC and be destroyed in spleen
However some people - these complexes may insert themselves in BV’s where they become fixed and start to induce complement activation and neutrophil binding
Immune cells try and destroy fixed complex, but it is too big so end up secreting damaging substances onto nearby cells which become damaged (Self-harm)
Immune complex mediated hypersensitivity important in immune complex mediated vasculitis e.g. erythema multiforme and SLE
Type IV hypersensitivity
Extrinsic antigen gets into mucosa
Langerhan’s cells in oral mucosa intercept and process as Ag and secrete molecules that prime infected part of epithelium. Ag stimulates keratonicytes to release TNF.
Langerhan’s cells then migrate into draining lymph nodes e..g neck where they display Ag on their surface for T cells. Ag specific T cells activated and clonal expansion and preferentially circulate to oral mucosa (from lymph)
Primed epithelial cells secrete TNF which activates local BVs. T cells stick to BV and then oral mucosa secretes CCL5 which recruits activated T cells into tissue.
TNF and INF released which stimulate keratinocytes to express ICAM-1 and MHC-II which allows T cells to bind to basal kertinocytes and migrate between them. Keratinocytes present Ag to T cells which results in activation and proliferation of Ag specific T cells. Cytotoxic B cells kill basal keratonicytes
Hxt: dense band of T cells under epi without some infiltrating into epi
Relevant for: Delayed type hypersensitivity reactions Contact dermatitis Lichenoid reactions Lichen planus
T cell mediated killing mechanisms:
Fas/Fas-ligand mediated apoptosis
Perforin/Granzyme B
Allergies
Growing problem
Increase in children suffering from asthma and allergic diseases amongst adults
Dentists and nurses becoming increasingly senstised to latex, dental materials
Pt’s increaseingly sensitised to latex, drugs, materials used in dental surgery
Sources of pigment
Melanin (majority)
Haemosiderin - breakdown product from RBC, brown
Amalgam or heavy metals
Chromogenic bacteria
Melanin
Produced by melanocytes
Found in basal 3rd of epithelium - normal
Melanocytes package melanin in melanosomes (organelle) which are distributed to basal cells so appear pigmented
Brown pigment on H&E slides
Melanin transferred to adj keratinocytes via melanosomes
Melanocytes not visible as are clear cells, only become visible if atypical
Increased melanin production without numbers of melanocytes = NORMAL cause of pigmented lesions
Increased number of melnocytes or increased size melanocytes = worrying sign, could indicate melanoma
Haemosiderin
Breakdown product of RBC - endogenous
When haem broken down into iron, can be stored in diff ways
One way it is stored is via haemosiderin which is stored in cells and macrophages
Brown on h&e slides
Amalgam or heavy metals
Include bismuth, lead, silver, mercury, amalgam, arsenic, gold
Usually exogenous e.g. from metal restorations
Can be deposited due to drugs e.g. pepto-bismol contains bismuth which can react with sulphur in saliva and create bismuth sulphide - grey/black pigmentation, can be seen on tongue
Sources of exposure can also be occupation
Chromogenic bacteria
Bacteria that produce pigment
Aspergillus and actinomyces
Often seen in hairy tongue
Bacterial enzymes act on iron in saliva
EXOGENOUS pigmented lesions
Amalgam tattoo
Foreign body tattoo
Heavy metal (occupational or drugs)
Black hairy tongue (bacteria)
ENDOGENOUS pigmented lesions
Developmental
Acquired
Neoplastic
DEVELOPMENTAL: Phsyiological (M) Peutz-Jehgers syndrome (M) Haemochromatosis (H) Pigmented naevus (M)
ACQUIRED: Addison's disease (M) Drug induced (M) Post inflammatory (M) Smokers melanosis (M) Melanotic macule (M)
NEOPLASTIC:
Melanoma (M)
Amalgam tattoo
Silver/grey colour, would appear adjacent to amalgam restoration
Histology shows keratinised stratified squamous epithelium with black pigment in CT running along collagen fibres and around BVs - characteristic of AT
Wouldn’t biopsy as radiograph can confirm presence of radiopaque deposits of amalgam
Heavy metal
Pigmentation along gingival margin - common place for heavy metal staining due to more bacteria in gingival crevices
Histology similar to amalgam tattoo
Wouldnt biopsy because characteristic appearance
Increasingly rare now
Black hairy tongue
Affects posterior dorsal tongue
Decrease in normal desquamation process - associated with soft diet, smoking, Abs
Enlongated filiform papillae - can be black. brown, white
Discoloration caused by chromogenic bacteria, chlorhexidine, foods, smoking
Wouldn’t routinely biopsy as characteristic appearance
Hst: blue areas on filiform papillae (keratin peaks) are aspergillus
Txt: reassurance, tongue scraper, normal diet, smoking cessation
Phsyiological
Increased melanin production in darker skinned individuals
Peutz-jehgers
Genetic disorder - AD
Pigmented mucocutaneous macules
GI polyps, increased risk of malignant change
Melanotic spots around mouth, small and multiple, distinct around lips.
Lip lesions can occur before other manifestations of PJ so early diagnosis/referral
Characteristic appearance so no biopsy but histology would show excess melanin pigment in basal layer
Haemochromatosis
Genetic disorder - AR
Accelerated rate of intestinal iron absorption - excess iron difficult to excrete so accumulates in body
Bloods would show raised ferritin and transferrin
Excess iron stored as haemosioderin - gives bronze appearance to skin
Can accumulate in liver causing scarring or cirrhosis - inc. risk of hepatic cancer
Also inc risk of diabetes mellitus
Individuals tend to feel chronically tired, more prone to bacterial infections with bacteria that favour high iron environments
Common in Celtic pops
Treated with regular venesection
Melanocytic naevus
Moles - can occur on palette Well defined - not worrying Ill-defined - might warrant biopsy Melanin synthesised by melanocytes but can also be synthesised by nevus cells which are derived from neural crest Types of nevus: Junctional (epithelium) Intradermal/mucosal (CT) Compound (both)
Addison’s disease
Destruction of entire adrenal cortex
90% cases caused by autoimmune disease
Lack of adrenocortical hormone = production of adrenocorticotropic hormone (ACTH) by anterior pituitary
ACTH induces melanocyte-stimulating hormone = pigmentation of skin and oral mucosa
Diffuse brown patches oral mucosa, palate, tongue, gingivae
Melanotic macule
Patients usually just have 1
Can occur anywhere in mouth
Histology would show excess melanin in basal 3rd epithelium but no increase in size or number of melanocytes
Drug induced
Blue/grey hue of gingiva - is bone that has become pigmented showing through gingiva Drugs associated with pigmentation: Antimalarials - chloroquine, hydroxychloroquine Quinidine Zidovudine Chlorprozamine Tetracycline Minocycline Oral contraceptives Clofazamine Ketoconazole Amiodaron Bleomycin Doxorubicin - chemo drug
Pigmentation induced in 3 ways:
1. stimulate melanocytes to produce excess melanin
2. deposition of heavy metals in tissues (exogenous)
deposition of iron after damage to mucosal vessels
Post inflammatory
Smokers melanosis
In individuals with darker skin/mucosa there is melanin accumulation when there has been inflammatory insult
E.g. lichen planus, mucosa damaged, melanocytes stimulated
Histology would show damaged basal layer so as a result melanin that would be present in this layer normally, has dropped out into LP
Similar appearance in smokers - smokers melanosis. Smoking stimulates melanocytes to produce excess melanin - occurs 21.5% smokers
Malignant melanoma
<1% all oral malignancies
Proliferation of malignant melanocytes along the junction between epithelial and CTs as well as within CT
Anterior maxilla and hard palate most common
4th-7th decade life
Men > women
Asymptomatic, slow growing black or brown patch with asymmetric and irregular borders vs rapidly enlarging mass associated with ulceration, bleeding, pain, bone destruction
Can be either
Treatment: radical excision with clear margins. Radiotherapy and chemo ineffective for this type of malignancy
Overall 5 year survival : 15%
V aggressive - normal tumour staging from T1-T4 but all malignant melanomas start from T3
Kaposis sarcoma
Malignant tumour caused by HHV-8 Associated with immunosupression Hallmark of AIDS Black/purple lesions orally - commonly gingivae Excision +/- chemo/radio
Exam Q - describe pigmented lesions of the oral mucosa
Mucocutaneous disease:
Autoimmune bullous diseases - pemphigus, pemphigoid, dermatitis herpetiformis (type II)
Epidermolysis bullosa congenita - congenital abnormality
Erythema multiforme (type III/IV)
Oral lichen planus and lichenoid reactions (type IV)
Pemphigus
0.5-3.2 per 100,000
40-60 years
M : F 1 : 1
Mouth involved in most cases and only site involved in some
Palate, buccal mucosa and gingivae most affected
Bullae - short lived on skin and mouth due to fragility, rupture easy
Bursting of bullae causes shallow, non-healing ulcers - typical
Pathogenesis:
Circulating auto-Abs against binding proteins that keep epithelial cells together (desmosomes)
Desmoglein 3 or 1 - binding protein part of the desmosomal complex
Auto-Abs bind to desmoglein 3, acantholysis occurs and formation of intra-epithelial bulla
Intra epithelial bullae - so intact surface epi but fragile, so ruptures easily, but intact basement membrane still attached to CT
So no stimulus from body to heal as body doesn’t recognize partial thickness breach of epithelium
However - epithelial permeability barrier lost resulting in:
Infections can get in
Loss of tissue fluids
Together these can be life threatening
Pemphigus management and investigations
Biopsy of para-lesional and/or normal tissue
Send tissue to lab fresh - do not fix
Routine histology - seperate biopsy or part of fresh specimen
Direct immunofluoresence staining - used to detect whether Abs are present in tissue
Blood test to check for circulating desmoglein levels
Indirect immunofluoresence
Immunofluoresence - + direct immunofluoresence staining in epithelial cells shows fishnet pattern
Auto-Abs (IgG) target desmoglein3 in the desmosomes that join keratinocytes
Fluorescent labelled anti-human IgG attach desmoglein auto-Abs
Shows green where auto-Ab present - fishnet pattern
Management:
Exclude cancer
Immunosupression
Prednisalone alone or in combo with azathioprine
Occasionally other immunosupressants or plasmapheresis
Pemphigoid
Sub-epithelial bullae
Full thickness separation between epithelium and CT
Less fragile
On rupturing, exposed CT
Healing by secondary intention - epithelium migrates from edges, wound contraction e,g, scarring
Therefore pemphigoid not as life threatening as pemphigus
Pathogenesis:
Auto-Abs against components of hemidesmosomes - structures which glue epithelial cells to BM
Targeted part varies on which pemphigoid
Pemphigoid
Sub-epithelial bullae
Full thickness separation between epithelium and CT
Less fragile
On rupturing, exposed CT
Healing by secondary intention - epithelium migrates from edges, wound contraction e,g, scarring
Therefore pemphigoid not as life threatening as pemphigus
Pathogenesis:
Auto-Abs against components of hemidesmosomes - structures which glue epithelial cells to BM
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Types of pemphigoid
Bullous pemphigoid
Mucous membrane pemphigoid
Dermatitis herpetiformis
Bullous pemphigoid
Skin usually involved with bullae and large shallow ulcers or erosions
Mouth and other mucous membranes frequently involved
Auto-Abs against BP180 and BP230 antigens in hemidesmosomes
Mucous membrane pemphigoid
Chronic disease of elderly
Desquamative gingivitis is 90% cases
Buccal mucosa and palate often involved
Eyes may be severely damaged caused by scarring - cicatricial pemphigoid
Skin lesions rare in MMP
Auto-Abs directed against BP230, laminin and a6b4
Well marginated ulcers
Healing 3-4 weeks - risk of scarring if eyes, larynx, oesophagus
Erythematous, fribale tender gingiva
Nikolsky signs +
Signs - symblepharon (eyeball stiks to lid), ankyloblepharon (eyelids stick together), lid inversion/Entropion, trichasis
Mucous membrane pemphigus investigations and management
Biopsy of para-lesions and /or normal tissue
Send to lab fresh - not fixed
Routine histology
Direc timmunofluoresence staining - to detect auto-Abs in tissue
Immunofluoresence would show IgG or IgM at level of basement membrane
Indirect immunofluoresence usually negative
Manegement:
Requires urgent referral as pt can lose sight
Plaque reduction - poor OH can make symptoms worse. Chlorhexidine
Topical or systemic steroids
Sulphonamides or dapsone
Mycrophenolate mofetil
Occula rexamination essential
Dermatitis hepetiformis
Similar to BP but younger age group including children
Smaller bullae and vesicles
Association with coeliac
Mgt: gluten free diet
May responds to sulphonamides and dapsone (anti-microbials)
Histology: small islands of epithelial seperation at level of basement membrane
n
Dermatitis hepetiformis
Similar to BP but younger age group including children
Smaller bullae and vesicles
Association with coeliac
Mgt: gluten free diet
May responds to sulphonamides and dapsone (anti-microbials)
Histology: small islands of epithelial seperation at level of basement membrane
Neutrophil/eosinophil ‘abscesses’
Mixed inflammation in CT
Immunofluoresence - speckled/granular IgA, basement memrbane and adjacent CT
Epidermolysis bullosa congenita
Not autoimmune (inherited)
Genetic defects in key proteins associated with epithelial integrity or anchoring to CT
Variable clinical picture depending on which protein defective
Mainly affects children - often present at birth
Some forms are severe, mutilating, fatal
Erythema multiforme
Acute onset, short duration 2-3 weeks Mucocutaneous blistering disorder Peak age range 20-30 Complex pathogensis Some cases immune mediated - type III Some recurrent cases - type IV hypersensitivity to Herpes antigens
Clinical features: Oral - haemorrhagic crusting of lips Extensive irregular mucosal ulceration, erythema and blistering Ocular - conjunctivitis Skin - 'target' lesions Severe cases - Steven Johnson syndrome
Causes:
Single episode: drugs, mycoplasma pneumonia, radiotherapy, idiopathic
Recurrent - recurrent Herpes simplex virus
Mgt: remove trigger/avoid Short, reducing course of steroids Chlorhexidine/benzydamine MW Gengigel/gelclair Anlgesics Soft diet May require admission for parenteral nutrition and intensive therapy Recurrent - prevention with systemic Acyclovir
Oral lichen planus
Type IV hypersensitivity Common, 1.5% pop Onset 30-50 Cell mediated auto-immune process May be exacerbated by stress Chronic, difficult to treat 1-3% reported risk of malignant change
Different clinical presentations: Reticular striations Plaque like Erosive Desquamative gingivitis Bullous Symmetrical and bilateral lesions
Skin involvement:
<10% with oral lesions have skin lesions, ~50% with skin lesions have oral lesions
Purple, itchy papules and Wickhams striae
Lesions particularly on flexor surface of wrists and shins
Other mucosal sites - oesophagus, genital , anal
OLP pathology
Band like accumulation of T lymphocytes next to epithelium
Start to attack epithelium and basal epithelial cells
Lymphocytes start to enter epithelium
Damage to basal cells, stimulates attempt at repair by body - stimulating keratin and more epithelial cells on surface
If rate of repair exceeds damage = epithelial thickening, marked keratinisation e.g. reticular and plaque like lesions
If rate of damage exceeds rate of repair = epithelial thinning i.e. atrophic/erosive lesions, or ulceration
Complication OLP and treatment
Typically lifelong
1-3% risk malignant transfomration - higher rate in: lichenoid, smokers, erosive lesions, viral infections (hep C, HPV)
Treatment:
Symptomatic relief
Diet advice - soft, non-spicy, warm not hot
OH improvement
Discussion re premalignant potential
Topical analgesics - difflam
Topical corticosteroids - prednisalone, betamethasone, beclomethasone
Topical immunosupressants - topical tacrolimus 0.1%, cyclosporin mouthrinse
Systemic immunosupressants - prednisalone, azathioprine, mycophenolate, dapsone, hydroxychloroquine, retinoids
Lichenoid reactions
Clinically and histologically same as LP
But know antigenic cause
Contact sensitivity e.g. amalgam. Positive patch test
Lesions closely associated to filling material
Removing/replacing restoration should result in lesions resolving within 3-6 months
Or reactions with systemic drugs e.g. anti-malarials, NSAIDs, diabetes treatments, anti-hypertensives
SLE/DLE
GvH disease - results of bone marrow transplant. T cells are from donor so any mismatch in HLA markers can make new T cells think own T cells are foreign and attack, damaging basal keratinocytes
