5- Oral Ulceration

7/30/2019 5- Oral Ulceration

1/8

Dr. Tahani Abualteen

/81

Oral Ulceration

Definition: Ulcer = localized defect in the surface epithelium

exposing the underlying connective tissue base leading to

inflammation

Most common lesion of the oral mucosa May be a manifestation of many disease entities (local and

general disorders) Erosion = superficial ulcer (partial loss of epithelial

thicknessnot exposing the connective tissue base)

Causes of oral ulceration: Infective (viral, bacterial, fungal) Traumatic (mechanical, chemical, thermal, factitious injury, radiation, eosinophilic ulcer "traumatic

granuloma") Idiopathic (recurrent aphthous stomatitis "major, minor, herpetiform") Neoplastic (SCC, other malignant neoplasms) Associated with systemic diseases (GIT diseases, hematological diseases, Behcets disease, HIV

infection) Associated with dermatologic diseases (lichen planus, chronic discoid lupus erythematosus,

vesiculobullous diseases)** All these should be kept in mind as differential diagnoses for ulcers

Traumatic Ulceration:1- Mechanical Ulceration:

o Three criteria for diagnosis: Define a cause of trauma (e.g. sharp cusps, biting,

outstanding teeth, ill-fitting appliances) Cause must fit size, shape and location of ulcer On removal of the cause, ulcer must show signs of

healing within 10 dayso

Mechanical ulcers don't usually present a problem inclinical diagnosis

o Problems in diagnosis arise with chronic traumatic ulcerso Chronic Traumatic Ulcers

Present forseveral weeks Present as deep crater-like lesions with rolled everted margins and Induration on

palpation (due to surrounding fibrosis)

Differentiation of chronic traumatic ulcers from a neoplastic ulcer may be difficulto When is biopsy indicated?

If we remove the cause and the presumed chronic traumatic ulcerdoes NOT show signs ofhealing within a period of 10-14 days


2/8


/82

2- Chemical ulceration:o Wide variety of chemicals may cause oral ulcerationso Highly concentrated or caustic materials used in

dental practice (e.g. hydrogen peroxide) that may be

accidentally applied to oral mucosa orpreparationsused by patients in self-treatment of oral complaints

(e.g. local use of aspirin to relieve toothache,

inadequately diluted mouth washes)

o Reaction varies in severity (edema to necrosis), so theconcentration and duration of the irritant is important

o Recall: Low-grade chronic irritationhyperplasia or hyperkeratosis High-grade or severe acute traumaulceration or necrosis

o Aspirin burn: Caustic action of aspirin is dose and time related Reactions vary in severity from edema of epithelium

(resembling Leukoedema) to necrosis of epithelium

(presenting as white patches which slough off leaving

areas of ulceration)

Painful Patients history and location of the lesion are

important for clinical diagnosis

o Hydrogen peroxide burn: Hydrogen peroxide is an agent used in bleaching or as an

antimicrobial irrigant

Leakage into soft tissues may induce ulcerationso Anesthetic necrosis:

NOT clearly understood! May be due to tissues being stretched or damaged by giving

too much solution Or due adrenaline which is a vasoconstrictor in anesthetic

solutions

o Formocresol burn: Formocresol is an agent used in pulpotomy (extirpation of

pulp in deciduous teeth)

Leakage into soft tissues may induce ulcerations3- Thermal ulceration:

o E.g. hot foodsPizza burn and hot drinks "coffee, tea burns"o Can occur in any part of the oral mucosa but is most commonly

seen in the palate

4- Factitious ulcerations (self-induced):o Self-inflicted ulcers (induced on purpose!)


3/8


/83

o May be a manifestation of stress, anxiety, or moresevere emotional disturbance

o Appearances and distribution vary considerablydepending on how they are induced

oCommon causes are: biting/chewing of lips, cheeks, ortongue, and damage to the gingiva from sharp finger-nails

5- Radiation ulceration:o In patients undergoing radiotherapy for head and neck

cancer, the oral mucosa may suffer from:

Damage to the epithelium (resulting in Erythema,radiation mucositis, and ulceration)

Damage to blood vessels (resulting in epithelialatrophy)

Damage to lymphatics (resulting in edema)o Thin atrophic epithelium is prone to traumatic ulcerso Differentiation of radiation ulcers form neoplastic

ulcers may be difficult but radiation ulcers (mucositis)

are generally painful while pain is not a common feature of early malignant disease

6- Eosinophilic ulcer (traumatic ulcerative granuloma):o Unusual type of ulcerationo Etiology: chronic trauma and crush injury to skeletal

muscles

o Pathogenesis is still unclear but probably injury causescertain proteins or antigens to leak resulting in

inflammatory or allergic response

o Occurs most commonly in the tongueo Clinical appearance: chronic, well-demarcated ulcer

which may mimic Sequamous cells carcinomaulcer

(indurated and fixed due to histiocytes infiltration)

o Histopathological features Ulcercovered with a thick layer of fibrinous exudate Dense chronic inflammatory cell infiltrate in the base of the ulcer involving underlying

damaged muscle

Deeper parts of the lesion are characterized by an infiltrate rich in histiocytes & Eosinophils** Called eosinophilic ulcer because it is microscopically infiltrated with Eosinophils

o True granulomas aren't present and the condition has no relation to eosinophilic granulomaof bone

o Treatment: remove the cause and follow-up to see signs of healing Idiopathic ulceration:

Recurrent aphthous stomatitis (RAS):o Idiopathic orimmune mediated ulcers


4/8


/84

o Natural history is characterized by frequent recurrences** Ulcers associated with mechanical trauma & dermatological diseases may recur too

o 3 types of ulcers are recognized based on their clinical features: minor major and herpetiform** Any of the 3 types may be associated with Behcet's diseases (syndrome)

o Clinical features of RAS: Prodromal symptoms at the sites of future ulcers are recognized by manypatients 1-2 days

before the onset of ulceration

- Soreness, tingling or burning sensations- Red macule

Minor aphthous ulceration:- Accounts for80% of RAS- 1-5ulcers (that are shallow, round or oval, with

grey/yellow base and an erythematous margin)

- Affect non keratinized mucosa- Less than 10 mm in diameter- Heal without scarring within 10 days- Recur in 1-4 month intervals

Major aphthous ulceration:- 1-10 ulcers- Affect any area in the mouth (keratinized &

non-keratinized mucosa)

** Common sites: lips, soft palate, tonsils,

oropharynx

- Greater than 10 mm in diameter- Heal with scarring within 4-6 weeks- Recur in less than 1 month (in severe cases,

ulceration of the oral cavity is continuous and

may be associated with severe discomfort and

with difficulty in eating & speaking)

- Extends deeper than the shallow minor aphthaeand may present as crater-like ulcer with rolled

everted margins an Induration on palpation** Differentiation of isolated major aphthous

ulcer from a neoplastic ulcer may be difficult

** History of recurrence guide the diagnosis

Herpetiform Ulceration:- The least common- Affects older age group- Hundreds of small pin point ulcers resembling

herpetic ulcers

- Affect any area in the mouth (keratinized &non-keratinized mucosa)


5/8


/85

- 1-2 mm in diameter- When several ulcers are clustered together, coalescence can result in larger areas of

ulceration of irregular outline

- Heal in 2-3 weeks (large coalesced ulcers may take longer time to heal and may healwith scarring)- Recur in less than 1 month (in severe cases, ulceration of the oral cavity is continuousand may be associated with severe discomfort and with difficulty in eating &

speaking)

** Major Aphthous ulcers are usually associated with more severe symptoms

** Differential diagnosis between the three types is based entirely on clinical features

o Etiology of RAS: Most likely immune mediated (there is increasing evidence that damaging immune

responses are involved)

A number ofCo factors (local and general factors) may play a contributory role in a

proportion of cases

Pathogenesis of RAS:- Epithelial destruction is most likely the result ofT-cell mediated cytotoxicity- Epithelial antigen(s) which are responsible for triggering the immune response leading

to the Cytotoxic damage remain unknown

- However, it is suggested that immune mediated damage may be due to cross-reactivitybetween streptococcal protein antigens and epithelial plasma membrane proteins

** Cross-reactivity between bacterial and epithelial heat shock proteins (HSP) has

been demonstrated** In susceptible individuals, the host's immune response to streptococcal antigens

may also damage the oral epithelium

- T cell mediated cytotoxicity: CD4 + T cells predominate in the pre-ulcerative phase CD8+ Cytotoxic T cells predominate ulcerative phase CD4 + T cells predominate in the healing phase

Associated factors:- Hereditary predisposition

45% of patients have family history Mode and pattern of inheritance hasn't been established

- Trauma May precipitate and influence the site of some ulcers Doesn't play an essential role in the etiology of RAS

- Emotional stress Precipitating factor Unlikely to be the direct cause of ulceration Stress may be associated with pernicious habits, such as: check biting, which may

precipitate and influence the pattern of ulceration


6/8


/86

- Cigarette smoking Reverse relation (protect against RAS) Cessation of smoking onset of RAS Protective effect is maybe due to increased keratinization orsystemic mechanism

- Infective agents? Various microorganisms have been isolated from recurrent oral ulcers but attempts toincriminate them as causal factors have been largely unsuccessful

Suggestions: Hypersensitivity to Streptococcus sanguis antigens has been implicated in the

pathogenesis of RAS but studies have produced conflicting results

Cross-reacting antigens between streptococcus sanguis and oral mucosa hassome evidence and there is a possibility that these could be involved in the

immune-pathogenesis of RAS

Adenoviruses have been isolated from RAS but there's no evidence that they arecausal. Their presence may be purely incidental, as so called passenger viruses

A rise in IgM antibody titers to Varicella-zoster and CMV at times ofrecurrences has also been reported but the significance of this is unknown

- Allergic disorders: Food allergy

Some patients with RAS associate the onset of ulceration with certain foodsand this, together with the raised IgE found in some patients, has led to the

claim that food allergies play a role in the etiology of RAS

Results from controlled studies in which patients were challenged with specificfoods are inconclusive

- Hematological disorders Hematological abnormalities associated with deficiencies of hematinics may be

found in 20% of patients with RAS

Iron (ferritin) deficiency occurs most frequently Deficiencies in folic acid and/or vitamin B12 are also associated with RAS, but

much less frequently that Iron

The role of hematological deficiency states in the etiology of RAS is unclear,although it is known that deficiencies in Iron, folic acid and vitamin B12 can produce

atrophic changes in the oral mucosa Ulceration in some patients improves when the deficiency is corrected, suggesting

a causal role- Gastrointestinal diseases

RAS has been reported in patients with a variety of gastrointestinal diseases, someof which are associated with secondary hematological abnormalities as a result of

malabsorption or chronic blood loss

Association between RAS and Celiac disease (idiopathic gluten hypersensitivity)is well recognized Incidence of celiac disease in patients with RAS is low (about 2-4%) Minor aphthous type is a common symptom amongst patients with celiac disease


7/8


/87

Ras may also be seen in patients with Ulcerative colitis & Crohn`s disease- Hormonal disturbance:

In small number of female patients a relationship between RAS and the menstrualcycle has been reported

Hormonal association in some patients has also been suggested by observations thatthe onset of ulceration may coincide with puberty and that remissions may occur

in pregnancy

No consistent association between RAS and the menstruation, pregnancy, or themenopause has been established

o Histopathology of RAS: In the pre-ulcerative stage, there is infiltration

of the lamina propria by lymphocytes

Small number of lymphocytes also infiltratethe epithelium

As the ulcerative stage approaches, there'sincreased infiltration of the tissuesby

lymphocytes (especially the epithelium)

associated with damage to epithelial cells

leading eventually to theirdeath and the

formation of an ulcer

In the healing phase, the number oflymphocytes decreases

** The fluctuations in lymphocytic infiltration throughout the ulcerative cycle suggests thatimmune mechanisms are involved in the pathogenesis of RAS

** As the ulcerative phase begins, the population ofT lymphocytes capable of inducing

Cytotoxic effects (CD8+) in epithelial cells increaseswithin the epithelial infiltrate

** Current evidence suggests that RAS is due to immune-mediated Cytotoxic damage to

oral epithelial cells through the activity of T lymphocytes

o Diagnosis: Clinical features (site, number, history of recurrence, family history) Histopathological features (non-specific to RAS)

Behcet's disease (syndrome):o Characterized by RAS and at least 2 of the following:

Genital ulcers Eye lesions Skin lesions Positive Pathergy test (rapid acute inflammation

of skin in response to minor trauma)

** Cutaneous Pathergy test = development of

sterile papule of the skin 1 day after injection of

saline


8/8


/88

o Rare disorder in western countries, and is seen mainly in countries from eastern Mediterraneanare to the far east corresponding to the route of the ancient silk traders

o Pathogenesis: Genetic predisposition

- Strong genetic link with the histo-biocompatibility antigen HLA- B51 Immune mediated mucosal damage (as discussed for RAS) Vasculitis

- Associated with the hyper reactivity of polymorph-neutrophils

Documents

5- Oral Ulceration