ALLERGIC AND IMMUNOLOGIC

DISEASE OF THE ORAL CAVITY

Guided By:
Dr.Pratibha Poudel Presented by:
Dr. Bhoj Raj Adhikari Diksha Shah
Roll no.:36
 Contents
1. Recurrent Aphthous Stomatitis
2. Behcet’s Syndrome
3. Wegener’s Granulomatosis
4. Angioedema
5. Contact stomatitis and Dermatitis
 INTRODUCTION
Allergy
• Hypersensitive state
• Exposure to specific material
• Altered capacity of living organism to react upon re-exposure
to it .

Allergen
• An antigen that cause allergic symptoms.
Allergic reaction
• 2 types
1. Immediate reaction
2. Delayed reaction
Immediate reaction
associated with antibodies circulating in the serum of allergic
person
includes:
anaphylaxis
hay fever
asthma
serum sickness
angioedema
Delayed reaction
• Attain antigenic properties by combining with the tissue of
individual
• Not associated with circulating antibodies
• Causative agent are not strictly antigen
• Not manifested clinically for several hours
after exposure
Includes :
• Drug allergies
• Allergies of certain infection
• Contact reaction to vast variety of materials
 RECURRENT APHTHOUS STOMATITIS
• Synonyms
(aphthous ulcers, aphthae, canker sores)

• Common
• Painful,recurring
• Solitary or multiple ulcerations
• Similar to herpes simplex infections
 Etiology

1. Bacterial infection
2. Genetic history
3. Immunologic abnormalities
4. Nutritional deficiency
 Etiology

1. Bacterial infection
pleomorphic, transitional, L-form of an alpha-hemolytic
sterptococcus, sterptococcus sanguis - causative agent of the
disease
• T-cell mediated immune response to Streptococcus sanguis

Cross reaction between sterptococcal heat shock protein

and oral mucosa

Mucosal damage
2. Genetic history
Positive family history
Associated with HLA-B51
3. Immunologic abnormalities
Recurrent aphthous ulcer may be the result of an autoimmune
response of oral epithelium

4. Nutritional deficiency
Iron,vitamin b12 or Folic acid deficiency
 Precipitating factor
1. Trauma
2. Endocrine conditions
3. Psychic factor
4. Allergic factors
 Precipitating factor

Trauma
 Comprises 75%
 local trauma like
• self inflicted bites,
• oral surgical procedures,
• tooth brushing,
• dental procedures needle injections and
• dental trauma
Endocrine conditions
• Exists relationship between occurrence
of menstrual period, pregnancy
menopause, post ovulation period and
the development of aphthous ulcers.
Psychic factor
• Stress or acute psychological
problems

Allergic factors
• Asthma, hay fever, or food or drug allergies
• Negative correlation between aphthous ulcers and smoking
 Systemic diseases

Occurs in various systemic disease like:

Behcet’s syndrome
Cyclic neutropenia
Magic syndrome( Major aphthous and generalized inflamed
cartilage)
PFAPA syndrome( periodic fever, aphthae, pharyngitis, and
cervical adenitis)
HIV infections
Also occur in systemic illness like:
Crohn’s disease
Ulcerative colitis
Gluten sensitive enteropathy
 CLASSIFICATION
• Based on clinical manifestations
1. Recurrent aphthous minor
2. Recurrent aphthous major
3. Recurrent herpetiform ulcerations
4. Recurrent ulcers associated with Behcet's Syndrome .
 1 ) Recurrent aphthous minor

 Most common
 Also known as Canker Sore
 1 to100
 Size- 2 to 3mm to over 10 mm
 Labial mucosa
 7 to 14 days- heals without scar
 2 ) Recurrent aphthous major

• Severe form of Recurrent aphthous minor

• Previously known as separate entity .
• As periadenitis mucosa necrotica recurrens
( Mikulicz's Scarring aphthae or Sutton's disease)
• 1 to 10
• Size > 1 cm
• Lips, cheeks, tongue, soft palate
• Occurs after puberty and persist upto 20 years
• 6 weeks- scarring upon healing
• HIV
 3 ) Recurrent herpetiform ulcerations

• consists of clusters of ulcers

• resembling herpetic lesion
• Not associated with herpes virus
• Crops of multiple small, shallow ulcers
• Often upto 100 in number
• Female predisposition
• Small pinhead sized erosions that
gradually enlarge and coalesce
• More painful
• Present almost continuously for 1 to 3 years
• 4 ) Recurrent ulcers associated with Behcet's Syndrome .
 Recurrent aphthous Recurrent apthous Recurrent
minor major herpetiform ulcers
AGE 10 to 30 years After puberty and Young adults
persists upto 20 years
and more
SIZE 2 to 4 mm to over 100 >1 cm Initially tiny but ulcer
mm coalesce
NUMBER 1 to 100 1 to 10 Upto 100 in number
OF
LESIONS
DURATION 7 to 14 days Upto 6 weeks Upto 1 month

SCARING Absent Present Absent

SITE Buccal mucosa, labial Lips , cheeks, tongue, May occur in any site
mucosa, tongue, soft soft palate of oral cavity
palate , gingiva
 Clinical features
• Female > Male
• Majority onset 10-30 years age
• One or more small nodules
• burning sensation
• erythema
• Generalised edema of
oral cavity , esp. tongue
• Paresthesia
• Malaise
• Low grade fever
• Localized lymphadenopathy
• Vesicle- like lesions containing mucus
 Histological features
• Epithelium - fibropurulent membrane
covering the ulcerated area
• Superficial colonies of microorganisms
• Epithelial proliferation present at
margin and lesion
• Connective tissue- Intense inflammatory
cell infiltration
 Cytology
• Anitsckow cells- consist of cells with elongated nuclei
containing a linear bar of chromatin with radiating chromatin
towards nuclear membrane
Anitschkow cells also seen in
• Sickle cell disease
• Megaloblastic anemia
• Iron deficiency anemia
 Differential diagnosis
• Herpetic stomatitis
• Herpangina
• Erythema multiforme
• Erosive lichen planus
• Pemphigus
• Pemphigoid
 Treatment
• Tetracycline mouthwash
• Steroid ointment
• Hydrocortisone acetate- lozenges
• Nutritional supplements for B12,ferritin and folate
 Behcet’s syndrome
• Multisystemic,
• chronic disorder
• Characterized by oral and
genital aphthous ulcers,
arthritis, and cutaneous lesion,
ocular, gastrointestinal and
neurological manifestation.
 Hulusi behcet made an extensive study
 Triad of recurrent aphthous oral ulcer, genital ulcer and ocular
lesions
 Etiology
1.Genetic history
2. Environmental factors
3. Bacterial infection
4. virus
 Etiology
1. Genetic history
positive family history
Associated with allele HLA-B*51
(chromosome 6p21)
2. Environmental factors
organoophosphates,
organochlorides,
heavy metal intoxication
and allergens
- may trigger or exaggerate
3. Bacterial infection
• Streptococcus sanguis and s. oralis
4. virus
hepatitis virus, parvo virus B19;
 Clinical features
• Young adults 25-40 yrs more common
• 5-10 times M > F
Characterized by
i. Oral & genital ulcerations
ii. Ocular lesions
iii. Skin lesions .
 Oral lesions –
• painful , similar to
recurrent aphthous ulcers

• Ulcers have an
erythematous border &
covered by gray or yellow
to exudate
Genital ulcers –
Small , located on Scrotum , root of penis or labia majora
Ocular lesions –
• Begins as photophobia and
irritation .
• May range from simple
conjunctivitis , to uveitis &
finally hypopyon
 Skin lesions - Small pustules &
papules on trunk or limb and
around genitalia

• Various forms of pyoderma ,

erythema nodosum & erythema
multiforms have been reported
• Arthralgia thrombophlebitis and central nervous system ,
Cardiac or pulmonary involvement - Occasional complication
 Histologic features
• Non-specific
• Endothelial proliferation
• Vasculitis appears
• Fibrinoid necrosis of blood vessel walls

•
 Lab findings
• Hypergammaglobulinemia
• Leukocytosis
• Eosinophilia
• ESR ↑
• Elevated C reactive protein
• Elevated C9,C3,C4 complement
• Elevated immunoglobulins (IgM and IgG)
• Elevated immune complex
• Platelet rosette formation around neutrophils- in acute phases
Treatment
• No specific treatment
• Symptomatic or supportive measures .
• May undergo remission or may progress to serious
complication & even result in death
 Wegener's Granulomatosis
• Disease of Unknown etiology
• involves vascular , renal & respiratory systems
• involves nose , paranasal sinuses , respiratory tract , gut ,
joint , nervous systems & kidneys

• Involvement of kidney- common cause of death .

 Etiology
• Abnormal immune reaction secondary to non-specific infection
or a hypersensitivity reaction to a unknown antigen

• Formation of anti-neutrophil cytoplasmic antibodies

• Organs involved exhibit inflammation with granuloma
formation against a non - specific inflammatory
background

 necrotizing granulomata of upper and lower respiratory

tract
 necrotizing vasculitis- affecting vessels
 focal glomerulonephritis

• Hereditary predisposition
Clinical features
• Any age from infants to elderly
• 4th and 5th decade of life
• M>F
• Multisystem disease
• Firstly - development of rhinitis , Sinusitis , and otitis or ocular
symptoms

• Soon develops a cough & hemoptysis , fever & joint pain

• Hemorrhagic or vesicular skin lesions
• Granulomatous lesions of lungs on radiograph
• Glomerulonephritis which develops ultimately leads to uremia
and terminal renal failure .
• Sensory neuropathy may be occasional finding .
Oral manifestation
• Most common manifestation –
Strawberry gingivitis
• Gingival lesions- ulcerations, friable
granular lesions, or simply enlargement
of gingiva
• bone loss
• tooth mobility
• palatal ulceration from nasal extension
• small ulcerations resembling aphthae ,
• diffuse ulcerative stomatitis
• spontaneous exfoliation of teeth ,
• failure of tooth sockets to heal
following extraction
Lab findings
• Anemia
• Leukocytosis
• Elevated sedimentation rate
• Hyper - globulinema
• Hematuria with albumin , caste & leukocytes in urine
• circulating immune complexes
Histologic findings
• Mixed inflammation around
blood vessels .
• Lesion in upper respiratory tract
& lungs consists of giant cell
necrotizing granulomatous
• lesions showing vasculitis
• pseudoepitheliomatous hyperplasia and subepithelial
abscesses .

• Gingival and other lesions shows a non-specific granulomatous

process with scattered giant cells
Treatment
• Majority cases - terminated fatally
• Mean survival rate of untreated pt 5 years .
• Cytotoxic agent- Cyclophosphamide , prednisone
 Angioedema
Synonyms
• Angioneurotic edema
• Quinke’s edema
• Giant urticaria

 diffuse edematous swelling of the skin , mucosa and submucosal

connective tissues .
 Results in death when GI or Respiratory tract involved
 “Angioneurotic edema " in past
Pathogenesis

• Alteration in vascular permeability

Result in angioedema
 Etiopathogenesis
1. Allergic angioedema( due to mast cell degranulation )
"Mast cell degranulaton , which leads
to histamine release and the typical
clinical manifestation, seen commonly
in IgE mediated hypersensitivity reaction
• caused by drugs , foods , plants , dust and inhalants .

• contact allergic reactions to foods , cosmetics , topical

medications of even rubber dams .

• Most cell degranulation can result even from physical stimuli

such as heat , cold , physical exercise , emotional stress & solar
exposure .
2. Associated with use of angiotensin
converting enzyme ( ACE ) inhibitors
 angioedema - related to use of ACE
inhibitors , used in treatment of
hypertension
• These drugs causes angioedema by
increasing level of bradykinin
(potent vasodilator)

• This type of edema usually arise

within hours of initial use of drug .
3. Activation of complement Pathway
1. Hereditary form
2. Acquired form

Hereditary form
2 rare autosomal dominant
hereditary forms are seen
i. Type 1
ii. Type 2
 Type 1
• comprising 85 % cases
• Quantitative reduction in the inhibitor that prevent the
transformation of C1 to C1 esterase without adequate level of
this inhibitor (C1- INH ), C1 esterase cleaves C4 and C2 and
result in angioedema
 Type2
• Exhibit normal levels of C1-INH but inhibitor is non-functional
 Acquired form
• Seen in association with certain type of lymphoproliferative in
patient who develop specific antibodies
• Lymphoid proliferation increases the consumption of C1-INH
and the autoantibodies prevent the binding of C1-INH to C1
4. Due to presence of high level
of antigen antibody complexes
(eg in lupus erythematous,
bacterial or viral infection)

5. In patient with grossly elevated

peripheral blood eosinophil count
 Clinical features
• Site: face, lip, chin, eye,tongue, phaynx
and larynx
• Rarely: Hands, legs, genitals, buttocks
• Sex:Male=Female
• Age:May originate at puberty
• Soft, non-tender, diffuse edematous
• rapid onset or when wakens in morning
• solitary or multiple
• Enlargement- several centimeter
in diameter
• Eyes-swollen and shut
• Lips – exteremly puffy
• Urticarial swelling
• Skin color- normal or slightly pink
• Perioral or periorbital edema are
characteristic
• Intraoral edema – allergic edema or edema related ACE
inhibitor
• Enlargement - resolve within 24-72 hours
or persist for several days
• Frequency – appear daily or inerval of months or year
Note :
• Hereditary form – dangerous
because of involvement of
respiratory and gastrointestinal
system
 Treatment
• Removal of etiologic agent
• Antihistamine drugs
• Intramuscular epinephrine
• Intravenous corticosteroids and antihistamines
• Intubation and tracheostomy
• C1-INH concentrate and esterase
• inhibiting drugs
• Avoid violent physical activity and trauma
• Prophylaxis if more than three attack per year
• Androgen, danazol, stanozol induce hepatic synthesis of C1-INH
• Corticosteroids
 Contact stomatitis & Dermatitis
Synonyms
• Stomatitis
• Dermatitis venenata

a type of reaction in which a lesion of skin or mucous membrane

occurs at a localized site after repeated contact with the causative
agent .
 Pathophysiology
• causative agents are chemicals in nature ( haptens ) and
require conjugation with proteins to become effective

• This process occurs with the aid of intraepithelial Langerhans

cell where the hapten is converted into a competent antigen
 Causative agent
Materials which may cause stomatitis venenata are
1. Dental or cosmetic preparation
 Dentifrices
 Mouthwashes
 Denture powder
 Lipstick, candy, cough drops, chewing gum
2. Dental material
 Rubber dam
 Vulcanite
 Acrylic
 Metal alloy base
3. Dental therapeutic agents
 Alcohols
 Antibiotics
 Iodides
 Phenols
 Procaine
 Volatile oils
 Clinical features

• Itching or burning sensation at

the site of contact
• appearance of an erythema
• Vesicle formation
may become extensive
• If Secondary infection occurs , lesion may be serious
• In chronic contact , skin may become thickened & dry .
 Oral manifestations
• Rare
• Mucosa - inflammed and edematous
• Gingiva- uniformly bright red in all quadrant
• Swollen & edematous features
• erosion & ulcerations, which is more
common in lips
Histological Features
• Intra & Inter cellular edema
of the epithelium
• Vesicle formation within the
epithelium or at the
basement membrane
• Engorged & dilated blood vessel
seen in connective tissue
• Infiltrate of lymphocytes &
plasma cells
• Increased number of
eosinophils
Diagnosis

• Patch test → useful investigation

 Treatment & prognosis

• Discontinuing all contact with the offending material .

 Contact stomatitis from Cinnamon flavoring
•

• cinnamon oil used as flavoring agent in-

confectionery, ice-cream,soft drinks, alcoholic beverages, processed
meat,gum, candy, toothpastes, breath freshners, mouth wash and
even dental floss.
• Flavoring constitutes up to 100 times that in natural spice .

• Therefore , oral lesions documented with the prolonged or

frequent contact with such products .
 Clinical Features
• Most frequent site -gingiva
• Due to toothpaste - more diffuse , plasma cell gingivitis like
lesions of gingiva
• associated with enlargement , edema & erythema
• Erythematous mucositis of buccal mucosa , tongue
• Exfoliative cheilitis & circumoral dermatitis .
• Buccal mucosa - Hyperkeratotic lesions with an erythematous
base alinged along occlusal plane .
• Lesions may be observed on lateral border of tongue

• Lingual Keratosis may mimic oral hairy leukoplakia or

Carcinoma
 Histological Features
• Acanthotic epithelium ,
elongated rate ridges
• Thinned suprapapillary plates ,
hyperkeratosis & neutrophils
exocytosis
• Diffuse infiltration of inflammatory
cells predominantly lymphocyte
• Characteristic perivascular infiltration
of lymphocyte
 Treatment
• Discontinuation of cinnamon product
Contact stomatitis from chronic oral Mucosal contact with Dental Amalgam

• Termed as contact
lichenoid reactions to amalgam
• Clinically and histopathologically
similar to lichen planus
• But demonstrate a difference
in evolution
 Clinical features
• common site:
 posterior buccal mucosa
 ventral border of tongue
 gingival cuffs adjacent to
subgingival amalgam restorations
• Lesions- white or erythematous
with or without striae
 Histological Features
• Similar to lichen planus .
• Hydropic degeneration of basal cell layer
• hyperkeratonic or atrophic epithelium
• Dense band of chronic inflammatory infiltrate
• Ocassionally , perivascular lymphoid aggregates
 Treatment
• Improving oral hygiene , smoothening , polishing &
recontouring of the restoration
• If unsuccessful amalgam should be removed and replaced
with non - metallic restoration
 CONCLUSION
Recurrent aphthous stomatitis
• Painful ulcerations
Classification
1. Recurrent aphthous minor
2. Recurrent aphthous major
3. Recurrent herpetiform ulcerations
4. Recurrent aphthous ulcers associated with behcet’s syndrome
Behcet’s Syndrome
• Multisystem disease
• Characterstic feature are
oral and genital ulcers, arthritis and cutaneous lesions
along with ocular, gastrointestinal and neurological
manifestation
Clinical features
• Oral ulcers- resembling aphthous ulcers
• Genital ulcers- small ulcers in and around genitalia
• Skin problems- pustules and papules in trunk and limb region
• Ocular lesion- initially photophobia and irritation
severe- uveitis and hypopyon
Wegener’s Granulomatosis
• Multisystem disease
• Involve vascular, renal and respiratory systems
• Pathogenesis
• Abnormal immune reaction to an inhaled environmental
antigen or infectious agent
• Formation of ANCA bodies
• Act against vascular, renal and respiratory systems
 Oral manifestation
• Common and characterstic manifestation- strawberry gingivitis
• Deep ulcerations extending to palate till nose and nasal septum
• Spontaneous exfoliation of teeth
• Improper healing of extraction socket
Angioedema
• Oedematous swelling of skin, mucosal and sub mucosal
connective tissue
Pathogenesis
• Alteration in vascular permeability, resulting edema formation
Clinical features
• Soft, non tender swelling of skin, lips, eyes
• Diffuse edematous swelling of both the lips
• Puffy and shut eyes
• Hands, arms, buttocks swelling
• Tenseness or an itching or prickly sensation- Urticaria
• Hereditary- dangerous- respiratory and gastrointestinal
systems
• Contact stomatitis and dermatitis
• Lesion occurs at localized site after repeated contact with the
causative agent
• Itching or burning sensation
• Erythema and then vesicle formation
• Erosion
• Oral manifestation
• Mucosa become remarkably inflamed and edematous
• Smooth, shiny, appearance to the surface
• Severe burning sensation, itching, stinging, tingling and edema
 References:
• Shafer’s Textbook of oral pathology, Ninth edition.
• Neville’s oral and Maxillofacial Pathology, fourth edition.
 Past questions
1. Differential diagnosis of acute ulcer
2. Differential diagnosis of Aphthous stomatitis and herpetic
stomatitis
3. Short note on Aphthous stomatitis
4. Describe in detail the precipitating factor, clinical features and
histological features of recurrent aphthous stomatitis
 MCQS

1. Anitschkow cells are seen in

a. Recurrent aphthous stomatitis
b. sickle cell anemia
c. megaloblastic anemia
d. all of the above
1. Anitschkow cells are seen in
a. Recurrent aphthous stomatitis
b. sickle cell anemia
c. megaloblastic anemia
d. all of the above
2. Behcet’s Syndrome is triad of
a. Oral ulcers, genital ulcers and hypopyon uveitis
b. Oral ulcers, genital ulcers and arthritis
c. Oral ulcers, genital ulcers and cutaneous lesion
d. Non of the above
2. Behcet’s Syndrome is triad of
a. Oral ulcers, genital ulcers and hypopyon uveitis
b. Oral ulcers, genital ulcers and arthritis
c. Oral ulcers, genital ulcers and cutaneous lesion
d. Non of the above
3. Strawberry gingivitis is the feature of
a. Aphthous ulcer
b. Behcet’s syndrome
c. Wegener’s granulomatosis
d. Angioedema
3. Strawberry gingivitis is the feature of
a. Aphthous ulcer
b. Behcet’s syndrome
c. Wegener’s granulomatosis
d. Angioedema
4. The aetiology of Angioedema is
a) Sensitivity to acrylic resin
b) Using ACE inhibitors
c) Hereditary
d) All of the above
4. The aetiology of Angioedema is
a) Sensitivity to acrylic resin
b) Using ACE inhibitors
c) Hereditary
d) All of the above