ALLERGIC AND IMMUNOLOGIC DISEASES

RECURRENT APTHOUS STOMATITIS

 Synonyms  Canker sores/
Aphthous ulcers/ Apthae
 Commonly known as “ Mouth ulcer”
 Frequently occurring non-traumatic
ulcers of oral mucosa.
 Recurrent Aphthous Stomatitis (RAS)
 Characterised by development of
Introduction painful and recurring solitary or
multiple ulcers of the oral mucosa.
 Greek term “ aphthae”  denotes “
disorders of the oral cavity “
credited to Hippocrates (460 B.C)
First described  Von Mikulicz and
Kummel in 1898 and later by Sibley in
1899
 Microbial factors  Bacterial
Probable Etiologic Factors
infection.
 Causative agent of the disease  L-
form of α-hemolytic Streptococcus &
Streptococcus sanguis.
 Genetic History  Positive family
history and development is
associated with HLA- B51.
 Allergies  Patients with history of
asthma, hay fever, or food or drug

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allergies.
 Immunologic factors  T-cell
mediated
 Nutritional deficiency  Vitamin B12,
B9 & iron deficiencies.
 Traumatic injuries  Oral surgical &
dental procedures, needle injections,
dental trauma
 Toothbrushing and self-inflicted
bites, ,
 Hormonal influences  Incidence of
aphthae is higher in premenstrual &
post-ovulation period  relating to
the blood levels of progesterone.
 Stress
Systemic diseases  Behçet’s syndrome,
cyclic neutropenia, HIV infection, Reiter’s
disease, Sweet syndrome, Celiac disease,
nuntritional deficiencies, MAGIC
syndrome (major aphthous and
generalised inflamed cartilage) & PFAPA
syndrome (periodic fever, aphthae,
pharyngitis,and cervical adenitis)
 Clinically  Categorised in 3 classical
Clinical Features
forms
Minor aphthae (Canker sore)  Most
common form of RAS & accounts for 70%

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- 80% cases of RAS

 Small, round, clearly defined,
painful recurring ulcers with
central shallow necrotic region.
 Ulcers are 5–10 mm in diameter
with gray-white
pseudomembrane.
 Heal within 10–14 days without
scarring.
 commonest location Non-
keratinized mucosa of oral cavity.
Major aphthae (Sutton's disease,
Mikulicz aphthae, peradenitis mucosa
necrotica recurrens)  2nd most common
form of RAS.
 More severe than minor type of
RAS
 Ulcers are greater than 10 mm in
diameter appear deeper with scar
 onset after puberty and chronic,
persisting up to 20 or more years
 Found on the movable
nonkeratinizing surfaces of oral
cavity
Herpetiform aphthae  Least common
variant of RAS
 Seen commonly in females

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 Characterised by multiple small

group of pinpoint ulcers
 Irregular lesion with small (2–3
mm) and large number (10 to 100
ulcers) 
 Heals within 7–30 days and have
tendency to scar
 Other common symptoms 
Tenderness and discomfort
Difficult
y in eating speaking & deglutition
Sorene
ss of the mouth,

Burning
& prickling sensation
 Pre-ulcerative lesion
Histopathology
 Exhibits focal vacuolation and
supra basal epithelial cell
degeneration.
 Lymphocyte infiltration in the
lamina propria
 Deeper stroma  Presents with
periductal and perivascular
distribution of these cells.
 Neutrophil margination may also
be observed.

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 Ulcerative lesion
 Reveals fibro purulent area
covering the ulcer
 Occasionally superficial colonies
of the micro-organisms are also
noted
 Neutrophilic infiltration is seen
beneath the ulcer in the connective
tissue
 Lymphocytes prevail in deeper
areas, causing perivascular and
periductal fibrosis
Margins of the lesion show increased
endothelial & fibroblastic proliferation
with granulation tissue at the base of the
lesion
 Smear taken from areas around the
Cytological Smear
aphthae  Epithelial cells presents
with elongated nuclei, containing a
linear bar of chromatin
 Radiating process of chromatin
extending towards the nuclear
membrane.
 These cells are called 
Antischkow's cells
 Seen abundantly in patients with

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RAS
 Also found in Patients  Sickle cell
and iron deficiency anemia
Children
with chemotherapy treatment for
cancer
Sometimes in
normal individuals.
 Differential diagnosis for multiple
aphthous ulcers:
 Intraoral recurrent herpes simplex
infection (IRHS)
 Erythema multiforme
 Pemphigus vulgaris
 Cicatricial pemphigoid
Differential Diagnosis  Erosive lichen planus

 Differential diagnosis for single major

aphthous ulcers:
 Traumatic ulcer
 Squamous cell carcinoma
 Necrotizing sialo metaplasia
Gumma

Herpetiform
Feature Minor Aphthae Major Aphthae
Aphthae

Gender M=F M=F M<F

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predilection

Age of onset 10 to 19 years 10 to 19 years 20 to 29 years

Particularly in non-
keratinized
movable mucosa
 Most frequently Occurs 
affected  Everywhere in the
Labial mucosa, oral cavity,
Labial mucosa and
including
Sites affected buccal mucosa, tongue soft palate,
keratinized
mucobuccal fold tonsillar fauces,
portions
Less frequently particularly gingiva
affecte  Floor of and hard palate
the mouth, tongue,
faucial pillars and
soft palate

1 to 10 ulcers Clusters of 10 to
< 5 ulcers present
No. of ulcers present at any one 100 individual
at any one time
time ulcers
 Painful ulcers  Larger (>1 cm),  Ulcers resemble
that are shallow, more destructive those seen in
round or oval,  Deeper ulcers primary herpes
Clinical
 hence the
presentation of the well-demarcated that last longer &
name
ulcers  Small (<1 cm; recur more herpetiform
usually about 3– frequently than  Numerous,
5 mm in minor aphthae. pinhead-sized,

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diameter)
 Covered with
 Painful &
gray membrane
bleeding ulcers gray-white

 Crateriform and erosions(1 to 2
fibrinopurulent mm in diameter)
asymmetric
pseudomembran  Individual
 Unilateral ulcers
e  can be lesions coalesce
with a red raised to form large
removed by
inflammatory ulcers
rubbing  red
border Borders are less
bleeding ulcer
AIDS patients  sharp than those of
base exposed.
Similar ulcers major aphthae &
Prominent develop on vagina, wide spread area
erythematous penis, rectum & of erythema
border surrounds larynx.
the fibrinous
pseudomembrane.

During an attack 
New lesions may
continually appear
Persists for 4 to 6 Lasts for 2 to 3
Duration for 3 to 4 week
weeks weeks.
period, with each
lesion lasting for
10 to 14 days

1 to 4 months Less than monthly Less than monthly

Rate of recurrence
interval interval interval

Scarring No scar formation Heal with scar Heals with or

on healing formation without scar

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formation

BEHCET’S SYNDROME/OCULO-ORAL-GENITAL SYNDROME

 Behcet syndrome Titled after the
Turkish dermatologist Hulusi 
Behçet who reported this ulcerative
disorder in 1937.
 Multisystemic, chronic disorder
 Characterized by oral and genital
Introduction
aphthous ulcers, arthritis, and
cutaneous lesions
 Ocular, gastrointestinal &
neurological manifestations are also
noticed
Triad  Oral cavity, eye and genitals
 Appears  Immunodysregulation 
Primary or secondary that triggers
factors like environmental factors
(organophosphates, organochlorides,
Etiopathogenesis
heavy metal intoxication, allergens),
viruses, bacteria, or pesticides.
 HLA-B51  Related closely to
Behçet’ssyndrome
 Age  20 to 30 years
 Gender  M > F
Clinical Features
 Clinical presentation
o Oral ulcers  First sign of disease

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 about 50% of patients.

o Most often occur in crops of six or
more on the soft palate and
oropharynx (infrequent sites for
routine aphthae).
o Other sites affected  Lips, buccal
mucosa, tongue, gingiva, tonsils &
uvula.
o Genital ulcers  Involve the
mucosa or skin & tend to be smaller
and less common than the oral
lesions.
o Located  Root of the penis or
labia majora and scrotum
o Eye manifestations  Photophobia,
conjunctivitis, & posterior uveitis.
Cutaneous lesions  Cutaneous ulcers
and nodules, cellulitis type lesions,
papulopustular lesions (acneiform) or
pseudofolliculitis, erythema nodosum-like
lesions, superficial thrombophlebitis,
Sweet’s syndrome & gangrenous
pyoderma
 Intraoral ulcers  Non-specific 
Remarkably like recurrent aphthous
Histopathology
ulcers.
Leukocytoclastic vasculitis is seen.

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Diagnosis  Recurrent oral ulceration Minor,

major or herpetiform ,
o Recurrent genital ulcerations 
Aphthae-like ulcers
o Eye lesions  Retinal vasculitis,
anterior or posterior uveitis and
cells in the vitreous on slit-lamp
examination
o Skin lesions  Papulo pustular
lesions, erythema nodosum &
pseudo-folliculitis
o Acnei form nodules consistent with
Behcet’s disease
o Noticed in post-adolescent patients
who not taking corticosteroids
o Positive pathergy test  Unique
test to Behçet’s syndrome
o Development of papule or pustule
or erythematous induration noticed
on the site after 24 to 48 hrs of
injection with an inert substance
(ex: sterile saline)
 Behçet’s syndrome & RAS appear
clinically indistinguishable.
 RAS shows oral ulcers as the only
manifestation of the disease,
 Where as Behçet’s syndrome must

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present with atleast 2 of classic triad

of the disease:
 Recurrent oral ulcers
 Recurrent genital ulcer
Ocular inflammation
REITER’S SYNDROME
 Reiter’s syndrome  Combination of
conjunctivitis, balanitis, urethritis &
mucocutaneous lesions.
Introduction
 Most common complications 
Nonspecific urethritis
C linically resembles gonorrhea
 Disease of unknown etiology
 Considered to be an infectious origin
 Pleuro-pneumonia-like organisms
(PPLO) have also been suspected
Etiopathogenesis  Bedsonia group virus thought to
isolated from patients with the
disease
Mycoplasmal and chlamydial species
also involved
Clinical Features  Age  20 to 30 years
 Gender  M > F
 Clinical presentation
o Typical Tetrad of syndrome 
Nongonococcal urethritis, arthritis,

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conjunctivitis and mucocutaneous

lesions.
o Urethritis  First sign of the
syndrome.
o Urethral discharge Associated
with itching & burning sensation.
o Arthritis  Occurs bilaterally and
symmetrical, generally
polyarticular
o Conjunctivitis  Occurs usually,
but so mild
o Cutaneous lesions  Mimicking to
those found in keratoderma
blennorrhagica
o Characterised by red or yellow
keratotic macules or papules &
later desquamates
 Oral Manifestations  Present as
painless, red & slightly elevated areas
 Lesion appear as granular or even
vesicular with a white circinate border
 Location  Buccal mucosa, lips, and
gingiva.
 Palatal lesions  Shows small, bright
red purpuric spots which later darken
and coalesce
 Lesions on the tongue mimicks

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"geographic" tongue.
Clinically Lesions seen on the glans
penis, produces circinate balanitis
 Epithelium  Parakeratinized
stratified squamous epithelium,
acanthosis & polymorphonuclear
leukocyte infiltration
Histopathology
 Sometimes with microabscess
formation seen like psoriasis
Connective tissue  Lymphocyte &
plasma cell infiltrate
 Erythrocyte sedimentation rate (ESR)
 Elevated in the acute stage of the
disease & remains after arthritis
resolves.
Diagnosis  By tissue typing  Over 70% of
patients will have the HLA-B27
genotype.
Mild leukocytosis & pyuria also be
noticed.
SARCOIDOSIS

Introduction  Greek meaning of Sarcoidosis  Flesh

like condition
 Synonyms  Boeck’s sarcoid /
Besnier-Boeck-Schaumann disease
 Represented as “ multisystem

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granulomatous disease”
 Disease of unknown etiology
 CurrentlyInfectious etiology is more
favored mostly  Mycobacterium and
Propionibacterium
Etiopathogenesis
Studies stated  Interferon gamma (IFN-
γ) and cytokines like TNF-α, IL-12 and IL-
18  have a significant role in the
development of granulomatous lesions
Clinical Features  Age  1 peak -- 25 & 35 years, 2
st nd

peak -- 45 & 65 years

 Gender  M > F
 Organs involved  Lungs, lymph
nodes, skin, eyes & salivary glands
 Clinical presentation
o Lymph node involvement 
Bilateral hilar lymphadenopathy
o Cutaneous manifestations 
Chronic, violaceous and indurated
lesions
o Lupus pernio  Ears, lips , nose &
face are also involved.
o Erythema nodosum noticed in 15%
of the patients.
o Ocular manifestations  Uveitis,
keratoconjuctivitis sicca
o Salivary gland involvement 

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Enlargement and xerostomia.

o Oral manifestations  Lesions on
the lip
o Characterised clinically  Small,
plaques or papular nodules or
similar to herpetic lesions or ‘fever
blisters’.
o Lesion on palate and buccal
mucosa
o Presented as bleb-like, or as solid
nodules , sometimes contains a
clear yellowish fluid
o 2 syndromes related with acute
sarcoidosis:
 Lofgren’s syndrome  Bilateral
hilar lymphadenopathy
,erythema nodosum,
arthralagia
Heerfordt’s syndrome/ Uveoparotid fever
 Anterior uveitis of the eye, parotid
enlargement, facial paralysis & fever
Histopathology  Shows a picture of
granulomatous inflammation
 Group of histiocytes along with
Langhan’s or foreign body giant cells
form clusters, these are surrounded by
lymphocytes.

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 Laminated basophilic
calcifications present within the
granulomas  Schaumann bodies
may be present.
Stellate inclusions  asteroid bodies 
may also be present within the
granulomas
 An intracutaneous test of sarcoidosis
 Kveim-Siltzbach test,  The test
agent  Sterilized suspension of
human sarcoid tissue by intradermal
injection
 Within 4 to 6 weeks of interval
Papulonodular lesion noticed in
Diagnosis injected site of a affected patient.
 Serum angiotensin converting enzyme
(ACE) levels Elevated
 ESR & serum calcium levels
Elevated
Eosinophilia, leukopenia, anemia,
thrombocytopenia are also noticed in
blood picture
WEGNER’S GRANULOMATOSIS
 Serious, systemic disease of unknown etiology
 Related to inflammatory condition
 Affects the vascular, renal and respiratory systems of the human body.

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Clinical Features
 Age  4th & 5th decade
 Gender  M>F
 Clinical presentation  Multi-organ involvement
 Usually first characterized by  Presence of rhinitis, sinusitis and otitis or ocular
symptoms.

 Patient also developsCough and hemoptysis along with joint pains & fever.
 Skin lesions Hemorrhagic or vesicular lesions
 Oral manifestations  Gingiva, the most common site  represented as
“strawberry gingivitis”
 Oral ulcerations  Non-specific & occurs on any mucosal surface.

Histopathology
 Pattern of mixed inflammatory infiltrate found centrally around the blood
vessels.
 Gingival & other lesions  Nonspecific granulomatous process with scattered
giant cells.

ANGIOEDEMA/ANGIONEUROTIC EDEMA/GIANT URTICARIA

 Angioedema  Diffuse edematous swelling of the skin, mucosa & soft tissues
 Frequently involved Subcutaneous & submucosal connective tissues.

Etiopathogenesis

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 Allergic angioedema  Due to mast cell degranulation that leads to release of

histamine
 Causing substances  Drugs, food, plants, dust, cosmetics, dental rubber dams
etc.  initiate an IgE mediated hypersensitivity reaction mast cell
degranulation.
 Related to the use of angiotensin-converting enzyme (ACE) inhibitors.
 Associated with the presence of higher levels of antigen -antibody complexes
 Noticed in patients with higher eosinophil counts in peripheral

Clinical Features

 Sites involved  Tongue, chin, eyes, face around the lips, , pharynx and larynx.
 Sometimes Hands, arms, legs buttocks and genitals are involved.
 Clinical presentation
 Angioedema Soft, non-tender diffuse edematous swelling of relatively
rapid onset, which may be solitary or multiple.
 Eyes  Swollen and lips are extremely puffy

 Hereditary forms of angioedema  More dangerous and affects the

respiratory & gastrointestinal systems
 Hoarseness of voice & difficulty in breathing
 Results in life threatening condition due to the involvement of the upper air
way.

CONTACT STOMATITIS / STOMATITIS VENENATA

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 Type of allergic reaction of the oral mucosa

 Develops at the site of exposure to causative agent.
 Causative agents  Tooth pastes, mouth rinses, topical drugs, food, dental
materials
 Itching and burning sensation of the affected site
 Exhibits red & inflamed region with formation of vesicles & erosions.

Oral manifestations :

Gingiva  brightly –red

Buccal muocsa  Puffy & dark & red due to engorged & ejected blood vessles
In chronic cases  Mucosa may be more erythematous ,sometimes white or
hyperkeratotic

Histopathology:

 Stratified epithelium with intercellular edema

 Vesicle formation seen within the epithelium
 Dilated blood vessels and engorged with red blood cells.
 Presence of large number of eosinophils in the connective tissue is the
diagnostic feature for allergic reaction.

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