Ulcerative

ULCERATIVE AND
VESICULO BULLOUS
LESIONS OF THE ORAL
CAVITY
1
CONTENTS
 Terminologies
 Introduction
 Classifications
 The Patient with Acute Multiple Lesions
 The Patient with Recurring Oral Ulcers
 The Patient with Chronic Multiple Lesions
 The Patient with Single Ulcers
 Conclusion
 References
2
TERMINOLOGIES
 The diagnosis of oral lesions requires knowledge of basic

dermatology because many disorders occurring on the oral mucosa
also affect the skin.
 Dermatologic lesions are classified according to their clinical

appearance and include the following frequently used terms that
are also applicable in the oral mucosa.
3
TERMINOLOGIES
MACULES : These are well-circumscribed, flat

lesions that are noticeable because of their
change from normal skin or mucosa color.
They may be red due to increased vascularity

or inflammation, or pigmented due to the
presence of melanin, hemosiderin, and
foreign material or ingestion of medications.
A good example in the oral cavity is the

melanotic macule.
4
TERMINOLOGIES
Papules : These are solid lesions raised

above the skin or mucosal surface that are
smaller than 1 cm in diameter.
Papules may be seen in a wide variety of

diseases, including erythema multiforme,
rubella, lupus erythematosus, and
sarcoidosis.
In the oral cavity, hyperplastic candidiasis

often presents as yellow-white papules.
5
TERMINOLOGIES
Plaques : These are solid raised

lesions that are greater than 1 cm
in diameter;
They are large papules.
6
TERMINOLOGIES
Nodules : These lesions are present

deeper in the dermis or mucosa.
The lesions may also protrude above

the skin or mucosa but are generally
wider than they are high.
A good example of an oral mucosal

nodule is the Irritation fibroma.
7
TERMINOLOGIES
Vesicles : These are elevated

blisters containing clear fluid
that are less than 1 cm in
diameter.
8
TERMINOLOGIES
Bullae : These are elevated

blisters containing clear fluid
that are greater than 1 cm in
diameter.
9
TERMINOLOGIES
Erosions : These are red lesions

often caused by the rupture of
vesicles or bullae or trauma and
are generally moist on the skin.
10
TERMINOLOGIES
Pustules : These are blisters

containing purulent material.
11
TERMINOLOGIES
Ulcers : These are well-

circumscribed, often depressed
lesions with an epithelial defect
that is covered by a fibrin clot,
causing a yellow-white
appearance.
A good example is an Aphthous

Ulcer.
12
TERMINOLOGIES
Purpura : These are reddish to purple

bruises caused by blood from vessels
leaking into the connective tissue.
These lesions do not blanch when

pressure is applied and
Classified by size as
Petechiae (less than 0.5 cm)

Ecchymoses (more than 0.5 cm).
13
14
INTRODUCTION
 Many ulcerative or vesiculobullous disease of the mouth have

a similar clinical appearance.
 The oral mucosa is thin, causing vesicles and bullae to break
rapidly into ulcers;
- Ulcers are easily traumatized from teeth and food, and
- They become secondarily infected by the oral flora.
These factors may cause lesions that have a characteristic

appearance on the skin to have a nonspecific appearance on the oral
mucosa. 15
INTRODUCTION
 Three pieces of information in particular help the clinician rapidly

categorize a patient’s disease and simplify the diagnosis:
 This information serves as an excellent starting point for the

student who is just learning to diagnose these disorders, as well
as the experienced clinician who is aware of the potential
diagnostic pitfalls.
16
Acute
► Length of time
Chronic
Primary
► Past history
Recurrent
Single
► Number of lesions
Multiple
Three pieces of information

17
CLASSIFICATION
1. Patients with Acute Multiple Lesions
2. Patients with Recurring oral ulcers
3. Patients with chronic Multiple Lesions
4. Patients with single ulcers
18
Based on clinical presentation
(Burket’s Oral Medicine: Diagnosis &Treatment, 10th edi)
I. Patients with Acute Multiple Lesions :
 Herpes virus Infections

 Primary Herpes Simplex Virus Infections
 Coxsackievirus Infections
 Varicella-Zoster Virus Infection
 Erythema Multiforme
 Contact Allergic Stomatitis
 Oral Ulcers Secondary to Cancer Chemotherapy
 Acute Necrotizing Ulcerative Gingivitis
19
II. Patients with Recurring oral ulcers :
 Recurrent Aphthous Stomatitis

 Behçet’s Syndrome
 Recurrent Herpes Simplex Virus Infection
20
III. Patients with chronic Multiple Lesions :
 Pemphigus
 Subepithelial Bullous Dermatoses
 Herpes Simplex Virus Infection in Immunosuppressed Patients
21
IV. Patients with single ulcers :
 Histoplasmosis
 Blastomycosis
 Mucormycosis
22
ACCORDING TO A.G.GHOM(2nd ed)
I. VESICULAR LESION  Herpes zoster
 Smallpox
A. Nonfebrile Lesion
 Recurrent herpes labialis II.BULLOUS LESION
 Recurrent herpes stomatitis
 Reiter’s syndrome  Pemphigus
 Contact stomatitis  Familial benign chronic pemphigus
 Impetigo  Bullous pemphigoid
 Dyskeratosis congenita  Benign mucous membrane
B. Febrile Lesion pemphigoid
 Hrpetic gingivostomatitis  Epidermolysis bullosa
 Herpangina  Dermatitis hepetiformis
 Hand-foot and mouth disease  Erythema multiforme
 Chicken pox  Stevens-johnson’s syndrome
Accod to Ongole
Predominantly vesicular Predominantly Bullous
HSV Infections Pemphigus vulgaris

Varicella Infections Bullous pemphigoid
Hand foot and mouth disease Benign mucous membrane pemphigoid
Herpangina Erythema multiforme
Dermatitis herpetiformis Steven Johnson Syndrome
Epidermolysis Bullosa
Linear IgA Disease
Based on histology
INTRA EPITHELIAL VESICOBULLOUS
LESIONS:
The lesion is formed within the epithelium

 HSV Infections
 Varicella Infections
 Hand foot and mouth disease
 Herpangina
 Pemphigus
 Familial benign chronic pemphigus
 Epidemolysis bullosa
 Mucosal erythema multiforme

SUB EPITHELIAL VESICOBULLOUS LESIONS: Lesions formed
between the epithelium and the lamina propria
 Dermal Erthyma multifome
 Cicatricial Phempigoid
 Dermatitis herpetiformis
 Epidermolysis bullosa
 Bullous pemphigoid
 Linear IgA Disease
(Burket’s Oral Medicine: Diagnosis &Treatment, 11th edi)
I. Patients with Acute Multiple Lesions :

 Herpes Simplex Virus Infections
 Varicella-Zoster Virus Infections
 Cytomegalovirus Infections
 Coxsackievirus Infections
 Necrotizing Ulcerative Gingivitis and Periodontitis
 Erythema Multiforme
 Stevens Johnson Syndrome and Toxic Epidermal Necrolysis(Lyell disease)
 Oral Hypersensitivity Reactions
27
 Recurrent aphthous stomatitis
 Behcet disease (Behcet syndrome)
28
III. Patients with chronic Multiple Lesions :
 Pemphigus Vulgaris
 Paraneoplastic Pemphigus
 Pemphigus Vegetans
 Bullous Pemphigoid
 Mucous Membrane Pemphigoid (Cicatricial Pemphigoid)
 Epidermolysis Bullosa Aquisita

29
 Chronic Bullous Disease of Childhood

IV. Patients with single ulcers :
 Traumatic Injuries Causing Solitary Ulcerations
 Traumatic Ulcerative Granuloma (Eosinophilic Ulcer of Tongue)
 Histoplasmosis
 Blastomycosis
 Mucormycosis (Phycomycosis
30
INFECTIOUS CAUSES OF
ORAL ULCERATIONS
“ACUTE MULTIPLE LESIONS”
Herpes simplex
 Primary herpetic gingivostomatitis
 Recurrent herpes labialis
 Recurrent intraoral herpes
Varicella zoster
 Chickenpox
 Shingles
Coxsackievirus
 Herpangina
 Hand foot and mouth disease
HISTORY
 HSV- THE FIRST HUMAN HERPES VIRUS TO BE

RECOGNISED
 HERPES –DERIVED FROM GREEK WORD MEANING TO

CREEP
 VIRAL ETIOLOGY ESTABLISHED IN 1919
 SIMPLEX WAS DERIVED TO DISTINGUISH MORE BENIGN

LESIONS FROM HERPES ZOSTER.
35
Herpes Simplex Virus Infection
 Herpes simplex type 1: Causes
oral and pharyngeal infection,
meningeoencephalitis and
dermatitis above the waist.
 Herpes simplex type 2: Causes

genital infection and dermatitis
below the waist.
HSV-1
HSV-1, an alpha-herpes virus, is a ubiquitous virus
2 types of infection:
1.Primary infection: first time virus is contacted by the
patient
 At this point, virus is taken up by sensory nerves and

remain latent in sensory ganglia
2.Secondary infection: occurs with reactivation of the

virus
Pathogenesis of herpes simplex infection
Initial contact with mucosa, skin, eye and infected secretions

HSV Immunopathogenesis, Latency, and
Reactivation:
HSV binds to the surface receptors on nerve terminals in
epithelium and gains entrance into the epithelial cells of
the oral mucosa
Reaches the cell nucleus and virus replication takes place
As more epithelial cells become infected, degenerative and

oedematous changes give rise to vesicular formation
 Incubation period: 2 to 7 days
 Within first week of onset of clinical manifestations
(within 2 weeks of viral infection) sensitized
lymphocytes to HSV can be detected in serum, no
significant antibodies.
 After 2 to 3 weeks, significant antibodies titers appear

hence the fourfold rise in antibody titre between acute
and convalescent sera.
Latency
 Latent viral infection is a type of persistent viral infection which

is distinguished from a chronic viral infection.
 Latency is the phase in certain viruses life cycles in which, after

initial infection, proliferation of virus particles ceases.
 However, the viral genome is not fully eradicated. The result of

this is that the virus can reactivate and begin producing large
amounts of viral progeny without the host being infected by
new outside virus, denoted as the lytic part of the viral life cycle,
and stays within the host indefinitely.
Latency
 Mechanism is unknown.
 It has been suggested that as the neurons are nonreplicating

cells, it may lack the specific transcriptase capable of producing
the virus, so that both the virus and host cell are maintained.
 Considerable progress has been made recently that IgG

antibodies to HSV are necessary for latency.
Reactivation:
 Trigger factors cause weakening of IgG antibody bound

to HSV surface.
 This induce activation of HSV which may then undergo

replication.
 Virus migrate centrifugally along the axon and shed at the

nerve endings.
 Lesions may still not appear if the cellular immunity is intact.

 A number of cellular defects have been detected in
patients with recurrent lesions:
-Decreased interferon production by T-cells.

-Minimal lymphoproliferative response.
-Decreased cytotoxicity by sensitized lymphocytes.
 Constant site of recurrence is usually labial, probably
because of: Involvement of some neurons which
innervate a restricted peripheral epithelial area.
 The most common sites of infection are the oral and
genital mucosa and the eye.
 HSV infection of the cornea (keratitis) is a major cause

of blindness in the world.
 Other HSV-1 infections include herpes gladiatorum

(infections of the skin spread through the sport of
wrestling), herpes encephalitis, HSV esophagitis, and
Herpetic Whitlow
HSV-1 or -2 may cause herpes whitlow, an infection of the

fingers when virus is inoculated into the fingers through a
break in the skin.
This was a common occupational hazard (including within
the dental profession) before the widespread use of gloves.
Primary gingivostomatitis
 Caused by HSV I
 Incidence common in lower
socioeconomic conditions
 Age mainly in children &
teenagers.
 Sex both sexes are affected
 Geographic common in
children in developing world
Clinical manifestations
 1-3 days prodome of fever, loss of appetite accompanied by
myalgia and headache.
 Oral pain causes poor oral intake & patient may require
hospitalization for hydration.
 Disease is self limiting & resolves within 7-14 days.
Oral manifestations
Within few days of prodrome,
erythema & clusters of vesicles
appear on keratinized & non-
keratinized mucosa.
break down
Ulcers [ 1-5 mm]
coalesce
Large ulcers with scalloped borders &
marked surrounding erythema
 Gingiva is fiery red and mouth is
extremely painful causing difficulty in
eating and a diagnostic feature is
acute marginal gingivitis.
 Pharyngitis causes swallowing
difficulty.
Recrudescent oral HSV infections
The term recrudescent HSV should be used to refer to the actual ulcerations caused by
reactivated virus.
Incidence upto 15% of population

Age mainly in adults
Sex both sexes are affected
Geographic Herpes labialis is the most common form of recurrence & is mainly in sunny climate.
Predisposing factors
Reactivating factors include:
 Fever - trauma to lips during dental extraction
 Sunlight - fatigue
 Trauma - mensuration
 Immunosuppression -pregnancy
 Stress - upper respiratory infection
 surgery
Clinical features in recurrent herpes labialis
 On the lips is called recurrent herpes labialis( ‘cold’ sores )
 Prodrome of itching, tingling, burning approx. 50 % of times
 Papules vesicles (48 hrs) pustules (72-96 hrs)
crusting resolution of lesion without scarring.
 Pain is during first 2 days.
“There is a suggestion that patients who do not
experience a prodrome develop lesions from
extraneural latent HSV within the epithelium and
these lesions are less responsive to topical therapy”.
Recurrent intraoral Herpes Stomatitis
 Intraoral recrudescent HSV in the

immunocompetent host occurs chiefly on the
keratinized mucosa of the hard palate, attached
gingiva, and dorsum of the tongue. Such lesions
are called recurrent intraoral HSV (RIH) infection.
 They present as 1 to 5 mm single or clustered

painful ulcers with a bright erythematous
border.
 One common presentation is the complaint of

pain in the gingiva 1 to 2 days after a scaling and
prophylaxis or other dental treatment.
Recurrent Herpes Simplex Lesion
Recurrent Herpes Libialis Recurrent Intra Oral Herpes
 Reactivation of latent virus (20-30 %)  Clusters of small vesicles

leading to cold sores.
Break into
 Prodrome (burning sensation – Parsesthesia)
 Erythema  Ulcers ( 1-2 mm – On keratinized

1-2 hrs mucosa e.g. gingiva, hard palate)
 Vesicles (Clusters at the mucocutaneous

junction of the lips – can extend)
Chronic Herpes Simplex
 Enlarge, Coalesce & weep exudates
2-3 days Immunocompromised patient
 Rupture & crust • Skin & mucosa
• As recurrent herpes but duration
 Healing with no scarring is weeks to months and develop
into large ulcers (several Cm)
COMPARISION- ref by Wood & Goaz 3rd
RAU edi RIHS
 Age- any  Adult or old age group
 Nonkeratinized mucosa  Keratinized mucosa
 Erythematous macule or papule  Clusters of small discrete vesicles
with central blanching followed by  No erythematous halo
necrosis and ulceration  Vesicle rupture
 Large shallow ulcers 5mm – 3cm  small(1-2mm)multiple round
in dia. ulcers in clusters in small localized
 Mostly single,1 or 2 may be widely area
distributed
Single RIH ulcers are indistinguishable from recurrent aphthous

ulcers if they occur on a nonkeratinized site. These ulcers are
painful and similar to those seen in immunocompetent patients
except that they may be larger. They appear slightly depressed
with raised borders. The presence of 1 to 2 mm vesicles or satellite
ulcers at the edges of the main ulcer is a helpful sign.
Clinical features in recurrent intraoral herpes in
immunocomromised patients
 Undergoing chemotherapy
 Organ transplantation
 AIDS
CLINICAL FEATURES
 Atypical appearing ulcers which are several cm in size.

 Last several weeks or months if undiagnosed or untreated.
 Lesions are frequently on the dorsum of the tongue.
 Painful.
 Slightly depressed & raised borders.
Differential Diagnosis
 Coxsackievirus infections (especially hand-foot-and-mouth

disease)
 It may present with widespread ulcerations of the oral cavity

mimicking primary herpetic gingivostomatitis, but ulcers are
generally not clustered and the gingiva is not involved.
 A viral culture or a cytology smear differentiates between the

two.
 Necrotizing Ulcerative Gingivitis :
 RIH infection in the immunocompetent patient on the gingiva may

resemble a localized area of necrotizing ulcerative gingivitis, but
there is usually a precipitating cause, such as dental treatment.
 Cultures are positive for HSV, and lesions of necrotizing ulcerative

gingivitis are widespread and diffuse rather than localized, as is
often seen in RIH.
 Recurrent aphthous ulcers :
 RIH infection in the immunocompromised host may occur

anywhere intraorally and can be differentiated from aphthous
ulcers when necessary with a cytology specimen or culture.
 Varicella-chicken pox : Unilateral painful
grouped vesicles, ends at midline,
trigeminal course.
 Herpes zoster (shingles) : h/o recurrence.
 Erythema multiforme : No gingival lesions,

skin-bull’s eye or target appearance.
In the immunocompromised population, ulcers

secondary to CMV infection, fungal infection, and
neutropenia must also be considered. Differentiation
from these entities is accomplished by biopsy, culture,
and blood tests.
Diagnosis
 Largely clinical
 Viral studies include

 Culture- HSV isolation is gold standard
 PCR
 Cytological smear ( Wight, Giesma (Tzanck preparation), Papanicolaou stain to

demonstrate the characteristic multinucleated giant cells or intranuclear inclusions as seen
on histopathology. However, this does not distinguish between HS V or VZV.
 Direct fluorescent antigen testing is more accurate than routine cytology.
 Antibody titres : Primary HSV infection is associated with elevated immunoglobulin (Ig)M
titers followed several weeks later by permanent IgG titers (seroconversion) that indicate
previous infection but confer no protection against reactivation. Recurrent infection is
associated with a rise in IgG antibody titer in acute and convalescent sera.
Cell Culture :
 HSV isolation by cell culture is the gold standard test for the
diagnosis for HS V-1 infections since it grows readily in tissue culture.
A swab of the oral ulcers is performed, and the specimen should be
refrigerated while awaiting pick-up since the virus is temperature
sensitive.
 Advantage : It has high sensitivity and specificity and allows for

amplification of virions, subtyping, and testing for sensitivity to
antiviral drugs.
 Disadvantage: It needs specialized equipment, is expensive, and may

take up to several days for a final result. HSV that reactivates in the
saliva (asymptomatic shedding) will also grow in culture and may
lead to an incorrect diagnosis of HSV of a coincidental lesion.
64
POLYMERASE CHAIN REACTION (PCR) :
 More recently, polymerase chain reaction (PCR) from swabs has

been shown to detect HS V antigen three to four times more
often than culture.
 However, it is expensive and detects antigen and not whole

infectious particles, so a positive PCR test for HSV does not equate
with active infection.
65
BIOPSY
 HSV lesions are not generally biopsied because the clinical

appearance and history are characteristic, and infection is readily
confirmed with a culture or cytologic specimen when necessary.
 However, if a biopsy is obtained, it will show the presence of

multinucleated giant epithelial cells at the edge of the ulcer. The
nuclei exhibit typical molding and have a ground-glass
appearance.
 Since intact epithelium is necessary for the diagnosis, a biopsy for

a lesion suspicious for HSV must always include epithelium
adjacent to the ulcer. 66
Immunomorphologic tests
The diagnosis of herpes virus infections can be

made more quickly and accurately by using
immunomorphologic techniques . In the direct
fluorescent assay (DFA), the specimen is incubated
with fluorescein isothiocyanate–labeled HSV type-
specific monoclonal antibody. The positively
infected cells are fluorescent green when examined
under a fluorescent microscope.
Dent Clin N Am 49(2005) 15-29

Management of Primary HSV
Management of Primary HSV
1. Symptomatic and supportive
Antipyretics, analgesics, hydration
2. Antiviral
Acyclovir-(zorivax)
topical-5% cream/ointment for 1
week
800mg 5 times/day for 1 week
Pencyclovir-(denavir)
topical-1%cream 2 hrly for 4 days
Docosanol-(Abreva)
10%cream qid until healed
3. Anesthetic-
Dyclonine hydrochloride
Treatment
Analgesic & antipyretic-

 Paracetamol - 500mg-1gm tds
 Ibuprofen- 200-600mg tds
 Choline salicylate gel
 Lidocaine gel
Topical antiviral agents:
 Aciclovir 5% cream
 Penciclovir 1% cream 4-5 days.
Oral antiviral agents:
 Indicated in severe episodes.
Laser treatment
 Laser therapy decreases pain and reduces the number of
recurrences
Management of recurrent HSV
 Reducing trigger factors such as wearing sunscreen

 Topical antiviral medication reduces shedding,
infectivity and size of lesion
5% Acyclovir, 3% penciclovir cream,
10 % docosanol cream 3 times daily for 7 days.
 Systemic antiviral medication usually famciclovir (500-
1000 mg three times daily )
 Symptomatic treatment.
Management of HSV in immunocompromised
patients
 Systemic antiviral medication to prevent dissemination to other site.
 Symptomatic treatment
 Acyclovir-resistant HSV is most frequently seen in this group of patients, where

the virally derived thymidine kinase that activates acyclovir is mutated.
 In such cases, foscarnet is the drug of choice.
 The dosage of the acyclovir family of drugs should be adjusted for age and renal
health.
 A number of vaccines against HSV are currently under development.

VARICELLA ZOSTER
 Primary infection with VZV, an a-herpesvirus, leads to varicella (chicken pox). As

with all herpesviruses, the virus then becomes latent, usually in the dorsal root
ganglia or ganglia of the cranial nerves.
 Reactivation produces herpes zoster infection (HZI), commonly called shingles.

 The incidence of HZI increases with age and the degree of immunosuppression.
 Therefore, it is not uncommon to see HZI in the elderly, in patients undergoing

cancer chemotherapy, in patients on chronic immunosuppressive drug therapy
(such as those who have received organ transplants), and in patients with AIDS.
 As with HSV, this virus is cytopathic to the epithelial cells of the skin and mucosa,
causing blisters and ulcers.
 Transmission is usually by the respiratory route, with an incubation period of
 2 to 3 weeks.
 Herpes zoster (HZ) results from the involvement of second and third branch.
 Primary infection remains latent in the neurons of sensory ganglion, especially

dorsal roots of ganglion of the spinal nerves and extramedullar ganglion of the
cranial nerves.
 Trigeminal nerve V1 -upper eyelid, forehead & scalp
 V2 -midface & upper lip [i/o hard palate & buccal gingiva]
 V3 -lower lip & face [i/o mandibular gingiva & tongue]

 Postherpetic neuralgia, a morbid sequela of HZI, is a neuropathia resulting from
peripheral and central nervous system injury and altered central nervous system
processing.
Trigeminal nerve involvement
Etiology-
 Varicella-zoster virus (VZV)- Human Herpes Virus

III (HHVIII)
 Primary VZV (varicella /chickenpox): a childhood
exanthem
 Secondary VZV (recurrent): (herpes
zoster/shingles) infection
 Spread by respiratory droplets and less

commonly by direct contact
Clinical Presentation
Varicella (chickenpox)-
primary infection
 1st or 2nd decade of life

 Fever, headaches, malaise, and a rash
 Buccal mucosa & hard palate with short-lived vesicles
 Shallow, defined like aphthous ulcers
 Skin with widespread vesicular eruption
 ’’dewdrop like’’ Vesicles -> pustules -> rupture (ulcers) -> crust -
>healing by 2-3 wks
secondary infection
Herpes zoster (shingles)-
 HZI of the skin (shingles) is more common in adults and starts with a
prodrome of deep, aching, or burning pain.
 There is usually little to no fever or lymphadenopathy. This is followed within

2 to 4 days by the appearance of crops of vesicles in a dermatomal or
“zosteriform” pattern.
 This pattern describes the unilateral, linear, and clustered distribution of the
vesicles, ulcers, and scabs in a dermatome supplied by one nerve.
Secondary infection (Shingles)
Triggered by immune suppression.

Common in-
o Elder persons,
o Immunocompromised
o HIV positive individuals,
o malignant blood dyscrasias,
o Malignant tumours,
o Pt. Undergoing radiotherapy.
 Thoracic/lumbar dermatomes are the most frequently involved,
followed by the craniofacial area.
 Lesions heal within 2 to 4 weeks, often with scarring and

hypopigmentation.
 Occasionally, HZI may occur without the appearance of dermatomal

lesions (zoster sine eruptione or zoster sine herpete), which makes the
diagnosis of this condition challenging; these patients often present with
facial palsy.
 A serious and occasional side effect80of HZI is acute retinal necrosis.

Maculopapular rash-> vesicles -> pustules -> ulcerations ->
crust -> heals by 2-4 wks -> scarring & hypopigmentation
Complication of HZ infection
 Postherpetic neuralgia (PHN)
 Paresthesia of ant 2/3rd of tongue
 persist for months and year.
 Neuralgic pain is frequently associated with

sensory loss.
 Ramsay Hunt syndrome
HZ inf of Facial ns
 Blindness
 Encephalitis
 Pneumonia,
 Myocarditis
 Hepatitis
Postherpetic neuralgia (PHN)
 One of the most important complications of HZI is postherpetic neuralgia, defined as pain
that lingers for 30 days or 120 days after the onset of the acute rash.
 Postherpetic neuralgia affects approximately 8 to 70% of patients over age 50; up to 50% of
patients over age 50 have debilitating pain lasting more than 1 month.
 Some unfortunate patients experience pain for years.
 Predisposing factors include older age, prodromal pain, and more severe clinical disease
during the acute rash phase.
 Immunocompromised patients often experience more severe VZI that may appear atypical,
be bilateral, and involve multiple dermatomes; retinitis, pneumonitis, and encephalitis have
been reported as complications in this patient population.
 On rare occasions, HZI may involve not just83the dorsal root ganglion but also the anterior
horn cells, leading to paralysis.
 Ramsay Hunt syndrome type is the reactivation syndrome of herpes zoster in
the geniculate ganglion.
 It has variable presentation which may include a lower motor neuron lesion of the
facial nerve, deafness, vertigo, and pain.
 Patients develop Bells palsy, vesicles of the external ear, and loss of taste sensation
in the anterior two-thirds of the tongue.
 HZI has been reported to cause resorption and exfoliation of teeth and
osteonecrosis of the jawbones, especially in patients with HIV disease.
84
Differential diagnosis
 Pulpitis
 Primary herpes simplex/acute herpetic gingivostomatitis
 Recurrent intraoral herpes simplex
 Pemphigus vulgaris
 Pemphigoid
Diagnosis
 Clinical picture usually all that is needed

 Viral isolation using cell culture is still the best way to confirm a diagnosis of
VZV infection
 Direct fluorescent antibody test-highly sensitive
 PCR
 After primary infection, the patient seroconverts and IgG against VZV is
detectable in the serum. HZI causes a transient rise in IgM and an increase in
levels of IgG, but these are not eliable for diagnostic purposes.
BIOPSY
 Biopsy is usually not required and not the diagnostic test of choice
since the clinical presentation is usually characteristic.
 If one should be performed, tissue should always include the intact

epithelium since that is where the cytopathic effect is best seen.
 VZV and HZI are cytopathic to the epithelial cells and result in the
formation of multinucleated epithelial cells with viral inclusions,
similar to HSV infection.
87
Treatment
 Prevent or lessen severity of infection with vaccination

 Supportive care (Antipyretics, analgesics, hydration)
 Antiviral-
Valacyclovir-1000mg -3 times/day for 7 days
Acyclovir- 800mg -5 times/day for 7 days
Famciclovir -500mg -3 times/day for 7 days
 Postherpetic neuralgia-
Gabapentine & 5% lidocaine patch
 Treatment of primary VZV infection includes the use of acyclovir (800
mg five times a day).
 This reduces infectivity, the severity of lesions, and hospitalizations for

complications.
 However, acyclovir has poor bioavailability.
 Valacyclovir (1,000 mg three times a day) or famciclovir (500 mg three

times a day) for 7 days is effective in treating HZI and should be
started within 72 hours of disease onset.
 These drugs also reduce the incidence of postherpetic neuralgia when

compared with acyclovir.
Cytomegalovirus (CMV) infection
 CMV is a beta-herpesvirus, and 60 to 70% of the adult
population has been exposed.
 Primary infection may be asymptomatic or cause an

infectious mononucleosis–like disease.
 Manifestations of infection and disease are most

evident in the immunocompromised population, such
as patients who have received organ transplants or
those who have AIDS.
 It is the most common cause of pneumonia within the

first 120 days after hematopoietic stem cell
transplantation. Once exposed to CMV, this virus
establishes latency within the connective tissue cells,
such as the endothelium of blood vessels,
Cytomegalovirus (CMV) infection
 CMV within endothelial cells may contribute to
vascular inflammation, vascular occlusion, and end-
organ damage.
 Transmission is by direct transfer of infected white

blood cells through intimate contact and through
blood products.
 In organ transplant recipients, CMV in the donor

organ leads to CMV infection in the recipient.
 There is growing evidence that CMV infection is

associated with Guillain-Barré syndrome, as well as
polyradiculopathy and myopathy in patients with
AIDS.
Clinical presentation
General
 Fever
 Lymphadenopathy
 Spleenomegaly
 Meningoencephalitis
 Myocarditis
 Thrombocytopenia
Oral manifestations-
 Gingivitis and gingival hyperplasia
 Single large necrotic ulcer
 Painful
 Sustain weeks or months
 Any site
 Coinfected with HSV and VZV
Lab diagnosis
 Blood culture
 PCR-CMV DNA
 Biopsy
Differential diagnosis
 Sq cell carcinoma
 Benign or malignant salivary gland tumors
 Traumatic ulcer
 Ulcerative granuloma
 Biopsy for microscopic examination and/or to obtain tissue for culture
is the test of choice for identification of CMV in such ulcers.
 CMV infection produces large intranuclear inclusions (representing

nucleoprotein cores) within endothelial cells and monocytes within
the connective tissue, with an associated nonspecific chronic
inflammation.
 The use of immunohistochemical staining helps identify CMV if there

are only a few infected cells.
 A biopsy has the advantage of also ruling out any of the other
differential diagnoses discussed.
 It is important to make sure that the biopsy includes normal

epithelium because if the ulcer is coinfected with HSV or VZV, these
would be identified on the biopsy in the intact epithelium adjacent to
the ulcer. 94
 Treatment
 Topical anaesthetics
 Systemic analgesic
 Soft diet
 Hydration
 Antivirals-
o ganciclovir-i.v. 10mg/kg/day
to prevent blindness
o valganciclovir
o cidofovir
o α interferon
Coxsackievirus infection
 Ribonucleic acid (RNA) enteroviruses
 Type-A-24 types
 Type-B-6 types
 The viruses replicate first in the mouth and then extensively in the lower
gastrointestinal tract, where they shed. Transmission is therefore primarily by
the fecal-oral route, although some shedding occurs in the upper respiratory
tract.
 In the oral cavity, C V infections lead to three disease entities: HFM disease,
herpangina, and lymphonodular pharyngitis.
Hand-Foot-and-Mouth Disease
 Of all the CVs, C VA16 is the most common cause of this vesicular exanthem.
 Enterovirus (EV)71 (related to C VA16) is a common cause of HFM disease and has been
seen in large outbreaks in Southeast Asia.
 HFM disease, as with many CV infections, including herpangina, tends to be seasonal

(usually summer), occurs in epidemic clusters, and has high transmission rates.
 HFM disease usually afflicts children younger than 10 years in summer. Patients have a
low-grade fever and sore mouth; 75 to 100% of patients have a skin rash, especially on
the hands and feet (dorsa, palms and soles) and 30% on the buttocks.
 The rash is first red and macular and then becomes vesicular.
Oral manifestations
 Symptoms-Sore mouth and throat, red and

edematous tongue more extensive herpangina
 Erythematous macules→ vesicles→ ulcers
 Site- hard palate, tongue, and buccal mucosa .
 Oral mucosal lesions with focal herpes simplex–
like appearance,
 Short course -3 to 7 days

Diagnosis
• Concomitant oral and cutaneous lesions
• Skin lesions- hands, feet and buttocks.
• Antibody-titer increase measured between acute and recovery phases.
• Herpangina
• Herpes simplex infection
• Acute lymphonodular pharyngitis
Treatment
 Self limiting disease
 Symptomatic treatment only
Prognosis
 Excellent
Herpangina
Apthous pharyngitis/Vesicular pharyngitis

 The word herpangina derives from herpes, meaning “vesicular eruption,” and
angina, meaning “inflammation of the throat.”
 CVA (serotypes 1–10, 16, and 22) are the most common viruses isolated from
this disease. But CVB1–5, echoviruses, and E V71 have also been identified in
this condition.
 children under 10 are usually afflicted and outbreaks usually occur in epidemics
in summer.
 Patients develop fever, headache, and myalgia that usually last only 1 to 3 days.
 The first oral symptoms of herpangina are sore

throat and pain on swallowing.
 There may be erythema of the oropharynx, soft
palate, and tonsillar pillars.
 Small vesicles form, but these rapidly break down
to 2 to 4 mm ulcers.
 These persist for 5 to 10 days.
 Lymphonodular pharyngitis is considered a variant

of herpangina and is associated with CVA.
 Patients report a sore throat, but rather than
presenting with vesicles that break down to ulcers,
patients develop diffuse small nodules in the
oropharynx.
Diagnosis
• Other viral illnesses to be ruled out or separated
• Course, time of year, location of lesions, contact with known infected individual
• Hand-foot-and-mouth disease
• Varicella
• Acute herpetic gingivostomatitis
Comparing with HSV infection
Herpangina HSV infections

1. occurs in epidemic 1. do not.
2. Milder 2. Painful
3. site- pharynx and posterior portions of 3. anterior portion of the mouth.
the oral mucosa
4. does not cause a generalized acute 4. Causes acute generalized gingivitis
gingivitis 5. Larger than herpangina
5. Smaller
Necrotizing Ulcerative Gingivitis
 NUG, formerly known as acute necrotizing ulcerative gingivitis (ANUG), and its more
severe counterpart, necrotizing ulcerative periodontitis (NUP), were reclassified in
1999 by the American Academy of Periodontics under the category of “Necrotizing
Periodontal Disease.”
 These are acute ulcerative-inflammatory conditions of the gingiva and periodontium,

respectively, that are associated with polymicrobial infection.
 NUG and NUP have strong associations with immune suppression (especially AIDS),
debilitation, smoking, stress, poor oral hygiene, local trauma, and contaminated food
supply. Diabetes may also be a risk factor.
 It is unclear if NUG is a forerunner of NUP, but they are often seen in patients with
AIDS.
 Etiology : The more important and constant of the microbes involved
include Treponema species, Prevotella intermedia, Fusobacteria
nucleatum, Peptostreptococcus micros, Porphyromonas gingivalis,
Selenomonas species, and Campylobacter.
Local factors-
 Poor oral hygiene
 Pre-existing marginal gingivitis
 Faulty dental restorations
 Periodontal pockets
 Traumatized gingiva
 Smoking
 Emotional stress
Systemic-
 Nutritional deficiency
 Debilitating disease-HIV, anemia, leukemia
 Marked malnutrition
Clinical features
 Age - 16 and 30 yrs ,low socio-economic group
 Sudden onset, tenderness, profuse salivation,

metallic taste, spontaneous bleeding from
gums, loss of taste sensation, fetid odor.
 Teeth- extruded, sensitive to tender, woody

sensation, difficulty in chewing food.
 Necrotic punched out-crater like ulcerations

on interdental and marginal gingiva.
 Gingiva covered by gray pseudomembranous

slough, painful & raw on removing.
 Severe form- noma, a large necrotic ulcer.

Differential diagnosis:
 The acute onset of erythematous and ulcerated gingiva of NUG

may suggest a diagnosis of primary herpetic gingivostomatitis.
 Desquamative gingivitides (such as mucous membrane

(cicatricial) pemphigoid, pemphigus vulgaris, lichen planus, and
hypersensitivity reaction) may present primarily on the gingiva,
with no skin findings.
 However, these conditions are not of acute onset but rather

chronic and/or progressive over months and years and are
characterized by inflammation rather than necrosis.
Diagnosis
 Secretions from the gingival sulcus grow mixed flora but in particular will be
culture positive for Treponema species, P. intermedia, F. nucleatum.
 Necrotizing gingival lesions may also be caused by microbes other than

fusospirochetes, such as Pseudomonas aeruginosa.
 A biopsy usually is not helpful in making a diagnosis, although biopsies may

be performed to rule out some other condition that may have a similar
clinical presentation.
Treatment
Local
 Debridgement, ultrasonic scaling,
 Rinses of chlorhexidine
 3% hydrogen peroxide+saline- 12 times a day
 Topical povidone iodine
Systemic antibiotics-
 Penicillin-500mg qid for 5 days
 Tetracycline-250-500mg 6 hrly
 Metronidazole-200-400mg tds
15mg/kg body wt 6 hrly I.V.
Eliminating predisposing factors
Maintainance of oral hygiene
Prognosis
 Excellent
ERYTHEMA MULTIFORME
 EM is an acute, self-limited, inflammatory mucocutaneous disease that

manifests on the skin and often oral mucosa, although other mucosal
surfaces, such as the genitalia, may also be involved.
 It is an acute inflammatory disease of skin & mucous membranes that

causes a variety of skin lesions - hence the name “multiforme”.
 Two subtypes :
(i) EM minor
(ii) EM major (Stevens Johnson Syndrome,
Toxic Epidermal Necrolysis / Lyell’s syndrome)
ERYTHEMA MULTIFORME
 EM minor if there is less than 10% of skin involvement

and there is minimal to no mucous membrane
involvement, whereas
 EM major has more extensive but still characteristic skin

involvement, with the oral mucosa and other mucous
membranes affected.
Trigger factors:
(a) Infection
 EM is a hypersensitivity reaction, and the most common inciting
factors are infection, particularly with HSV.
 Herpes Simplex Virus 1 & 2 : 70 to 80 % cases
 The viral, bacterial, fungal, and protozoal infections and
medications may also play a role.
 Because it is a hypersensitivity reaction, HSV is not cultured from
lesions.
(b) Drug reactions

• Sulfonamides, NSAIDs, Penicillin, Anticonvulsants.
• Drugs account for 95% of cases of TEN & atleast 50% of cases
of SJS
(Khalid A. Al-Johani: OOO 2007,103:642-54)
(C) Others:
• Progesterone
• Mycoplasma pneumoniae
• Vaccines (Diphtheria-tetanus, Hepatitis B)
• Radiotherapy
• Crohn’s disease
• Histoplasmosis
• Infectious mononucleosis
Pathogenesis:
immune complex vasculitis
complement becomes fixed,
culminating leukocytoclastic
destruction of vascular walls, small
blood vessel occlusion
subsequent ischemic
necrosis of epithelium &
underlying connective tissues
L.R Eversole OOO 1994;77:555-71

Clinical Features
 EM generally affects those between ages 20 and 40 years, with

20% occurring in children.
 Patients with recurrent EM have an average of 6 episodes a year

(range 2–24), with a mean duration of 9.5 years; remission
occurred in 20% of cases.
 Episodes usually last several weeks.
 There is often a prodrome of fever, malaise, headache, sore

throat, rhinorrhea, and cough.
 These symptoms suggest a viral (especially respiratory tract)

infection, and this is not surprising since infectious agents are
known to trigger EM.
SIGN and
SYMPTOMS
 Skin lesions appear rapidly over a

few days and begin as red macules
that become papular, starting
primarily in the hands and moving
centripetally toward the trunk in
a symmetric distribution.
 The most common sites of

involvement are the upper
extremities, face, and neck.
 The skin lesions may take several

forms—hence the term
multiforme.
SIGN and
SYMPTOMS
 The classic skin lesion consists of a

central blister or necrosis with
concentric rings of variable color
around it called typical “target” or
“iris” lesion that is pathognomonic of
EM; variants are called “atypical
target” lesions.
 The skin may feel itchy and burnt.
 Postinflammatory hyperpigmentation
is common in dark-skinned individuals
and may be worsened by sun
exposure.
-Target lesion has a regular round shape & 3 concentric
zones:
a) A central dusky or darker red area
b) A paler pink or edematous zone
c) A peripheral red ring
ORAL FINDING
 The oral findings in EM range from mild

erythema and erosion to painful
ulcerations.
 When severe, ulcers may be large and

confluent, causing difficulty in eating,
drinking, and swallowing, and patients
with severe EM may drool blood-tinged
saliva.
 Oral lesions are present in 23 to 70% of

patients with recurrent EM. The most
commonly affected sites are the lips (36%),
buccal mucosa (31%), tongue (22%), and
labial mucosa(19%).
 Genital and ocular sites are affected in 25

and 17% of cases, respectively.
ORAL FINDING
 The concept of pure oral EM is

controversial and not universally
accepted since some dermatologists does
not believe.

 Nevertheless, cases of oral EM without
skin involvement have been reported.
 Lesions may present intraorally only or

also involve the lips and skin.
 Intraoral lesions are irregular bullae,

erosions, or ulcers surrounded by
extensive areas of inflammation.
 Severe crusting and bleeding of the lips

are common.
 Primary HSV gingivostomatitis

 Pemphigus
 Pemphigoid
 Recurrent aphthous ulcers
 Paraneoplastic pemphigus
 Primary HSV gingivostomatitis :
 Primary HSV gingivostomatitis with its viral prodrome and

erosions and ulcerations may resemble EM, but these lesions are
culture positive for HSV and do not usually present with the
typical skin rash. Lesions of HSV are usually smaller and well
circumscribed, whereas EM lesions are larger.
 Pemphigus and Pemphigoid :
 Autoimmune vesiculobullous disease such as pemphigus and

pemphigoid may have oral ulcers and skin lesions, although skin
lesions are bullous in nature and not maculopapular, with a
centripetal progress such as is seen in EM.
 They are chronic, slowly progressive diseases that usually

persist for months, whereas EM heals within weeks.
Recurrent oral EM in the absence of skin findings may be

confused with recurrent aphthous ulcers, but aphthous ulcers
present as discrete lesions, whereas lesions of EM are more diffuse.
 Paraneoplastic pemphigus :
 Some cases of severe EM causing hemorrhagic crusts to form on

the lips may resemble paraneoplastic pemphigus.
 These lesions are usually present for months and are associated
with malignancy and with severe conjunctival and skin lesions.
Erythema multiforme v/s Herpes infection
Features Erythema multiforme Herpes infection
Age Young adults Children

Sites Lips, alveolar mucosa, Gingiva, lips, alveolar
palate, skin mucosa, Palate
Symptoms Mild to severe Moderate to severe
Appearance Large, deep, irregular oral Small round, shallow,
& lip ulcers symmetric oral ulcers
Target skin Present Absent
lesions
Erythema multiforme v/s Pemphigus
Features Erythema Pemphigus

multiforme
Age Primarily in young Older patients
adults
Duration Acute disease Chronic disease
Appearance Erosive crusty Pustulopapular
changes vegetation
Skin changes Target lesions No target lesions
Nikolsky’s sign Negative Positive

Investigations & diagnosis
 There are no specific laboratory tests that are useful, and the diagnosis is made
primarily on clinical findings and sometimes it is supported by perilesional tissue
biopsy.
 Early lesions show lymphocytes and histiocytes in the superficial dermis around
superficial dermal vessels. This is followed by hydropic degeneration of basal
cells, keratinocyte apoptosis and necrosis, subepithelial bulla formation, and a
lymphocytic infiltrate.
 Leukocyte exocytosis is also usually noted. Similar changes are seen in the
biopsies of patients with oral EM.
 British Journal of Oral and Maxillofacial Surgery 46(2008)90-95

Treatment:
Erythema multiforme
Mild cases:
 Topical anesthetic mouthwashes:
5% lignocaine(Xylocain),
0.15% benzydamine (Tantum oral rinse)
 Topical steroids-
0.1% triamcinolone acetonide (Kenacort) in Orabase to be applied
after every meal and at bed time
 Soft / liquid high protein diet, intravenous fluids
Moderate to severe cases: Short term-high dose systemic steroids are useful in
reducing intensity of symptoms and may shorten healing time, especially when
started early in the course of disease.
 Prednisolone (Wysolone), 20 mg tablet, twice a day for 5 days
 Betamethasone (Betnesol), 0.5 mg tablet, thrice daily for 5 days
Recurring attacks:
Early treatment of recurrent HSV infection to prevent recurring
attacks of EM
 Famciclovir 500 mg 2 times a day for 5 days
 Valacyclovir 1000 mg 2 times a day for 5 days
Dapsone (100–150 mg/d) and antimalarials are partially successful

in suppressing recurrent outbreaks but may be associated with
significant side effects.
Stevens-Johnson Syndrome
 Studies done within the last 10 to 15 years now support the concept that SJS is a
less severe variant of TEN and separate clinically and etiopathogenetically from
EM.
 Although all three are hypersensitivity reactions and give rise to oral bullae,
erosions, ulcers, and crusted lips, the skin lesions of SJS and TEN are different from
EM.
 They are more severe and tend to arise on the chest rather than the extremities on
erythematous and purpuric macules; these lesions are called “atypical targets.”
 SJS is much more likely to be associated with medication use and Mycoplasma
pneumoniae infection and rarely with HSV infection, whereas EM is much more
likely to be associated with HSV infection.
GENERAL
 Eye (conjunctival), Genital, Cutaneous,
 Iris or target lesions are characteristic on skin.
Oral Lesions
 Labial vermilion and anterior portion of oral cavity
 Early phase is macular followed by erosion,

sloughing, and painful ulceration
 Lip ulcers- crusted and hemorrhagic.
 Pseudomembrane; foul-smelling
 Vesicle→ painful erosions → grayish-white

/hemorrhagic pseudomembranes.
 Posterior oral cavity and oropharyngeal

involvement - odynophagia, sialorrhea, drooling
Treatment
 Hydration
- Oral rinses
- Topical steroids–
- hydrocortisone-wycort 2.5% ointment
- Orabase 0.5%
- Triemcinolone-kenolog cream o.1%
Prognosis
- Betamethasone-valisone cream 0.1% Good;
 Systemic corticosteroid – self-limiting usually
Tab.cortin 100 mg 6 hrly Recurrences common
Tab.wysolon 60 mg in div doses
 Antiviral -Acyclovir, famciclovir, valacyclovir
 May require admission to hospital burn unit
 Intravenous immunoglobulin, and thalidomide
 May also be required.
Plasma Cell Stomatitis and Oral Hypersensitivity
Reactions
Etiology and Pathogenesis
 This is a group of conditions that have protean

manifestations. Oral hypersensitivity reactions may
take the following forms:
 1. Acute onset of ulcers such as in oral EM.

 2. Red and white reticulated lesions of a lichenoid
hypersensitivity reaction.
 3. Fixed drug eruption.
 4. Marked erosions and erythema with or without
ulceration called plasma cell stomatitis (PCS).
 5. Swelling of the lips/angioedema.
 6. Oral allergy syndrome that presents mainly with
symptoms of itching with or without swelling of the
oral structures and oropharynx.
plasma cell stomatitis (PCS)
 PCS is a hypersensitivity reaction that was first described

in the late 1960s and early 1970s and was likely a
contact stomatitis to a component of chewing gum.
 Since then, sporadic cases have continued to be

reported, and these are all likely caused by a sensitizing
contactant, whether or not the contactant is identified.
 These include khat (Catha edulis), components of

toothpaste, mint candies, and household cleaners.
 Sometimes, the terms mucous membrane plasmacytosis

and plasma cell orificial mucositis are used because
there may be involvement of the upper respiratory tract.
Clinical presentation
 PCS occurs within days of exposure to the contactant,

with most signs and symptoms limited to the oral cavity.

 Some lesions may affect the periorificial tissues or the
oropharynx, leading to upper airway symptoms of
hoarseness, dysphagia, and mild airway obstruction
 .
 Endoscopy may reveal erythematous and thickened
mucosa, often with a cobblestoning pattern from the
edema. An obvious allergen/contactant is not always
identified.
Oral manifestation :
 PCS occurs within a few days of exposure. It

presents as brightly erythematous macular areas
of the oral cavity, almost always involving the
marginal and attached gingiva or alveolar
mucosa and often involving other soft tissues,
such as the maxillary and mandibular sulcus or
buccal mucosa.
 Ulcers may be present, and there may be

epithelial sloughing and desquamation.
 The gingiva may also be swollen and edematous.

Patients may complain of pain and sensitivity
and bleeding of the gingiva on brushing.
 Angular cheilitis with fissuring and dry, atrophic

lips have been reported.
Treatment-
 PCS is self-limiting and will generally, but not always, regress if the contactant is
identified and removed. Nevertheless, pain control and anti-inflammatory
agents may be helpful during the healing process.
 Topical steroids may help reduce inflammation and speed healing.
 Some lesions have resolved with intralesional triamcinolone injections,

although the gingiva is a particularly difficult location for such injections.
 Cases have also responded well to prednisone.
 Gingivectomies may be needed to recontour lesions that are long-standing and

more fibrotic.
 Recurrent aphthous stomatitis
 Behcet disease (Behcet syndrome)
141
Ulcer -Greek word- “Wound / Sore”
“ An ulcer may be described as a breach in

continuity of surface epithelium of skin or
mucous membrane to involve the
underlying connective tissue as a result of
micromolecular cell death.
(S .Das,Clinical Manual of Surgery)

ACCORDING TO BAILEY & LOVE’S SHORT PRACTICE OF SURGERY
‘ulcer’ is defined as a break in continuity of surface epithelium due

to progressive destruction and the base of ulcer may be
necrotic ,granulating or malignant.
143
PARTS OF ULCER
Margin
 Edge
 Floor
 Base
 Margins - Junction between normal epithelium and ulcer.
 Edges - Junction between margin and floor.
 Floor - Exposed surface within the ulcer (see).
 Base - On which the ulcer rest (feel).

Edges
 Sloping- Healing, traumatic
 Undermined- Tuberculous
 Punched out- Gumma/syphilis
 Raised, pearly white or beaded-

Rodent ulcer
 Rolled out/everted- Malignant

PATIENTS WITH RECURRING ORAL ULCERS
 Recurring oral ulcers are among the most common problems seen
by clinicians who manage diseases of the oral mucosa.
 There are several diseases that should be included in the
differential diagnosis of a patient who presents with a history of
recurring ulcers of the mouth, including
 Recurrent aphthous stomatitis (RAS),

 Behçet syndrome,
 Recurrent HSV infection, and
 Recurrent EM.
RECURRENT APHTHOUS
STOMATITIS
RECURRENT APHTHOUS STOMATITIS
 RAS is a disorder characterized by recurring ulcers confined to the

oral mucosa in patients with no other signs of disease.
 RAS is considered a diagnosis of exclusion since hematologic

deficiencies, immune disorders, and connective tissue diseases may
cause oral lesions clinically similar to RAS.
SYNONYMS
RECURREN
T ULCERS
CANKER
APHTHAE
SORES
The term CANKER
"aphthous"
LATIN
Greek word WORD
"aphtha" CANCER
BUT NOT A
ulceration. TYPE OF
CANCER
DEFINITION
It is a most common disease charecterized by the

development of painful,recurring ,solitary or multiple
ulcerations of the oral mucosa.
ETIOLOGY
BACTERIAL INFECTION- a pleomorphic transitional L-form of an α-
hemolytic streptococci,streptococcus sanguis play a significant
role.
IMMUNOLOGIC ABNORMALITIES
Iron, vitamin B12, folic acid deficiency
TRAUMA- due to self –inflicted bites,oral surgical

procedures,tooth brushing,dental procedures,needle
injections,dental trauma
ENDOCRINE CONDITION-during premenstrual period and at

postovulation period.
ALLERGIC FACTORS- hay fever,asthma,drug/food allergy.

PATHOGENESIS
PRIMARY DECREASE IN INCREASE IN

IMMUNE MUCOSAL ANTIGENIC
DYSREGULATION BARRIER EXPOSURE
REDDUCTION OF ↑ CYTOTOXIC
CD4 + NUTRITIONAL
TRAUMA DESTRUCTION
DEFICIENCY
T- LYMPHOCYTE OF MUCOSA
TYPES
RECURRENT APHTHOUS
MINOR
RECURRENT APHTHOUS
MAJOR
RECURRENT HERPETIFORM
ULCERATIONS
CLINICAL FEATURES
RECURRENT APHTHOUS MINOR
 AGE-10-30yr
 GENDER-women>men
 SITE-common on non-keratinized mucosa e.g –buccal
&labial mucosa,buccal & lingual sulci,tongue,soft
palate,pharynx,gingiva.
 APPEARANCE-begins as a single or multiple superficial
erosions covered by greyish – white removable
fibrinopurulent membrane encircled by erythematous halo.
 SIZE-2-3 mm to 10 mm in diameter.
 Persist for 7-14 days & heal without scarring.
MINOR APHTHOUS ULCER
Area of ulceration with surrounding erythema present on

movable mucosa of left maxillary muco-buccal fold.
MINOR APHHOUS ULCER
.
RECURRENT APHTHOUS
MAJOR
 Previously it represent a separate disease entity k/n as

periadenitis mucosa necrotica recurrens (mikulicz’s
scarring aphthae or sutton’s disease)
 It is now regarded as severe expression of aphthous
stomatitis.
 COMMON SITE- lips,cheeks,tongue,soft
palate,fauces,cause severe pain & dysphagia.
 Also involve keratinized mucosa
 INCIDENCE – common in HIV patient.
 SIZE – Larger than the minor apthous ulcer diameter
more than 10mm.
 No.- 1-10 in no.
 Takes 4-6 weeks to heal.
 Heal with scarring
 Recurrs in less than a month time.
 APPEARANCE- extend deeper and may
present as crater-like ulcers with rolled
margins which are indurated on
palpation because of underlying fibrosis.
MAJOR APHTHOUS ULCER
RECURRENT HERPETIFORM
ULCERS
RECURRENT HERPETIFORM ULCERATIONS
consist of clusters crops of ulcer

due to tendency resemble herpetic
to reccur lesions. present
Clinical features
 SITE- any intra oral site

 SIZE-1-3 mm in diameter
 APPEARANCE – charecterized by crop of small,shallow ulcers ,that
may be joined together and form large ulcer.
 No. – 10 – 100
 Healing occur in 1 to 2 weeks.
 Heal with scarring.
 Lesions persist for 1 to 3 year, with short remissions
RECURRENT HERPETIFORM ULCERATIONS
CONTRASTING FEATURES
MINOR MAJOR HERPETIFORM

SIZE <0.5 cm >0.5 cm <0.5 cm
SHAPE Oval Ragged oval
oval,crateriform
NUMBER 1-5 1-10 10-100
LOCATION Non-keratinized Non-keratinized Any intra oral site
mucosa mucosa
TREATMENT Topical Topical/systemic/ Topical/systemic
corticosteroids, intralesional corticosteroids,
tetracycline corticosteroids, tetracycline
mouthrinse immunosuppressives mouthrinse
 The first episodes of RAS most frequently begin during the second decade of life.
 The lesions are confined to the oral mucosa and begin with prodromal burning any
time from 24 to 48 hours before an ulcer appears. During this initial period, a
localized area of erythema develops.
 Within hours, a small white papule forms, ulcerates, and gradually enlarges over the
next 48 to 72 hours. The individual lesions are round, symmetric, and shallow
(similar to viral ulcers), but no tissue tags are present from ruptured vesicles, which
helps distinguish RAS from diseases that start as vesicles, such as pemphigus, and
pemphigoid.
 Multiple lesions are often present, but the number, size, and frequency vary
considerably.
 The buccal and labial mucosae are most commonly involved. Lesions are less
common on the heavily keratinized palate or gingiva.
166
HISTOPATHOLOGY
Fibrinopurulent Inflammatory cells

Central zone of CYTOLOGICAL SMEAR
membrane covers – neutrophils and :
ulceration.
the ulcer. lymphocytes seen •
Anitschkow cells
ANITSCHKOW CELL
DIFFERENTIAL DIAGNOSIS
i). Recurrent Herpes Simplex Virus infection.

ii). Behcet’ syndrome.
iii). Cyclic neutropenia.
iv). Recurrent erythema multiforme.
170
BEHCET’S SYNDROME
 Behcet’s syndrome is a chronic multisystemic inflammatory disease and it
involves the several areas of the body.
 The mucosal surfaces of the eyes, mouth, and genitals are affected by
ulcerations that appear similar to aphthous ulcers.
 The ulcerations are very similar in size to the minor form of aphthae.
 The ulcerations heal in 7 to 10 days, but recurrence is frequent.
 In contrast to aphthae, Behcet’s ulcerations appear six or more at a time, and

have a larger erythematous ragged border.
 One diagnostic method is a pathergy test. This is a tuberculin-like skin reaction

from an injection of an inert substance171such as sterile saline solution.
CYCLIC NEUTROPENIA
 Cyclic neutropenia is manifested by cyclic reduction in the number of circulating
neutrophils. The reduced number of neutrophils occur routinely at 3-week
intervals, and last for 1 to 3 days.
 The recovery period is 5 to 8 days. The condition is usually seen in infants and
young children, but can appear at any age. During episodes of reduced numbers
of neutrophils, symptoms include a low-grade fever, malaise, headaches, skin
infections, and alveolar bone loss.
 These oral ulcerations are painful, with a central whitish pseudomembrane and
an erythematous border. The ulcerations are generally less than 1 cm in
diameter. They can appear anywhere in the oral cavity. The diagnosis is made by
following the number of circulating neutrophils over a period of 6 to 8 weeks.
172
Recurrent oral EM in the absence of skin findings may be

confused with recurrent aphthous ulcers, but aphthous ulcers
present as discrete lesions, whereas lesions of EM are more diffuse.
TREATMENT
a). For milder cases:

(with two or three small lesions)
i). Protective emollients e.g.

orabase, zelactin etc.
ii). Topical anesthetic agents.
iii). Topical NSAID’S e.g. diclofenac to
relieve pain.
b). In more severe cases:
i). The use of a high potency topical steroid preparation :

Fluocinonide,
Clobetasol,
Betamethasone etc.
 It can be placed directly on the lesion, shortens healing time and reduces
the size of the ulcers.
 The effectiveness of the topical steroid is partially based upon good
instruction and patient compliance regarding proper use.
 The steroid gel can be carefully applied directly to the lesion after meals
and at bedtime two to three times a day or mixed with an adhesive such
as Orabase prior to application.
 Larger lesions can be treated by placing a gauze sponge containing the
topical steroid on the ulcer and leaving it in place for 15 to 30 minutes to
allow for longer contact of the medication.
ii) Amelaxanox paste.
iii)Tetracycline mouthwash.
 These other topical

preparations that have been
shown to decrease the healing
time of RAS lesions and these
can be used either as a
mouthrinse or applied on
gauze sponges.
 Intralesional steroids can be

used to treat large indolent
major RAS lesions.
c). The lesions not responding to topical steroids,
systemic therapy is given using:
Colchicines,
Dapsone,
Thalidomide etc.
 Thalidomide, a drug originally marketed as a nonaddicting hypnotic in the
1950s, was withdrawn from the market in the early 1960s due to its association
with multiple, severe, deforming, and life-threatening birth defects.
 Further investigation demonstrated that thalidomide has significant

antiinflammatory and immunomodulatory properties and is useful in treating a
number of diseases, including erythema nodosum leprosum, discoid lupus
erythematosus, graftversus- host disease, multiple myeloma, and Behçet
syndrome.
 The drug has also been shown to reduce both the incidence and severity of
major RAS in both HIV-positive and HIV negative patients. The use of
thalidomide for RAS should be reserved for management of severe major RAS
where other less toxic therapies, including high-potency topical steroids,
colchicine, and pentoxifylline, have failed to control the disease.
 Thalidomide must be used with extreme caution in women during childbearing

years owing to the potential for severe life-threatening and deforming birth
defects.Other side effects of thalidomide include peripheral neuropathy,
gastrointestinal complaints, and drowsiness.
178
BEHCET’S SYNDROME
 Behçets disease (BD) was initially described by the

Turkish dermatologist Hulusi Behçet as a triad of
symptoms including
Recurring oral ulcers,

Recurring genital ulcers, and
Eye involvement.
ETIOLOGY
 The cause of BD is unknown, but immune dysregulation, including

circulating immune complexes, autoimmunity, cytokines, and heat
shock proteins, is a major factor in the pathogenesis of BD.
 The HLA -B51 genotype is most frequently linked to BD, especially

in patients with severe forms of the disease in Asia, but the exact
nature of genetics in the etiology of BD is unclear.
 It is theorized that BD results when a bacteria or virus triggers an

immune reaction in a genetically predisposed individual.
CLINICAL PRESENTATION
 Highest incidence is in young adults between
the ages of 25 and 40.
 The most common site of involvement is oral

mucosa. The genital area is the second most
common site of involvement and presents as
ulcers of the scrotum.
 The eye lesions consist of uveitis, retinal

vasculitis, vascular occlusion, optic atrophy,
and conjunctivitis.
 Blindness is a common complication of the

disease, and periodic evaluation by an
ophthalmologist is necessary.
 Generalized involvement occurs in over half of patients with BD. Arthritis occurs in
greater than 40% of patients and most frequently affects the knees, ankles, wrists,
and elbows. The affected joint may be red and swollen, as in rheumatoid arthritis,
but involvement of small joints of the hand does not occur, and permanent
disability does not result.
 In some patients, central nervous system involvement is the most distressing

component of the disease. This may include brainstem syndrome, involvement of
the cranial nerves, or neurologic degeneration resembling multiple sclerosis that
can be visualized by MRI of the brain.
 Other reported signs of BD include thrombophlebitis, intestinal ulceration, venous

thrombosis, and renal, cardiac, and pulmonary disease.
 Both pulmonary involvement and cardiac involvement are believed to be

secondary to vasculitis.
 Involvement of large vessels is life threatening because of the risk of arterial

occlusion or aneurysms.
 A variant of BD, MAGIC syndrome, has been described. It is characterized by mouth

and genital ulcers with inflamed cartilage.
182
The lesions precipitated by trauma, and it is common for patients
with Behçet’s syndrome to have a cutaneous hyper-reactivity to
intracutaneous injection or a needlestick (PATHERGY).
 Positive pathergy is defined as

an inflammatory reaction forming
within 24 hours of a needle
puncture scratch, or saline
injection.
 A positive pathergy test, which is

performed by placing a 20 gauge
needle 5 mm into the skin of the
forearm. The test is positive if an
indurated papule or pustule greater
than 2 mm in diameter forms
within 48 hours.
ORAL MANIFESTATIONS
 The most common single site of involvement

is the oral mucosa.
 Recurring oral ulcers appear in over 90% of

patients; these lesions cannot be
distinguished from RAS .
 Some patients experience mild recurring oral

lesions; others have the deep large scarring
lesions characteristic of major RAS.
 These lesions may appear anywhere on the

oral or pharyngeal mucosa.
DIAGNOSIS
 Because the signs and symptoms of Behçet’s syndrome overlap with

those of several other diseases, particularly the connective-tissue
diseases, it has been difficult to develop criteria that meet with
universal agreement.
 Five different sets of diagnostic criteria have been in use during the
past 20 years. In 1990, an international study group reviewed data
from 914 patients from seven countries.
 A new set of diagnostic criteria was developed that
includes recurrent oral ulceration occurring at least three
times in one 12-month period plus two of the following
four manifestations:
 Recurrent genital ulceration.
 Eye lesions including uveitis or retinal vasculitis.
 Skin lesions including erythema nodosum, pseudofolliculitis,

papulopustular lesions, or acneiform nodules in post adolescent
patients not receiving corticosteroids.
 A positive Pathergy test.

 This is from other oculomucocutaneous syndromes:
 Sweet Syndrome : oral ulcers, conjunctivitis, episcleritis,

Inflamed tender skin papules or nodules.
 Erythema Multiforme: erosions, target(iris) lesions.
 Pemphigoid: bullae, erosions.
 Pemphigus : erosions, flaccid skin bullae.
 Reiter syndrome: ulcers, conjunctivitis,
 Herpes simplex virus
 Lupus erythematosus
TREATMENT
The management of Behçet’s syndrome depends on the severity and the sites of
involvement.
 Azathioprine combined with prednisone has been shown to reduce ocular

disease as well as oral and genital involvement.
 Pentoxifylline, which has fewer side effects than do immunosuppressive drugs

or systemic steroids, has also been reperted to be effective in decreasing disease
activity, particularly of oral and genital lesions.

 Dapsone, colchicines and thalidomide have also been reported to be effective
to treat mucosal lesions of Behcet’s disease.
 Agents that are active against the cytokine TNF-a, such as infliximab and
ethanercept, have demonstrated potential effectiveness against the
mucocutaneous and ocular manifestations of BD.
PATIENTS WITH CHRONIC MULTIPLE LESIONS
 Patients with an oral mucosal disease characterized by chronic multiple lesions,

which are continuously present, are frequently misdiagnosed for weeks to
months since their lesions are frequently confused with recurring oral mucosal
disorders such as RAS and HSV-associated lesions.
 The clinician can avoid misdiagnosis by carefully questioning the patient on the
initial visit regarding the natural history of the lesions.
 In recurring disorders such as severe aphthous stomatitis, the patient may

experience continual new episodes of ulceration of the oral mucosa, but
individual lesions heal and new ones form.
 The same lesions are present for weeks to months.

PATIENTS WITH CHRONIC MULTIPLE LESIONS
 The major diseases in this group are :
 Pemphigus Vulgaris
 Paraneoplastic Pemphigus
 Pemphigus Vegetans
 Bullous Pemphigoid
 Mucous Membrane Pemphigoid (Cicatricial Pemphigoid)
 Epidermolysis Bullosa Aquisita
 Chronic Bullous Disease of Childhood
PEMPHIGUS
 The term 'pemphigus, is derived from Greek word Pemphix which literally means
a Blister or Bubble.
 Pemphigus includes a group of autoimmune, potentially life-threatening diseases

that cause blisters and erosions of the skin and mucous membrane.
 Pemphigus is an autoimmune disease characterized by intraepithelial blister

formation due to a breakdown in intercellular adhesion.
 This breakdown process is referred to as primary acantholysis.
Burket’s Oral Medicine, 11th Edition. 191

 Pemphigus occurs more frequently among Ashkenazi Jews, in whom
studies have shown a strong association with HLA -DR4 and DQ8
haplotypes.
 The DR6 and DQ5 haplotypes are more common in non-Jewish

patients.
 Desmoglein 1 (DSG1), a glucoprotein adhesion molecule, is primarily

found in the skin, whereas desmoglein 3 (DSG3) is chiefly detected in
mucosal epithelium.
 The immune reaction against these glycoproteins causes a loss of

cell-to-cell adhesion, resulting in the separation of cells and the
formation of intraepithelial bullae.
192
PF; Pemphigus foliaceus, PNP; Paraneoplasic pemphigus,
PV; Pemphigus vulgaris, SPD; Subcorneal pustular
dermatosis
S Wolff, et al., Fitzpatric’s Dermatology in General Medicine, 7th edition, 2008.

In pemphigus foliaceus, the blister occurs in the
superficial granular cell layer, whereas in PV, the lesion is
deeper, just above the basal cell layer.
194
P foliaceous
Pemphigus vulgaris
P erythematosus
200
AGE OF ONSET
Pemphigus vulgaris Middle age (40-60 yrs)

Pemphigus foliaceus Middle age
Paraneoplastic pemphigus Adult, children
Bullous pemphigoid Elderly (60-75 yrs)
Mucous membrane pemphigoid Old age (60-80 yrs)
Pemphigoid gestationis Pregnant women
Dermatitis herpetiformis Adult
Linear IgA disease Before 5 & after 60 yrs
EBA Adults & children
Hailey- hailey disease Adults
Epidermolysis bullosa At birth or during infancy
INITIAL SITE
Pemphigus vulgaris Oral mucosa
Pemphigus foliaceus Scalp, chest
Bullous pemphigoid extremities
Mucous membrane pemphigoid Oral or other mucosa
Pemphigoid gestationis Periumblical, extremities
Dermatitis herpetiformis Trunk, scalp
Linear IgA disease Genital in children; no predilection in

adults
EBA Mucosa, extremities

Hailey- hailey disease Friction sites
MUCOSAL INVOLVEMENT
Pemphigus vulgaris Almost all

Pemphigus foliaceus None
Intercelluar IgA dermatosis Uncommon
Paraneoplastic pemphigus Severe mucositis
Bullous pemphigoid 10 – 40%, transient, mild
Mucous membrane pemphigoid Almost all
Pemphigoid gestationis Rare
Dermatitis herpetiformis Rare
Linear IgA disease 80%
EBA 50%
Hailey- hailey disease Uncommon
DISTRIBUTION OF LESIONS
Pemphigus vulgaris Scalp, face, flexures, trunk
Pemphigus foliaceus Seborrhoeic distribution
Intercelluar IgA dermatosis Axillae, groins, face, scalp, proximal limbs
Paraneoplastic pemphigus Upper body, palmoplantar
Bullous pemphigoid Trunk, limbs, flexures
Mucous membrane pemphigoid Infrequent; head, neck, upper trunk

DISTRIBUTION OF LESIONS
Pemphigoid gestationis Abdomen, extremities
Dermatitis herpetiformis Symmetrical over extensors of trunk including

elbows, knees.
Linear IgA disease Perineum, face, trunk, limbs
EBA Generalized, variable
Epidermolysis bullosa Sites of trauma
Hailey- Hailey disease Sides of neck, axillae, groins, perineum

LESIONS CHARACTERISTICS
Pemphigus vulgaris Flaccid blisters, erosions, flexural

vegetations
Pemphigus vegetans Vesicles, pustules, erosions, vegetating
Plaques
Pemphigus foliaceus Scaly papules, crusted erosions,
Erythroderma
Intercelluar IgA dermatosis Flaccid pustules annular or circinate

configuration
Paraneoplastic pemphigus Polymorphous, bullae, erosions, ‘target
lesions’
Bullous pemphigoid Urticated plaques, tense blisters, (milia)
Mucous membrane pemphigoid Erosions, blisters, gingivitis, milia, Scarring

LESIONS CHARACTERISTICS
Pemphigoid gestationis Urticated plaques, tense blisters
Dermatitis herpetiformis Papulovesicles
Linear IgA disease Urticated plaques, annular lesions, tense blisters
EBA Urticated plaques, tense blisters, milia ,Scarring
Hailey- Hailey disease Flaccid vesicopustules, crusted erosions or

expanding circinate plaques appear in areas
exposed to friction
MORPHOLOGY OF LESIONS
CHARACTERISTICS OF BULLAE BASED ON LEVEL OF SPLIT
NIKOLSKIY SIGN
 Nikolsky’s sign is a well-described clinical sign that can be helpful in
differentiating some of the autoimmune skin disorders and even
determining their prognosis.
 Pyotr Vasilyewich Nikolsky (1858–1940) was a Russian dermatologist

who studied at the University of Kiev and published a thesis on
pemphigus in 1895.
 Nikolsky first described the sign that bears his name in 1896. He
related how, after rubbing the skin of patients who had pemphigus
foliaceus, there was a blistering or denudation of the epidermis with a
glistening, moist surface underneath. According to his explanation, the
skin showed a weakening relationship and contact between the
corneal (horny) and granular layers on all surfaces, even in places
between lesions (eg, blisters, excoriations) on seemingly unaffected
skin. Nikolsky’s observations were later confirmed by Lyell in 1956, who
described a Nikolsky sign in patients with toxic epidermal necrolysis.
(a) Eliciting Nikolsky's sign on perilesional skin. Note the tangential pressure,
(b) (b) Eliciting Nikolsky's sign, peeling of skin revealing moist erosion
 One study described 2 distinctly different versions of the sign: the
so called “wet” Nikolsky’s sign, in which a moist, glistening base of
eroded skin is seen after pressure is exerted on the skin; and the
so-called “dry” Nikolsky’s sign, in which a dry base of eroded skin
is seen after pressure is exerted on the skin. In patients with active
pemphigus vulgaris, a wet sign is expected, whereas the presence
of the dry sign may indicate reepithelialization beneath a
pemphigus blister, which could signify healing and thus be a
favorable finding.
 It help distinguish pemphigus vulgaris, which is strongly associated

with the sign, from bullous pemphigoid, in which the sign is
usually absent.
 There are a number of other diseases associated with a positive

Nikolsky’s sign. Patients with toxic epidermal necrolysis,
staphylococcal scalded skin syndrome, bullous impetigo, and
epidermolysis bullosa all can exhibit the sign.
214
ASBOE-HANSEN SIGN
 This ''bulla spread sign'' refers to the extension of a blister to adjacent unblistered
skin when pressure is put on the top of the bulla.
 This sign is named after Gustav Asboe-Hansen (1917-1989), a Danish physician

The Asboe-Hansen sign in fact could be considered as a variation of the bulla
spread sign. It applies to smaller, intact, tense bullae where the pressure is applied
to the center of the blister.
 In the traditional ''bulla spread'' sign also called Lutz sign, the margin of an intact
bulla is first marked by a pen. Slow and careful unidirectional pressure applied by a
finger to the bulla causes the bulla to extend beyond the marked margin.
 While a regular rounded border is observed in bullous pemphigoid and other

subepidermal blistering disorders irregular angulated border is seen in pemphigus
vulgaris. The sign may also be elicited on a burst blister if an adequate portion of
the roof is intact.
216
ASBOE-HANSEN SIGN
 The bulla spread sign is positive in all varieties of blistering

diseases like the pemphigus group of diseases and many cases of
subepidermal blisters, including bullous pemphigoid, dermatitis
herpetiformis, epidermolysis bullosa acquisita, cicatricial
pemphigoid, dystrophic epidermolysis bullosa, bullous drug
eruptions, Stevens-Johnson syndrome and toxic epidermal
necrolysis.
 Due to fragility of the roof of the blister Asboe Hansen sign is

usually negative in Hailey-Hailey disease and staphylococcal
scalded skin syndrome.
Differential History Examination

Herpes simplex primary or recurrent outbreak of grouped vesicles on an
herpes simplex virus (HSV) vesicles erythematous base, may
associated with tenderness, burning, or evolve to pustules or
tingling; HSV-1 is spread primarily erosions, lesions resolve
through direct contact with infected within 2 to 6 weeks
saliva or other infected secretions, HSV-
2 is spread primarily through sexual
contact, symptoms typically start within
1 week after exposure
Herpes zoster prior history of varicella infection, painful, grouped vesicles on

(shingles) presents with prodrome of pain, an erythematous base in a
itching, hyperesthesia followed by sensory dermatomal
vesicular eruption distribution, rarely crosses
midline
Varicella, initial viremia between days 4 and successive crops of lesions

acute(chickenpox) 6; appearance of characteristic appear over several days on
vesicular eruption on erythematous trunk, face, and oral mucosa;
base, often referred to as typically lesions are in different
"dewdrops on rose petals," low- stages of evolution from vesicles
grade fever, malaise, and headache to crust and do not scar
Impetigo typically occurs in children, very bullae are ≥2 cm in diameter

contagious, risk factors include and initially clear, subsequently
increased humidity, poor hygiene, becoming turbid; buccal mucosa
malnutrition and overcrowding, may be involved, classic facial
concomitant skin disease yellowish to golden crusting,
streptococcal form tends to
have thicker and darker crusts
Nutritional inherited or acquired deficiency, dermatitis is bullous or

deficiencies (zinc, breastfed newborns, history of pustular, periorificial and acral
biotin, niacin, parenteral nutrition, characteristic locations, associated
essential fatty cutaneous finding is a photosensitive erythematous eroded, crusted
acids) eruption (preferentially involving the patches; with repeated sun
face, neck, upper chest, dorsal exposure, the involved areas
hands, and extensor forearms), become thickened, scaly, and
which worsens in spring and summer hyperpigmented
Diabetic bullae longstanding history of diabetes, painless noninflammatory

(bullosis spontaneously healing blisters within blisters typically on acral
diabeticorum) 4 to 5 weeks of onset locations, including
amputation sites
Mastocytosis acquired solitary or widespread 5 mm to 15 mm papules,

cutaneous eruption, lesion yellow-brown to yellow-red in
periodically urticates and blisters color; edema, urtication, and
then returns to original form vesicle and bullae formation,
urticaria surrounding
erythematous flare when
rubbed (Darier sign)
Bullous lupus occurs in patients with a diagnosis of lesions are not pruritic or
erythematosus systemic lupus, sun-exposed skin is symmetric, do not have a
preferentially involved predilection for extensor
surfaces of arms, elbows,
knees, or scalp; vesicles and
bullae typically photo-
distributed or widespread,
asymptomatic
Erythema ingestion of new medications in the characterized by atypical

multiforme days or weeks before onset, targetoid lesions, macules,
implicated medications include vesicles, bullae on palms and
antibiotics (trimethoprim- soles; may be generalized
sulfamethoxazole), anticonvulsants
(lamotrigine), NSAIDs, and allopurinol
Stevens-Johnson more fulminant form of erythema palms, soles, and extensor

syndrome multiforme with systemic and surfaces with macules, may
mucosal involvement of <10% of evolve to papules, vesicles,
body surface area, severe bullae, urticarial plaques, or
mucocutaneous reaction with confluent erythema; center of
prodrome of fever, malaise, chills, 1 lesions purpuric, vesicular, or
day to 2 weeks before onset necrotic imparting targetoid
appearance, secondary
infection follows
Erythema multiforme v/s Pemphigus
Features Erythema Pemphigus

multiforme
Age Primarily in young Older patients
adults
Duration Acute disease Chronic disease
Appearance Erosive crusty Pustulopapular
changes vegetation
Skin changes Target lesions No target lesions
Nikolsky’s sign Negative Positive

LABORATORY TESTS
 PV is diagnosed by biopsy. Biopsies are best done on intact

vesicles and bullae less than 24 hours old; however, because
these lesions are rare on the oral mucosa, the biopsy
specimen should be taken from the advancing edge of the
lesion, where areas of characteristic suprabasilar
acantholysis may be observed by the pathologist.
 Specimens taken from the center of a denuded area are
nonspecific histologically as well as clinically.
224
LABORATORY TESTS
 Sometimes more than one biopsy is necessary before the

correct diagnosis can be made. If the patient shows a
positive Nikolsky sign, pressure can be placed on the
mucosa to produce a new lesion; biopsy may be done on
this fresh lesion, taking care to include the blister base.
225
226
Histopathology
 On biopsy, pemphigus vulgaris may
show intraepidermal vesicles with
eosinophilic spongiosis in early
stages, but eventually suprabasilar
acantholysis can be identified.
 The basilar keratinocytes remain

attached to the floor of the
separation but appear to separate
from one another, producing the so-
called “row of tombstones”
appearance. A few acantholytic cells
are identified within the blister.
 The separation of cells, called acantholysis, takes place in the lower
layers of the stratum spinosum. Electron microscopic observations
show the earliest epithelial changes as a loss of intercellular cement
substance this is followed by a widening of intercellular spaces,
destruction of desmosomes, and, finally, cellular degeneration.
 This progressive acantholysis results in the classic suprabasilar

bulla, which involves increasingly greater areas of epithelium,
resulting in loss of large areas of skin and mucosa.
228
TZANCK SMEAR
 Is a quick bedside test.

 A fresh blister is ruptured, the roof detached and the floor
scraped using a scalpel blade.
 If blister not present, then taken from erosion, after removing the
crust.
 The material so obtained is spread on a glass slide and stained
with Giemsa stain.
PEMPHIGUS VULGARIS
 It reveals multiple acantholytic

cells (Tzanck cells).
 A typical Tzanck cell

 Large round keratinocyte
 Hypertrophic nucleus,
 Hazy or absent nucleoli, and
 Abundant basophilic cytoplasm.
 The basophilic staining is deeper

peripherally on the cell leading to
a perinuclear halo.
232
TZANCK SMEAR FINDINGS IN BULLOUS DISORDERS
 A second biopsy, to be studied by DIF, should be performed whenever
pemphigus is included in the differential diagnosis.
 This study is best performed on a biopsy specimen that is obtained from

clinically normal-appearing perilesional mucosa or skin. In this technique
for DIF, ﬂuorescein-labeled antihuman immunoglobulins are placed over
the patient’s tissue specimen.
 Indirect immunofluorescent antibody tests have been described that are

helpful in distinguishing pemphigus from pemphigoid and other chronic
oral lesions and in following the progress of patients treated for
pemphigus.
 In this technique, serum from a patient with bullous disease is placed over
a prepared slide of an epidermal structure (usually monkey esophagus).
234
235
 Immunofluorescence (IF) studies, particularly direct IF but to a lesser extent indirect IF, play an
important role in the diagnosis of pemphigus. On direct IF, pemphigus vulgaris, pemphigus vegetans, and
paraneoplastic pemphigus show intercellular IgG and C3 deposition involving the full thickness of
epidermis, although sometimes staining of upper layers of the epidermis may be diminished. This
staining may be linear (producing the so-called “chicken wire” appearance) or particulate.
 In pemphigus foliaceus, intercellular staining for IgG and C3 is sometimes restricted to superficial
portions of the epidermis, reflecting the primary location of the target antigen, desmoglein 1. However,
in some cases staining of the full thickness of epidermis is seen, in the manner of pemphigus vulgaris. In
fact, the majority of the author’s cases of pemphigus foliaceus have shown the latter staining pattern.
236
DIF: PV deposition of IgG DIF: PNP faint deposition of IgG
around epidermal cells around epidermal cells
DIF: BP continuous deposition of C3 along the epidermal

basement membrane. B, DIF 237
following salt-split processing
 Indirect IF has been commonly used in the diagnosis of pemphigus, particularly pemphigus
vulgaris, but it also has been used as a means of following the course of the disease.
 The procedure involves layering of various dilutions of patient sera on an epithelial

substrate, staining with anti-human IgG antibodies, and determining the antibody titer by
finding at what dilution intercellular fluorescence can no longer be detected in the
substrate.
 It is known that antibody titers reflect disease activity. However, they do not
always predict disease activity, and therefore many consider clinical evaluation of the
patient a better means of assessment.
 Regarding the diagnostic uses of indirect IF in pemphigus, there has been some controversy

about whether direct or indirect IF methods are more reliable. Indirect IF, this method when
the proper substrate is used, and the best substrate is considered to be monkey esophagus.
 There are certainly selected situations in which indirect IF might be preferable (e.g., in
patients who have only mucous membrane disease, where blood drawing might be a
technically easier procedure, or very young or elderly patients who might tolerate obtaining
of a blood sample better than a skin biopsy).
238
IMMUNOPATHOLOGY
ELISA: More sensitive and specific than

immunofluorescence for DDx PV from PF
Can be used to identify:

Anti-Dsg3 only: patient with predominantly
mucosal disease
Anti-Dsg1and anti-Dsg3: patient with
widespread disease
Sterry, et al., Dermatology , 2006.

S Wolff, et al., Fitzpatric’s Dermatology in General Medicine, 7th edition,
2008.
239
TREATMENT
 The aim of treatment is to :
 Decrease blister formation,

 Promote healing of blisters and erosions,
 Determine the minimal dose of medication necessary to control the
disease process.
CORTICOSTEROIDS
 Systemic glucocorticoids are the cornerstone of treatment. The advent of corticosteroids in

the 1950s was accompanied by a 45% reduction in mortality however, the long-term, high-
dose courses of systemic corticosteroids often used to control pemphigus are associated
with significant sequelae.
 There is no standardized approach to the administration of corticosteroids in pemphigus,

although continuous oral administration is the most common. Clinical improvement may be
observed within days of starting treatment, although cessation of new blister formation may
take 2–3 weeks with full healing occurring at 6–8 weeks.
 Glucocorticoids are the mainstay of treatment for most bullous disorders. They have anti-
inflammatory and immunosuppressive effects from the inhibition of the production of
proinflammatory cytokines.
 They diminish the number of circulating T-cell lymphocytes and reduce their responsiveness
to antigens. In addition, glucocorticoids decrease antibody production.
241
CORTICOSTEROID DOSING
 In a study, 22 newly diagnosed pemphigus patients were randomized to low-dose

(45–60 mg) or high-dose (120–150 mg) prednisolone and followed-up for 5 years.
All patients achieved resolution of blister formation and were seronegative for
autoantibodies at 3 months.
 There was no significant difference in the duration of treatment required to

achieve initial remission, indicating that there was no advantage to a high-dose
regimen.
 A dosing schedule has been advocated according to disease severity and a

modified regimen should be suggested. Patients with mild disease are treated
with initial Prednisolone doses of 40-60 mg day and in more severe cases, 60-
100 mg day. If there is no response within 5-7 days, the dose should be increased
in 50-100% increments until there is disease control.
242
PULSED CORTICOSTEROID THERAPY
 Pulse therapy refers to discontinuous intravenous infusion or oral dosing of high-

dose glucocorticoids in short bursts.
 It is based on the rationale that the steroid pulses may cause rapid control of
disease and decrease the need for long-term steroid use, thereby reducing the
complications of long-term usage.
 The theoretical aims of pulsing are to achieve more rapid and effective disease
control compared with conventional oral dosing, thus allowing a reduction in
long-term maintenance corticosteroid doses and their side effects.
243
VARIOUS ADJUVANT THERAPIES
EMPLOYED
 Azathioprine,
 Mycophenolatemofetil,
 Cyclophosphamide,
 Ciclosporin,
 Methotrexate,
 Chlorambucil,
 Gold,
 Dapsone, and
 Tetracycline/nicotinamide.
 These agents typically require 4–12 weeks to demonstrate any therapeutic

effect, thus their use is essentially in maintaining remission, rather than
inducing it. 244
 In PT, doses of each pulse are not standardized but
are
DRUG DOSAGE BODY WEIGHT
METHYL- 250-500mg 10-20 mg/kg of body

PREDNISOLONE weight
DEXAMETHASONE 50-200mg 2-5 mg/kg of body

weight
 Single doses of 500 mg of methylprednisolone and 100 mg of

dexamethasone are both considered equivalent to 625 mg of
prednisone.
245
 These high doses, sometimes termed megadoses, are usually
given as intravenous infusions over 30 minutes to 1 hour daily
or every other day for a total of 1 to 5 administrations.
 In most indications, pulse glucocorticoid therapy is

accompanied and/or followed by the continuous
administration of lower intermediate-dose glucocorticoids
and/or immunosuppressive agents like cyclophosphamide and
azathioprine.
246
 Recently, a variant of pulse therapy has been proposed for
patients with significant corticosteroid related toxicity and
unresponsiveness to multiple immunosuppressive adjunctive
therapies.
247
 Here, cyclophosphamide is given intravenously at the dosage
of 50 mg/kg/day for four consecutive days and followed by
the administration of granulocyte-colony stimulating factor
(GCSF), 5μg/kg/day, beginning six days after last day of
cyclophosphamide until the absolute neutrophil count exceeds
1000/ mm3.
 Febrile neutropenia and sepsis are common side effects of this

immunoablative therapy.
248
References
 Text book of oral pathology. Shafer 5th ed
 Oral and maxillofacial pathology. Neville
 Burkits oral medicine 11th ed Greenberg and Glick
 Text book of oral medicine, oral diagnosis and radiology 2nd ed
Ravikumar ongole
 British Journal of Dermatology 2003
 Direct and indirect immunofluorescence An Bras Dermatol. 2010
 Mayo clinic atlas of immunofluorecence in dermatology
 Dermatology in medicine – Fitzpatrick
 Sensitivity of direct immunofluorescence in oral diseases. Med Oral
Patol Oral Cir Bucal. 2008
249
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ULCERATIVE AND

 The diagnosis of oral lesions requires knowledge of basic

 Dermatologic lesions are classified according to their clinical

MACULES : These are well-circumscribed, flat

They may be red due to increased vascularity

A good example in the oral cavity is the

Papules : These are solid lesions raised

Papules may be seen in a wide variety of

In the oral cavity, hyperplastic candidiasis

Plaques : These are solid raised

They are large papules.

Nodules : These lesions are present

The lesions may also protrude above

A good example of an oral mucosal

Vesicles : These are elevated

Bullae : These are elevated

Erosions : These are red lesions

Pustules : These are blisters

Ulcers : These are well-

A good example is an Aphthous

Purpura : These are reddish to purple

These lesions do not blanch when

Petechiae (less than 0.5 cm)

 Many ulcerative or vesiculobullous disease of the mouth have

These factors may cause lesions that have a characteristic

 Three pieces of information in particular help the clinician rapidly

 This information serves as an excellent starting point for the

Three pieces of information

1. Patients with Acute Multiple Lesions

2. Patients with Recurring oral ulcers

3. Patients with chronic Multiple Lesions

4. Patients with single ulcers

I. Patients with Acute Multiple Lesions :

 Herpes virus Infections

 Recurrent Aphthous Stomatitis

Predominantly vesicular Predominantly Bullous

HSV Infections Pemphigus vulgaris

The lesion is formed within the epithelium

 Mucosal erythema multiforme

I. Patients with Acute Multiple Lesions :

 Subepithelial Bullous Dermatoses

 Mucous Membrane Pemphigoid (Cicatricial Pemphigoid)

 Linear IgA Disease

 Epidermolysis Bullosa Aquisita

 Chronic Bullous Disease of Childhood

 HSV- THE FIRST HUMAN HERPES VIRUS TO BE

 HERPES –DERIVED FROM GREEK WORD MEANING TO

 VIRAL ETIOLOGY ESTABLISHED IN 1919

 SIMPLEX WAS DERIVED TO DISTINGUISH MORE BENIGN

 Herpes simplex type 2: Causes

 At this point, virus is taken up by sensory nerves and

2.Secondary infection: occurs with reactivation of the

Initial contact with mucosa, skin, eye and infected secretions

Reaches the cell nucleus and virus replication takes place

As more epithelial cells become infected, degenerative and

 After 2 to 3 weeks, significant antibodies titers appear

 Latent viral infection is a type of persistent viral infection which

 Latency is the phase in certain viruses life cycles in which, after

 However, the viral genome is not fully eradicated. The result of

 It has been suggested that as the neurons are nonreplicating

 Considerable progress has been made recently that IgG

 Trigger factors cause weakening of IgG antibody bound

 This induce activation of HSV which may then undergo

 Virus migrate centrifugally along the axon and shed at the