Vesiculobullous lesion of oral cavity.pptx

Vesiculobullous lesion of oral
cavity
DR PRIYANKA
SENIOR LECTURER
ORAL MEDICINE AND RADIOLOGY

Introduction
• Vesiculobullous (VB) diseases are a distinct group of oral disorders characterized by the formation of vesicles or
bullae.
• Clinicians must bear in mind that it is uncommon to see vesicles or bullae intraorally, as they soon rupture,
leaving erosions or ulcers
• This group includes viral diseases, autoimmune mucocutaneous diseases, diseases that probably have an
immunologically mediated mechanism, and genetic diseases. The diagnosis of VB diseases should be made on
clinical, histopathological, and immunological ground

Terminologies
Macules.
• are flush with the adjacent mucosa and that are noticeable because of their difference in color from normal skin
or mucosa.
• may be red due to increased vascularity or inflammation, or pigmented due to the presence of melanin,
hemosiderin, and foreign materials (including the breakdown products of medications).
• A good example - is the melanotic macule
Papules.
• raised above the skin or mucosal surface that are smaller than 1.0 cm in diameter (some use 0.5 cm for oral
mucosal lesions).
• slightly domed or flat-topped.
• Papules are seen in a wide variety of diseases, such as the yellow-white papules of pseudomembranous
candidiasis
Plaques.
• raised lesions that are greater than 1 cm in diameter; they are essentially large papules

Nodules.
• present within the dermis or mucosa.
• protrude above the skin or mucosa forming a characteristic dome-shaped structure.
• A good example - irritation fibroma.
Vesicles.
• small blisters containing clear fluid that are less than 1 cm in diameter.
Bullae.
• elevated blisters containing clear fluid that are greater than 1 cm in diameter (some use 0.5 cm for oral lesions).
Pustules.
• blisters containing purulent material and appear yellow

Erosions.
• red lesions often caused by the rupture of vesicles or bullae, or trauma and are generally moist on the skin.
• may also result from thinning or atrophy of the epithelium in inflammatory diseases such as lichen planus.
• should not be mistaken for ulcers that are covered with fibrin and are yellow although erosions may develop
into ulcers.
Ulcers.
• well-circumscribed, sometimes depressed lesions with an epithelial defect that is covered by a fibrin clot,
resulting in a yellow-white appearance.
• A good example is an aphthous ulcer.
Purpura.
• reddish to purple discolorations caused by blood from vessels leaking into the connective tissue.
• do not blanch when pressure is applied and are classified by size as petechiae (less than 0.3 cm), purpura (0.4–
0.9 cm), or ecchymoses (greater than 1 cm)

Classification burket 12th edition
THE PATIENT WITH ACUTE MULTIPLE ULCERS
• Herpes Simplex Virus Infections
• Varicella-Zoster Virus Infections
• Cytomegalovirus Infections
• Necrotizing Ulcerative Gingivitis and Necrotizing Ulcerative Periodontitis
• Erythema Multiforme Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis
• Lyell Disease
• Plasma Cell Stomatitis and Oral Hypersensitivity Reactions
THE PATIENT WITH RECURRING ORAL ULCERS
• Recurrent Aphthous Stomatitis
• Behçet Disease (Behçet Syndrome)

THE PATIENT WITH CHRONIC MULTIPLE ULCERS
• Pemphigus Vulgaris
• PNPP
• Pemphigus Vegetans
• Subepithelial Bullous Dermatoses
• Bullous Pemphigoid
• Mucous Membrane Pemphigoid (Cicatricial Pemphigoid)
• LAD and Chronic Bullous Disease of Childhood
• EBA
THE PATIENT WITH SINGLE ULCERS
• Traumatic Injuries Causing Solitary Ulcerations
• Traumatic Ulcerative Granuloma (Eosinophilic Ulcer of Tongue)
• Infectious Ulcers

THE PATIENT WITH ACUTE
MULTIPLE LESIONS

Herpes Simplex Virus Infection

Introduction
• In general, infections above the waist are caused by HSV-1 and those below the waist by HSV-2, although
with changing sexual practices, it is not uncommon to culture HSV-2 from oral lesions and vice versa
• The primary infection, which occurs on initial contact with the virus, is acquired by inoculation of the mucosa,
skin, and eye with infected secretions.
• The virus then travels along the sensory nerve axons and establishes chronic, latent infection in the sensory
ganglion (such as the trigeminal ganglion).
• Extraneuronal latency (i.e., HSV remaining latent in cells other than neurons such as the epithelium) may
play a role in recurrent lesions of the lips.
• Recurrent HSV results when HSV reactivates at latent sites and travels centripetally to the mucosa or the skin,
where it is directly cytopathic to epithelial cells, causing recrudescent HSV infection in the form of localized
vesicles or ulcers
• The most common sites - the oral and genital mucosa and the eye.
• HSV infection of the cornea (keratitis) is a major cause of blindness in the world.
• 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

• herpes gladiatorum (infections of the skin spread through the sport of wrestling), herpes encephalitis, HSV
esophagitis, HSV pneumonia and neonatal and disseminated infection, herpetic paronychia- herpes of nails,
herpes genitalis, herpetic conjunctivitis, Herpetic eczema.
•Clinical Manifestations
• Primary Gingivostomatitis
• Infection on in a person who is not exposed to this earlier.
• Infection is transmitted by droplets infection by saliva or direct contact like kissing.
• ONE- THREE DAY viral prodrome of fever, loss of appetite, malaise and myalgia, accompanied by
headache and nausea.
• Oral pain leads to poor oral intake, patient may require hospitalization for hydration
• Age- occur in children and teenagers, and young adult
• Site- both keratinized and non keratinized mucosa, mainly on keratinized include palate and gingiva

Clinical feature
Presence of 1-3 days prodromal feature like fever, headache, irritability, pain on swallowing, regional
lymphadenopathy
Within few days, erythema and cluster of vesicle or ulcer appear on keratinized mucosa(hard palate,
attached gingiva, dorsum of tongue, and non keratinized (mucosa, ventral tongue and soft palate)
Multiple vesicle which are clustered together
Vesicle rupture to form shallow ulcer (1-5mm) surrounded by erythematous halo
Painful mouth and gingiva become inflamed/ erythematous
On gingiva, multiple small ulcer seen as acute gingivitis desquamative gingivitis
Pharyngitis , difficulty in swallowing
Heal spontaneously within 10-14 days and leave no scar

Differential diagnosis
If ulcer is not site specific
• Apthous ulcer
• Herpangina
• Herpes zoster
• Hand foot mouth disease
• Erythema multiforme
• Pemphigus
• pemphigoid
If lesion is confined to
gingiva only
• Erosive and atropic lichen planus
• Pemphigus
• Pemphigoid
• Linear marginal erythema
• ANUG

Investigation
• Confirmatory laboratory diagnosis is required when c/f are atypical and pt seem to be immunocompromised
Isolation and tissue culture
• Gold standard test
• HSV can be demonstrated in lab by isolation of virus in tissue culture or DNA in scraping from lesion
• Isolation and neutralization of virus in tissue culture is most positive method of identification
Routine cytosmear/ exfoliative cytology
• Scraping obtained from base of lesion are stained with wright’s, giemsa stain(tzanck test) and Papanicolaou
stain
• Demonstrate balloon cells, multinucleated giant cell and intranuclear inclusion bodies
Cytosmear with direct fluorescent antigen testing
• Exfoliative cytology cannot distinguish between HSV and VZV so direct fluorescent is used
• A similar smear preparation can be used using a monoclonal ab ag HSV conjugated o fluorescent compound

Detection of viral DNA PCR technique
• PCR from swab shown to detect HSV ag 3-4 times more than culture
• Real time PCR shown to be highly sensitive and specific
Antibody titres/ serological methods
• Include detection of ag-ab herpes
• Primary infection associated with elevated IgM titre that occur within days, followed several weeks later by
permanent IgG titre
Biopsy
• Not generally biopsied because clinically appearance and history are characteristic and infection is confirmed
with culture or cytology

Recrudescent Oral HSV Infection
• Also called fever blister/ cold sore ( occur during feverish illness such as cold, cough , flu)
• Is recurrence of herpetic lesions in pt with previous exposure to primary infection due to different activating
factor
• lead to asymptomatic shedding of HSV, in the saliva and other secretions, an important risk factor for
transmission; it may also cause ulcers to form.
• Recurrence rate- 20-40%
• Seen in adult, F>M while primary infection is on children
• Site- at site of primary inoculation
• In adjacent area supplied by involved ganglion
• Develop on lips, mucosa that is tightly bound to periosteum (hard palate, attached gingiva and alveolar ridge)
• Trigger factor – internal ( unpreventable ) – fever, illness, menstruation, gi upset, diabetes,
hyperparathyroidism, presence of second viral infection, fatigue, immuncompromised
• External (preventable)- UV radiation, chilling, excitement, stress, drying of lips, allergic reaction to food,
physical injury, dental treatment
• Recrudescent HSV on lips called HERPES LABIALIS, occur in 20- 40 % of young adult population.

Clinical feature
Presence of prodromal symptoms like pain, burning, itching, at site where blisters will form
Erythema due to congestion and dilation of capillaries ( after 1-2 days)
Multiple vesicle ( after 2-3 days)
Vesicle rupture to form shallow ulcer (soft crust) 3rd day
Small ulcer combine to form a large ulcer
Formation of hard crust due to drying of ulcer ( 5-7 day)
Crustation is lost and re epithelization (7-10 day)
Normal skin ( 10 day)

If lesion confined to lips
• Herpes zoster
• Angular cheilitis
If lesion is intraorally
• Apthous ulcer
• Herpangina
• Herpes zoster
• Hand foot and mouth disease
• Pemphigus
• pemphigoid

Laboratory finding
• Cytosmear would be positive only for short time (24-72 hrs) because of rapid degradation of affected cell
• Isolation can be accomplished in tissue culture in early stage ( 24-72 hrs) of recurrent infection
• Because of this antiviral work only in initial 24-72 hrs

Herpetic gingivostomatitis in immunocompromised host
• Undergoing chemotherapy, who have undergone organ transplantation, or who have acquired immune
deficiency syndrome
• Occur at any site intraorally and may form ulcer (several centimeters ) for several weeks or months, if
undiagnosed or untreated
• Painful ulcer and similar to those seen in immunocompetent pt except may be larger and often occur on non
keratinized sites
• Appear slightly depressed with raised border
• Presence of 1-2mm vesicle or satellite ulcer at edge of main ulcer is helpful sign
• Is undiagnosed and left untreated, RIH inf may disseminate to other site and cause severe infection in
immune pt
• HSV inf in immune host should be treated with sytemic antiviral like acyclovir 400mg 3 times a day or
500mg valacyclovir twice a day.
• In acyclovir resistant –foscarnet or cidofovir is effective
• NUMBER OF VACCINES AND NEW THERAPIES AGAINST HSV ARE CURRENTLY UNDER
DEVELOPMENT.

Introduction
• Varicella is primary infection resulting from first exogeneous exposure of susceptible individual to VZV
• Virus becomes latent usually in dorsal root ganglia of cranial nerves.
• Herpes zoster occur as result of reactivation of VZV
• Zoster word derived from Greek means girdle/belt/zone due to characteristic belt like skin rash
• Transmission – respiratory route (incubation period- 2-3weeks)
• Age- >40 years (lack of zoster neutralizing Ab with age), M>F
• Site- thoracic > cervical > trigeminal > lumbar > sacral
• Predisposing factor- immunosuppression, stress, drugs (steroid, cyclosporine), uncontrol diabetes, leukemia,
HIV, kidney transplant pt.

Clinical feature
Presence of prodromal symptoms like deep, aching or burning pain, rashes, headache, low grade fever, malaise (last
for 1-4 days)
Within 2-4 days by appearance of crops of vesicle in dermatomal or zosteriform pattern.(unilateral,
linear and clustered distribution of vesicle, ulcer and scabs in dermatome supplied by one nerve)
Begin on trunk (centripetal distribution) and spread to face
and extremities (centrifugal spread)
Vesicle will be appeared as dewdrop like
Within 3-4days vesicle become cloudy, pustular and ulcerate
Form crusts after 7-10 days
Lesion heal within 2-4 weeks with scarring and hypopigmentation
or hyperpigmentation

Oral manifestation
• Involve face by infection of trigeminal nerve
• Unilateral involvement (characteristic feature)
• Extremely painful oral mucosa, unilateral, scattered vesicle/ulcer surrounded by erythematous zone
• Smaller ulcer can coalesce to form large ulcer similar to herpetic gingivostomatitis
• Ulcer heal within 10-14 days
• Site- anterior portion of tongue, soft palate, cheek

Syndrome associated with herpes zoster
James ramsay hunt syndrome
• infection of geniculate ganglion cause facial paralysis
• Pain of external auditory meatus and pinna of ear
• Vesicular eruption in oral cavity and oropharynx
• Other disturbance- hoarseness, tinnitus, vertigo
Crocodile tear syndrome (bogorad syndrome)
• Characterized by profuse tearing during mastication
• As a result of faulty regeneration of facial nerve during recovery of HZ involving facial nerve
• Other feature- pain in ear, taste loss in anterior two third of tongue, dry mouth and eyes, vesicle formation in ear
canal, tongue and hard palate

Laboratory investigation
Isolation and tissue culture- gold standard
A simple smear
• stained with a standard laboratory stain –
• presence of multinucleated epithelial cells, but this does not distinguish between HSV and VZV
Cytosmear with Direct fluorescent antibody testing
• using a smear has greater sensitivity.
• smear obtained by scraping the lesion and staining it with antibody against VZV conjugated to a fluorescent
compound.
PCR and real-time PCR
• expensive and highly sensitive (VZV antigen does not always equate with active infection)

Serological method
• After primary infection, IgG against VZV is detectable in the serum,
• HZI causes a transient rise in IgM and an increase in levels of IgG (not reliable for diagnostic purposes)
Biopsy
• not required and not the diagnostic test

Management
To relieve pain
Topical analgesic
• Lignocaine patch- 5% patch
• EMLA cream (eutectic mixture of
lidocaine 2.5% and prilocaine
2.5%)
• Capsaicin cream – 0.025-0.075%
Systemic analgesic
• Paracetamol/ acetaminophen-
500 mg 3-4 times a day
• Ibuprofen- 400mg 3-4 times a day

To decrease viral load
Antiviral therapy
• Acyclovir- 800mg, orally 5 times
daily for 7-10 days
• Valacyclovir- 1000mg tid for 7 days
• Famciclovir- 500 mg tid
• Foscarnet- iv foscarnet
(200mg/kg/d)
To relieve chronic pain and to prevent
chance of post herpetic neuralgia
Tricyclic antidepressants
• Amitriptyline- 10-25mg orally at bedtime; increase
dosage by 25mg every2-4weeks
• Nortriptyline- 10-25mg orally at bedtime; increase
dosage by 25 mg every 2-4 weeks

• Coxsackie (CV), a ribonucleic acid (RNA) virus, has features in common with poliovirus;
• replicate first in the mouth and then extensively in the lower gastrointestinal tract, where they shed.
• Transmission - primarily by the fecal-oral route, although some shedding occurs in the upper respiratory tract.
• In the oral cavity, CV infections lead to three disease entities:
• HFM disease,
• herpangina, and
• lymphonodular pharyngitis.

HFM DISEASE
• EV 71 (closely related to CVA16) 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.
• Atypical HFM disease exhibits widespread oral and skin involvement and onychomadesis (separation of the
nail plate from the nail bed) and is caused by CVA6.
• While comparing cases of HFM disease caused by EV71 with those caused by CVA16, EV71 is much more
likely to be associated with severe central nervous system disease (such as meningitis and brainstem
encephalitis), paralysis, pulmonary edema, and death.

CLINICAL FEATURES
• usually afflicts children younger than 10 years in summer.
• Patients have a low-grade fever and sore mouth; 75%–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.
• Patients are febrile and complain of a sore mouth and throat.
• SITE- tongue, hard and soft palate, and buccal mucosa but can present on any oral mucosal surface

HERPANGINA
• The word herpangina derives from herpes, meaning “vesicular eruption,”
and angina, meaning “inflammation of the throat.”
• Clinical Findings-
• AGE- children younger than 10 years are usually afflicted, and
• outbreaks usually occur in epidemics in summer.
• Patients develop fever, headache, and myalgia that usually last only one to three 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 2–4 mm ulcers and these persist for 5 to 10 days

Differential Diagnosis
• Lesions of both HFM disease and herpangina may resemble primary herpetic gingivostomatitis.
• HFM DISEASE- lesions on the palms and soles
• HERPANGINA- ulcers in the posterior oral cavity.
• HSV infection- Bright red and painful gingiva
MANAGEMENT
• CV infections are self-limiting (unless complications arise or the patient is immunocompromised),
• management is directed toward control of fever and mouth pain, supportive care, and limiting contact with
others to prevent spread of the infection.
• Effective antiviral agents for CV are not available.

Necrotizing Ulcerative Gingivitis
and Necrotizing Ulcerative
Periodontitis

• 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), smoking, stress, poor
oral hygiene, local trauma, and contaminated food supply.
• Diabetes may also be a risk factor.

Clinical Findings
• NUG and NUP may or may not be associated with fever and malaise, although submandibular
lymphadenopathy is usually present.
• NUG has a rapid and acute onset.
• The first symptoms include excessive salivation, a metallic taste, and sensitivity of the gingiva.
• This rapidly develops into extremely painful and erythematous gingiva with scattered punched-out
ulcerations, usually on the interdental papillae, although any part of the marginal gingiva may be affected.
• There is accompanying malodor, and there may be gingival bleeding.
• Patients who are immunocompromised and neutropenic are prone to developing such lesions.
• The orofacial lesions are cone shaped, with the base of the cone within the oral cavity and the tip at the skin
aspect.

Management
• Definitive treatment first few visits - gentle debridement to remove as much of the debris and plaque as
possible; this is best accomplished with topical anesthesia.
• The use of chlorhexidine digluconate mouthrinse led to resolution in >90% of cases.
• Interestingly, metronidazole, which has little activity against spirochetes, also is effective, suggesting that
resolution can occur without treatment of the entire microbial complex.
• Once the acutely painful episodes have resolved, scaling and root planing to completely remove all residual
plaque and calculus are indicated. Periodontal surgery may be necessary to correct gingival and periodontal
defects.
• It may be appropriate to test the patient for HIV or other immunosuppressive conditions,

• 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 represents a hypersensitivity reaction to infectious agents (majority of cases) or medications.
• In general, EM is classified as 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.
• However, there is likely a subset of EM that affects the oral mucosa only without skin involvement.
• Historically, fulminant forms of EM were labeled Stevens–Johnson syndrome (SJS) and toxic epidermal
necrolysis (TEN [Lyell disease]).

PATHOGENESIS
Presence of cell antigen (viral DNA fragment, drug metabolites, etc.)
Stimulation of CD4 T-cells
Production of pro-inflammatory mediators like interferon-gamma (IFN-Y) and tumour necrosis factor alpha (TNF-
a)
IFN-y, TNF-a stimulates the production of additional| cytokines and chemokines, cytotoxic T-cells and natural
killer cells
These cytotoxic T-cells, NK cells or chemokines can all induce epithelial damage
So, erythema multiforme appears to be the result of a cell-mediated immune reaction to the precipitating agent
(Type IV hypersensitivity reaction)

CLINICAL FEATURES
• Age- 20 and 40 years, with 20% occurring in children.
• Patients with recurrent EM have an average of six 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 may be a prodrome of fever, malaise, headache, sore throat and cough.
• These symptoms suggest a viral (especially respiratory tract) infection, and this is not surprising since
infectious agents are known to trigger EM.
• 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 - upper extremities, face, and neck.
• The skin lesions may take several forms—hence the term multiforme.
• 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.

ORAL MENIFESTATION
• The oral findings in EM range from mild erythema and erosion to large 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.
• Extensive lip involvement with inflammation, ulceration, and crusting is common.
• Oral lesions are present in 23%–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.
• Intraoral lesions take the form of irregular bullae, erosions, or ulcers surrounded by extensive erythema.
• Crusting and bleeding of the lips are common, but not always present.

DIFFERENTIAL DIAGNOSIS
• Primary HSV gingivostomatitis - these lesions are culture positive for HSV and do not usually present with
the typical skin rash.
• Oral ulcers of HSV are usually smaller and well circumscribed, whereas EM lesions are larger and irregular.
• pemphigus and pemphigoid may have oral ulcers and skin lesions, although skin lesions are bullous in nature
and not maculopapular, without the centripetal progression 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 ovoid or round ulcers, whereas ulcers of EM are more diffuse and irregular
with marked erythema.

MANAGEMENT
Mild forms
• Mild cases usually heal in 2-6 weeks
• Local wound care
• Topical analgesics or anaesthetics for pain control
• Diphenhydramine hydrochloride syrup mixed with equal amount of antacid liquid in a swish and Swallow
method 3-4 times daily
• Topical steroids Clobetasol propionate - 0.05%, Triamcinolone acetonide 0.1%, apply 3-4 times a day
For more severe
• Systemic corticosteroids cases (for EM major Prednisolone 60-100 mg daily and SIS) (1.0-2.0 mg/kg/day)
If patient is resistant, unresponsive or allergic to steroid
• immunosuppressive drugs/ steroid sparing drugs Azathioprine, Methotrexate, Cyclophosphamide, Cyclosporine,
etc.
In cases suspecting herpes associated EM
• Acyclovir (400 mg, 2 times/day), Valacyclovir (500-1000 mg/day), Famciclovir (125-250 mg/day)

Stevens-Johnson Syndrome and
Toxic Epidermal Necrolysis

• Studies done within the last 10 to 15 years now support the concept that Stevens-Johnson Syndrome (SJS) is a
less severe variant of Toxic Epidermal Necrolysis (TEN) and separate clinically and etiopathogenetically from
EM.
• 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.
• 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
(especially in children) and rarely with HSV infection, whereas EM is much more likely to be associated with
HSV infection.
• The more common inciting drugs include antibacterial sulfonamides, penicillin, anticonvulsants, and NSAIDs
in children and allopurinol, oxicams, and nevirapine in adults.
• The typical oral manifestation is extensive oral ulceration with hemorrhagic crusts on the vermilion and
oral and other mucosal surfaces

THE PATIENT WITH RECURRING
ORAL ULCERS
Recurrent Aphthous Stomatitis

• RAS is a common disorder characterized by recurring ulcers confined to the oral mucosa in patients with no
other signs of systemic disease.
• RAS affects approximately 20% of the general population, but when specific ethnic or socioeconomic groups
are studied, the incidence ranges from 5% to 50%.
• RAS is classified according to clinical characteristics: minor ulcers, major ulcers (Sutton disease, periadenitis
mucosa necrotica recurrens), and herpetiform ulcers

ETIOLOGY
• The major factors - genetic factors, hematologic or immunologic abnormalities, and local factors, such as
trauma and smoking.
• There is increasing evidence linking local immune dysfunction to RAS, although the specific defect remains
unknown.
• During the past 30 years, research has suggested a relationship between RAS and lymphocytotoxicity, antibody-
dependent cell-mediated cytotoxicity, defects in lymphocyte cell subpopulations, and an alteration in the CD4 to
CD8 lymphocyte ratiO
• A unified model of etiology postulates that triggers such as stress, or hormonal changes trigger a cascade of
proinflammatory cytokines directed against oral mucosa
• Hematologic deficiency, particularly of serum iron, folate, or vitamin B12, appears to be an etiologic factor in
5%–10% patients with aphthous-like ulcers although these sometimes occur on keratinized mucosa.

CLINICAL FINDINGS
• second decade of life.
• confined to the oral mucosa and begin with prodromal burning or the sensation of a small bump in the
mucosa from 2 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 48–72 hours.
• 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 rarely occur on the heavily keratinized palatal mucosa or gingiva.
• In mild RAS, the lesions reach a size of 0.3–1.0 cm and begin healing within a few days.
• Healing without scarring is usually complete in 10–14 days.

MAJOR RAS
• Patients with major ulcers develop deep lesions that are larger than 1 cm in diameter and last for weeks to
months.
• In the most severe cases, large portions of the oral mucosa may be covered with large deep ulcers that can
become confluent, and are extremely painful, interfering with speech and eating.
• These patients may require hospitalization for intravenous feeding and treatment with systemic corticosteroids.
• The lesions may last for months and sometimes be misdiagnosed as squamous cell carcinoma, granulomatous
disease, or blistering disease.
• The lesions heal slowly and leave scars that may result in decreased mobility of the uvula and tongue.

herpetiform type
• least common
• tends to occur in adults.
• The patient presents with more than 10 small punctate ulcers, measuring <5MM.

MANAGEMENT
• In mild cases with two or three small lesions, use of a protective emollient such as OrabaseTM often alleviates
pain and facilitates healing.
• Pain relief of minor lesions can be effected with a topical anesthetic agent such as benzocaine or lidocaine.
• In more severe cases, the use of a high-potency topical steroid preparation, such as fluocinonide,
betamethasone, or clobetasol, placed directly on the lesion, shortens healing time and reduces the size of the
ulcers.
• The steroid gel should be 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 15–30 minutes to allow for longer contact of the medication.
• Other topical preparations that have been shown to decrease the healing time of RAS lesions include
amlexanox paste and a topical tetracycline or doxycycline, which can be used either as a mouthrinse or
applied as a paste directly to the lesions.
• Intralesional steroid injections can be used to treat large indolent major RAS lesions.

Behçet Disease (Behçet
Syndrome)

Etiology and Pathogenesis
• BD is a systemic vasculitis characterized by hyperactivity of neutrophils with enhanced chemotaxis and
elevated proinflammatory cytokines IL-8 and IL-17, with TNF-α playing a major role in the pathogenesis.
• The HLA-B51 genotype is most frequently linked to BD, especially in patients with severe forms of the
disease in Asia.

Clinical Manifestations
• The highest incidence of BD is in young adults between the ages of 25 and 40, with the oral mucosa as the
most common site of involvement.
• The genital area is the second most common site of involvement and presents as ulcers of the scrotum and
penis in males and ulcers of the labia in females.
• 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.
• These lesions may be precipitated by trauma, and it is common for patients with BD to have a cutaneous
hyperreactivity to intracutaneous injection or a needlestick (pathergy).
• 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.
• Oral lesions are the presenting symptom in more than 95% of children with BD.
• A variant of BD, characterized by mouth and genital ulcers with inflamed cartilage, is associated with
relapsing polychondritis.

Oral Findings
• The most common site of involvement of BD is the oral mucosa.
• Recurring oral ulcers appear in more than 90% of patients; these lesions cannot be distinguished either
clinically or histologically from RAS.
• Some patients experience mild recurring oral lesions; others have deep, large, scarring lesions characteristic of
major RAS.
• These lesions may appear anywhere on the oral or pharyngeal mucosa.

Management
• The management of BD depends on the severity and the sites of involvement.
• Patients with sight-threatening eye involvement or central nervous system lesions require more aggressive
therapy with drugs, with a higher potential for serious side effects.
• Azathioprine and other immunosuppressive drugs combined with prednisone have been shown to reduce
ocular disease as well as oral and genital involvement.
• Pentoxifylline, which has fewer side effects than immunosuppressive drugs or systemic steroids, has also been
reported to be effective in decreasing disease activity, particularly of oral and genital lesions.
• Therapy with monoclonal antibodies such as infliximab is playing an increasing role in therapy of BD
particularly in patients who do not respond to anti-inflammatory and immunosuppressive drugs.

THE PATIENT WITH CHRONIC
MULTIPLE ULCERS

Introduction
• group of potentially life-threatening, autoimmune, mucocutaneous diseases
• characterized by intraepithelial blistering and erosions of the skin and mucous membranes.
• derived from word 'Pemphix' - blister.
• Pemphigus vulgaris (PV) - most common form, more than 80% of cases.
• Variants
1. Pemphigus vulgaris (PV)
2. Pemphigus vegetans (variant of pemphigus vulgaris)
3. Pemphigus foliaceus
4. Pemphigus erythematosus (variant of pemphigus foliaceus)
5. Paraneoplastic pemphigus (PNPP)
6. Drug-related pemphigus
• Each form of this disease has antibodies directed against different target cell surface antigens resulting in a
lesion forming in different layer of the epithelium.

A) Pemphigus Vulgaris
• Possible Aetiological Factors
a) Drugs
• Penicillamine - immunosuppresive
• Captopril- antihypertensive
• Enalapril - antihypertensive
• Penicillins- antibiotic
• Cephalosporins - antibiotic
• Piroxicam- antibiotic
b) Viruses
• Herpes viruses 8
c) Other autoimmune disorders
• Rheumatoid arthritis
• Myasthenia gravis
• Lupus erythematosus
• Pernicious anaemia

• classical lesion - thin-walled bulla arising on otherwise normal skin or mucosa.
• The bulla rapidly breaks but continues to extend peripherally, eventually leaving large areas denuded of
skin.
• Different characteristics signs seen are discussed be low.
Niklosky’s sign
• first described by Dr Pyotr Vasilyewich Nikolsky.
• elicited by applying tangential/lateral pressure by a thumb or a finger in the normal skin surrounding the
lesion which dislodges upper layers of epidermis from lower layers
• The core pathophysiology behind this sign is acantholysis.
• "Acantholysis" is the loss of coherence between epidermal cells because of the breakdown of their intercellular
bridges.

Types of Nikolsky's sign
a) Wet and dry Nikolsky's sign
i) "Wet Nikolsky's sign" - When the eroded base is found to be moist, glistening and exudative, suggestive
of active disease.
ii) "Dry Nikolsky's sign" - When the base of eroded skin or oral mucosal surface is dry
b) Marginal and direct Nikolsky's sign
i) "Marginal Nikolsky's sign" - When the erosion is seen on rubbing surrounding normal area near or to
the existing lesions
ii) "The direct Nikolsky's sign" - It includes the inductions of the erosion on the normal skin that are far
from the lesions.
-A positive direct Nikolsky's sign indicates severe activity of the disease in pemphigus.

Seen in
• Pemphigus vulgaris
• Pemphigus foliaceus
• Pemphigus vegetans
• Toxic epidermal necrolysis

Microscopic nikolsky’s sign
• Pathological changes induce after applying tearing tangential pressure to skin/ mucosa at subclinical level
• Seen in
Pemphigus vulgaris
Pemphigus foliaceus
Pemphigus vegetans
Toxic epidermal necrolysis

Bulla spread sign
• Also called Lutz sign
• It refers to the peripheral extension of a blister to adjacent unblistered skin when pressure is put on the
top of the bulla
• Positive in all variants of blistering disease like pemphigus, pemphigoid, epidermolysis bullosa, steven johnson
syndrome, toxic epidermal necrolysis

Asboe Hansen sign/ modified bulla spread sign
• When pressure is applied to the centre of the lesion will lead to peripheral extension of a blister to
adjacent unblistered skin.
• This sign was first given by Asboe-Hansen
• Positive in all variants of blistering disease like pemphigus, pemphigoid, epidermolysis bullosa, steven johnson
syndrome, toxic epidermal necrolysis

Premlatha sign
• One of the characteristic feature of pemphigus vegetans is tongue involvement with typical sulci and gyri
pattern over the dorsum of the tongue called "Cerebriform tongue"/"Premalatha sign"
• This morphological sign was observed by Dr Premalatha
• Seen in pemphigus vegetans

Oral Manifestations
• Age: Adults, rarely in childhood
• Site: Most commonly the lesions start on the buccal mucosa.
The palate, tongue and gingiva are other common sites of involvement.
• Clinically:

a) Mucous membrane pemphigoid (MMP)/Bullous pemphigoid (BP)
• Bulla in BP/MMP is tensed, firm thick walled as compares to thin fragile bulla in pemphigus.
• Pemphigus is more common in middle aged people while BP is more common in elderly people.
• Nikolsky's sign is either absent or less prominent in pemphigoid compare to pemphigus.
• Desquamative gingivitis is more commonly seen in pemphigoid compared to pemphigus.
b) Erythema multiforme
• Pemphigus shows positive Nikolsky and Asboe Hensen sign, absent in EM.
• EM shows target lesion, which is absent in pemphigus.
• Pemphigus extends central to peripheral (centrifugal) while EM from peripheral to central (centripetal).

Treatment plan
Very mild disease ( only oral pemphigus)
Topical corticosteroid
• Fluocinonide- 0.05%, 2-3 times per day
• Clobetasol propionate- 0.05%, 2-3 times per day
• Triamcinolone acetonide - 0.1-0.5% .
• For desquamative gingivitis - drug should be load in tray
*Topical steroid should be combined with antifungal drugs like clotrimazole to prevent side effect of candidal
infection
Moderate cases (oral pemphigus with mild skin involvement)
• Prednisolone doses of 40-60 mg daily (give morning dose).
• Systemic steroids may be combined with high-potency topical steroids such as clobetasol to control oral lesions.

More severe cases (with severe skin lesion)
• Prednisolone 60-100 mg daily (1.0-2.0 mg/kg/day).
• If there is no response within 5-7 days, the dose is increased by 50% every 4-7 days, until there is disease
control.
• Once remission is achieved and maintained, with healing of most of the lesions, the dose can be slowly tapered.
• A single morning dose is safer for long-term use, but divided doses have more anti-inflammatory effect.

If prednisolone doses above 100 mg daily are unresponsive (pulsed intravenous therapy)
• Pulsed intravenous therapy with 1 g of methylprednisolone in 150 mL of dextrose and water, administered on
1-5 consecutive days, may be considered.
• Goal of this approach is to quickly achieve disease control and allow a reduction in long term maintenance
doses and side effect and usually applied to young, healthy patients

If patient is resistant, unresponsive or allergic to steroid
(adjuvant drugs)
• Adjuvant drugs are commonly used in combination to increase efficacy and have a steroid-sparing effect,
thereby allowing reduced maintenance doses and less side effects of systemic corticosteroids.
• Immunosuppressive drugs/Steroid sparing drugs:
• Azathioprine
• Cyclophosphamide
• Cyclosporine
• Methotrexate
• Anti-inflammatory drugs:
• Gold
• Dapsone
• Tetracycline
• Plasmapheresis - This process removes the pathogenic autoantibodies

INTRODUCTION
• It is a relatively benign variant of PV because the patient demonstrates the ability to heal the denuded ar eas.
• It accounts for 1-2% of pemphigus cases.
• Forms of Pemphigus Vegetans
a) The Neumann type
• The Neumann type is more common.
• The early lesions are similar to
Pemphigus Vulgaris, with large bullae
and denuded areas.
• Attempts at healing result in
vegetations of hyperplastic
granulation tissue.
b) The Hallopeau type
• In the Hallopeau type is milder.
• Initial lesions are pustules, not bullae.
• These pustules are followed by
verrucous hyperkeratotic vegetations.

ORAL MENIFESTATION
• Oral lesions are common in both forms of pemphigus vegetans and may be the initial sign of disease.
• Gingival lesions may be lace-like ulcers with a purulent surface on a red base or have a granular or
"cobble stone appearance."
• One of the characteristic feature of pemphigus vegetans is tongue involvement with typical sulci and gyri
pattern over the dorsum of the tongue called "Cerebriform tongue"/"Premalatha sign".

TREATMENT
• SAME AS PEMPHIGUS VULGARIS

• Paraneoplastic pemphigus is a severe blistering disease This condition is also referred to as "Paraneoplastic
autoimmune multiorgan syndrome" because of the involvement of other systems such as the lungs and the
variable skin findings, namely, pemphigus, pemphigoid, etc.
• It involves multiorgan associated with an underlying neoplasm.
• Different neoplasms associated are:
• Non-Hodgkin lymphoma,
• Chronic lymphocytic leukaemia or thymoma,
• Castleman disease,
• Waldenström macroglobulinaemia.
• Intraorally, the lesions are frequently inflamed and ne crotic, with large erosions covering the lips, tongue and
soft palate.

MUCOUS MEMBRANE
PEMPHIGOID/ CICATRICAL
PEMPHIGOID

INTRODUCTION
• Mucous membrane pemphigoid (MMP) is a rare group of chronic autoimmune disorders characterized by
sub epithelial blistering producing lesions that primarily affects various mucous membranes of the body.
• It is most likely to occur in the oral cavity and eyes although other mucous membranes of the body like
larynx, subglottis, oesophagus or nasal, vulva, penis or anus may also be affected.
• Also called as cicatrical pemphigoid (cicatrical is derived from the word "cicatrix" meaning "scar").

ORAL LESIONS (ORAL PEMPHIGOID)
• The oral lesions may begin as the classic bulla, which rapidly break and form shallow irregular painful ulcers.
• The lesions in their onset and symptoms are similar to PV but are generally smaller.
• The vesicles or bullae appear to be relatively thick walled, and for this reason, may persist intact for 24 48 hrs
before rupturing and desquamating.
• Eventually their rupture does occur leaving a raw, eroded, bleeding surface.
• The gingiva frequently demonstrates an erythema persistent for weeks or even months after the original
erosions have healed.
• Desquamative gingivitis is exclusively seen in pemphigoid.
• Nikolsky's sign is mostly negative.

OCULAR LESION (OCULAR PEMPHIGOID)
• Ocular involvement is a important features of this disease.
• Chronic conjunctivitis with symptoms of burning, irritation, photophobia and excess tearing.
• Vesicles and ulceration is seen only in advanced aggressive disease.
• The conjunctiva may contract and invert the eyelid margins (Entropion), leading to inversion of eyelashes onto
the corneal surface with subsequent irritation (trichiasis).

DIFFERENTIAL DIAGNOSIS
• Pemphigus
• Erosive/Bullous lichen planus

INVESTIGATION
a) Biopsy
• The biopsy should be taken from the edge of an ulcer, vesicle, or erythema and tissue.
• Histopathology reveals subepithelial clefting.
b) Direct Immunofluorescence (Salt split technique)
• This technique includes immunofluorescent staining of skin that has been split at the basement membrane zone
with the use of 1M sodium chloride prior to direct immunofluorescence.
• IgG is directed against antigens.
• Results of salt split technique shows:
• a) Antigen on the epidermal side of the salt-split skin-BPAg2 (BP180).
• b) Antigen on the dermal side of the salt-split skin Laminin- 5 (Laminin-332/ Epiligrin).

BULLOUS PEMPHIGOID
It is quite similar to mucous membrane pemphigoid except the following differences:
• Auto antibodies is against basement membrane zone laminin and so-called bullous pemphigoid antigens 230
(BP230) and 180 (BP 180), which are found in hemidesmosomes and in the lamina lucida of basement
membrane.
• Lesions are mainly occurring in skin while oral manifestations are lesser.
• After erythematous papular eruption tense vesicles and bullae are typically noted.

• tense blister on an inflamed base accompanied by urticarial plaques that chiefly involve the scalp,
abdomen, extremities, axilla, and groin.
• Pruritus is a common feature of the skin lesions, which may initially present
• The disease is self-limiting but can last for months to years without therapy.
• Patients with BP may experience one episode or recurrent bouts of lesions.
• Unlike pemphigus, BP is rarely life threatening since the bullae do not continue to extend at the periphery to
form large denuded areas, although death from sepsis or cardiovascular disease secondary to long-term steroid
use has been reported to be high in groups of sick elderly patients.

Oral Findings
• Oral involvement occurs in 10%–20% of BP patients.
• The oral lesions of BP are smaller, form more slowly, and are less painful than those seen in PV; the often
extensive labial involvement seen in PV is not present.
• Desquamative gingivitis has also been reported as the most common oral manifestation of BP, and the gingival
lesions may be the only site of oral involvement.
• The gingival lesions consist of generalized edema, inflammation, and desquamation with localized areas of
discrete vesicle formation.
• The oral lesions are clinically and histologically indistinguishable from oral lesions of MMP, but early remission
of BP is more common.

Differential Diagnosis
• erosive form of lichen planus, PV, and the other subepithelial bullous dermatoses.
• The erosive and ulcerative forms of LP frequently exhibit white Wickham striae at the periphery along with
ulcerations and erosions.
• PV usually has more extensive erosion of mucosa as well as skin involvement, and the lesions do not have the
inflammation associated with MMP.
• The other subepithelial bullous dermatoses appear clinically similar to MMP and can only be distinguished by
immunofluorescent and molecular techniques.

Management
• Patients with localized oral lesions of BP may be treated with high-potency topical steroids, such as clobetasol
or betamethasone, whereas patients with more extensive disease require use of systemic corticosteroids alone or
combined with immunosuppressive drugs such as azathioprine, cyclophosphamide, mycophenolate, or
rituximab.
• Patients with moderate levels of disease may minimize the use of systemic steroids by the use of dapsone or
tetracycline, doxycycline, or minocycline, which may be combined with niacinamide.

THE PATIENT WITH SINGLE
ULCERS
Traumatic Injuries Causing Solitary Ulceration

• Single mucosal ulcers may be caused by direct physical/ mechanical, thermal, or chemical trauma to the
mucosa or even vascular compromise, causing tissue damage and ulceration.
• Traumatic injuries may also result from. malocclusion, ill-fitting dental prostheses, overzealous
toothbrushing and flossing, self-injurious habits, and oral piercings
• Thermal injuries including electrical burns are infrequently seen in children who inadvertently chew on
electrical wiring.
• More commonly, thermal burns occur on the palatal mucosa from ingesting hot foods and beverages (such as
hot pizza or coffee).
• An iatrogenic cause of thermal injury is from a heated dental instrument inadvertently contacting the mucosa.
• The burn is usually more serious if the mucosa has been anesthetized and there is prolonged contact
• Chemical trauma is caused by patients or dentists placing noxious and caustic substances directly on the
mucosa either as a therapeutic measure or unintentionally.

Oral Findings
• These present as acute ulcerations and necrosis of the mucosa with a clear antecedent history of injury.
• The extent of the ulceration depends on the agent involved and the site depends on the activity involved.
Electrical burns in particular are caused by high heat, are generally fairly extensive, involve the lips, and are
generally seen in young children and toddlers.
• The initial lesions are charred and dry-appearing.
• However, after a few days, this charred crust sloughs, and there may be excessive bleeding when the underlying
vital structures are exposed.
Burns from hot foods and beverages are generally small and localized to the hard palatal mucosa or lips and are
usually seen in teenagers and adults.
• The area usually presents as an area of tenderness and erythema that develops into ulcers within hours of the
injury.
• It may take several days to heal depending on the extent of the injury.
• Ulcers from vascular compromise such as necrotizing sialometaplasia and vasculitic lesions last for weeks and
months.

Management
• Smaller lesions caused by less severe thermal or chemical injury heal on their own once the irritant is removed.
• Pain control can be achieved with topical anesthetics (such as viscous lidocaine).
• Topical steroids or intra-lesional steroid injections may be useful.
• Avoidance of reinjury is also important, and this may be effected by counseling patients regarding the
avoidance of use of caustic substances and the correct use of medications.
• Antibiotics may be necessary to prevent a secondary infection since these burns often take several weeks to
heal.
• Necrotizing sialometaplasia heals on its own while ulcers of vasculitic origin will generally require treatment
with systemic corticosteroids.

Traumatic Ulcerative Granuloma
(Eosinophilic Ulcer of Tongue)

• This ulcerative condition of the oral cavity is considered traumatic in nature, although less than 50% of
patients recall a history of trauma.
• These lesions have been experimentally induced in animals by inflicting crush injury on the tongue, the most
common site of these lesions.
• It is likely that the penetrating nature of the inflammation results in myositis that leads to chronicity.
• As such, other acute or chronic ulcerative conditions left untreated may become deep and penetrating.
• Similar lesions are seen on the ventral tongue in infants caused by the tongue rasping against newly erupted
primary incisors, a condition known as Riga–Fede disease.
• Patients with familial dysautonomia and other conditions, such as Riley–Day syndrome and Lesch–Nyhan
syndrome, who have congenital incapacity to sense pain often also develop similar ulcerative and necrotic
ulcers because they are unaware of the self-inflicted injury

• There is a bimodal age distribution with one group in the first two years of life, where lesions are associated
with erupting primary dentition.
• The second group is in adults in the fifth and sixth decades

Oral Findings
• In children, the ulcers are always on the anterior ventral or dorsal tongue associated with erupting
mandibular or maxillary incisors, respectively.
• The tongue is the site of involvement in approximately 60% of adult cases, usually on the posterior and lateral
aspects.
• An ulcer develops that may not be painful in two-thirds of cases and may persist for months.
• A history of trauma is elicited in only 20%–50% of cases.
• The ulcer generally appears cleanly punched out, with surrounding erythema and keratosis if present for
weeks or months.
• They range from 0.5 cm to several centimeters in size.
• The surrounding tissue is usually indurated.
• Other sites that may be involved include the buccal mucosa and labial mucosa, floor of the mouth, and
vestibule, all sites where there is abundant underlying skeletal muscle.
• Five percent are multifocal, and recurrences are not uncommon.
• In some cases, the lesions present as an ulcerated mass on the lateral tongue.

Management
• A careful history is important to rule out continued trauma to the site, although this is sometimes difficult to
elicit and sometimes to prevent, especially if trauma occurs during sleep.
• Intralesional steroid injections performed over a few weeks will often resolve these lesions.
• Wound debridement also often leads to complete resolution, although up to onethird of cases recur.
• The use of a nightguard on the lower teeth may help reduce nighttime trauma

Vesiculobullous lesion of oral cavity.pptx

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