SKIN DISORDERS AFFECTING

ORAL CAVITY

DR. Parul Khare

III MDS
SARSAWATI DENTAL COLLEGE
 Epidermolysis Bullosa
 Is a group of rare, genetically determined disorders characterized by bullae & vesicles
that form on the skin & mucous membranes. The blisters are frequently the result of
minor trauma, heat & occasionally an unknown cause.
CLASSIFICATION
1.EB simplex :–
a. EBS-Weber-Cockayne
b. EBS-Kobner
c. EBS Dowling – Meara
d. EBS with muscular dystrophy
2. Junctional EB :-
a. Herlitz
b. Non - Herlitz
3. Dystrophic EB :-
a. Dominant DEB
b. Recessive DEB
ETIOPATHOGENESIS
EBS – Defect in Tonofilaments of Keratinocytes in basal
keratinocyte layer.
JEB – Defect in Hemidesmosomes in the Lamina Lucida.
DEB – Defect in Anchoring filaments underneath the
basement membrane.

HISTOPATHOLOGICAL FEATURES
Bullae are intra-epidermal and suprabasal in location.
Dissolution of organelles & tonofibrils.
Elastic , pre – elastic & oxytalan fibers in the connective
tissue.
 
 DERMATITIS HERPETIFORMIS
Is a rare, benign, chronic, recurrent, immune – mediated blistering
dermatologic disease with an associated, most often asymptomatic, gluten
sensitive enteropathy (GSE).

Characteristic skin lesions found in patients with dermatitis herpetiformis

are extremely located on extensor surfaces.

The pathogenesis of DH is associated with the presence of GSE an

increased expression of human leukocyte antigen 1 (HLA- A1), human
leukocyte antigen B8 (HLA –B8), human lkeukocyte antigen DQ2 (HLA
–DQ2) haplotypes, & granular deposition of IgA at the dermal epidermal
junction of the skin.

 
CLINICAL FEATURES:

The disease occurs chiefly between 20-55 years of age, although

children are occasionally involved.

Slight male predilection.

First manifestations of disease are – usually pruritus & severe burning,

followed by the development of erythematous papules, vesicles, bullae
or pustules.

Occurs in extremities, trunk & buttocks as well as on the face, scalp &
sometimes oral cavity

 
 Acrodermatitis Enteropathica
Is an autosomal recessive disorder characterized by perioral
and acral dermatitis, alopecia, and diarrhea.

Two new fibroblast of patients with acrodermatitis

enteropathica have recently been discovered. These proteins
may be responsible for decreased zinc uptake and abnormal
zinc metabolism. Symptoms occur within the first few
months after birth and tend to appear shortly after
discontinuation of breastfeeding.
CLINICAL FEATURES:
The disease begins in the first few weeks or months of life
with a localized eruption of the skin, particularly near the body
orifices.
There is loss of hair & gastrointestinal disturbance
accompanied by diarrhea.
The skin lesions are vesiculobullous in nature and tend to
occur in crops.
These lesions rupture and become crusted & ultimately
erytheromatous, scaling with a psoriasiform pattern.
The skin lesions, and oral lesions as well, are prone to
secondary infection, especially by candida albicans.
Oral Manifestation – the oral mucosa, chiefly the buccal
mucosa, becomes erythematous and edematous with erosive
desquamative lesions.
HISTOLOGIC FEATURES:

 reveal parakeratosis of the stratum orneum with occasional

neutrophils and intracellular edema.
The granular cell layer is diminished, and the upper
epidermis demonstrates pallor & edema.
Focal dyskeratosis is seen.
The epidermis may be psoriasiform or atrophic.
Occasionally subcorneal pustules are seen.
 
LABORATORY FINDINGS - plasma zinc levels are low
Determining hair, urine, and parotid saliva zinc levels as well
as serum alkaline phosphatase activity may be helpful.
 
 SYSTEMIC SCLEROSIS
Scleroderma is a multisystem chronic connective tissue disease
of unknown etiology that involves hardening of skin and
mucosae with smooth muscle atrophy and fibrosis of internal
organs.
There will be characteristic appearance of circumscribed or
diffuse, hard, smooth, ivory colored areas that are immobile
upon the underlying tissue that gives the characteristic
hidebound skin.
Since oral involvement is one of the feature characterized by
trismus, burning sensation and classical facial appearance here
comes the role of a dentist to identify this condition which shares
similar features with other oral diseases.
Origin: Greek word –“Scleros” hard/indurated and “derma” skin.
 
Localized scleroderma
Women 3 times >men
Whites >blacks
20-50 years (any age).
 9 year old ( Pediatr Dent 1993;15;275-79)
Linear scleroderma – 1st and 2nd decade

 
Systemic Scleroderma
F:M::4 :1
Black >whites
Incidence : 17 /million

 
Etiology
Association factors

Autoimmune disease its association with Ags from

human leukocyte antigen (HLA) histocompatibility
complex including HLA-B8, HLA-DR5, HLA-DR3,
HLA-DR52, HLA-DQB2
 
Genetic disorders
Phenylketoneuria
Progeria
Rothmund-thomson syndrome
Werner’s syndrome
Occupational factors
Jackhammer and chainsaw operators
 
Chemicals
PVC
Silica
Epoxy resins
Bleomycin
Carbidopa
L-tryptophan

Metabolic
Porphyria cutanea tarda
Primary systemic amyloidosis
Hashimoto’s disease
Carcinoid syndrome
 
Immunological factors.
Childhood diabetes mellitus
Graft V/S host reaction
 
 
ORAL MANIFESTATION:

 The tongue, soft palate and larynx are the intraoral structures
usually involved in progressive systemic sclerosis.
 Early mild edema of these structures is gradually followed by
atrophy and induration of mucosal & muscular tissues.
 The tongue often becomes stiff and boardlike, causing the
patient difficulty in eating & speaking. The gingival tissues are
pale and usually firm.
 The lips become thin, rigid and partially fixed, producing
microstomia.
 Dysphagia, a chocking sensation, inability to open and close the
mouth & difficulty in breathing also occur.
 Limitation in mouth opening make dental care very difficult.
ROENTGENOGRAPHIC FEATURES:

 Extreme widening of the periodontal ligament, two or four

times normal thickness.

Bone resorption of the angle of the mandibular ramus,

usually bilaterally.

Partial or complete resorption of condyles & or coronoid

process of the mandible.
HISTOLOGIC FEATURES:
diffuse systemic sclerosis is characterized microscopically by
thickening and hyalinization of the collagen fibers in the skin, the
loss of dermal appendages, particularly the sweat glands, and
atrophy of the epithelium with loss of rete pegs & increased
melanin pigmentation.
There is an increase in PAS positive. Diastase resistant material
present in the areas of the homogenous collagen.
Subcutaneous fat disappears and the walls of the blood vessels
become sclerotic.
Mucous membrane changes are similar to those occurring in skin.
Microscopic changes in the periodontal ligament consists of a
widening due to an increase of collagen and oxytalan fibers as well
as an appearance of hyalinization and sclerosis of collagen with a
diminution in the number of connective tissue cells usually found.
Ehlers – Danlos Syndrome

EDS is the name given to a group of more than 10 different inherited

disorders; all involve a genetic defect in collagen & connective tissue
synthesis & structure.

EDS can effect the skin, joints and blood vessels.

The syndrome is clinically heterogenous, the underlying collagen

abnormality is different for each type.

ETIOLOGY – EDS is a heterogenous group of inherited connective

tissue disorders characterized by joint hypermobility, cutaneous
fragility & hyperextensibility.
 
 
CLINICAL FEATURES: hyperelasticity of skin
Hyperextensibility of the joints & fragility of the skin &
blood vessels resulting in excessive bruising as well as
defective healing of skin wounds.
Hyperextensibility of skin & joints is striking in EDS I and
EDS III but very limited in EDS II and EDS IV is often
called the ecchymotic type, since rupture of even lrge
arteries as well as the intestine often occurs, producing a life
threatening situation.
In instances in which the skin extensibility is pronounced,
the patient has become known as the circus ‘ rubber man’.
The facies are frequently distinctive with
hypertelorism, a wide nasal bridge & epicanthic folds
being common features.
Protruding ears & frontal bossing are oftn present.
Freely movable subcutaneous nodules are frequently
found, and these appear to represent fibrosed lobules
of fat.
The scarring of the skin following wound healing in
these patients is unusual inasmuch as the scars tend to
spread rather than contract in time.
ORAL MANIFESTATION –

Normal mucosa normal in color but excessive fragile &

bruised easily. Although the mucosa did not hold sutures
satisfactorily, healing was only slightly retarded & there was
no defective scar formation.
No remarkable hyperextensibility of mucous membrane could
be demonstrated, and the patients had no difficulty in wearing
dentures.
The gingival tissue appeared fragile & bled after tooth
bruishing, gingival hyperplasia and fibrous nodules were also
noted.
Hypermobility of temporomandibular joint, resulting in
repeated dislocation of the jaw, has been reported.
Alteration in the structure of the teeth have also been
reported. These consist of lack of normal scalloping of the
DEJ, the passage of many dentinal tubules.

into the enamel, the formation of much irregular dentin &

an increased tendency to form pulp stones.

Hypoplastic changes in the enamel have also been

reported, the teeth have been reported to be fragile & have
a tendency for fracture.
HISTOLOGIC FEATURES
Routine techniques generally fails to reveal any
characteristic or diagnostic abnormality.
Ultrastructural changes in collagen have been reported.
 Focal Dermal Hypoplasia Syndrome
FDH is an uncommon genetic disorder characterized by
distinctive skin abnormalities and a wide variety of defects that
affect the eyes, teeth and skeletal, urinary, gastrointestinal,
cardiovascular and central nervous system.

 Mnemonic FOCAL can be used for key features of this

syndrome : Female sex, Osteopathia striata, coloboma absent
ectodermis, mesodermis, and neurodermis derived elements
and lobster claw deferomity.

Affected individuals are recognized at birth or prenatally, but

cases involving a minor expression of syndrome may be
diagnosed latter.
ETIOLOGY - X linked dominant inheritance pattern & is
usually lethal in males.

The underlying molecular defect in FDH is not clear.

On the basis of common findings of syndactly, oligodactyly

& polydactyly the fetal expression of FDH is postulated to
occur before the eighth week of gestation, by the eighth
week, the hands & feet have differentiated and developed
separate & elongated digits
CLINICAL FEATURES- focal absence of the dermis
associated with herniation of the subcutaneous fat into the
defects, skin atrophy, streaky pigmentation & telangiectasia,
multiple papillomas of the mucosa & / or skin, anomalies of
the extremities including syndactyly, polydactyly and
adactyly, an asymmetrical face with pointed chin & notched
nasal alae, asymmetrical ears, sunken eyes with sparse eye
brows & scalp hair, eye anomalies, most frequently iris &
dental & oral anomalies.
Mental retardation is often present as is some retardation of
physical growth.
 ORAL MANIFESTATION

papillomas of the lips have been a stiking features in a

number of these patients as well as papillomas of the
buccal mucosa or gingival.

Teeth are commonly defective in size, shape or structure.

Microdontia is a common finding as is enamel hypoplasia.

Cleft lips/ cleft palate has also been described.

 HISTOLGIC FEATURES
The atrophic reticulated patches of skin reveal attenuation of dermal collagen
fibers with partial to complete absence of significant portion of dermis.

An accompanying change is the appearance of adipose cells in the dermis.

In mild cases, adipocytes may be noted may replace all or part of the dermal
connective tissue.

A layered effect sometimes occurs, with attenuated collagenous connective

tissue lying both above and beneath an adipose layer.

Papilomatous lesions typically consist of a fibrovascular stalk composed of

loose connective tissue with dilated vessels and a variable perivascular
admixture of inflammatory cells.
 SOLAR ELASTOSIS

Is a dermatologic disease which is essentially a degenerative

condition of skin associated with the general process of
aging which itself may be influenced by hereditary factors
including skin coloration or pigmentation or its absence,
and exposure to the elements, especially sunlight & wind.
CLINICAL FEATURES - this disturbance seldom occurs
on the oral mucous membranes, but does involve the lip
with considerable frequency .

The affected skin is wrinkled and appears dry, atrophic

and flaccid.

On the lip there may be mild keratosis and subtle blending
of the vermilion with the skin surface.
HISTOLOGIC FEATURES:

 the chief microscopic characteristic is the apparent

increase in the amount of elastic connective tissue fibers, a
phenomenon that is best observed in special stains.

In H & E stained sections, the connective tissue may

appear hyalinized, but it stains with hemotoxylin rather
than with eosin & this has been termed basophilic
degeneration.
ECTODERMAL DYSPLASIA
.
 It represents a group of the inherited disorder in which
two or more ectodermally derived anatomic structures fail
to develop, thus hyperplasia or aplasia develops.
example-skin, teeth, nails, hair.

 The most common syndrome associated within this group

include are hypohidrotic ED and hidrotic ED.
CLINICAL FEATURES:
EDS is most common in males, females are carrier
Dental, nail and hair anomalies are evident during childhood and
infancy.
Such patient are intolerant to heat to the decreased sweat glands. Hence
cannot regulate body temperature.
Salivary gland are developed ectodermally hence shows marked
xerostomia.
Decreased no of mucous salivary gland.
Decreased lacrimal gland secretion.
Deficient hearing and vision.
Nails are brittle or deformed
Hair are sparse or there is complete absence
Tooth shows abnormal morphology.
Lack of breast development.
Saddle shaped nose.
 WHITE SPONGE NEVUS

Familial white folded dysplasia of mucous membrane,

cannons disease, white folded gingivostomtitis.

It is an uncommon condition of oral mucosa.

Clinical features-
This mucosal abnormality is congenital in many instances.

It does not appear until infancy, childhood, or even

adolescence, by this time it reaches its full extent.
Oral lesions-

The lesions involve the

cheek ,
 palate,
gingiva,
floor of the mouth
and portions of the mouth.
 The mucosa appear thickened and folded or corrugated with
a soft or spongy texture and a peculiar white opalescent hue.
Sometimes a minimal amount of folding is present.
Ragged white area can be scrapped out without ensuing
bleeding.
Histological features-

Epithelium is thickened.
Hyperkeratosis and Acanthosis.
Basal layer is intact.
Intercellular edema.
Vacuolated cells may show pyknotic nuclei.
Para keratin plugs running deep into the spinous layer.
Sub mucosa may show mild inflammation.
Treatment and prognosis-
There is no t/t.
Its benign, the prognosis is excellent.
Has no complication.
 Hereditary benign intraepithelial dyskeratosis
The disease appears superficially similar to familial white folded
dysplasia or white sponge nevus in its hereditary pattern the clinical
& microscopic features are different.

CLINICAL FEATURES –
Appear generally as white, spongy, macerated lesions of the buccal
mucosa, with or without folds.
They are described on the floor of the mouth, ventral and lateral
surfaces of the tongue, the gingiva and palate.
These lesions vary from delicate, opalescent white membranous
areas to a rough, shaggy mucosa.
Lesions frequently involve the corners of the mouth and appear as
soft plaques with pinpoint elevation when the mucosa is stretched.
 
Lesions of eye characterized by superficial, foamy,
gelatinous white plaques overlying the cornea, producing
temporary blindness.

Conjunctivae are usually intensely congested.

These eye lesions in some cases show a seasonal

variation, tending to appear or increase in severity in the
spring & disappear, sometimes by spontaneous shedding
of the pseudomembrane, in late summer of fall.
HISTOLOGIC FEATURES – Sections of the buccal
mucosa exhibit thickening of the epithelium with
pronounced hydropic degeneration.

Numerous round, waxy appearing eosinophilic cells

resembling minute epithelial pearls are evident, the
‘dyskeratotic’ cells.
 PANCHYONYCHIA CONGENITAL

Is a group of rare genodermatoses that are usually inherited

as an autosomal dominant trait.

The nails are dramatically affected in most patients, but oral

lesions are seen only in patients affected by the Jadassohn –
Lewandowsky form of the disease.
CLINICAL FEATURES - virtually all patients with pachyonychia
congenita exhibit characteristic nail changes, either at birth or in the
early neonatal period.

The free margins of the nails are lifted up because of an accumulation

of keratinaceous material in the nail beds.

This results in a pinched, tubular configuration.

Ultimately, nail loss may occur.

Other skin changes that may occur include hyperkeratosis of the

palmar & plantar surfaces, producing thick, callous like lesions.

Hyperhidrosis of the palms & soles is also commonly present.

The rest of the skin shows punctate papules, representating an
abnormal accumulation of keratin in the follicles.

Disabling feature of the syndrome is the formation of painful

blisters on the soles of the feet after a few minutes of walking
during warm weather.

Oral lesions consists of thickened white plaque that involve the

lateral margins & dorsal surface of the tongue.

Neonatal teeth have been reported in patients affected by the JL

form, but these individuals do not have oral white lesions.

Hoarseness & dyspnea have been described in some patients as a

result of laryngeal mucosal involvement.
 
 Xerdoerma pigmentosum

Is rare genodermatosis in which numerous cutaneous malignancies develop at a verly age.
The condition is inherited as an autosomal recessive trait and its caused by one of several defects in the
excision repair and / or postreplication repair mechanism of DNA.
As a result of the inability of the epithelial cells to repair ultra- vilot light induced damage, mutations in
the epithelial cells occur, leading to the development of skin cancer at a rate 1000 to 4000 times what
would normally be expected in people under 20 yrs of age.
CLINICAL FEATURES- during first few years patient show a markedly increased tendency to sunburn.
Skin changes such as atrophy freckled pigmentation, and patchy depigmentation, soon follow.
In early childhood, actinic keratosis begin developming, a process that normally does not take place
before 40 yrs of age.
These lesions quickly progress to squamous cell carcinoma, with basal cell carcinoma also appearing,
consequently, in most patients a nomelanoma skin cancer develops during first decade of life.
Melanoma develops in about 5% of patients with xeroderma pigmentosum, but it evolves at a slightly
later time.
As a consequence of sun exposure, the head & neck region is the site most frequently affected by these
malignancies.
Neurological manifestations include subnormal intelligence in 80% of affected individuals.
ORAL MANIFESTATION –
Development of squamous cell carcinoma of the lower lip & tip
of tongue.
Diagnosis of xeroderma pigmentosum is usually made when the
patient is evaluated for the cutaneous lesions.
It is a autosomal recessive trait.
 

HISTOPATHOLOGIC FEATURES: xeroderma pigmentosum are

relatively nonspecific, in that the cutaneous premalignant lesions
& malignancies that occur are microscopically indistinguishable
from those observed in unaffected patients.
 
 
 INCONTINENT PIGMENTI

Termed as Bloch- Sulzberger syndrome, is an X linked

dominant single gene disorder with neurologic,
ophthalmologic, and dental involvement as well as
cutaneous findings.
Is defined as clinical syndrome with a constellation of
unique features, which include typical cutaneous lesions.

ETIOLOGY –
The patchy distribution of the skin lesions is thought to be
the result of tissue mosaicism due to random X inactivation.
Normal X chromosomes are active in unaffected skin, and
mutated X chromosomes are active in skin affected with IP.
CLINICAL FEATURES -
95% Females are affected.

Characterized by the appearance of erythematous and

vesiculobullous lesions on the trunk & extremities which
frequently disappear, then reappear.

This phase is often associated with a marked eosinophilia.

These are gradually replaced by white keratotic, lichenoid,

papiilary or verrucous lesions which then persist for some
months.
The third type of characteristic skin lesion in these infants
are brownish gray macules in a streaked, patchy distribution
over the trunk & extremities, occurring subsequent to the
verrucous keratotic lesions.

This pigmentation begins to fade within a few years.

It is the heavy melanin pigmentation of the epithelium,

dropping down into clusters of chromatophres in the upper
dermis.

Associated defects – local & generalized cataracts, optic

atrophy, strabismus & retrolental fibroplasia, central nervous
system involvement and lesions of the skeletal system.
ORAL MANIFESTATION –

 oral changes in this disease have been limited.

Both deciduous and permanent dentition may be affected.
These dental changes have been described as consisting of
delayed tooth eruption, peg or cone shaped tooth crowns,
congenitally missing teeth, malformed teeth & additional
cusps.
The cone shaped teeth are very similar to those seen in
hereditary ectodermal dysplasia.
 DARIER’S DISEASE
Keratosis follicularis also known as Darier disease is a
dominantly inherited genodermatosis that is characterized by
hyperkeratotic papules in seborrheic regions & various nail
abnormalities.

ETIOLOGY –
abnormal cell- cell adhesion and aberrant epidermal
keratinization are the primary features of DD.
Electron microscopy reveals loss of desmosomes, breakdown
of desmosome keratin intermediate filament attachment and
perinuclear aggregates of keratin intermediate filaments.
Recently mutation in the gene ATP2A2 were found in
patients with DD.
 DARIER’S DISEASE
 CLINICAL FEATURES - manifested in childhood or adolescence
and has an equal gender distribution.
 The cutaneous lesions appear as small, firm papules, which are red
when they first appear, but characteristically become grayish
brown or even purple, ulcerate and crust over.
 Especially in the skin folds, the lesion tend to coalesce and
produce verrucous or vegetating macerated, foul smelling masses.
 They are generally distributed about the forhead, scalp, neck &
over the shoulders, but often spread to the limbs, chest & genitalia.
 Palmer & plantar keratotic thickening may be so severe cases, all
the intertriginous areas are involved.
 Nail change are also seen consisting of splintering, fissuring,
longitudinal streaking & sublingual keratosis.
ORAL MANIFESTATION – oral lesions appear as minute, whitish
papules which feel rough upon palpation.
Some cases have been described as rough, pebbly areas with
verrucous white plaques or as having a cobblestone appearance
Found frequently in gingival, tongue, hard and soft palates, buccal
mucosa and even the pharynx.
HISTOLOGIC FEATURES –
Skin lesions : hyperkeratosis, papillomatosis, acanthosis & a peculiar
benign dyskeratosis.
This benign dyskeratosis is characterized by rather typical cells
called corps ronds & grains.
The corps ronds are larger than normal squamous cells and have a
round homogenous basophilic nucleus with a dark eosinophilic
cytoplasm and a distinct cell membrane.
These are found usually in the granular layer are superficial spinous
layer.
 These are found usually in the granular layer are superficial
spinous layer.
 The grains are small elongated parakeratotic cells situated in the
keratin layer.
 Both corps ronds & grains represent partially keratinized cells and
are found also in the typical slitlike intradermal vesicle just above
the basal layer of cells, the typical suprabasilar cleavage.
 Acantholytic cells are commonly found floating in the lacunae
produced by this intraepithelial separation.
 The cytologic findings in scrapings taken from the deeper portion
of oral mucosal lesions have been described that some of the cells
might be mistaken for malignant cells, the general cell population,
the presence of grain cells and corps ronds and the leafing out
pattern of the parabasal cells should permit the correct diagnosis
from such cytologic smears.
 WARTY DYSKERATOMA
Is a lesion which bears marked histologic similarity to keratosis
follicularis but, in contrast to the latter, is usually a single isolated focus.
CLINICAL FEATURES: Skin lesions have occurred on the face, scalp or
neck & upper chest in the majority of reported cases.
They are almost invariably single lesions varying in size from only
1 -10mm in diameter.
They appear as elevated nodules, somewhat umbilicated, with a rised
border & varying in color from yellow or brown to gray or black.
Purulent discharge as well as bleeding frequently occurs.
ORAL MANIFESTATION –
 oral lesions are rare but do occur.
Small whitish areas of the mucosa with a central depression & were
situated on the alveolar ridge & palate.
 
 WARTY DYSKERATOMA
ORAL MANIFESTATION -
Oral lesions are rare but do occur.
Small whitish areas of the mucosa with a central depression & were situated on the
alveolar ridge & palate.

HISTOLOGIC FEATURES –
Findings of skin & mucosal lesions are identical except for the absence of a
pilosebaceous structure in the oral lesions.
The intra oral lesions exhibit a central orthokeratin or parakeratin core beneath which
the epithelium shows a suprabasilar separation resulting in cleft like space containing
acantholytic & benign dyskeratotic cells.
The connective tissue papillae are covered usually by a single layer of basal cells
while the underlying connective tissue shows a nonspecific inflammatory cell
infiltrate.

 
 
 PEUTZ JEGHERS SYNDROME

Is an autosomal dominantly inherited disorder characterized by intestinal

hamartomatous polyps in association with mucocutaneous melanocytic macules.
Cancer primarily is of the GI tract, including the pancreas & luminal organs & of
the female & male reproductive tracts & the lung.
 
ETIOLOGY –
Germline mutation of the STK11 gene
Penetrance of the gene is variable, causing varied phenotypic manifestation
among patients with Peutz Jeghers syndrome & allowing for a variable
presentation of cancer.
In cancer formation, STK11 inactivation appears to occur early and might be
followed by interruption of the APC/β catenin & p53 pathways, but this has not
been fully elucidated. STK11 may be a tumor suppressor gene in that its
overexpression can induce a growth arrest of a cell at the G1 phase of the cell
cycle & that somatic inactivation of the unaffected allele of STK11 often is
observed in polyps and cancers from patients with the Peutz Jeghers syndrome.
CLINICAL FEATURES – all races
- Female & male equal ratio
- Affected individual usually have family history
- principal causes of morbidity stem from the intestinal location of
the polyps
- Morbidity includes small intestinal obstruction & inussusception,
abdominal pain, hematochezia, & prolapsed of colonic polyp &
these typically occur in the second & third decade.
- Repeated bouts of abdominal pain in patients younger than 25yrs,
unexplained intestinal bleeding in a young patient or mensural
irregularities in females, cutaneous pigmentation of the perioral
region crossing the vermillion border, perinasal & perioral areas
are seen, pigmentation may also be present on the fingers & toes,
on the dorsal & volar aspects of the hands & feet & around thymus
& genitalia.
Mucous membrane pigmentation affects primarily buccal
mucosa.

Other syndrome include precious puberty, prolapse of

tissue from the rectum, rectal mass, testicular mass,
gynecomastia & growth acceleration.

HISTOLOGIC FEATURES – extensive smooth muscle

arborization throughout the polyp, with the appearance of
pseudoinvasion because some of the epithelial cells usually
from benign glands are surrounded by the smooth muscle.
 Hereditary hemorrhagic teleglectasia

Is an autosomal dominant disorder identified typically by the

triad of telangiectasia, recurrent epistaxis & a positive family
history for the disorder.
Major cause of morbidity & mortality due to this disorder lies
in the presence of multiorgan arteriovenous malformations &
the associated hemorrhage.
CLINICAL FEATURES- In white patients.
The spider like Telangiectases are occasionally present at or
shortly after birth, although in the majority of cases they do
not become conspicuous until after puberty.
They appear increase in number & prominence as the patient’s
ages.
Skin lesions are most common on the face, neck, and chest
Most commonly affected areas being the lips, gingival,
buccal mucosa & palate, as well as the floor of the mouth &
the tongue.
Often occurring in childhood & preceding the appearance of
telangiectasia, is epitaxis as well as bleeding from the oral
cavity.
The main areas of involvement are nasal mucosa, skin, the
GI tract, the pulmonary vasculature & the brain.
Similar telengiectases of skin & oral mucous membranes
may occur in a variety of other situation include – sclerosis
(scleroderma) and the CREST syndrome (calcinosis cutis,
Raynaud’s phenomenon, esophageal dysfunction,
sclerodactyly and telangiectasia), lupus erythematosus,
sarcoid & other rare disease.
HISTOLOGIG FEATURES: primarily defects in small
blood vessels of the skin & mucosa.
Actual cause of the hemorrhage is either a primary
intrinsic defect of the endothelial cells permitting their
detachment or a defect in the perivascular supportive
tissue bed which weakens the vessels, rather than a lack of
elastic fibers as was thought at one time.
Both clooting & bleeding times are normal, as are blood
elements although severe bleeding mild anemia and
thrombocytopenia may result.
 Multiple hamartoma syndrome
Is a rare condition that has important implication for the
affected patient, because malignancies, in addition to the
benign hamartomatous growths, develop in a high percentage
of these individuals.
Syndrome is inherited as an autosomal dominant trait
showing a high degree of penetrance and a range of
expressivity.
The gene responsible for this disorder has been mapped to
chromosome 10, and a mutation of the PTEN gene has been
implicated in its pathogenesis.
CLINICAL FEATURES –
 Cutaneous manifestation are present in almost all patients
with multiple hamartoma syndrome, usually developing
during the second decade of life.
The majority of skin lesions appear as multiple small
papules (less than 1mm) primarily on facial skin, especially
around the mouth, nose, and ears.
Microscopically, most of these papules represent hair
follicle hamartomas called trichilemmomas.
Other commonly noted skin lesions are acral keratosis, a
warty appearing growth that develops on the dorsal surface
of the hand and palmoplantar keratosis, a prominent
calluslike lesion on the palms or soles.
Cutaneous hemangiomas, xanthomas and lipomas have been
described.
Several types of benign and malignant tumors of the female
genitourinary tract occur more often than in the normal
population.
Oral lesions vary in severity usually consist of multiple papules
affecting gingivae, dorsal tongue, and buccal mucosa.
Oral findings include a high arched palate, periodontitis &
extensive dental caries.

HISTHOPATHOLOGIC FEATURES:
Nonspecific, essentially representing fibroepithelial hyperplasia.
Other lesions associated with this syndrome have their own
characteristic histopathologic findings, depending on the
hamartomatous or neoplastic tissue origin.
 Oral lichen planus
(lichen rubber planus)
It is relatively common chronic dermatological
disease that often effects oral mucosa.

This condition mainly affects the skin and the oral

mucosa.

It causes bilateral white striation ,papules and

plaque on tongue ,buccal mucosa and gingivae.
etiology-
1. drug induced(lichenoid drug
reaction)
2. Contact allergen in restorative
material or toothpaste.
3.mechinical trauma.
4.viral infection
5. in nervousness
This disease seldom occur in carefree
people.
Grins pan's syndrome-

it is an syndrome associated with oral

lichen planus which is an triad of lichen planus,
diabetes mellitus and vascular hypertension.
Clinical features-
Female to male ratio is 1.4:1
It mainly occur in adults older than 40 years.
Skin lesions of lichen planus appears as
 Small ,angular, flat topped papules only few
cm to mm in diameter.
These may be discrete earlier and later on
coalesce to form larger plaque. These are
covered by fine glistening scale.
They are demarcated from skin.
 the lesion may appear as reddish , purple ,or
violaceous hue. Later on dirty brownish color
develops.
Center of the papule is umblicated.
The surface of the lesion is covered with very
fine grayish-white lines called as Wickham's
striae.
Location-
Any where on the skin in the bilaterally
symmetrical pattern most often on the-
a) Flexor surface of the wrist and
forearm.
b) Inner aspect of knees, thighs and
trunk.
Oral manifestation

characterized by-
 radiating grey or white, velvety,
threadlike papules

Arrangement-
 In linear ,annular or retiform
arrangement forming lacy ,reticular
patches, rings or streak

Location-
 over buccal mucosa and to a lesser
extent to lips ,tongue and palate.
A tiny white elevated dot present at
the intersection of white lines is
known as striae of Wickham.
% of distribution of oral lesions-
85% -buccal mucosa
65% -tongue
20% -gingivae ,floor of the
mouth and palate.
Types of lichen planus
Bullous form of lichen planus
Erosive form of lichen planus-
 These lesions are more symptomatic.
Clinically they are atrophic erythematous
area with clinical ulceration of varying
degree.
• Atrophic form of lichen planus-
Appear clinically as smooth red poorly
defined area often but not always with
peripheral striae.
Hypertrophic form-
 it may also occur on the oral mucosa, as a well
circumscribed, elevated white lesion resembling
leukoplakia.
 In this case biopsy is necessary to establish the
diagnosis.

 The oral manifestation of lichen planus may occur weeks

or months before the appearance of the skin lesion.
 Other mucous membrane affected are of penis , vagina and
epiglottis.
There are variety of drugs that may cause lesion
similar to lichen planus they are termed as
lichenoid lesion.
Causes-
 inflammatory drugs
 Sulfonylurea's
 anti malarial
 beta blockers
 ACE inhibitors.
 idiopathic
In rare cases it may occur after dental restoration is
performed or when patient start wearing denture.
Histopathological finding
 Typical findings are-
 Hyperparakeratosis or hyperorthokeratosis with thickening of
granular layer
 Acanthosis with intercellular edema of spinous cell
 “SAW tooth” shaped rete pegs.
 Degenerating basal keratinocytes that form colloid bodies.
 Formation of MAX –JOSEPH SPACES
 Subepithelial collection of chronic inflammatory infiltration is
seen in a band like manner.
Differential diagnosis

1. Leukoplakia
2. Lichenoid reaction
3. Candidasis
4. Pemphigius
5. Erythema multiforme
6. Recurrant apthae
7. Lupus erythematous
PHEMPHIGUS –
Pemphigus is a serious chronic skin disease characterized
by the appearance of vesicles & bullae, small or large
fluid filled blisters that develops in cycle.

Pemphigus is derived from Greek word pemphix

meaning bubble or blister.

Describes a group of chronic bullous diseases originally

named by Wichman in 1791.
 Pemphigus is a VESICULO
BULLOUS LESION.
Classification of vesiculo bullous lesions –
FITZ PATRICK CLASSIFICATION-
1. ACC TO ANATOMICAL PLANE:
(A) Intraepidermal Blister Granular Layer -
- Pemphigus Foliaceous
- Frictional Blisters
(B) Spinous Layer -
- Familial benign pemphigus
- Herpes Virus infection
(c) Suprabasal -
- Pemphigus vulgaris
- Pemphigus Vegetans
(D) Basal Layer -
- Erythema multiforme
- Lichen planus
- Lupus Erythematous
2. Dermal- Epidermal junction zone----

(A) Lamina lucida

- Bullous pemphigoid
- Cicatrical pemphigoid

( B) Below basal lamina

- Erythema multiforme
- Epidermolysis bullosa dystrophica
Types of Pemphigus-
1. Pemphigus Vulgaris (accounts for 70% of pemphigus)
2. Pemphigus vegetans
3. Pemphigus Foliaceus (superficial pemphigus, fogo
selvagem)
4. Pemphigus erythematosus
5. Paraneoplastic Pemphigus
6. Drug induced Pemphigus
7. IgA pemphigus
8. Familial Benign Pemphigus (Hailey- Hailey disease)
Pemphigus Vulgaris –
(Vulgaris is Latin word meaning common)
 DEFINATION……

Pemphigus vulgaris is a desquamating condition of the oral

mucosa and skin in which autoantibodies destroy antigenic
components of the desmosomes producing epithelial
separation above the basal cell layer.
Epidemiology-

 Most commonly develops in 4th to 6th decades of life.

 A genetic prediposition linked to HLA class II alleles.

 Ashkenazi Jews & persons of mediterranean origin are

especially at risk for pemphigus.
Etiological factors……
1. Diet – Garlic may cause occasional cases of
pemphigus.

2. Drugs – capable of causing pemphigus fall into two

main groups according to their chemical structure-

i. Drugs containing sulfhydryl radical (thiol drugs,

e.g. penicillamine & captropril.

ii. Non thiol drugs, often sharing an active amide

group in their molecule, e.g. phenol drugs,
rifampicin, diclofenac & other ACE inhibitors
3. Viruses – the apparently transmissible nature of some
pemphigus variants (fogo selvagem) has suggested a role
for viruses.

 Herpes virus DNA has been detected in peripheral blood

mononuclear cells & skin lesions of patients with
pemphigus by PCR.
4. Other factors-
i. Lower number of smokers
ii. Higher exposure rates to pesticides
iii. Higher number of female patients who had been
pregnant & suggested that this may point to contribution
of estrogens in the disease process.
5. Association with other disorders- Pemphigus vulgaris
may occasionally be associated with other autoimmune
disorders such as rheumatoid arthritis, myasthenia gravis,
lupus erythematosus or pernicious anemia.
PATHOPHYSIOLOGY -
An autoimmune mechanism playa a major role in
development of pemphigus.

The patient develops immunoglobulin G (IgG) &

complements in his or her body, which are specifically
targeted against the intercellular cement substance
(desmosomes) of skin & mucous membrane.
Deposition of such autoantibodies in the skin or mucous
membrane initiates an immune reaction, that eventually
causes destruction & dissolution of the desmosomal
attachments b/w the cells leading to the loss of adhesion
b/w one cell to the other……… (ACANTHOLYSIS)
Further accumalation of fluid in the region eventually
leads to the development of INTRAEPITHELIAL
bullae & a SUPRA BASILAR split in the epithelium.
 Blisters occur in the epidermis & the mucous
membranes, where IgG autoantibodies target two
structural proteins of the desmosomes identified as-

1. Desmoglein 1(Dsg 1)
2. Desmoglein 3 (Dsg 3)

# A new pemphigus antigen , desmoglein 4 has recently

been discovered
Structure of desmosome
 Distribution of Dsg1 &Dsg3 -
Dsg 1 is found throughout all layers of the skin, whereas
Dsg 3 is found only in two or three layers of the deep
epidermis.

In contrast Dsg 3 is predominantly expressed throughout

the MUCOUS MEMBRANES (such as oral epithelium),
where Dsg 1 is minimally present.
 Two phenotypes of PV-

1. Mucosal dominant
2. Mucocutaneous
Mucosal- Dominant
Some patients develop mucosal lesions without skin
blisters……. Know as mucosal dominant PV

The serum of these patients contains high titers of

anti-Dsg 3 antibodies & low or no titers of anti- Dsg
1antibodies.

Hence the preserved function of Dsg1in the skin

prevents development of cutaneous lesions, Whereas
the impaired adhesive function of Dsg 3 causes
ACANTHOLYSIS in the oral cavity.
MUCOCUTANEOUS
As PV progresses many but not all patients develop
cutaneous disease.

Cutaneous lesions appear when antibodies to both

Dsg1 & Dsg3 develop……. & the picture of
Mucocutaneous PV.
When anti-Dsg1 antibodies persist & anti Dsg3
antibodies disappear the emerging condition
is……………. Pemphigus Foliaceous.
Besides IgG antibodies found in PV , IgA antibodies
against Dsg 3 also have been identified.

It is rare however to find oral lesions in IgA pemphigus

because autoantigens for IgA pemphigus may in fact not
be a component of desmosomes or anti Dsg
autoantibodies may not act alone to cause pemphigus.
Antigens targeted by autoantibodies & corresponding
forms of pemphigus

Antigens Forms of pemphigus

Desmoglein 3 Mucosal dominant PV
Desmoglein 3, 1 & Mucocutaneous PV
possibly 4
Desmoglein 1 Pemphigus foliaceous
Desmoglein 3, 1 & plakin Paraneoplastic pemphigus
proteins
 Formation of autoantibodies
(IgG & complements in body)

Deposition of IgG & complements against antigenic components

of desmosomes of skin & epithelium.

Intiation of Ag- Ab reaction

Destruction & Dissolution of desmosomes

Loss of intercellular bridge (acantholysis)

Accumalation of fluid

Formation of intraepithelial bullae & then Suprabasilar split in

epithelium
Clinical Features Of PV-
Most common

Rapidly developing vesicle or bullae on several areas

of the skin & mucous membrane which contain clear
fluid BUT later on there is formation of pus.

Vesicles or bullae rupture very soon & leave

extremely painful, erythematous ulcers that often
bleed profusely.

Gentle traction or oblique pressure on the unaffected

areas around the lesion causes stripping of the normal
skin or mucous membrane called NIKOLSKY’s
SIGN
Oral lesions in pemphigus vulgaris may involve any part
of the oral cavity but are more frequently found in those
areas which are often subjected to trauma e.g cheek, palate
& gingiva.

Intact vesicles are rarely found inside the oral cavity as

these are quickly ruptured soon after their formation and
the resultant ulcerated lesions are often covered by a blood
tinged exudate.
HISTOPATHOLOGY….

Pemphigus as an entity is characterized microscopially by

the formation of a vesicle or bulla entirely
intraepithelially, just above the basal layer producing the
distinctive SUPRABASILAR SPLIT.

Prevesicular edema appears to weaken this junction & the

intercellular bridges b/w the epithelial cells disappear.
This results in loss of cohesiveness or acantholysis &
because of this clumps of epithelial cells are often found
lying free within the vesicular space.

These have been termed “TZANCK Cells” (charcterized

particularly by degenerative changes which include
swelling of the nuclei & hyperchromatic staining)
Laboratory tests…….

 Biopsy specimen is fundamental.

 Helps to differentiate b/w-

i. Pemphigus
ii. Paraneoplastic pemphigus
iii. Lichen planus
iv. Mucous membrane pemphigoid
v. Epidermolysis bullosa
vi. Linear IgA disease
vii. Lupus erythematosus
viii. Erythema multiforme
ix. Graft- vs - host disease
Pemphigus vulgaris is an autoimmune bullous
disorder in which IgG antibodies are detected in the
intercellular substance and in the serum of the patients
by direct and indirect immunofluorescence tests.

Demonstration of immunoglobulins especially IgG

and complement in the intercellular space by DIF is a
very reliable diagnostic test for pemphigus, it
becomes positive early at the onset and remains
positive for a long period after clinical remission.
The Direct Test….
The antibody is itself conjugated with the
fluorochrome and applied directly to a monolayer of
cells or to frozen tissue on a slide.
 When examined with a fluorescence microscope, the
antibody labelled with the fluorescent moiety
identifies the localized antigen.
Two different antigens can be identified
simultaneously, in the same preparation by using
antisera conjugated to dyes active at different
wavelengths.
The Indirect Test…..

Unlike the direct test, the indirect test is a double-layer

technique.
The unlabelled antibody is applied directly to the tissue
substrate and then treated with a fluorochrome-conjugated
anti-immunoglobulin serum
Indirect immunofluorescence enable a search for
circulating autoantibodies in the patients serum & are
usually performed after DIF studies reveal antibody
deposits in the mucosa or skin.
IIF requires serum specimens that are collected without
anticoagulant.
The blood sample is centrifuged & the serum refrigerated
until it is mailed, if arrival time at the lab is expected to
exceed 2 days.
For analysis the serum is incubated with an epithelial
substrate, usually monkey esophagus & then incubated
with fluoresceinated anti-human IgG.
FISH NET PATTERN
DIAGNOSIS…..
Difficult to differentiate clinically .

Clinical features such as positive NIKOLSKYS SIGN

are not specific.

It is crucial to establish the diagnosis of PV clearly &

as early as possible, so that adequate treatment can be
commenced.

So in addition to a full history & examination biopsy

examination & appropriate histopathologic and
immunological investigations are frequently indicated.
Assay of serum antibody titers by IIF may also help
guide prognostication & therapy.

Critical evaluation of two enzyme linked

immunosorbent assay (ELISA) for the detection of
antibodies to Dsg1 & Dsg3 comparing two substrate,
normal human skin (HS) & monkey oesophagus (MO)
showed that using PV serum the senstivity of IIF was
83% on HS & 90% on MO.

This will not only increase the senstivity of detecting

pemphigus antibodies BUT would aid in
differentiation of PV from PF
This strongly suggests that both substrates should be
used in diagnosis of PV as patients with predominantly
oral disease may only have Dsg3 antibodies which are
not always detectable using HS.
MANAGEMENT…..

Prednisone – mainstay of therapy

Various medications are being used as steroid sparing

agents in an attempt to reduce the adverse effects of
long term steroid treatment.

Topical therapies cannot replace systemic medication

but may be useful for palliative treatment of painful
oral lesions
Alternative treatments to corticosteroids….
Azathipoprine, chlorambucil or cyclophosphamide can be
effective.

Newer Drugs…..
Rituximab,proteinase inhibitors, chimeric molecules.

Plasmapheresis
Intravenous immunoglobulins-safe in steroid resistant PV
Maintaining and improving the oral hygiene and
minimizing irritation of the lesion are part of general
supportive regimen.
PEMPHIGUS VEGETANS…..
Uncommon variant of pemphigus vulgaris.
It occurs in 1-2% of pemphigus vulgaris cases.
Median age of onset is 40-50 years.
Two clinical subtypes of pemphigus vegetans exists,
characterized initially by flaccid bullae & erosions
(Neumann) or pustules (Hallopeau).
Oral involvement is present in nearly all pemphigus
vegetans cases.
A characteristic feature of pemphigus vegetans is
the cerebriform tongue, characterized by a pattern of
sulci & gyri on the dorsum of the tongue.
Oral manifestations..…..

Mucous membranes typically are affected first in PV.

 Mucosal lesions may precede cutaneous lesions by

months.

Disease involves mucosa in 50-70% of patients.

Intact bullae are rare in mouth.

More commonly, patients have ill defined, irregularly

shaped , gingival , buccal or palatine erosions, which
are painful and slow to heal.
The erosions extend peripherally with shedding of the
epithelium.

Erosions may be seen on any part of oral cavity & can be

scattered & often extensive.

Erosions may spread to involve the larynx with

subsequent hoarseness.

The patient is often unable to eat or drink as the lesions

are so uncomfortable
PEMPHIGUS FOLIACEOUS…….
 Characterized by a chronic course, with little or no
involvement of the mucous membranes.

 It includes the following six subtypes-

1. Pemphigus erythematosus
2. Pemphigus herpetiformis
3. Endemic pemphigus foliaceous
4. Immunoglobulin A ( IgA) pemphigus foliaceous
5. Paraneoplastic pemphigus foliaceous
6. Drug induced pemphigus foliaceous
PARANEOPLASTIC PEMPHIGUS…..

Anhalt et al , first described paraneoplastic pemphigus in

1990.

He initially suggested five criteria for the diagnosis of

PNP & recently presented four revised minimal criteria for
diagnosis of PNP-
1. Painful, progressive stomatitis with preferential involvement
of the tongue. (This finding is so consistent that it is
unreasonable to consider the diagnosis in its presence).

2. Histopathologic changes of acantholysis, keratinocyte necrosis

& interface dermatitis.

3. DIF typically reveals IgG & complement with in the epidermal

intercellular spaces as well as the epidermal basement
membrane.

4. IDIF observation of circulating antibody specific for stratified

squamous or transition epithelia is found.

5. Immunoprecipitation of complex of proteins

PATHOPHYSIOLOGY…..
Poses antibodies to Dsg3 & Dsg 1.

More importantly an additional second group of

antibodies are present, targeting molecules of plakin
family.

The plakin proteins (desmoplakin I & II, BPAG1,

envoplakin, perplakin & plectin) form the portion of
the desmosomes just under the plasma membrane,
linking the cytoskeleton to the transmembrane protein
of the desmosomes (DESMOGLEIN) & are essential
in maintaining cell adhesion.
Autoantibodies against these
plakin proteins are the most
reliable marker for PNP.
The route by which circulating antibodies comes into
contact with these cytoplasm proteins & the potential
mechanism by which malignant tumors may induce
autoimmunity against epithelial proteins remains
speculative.
One hypothesis suggests that pathologic antigens derived
from the associated malignancy may stimulate the
generation of Ab that then cross react with normal
epithelial proteins.

BUT this has not been showed that tumor cells

produce the pathogenetic Ab that cause epithelial
breakdown.
On the other hand it has been observed that
subpopulations of tumor or cell lines from many
neoplasms associated with PNP secrete IL-6 & that serum
levels of IL-6 in PNP patients are elevated.

Causative link has not proven for the above.

 The most common malignancy associated with PNP
is non Hodgkin's Lymphoma.

 Others are---
1. Chronic lymphocytic leukemia
2. Castleman tumor
3. Giant cell lymphoma (reticulum cell sarcoma)
4. Poorly differentiated sarcoma.
CLINICAL FEATURES….
Palmar or plantar bullae may be evident, a feature that
is uncommon in PV.

Lips often show hemorrhagic crusting similar to that of

erythema multiforme.

Oral mucosa shows multiple areas of erythema &

diffuse, irregular ulceration affecting virtually any oral
mucosal surface.
The lesions differ in appearance from those seen in PV
because of the presence of epithelial necrosis & lichenoid
changes.

Their presence alone or in combination with

polymorphous skin eruptions is an important diagnostic
criterion.

30-40% of cases develop pulmonary involvement which

is never found in patients with PV.
HISTOPATHOLOGIC FEATURES……

The features of PNP on light microscopic examination

may be as diverse as the C/F.

In most cases a lichenoid mucositis is seen usually

with Subepithelial clefting (like pemphigoid) or
intraepithelial clefting (like pemphigus)
LABORATORY TEST….
The most important initial laboratory test for diagnosing
PNP is IIF.

In case of suspected PNP rodent bladder is used as a

substrate in addition to monkey esophagous because the
technique can distinguish PNP from the other types of
pemphigus with approx. 75-80% senstivity and specificity
This technique works because PNP
autoantibodies bind to simple, columnar,
transitional & stratified squamous epithelium.
Whereas , PV autoantibodies bind only to
stratified squamous epithelium.
TREATMENT….

Very serious condition.

High morbidity and mortality rate.

The disease resolve in 6-12 months when an

underlying benign or localized tumor can be
completely excised.

For those cases associated with malignancy treatment

essentially consist of systemic prednisone, typically
combined with another immunosuppressive agent,
such as azathioprine, methotrexate.
 Erythema multiforme
(Stevens-Jhonsons syndrome)

It is an ulcerative mucocutaneous disease of

uncertain pathogenesis.

In erythema multiforme there is mild skin

eruption and mucosal involvement whereas in
erythema multiforme and in Stevens Johnson's
syndrome there is severe skin and mucosal
involvement.
Differentiation b/w Stevens
Johnson's syndrome can only be
made by there lesions

In EM the lesions is raised atypical

target and mucosal erosion

Whereas in SJS there is mucosal

erosion with flat atypical target cells

Etiology-
1.It is caused by drugs such as sulpha drugs.
2.herpes simplex virus.
3.mycoplasm infection.

Clinical feature-
 It mainly occur in adults.
 It may occur at any age.
 It is most common in 2 and 3 decade.
 It is more common in males than females.
It is characterized by-
Occurrence of
asymptomatic,vividly
erythematous discrete
macules,papule,vesicle ,or
bullae in symmetrical pattern
over hand arms feet legs face
and neck.

Lesion may vary from few cm

to mm in diameter.
 A concentric ring like appearance of lesion
-resulting from varying shade of erythema and
this gives rise to the term target , iris or bull’s
eye.
They are most common on hands, wrist , and
ankles.
Mucous membrane involvement, including the
oral cavity is common.
Lesions appears within few days or two and
persist for several days to few weeks and
gradually disappears.
Oral mucous membrane-

•Lesions are usually not so

significant except the pain and
the discomfort it may cause.
•Hyperemic papule ,macules ,or
vesicles may erode and bleed
profusely.
•Tongue , palate , gingiva are
commonly involved
Stevens Johnsons syndrome-
it is an severe form of erythema
multiforme with widespread
involvement of skin , oral cavity ,
eye and genital.
Oral mucous membrane lesion-
1.difficulty in chewing and
mastication
2.severe bleeding and crusting of
the lips
Eye lesion-
Conjunctivitis
Corneal ulceration.
Keratoconjunctivitis
Blindness may occur.
Genital lesions-
Urethritis
Vaginal ulcers.
Balanitis.
Histological features
Cutaneous and mucosal lesion usually exhibit
intercellular edema.
Edema of superficial CT tissue.
Zone of severe liquefaction degeneration I the
upper layer of the epithelium.
Interepithelium vesicle formation and thinning or
absence of basement membrane.
Dilatation of superficial cappilaries.
Varying degree of inflammatory cell infiltrate.
Differential diagnosis-
1. Apthous stomatitis.
2. Contact dermatitis.
3. Stomatitis.
4. Acute necrotizing gingivitis.
5. Pemphigius
6. Dermatitis
7. Bullous lichen plan us.
8. Herpes zoster.
9. Chicken pox.
10. Toxic epidermal necrolysis.
Q- How is lupus
diagnosed?
Since patients with SLE can have a wide variety of
symptoms and different combinations of organ
involvement, no single test establishes the
diagnosis of systemic lupus.
To help doctors improve the accuracy of the
diagnosis of SLE, eleven criteria were established
by the American Rheumatism Association.
These eleven criteria are closely related to the
symptoms.
Some patients suspected of having SLE may never
develop enough criteria for a definite diagnosis. Other
patients accumulate enough criteria only after months
or years of observation. When a person has four or
more of these criteria, the diagnosis of SLE is strongly
suggested
The eleven criteria used for diagnosing systemic lupus
erythematosus are:

1. malar (over the cheeks of the face) "butterfly" rash.

2.Discoid skin rash: patchy redness that can cause scarring
3.Photosensitivity: skin rash in reaction to sunlight
exposure
4.Mucus membrane ulcers: ulcers of the lining of the
mouth, nose or throat
5.Arthritis: 2 or more swollen, tender joints of the
extremities
6.Pleuritis/pericarditis: inflammation of the lining tissue
around the heart or lungs, usually associated with chest
pain with breathing
7.Kidney abnormalities: abnormal amounts of urine protein
or clumps of cellular elements called casts
8.Brain irritation: manifested by seizures (convulsions)
and/or psychosis
9.Blood count abnormalities: low counts of white or red
blood cells, or platelets
10.Immunologic disorder: abnormal immune tests include
anti-DNA or anti-Sm (Smith) antibodies, falsely positive
blood test for syphilis, anticardiolipin antibodies, lupus
anticoagulant, or positive LE prep test
11.Antinuclear antibody: positive ANA antibody
testing.
Other tests can be helpful in evaluating patients
with SLE to determine the severity of organ
involvement. These include-
1. routine testing of the blood to detect inflammation
(for example, a test called the sedimentation rate),
2. blood chemistry testing,
3. direct analysis of internal body fluids,
4. and tissue biopsies. Abnormalities in body fluids
and tissue samples (kidney, skin, and nerve
biopsies) can further support the diagnosis of SLE.
 Oral manifestation-

Oral mucous mem involvement is reported in 20-50 %

cases of discoid lupus erythematosus and slightly more
frequently in systemic form of the disease.
Oral lesion are formed either prior to or following the
development of skin lesions or even in the absence of
skin lesion.
Oral lesion in SLE are very similar to that to DLE
except that hyperemia, edema and extension of the
lesion is more pronounced and there may be more
tendency towards bleeding, petechiae and superficial
ulceration which is surrounded by red halo as a result of
superficial telengiectasis.
Histological finding-

Histological appearance of SLE and DLE is

similar, only differs in in the degree of certain
findings.
Laboratory finding-
A specific test have been estb for its diagnosis-
the test consist of addition of blood serum from a person under
suspicion to the buffy coat of normal blood. if the patient is suffering
from SLE ,typical LE cells will develop. this cell or phenomena
consist of a rosette of neutrophils surrounding a pale nuclear mass
apparently derived from a lymphocytes.
There is also anemia ,leukoplakia thrombocytopenia
and elevated sedimentation rate as well as elevated
serum gamma globulin level and a positive Coombs
test, in a significant % of people with either SLE or
DLE.
Antinuclear antibodies can be demonstrated in patient
of SLE and DLE.
Treatment-
The most imp tool is careful and frequent clinical and
laboratory evaluation to tailor medical regime.
There is no permanent cure for SLE. The goal of
treatment is to relieve symptoms and protect organs by
decreasing inflammation.
Many patients with mild symptoms may need no
treatment or only intermittent courses of anti-
inflammatory medications.
Those with more serious illness involving damage to
internal organ(s) may require high doses of
corticosteroids in combination with other medications
that suppress the body's immune system.
Patients with SLE need more rest during periods of
active disease. Researchers have reported that poor
sleep quality was a significant factor in developing
fatigue in patients with SLE
Nonsteroidal anti-inflammatory drugs (NSAIDs) are
helpful in reducing inflammation and pain in muscles,
joints, and other tissues. Examples of NSAIDs include
aspirin, ibuprofen (Motrin), naproxen (Naprosyn), and
sulindac (Clinoril). S
 Discoid lupus erythematosus
It is an chronic scarring atrophy producing
photosensitive dermatosis.
Discoid lupus erythematosus (DLE) is a
disease in which coin-shaped (discoid) red
bumps appear on the skin.
The disease called discoid lupus
erythematosus only affects the skin,
although similar discoid skin lesions can
occur in the serious disease called systemic
lupus erythematosus (SLE)..
The tendency to
develop DLE seems to
run in families.
Although men or
women of any age can
develop DLE, it occurs
in women three times
more frequently than in
men. The typical DLE
patient is a woman in
her 30s.
Etiology-
It mainly occur in genetically predisposed
individual.
It has been sugested that heat shock protein is
induced in the keratinocytes following ultraviolet
light exposure and stress and the protein may act as
a target for T-cell.
Clinical features-

In DLE, the characteristic skin lesion is circular

and raised.
The reddish rash is about 5-10 mm in diameter,
with the center often somewhat scaly and lighter in
color than the darker outer ring. The surface of
these lesions is sometimes described as "warty.“
 There is rarely any itching or pain associated with
discoid lesions.
They tend to appear on the face, ears, neck, scalp,
chest, back, and arms.
DLE lesions heal, they leave thickened, scarred
areas of skin. When the scalp is severely affected,
there may be associated hair loss (alopecia).
People with DLE tend to be quite sensitive to the
sun. They are more likely to get a sunburn, and
the sun is likely to worsen their discoid lesions.
The typical cutaneous lesion are slightly
elevated red or purple macules that often covered
with gray or yellow adherent scales. forceful
removal of scales revel numerous ‘carpet tack’
extensions which is dipped into enlarged
pilosebaceous ca
The lesion increase in size by peripheral growth
this is its typical feature.
The periphery of the lesion appear pink or red
while the center exhibit an atrophic scarred
appearance indicative of long standing nature
of the disease with characteristic healing.
 the discoid form of the disease may also
assume a typical ‘butterfly’ distribution on the
malar process of the nose. since it is not a
constant feature as it may appear in some
other disease also. so its diagnostic
significance should not be overemphasized.
Oral manifestation-
There is 20-25 % of oral mucous mem involvement in
DLE.
Oral mucosa is either involved prior or following the
development of the skin lesion. The oral lesion begin
as erythematous area ,sometimes slightly elevated but
more often depressed usually without induration and
typically with white spots.
Superficial ulcers with crusting or bleeding may form
but without actual scales. Margins of lesions are not
sharply demarcated but shows narrow zone of
keratinization.
Central healing may result in depressed
scarring.
Lesions are mainly on buccal mucosa
,palate and tongue.
In case of tongue atrophy of papillae Ulceration of the palate

and severe fissuring is seen.

Vermillion border of the lip is also
involved.
The erythematous atrophic plaque
surrounded by a kera5otic border may
involve the entire lip. Ulceration of buccal mucosa
 Histological finding-

It is characterized
by hyperkeratosis
with keratotic
plugging, atrophy
of rete pegs,
perivascular
infiltration of
lymphocytes and
their collection in
dermal appendages
Liquefaction
degeneration of basal
layer of cell.
Discoid form of the
lesion exhibit
hyperorthokeratosis hyper
parakeratosis.
Acanthosis and
pseudoepitheliomatous
hyperplasia.
Hydrophobic
degeneration and
liquefaction necrosis of
basal cell layer occurs
Thickening of the basement mem can be
demonstrated as a homogenous broad
eosinophillic and PAS positive band.
Diffuse infiltration of lymphocytes with
smaller number of plasma cells and
occasionally polymorphonuclear leukocytes in
superficial in deep CT tissue.
Diagnosis-
Diagnosis of DLE usually requires a skin
biopsy.
A small sample of a discoid lesion is removed,
specially prepared, and examined under a
microscope. Usually, the lesion has certain
microscopic characteristics that allow it to be
identified as a DLE lesion.
Blood tests will not reveal the type of antibodies
present in SLE, and physical examination usually
does not reveal anything other than the skin
lesions. If antibodies exist in the blood, or if other
symptoms or physical signs are found, it is
possible that the discoid lesions are a sign of SLE
rather than DLE.
Treatment-
Treatment of DLE primarily involves the use of a
variety of skin creams. Sunscreens are used for
protection. Steroid creams can be applied to
decrease inflammation. Occasionally, small
amounts of a steroid preparation will be injected
with a needle into a specific lesion. Because of
their long list of side effects, steroid preparations
taken by mouth are avoided. Sometimes, short-
term treatment with oral steroids will be used for
particularly severe DLE outbreaks. Medications
used to treat the infectious disease malaria are
often used to treat DLE.
Alternative treatment-

Alternative treatments for DLE include eating a

healthy diet, low in red meat and dairy products
and high in fish containing omega-3 fatty acids.
These types of fish include mackerel, sardines, and
salmon. Following a healthy diet is thought to
decrease inflammation. Dietary supplements
believed to be helpful include vitamins B, C, E,
and selenium. Vitamin A is also recommended to
improve DLE lesions. Constitutional homeopathic
treatment can help heal DLE as well as help
prevent it developing into SLE.
Prognosis-

For the most part, the prognosis for people with

DLE is excellent. While the lesions may be
cosmetically unsightly, they are not life threatening
and usually do not cause a patient to change his or
her lifestyle. Only about 10% of patients with DLE
will go on to develop SLE.
Prevention-
DLE cannot be prevented. Recommendations to
prevent flares of DLE in patients with the disease
include avoiding exposure to sun and consistently
using sunscreen.
 
 ERYTHEMA MULTIFORME
(STEVENS-JHONSONS SYNDROME)
It is an ulcerative mucocutaneous disease of uncertain pathogenesis.
In erythema multiforme there is mild skin eruption and mucosal
involvement whereas in erythema multiforme and in Stevens
Johnson's syndrome there is severe skin and mucosal involvement.
Differentiation b/w Stevens Johnson's syndrome can only be made by
there lesions
In EM the lesions is raised atypical target and mucosal erosion
Whereas in SJS there is mucosal erosion with flat atypical target cells
It is characterized by-
 Occurrence of asymptomatic,vividly erythematous discrete macules,papule,vesicle ,or bullae
in symmetrical pattern over hand arms feet legs face and neck.
 Lesion may vary from few cm to mm in diameter.
 A concentric ring like appearance of lesion

 -resulting from varying shade of erythema and this gives rise to

The term target , iris or bull’s eye.
 They are most common on hands, wrist , and ankles.
 Mucous membrane involvement, including the oral cavity is common.
 Lesions appears within few days or two and persist for several days to few
weeks and gradually disappears.

Oral mucous membrane-

 Lesions are usually not so significant except the pain and the discomfort
it may cause.
 Hyperemic papule ,macules ,or vesicles may erode and bleed profusely.
 Tongue , palate , gingiva are commonly involved
 Stevens Johnsons syndrome-
 it is an severe form of erythema multiforme with widespread
involvement of skin , oral cavity , eye and genital.
 Oral mucous membrane lesion-
 1.difficulty in chewing and mastication
 2.severe bleeding and crusting of the lips
 Eye lesion-
 Conjunctivitis
 Corneal ulceration.
 Keratoconjunctivitis
 Blindness may occur.
 Genital lesions-
 Urethritis
 Vaginal ulcers.
 Balanitis.
 Histological features
 Cutaneous and mucosal lesion usually exhibit intercellular edema.
 Edema of superficial CT tissue.
 Zone of severe liquefaction degeneration I the upper layer of the epithelium.
 Interepithelium vesicle formation and thinning or absence of basement membrane.
 Dilatation of superficial cappilaries.
 Varying degree of inflammatory cell infiltrate.
Differential diagnosis-
Apthous stomatitis.
Contact dermatitis.
Stomatitis.
Acute necrotizing gingivitis.
Pemphigius
Dermatitis
Bullous lichen plan us.
Herpes zoster.
Chicken pox.
Toxic epidermal necrolysis.
 ERYTHEMA MIGRANS (GEOGRAPHIC TONGUE;
BENIGN MIGRATORY GLOSSITIS)
Is a common benign condition that primarily affects tongue.
3% population affected.
Females are affected
Etiopathogenesis still unknown
Some have suggested that it occurs with increased
frequency in atopic individuals, thus raising the possibility
that it represent a type of hypersensitivity to an
environmental factor.
 
CLINICAL FEATURES –
 seen on anterior 2/3rd of dorsal tongue mucoa.
Multiple well demarcated zones of erythema, concentrated on the tip and lateral
borders of the tongue.
Erythema is due to atrophy of the filiform papillae, aand these atrophic areas
are typically surrounded at least partially by a slightly elevated, yellowish
white, serpentine or scalloped border.
Lesion as appearing quickly in one area, healing within a few days or weeks,
then developing in a very different area.
Lesion begin as small white patch, which then develops a central erythematous
atrophic zone & enlarge centrifugally.
The lesions are usually asymptomatic, although a burning sensation or
sensitivity to hot or spicy foods may be noted.
Other lesions develop on the buccal mucosa on the labial mucosa & on soft
palate.
They can be identified by a yellowish white serpentine or scalloped border that
surrounds an erythematous zone.
 
HISTOPATHOLOGIC FEATURES -

hyperparakeratosis, spongiosis, acanthosis, and elongation

of the epithelial rete ridges are seen.
Collection of neutophils involve the lamina propria.
The intense neutrophilic infiltrate may be responsible for
the destruction of the superficial portion of the epithelium,
thus producing an atrophic reddened mucosa as the lesion
progresses.
Because these histopathologic features are reminiscent of
psoriasis this is called psoriasiform mucositis.
 REITER’S SYNDROME
Is an uncommon disease that most likely represents an
immunologically mediated condition.
Current evidence suggest that the disorder may be triggered
by any one of several infectious agents in a genetically
susceptible person.
A classic triad of signs has been described-
Nongonococcol urethritis
Arthritis
Conjunctivitis
It is been reported with some frequency in patients infected
with the human immunodeficiency virus (HIV).
CLINICAL FEATURES –

In young adult men

M:F 9:1
Syndrome usually develops 1 to 4 weeks after an episode of dysentery or
venereal diseases.
Urethritis is often the first sign seen in both affected males & females.
Female may also have inflammation of the utrine cervix.
Arthritis usually affects the joints of the lower extremities.
Skin lesions often take the form of a characteristic lesion of the glans penis
(balanitis circinata)
These lesions develop in about one third of patients with Reiter’s syndrome &
they appear as well circumscribed erythematouss erosions with a scalloped,
whitish linear boundary.
Some mention painless erythematous papules distributed on the buccal mucosa
& palate other reports describe shallow, painless ulcers that affect the tongue,
buccal mucosa palate & gingiva.
 
 
HISTOPATHOLOGIC FEATURES –

The histopathologic findings of the cutaneous lesions in

patients with Reiter’s Syndrome are frequently similar to
those found in patients with psoriasis, particularly with
respect to the presence of microabscess within the
superficial layers of the surface epithelium.

Other features in common with psoriasis include

hyperparakeratosis with elongated, thin rete ridges.
 GRAFT VERSUS HOST DISEASE
GVHD occurs mainly in recipients of allogenic bone marrow
transplantation
To treat life threatening disease of the blood or bone marrow, such as
leukemia, aplastic anemia or disseminated metastatic disease.
Unfortunately the HLA match is not always exact & despite the use of
immunomodulating & immunosuppressive drugs, the engrafted cells
recognize that theyare not their own environment.
When this happens, cells start attacking what they perceive as a foreign
body.
The result of this attack is known as graft versus host disease & it can be
quite devastating to the patient.
CLINICAL FEATURES –
 The systemic signs of GVHD are varied, depending on the organ system
involved & weather the problem is acute or chronic.
Acute GVHD and Chronic GVHD
HISTOPATHOLOGIC FETURES –

 Of GVHD resemble those of oral lichen planus to a

certain degree.
Both display hyperorthokeratosis, short, pointed rete ridges
and degeneration of the basal layer.
The inflammatory response in GVHD is usually not as
intense as in lichen planus.
With advanced cases, an abnormal deposition of collagen
is present, similar to the pattern in systemic sclerosis.
Minor salivary gland tissue usually shows periductal
inflammation in the early stages, with gradual acinar
destruction and extensive fibrosis appearing later
 SYSTEMIC SCLEROSIS

Is a relatively rare condition that probably has an

immunologically mediated pathogenesis.
Most dramatic effects are seen in association with the skin,
the disease is often quite serious with most organs of the
body affected.
CLINICAL & RADIGRAPHIC FEATURES –
Women three times more frequently affected.
Patients are adults
Raynaud’s phenomenon, a vasoconstrictive event triggered
by emotional distress or exposure to cold.
R
 PSORIASIS
 
Introduction
Term psoriasis was given by Ferdinand von Hebra
Derived from greek word “psora” means to itch.
 
Definition
A Chronic (long lasting) skin disease characterized by scaling and inflammation. Scaling occurs when cells in
the outer layer of skin reproduce faster than normal and pile upon the skin’s surface.
Normal turnover of skin is 26 days but in psoriasis it is 4-6 days.
 
Types
Plaque psoriasis /psoriasis vulgaris-
 - affects 80-90% patients with psoriasis.
 - typically appears as raised areas of inflamed skin covered with silvery white scaly skin
Flexural psoriasis /seborrhoeic /inverse
smooth inflamed patches
occurs in skin folds, around the genitals, armpits
Guttate psoriasis /eruptive psoriasis
 - numerous small round spots
 - spots appear over large areas of the body, such as the trunk, limbs, and scalp
 -associated with streptococcal throat infection.
Pustular psoriasis
 - appears as raised bumps that are filled with non-infectious
pus (pustules)
 - can be localised, commonly to the hands and feet
(palmoplantar pustulosis), or generalised with widespread
patches
Nail psoriasis
 - discolouring under the nail plate
 - pitting of the nails,
 -lines going across the nails,
 -thickening of the skin under the nail
 -the loosening (onycholysis)
 - crumbling of the nail.
 -subungual hyperkeratosis, or the oil-drop sign
 
Psoriatic arthritis
- affect any joint but is most common in the joints of the
fingers and toes
-About 10-15% of people who have psoriasis also have
psoriatic arthritis.
Erythrodermic psoriasis
 -involves the widespread inflammation and exfoliation
of the skin over most of the body surface.
 -accompanied by severe itching, swelling and pain.
 -exacerbation of unstable plaque psoriasis, particularly
following the abrupt withdrawal of systemic treatment
CLINICAL CLASSIFICATION
It is divided into –
Pustular psoriasis
Nonputular psoriasis.
 
Non pustular psoriasis-
Further divided into-
Psoriasis vulgaris (chronic stationary psoriasis)
Psoriatic erythroderma
 
Pustular psoriasis-
Generalized pustular psoriasis (von Zumbusch)
Pustulosis palmeris et plantaris
Annular pustular psoriasis
Impetigo herpetiformis
 
Also classified as-
Type I-
- Also called early-onset type psoriasis, begins before the age of 40
(usually at 16-22 years of age).
- positive family history
 
Type II-
occurs after the age of 40 (usually at 57-60 years).
presents with minor hereditary association and no family history
 
Incidence-
About 1 to 2% of the U.S population or 5.5 million people get infected.
Mostly common between the age 15 to 35 years old.
Mostly frequently occurs in Caucasians population.
It is also inherited
Clinical features-

It is uncommon in children

Seldom does primary attack occur after age of 45 years.
Most frequent in 2-3 decade of life, median age 28 yrs.
Slightly more common in females
Characterized by small sharply delineated, dry papules, each covered by a
delicate silvery scale which resembles a thin layer of mica
If scales are removed, one or more tiny bleeding points are disclosed-
AUSPITZ’S SIGN
(Koebner reaction) typically occurs 7-14 days after the skin has been
injured and has been found in 38-76% of patients with plaque psoriasis.
Reverse-Koebner reactions have also been noted in which preexisting
psoriatic plaques actually clear after injury or trauma to the skin
 
 
 
Lesion
Plaques: elevated lesions that vary in size from one to several
centimeters, being raised and easily palpable.
Well-circumscribed margins- (the halo or ring of Woronoff)

ORAL MANIFESTATIONS-
Extremely rare
Angular cheilosis/fissured tongue/benign migratory glossitis.
Lesions are seen on lips,buccal,palate,gingiva ,floor of mouth.
Lesion-gray,yellowish white plaques ,as silvery white, scaly
white, scaly lesions with erythematous base.
Or as multiple papular eruptions which may be ulcerated.
Etiology
Cause is not fully understood. Two hypothesis are given-
First-psoriasis is primarily disorder of excessive growth and
reproduction of skin cells.
Second-immune mediated disorder,excessive reproduction of skin
being secondary to immune system.
 2.Genetics
Around one-third of people with psoriasis report a family history of
the disease
monozygotic twins suggest a 70% chance & around 20% for
dizygotic twins
Onset before age 40 usually indicates a greater genetic susceptibility
Identified nine loci on different chromosomes.
They are called psorasis susceptibility 1 through 9 (PSOR1-PSOR9).
PSOR1 accounts for 35-50% of heritability.
 
Associated with several triggering factors -
1.Cutaneous trauma (sunburn, surgery, trauma from
scratching)
2. psychological stress
3. Several drugs (beta-blockers, angiotensin-converting
enzyme inhibitors, antimalarials, lithium)
4. bacterial, viral, and yeast infections are triggers
(Ortonne 1999)
5. alcohol consumption, smoking, and obesity
6.koebners phenomenon
PATHOGENESIS
Stimulus is unknown
Stimulates receptors on plasmacytoid dendritic cells
These produce interferon alpha.
Also in psoriasis keratinocytes produce amtimicrobial peptides.
Under influence of T cells and dendritic cells keratinocytes
produce interleukin 1/6,TNF-α
T cells move from dermis to epidermis.
Attracted to epidermis by alpha1 beta 1 integrin.
These T cells secrete interferon gamma and interleukin-17.
Interleukin 17 is associated with interleukin 22 which causes
keratinocytes to proliferate.
'IL-23/Th17 axis' model for psoriasis
HISTOLOGICAL FEATURES-

Epithelial changes-
A marked epidermal thickening a result of hyperplasia of basal and suprabasal keratinocytes .
Marked Hyperkeratosis, parakeratosis and increased shedding of epidermal scale .
absent granular layer.
Acanthosis
Elongation of rete ridges
Thinning of suprapappilary epidermis
Neutrophils invade the epidermis, accumulate as small spongiform Kogoj pustules, migrate up to
the stratum corneum forming Monro’s microabscesses
Elongation and edema of dermal pappillae.
Dilated tortuous capillaries.
Neoangiogenesis-
characteristic of psoriatic plaque formation .
four-fold increase in endothelium of the superficial, but not of the deeper
The dermal papillae are extremely high and oedematous
in the tips of dermal papillae a prominent perivascular infiltrate of mainly mononuclear cells with a
few neutrophils can be seen
 
 
THANK YOU

Dr. R M Mathur

Dr. Shaleen
Chandra

Dr. Vineet Raj