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Diseases of Skin
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INTRODUCTION
SSE ~ complex structure
Keratinocytes adherent ~each other & underlying EBM & thus lamina propria
Continuous barrier ~external environment
Array of molecules ~ required to maintain epithelial integrity
and health
Cohesion among keratinocytes is very important for
preserving the tissue architecture and epithelial function
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Macule. - Focal area of color change which is not elevated or
depressed in relation to its surroundings.
Papule. - Solid, raised lesion which is less than 5 mm in diameter.
Nodule. - Solid, raised lesion which is greater than 5 mm in dia.
Vesicle. - Superficial blister, 5 mm or less in dia., filled with fluid.
Bulla. - Large blister, greater than 5 mm in diameter.
Pustule. -Blister filled with purulent exudate
Plaque. - Lesion that is slightly elevated and is flat on its surface.
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Genodermatosishereditary skin disorders
accompanied by various systemic manifestationsof altered enzyme functions
GenokeratosesGenodermatosis characterized
particularly by alterations in normal keratin
process
Example : Leukoedema, White Spongy nevus, Hereditary
Benign Intraepithelial Dyskeratoses, Follicular
Keratosis (Dariers Disease)
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Ectodermal dysplasia syndrome
Oral lichen planus
Psoriasis
Erythema multiforme
Pemphigus vulgaris
Mucous membrane pemphigoid
Bullous pemphigoid
Epidermolysis bullosa
SLE
Scleroderma
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Ehlers Danlos Syndrome
Dariers Disease
White sponge nevus Acrodermatitis enteropathica
Gorlin Syndrome
Dermatitis herpetiformis
Linear Ig A disease
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ECTODERMAL DYSPLASIA
SYNDROME Inherited disorders,
may affect skin, hair, nails, eccrine glands & teeth
Structures not affectedSalivary glands ????
Etiology
Aberrant development of ectodermal derivatives in early
embryonic life
X-linked recessive - hypohidrotic ED -Xq-12-q13.1-gene ED1Decreased expression of EGFR
Hidrotic ED (Clouston syndrome) -GJB6,
encodes for connexin-30- 13q
Mutations of gene PVRL1, encoding a cell-to-cell adhesion
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HYPOHIDROTIC (ANHIDROTIC) ED(CHRIST- SIEMENS-TOURAINESYNDROME)
Hypohidrosis
Hypodontia (Anomalous dentition)
Hypotrichosis
Onychodysplasia
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frontal bossingsunken cheeks
saddle nose
thick, everted lips ~
pseudorhagades
wrinkled,
hyperpigmented skin
around eyeslarge, low set ears
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Dentalmanifestations
Hypodontia or
anodontia
Delayed eruption ~
perm. teeth
Conical/ pegged teeth
Normal jaw growthDecreased V.D
High arched palate
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HIDROTIC ED (CLOUSTONSYNDROME)
Nail dystrophy, hair defects & palmoplantar
dyskeratosis
Nails ~ thickened & discolored; persistent
paronychial infections are frequent
Scalp hair ~ sparse, fine, and brittle
Eyebrows ~ thinned or absent
Patients have normal facies, normal sweating &
no specific dental defect
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Oral Lichen Planus Common, chronic mucocutaneous disease
Erasmus Wilson ~ 1869
Lichen are primitive plants (symbiotic algae and
fungi)
Planus flat topped
These lesions were thought to resemble lichen
growing on rocks
Disease of adulthood, F > M (3:2)
Affect 0.51 % worlds population
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Immune mediated mucocutaneous disorder Genetic predisposition
Infectionanerobic bacilli, spirochaetes, Candida
albicans, HIV, HPV, HSV, EBV infection
Psychogenic factors - Stress induced, Nervous, highlystrung (Shaler, 1983)
Systemic diseases (Diabetes mellitus, Hypertension
Intestinal diseases - ulcerative colitis,
Liver diseasesHCV hepatitis)
Habits - Tobacco or betel chewing
Vitamin deficiencies
Other etiologic factors ~ UV rays, other autoimmune ds,
trauma
ETIOLOGY
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Skin lesions: 5 P Pruritic, Planar, Polygonal, Purple Papules
Primary lesion ~ 2 to 10 mm flat topped papule
Koebners phenomenon
Lacy, reticular pattern of criss crossed whitishlines (Wickhams striae)
Histologically, they are areas of focal epidermalthickening
Mostly affects the flexor surface of the wrist &forearms, inner aspects of knees & thighs, trunk
CLINICAL FEATURES
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ORAL LICHEN PLANUS- CLINICAL FEATURES Primary lesion - PAPULE
Most common sites ~ buccal mucosa, tongue, lips,
gingiva Bilaterally symmetrical
Burning sensation
6 types (Andreason, 1968) ~
reticular, papular, plaque-like ~ painless, whitekeratotic lesions
erosive, atrophic, bullous ~ severe pain, burningsensation
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NOT A TYPE - verrucous
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PATHOGENESIS OF LICHEN PLANUS Bosinic S et al, 1990 ~ immunologically induced basal cell degeneration
Cell mediated ~Langerhans cells & macrophages
(antigen presentation to Tlymphocytes)
Histochemical studies
~ T- cell origin,
CD4 ~ fewer, helper cells
CD8 ~ more, destroyer cells
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HISTOLOGICAL FEATURES Typical findings
Hyperparakeratoses or hyperorthokeratoses
Thickening of granular layer
Acanthosis
Saw toothed rete pegs
Band like subepithelial mononuclear infiltrate of
T lymphocytes and histiocytes
Degenerating basal keratinocytes which appear
as homogenouseosinophilic globulesCivatte,
hyaline, cytoid, fibrillar, colloid bodies
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MAX JOSEPH SPACE
Histological clefts seen
Due to weak epithelial connective tissue
interface
Because of degeneration of basal
keratinocytes and disruption of anchoring
elements of EBM (hemidesmosomes,
filaments and fibrils) and basal
keratinocytes.
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Lichen planuscan undergo
Malignant transformation
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LICHENOID REACTIONS
Are drug induced
Exhibit histopathological featuressimilar to lichen planus
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Common drugs implicated in oral lichenoid
reactions are
Antihypertensives
NSAIDS
Pencillamine
dapsone, ketocanazole,
streptomycin,
sulfamethoxazole,
tetracycline,
chloroquine and
oral hypoglycemic agents etc.
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Diseases exhibiting lichenoid reactions
Lichen planus
Erythema multiforme
Secondary syphllis
Lupus erythematosus
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GRINSPANS SYNDROME Diabetes mellitus
Vascular hypertension
Lichenoid Reaction
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PSORIASIS Non contageous skin disorder
Inflamed edematous skin lesions covered
with silvery white scales
Most common typeplaque psoriasis
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ETIOLOGY Unknown
Genetic predisposition
HLA Cw6 and B57 association
Many other genes
Auto immune disease Stress related
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Increase in turnover rate of dermal cells
Normal turnover = 23 days
In Psoriasis = 2-5 days
Dramatic increase in mytotic index of
psoriatic skin which is said to even surpassthat of epidermoid carcinoma
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CLINICAL FEATURES Small sharp dry papules
Covered by delicate silvery scaleresembling
thin layer of mica
Auspitzs signtiny bleeding points aredisclosed if deep scales are removed, surface of
skin is red and dusky
Severe in winter
Less in summer due to increased exposure to UV
light
Arthiritis is a complication
Koebners phenomenon
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PSORIASIFORM LESIONS
Psoriasis
Reiters syndrome
Benign migratory glossitis
Ectopic geographic tongue
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HISTOLOGIC FEATURES Uniform parakeratoses
Absence of stratum granulosum
Elongation and clubbing of rete pegs
Epithelium over CT papillae is thinned
Form these points bleeding occurs whenscales are peeled off
Tortuous dilated capillaries extendign high
in papillae
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Munros abscesses
Intra epithelial micro abscesses in oral
psoriasis
With elongated rete ridges are seen in
Benign migratory glositis
Without elongated rete ridges are seen in
Reiters syndrome
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TREATMENT UV-A light
Psoralen plus UV-A light (PUVA)
Retinoids (isotretinoin, acitretin)
Methotrexate
Cyclosporine Alefacept
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Erythema multiforme minorlocalized
eruption of skin with wild or no mucosal
involvement
Erythema multiforme majorand Steven
johnson syndrome more severe forms,
life threatening
Herpes induced EM major
Herpes ass. EM
ERYTHEMA MULTIFORME
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ETIOLOGY Immune mediated
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Acute inflammatory mucocutaneous diseasethat can occur inboth the genders at any age.
CAUSES A VARIETY OF LESIONSHENCE THE NAME MULTIFORME.
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PATHOGENESIS
Initiated either by
deposition ofimmune complexes in the
superficial microvasculature of skin and
mucosa or
cell mediated immunity
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TRIGGERING FACTORS
Infections (hsv, tb, histoplasmosis)
Drugs (barbiturates & sulfanamides)
Other factors : malignancy, vaccination,autoimmune disease and radiotherapy.
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CLINICAL FEATURES Usually young adults.
Prodromal symptoms.
Self limiting ( 2- 6 weeks).
Recurrent episodes (in spring and autumn).
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The most common cutaneous areas
involved are the extensor surfaces of the
elbows and knees.
Face and neck are commonly involved.
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Asymptomatic, vividly
erythematous discrete
macules/papules or
occasional vesicles and
bullae.
TARGET Lesion
IRIS Lesion
BULLS EYE Lesion
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ORAL MANIFESTATIONS
Erythematous patches.
Epithelial necrosis.
Shallow ulcerations and Erosions.
PSEUDOMEMBRANE FORMATION
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Hemorrhagic crustingof the vermillion zonesof the lips.
Tongue, palate, gingivaand buccal mucosa are
commonly diffuselyinvolved.
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IMMUNOPATHOLOGIC STUDIES
Epithelium shows negative staining for
immunoglobulins.
Have shown to have IgM complement and fibers in
their walls (immune comlex vasculitis)
Autoantibodies to desmoplakins 1 &2 have been
identified.
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DIAGNOSIS
Sudden onsetand development of lesions.
Symmetric arrangement.
Charecteristic iris lesion.
Involvement ofvermillion border of lip
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DIFFERENTIAL DIAGNOSIS
Pemphigus vulgaris.
Benign mucous membrane pemphigoid.
Bullous lichen planus.
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TREATMENT
MILD : Topical anesthetic mouth washes
and soft/liquid diet.
MODERATE to SEVERE : 30-50mg/day
of prednisone for several days which is
then tapered.
RECURRENT CASES : Dapsone,
azathioprine, levamisole or thalidomide.
Antiherpes drugs in susceptible patients.
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PEMPHIGUS VULGARIS Greek word Pemphix, meaning bubble or blister
Wichman in 1791
Is an autoimmune mucocutaneous ds. ~ Intraepithelial blister
Breakdown of intercellular adhesion ~ acantholysis
Epidemiology:
-Annual incidence of 1 to 5 per million population per year
-A genetic predisposition linked to HLA class II alleles
-Ashkenazi Jews & persons of Mediterranean & South Asian origin
2 phenotypes of PV, mucosal-dominant & mucocutaneous
(Dominik A. Ettlin DCNA 2005; 49:107-125)
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Pemphigus vulgarisPathophysiology:-Intraepithelial lesion is formed when Ig G Abs target 2 structural
proteins of desmosomes, desmoglein1 (Dsg1) & desmoglein3 (Dsg3)
(Nishikawa T et al: J Dermatol Sci 1996; 12: 1-9)
- Dsg 4
- (Kljuic et al. Cell 2003;113(2): 249-60)
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CK = cytokeratin DG = desmoglein
DP = desmoplakin PG = plakoglobin
Desmoglein Ag
IgG, IgA
Complement
Tzanck cell
PGDG
DPCK
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-Exogenous inducing or perpetuating factors: Dietary components: Garlic
Drugs
Viruses: Human Herpesvirus 8
Association with other disorders: RA,
LE, myesthenia gravis
Clinical features
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Clinical features
Age: 4rth to 6th decades
Gender:No gender predilection
Site: Skin & mucosa
Symptoms:
-Chronic, painful ulcers preceded by
bullae
-1st
signs of ds. ~ OM in 60% cases,precede cutaneous lesions1 year
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Nikolskys sign is positive:Gentle traction on clinically unaffected mucosa may
produce stripping of epithelium
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NIKOLSKYS SIGN +VE IN
Pemphigus
Mucous membrane pemphigoid
Familial benign chronic pemphigus
(Hailey Hailey Disease)
Paraneoplastic pemphigus
Recessive dystrophic epidermolysis bullosa
Oral lichen planus
LE
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VARIANTS P. vegetans
P. foliaceous (Fogo Selvagem)
P. erythematosus
Pemphigus vegetans
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Pemphigus vegetans
-Is a relatively benign variant of pemphigus vulgaris
-2 forms:
a)Neumann type: Large bullae & denuded areas which attempt healing by
developing vegetations of hyperplastic granulation tissue
b) Hallopeau type: Less aggressive with pustules being the initial lesionsfollowed by verrucous hyperkeratotic vegetations
Oral manifestations:
-Gingival lesions may be lace-like ulcers with a purulent surface
on a red base or have a granular or cobblestone appearance
-Cerebriform tongue: Sulci & gyri on dorsum
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Pemphigus foliaceus
Loss of intercellular adhesion of keratinocytes in upper part of epidermis,
resulting in formation of superficial blisters
Chronic course with little or no mucous membrane involvement
Pathogenesis:IgG Abs against desmoglein 1
Clinical features:
Age: Older adults
Appearance: Early bullous lesions which rupture rapidly & dry to
leave masses of flakes or scales
Brazilian pemphigus (Fogo selvagem or Brazilian Wildfire): Is a mild
endemic form of PF found in tropical regions, particularly Brazil, that
often occurs in children & frequently in family groups
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Pemphigus erythematosus
(Senear-Usher Syndrome)
- Is characterized by occurrence of bullae &
vesicles with concomitant appearance ofcrusted patches resembling seborrheic
dermatitis or lupus erythematosus
- Terminates in pemphigus vulgaris or foliaceus
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Investigations & diagnosis:
a) Nikolskys sign
b) Histological examination Formation of a vesicle or bulla
intraepithelially, just above basal
layer producing the distinctive
suprabasilar split
Loss of cohesiveness or acantholysis
Clumps of epithelial cells lying free
within vesicular space: Tzanck cells
Scarcity of inflammatory cell
infiltrate in vesicular fluid & at base
of vesicle or bulla
FNAC
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c) Immunofluorescence:
-DIF: Presence of IgG predominantly with C3, IgA & IgM in
intercellular spaces or substance in epithelium
-IIF: Antikeratinocyte Abs against intercellular substances
d) ELISA: For direct measurementof Dsg1 and Dsg3 antibodies in
serum
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TREATMENT
According to Rook and Colleagues the
photochemotherapy for drug resistant
pemphigus vulgaris include administration
of8-methoxypsoralen followed by
exposure of peripheral blood to ultravioletradiation (PUVA Therapy)
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Paraneoplastic pemphigus (Neoplasia induced pemphigus)
Is a severe variant of pemphigus that is associated with an
underlying neoplasm- non-Hodgkins lymphoma,
chronic lymphocytic leukemia or thymoma
Pathophysiology:
Abs against Dsg3, Dsg1 & plakin proteins
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Clinical featuresAge: age at onset is 60 years (7-76 years)
Gender: M:F=1:1Symptoms:
-Painful eroded areas
-Skin eruptions
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Oral erosions affecting all surfaces of oropharynx &
involveslateral borders of tongue & vermillion border of lips
Hemorrhagic crusting of lips
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Investigations & diagnosis:
a) 4 diagnostic criteria by Anhalt (2004):
(i) Painful, progressive stomatitis, with preferential involvement of tongue
(ii) Histologic features ofacantholysis or lichenoid or interface dermatitis
(iii) Demonstration ofantiplakin autoAbs
(iv) Demonstration of underlying lymphoproliferative neoplasm
(Anhalt GJ: J Investig Dermatol Symp Proc 2004; 9(1): 29-33)
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MUCOUS MEMBRANE PEMPHIGOID/CICATRICIAL PEMPHIGOID
Is a chronic autoimmune subepithelial disease
that primarily affects the mucous membranes,
resulting in mucosal ulceration & subsequentscarring
Incidence ~ 1 of every 15,000 to 40,000
individuals
MMP occurs up to 3 times more frequently than
pemphigus
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Pathogenesis:
Primary lesion occurs when autoantibodies
IgG & A are directed against proteins-
BPAG2, BPAG1, Laminin-5, 64 integrin
inbasement membrane zone
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Pathogenesis of BMMP
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Majority cases of mucous membranepemphigoid
or cicatrial pemphigoid demonstrate IgG directed
against antigens of the epidermal side of the salt-split skin, which have been identified as BP 180
or XVII collagen.
The antigen present on the dermal side is epiligrin
(laminin 5)
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Clinical features
Age: Over 50 years
Gender: Female predominance,F:M=2:1
Sites: Oral cavity, eyes, pharyngeal &
laryngeal mucosa, nasal,
esophageal & vaginal mucosa
Symptoms: Oral pain caused by ulcers
Inability to effectively clean the
dentition
Regular gentle brushing may
cause profuse Bleeding gums
Loss of epithelium from attached
gingiva of both arches
Halitosis
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Extraoral manifestations
Scarring & adhesions developing between bulbar &
palpebral conjunctiva: SYMBLEPHARON
Corneal damage, scarring lead to blindness
Skin lesions in 20-30% cases
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Investigations & diagnosisa) Histologic features
Vesicles & bullae are subepithelial
In BMZ
Non-specific chronic inflammatoryinfiltrate in connective tissue,
lymphocytes, plasma cells &
eosinophils
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b) Immunofluorescence
DIF shows a uniform, linear deposition of IgG & complement
along BMZ
IIF demonstrates presence & titres of circulating IgG & IgAautoAbs to BMZ Ags
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BULLOUS PEMPHIGOID(PARAPEMPHIGUS)
Is a chronic, autoimmune, subepidermal, blistering skin disease
that rarely involves mucous membranes
Pathogenesis:IgG autoAbs against hemidesmosomal bullous pemphigoid Ags
BP230 & BP180
results in defect in lamina lucida region of basement membrane
Clinical features:
Age: Over 60 years
Gender:No gender predilection
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Sites:Scalp, arms, legs, axilla, groin
Signs:
Urticarial or erythematous rash
on limbs persisting for several
weeks to months
Vesicles & bullae in theprodromal
skin lesions & in normal skin
Ruptured vesicles leave a raw,
eroded area
Pruritis
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Oral lesions are vesicles, areas of erosion & ulceration
Involvement of buccal mucosa, palate, floor of mouth & tongue
Gingiva: Erythematous & may desquamate
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Histologic features Vesicle & bullae are subepidermal
Epithelium appears relatively normal
Vesicle contains fibrinous exudate admixed with occasional
inflammatory cells
Immunofluorescence:
DIF demonstratesIgG bound to basement membrane zone
IIF demonstrates circulating IgG Abs against BM Ag
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EPIDERMOLYSIS BULLOSA
A large group of clinically similar desquamating diseaseprocesses of the skin and mucosa that have in common the
separation of the epithelium from the underlying
connective tissue and the formation of large blisters that
frequently result in extensive and often immobilizing scar
formation.
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Type Genetic Pattern Separation Level Defec. Structure
HereditarySimplex Autosomal dominant Intraepithelial Linking proteins
Junctional Autosomal recessive Lamina lucida Anchoring filaments
Dystrophic Autosomal dominant Sublamina densa Type VII collagen
Acquired
Acquisita None/autoimmune Sublamina densa Type VII collagen
Major categories of Epidermolysis Bullosa
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EPIDERMOLYSIS BULLOSA
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Clinical features
1. Epidermolysis Bullosa Simplex Mild form; autosomal dominant
Sites of trauma/friction
Involve hands, feet and neck; occ. kneesand elbows
Intraoral blisters seen Appears during infancy
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2. Junctional Epidermolysis Bullosa
Severe form; autosomal recessive
Haemorrhagic blisters; loss of nails, large blisters offace, trunk and extremities
Generalized scarring and atrophy Intraorally-haemorrhagic blisters of palate, perioral
and perinasal areas
Erupted teeth exhibit hypoplastic and severely pitted
enamel prone to caries
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3. Dystrophic Epidermolysis Bullosa
Both autosomal dominant and recessive; recessive is severe
Lesions ~ birth; arise at pressure sites
Blisters rupture leaving painful ulcers which heal with large
scars that undergo contractures, leading to loss of motility andclaw-like hands (Mitten Deformity)
Teeth exhibit delayed eruption and enamel hypoplasia withrapid caries development
Scarring around mouth leads to diminished opening,ankyloglossia
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Histopathology
Simplex type exhibits zone of cleavage
(intra-epithelial) above basal cell layer.
Remaining types have sub-epithelial
separation
Immunofluoroscence
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SLE
SKIN LESIONS.
KIDNEY INVOLVEMENT.
CARDIAC INVOLVEMENT.
HEMATOLOGIC DISEASES.
ARTHRITIS.
ORAL LESIONS.
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SLE Auto immune disease
Characterized by auto antibodies, immune
complexes and immune dysregulation
Damage to any organincludes kidney,
skin, blood cells, CNS
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ETIOLOGY Genetics
Hormones
Environment (sunlight, drugs)
Cell mediated auto immune role
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CLINICAL FEATURES Cutaneous systemic disorder
Repeated remissions and exacerbations
Peak age of onset30 years in females, 40
years in males
F:M=2:1 before puberty, 4:1 after puberty
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Erythamatous patches on face forming
symmetrical pattern over cheeks and across
the bridge of nosebutterfly rash Severity intensified by exposure to sunlight
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In kidney, fibrinoid thickening of
glomerular capillaries occurs, which
produces characteristic wire loops
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COLLAGEN DISEASE
Rheumatic fever
Rheumatoid arthiritis
Polyarteritis nodosa
Scleroderma
Dermatomyositis
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Oral lesions simulate other diseases chiefly
leukoplakia and lichen planus
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LAB FINDINGSLE cell phenomenon
Given by Hargraves
Addition of blood serum from a patient to buffy coat of
normal blood leads to development of LE cell
LE cellconsist of rosette of neutrophils surrounding a
pale nuclear mass derived from lymphocyte
Basis of test appears to lie in gamma globulin of patients
serum
Anemia, leukopenia, thrombocytopenia, alleviated ESR
Anti nuclear antibodies
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SCELODERMA Systemic Sclerosis
Dermatosclerosis
Hidebound disease
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ETIOLOGY Auto immune
HLA histocompatibility complex including
HLA-B8, HLA-DR5, HLA-DR3, HLA-DR52, and HLA-DQB2 are involved
Apoptosis and generation of free radicals
may be involved
Increased collagen deposition of tissues
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CLINICAL FEATURES Ultimate induration of skin
Fixation of epidermis to the deeper
subcutaneous tissues
F>M (3-6:1)
Begins on face, hand and trunk
Multiple palmer keratosis
Yellow, gray or ivory white waxy skin
appearance
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Sometimes deposition of calcium in
affected areas
Firm fixation to deep connective tissue Skin becomes hardened and atrophic
Skin cannot be wrinkled or picked up
Mask like appearance to face
Claw like appearance to hands
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CREST syndrome
Calcinosis cutis
Raynauds pehnomenon
Esophageal dysfunction
Sclerodactyly
Telangiectasia
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Morpheacircumscribed scleroderma
well defined, elevated or depressed cutaneous
patches White or yellowish
Surrounded by violaceous halo
Occurs on sides of chest and thighs Linear Scleroderma
On forehead, chest and trunk or extremity
Coup de sabre
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ORAL MANIFESTATION Tongue, soft palate and larynx are involved
Tightening of oral mucosa and pdl involvement
Early edema followed by atrophy and indurationof mucosal and muscular tissue
Tongue become stiff and board like
Lips becomes thin, rigid and partially fixedproducing microstomia
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ORAL MANIFESTATION Dyspahgia
Involvement of peritemporomandibular joint
tissue Minor salivary glands characteristic ofSjogrens
syndrome
Lymphocyte infiltration
Duct cell proliferation
Collagen infiltration
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RADIOGRAPHIC FEATURES Extreme widening of periodontal ligament
(2-4 times)
Bone resorption of the angle of mandibularramus (bilaterally)
Partial or complete resorption of condyles
and/or coronoid processes
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HISTOLOGICAL FEATURES Thickening and hyalinization of collagen
fiber in skin
Loss of dermal appendages particularlysweat glands
Atrophy of epithelium with loss of rete
pegs Increased melanin pigmentation
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CHANGES IN PDL Widening of PDL due to increase in
collagen and oxytalan
Halinization and sclerosis of collagen
Decrease in number of CT cells
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EHLERS-DANLOS SYNDROME Genetic defect in collagen & connective-tissue synthesis & structure
Skin, Joints, Blood vessels
Etiology Types I and II- COL5Al, COL5A2, and tenascin-X genes
Type IVdecreased type III collagen
Types V and VI -deficiencies in hydroxylase & lysyl oxidase
Type VII -amino-terminal procollagen peptidase deficiency
Type IX - abnormal copper metabolism
Type X -nonfunctioning plasma fibronectin
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Other names TenascinX deficiency syndrome
Iysyl hydroxylase deficiency syndrome
Cutis hyperelastica
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Numerous cigarette paper scars of face, flat nasal
bridge
Easy eversion of upper lids (Metenier sign)
Hypertelorism
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Hypertelorism
Protruding-ears &frontal bossing
Freely movable
subcutaneous nodulesfrequently found~fibrosed lobules of fat
Papyraceous scars ofknees withpseudotumor belowleft knee
Oral Manifestations
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Oral mucosa -fragile & bruisedeasily
Unusual extensibility of tongue
Hypermobility of TMJ ~repeated dislocations of jaw
Lack of normal scalloping ofDEJ, passage of manydentinal tubules into enamel
Irregular dentin & increasedtendency to form pulp stones
GORLINS SIGN
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AUTOSOMAL DOMINANTLY
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AUTOSOMAL DOMINANTLYINHERITED GENODERMATOSES.
Benign dyskeratosis
TRIAD : Greasy hyperkeratotic papules in seborrheic
region.
Nail abnormalities. Mucous membrane changes
Involvement of oral epithelium and skin
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PATHOPHYSIOLOGY
Mutation of a gene [ATP2A2 on 12q23-24.1]
that encodes an intracellular
calcium pump has been identified to cause
Dariers disease.
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Associated with
VITAMIN A DEFICIENCY
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CLINICAL FEATURES
Usually is manifested during childhood/
adolescence and has an equal sexdistribution.
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HISTOPATHOLOGIC PICTURE
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Characteristic findings in skin lesions are
hyperkeratosis, papillomatosis, acanthosis and
a peculiar benign dyskeratosis.
Dyskeratotic process is characterized by
typical cells called corps ronds and grains.
HISTOPATHOLOGIC PICTURE
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Corps rondslarger than normal cells
Seen in granular and superficial cell layer
Grainssmall,elongated parakeratotic cells
in keratin layer
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WHITE SPONGE NEVUS Oral epithelial nevus
Congenital leukokeratosis
Cannons disease
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Hereditary disease
Autosomal dominant trait
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ACRODERMATITIS
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ACRODERMATITIS
ENTEROPATHICA Zinc deficiency
Autosomal recessive
Perioral and acral dermatitis
Alopecia
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ETIOLOGY Two new fibroblast proteins absent in
fibroblast
These proteins may be responsible fordecreased zinc uptake and abnormal zinc
metabolism
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HISTOLOGICAL FEATURES Parakeratoses
Stratum cornium with neutrophils
Diminished granular cell layer
Focal dyskeratoses
Subcorneal pustules
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LAB FINDINGS Plasma zinc levels low
Hair, urine and parotid saliva zinc levels
and serum alkaline phosphatase levelslowers later in disease
Analysis of maternal breast milk zinc level
help in differentiating it from acquired zincdeficiency
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FOCAL DERMAL HYPOPLASIASYNDROME(GOLTZ'S GORLIN SYNDROME)
FOCAL Female sex
Osteopathia striata
Coloboma
Absent ectodermis, mesodermis-,and neurodermis-derived elements
Lobster claw deformity
Etiology
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Etiology Genetic disorder
Underlying moleculardefect not clear
Clinical Features Focal absence of dermis
ass. with herniation ofsubcutaneous fat into
defects; skin atrophy,streaky pigmentation &telangiectasia
Syndactyly,polydactyly
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polydactyly
Sunkeneyes withsparseeyebrows &
scalp hair;eyeanomalies
Osteopathia striata isconstantfinding
Oral
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Oral
Manifestations
Papillomas of lips ,buccal mucosa or
gingiva
Hamartomatous massof dorsum of tongue
Teeth ~ Severlyhypoplastic enamel,defective in size, shape
or structure
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DERMATITIS HERPETIFORMIS
Etiology n pathogenesis
Deposits of Ig A in tissue, no demonstrable circulatingantibodies
Ass. b/w skin ds & gluten sensitive enteropathy
Clinical features
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Chronic ds
Young, middle age
Male predilection
Cutaneous lesions ~ papular, erythematous, vesicular,
intensely pruritic
Lesions ~ symmetric, extensor surfaces, elbows,
shoulders, sacrum, buttocks
Frequent involvement of scalp and face ~ diagnostic
significance
Lesions ~ aggregated (herpetiform)
Rare in oral cavity
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Collections of neutrophils, eosinophils, fibrin at papillary tips of dermis
Subsequent exudation ~ epidermal separation
Lymphophagocytic infiltrate in perivascular spaces
Granular Ig A deposits at tips of C.T papillae ~ specific, C3 in lesionaln perilesional location
Histopathology and immunopathology
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LINEAR IG A DISEASEAutoimmune subdermal vesiculobullous disease that may be idiopathic or drug
induced.
In children the disease manifests as Chronic bullous disease of childhood.
Pathophysiology :
Autoimmune disease characterized by deposition of Ig A rather than Ig G inthe basement membrane zone .
Antigenic sites are lamina lucida or lamina densa.
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Clinical features
Period of Pruritis or burning before the skin lesions appears.
Skin lesions are clear hemorrhagic round vesicles or bullae on
normal or Erythematous skin .
Other manifestations includesmacules , papules , erythemamultiforme like eruptions.
Crusts , excortications , erosions and ulcers may be seen .
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Ocular manifestations :
Burning , grittiness , subconjunctival fibrosis
Oral manifestations : ulceration , vesicles,
Erythematous patches , erosions , desquamative
gingivitis , that may precede skin lesions
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MICROSCOPICALLY
DISEASE CLINICAL FEATURES
PEMPHIGUSMultiple painful ulcers, preceded by bullae, middle age, +veNikolskys
Sign(NS) progressive disease remissions CAUSE Autoimmune Abs
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PEMPHIGUS
VULGARISSign(NS), progressive disease, remissions, CAUSE ~ Autoimmune,Ab s ~
desmosome ass. Protein, desmoglein 3
MUCOUSMEMBRANE
PEMPHIGOID
Mutiple painful ulcers preceded by vesicles & bullae, may heal with scar,+ve NS, Affect mucous memb. Of oral cavity, eyes & genitals, middle-aged/
elderly women, CAUSE ~ Autoimm., Abs~ BMAs , Laminin 5, BP 180
BULLOUS
PEMPHIGOID
Skin ds., (trunk & extremities), infrequent oral lesions, ulcers preceded by
bullae, no scarring, elderly persons, CAUSE ~ BMautoAbs are detected in
tissue & serum
DERMATITIS
HERPETIFORMIS
Skin ds., rare oral involvement, vesicles & pustules, pruritic exacerbations &
remissions are typical, young & middle aged adults, CAUSE ~ Unknown, Ig
A deposits in site of lesions, usually ass. With gluten enteropathy
LINEAR Ig A
DISEASE
Skin ds., lesions ~ urticarial, annular, targetoid or bullous, I/O ~ gingiva,
ulcerative preceded by bullae, ocular lesion ~ majority cases, CAUSE ~ Ig
A deposits at epiCT interface, target ~ 120 kd protein
EPIDERMOLYSIS
BULLOSA
Multiple ulcers preceded by bullae, +ve NS, recessive, adult inheritance
pattern determines age of onset during childhood & severity, may heal with
scar, primarily a skin ds., but oral lesions often present, Rare, CAUSE ~
Hereditary, AD or AR, acquired adult form also exists
Intra epithelial CLASSIFICATION
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Acantholytic lesions
Pemphigus Pemphigus vulgaris
Pemphigus foliaceous
Pemphigus vegetans
Familial benign chronic Pemphigus
(hailey-hailey diseases)
Dariers disease
Non acantholytic lesions
Viral infections
Herpes simplex viral infections
Herpes zoster
Coxsackie infections
Sub epithelial Vesiculobullous diseases
Erythema multiforme Pemphigoid group
Bullous pemphigoid
Benign mucous membranecicatrical pemphigoid
Dermatitis herpetiformis Linear IgA diseases
Epidermolysis bullosa group
Inherited forms
Epidermolysis bullosa acquisitica
(acquired type) Oral blood blisters (angina bullosa
heamorrhagica)
Bullous lichen planus
(REF: Oral pathology :JV Soames and JC Southam)
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JOINT EROSIONS seen in
Rheumatoid arthritis
Psoriasis
Multicentric reticulohistiocytosis
NOT SEEN IN - SLE
DISEASE TYPE OF FLOURESCENCE
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DISEASE TYPE OF FLOURESCENCE
Pemphigus Garnular intercellular spacefluorescence
Lichen planus Fluorescence along the basement
membrane zone with numerous
extensions into the lamina propria
Pemphigoid
Erythema
multiformae
Patchylinear pattern along the
basement membrane
Lupus
erythematosus
Speckled or Particulate pattern
at the basement membrane
Intraepithelial bulla Subepithelial bulla
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Intraepithelial bulla Subepithelial bulla
Herpes simplex Herpes zoster
Chicken pox
Pemphigus
Familial benignpemphigus (Hailey-
Hailey disease)
Epidermolysis bullosa-
dystrophic
Pemphigoid Bullous pemphigoid
(most common
subepithelial blistering
disease) Bullous lichen planus
Dermatitis herpeti-formis
Epidermolysis bullosa
Skin lesions of erythema
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