diseases of skin

7/28/2019 Diseases of Skin

1/152

Diseases of Skin


2/152

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


3/152

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.


4/152

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)


5/152

Ectodermal dysplasia syndrome

Oral lichen planus

Psoriasis

Erythema multiforme

Pemphigus vulgaris

Mucous membrane pemphigoid

Bullous pemphigoid

Epidermolysis bullosa

SLE

Scleroderma


6/152

Ehlers Danlos Syndrome

Dariers Disease

White sponge nevus Acrodermatitis enteropathica

Gorlin Syndrome

Dermatitis herpetiformis

Linear Ig A disease


7/152

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


8/152

HYPOHIDROTIC (ANHIDROTIC) ED(CHRIST- SIEMENS-TOURAINESYNDROME)

Hypohidrosis

Hypodontia (Anomalous dentition)

Hypotrichosis

Onychodysplasia


9/152

frontal bossingsunken cheeks

saddle nose

thick, everted lips ~

pseudorhagades

wrinkled,

hyperpigmented skin

around eyeslarge, low set ears


10/152

Dentalmanifestations

Hypodontia or

anodontia

Delayed eruption ~

perm. teeth

Conical/ pegged teeth

Normal jaw growthDecreased V.D

High arched palate


11/152

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


12/152

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


13/152

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


14/152

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


15/152

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


16/152


17/152

NOT A TYPE - verrucous


18/152

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


19/152

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


20/152

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.


21/152

Lichen planuscan undergo

Malignant transformation


22/152

LICHENOID REACTIONS

Are drug induced

Exhibit histopathological featuressimilar to lichen planus


23/152

Common drugs implicated in oral lichenoid

reactions are

Antihypertensives

NSAIDS

Pencillamine

dapsone, ketocanazole,

streptomycin,

sulfamethoxazole,

tetracycline,

chloroquine and

oral hypoglycemic agents etc.


24/152

Diseases exhibiting lichenoid reactions

Lichen planus

Erythema multiforme

Secondary syphllis

Lupus erythematosus


25/152

GRINSPANS SYNDROME Diabetes mellitus

Vascular hypertension

Lichenoid Reaction


26/152

PSORIASIS Non contageous skin disorder

Inflamed edematous skin lesions covered

with silvery white scales

Most common typeplaque psoriasis


27/152

ETIOLOGY Unknown

Genetic predisposition

HLA Cw6 and B57 association

Many other genes

Auto immune disease Stress related


28/152

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


29/152

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


30/152

PSORIASIFORM LESIONS

Psoriasis

Reiters syndrome

Benign migratory glossitis

Ectopic geographic tongue


31/152

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


32/152

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


33/152

TREATMENT UV-A light

Psoralen plus UV-A light (PUVA)

Retinoids (isotretinoin, acitretin)

Methotrexate

Cyclosporine Alefacept


34/152

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


35/152

ETIOLOGY Immune mediated


36/152

Acute inflammatory mucocutaneous diseasethat can occur inboth the genders at any age.

CAUSES A VARIETY OF LESIONSHENCE THE NAME MULTIFORME.


37/152

PATHOGENESIS

Initiated either by

deposition ofimmune complexes in the

superficial microvasculature of skin and

mucosa or

cell mediated immunity


38/152

TRIGGERING FACTORS

Infections (hsv, tb, histoplasmosis)

Drugs (barbiturates & sulfanamides)

Other factors : malignancy, vaccination,autoimmune disease and radiotherapy.


39/152

CLINICAL FEATURES Usually young adults.

Prodromal symptoms.

Self limiting ( 2- 6 weeks).

Recurrent episodes (in spring and autumn).


40/152

The most common cutaneous areas

involved are the extensor surfaces of the

elbows and knees.

Face and neck are commonly involved.


41/152

Asymptomatic, vividly

erythematous discrete

macules/papules or

occasional vesicles and

bullae.

TARGET Lesion

IRIS Lesion

BULLS EYE Lesion


42/152

ORAL MANIFESTATIONS

Erythematous patches.

Epithelial necrosis.

Shallow ulcerations and Erosions.

PSEUDOMEMBRANE FORMATION


43/152

Hemorrhagic crustingof the vermillion zonesof the lips.

Tongue, palate, gingivaand buccal mucosa are

commonly diffuselyinvolved.


44/152


45/152

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.


46/152

DIAGNOSIS

Sudden onsetand development of lesions.

Symmetric arrangement.

Charecteristic iris lesion.

Involvement ofvermillion border of lip


47/152

DIFFERENTIAL DIAGNOSIS

Pemphigus vulgaris.

Benign mucous membrane pemphigoid.

Bullous lichen planus.


48/152

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.


49/152

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)


50/152

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)


51/152

CK = cytokeratin DG = desmoglein

DP = desmoplakin PG = plakoglobin

Desmoglein Ag

IgG, IgA

Complement

Tzanck cell

PGDG

DPCK


52/152

-Exogenous inducing or perpetuating factors: Dietary components: Garlic

Drugs

Viruses: Human Herpesvirus 8

Association with other disorders: RA,

LE, myesthenia gravis

Clinical features


53/152

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


54/152

Nikolskys sign is positive:Gentle traction on clinically unaffected mucosa may

produce stripping of epithelium


55/152

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


56/152

VARIANTS P. vegetans

P. foliaceous (Fogo Selvagem)

P. erythematosus

Pemphigus vegetans


57/152

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


58/152

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


59/152

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


60/152

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


61/152

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


62/152

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)


63/152

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


64/152

Clinical featuresAge: age at onset is 60 years (7-76 years)

Gender: M:F=1:1Symptoms:

-Painful eroded areas

-Skin eruptions


65/152

Oral erosions affecting all surfaces of oropharynx &

involveslateral borders of tongue & vermillion border of lips

Hemorrhagic crusting of lips


66/152

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)


67/152

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


68/152

Pathogenesis:

Primary lesion occurs when autoantibodies

IgG & A are directed against proteins-

BPAG2, BPAG1, Laminin-5, 64 integrin

inbasement membrane zone


69/152


70/152

Pathogenesis of BMMP


71/152

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)


72/152

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


73/152

Extraoral manifestations

Scarring & adhesions developing between bulbar &

palpebral conjunctiva: SYMBLEPHARON

Corneal damage, scarring lead to blindness

Skin lesions in 20-30% cases


74/152

Investigations & diagnosisa) Histologic features

Vesicles & bullae are subepithelial

In BMZ

Non-specific chronic inflammatoryinfiltrate in connective tissue,

lymphocytes, plasma cells &

eosinophils


75/152

b) Immunofluorescence

DIF shows a uniform, linear deposition of IgG & complement

along BMZ

IIF demonstrates presence & titres of circulating IgG & IgAautoAbs to BMZ Ags


76/152

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


77/152

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


78/152

Oral lesions are vesicles, areas of erosion & ulceration

Involvement of buccal mucosa, palate, floor of mouth & tongue

Gingiva: Erythematous & may desquamate


79/152

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


80/152

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.


81/152

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


82/152

EPIDERMOLYSIS BULLOSA


83/152

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


84/152

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


85/152

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


86/152


87/152

Histopathology

Simplex type exhibits zone of cleavage

(intra-epithelial) above basal cell layer.

Remaining types have sub-epithelial

separation

Immunofluoroscence


88/152

SLE

SKIN LESIONS.

KIDNEY INVOLVEMENT.

CARDIAC INVOLVEMENT.

HEMATOLOGIC DISEASES.

ARTHRITIS.

ORAL LESIONS.


89/152

SLE Auto immune disease

Characterized by auto antibodies, immune

complexes and immune dysregulation

Damage to any organincludes kidney,

skin, blood cells, CNS


90/152

ETIOLOGY Genetics

Hormones

Environment (sunlight, drugs)

Cell mediated auto immune role


91/152

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


92/152


93/152

Erythamatous patches on face forming

symmetrical pattern over cheeks and across

the bridge of nosebutterfly rash Severity intensified by exposure to sunlight


94/152

In kidney, fibrinoid thickening of

glomerular capillaries occurs, which

produces characteristic wire loops


95/152

COLLAGEN DISEASE

Rheumatic fever

Rheumatoid arthiritis

Polyarteritis nodosa

Scleroderma

Dermatomyositis


96/152

Oral lesions simulate other diseases chiefly

leukoplakia and lichen planus


97/152

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


98/152

SCELODERMA Systemic Sclerosis

Dermatosclerosis

Hidebound disease


99/152

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


100/152

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


101/152

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


102/152

CREST syndrome

Calcinosis cutis

Raynauds pehnomenon

Esophageal dysfunction

Sclerodactyly

Telangiectasia


103/152

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


104/152

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


105/152

ORAL MANIFESTATION Dyspahgia

Involvement of peritemporomandibular joint

tissue Minor salivary glands characteristic ofSjogrens

syndrome

Lymphocyte infiltration

Duct cell proliferation

Collagen infiltration


106/152

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


107/152

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


108/152

CHANGES IN PDL Widening of PDL due to increase in

collagen and oxytalan

Halinization and sclerosis of collagen

Decrease in number of CT cells


109/152

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


110/152

Other names TenascinX deficiency syndrome

Iysyl hydroxylase deficiency syndrome

Cutis hyperelastica


111/152


112/152

Numerous cigarette paper scars of face, flat nasal

bridge

Easy eversion of upper lids (Metenier sign)

Hypertelorism


113/152

Hypertelorism

Protruding-ears &frontal bossing

Freely movable

subcutaneous nodulesfrequently found~fibrosed lobules of fat

Papyraceous scars ofknees withpseudotumor belowleft knee

Oral Manifestations


114/152

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


115/152

AUTOSOMAL DOMINANTLY


116/152

AUTOSOMAL DOMINANTLYINHERITED GENODERMATOSES.

Benign dyskeratosis

TRIAD : Greasy hyperkeratotic papules in seborrheic

region.

Nail abnormalities. Mucous membrane changes

Involvement of oral epithelium and skin


117/152

PATHOPHYSIOLOGY

Mutation of a gene [ATP2A2 on 12q23-24.1]

that encodes an intracellular

calcium pump has been identified to cause

Dariers disease.


118/152

Associated with

VITAMIN A DEFICIENCY


119/152

CLINICAL FEATURES

Usually is manifested during childhood/

adolescence and has an equal sexdistribution.


120/152


121/152


122/152

HISTOPATHOLOGIC PICTURE


123/152

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


124/152

Corps rondslarger than normal cells

Seen in granular and superficial cell layer

Grainssmall,elongated parakeratotic cells

in keratin layer


125/152


126/152

WHITE SPONGE NEVUS Oral epithelial nevus

Congenital leukokeratosis

Cannons disease


127/152

Hereditary disease

Autosomal dominant trait


128/152


129/152

ACRODERMATITIS


130/152

ACRODERMATITIS

ENTEROPATHICA Zinc deficiency

Autosomal recessive

Perioral and acral dermatitis

Alopecia


131/152

ETIOLOGY Two new fibroblast proteins absent in

fibroblast

These proteins may be responsible fordecreased zinc uptake and abnormal zinc

metabolism


132/152


133/152

HISTOLOGICAL FEATURES Parakeratoses

Stratum cornium with neutrophils

Diminished granular cell layer

Focal dyskeratoses

Subcorneal pustules


134/152

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


135/152

FOCAL DERMAL HYPOPLASIASYNDROME(GOLTZ'S GORLIN SYNDROME)

FOCAL Female sex

Osteopathia striata

Coloboma

Absent ectodermis, mesodermis-,and neurodermis-derived elements

Lobster claw deformity

Etiology


136/152

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


137/152

polydactyly

Sunkeneyes withsparseeyebrows &

scalp hair;eyeanomalies

Osteopathia striata isconstantfinding

Oral


138/152

Oral

Manifestations

Papillomas of lips ,buccal mucosa or

gingiva

Hamartomatous massof dorsum of tongue

Teeth ~ Severlyhypoplastic enamel,defective in size, shape

or structure


139/152


140/152

DERMATITIS HERPETIFORMIS

Etiology n pathogenesis

Deposits of Ig A in tissue, no demonstrable circulatingantibodies

Ass. b/w skin ds & gluten sensitive enteropathy

Clinical features


141/152

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


142/152

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


143/152

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.


144/152

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 .


145/152

Ocular manifestations :

Burning , grittiness , subconjunctival fibrosis

Oral manifestations : ulceration , vesicles,

Erythematous patches , erosions , desquamative

gingivitis , that may precede skin lesions


146/152

MICROSCOPICALLY

DISEASE CLINICAL FEATURES

PEMPHIGUSMultiple painful ulcers, preceded by bullae, middle age, +veNikolskys

Sign(NS) progressive disease remissions CAUSE Autoimmune Abs


147/152

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


148/152

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)


149/152

JOINT EROSIONS seen in

Rheumatoid arthritis

Psoriasis

Multicentric reticulohistiocytosis

NOT SEEN IN - SLE

DISEASE TYPE OF FLOURESCENCE


150/152

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


151/152

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


152/152

diseases of skin

Documents