Diseases of Skin

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

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.

Genodermatosis hereditary skin disorders accompanied by various systemic manifestations of altered enzyme functions Genokeratoses Genodermatosis characterized particularly by alterations in normal keratin process Example :

Leukoedema, White Spongy nevus, Hereditary Benign Intraepithelial Dyskeratoses, Follicular Keratosis (Dariers Disease)

Ectodermal dysplasia syndrome Oral lichen planus Psoriasis Erythema multiforme Pemphigus vulgaris Mucous membrane pemphigoid Bullous pemphigoid Epidermolysis bullosa SLE Scleroderma

Ehlers Danlos Syndrome Dariers Disease White sponge nevus Acrodermatitis enteropathica Gorlin Syndrome Dermatitis herpetiformis Linear Ig A disease

ECTODERMAL DYSPLASIA SYNDROME

Inherited disorders, may affect skin, hair, nails, eccrine glands & teeth Structures not affected Salivary glands ???? Etiology Aberrant development of ectodermal derivatives in early embryonic life X-linked recessive - hypohidrotic ED -Xq-12-q13.1-gene ED1 Decreased expression of EGFR Hidrotic ED (Clouston syndrome) -GJB6, encodes for connexin-30- 13q Mutations of gene PVRL1, encoding a cell-to-cell adhesion

HYPOHIDROTIC (ANHIDROTIC) ED (CHRIST- SIEMENS-TOURAINE SYNDROME)

Hypohidrosis Hypodontia (Anomalous dentition) Hypotrichosis Onychodysplasia

frontal bossing sunken cheeks saddle nose thick, everted lips ~ pseudorhagades wrinkled, hyperpigmented skin around eyes large, low set ears

Dental manifestations Hypodontia or anodontia Delayed eruption ~ perm. teeth Conical/ pegged teeth Normal jaw growth Decreased V.D High arched palate

HIDROTIC ED (CLOUSTON SYNDROME) 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

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 0.5 1 % worlds population

ETIOLOGY

Immune mediated mucocutaneous disorder Genetic predisposition Infection anerobic bacilli, spirochaetes, Candida albicans, HIV, HPV, HSV, EBV infection Psychogenic factors - Stress induced, Nervous, highly strung (Shaler, 1983) Systemic diseases (Diabetes mellitus, Hypertension Intestinal diseases - ulcerative colitis, Liver diseases HCV hepatitis) Habits - Tobacco or betel chewing Vitamin deficiencies Other etiologic factors ~ UV rays, other autoimmune ds, trauma

CLINICAL FEATURES

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 whitish lines (Wickhams striae) Histologically, they are areas of focal epidermal thickening

Mostly affects the flexor surface of the wrist & forearms, inner aspects of knees & thighs, trunk

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, white keratotic lesions erosive, atrophic, bullous ~ severe pain, burning sensation

A/c to George F. Murphy,

Reticular - Lace like striae Papular - Small white papules Hyperplastic / Plaque like - Elevated white lesions that resemble hyperkeratotic plaques Atrophic - Poorly defined, smooth, erythematous areas Erosive - Superficial erosion on a reticular or atrophic background Bullous - Subepithelial bullae / vesicles that subsequently rupture Linear - Fine white striae Annular - Discrete lesions usually found on tongue

NOT A TYPE - verrucous

PATHOGENESIS OF LICHEN PLANUS

Bosinic S et al, 1990 ~ immunologically induced basal cell degeneration Cell mediated ~ Langerhans cells & macrophages (antigen presentation to T lymphocytes)

Histochemical studies ~ T- cell origin, CD4 ~ fewer, helper cells CD8 ~ more, destroyer cells

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 homogenous eosinophilic globules Civatte, hyaline, cytoid, fibrillar, colloid bodies

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.

Lichen planus can undergo

Malignant transformation

LICHENOID REACTIONS

Are drug induced Exhibit histopathological features similar to lichen planus

Common drugs implicated in oral lichenoid reactions are

Antihypertensives NSAIDS Pencillamine dapsone, ketocanazole, streptomycin, sulfamethoxazole, tetracycline, chloroquine and oral hypoglycemic agents etc.

Diseases exhibiting lichenoid reactions Lichen planus Erythema multiforme Secondary syphllis Lupus erythematosus

GRINSPANS SYNDROME

Diabetes mellitus Vascular hypertension Lichenoid Reaction

PSORIASIS

Non contageous skin disorder Inflamed edematous skin lesions covered with silvery white scales Most common type plaque psoriasis

ETIOLOGY

Unknown Genetic predisposition HLA Cw6 and B57 association Many other genes Auto immune disease Stress related

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 surpass that of epidermoid carcinoma

CLINICAL FEATURES

Small sharp dry papules Covered by delicate silvery scale resembling thin layer of mica Auspitzs sign tiny bleeding points are disclosed 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

PSORIASIFORM LESIONS Psoriasis Reiters syndrome Benign migratory glossitis Ectopic geographic tongue

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 when scales are peeled off Tortuous dilated capillaries extendign high in papillae

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

TREATMENT

UV-A light Psoralen plus UV-A light (PUVA) Retinoids (isotretinoin, acitretin) Methotrexate Cyclosporine Alefacept

ERYTHEMA MULTIFORME

Erythema multiforme minor localized eruption of skin with wild or no mucosal involvement Erythema multiforme major and Steven johnson syndrome more severe forms, life threatening Herpes induced EM major Herpes ass. EM

ETIOLOGY

Immune mediated

Acute inflammatory mucocutaneous disease that can occur in both the genders at any age. CAUSES A VARIETY OF LESIONS HENCE THE NAME MULTIFORME.

PATHOGENESIS
Initiated either by deposition of immune complexes in the superficial microvasculature of skin and mucosa or cell mediated immunity

TRIGGERING FACTORS

Infections (hsv, tb, histoplasmosis)

Drugs (barbiturates & sulfanamides)

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

CLINICAL FEATURES

Usually young adults.

Prodromal symptoms. Self limiting ( 2- 6 weeks).

Recurrent episodes (in spring and autumn).

The most common cutaneous areas involved are the extensor surfaces of the elbows and knees.
Face and neck are commonly involved.

Asymptomatic, vividly erythematous discrete macules/papules or occasional vesicles and bullae. TARGET Lesion IRIS Lesion BULLS EYE Lesion

ORAL MANIFESTATIONS
Erythematous patches.

Epithelial necrosis.

Shallow ulcerations and Erosions. PSEUDOMEMBRANE FORMATION

Hemorrhagic crusting of the vermillion zones of the lips.

Tongue, palate, gingiva and buccal mucosa are commonly diffusely involved.

ERYTHEMA MULTIFORME MAJOR / STEVENS-JOHNSON SYNDROME

More severe form of the disease (drug>infection) Severe bullae and target lesions with erythema and halo Oral, Ocular and genital mucosa are involved. Type III hypersensitivity reaction

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.

DIAGNOSIS

Sudden onset and development of lesions. Symmetric arrangement. Charecteristic iris lesion.

Involvement of vermillion border of lip

DIFFERENTIAL DIAGNOSIS

Pemphigus vulgaris.
Benign mucous membrane pemphigoid. Bullous lichen planus.

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.

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)

Pemphigus vulgaris
Pathophysiology: -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)

Desmoglein Ag

IgG, IgA Complement

Tzanck cell

PG

DG

CK

DP

CK = cytokeratin DP = desmoplakin

DG = desmoglein PG = plakoglobin

-Exogenous inducing or perpetuating factors: Dietary components: Garlic Drugs Viruses: Human Herpesvirus 8 Association with other disorders: RA, LE, myesthenia gravis

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 lesions 1 year

Nikolskys sign is positive: Gentle traction on clinically unaffected mucosa may produce stripping of epithelium

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

VARIANTS

P. vegetans P. foliaceous (Fogo Selvagem) P. erythematosus

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 lesions followed 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

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

Pemphigus erythematosus (Senear-Usher Syndrome)

Is characterized by occurrence of bullae & vesicles with concomitant appearance of crusted patches resembling seborrheic dermatitis or lupus erythematosus

Terminates in pemphigus vulgaris or foliaceus

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

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 measurement of Dsg1 and Dsg3 antibodies in serum

TREATMENT According to Rook and Colleagues the photochemotherapy for drug resistant pemphigus vulgaris include administration of 8-methoxypsoralen followed by exposure of peripheral blood to ultraviolet radiation (PUVA Therapy)

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

Clinical features
Age: age at onset is 60 years (7-76 years) Gender: M:F=1:1 Symptoms: -Painful eroded areas -Skin eruptions

Oral erosions affecting all surfaces of oropharynx & involves lateral borders of tongue & vermillion border of lips Hemorrhagic crusting of lips

Investigations & diagnosis: a)

4 diagnostic criteria by Anhalt (2004):

(i) Painful, progressive stomatitis, with preferential involvement of tongue (ii) Histologic features of acantholysis or lichenoid or interface dermatitis (iii) Demonstration of antiplakin autoAbs (iv) Demonstration of underlying lymphoproliferative neoplasm (Anhalt GJ: J Investig Dermatol Symp Proc 2004; 9(1): 29-33)

MUCOUS MEMBRANE PEMPHIGOID/ CICATRICIAL PEMPHIGOID

Is a chronic autoimmune subepithelial disease that primarily affects the mucous membranes, resulting in mucosal ulceration & subsequent scarring Incidence ~ 1 of every 15,000 to 40,000 individuals MMP occurs up to 3 times more frequently than pemphigus

Pathogenesis: Primary lesion occurs when autoantibodies IgG & A are directed against proteinsBPAG2, BPAG1, Laminin-5, 64 integrin in basement membrane zone

Pathogenesis of BMMP

Majority cases of mucous membranepemphigoid or cicatrial pemphigoid demonstrate IgG directed against antigens of the epidermal side of the saltsplit skin, which have been identified as BP 180 or XVII collagen.

The antigen present on the dermal side is epiligrin (laminin 5)

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

Extraoral manifestations

Scarring & adhesions developing between bulbar & palpebral conjunctiva: SYMBLEPHARON Corneal damage, scarring lead to blindness Skin lesions in 20-30% cases

Investigations & diagnosis

a) Histologic features Vesicles & bullae are subepithelial In BMZ Non-specific chronic inflammatory infiltrate in connective tissue, lymphocytes, plasma cells & eosinophils

b) Immunofluorescence

DIF shows a uniform, linear deposition of IgG & complement along BMZ IIF demonstrates presence & titres of circulating IgG & IgA autoAbs to BMZ Ags

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

Sites: Scalp, arms, legs, axilla, groin Signs: Urticarial or erythematous rash on limbs persisting for several weeks to months Vesicles & bullae in the prodromal skin lesions & in normal skin Ruptured vesicles leave a raw, eroded area Pruritis

Oral lesions are vesicles, areas of erosion & ulceration Involvement of buccal mucosa, palate, floor of mouth & tongue Gingiva: Erythematous & may desquamate

Histologic features

Vesicle & bullae are subepidermal Epithelium appears relatively normal Vesicle contains fibrinous exudate admixed with occasional inflammatory cells

Immunofluorescence: DIF demonstrates IgG bound to basement membrane zone IIF demonstrates circulating IgG Abs against BM Ag

EPIDERMOLYSIS BULLOSA

A large group of clinically similar desquamating disease processes 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.

Major categories of Epidermolysis Bullosa

Type

Genetic Pattern

Separation Level

Defec. Structure

Hereditary Simplex Junctional Dystrophic

Autosomal dominant Autosomal recessive Autosomal dominant

Intraepithelial Lamina lucida Sublamina densa

Linking proteins Anchoring filaments Type VII collagen

Acquired Acquisita

None/autoimmune

Sublamina densa

Type VII collagen

EPIDERMOLYSIS BULLOSA

Clinical features
1.

Epidermolysis Bullosa Simplex Mild form; autosomal dominant Sites of trauma/friction Involve hands, feet and neck; occ. knees and elbows Intraoral blisters seen Appears during infancy

2.

Junctional Epidermolysis Bullosa Severe form; autosomal recessive Haemorrhagic blisters; loss of nails, large blisters of face, 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

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 and claw-like hands (Mitten Deformity) Teeth exhibit delayed eruption and enamel hypoplasia with rapid caries development

Scarring around mouth leads to diminished opening, ankyloglossia

Epidermolysis Bullosa Acquisita

Non-hereditary form; appears in adulthood Trauma/friction induced blisters of knees, elbows, hands and feet- heal with scars Intraoral blisters rare- when present same picture as JEB

Histopathology

Simplex type exhibits zone of cleavage (intra-epithelial) above basal cell layer. Remaining types have sub-epithelial separation

Immunofluoroscence

SLE

SKIN LESIONS. KIDNEY INVOLVEMENT. CARDIAC INVOLVEMENT. HEMATOLOGIC DISEASES. ARTHRITIS. ORAL LESIONS.

SLE

Auto immune disease Characterized by auto antibodies, immune complexes and immune dysregulation Damage to any organ includes kidney, skin, blood cells, CNS

ETIOLOGY

Genetics Hormones Environment (sunlight, drugs) Cell mediated auto immune role

CLINICAL FEATURES

Cutaneous systemic disorder Repeated remissions and exacerbations Peak age of onset 30 years in females, 40 years in males F:M=2:1 before puberty, 4:1 after puberty

Erythamatous patches on face forming symmetrical pattern over cheeks and across the bridge of nose butterfly rash Severity intensified by exposure to sunlight

In kidney, fibrinoid thickening of glomerular capillaries occurs, which produces characteristic wire loops

COLLAGEN DISEASE Rheumatic fever Rheumatoid arthiritis Polyarteritis nodosa Scleroderma Dermatomyositis

Oral lesions simulate other diseases chiefly leukoplakia and lichen planus

LAB FINDINGS
LE 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 cell consist 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

SCELODERMA

Systemic Sclerosis Dermatosclerosis Hidebound disease

ETIOLOGY

Auto immune HLA histocompatibility complex including HLA-B8, HLA-DR5, HLA-DR3, HLADR52, and HLA-DQB2 are involved Apoptosis and generation of free radicals may be involved Increased collagen deposition of tissues

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

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

CREST syndrome Calcinosis cutis Raynauds pehnomenon Esophageal dysfunction Sclerodactyly Telangiectasia

Morphea circumscribed scleroderma

well defined, elevated or depressed cutaneous patches White or yellowish Surrounded by violaceous halo Occurs on sides of chest and thighs On forehead, chest and trunk or extremity Coup de sabre

Linear Scleroderma

ORAL MANIFESTATION

Tongue, soft palate and larynx are involved Tightening of oral mucosa and pdl involvement Early edema followed by atrophy and induration of mucosal and muscular tissue Tongue become stiff and board like Lips becomes thin, rigid and partially fixed producing microstomia

ORAL MANIFESTATION

Dyspahgia Involvement of peritemporomandibular joint tissue Minor salivary glands characteristic of Sjogrens syndrome

Lymphocyte infiltration Duct cell proliferation Collagen infiltration

RADIOGRAPHIC FEATURES

Extreme widening of periodontal ligament (2-4 times) Bone resorption of the angle of mandibular ramus (bilaterally) Partial or complete resorption of condyles and/or coronoid processes

HISTOLOGICAL FEATURES

Thickening and hyalinization of collagen fiber in skin Loss of dermal appendages particularly sweat glands Atrophy of epithelium with loss of rete pegs Increased melanin pigmentation

CHANGES IN PDL

Widening of PDL due to increase in collagen and oxytalan Halinization and sclerosis of collagen Decrease in number of CT cells

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 IV decreased 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

Other names

Tenascin X deficiency syndrome Iysyl hydroxylase deficiency syndrome Cutis hyperelastica

Clinical Features

Hyperelasticity of skin Hyperextensibility of joints Fragility of skin & b/vs, excessive bruising

Circus Rubber man'

Numerous cigarette paper scars of face, flat nasal bridge Easy eversion of upper lids (Metenier sign)

Hypertelorism Protruding-ears & frontal bossing Freely movable subcutaneous nodules frequently found~ fibrosed lobules of fat Papyraceous scars of knees with pseudotumor below left knee

Oral Manifestations

Oral mucosa -fragile & bruised easily Unusual extensibility of tongue Hypermobility of TMJ ~ repeated dislocations of jaw Lack of normal scalloping of DEJ, passage of many dentinal tubules into enamel Irregular dentin & increased tendency to form pulp stones

GORLINS SIGN

DARIERS DISEASE
KERATOSIS FOLLICULARIS, DARIER-WHITE DISEASE, DYSKERATOSIS FOLLICULARIS.

AUTOSOMAL DOMINANTLY INHERITED GENODERMATOSES. Benign dyskeratosis TRIAD : Greasy hyperkeratotic papules in seborrheic region. Nail abnormalities. Mucous membrane changes Involvement of oral epithelium and skin

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

that encodes an intracellular calcium pump has been identified to cause Dariers disease.

Associated with

VITAMIN A DEFICIENCY

CLINICAL FEATURES

Usually is manifested during childhood/ adolescence and has an equal sex distribution.

SKIN LESIONS

NAIL CHANGES

LONGITUDINAL LINES, RIDGES, PAINFUL SPLITTING AND SUBUNGUAL KERATOSIS.

ORAL MANIFESTATIONS

HISTOPATHOLOGIC PICTURE

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.

Corps ronds larger than normal cells Seen in granular and superficial cell layer Grains small,elongated parakeratotic cells in keratin layer

TREATMENT

BASIC MEASURES : Sunscreens.

TOPICAL MEDICATION : Retinoids, Corticosteroids.

SYSTEMIC MEDICATION : Oral retinoids like acitretin, isotretinoin, etretinate.

WHITE SPONGE NEVUS

Oral epithelial nevus Congenital leukokeratosis Cannons disease

Hereditary disease Autosomal dominant trait

Clinical feature

Oral lesions cheeks, palate, gingiva, FOM, tongue Mucosa is thickened and folded or corrugated Soft spongy texture White opalescent hue Ragged white areas can be removed by gentle rubbing without any bleeding

Histological features

Epithelium thickened Hyper parakeratosis Akanthosis Basal layer is intact Intracellular edema of spinus layer Parakeratine plugs running deep into spinus layer are typically found

ACRODERMATITIS ENTEROPATHICA

Zinc deficiency Autosomal recessive Perioral and acral dermatitis Alopecia

ETIOLOGY

Two new fibroblast proteins absent in fibroblast These proteins may be responsible for decreased zinc uptake and abnormal zinc metabolism

CLINICAL FEATURES

Disease begin in first few weeks or months of life Localised eruption of skin near body orifices Loss of hair Diarrhoea Vesiculobullous skin legions rupture, crust and become erythamatous, scaling with psoriasiform pattern Oral mucosa, chiefly buccal mucosa becomes erythematous and edematous with erosive desquamative lesions

HISTOLOGICAL FEATURES

Parakeratoses Stratum cornium with neutrophils Diminished granular cell layer Focal dyskeratoses Subcorneal pustules

LAB FINDINGS

Plasma zinc levels low Hair, urine and parotid saliva zinc levels and serum alkaline phosphatase levels lowers later in disease Analysis of maternal breast milk zinc level help in differentiating it from acquired zinc deficiency

FOCAL DERMAL HYPOPLASIA SYNDROME (GOLTZ'S GORLIN SYNDROME)

FOCAL
Female sex Osteopathia striata Coloboma Absent ectodermis, mesodermis-, and neurodermis-derived elements Lobster claw deformity

Etiology

Genetic disorder Underlying molecular defect not clear

Clinical Features

Focal absence of dermis ass. with herniation of subcutaneous fat into defects; skin atrophy, streaky pigmentation & telangiectasia

Syndactyly, polydactyly
Sunken eyes with sparse eyebrows & scalp hair; eye anomalies

Osteopathi a striata is constant finding

Oral Manifestations

Papillomas of lips , buccal mucosa or gingiva Hamartomatous mass of dorsum of tongue Teeth ~ Severly hypoplastic enamel, defective in size, shape or structure

DERMATITIS HERPETIFORMIS
Etiology n pathogenesis

Deposits of Ig A in tissue, no demonstrable circulating antibodies Ass. b/w skin ds & gluten sensitive enteropathy

Clinical features

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

Histopathology and immunopathology

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 lesional n perilesional location

LINEAR

IG A DISEASE

Autoimmune 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 in the basement membrane zone . Antigenic sites are lamina lucida or lamina densa.

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 includes macules , papules , erythema multiforme like eruptions. Crusts , excortications , erosions and ulcers may be seen .

Ocular manifestations : Burning , grittiness , subconjunctival fibrosis Oral manifestations : ulceration , vesicles, Erythematous patches , erosions , desquamative gingivitis , that may precede skin lesions

MICROSCOPICALLY

DISEASE
PEMPHIGUS VULGARIS MUCOUS MEMBRANE PEMPHIGOID

CLINICAL FEATURES
Multiple painful ulcers, preceded by bullae, middle age, +ve Nikolskys Sign(NS), progressive disease, remissions, CAUSE ~ Autoimmune, Abs ~ desmosome ass. Protein, desmoglein 3 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 Skin ds., (trunk & extremities), infrequent oral lesions, ulcers preceded by bullae, no scarring, elderly persons, CAUSE ~ BM autoAbs are detected in tissue & serum 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 Skin ds., lesions ~ urticarial, annular, targetoid or bullous, I/O ~ gingiva, ulcerative preceded by bullae, ocular lesion ~ majority cases, CAUSE ~ Ig A deposits at epi CT interface, target ~ 120 kd protein 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

BULLOUS PEMPHIGOID

DERMATITIS HERPETIFORMIS

LINEAR Ig A DISEASE

EPIDERMOLYSIS BULLOSA

Intra epithelial Acantholytic lesions Pemphigus Pemphigus vulgaris Pemphigus foliaceous Pemphigus vegetans Familial benign chronic Pemphigus
(hailey-hailey diseases)

CLASSIFICATION
Sub epithelial Vesiculobullous diseases Erythema multiforme Pemphigoid group Bullous pemphigoid Benign mucous membrane cicatrical 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

Dariers disease Non acantholytic lesions Viral infections Herpes simplex viral infections Herpes zoster Coxsackie infections

(REF: Oral pathology :JV Soames and JC Southam)

JOINT EROSIONS seen in Rheumatoid arthritis Psoriasis Multicentric reticulohistiocytosis

NOT SEEN IN - SLE

DISEASE

TYPE OF FLOURESCENCE

Pemphigus
Lichen planus

Pemphigoid Erythema multiformae Lupus erythematosus

Garnular intercellular space fluorescence Fluorescence along the basement membrane zone with numerous extensions into the lamina propria Patchy linear pattern along the basement membrane
Speckled or Particulate pattern at the basement membrane

Intraepithelial bulla

Subepithelial bulla

Herpes simplex Herpes zoster Chicken pox Pemphigus Familial benign pemphigus (HaileyHailey disease) Epidermolysis bullosadystrophic

Pemphigoid Bullous pemphigoid (most common subepithelial blistering disease) Bullous lichen planus Dermatitis herpeti-formis Epidermolysis bullosa Skin lesions of erythema