Autoimmune Diseases of the Oral Cavity

8/4/2019 Autoimmune Diseases of the Oral Cavity

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AUTOIMMUNE DISEASES

OFTHE ORAL CAVITY



Autoimmunity is the failure of an organism to recognize its own

constituent parts as self , which results in an immune response

against its own cells and tissues.

Greek word ‘auto’ meaning self.

Due to failure of an organism to recognize its own constituentparts as self leading to an immune response against its own cellsand tissues.

Body’s own immune system begins to attack normal tissues cellsand organs within the body.

AUTOIMMUNITY



Autoimmune diseases are disorders in which the body'simmune system reacts against some of its own tissue and

produces antibodies to attack itself.

AUTO IMMUNE DISEASES



Auto antibodies are the antibodies that attack its own cells,

tissues, and/or organs. This causes inflammation and damageand it leads to autoimmune disorders.

AUTO ANTIBODIES



Distinguish self from non-self

Protect the body from foreign substances or pathogens

Hypersensitivity is an inappropriate, exaggeratedadaptive response that causes damage to the body

Reactions do not occur on the first contact

Gell and Coombs described four types

Functions of the Immune System



Immediate hypersensitivity

IgE mediated

Target organs are mucosal surfaces of the GI tract,respiratory tract and conjunctiva

Allergic rhinitis, urticaria, atopic dermatitis, asthma, GIsensitivity.

Type I Hypersensitivity



Antibody dependent cytotoxic hypersensitivity

IgG, IgM, NK cells and complement

Targets are circulating cells

Drug reactions, Goodpasture’s, pemphigus,myasthenia gravis, Lambert-Eaton, hemolytic diseaseof the newborn

Type II Hypersensitivity



Immune complex –– mediated hypersensitivity

Antigen-antibody complexes (IgG)

Target organs include blood vessels of the skin, joints,kidneys, lungs.

Serum sickness, SLE, glomerulonephritis

Type III Hypersensitivity



Delayed hypersensitivity

Cell-mediated (sensitized T lymphocytes)

Target organs include skin, lungs, CNS, thyroid

Three types:

Contact –– latex, nickel, poison ivy Tuberculin – 48 hours after PPD injection

Granulomatous leprosy, TB, sarcoidosis Crohn’s

Type IV Hypersensitivity



Immune reaction against self-antigen

Range: single organ (cell) disorder to multisystem

Connective tissue or collagen vascular disease

Self-tolerance: no immune response to self

Clonal deletion: loss of T cell clones during maturation

Clonal anergy: inactivation induced by antigens

Peripheral suppression by T cells

Autoimmune Diseases



Bypass of helper T-cell tolerance

Modification of molecule-drug complex

Costimulatory molecules (infection) Molecular mimicry

Microbes share epitopes with self-antigens

Streptococci and rheumatic heart disease

Polyclonal lymphocyte activation (Endotoxin, EBV)

Imbalance of suppressor/helper function

Emergence of sequestered antigens (e.g., eye, brain)

Mechanisms of AutoimmuneDisease (Loss of self-tolerance)



AUTO-IMMUNE BULLOUS DISEASES OF THEORAL MUCOSA

EPIDERMOLYSIS BULLOSA LICHEN PLANUS

RECURRENT APTHOUS STOMATITIS

ERYTEMA MULTIFORME

SJOGREN’SSYNDROME

SCLERODERMA

WEGENER GRANULOMATOSIS

SYSTEMIC LUPUS ERYTHEMATOSUS

TYPES OF AUTOIMMUNE DISEASES



Auto-immune Bullous Diseases of theOral Mucosa



Bulla or Blister a (cavity) of the mucosa, containing serosity

or bloodi. situated inside of the epithelium : intra-epithelial bulla

ii. beneath the epithelium : sub-epithelial bulla

due to loss of cohesion and separation

i. between adjacent keratinocytes ( intra-epithelialbullae )ii. in the basement membrane zone ( sub-epithelial bullae )

Bullae are different from

I. vesicles : smaller, due to necrosis or collected oedema

II. pustules : variable size and structure, and contain pus



intraepithelial bulla subepithelial bulla



Autoimmune disease.

Common in Ashkenazi and Mediterranean jews .

Middle aged females.

Other variants are:

Pemphius VegitansPemphigus Foliaceus & Erthematosus

Paraneoplastic pemphigus.

PEMPHIGUS VULGARIS



CLINICAL FEATURES:

Painful ulcers or bulla are formed which are fluidfilled.

They can be formed any where in the oral cavity .

The bulla is rapidly ruptured leaving a collapsed roof

of grayish membrane with a red ulcerated base.Theulcer may look like an apthous ulcer or may be largemap shaped.

Nikolsky sign is positive.

PEMPHIGUS VULGARIS



Some time the ulcers are joined together to make

a confluence this condition is very painful. It has a variable course might involve skin,

oesophagus, cervix.

Protein/fluid,electrolyte and weight loss/secondary infections.

Fatal if untreated.

PEMPHIGUS VULGARIS



PEMPHIGUS VULGARIS



Pemphigus vulgaris

Severe, potentially fatal Jewish and Italians

Intraepithelial bullae and acantholysis

Nikolsky’s sign

Loss of intracellular bridges Autoimmune response to desmoglein 3

Intraepithelial clefting

Pemphigus vulgaris



Pemphigus vulgaris



PATHOGENESIS:

It is an autoimmune disease There are circulating antibodies of type IgG. These antibodies are reactive against the

desmosomes or the tonofilament complex.

There destruction or disruption of thesetonofilament complex ,resulting in the loss ofattachment from cell to cell

PEMPHIGUS VULGARIS



The epithelial damage is directly proportion to

the number of the circulating antibobies. The tonofilament or desmosomes are

disrupted by a proteolytic enzyme which isreleased by these antibodies .

The cell to cell break down also takes placethrough a complement system but thisprocess is not clearly understood .

PEMPHIGUS VULGARIS



PEMPHIGUS VULGARIS



HISTOPATHOLOGY: Intra epithelial vesicles or bulla and cleft like spaces are produced

by acantolysis These changes are in the stratum spinosum or the prickle cell

layer The basal cell remain attach to the lamina propria and project

into the bulla like tombstones. Inflammatory cells are very scanty however eosinophils may be

seen. Acantholytic statum spinosum cells occur singly or are in the

forms of clumps lying freely within the blister fluid. These cellloose there polyhedral morphology rather they are smallrounded and contain hyper chromatic nuclei called the TAZANKCELLS.

PEMPHIGUS VULGARIS



PEMPHIGUS VULGARIShistology



PEMPHIGUS VULGARIStazank cells



PEMPHIGUS VULGARISimmunoflorecence



DIFFRENTIAL DIAGNOSIS:

Pempegiod

Erthema multiforme

Bullous lichen plannus

PEMPHIGUS VULGARIS



TREATMENT:

High mortality rates previously Introduction of systemic corticosteroids like

prednisolone in stable cases.

Prednisolone plus azathioprine methotrexate and

cyclophospamide in progressed or advance cases.

PEMPHIGUS VULGARIS



PEMPHGOID



PATHOLOGY Autoimmune disease Not life threatening

Elderly females above 60 yrs of age Loss of attachment and separation of full thickness

epithelium from the lamina propria. Alteration of rete pegs Epithelium forms the roof of the blisters Auto antibodies are formed against the

hemidesmosomes (BPAG-1,230kd;BPAG-2; 180kd. Inflammatory

cells(lymphocytes,neutrophils,eosinophils)are seen inthe later stages

PEMPHGOID



Mucous membrane pemphigoid (cicatricial) CIKA-

TRI-CIAL Bullous pemphigoid

PEMPHGOID



Bullous pemphigoid (BP) is a rare autoimmune subepidermal bullous diseaseprimarily affecting the elderly population after 60 years of age. Males are

equally as affected as females. In many cases, the cause of BP is suspectedto be medications. BP is mediated by the formation of autoantibodies binding to bullous

pemphigoid antigens 230 and 180, cytoplasmic and transmembrane portionshemidesmosomes of basal cells in the epidermis.

IgG autoantibodies are found in circulation and bound to the lamina lucidalayer of the basement membrane. These antigen-antibody complexes

trigger the release and activation of complement with leukocyte chemotaxisand subsequent degranulation. The release of proteolytic enzymes resultsin the degradation of the BMZ with separation of the epidermis from thedermis.

Bullous Pemphigoid



The presentation of BP is commonly oral blisters (24%), and is usuallytransient.

Initially there may be a localized erythematous plaque which may bepruritic, and subsequently enlarges with edema to become tense bullae. These lesions are usually generalized an most commonly affecting the lower

abdomen, groin, and flexor surfaces. There is a negative Nikolsky sign. These bullae usually rupture in a week, which leaves a localized are of

erosion which heals quickly. There are multiple variants of BP with vesicular, vegetating, hyperkaratotic,

and erythrodermic appearances. However, they all share the samehistologic and immunologic characteristics of BP.



I. The diagnosis depends on skin biopsy.

II. A subepidermal cleft with the present of eosinophils in the dermis and

bullous regions are common histologic findings.III. Direct immunofluorescence indicates the deposition of IgG, and/or C3,

and variably IgA, IgM, and fibrin in a linear fashion at the BMZ.

IV. Indirect immunofluorescence is needed to differentiate BP from otherbullous diseases.

V. Circulation IgG antibodies targeting the BP230 and BP180 antigensfound in BP.

VI. Mortality at 1 year is near 19% with treatment.



Treatment of BP is dependent on the extent and severityof disease.

Tetracycline, minocycline, or erythromycin with orwithout niacinamide has indicated excellent clinicalresponse for localized and generalized disease.

Topical steroid therapy has been to be effective for all

forms of BP and is superior to oral corticosteroids. Clobetasol proprionate cream (0.05%) has been

effectively used as a topical agent in treating BP.

Prednisone (0.5-1 mg/mg/daily) may be used ingeneralized BP



Mucous membrane pemphigoid (MMP), or cicatricialpemphigoid, is a rare chronic immune-mediated diseasecharacterized by blistering, ulcers, and scarring.

This disease usually affects adults from the age of 40 to 60and there is found in twice as often in woman than men.

It results from the production of autoantibodies againstantigens within the basement membrane zone of the laminalucida.

Mucous Membrane Pemphigoid(Cicatricial Pemphigoid)



CLINICAL FEATURES(MMP)

Oral mucosa is the first site- lesions are rarelywide spread Subepithelial bullae, ruptured in the later stages. Bleeding in the bullae – bleeding blisters

Slow progress, skin involvement absent or rare Involvement of eyes, nose larynx, pharynx and

osephaghus Nikolsky sign is positive



Diagnosis of MMP is established on biopsy taken from the lesionedge that includes ulcerated and nonulcerated portions.

Hematoxylin and eosin staining typically indicates separation ofthe mucosal epithelium from the underlying tissue at the level of

the lamina lucida between the basal cell layer and the laminadensa.

Definitive diagnosis requires clinical correlation with directimmunofluorescence findings.

There are linear deposits of one or a combination of IgG, IgA, andC3 at the basement membrane zone in a continuous andhomogeneous pattern.

MMP may be distinguished histologically from pemphigus by the

location of blisters.



Treatment for MMP may be treated topically by debridement ofnecrotic tissue and oral rinses of hydrogen peroxide,

Elixir of dexamethasone, and elixir of diphenhydramine (diluted1:4 or 1:6 with water.

Before meals, hydrogen peroxide rinse with diphenhydraminemay be used for cleaning and reducing pain.

Fluocinonide gel is an alternative and is adherent to ulcers withbetter patient compliance than triamcinolone in Orabase.

A soft acrylic appliance may be used when there is gingivalinvolvement.

Intralesional steroids may be injected into oral cavity lesions



CASCADEOF EVENTSAntibody antigen complex

Complement activation

Neutrophils & Eosinophils recruited

Release of proteases by the recruited cells

Sub epithelial blister formation



MANAGEMENT

Confirm diagnosis Topical corticosteroids

Ocular involvement –systemic steroids.



EPIDERMOLYSIS BULLOSA



Definition:

A large group of clinically similar desquamatingdisease processes of the skin and mucosa that have incommon the separation of the epithelium from theunderlying connective tissue and the formation oflarge 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 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




HEREDITARY TYPES:

Congenital absence of components

ACQUIRED TYPES:

Autoantibodies (IgG; sometimes IgA) to type VIIcollagen.





CLINICAL FEATURES

1. Epidermolysis Bullosa Simplex Mild form; autosomal dominant

Sites of trauma/friction

Involve hands, feet and neck; occ. knees and elbows

Teeth not affected; intraoral blisters seen Appears during infancy




2. Junctional Epidermolysis Bullosa

Severe form; autosomal recessive Haemorrhagic blisters; loss of nails, large blistersof face, trunk and extremities

Generalized scarring and atrophy Intraorally-haemorrhagic blisters of palate,

perioral and perinasal areas Erupted teeth exhibit hypoplastic and severelypitted enamel prone to caries




3. Dystrophic Epidermolysis Bullosa Both autosomal dominant and recessive; recessive is

severe Lesions are birth; arise at pressure sites Blisters rupture leaving painful ulcers which heal with large

scars that undergo contractures, leading to loss of motilityand claw-like hands (Mitten Deformity)

Teeth exhibit delayed eruption and enamel hypoplasia withrapid caries development

Scarring around mouth leads to diminished opening,ankyloglossia




Epidermolysis Bullosa Acquisita

Non-hereditary form; appears in adulthood Clinically resembles autosomal dominant type of JEB-

type VII collagen

Trauma/friction induced blisters of knees, elbows,

hands and feet- heal with scars Intraoral blisters rare- when present same picture

same picture as JEB




HISTOPATHOLOGY

Simplex type exhibits zone of cleavage (intra-epithelial) above basal cell layer.

Remaining types have sub-epithelial separation





MANAGEMENT No specific treatment available for hereditary

types Acquired form maybe treated with

corticosteroids and immuno-suppressants Maintenance of pt’s nutritional and oral hygiene

status

Wound healing techniques Prevention of infections Systemic use of Phenytoin (also acts as a

collagenase inhibitor)


Li IgA Di



Linear IgA is an acquired blistering disorder without a

definitive cause. There are two clinical types:

I. chronic dermatosis of childhood occurs in the firstten years,

II. adult linear IgA disease occurring later with peak

between 60 to 65 years.

(Note: These forms share the same histologic and immunologic findings,and may share the same target antigen.)

Linear IgA Disease



There are twice as many females affected by this disease than males,and may affect any skin site.

The lesions may be painful and pruritic.

Elevated erythrocyte sedimentation rate and circulating IgA may bepresent.

This blistering disorder has a tendency to occur in the trunk, limbs, face,perioral region, and hands.

This may clinically mimic dermatitis herpetiformis (also has IgA deposits),bullous pemphigoid, or other bullous diseases.

The oral mucosa is also affected and results in scarring.

This may resemble the presentation of desquamative gingivitis. Vesicularlesions may become confluent and form large bullae, and finally burst

leaving ulcerated areas.

Clinical Features



There are multiple antigens involved in linear IgA disease,

and the antibodies bind to multiple sites on a single antigen. The bullous pemphigoid antigen BP180 and its extracellular

domain LAD1 are most often implicated in the diseaseprocess.

Gluten sensitivity has been found in one quarter to one thirdof affected patients.

Other associated diseases include rheumatoid arthritis,ulcerative colitis, immune glomerulonephritis, andmalignancy including lymphoma.

Findings

Linear IgA Disease

Linear IgA Disease



Diagnosis of linear IgA disease depends upon biopsy ofperilesional areas with immunofluorescence.

Histologic appearance may indicate microabscesses andinfiltration of eosinophils in the superficial corium.

There may also be few lymphocytes present surroundingsmall vessels.

A homogeneous deposition of IgA, and possibly C3, is presentalong the basement membrane zone detected using direct

immunofluorescence in skin biopsy. This is in contrast to dermatitis herpetiformis, where IgA

deposits are present usually at the tips of connective tissuepapillae.

Diagnosis

Linear IgA Disease



Treatment of linear IgA disease may require combinationtherapy.

Topical and systemic steroids often do not effectively controlthis disease alone.

Dapsone, adult dosing 25-150 mg daily, is effective in most casesfor controlling symptoms of burning and itching,

TreatmentLinear IgA Disease



Lichen Planus



Lichen Planus

Lichen planus is an idiopathic inflammatory disorder involving

the skin and mucous membranes. The age of onset is about 40 years in men, and 46 years in

women. It is rarely found under the age of 5 years.

There is positive family history in 10% of patients, and an

increased frequency of HLA-B7 has been associated. There may be an association with hepatitis C virus.



variable and present as white striations (Wickhamstriae), white papules, white plaques, erythema(mucosal atrophy), erosions (shallow ulcers), orblisters.

The lesions predominantly affect the buccalmucosa, tongue, and gingivae, although otheroral sites are occasionally involved.

a T-cell–mediated autoimmune disease in whichautocytotoxic CD8 + T cells trigger the apoptosisof oral epithelial cells

Slightly increased risk of oral SCCa

Lichen Planus



Chronic disease of skin and mucous membranes

Destruction of basal cell layer by activatedlymphocytes

Reticular: fine, lacy appearance on buccal mucosa(Wickman’s striae)

Hypertrophic: resembles leukoplakia

Atrophic or erosive: painful

Lichen Planus



Lichen Planus

1. Spider web.

2. The buccal mucosa involved most often

3. reticular form most common

http://www.emedicine.com/DERM/IMAGES/LARGE/14271427LP_PLAQUE_BUCCAL.JPG



Reticular Oral Lichen Planus

http://www.emedicine.com/DERM/IMAGES/LARGE/14271427LP_PLAQUE_BUCCAL.JPG

http://www.emedicine.com/DERM/IMAGES/LARGE/14281428LP_RETICULAR_GINGIVAE.JPG




Lichen planus

Lichen Planus






Lichen Planus

A very high power viewof the dermoepidermaljunction

Civatte bodies (arrows),

keratinocyteenlargement, andcoarse collagen bundles

are illustrated.















Lichen planus (LP) is a self-limited disease that usuallyresolves within 8-12 months.

Mild cases can be treated with fluorinated topical steroids.

More severe cases, especially those with scalp, nail, andmucous membrane involvement, may need more intensivetherapy.












ERYTEMA MULTIFORME

ERYTEMA MULTIFORME





Mucocutaneous disease

Males adolosents , young adults are affected more

ERYTEMA MULTIFORME








ERYTEMA MULTIFORME





AETIOLOGY /PATHOLOGY

Unclear aetiology and pathogenesis Infections like HSV can trigger this disease

Drugs like Sulphonamides ,barbiturates

Suggested cause is also given as to a type III

hypersensitivity reaction

ERYTEMA MULTIFORME














CLINICAL FEATURES

Prodomal signs: Upper respiratory infection

Headache and malaise

Nausea and arthralgia

ERYTEMA MULTIFORME















Signs during the disease: Red macules – 1cm or more in diameter with

cyanotic center Lips grossly swollen ,split crusted bleeding Widespread fibrin covered erosions and erythema

in the mouth.

Mild fever Conjunctivitis may be associated Attacks recur at the intervals of several months Usually self limiting.

ERYTEMA MULTIFORME


























ERYTEMA MULTIFORME





HISTOPATHOLOGY

Necrosis of the kertinocytes Inter & intra cellular odema.

Subepithelial blisters are common

Infiltration of inflammatory cells.

ERYTEMA MULTIFORME














ERYTEMA MULTIFORME





MANAGEMENT

No specific treatment required , if HSV inf.. acycovir

Systemic steroids may give relief to the fever.

In severe cases antibiotics are used to prevent ant secondaryinfections.

Symptomatic –analgesics, antipyretics, antihistamines.

ERYTEMA MULTIFORME

















RECURRENT APTHOUSSTOMATITIS

( )







Most common ulcerative lesion of oral cavity

Recurrent, painful ulcers Confined to soft mucosa

Subdivided into three types: Minor aphthae

Major aphthae

Herpetiform aphthae

Recurrent Aphthous Stomatitis(RAS)



















ETIOLOGYThe etiology is not basically understood but increasing

evidence of damaging immune response is being given.How ever some of the factors are considered to be thecause.1.Immunological factors2.hereditary factors3.Microbiological factors4.Emotional stress5.Nutritional deficiencies6.Allergic disorders.7.Hematalogical factors.8.Gastrointestinal factors

Recurrent apthous stomatitis

h h i i ( )


















CLINICAL FEATURES Minor aphthae:

Heal completely in 7-10 days without scarring

Painful

Prodromal stage

Gray to yellow membrane

Clusters of up to 5 ulcers

Steroids

May be shallow and round effecting the non-keratinized part of the oral epithelium

Diameter of the ulcers is less than 10mm with red margins.

Site is usually the tongue, buccal mucosa soft palate floor of the tongue

Recurrent Aphthous Stomatitis(RAS)

h h i i ( )



























Minor apthae

Recurrent Aphthous Stomatitis (RAS)








Recurrent apthous stomatitisminor apthous ulcers

R h i i






MAJOR APTHOUS ULCERS

Larger than the minor apthous ulcer diameter more than 10mm.

Site similar to that of the minor apthous ulcers.

Also involve the keratinzed part of the epithelium.

They vary in number from 1-10.

Take 4-6 weeks to heal. Heal with scarring.

Recurs in less than a months time.


R A h h S i i (RAS)





















Major apthae

Recurrent Aphthous Stomatitis (RAS)








pmajor apthous ulcers

R t th t titi







HERPETIFORM ULCERATION

Multiple small pinhead size .Each ulcer1-2 mm in size.

Can occur at any part of the oral cavity and as many ashundreds of small ulcers may be present.

The ulcers are present in the form of clusters or corps andsometime these are joined together to form a very largeulcer.

They also heal with scarring.

Recur in less than a month time.

Associated with extreme pain and discomfort.























Recurrent apthous stomatitisherptiform ulcer

R t th t titi






HISTOPATHOLOGY(minor ,major, herptiform)

Mononuclear cells are found in the submucously in the preulcerative stage

These mononuclear cells are the T-4 lymphocytes and are soon

out numbered to T-8 lymphocytes as the ulcerative stagedevelops.

Macrophages and the mast cells are also present at the baseof the ulcer.


R t th t titi


















TREATMENT(Minor,Major,herptiform) Minor apthous ulcers require no treatment only topical

gels are used to minimize the pain ,as the ulcer is selflimiting and heals with in7-10 days Anti inflammatory gels and mouth washes are also used to

prevent any further infection and to control theinflammation caused by the ulcer

For major apthous ulcer topical corticosteriods may be

used In extreme severe cases systemic steroids such as

prednisilone in doses of 20-40mg daily have shownpromise























Sjogren’s Syndrome








Systematic, autoimmune disorder

Occurs in association with disorders such as

Rheumatoid arthritis Systemic lupus erythematosus: is a systemic autoimmune disease that can

affect any part of the body

Scleroderma:is a chronic systemic autoimmune disease characterized byfibrosis (or hardening), vascular alterations, and autoantibodies.

Polymyositis: many muscle inflammation.

Polyarteritis: a serious blood vessel disease in which small andmedium-sized arteries become swollen and damaged
























Keratoconjunctivitis sicca (dry eyes)

Xerostomia (dry mouth)

Immune-mediated destruction of lacrimal and salivary glands

Primary: “sicca syndrome” HLA-DR3

Secondary: with RA, SLE, etc. HLA-DR4

Women >40 yo

B cell lymphoma in 1%

Pseudolymphoma in 10%

Sjogren s Syndrome

























j g y

xerostomia and xerophthalmia

Sjögren’s Syndrome









Chronic autoimmune disorder

Major clinical manifestations resulting from changes inexocrine glands

Forms of Sjögren’s Syndrome










Primary Sjögren’s is characterized by inflammatory cellinvolvement of both the salivary and lacrimal glands

Secondary Sjögren’s includes other defined connectivetissue disease

Causes are unknown

Features of Sjögren’s Syndrome













Glandular epithelial cells participate in the autoimmune

disease process

Epithelial cells produce a number of immunologically

active mediators

May serve as antigen-presenting cells

Epithelial cell responses modulate mechanisms occurring in

the salivary glands

Is Sjögren’s Syndrome an Autoimmune















Described as an autoimmune exocrinopathy (Strandand Talal, 1980)

Grouped with other connective tissue diseases

Rheumatoid arthritis

Systemic lupus erythematosis (SLE)

What is the evidence that it is an autoimmunedisease?

gDisorder?

Evidence that Sjögren’s Syndrome is an



















A specific auto-immunogen and pathogenic

antibodies have not been identified Autoantibodies that have been found have

not been shown to have any directpathogenic effects on exocrine tissues

There is substantial circumstantial evidencethat tissue damage is the result ofautoimmunity

Autoimmune Disease

Polyclonal Hypergammaglobulinemia
















B-cell hyper-responsiveness

Marked elevations of IgG Production of rheumatoidfactors

Presence of anti-nuclear antibodies Extractable nuclear antigens Anti-SS-A (Ro) and anti-SS-B (La)

Antibodies are found directed against salivary duct

cells (90% of patients) Primarily against extractable nuclear antigens

Concentration does not correlate with gland destruction

Polyclonal Hypergammaglobulinemia

Other Characteristics





















Elevated sedimentation rates and decreased WBCcounts, as seen in other autoimmune connectivetissue diseases

Specific extended MHC haplotype at a higherfrequency than controls

MHC-encoded proteins

Induction of tolerance to self proteins Selection of the T-cell repertoire Binding and presentation of antigen to T-cells

Other Characteristics

Histopathology




















Mononuclear infiltrate consisting primarily of

T-cells (primarily CD4+

) Host of mediators

Altered cell adhesion molecules expression

Increased HLA class II antigens expression Immunosuppressive therapy often effective

Histopathology

Classical Histopathological Lesion


















Lympho-epithelial lesion affecting the parotidgland

Progressive replacement of the salivary tissue bydense lymphoid infiltrates

Formation of proliferating islands of ductalepithelial cells

Creates well-formed lymphoid follicles typical ofMALT and may give rise to lymphomas of theMALT type as an expansion of monoclonal B-cells

Classical Histopathological Lesion

















SalivaryGland

Structure






Conclusion




Numerous changes in immune factors in

Sjögren’s Syndrome Salivary glands appears as a highly active,

immune-mediated inflammatory sites

Salivary epithelial cells are immunologically-active participants in the disease process

Conclusion














WEGENER

GRANULOMATOSIS






Definition and etiology

Wegener granulomatosis is a rare chronic granulomatousdisease with a probably immunological pathogenesis

Wegener granulomatosis: large ulcer surrounded by an

erythematous zone on the tongue.












Clinical features

• The disease is characterized by necrotizinggranulomatous lesions of the respiratory tract,generalized focal necrotizing vasculitis, and necrotizing

glomerulitis.• The oral lesions are fairly common, and present clinically

as solitary or multiple irregular ulcers, surrounded by aninflammatory zone

• The tongue, palate, buccal mucosa, and gingiva are themost commonly affected areas.

• characteristic hyperplastic gingivitis (strawberrygingivitis).

• heavily inflamed granular exophytic lesions• deep necrotic oral ulceration.



























Laboratory tests

Histopathological examination, detection of antineutrophilcytoplasmantibod ies (ANCA) in the serum.







Differential diagnosis

Malignant granuloma,

tuberculosis,

non-Hodgkin lymphoma,

leukemia,

systemic mycoses,

squamous-cell carcinoma.

















Treatment

A combined regimen with steroids, azathioprine, andcyclophosphamide.








Scleroderma

Scleroderma





Scleroderma

Definition

Scleroderma is a progressive disease that affects theskin and connective tissue.

There are two major forms of the disorder.i. The type known as localized scleroderma mainly

affects the skin.

ii. Systemic scleroderma, which is also called systemicsclerosis, affects the smaller blood vessels andinternal organs of the body.

















Description

Scleroderma is an autoimmune disorder, which meansthat the body's immune system turns against itself.

In scleroderma, there is an overproduction ofabnormal collagen (a type of protein fiber present inconnective tissue).

This collagen accumulates throughout the body,causing hardening (sclerosis), scarring (fibrosis), andother damage.

Scleroderma
















Scleroderma

Raynauds phenomenon is seen as the first symptom.

Chronic multi-system disease characterized by diffuse fibrosis of skin and internalorgans.

Facial involvement results in restricted mouth opening & expressionless (mask-like)face.

Females aged 20-50 years.

Generalized widening of PDL space on oral radiographs.

Association with other autoimmune diseases : LE, RA, Sjögren’s syndrome suggestsautoimmune etiology.

Resricted Mouth opening is another major problem.























Treatment A drug called D-penicillamine has been used to interfere with the

abnormal collagen.

Taking vitamin D and using ultraviolet light may be helpful for localizedscleroderma.

Corticosteroids have been used to treat joint pain, muscle cramps, andother symptoms of inflammation.

The various complications of scleroderma are treated individually.

Raynaud's phenomenon requires that people try to keep their handsand feet warm constantly. Nifedipine is a medication that is sometimesgiven to help control Raynaud's.

Thick ointments and creams are used to treat dry skin. Exercise and massage may help joint involvement; they may also help

people retain more movement despite skin tightening. An exerciseregimen for stretching the mouth opening has been reported to be ahelpful alternative to surgery in managing this condition.


























Diagnosis

Diagnosis of scleroderma is complicated by the fact that

some of its symptoms can accompany other connective-tissue diseases. The most important symptom is thickened or hardened

skin on the fingers, hands, forearms, or face. The person's medical history may also contain important

clues, such as exposure to toxic substances on the job. There are a number of nonspecific laboratory tests onblood samples that may indicate the presence of aninflammatory disorder.


















Systemic Lupus Erythematosus

Systemic Lupus Erythematosus





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Definition

Lupus erythematosus is a chronic immunologically mediateddisease.

Systemic Lupus Erythematosus Criteria (4or more)










or more)

1. Butterfly rash

2. Discoid lupus

3. Photosensitivity4. Oral ulcers

5. Arthritis

6. Serositis

7. Neurologic dis

8. Hematologic dis

9. Renal disorder10. Immunologic dis: LE cell,

anti-DNA, anti-Sm, falsepos STS

11. Anti-nuclear antibody




























Incidence 1:2500

Female: male 10:1

2nd/3rd decade of life

More common and severe in Blacks Skin, kidney, serosal membranes, joints, heart

Many autoantibodies

Failure to maintain self-tolerance





















Etiology Autoimmune.

Clinical features

•Two main forms of the disease are recognized: discoid (DLE)and systemic (SLE).

•Oral lesions develop in 15–25% of cases in DLE and in 30–45% of cases inSLE, usually in association with skin lesions.

•The oral lesions are characterized by a well-defined central atrophic

red area surrounded by a sharp elevated border of irradiating whitishstriae (Fig. ).•Telangiectasia, petechiae, edema, erosions, ulcerations, and white

hyperkeratotic plaques may be seen.




























Laboratory tests

1. Histopathological examination2. Direct immunofluorescence.

Differential diagnosis

I. Lichen planus,

II. geographic glossitis,

III. Speckled

IV. leukoplakia,

V. erythroplakia,

VI. cicatricial pemphigoid,

VII. syphilis.

























Treatment

1. Steroids,

2. antimalarials.






Autoimmune Diseases of the Oral Cavity

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Transcript of Autoimmune Diseases of the Oral Cavity