AUTOIMMUNE DISEASES OF THE ORAL CAVITY

AUTOIMMUNITY
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 constituent parts as self leading to an immune response against its own cells and tissues. Bodys own immune system begins to attack normal tissues cells and organs within the body.

AUTO IMMUNE DISEASES

Autoimmune diseases are disorders in which the body's immune system reacts against some of its own tissue and produces antibodies to attack itself.

AUTO ANTIBODIES
Auto antibodies are the antibodies that attack its own cells, tissues, and/or organs. This causes inflammation and damage and it leads to autoimmune disorders.

Functions of the Immune System

Distinguish self from non-self Protect the body from foreign substances or pathogens Hypersensitivity is an inappropriate, exaggerated adaptive response that causes damage to the body Reactions do not occur on the first contact Gell and Coombs described four types

Type I Hypersensitivity
Immediate hypersensitivity IgE mediated Target organs are mucosal surfaces of the GI tract, respiratory tract and conjunctiva Allergic rhinitis, urticaria, atopic dermatitis, asthma, GI sensitivity.

Type II Hypersensitivity

Antibody dependent cytotoxic hypersensitivity IgG, IgM, NK cells and complement Targets are circulating cells Drug reactions, Goodpastures, pemphigus, myasthenia gravis, Lambert-Eaton, hemolytic disease of the newborn

Type III 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 IV 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 Crohns

Autoimmune Diseases
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

Mechanisms of Autoimmune Disease (Loss of self-tolerance)

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)

TYPES OF AUTOIMMUNE DISEASES

AUTO-IMMUNE BULLOUS DISEASES OF THE ORAL MUCOSA EPIDERMOLYSIS BULLOSA LICHEN PLANUS RECURRENT APTHOUS STOMATITIS ERYTEMA MULTIFORME SJOGRENS SYNDROME SCLERODERMA WEGENER GRANULOMATOSIS SYSTEMIC LUPUS ERYTHEMATOSUS

Auto-immune Bullous Diseases of the Oral Mucosa

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

i. ii.
i. ii. I. II.

situated inside of the epithelium : intra-epithelial bulla beneath the epithelium : sub-epithelial bulla
between adjacent keratinocytes ( intra-epithelialbullae ) in the basement membrane zone ( sub-epithelial bullae ) vesicles : smaller, due to necrosis or collected oedema pustules : variable size and structure, and contain pus

due to loss of cohesion and separation

Bullae are different from

intraepithelial bulla

subepithelial bulla

PEMPHIGUS VULGARIS

Autoimmune disease. Common in Ashkenazi and Mediterranean jews . Middle aged females. Other variants are: Pemphius Vegitans Pemphigus Foliaceus & Erthematosus Paraneoplastic pemphigus.

PEMPHIGUS VULGARIS

CLINICAL FEATURES:
Painful ulcers or bulla are formed which are fluid filled. 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.The ulcer may look like an apthous ulcer or may be large map 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 Nikolskys 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 these tonofilament complex ,resulting in the loss of attachment 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 is released by these antibodies . The cell to cell break down also takes place through a complement system but this process 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 cell loose there polyhedral morphology rather they are small rounded and contain hyper chromatic nuclei called the TAZANK CELLS.

PEMPHIGUS VULGARIS
histology

PEMPHIGUS VULGARIS
histology

PEMPHIGUS VULGARIS
tazank cells

PEMPHIGUS VULGARIS
immunoflorecence

PEMPHIGUS VULGARIS

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.

PEMPHGOID

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 in the later stages

PEMPHGOID

Mucous membrane pemphigoid (cicatricial) CIKATRI-CIAL Bullous pemphigoid

Bullous Pemphigoid
Bullous pemphigoid (BP) is a rare autoimmune subepidermal bullous disease primarily affecting the elderly population after 60 years of age. Males are equally as affected as females. In many cases, the cause of BP is suspected to be medications. BP is mediated by the formation of autoantibodies binding to bullous pemphigoid antigens 230 and 180, cytoplasmic and transmembrane portions hemidesmosomes of basal cells in the epidermis. IgG autoantibodies are found in circulation and bound to the lamina lucida layer of the basement membrane. These antigen-antibody complexes trigger the release and activation of complement with leukocyte chemotaxis and subsequent degranulation. The release of proteolytic enzymes results in the degradation of the BMZ with separation of the epidermis from the dermis.

 The presentation of BP is commonly oral blisters (24%), and is usually transient. Initially there may be a localized erythematous plaque which may be pruritic, 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 same histologic and immunologic characteristics of BP.

I. II.

The diagnosis depends on skin biopsy. 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 other bullous diseases. V. Circulation IgG antibodies targeting the BP230 and BP180 antigens found in BP. VI. Mortality at 1 year is near 19% with treatment.

 Treatment of BP is dependent on the extent and severity of disease. Tetracycline, minocycline, or erythromycin with or without niacinamide has indicated excellent clinical response 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 in generalized BP

Mucous Membrane Pemphigoid (Cicatricial Pemphigoid)

Mucous membrane pemphigoid (MMP), or cicatricial pemphigoid, is a rare chronic immune-mediated disease characterized by blistering, ulcers, and scarring. This disease usually affects adults from the age of 40 to 60 and there is found in twice as often in woman than men. It results from the production of autoantibodies against antigens within the basement membrane zone of the lamina lucida.

CLINICAL FEATURES(MMP) Oral mucosa is the first site- lesions are rarely wide 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 lesion edge that includes ulcerated and nonulcerated portions. Hematoxylin and eosin staining typically indicates separation of the mucosal epithelium from the underlying tissue at the level of the lamina lucida between the basal cell layer and the lamina densa. Definitive diagnosis requires clinical correlation with direct immunofluorescence findings. There are linear deposits of one or a combination of IgG, IgA, and C3 at the basement membrane zone in a continuous and homogeneous pattern. MMP may be distinguished histologically from pemphigus by the location of blisters.

 Treatment for MMP may be treated topically by debridement of necrotic tissue and oral rinses of hydrogen peroxide, Elixir of dexamethasone, and elixir of diphenhydramine (diluted 1:4 or 1:6 with water. Before meals, hydrogen peroxide rinse with diphenhydramine may be used for cleaning and reducing pain. Fluocinonide gel is an alternative and is adherent to ulcers with better patient compliance than triamcinolone in Orabase. A soft acrylic appliance may be used when there is gingival involvement. Intralesional steroids may be injected into oral cavity lesions

 CASCADEOF EVENTS Antibody 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

EPIDERMOLYSIS BULLOSA

Definition: 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.

EPIDERMOLYSIS BULLOSA
MAJOR CATEGORIES OF EPIDERMOLYSIS BULLOSA Type Hereditary Simplex Junctional Dystrophic Acquired Acquisita None/autoimmune sublamina densa type VII collagen Genetic Pattern Autosomal dominant autosomal recessive autosomal dominant Separation Level Intraepithelial lamina lucida sublamina densa Defec. Structure linking proteins anchoring filaments type VII collagen

EPIDERMOLYSIS BULLOSA

HEREDITARY TYPES:

Congenital absence of components

ACQUIRED TYPES: Autoantibodies (IgG; sometimes IgA) to type VII collagen.

EPIDERMOLYSIS BULLOSA

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 Teeth not affected; intraoral blisters seen Appears during infancy

EPIDERMOLYSIS BULLOSA

EPIDERMOLYSIS BULLOSA
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

EPIDERMOLYSIS BULLOSA

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 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

Epidermolysis Bullosa Acquisita Non-hereditary form; appears in adulthood Clinically resembles autosomal dominant type of JEBtype 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

EPIDERMOLYSIS BULLOSA

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

EPIDERMOLYSIS BULLOSA

EPIDERMOLYSIS BULLOSA
MANAGEMENT No specific treatment available for hereditary types Acquired form maybe treated with corticosteroids and immuno-suppressants Maintenance of pts nutritional and oral hygiene status Wound healing techniques Prevention of infections Systemic use of Phenytoin (also acts as a collagenase inhibitor)

Linear IgA Disease

Linear IgA is an acquired blistering disorder without a definitive cause. There are two clinical types:
I. II. chronic dermatosis of childhood occurs in the first ten years, 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.)

 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 be present. 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. Vesicular lesions may become confluent and form large bullae, and finally burst leaving ulcerated areas.

Clinical Features

Linear IgA Disease

Findings
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 disease process. Gluten sensitivity has been found in one quarter to one third of affected patients. Other associated diseases include rheumatoid arthritis, ulcerative colitis, immune glomerulonephritis, and malignancy including lymphoma.

Linear IgA Disease

Diagnosis
Diagnosis of linear IgA disease depends upon biopsy of perilesional areas with immunofluorescence. Histologic appearance may indicate microabscesses and infiltration of eosinophils in the superficial corium. There may also be few lymphocytes present surrounding small vessels. A homogeneous deposition of IgA, and possibly C3, is present along 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 tissue papillae.

Treatment

Linear IgA Disease

Treatment of linear IgA disease may require combination therapy. Topical and systemic steroids often do not effectively control this disease alone. Dapsone, adult dosing 25-150 mg daily, is effective in most cases for controlling symptoms of burning and itching,

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.

Lichen Planus
variable and present as white striations (Wickham striae), white papules, white plaques, erythema (mucosal atrophy), erosions (shallow ulcers), or blisters. The lesions predominantly affect the buccal mucosa, tongue, and gingivae, although other oral sites are occasionally involved. a T-cellmediated autoimmune disease in which autocytotoxic CD8 + T cells trigger the apoptosis of oral epithelial cells Slightly increased risk of oral SCCa

 Chronic disease of skin and mucous membranes Destruction of basal cell layer by activated lymphocytes Reticular: fine, lacy appearance on buccal mucosa (Wickmans striae) Hypertrophic: resembles leukoplakia Atrophic or erosive: painful

Lichen Planus

1. Spider web. 2. The buccal mucosa involved most often 3. reticular form most common

Reticular Oral Lichen Planus

Lichen planus

Lichen Planus
A very high power view of the dermoepidermal junction Civatte bodies (arrows), keratinocyte enlargement, and coarse collagen bundles are illustrated.

 Lichen planus (LP) is a self-limited disease that usually resolves within 8-12 months. Mild cases can be treated with fluorinated topical steroids. More severe cases, especially those with scalp, nail, and mucous membrane involvement, may need more intensive therapy.

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 secondary infections. Symptomatic analgesics, antipyretics, antihistamines.

RECURRENT APTHOUS STOMATITIS

Recurrent Aphthous Stomatitis(RAS)

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 apthous stomatitis

ETIOLOGY
The 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 the cause. 1.Immunological factors 2.hereditary factors 3.Microbiological factors 4.Emotional stress 5.Nutritional deficiencies 6.Allergic disorders. 7.Hematalogical factors. 8.Gastrointestinal factors

Recurrent Aphthous Stomatitis(RAS)

CLINICAL FEATURES
Minor aphthae:
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 Heal completely in 7-10 days without scarring

Recurrent Aphthous Stomatitis (RAS)

Minor apthae

Recurrent apthous stomatitis

minor apthous ulcers

Recurrent apthous stomatitis

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.

Recurrent Aphthous Stomatitis (RAS)

Major apthae

Recurrent apthous stomatitis

major apthous ulcers

Recurrent apthous stomatitis

HERPETIFORM ULCERATION
Multiple small pinhead size .Each ulcer1-2 mm in size. Can occur at any part of the oral cavity and as many as hundreds of small ulcers may be present. The ulcers are present in the form of clusters or corps and sometime these are joined together to form a very large ulcer. They also heal with scarring. Recur in less than a month time. Associated with extreme pain and discomfort.

Recurrent apthous stomatitis

herptiform ulcer

Recurrent apthous stomatitis

HISTOPATHOLOGY(minor ,major, herptiform)

Mononuclear cells are found in the submucously in the pre ulcerative stage These mononuclear cells are the T-4 lymphocytes and are soon out numbered to T-8 lymphocytes as the ulcerative stage develops. Macrophages and the mast cells are also present at the base of the ulcer.

Recurrent apthous stomatitis

TREATMENT(Minor,Major,herptiform)

Minor apthous ulcers require no treatment only topical gels are used to minimize the pain ,as the ulcer is self limiting and heals with in7-10 days Anti inflammatory gels and mouth washes are also used to prevent any further infection and to control the inflammation 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 shown promise

Sjogrens Syndrome

Sjogrens 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 by fibrosis (or hardening), vascular alterations, and autoantibodies. Polymyositis: many muscle inflammation.

Polyarteritis: a serious blood vessel disease in which small and

medium-sized arteries become swollen and damaged

Sjogrens Syndrome
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%

Sjogrens Syndrome

xerostomia and xerophthalmia

Sjgrens Syndrome
Chronic autoimmune disorder Major clinical manifestations resulting from changes in exocrine glands

Forms of Sjgrens Syndrome

Primary Sjgrens is characterized by inflammatory cell involvement of both the salivary and lacrimal glands Secondary Sjgrens includes other defined connective tissue disease Causes are unknown

Features of Sjgrens 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 Sjgrens Syndrome an Autoimmune Disorder?

Described as an autoimmune exocrinopathy (Strand

and Talal, 1980)

Grouped with other connective tissue diseases

Rheumatoid arthritis Systemic lupus erythematosis (SLE)

What is the evidence that it is an autoimmune disease?

Evidence that Sjgrens Syndrome is an Autoimmune Disease

A specific auto-immunogen and pathogenic antibodies have not been identified Autoantibodies that have been found have not been shown to have any direct pathogenic effects on exocrine tissues There is substantial circumstantial evidence that tissue damage is the result of autoimmunity

Polyclonal Hypergammaglobulinemia

B-cell hyper-responsiveness Marked elevations of IgG Production of rheumatoid factors 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

Other Characteristics

Elevated sedimentation rates and decreased WBC counts, as seen in other autoimmune connective tissue diseases Specific extended MHC haplotype at a higher frequency 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

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

Classical Histopathological Lesion

Lympho-epithelial lesion affecting the parotid gland Progressive replacement of the salivary tissue by dense lymphoid infiltrates Formation of proliferating islands of ductal epithelial cells Creates well-formed lymphoid follicles typical of MALT and may give rise to lymphomas of the MALT type as an expansion of monoclonal B-cells

Salivary Gland Structure

Conclusion

Numerous changes in immune factors in Sjgrens Syndrome Salivary glands appears as a highly active, immune-mediated inflammatory sites Salivary epithelial cells are immunologicallyactive participants in the disease process

WEGENER GRANULOMATOSIS

 Definition and etiology Wegener granulomatosis is a rare chronic granulomatous disease with a probably immunological pathogenesis Wegener granulomatosis: large ulcer surrounded by an erythematous zone on the tongue.

Clinical features
The disease is characterized by necrotizing granulomatous 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 an inflammatory zone The tongue, palate, buccal mucosa, and gingiva are the most commonly affected areas. characteristic hyperplastic gingivitis (strawberry gingivitis). heavily inflamed granular exophytic lesions deep necrotic oral ulceration.

Laboratory tests Histopathological examination, detection of antineutrophil cytoplasmantibod 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, and cyclophosphamide.

Scleroderma

Scleroderma

Definition Scleroderma is a progressive disease that affects the skin and connective tissue. There are two major forms of the disorder.
i.

ii.

The type known as localized scleroderma mainly affects the skin. Systemic scleroderma, which is also called systemic sclerosis, affects the smaller blood vessels and internal organs of the body.

Description Scleroderma is an autoimmune disorder, which means that the body's immune system turns against itself. In scleroderma, there is an overproduction of abnormal collagen (a type of protein fiber present in connective tissue). This collagen accumulates throughout the body, causing hardening (sclerosis), scarring (fibrosis), and other damage.

Scleroderma

Raynauds phenomenon is seen as the first symptom. Chronic multi-system disease characterized by diffuse fibrosis of skin and internal organs. 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, Sjgrens syndrome suggests autoimmune 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 localized scleroderma. Corticosteroids have been used to treat joint pain, muscle cramps, and other symptoms of inflammation. The various complications of scleroderma are treated individually. Raynaud's phenomenon requires that people try to keep their hands and feet warm constantly. Nifedipine is a medication that is sometimes given 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 exercise regimen for stretching the mouth opening has been reported to be a helpful alternative to surgery in managing this condition.

Diagnosis Diagnosis of scleroderma is complicated by the fact that some of its symptoms can accompany other connectivetissue 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 on blood samples that may indicate the presence of an inflammatory disorder.

Systemic Lupus Erythematosus

Systemic Lupus Erythematosus

Definition
Lupus erythematosus is a chronic immunologically mediated disease.

Systemic Lupus Erythematosus Criteria (4 or more)

1. 2. 3. 4. 5. 6. Butterfly rash Discoid lupus Photosensitivity Oral ulcers Arthritis Serositis 7. 8. 9. 10. Neurologic dis Hematologic dis Renal disorder Immunologic dis: LE cell, anti-DNA, anti-Sm, false pos 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 1525% of cases in DLE and in 3045% of cases in SLE, 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 whitish striae (Fig. ). Telangiectasia, petechiae, edema, erosions, ulcerations, and white hyperkeratotic plaques may be seen.

Laboratory tests
1. 2. Histopathological examination Direct immunofluorescence.

Differential diagnosis
I. II. III. IV. V. VI. VII. Lichen planus, geographic glossitis, Speckled leukoplakia, erythroplakia, cicatricial pemphigoid, syphilis.

Treatment
1. Steroids, 2. antimalarials.