Autoimmune Diseases of The Oral Cavity
Autoimmune Diseases of The Oral Cavity
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.
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.
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 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
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
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
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
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 (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
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:
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 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
Treatment
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
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
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.
Most common ulcerative lesion of oral cavity Recurrent, painful ulcers Confined to soft mucosa Subdivided into three types:
Minor aphthae Major aphthae Herpetiform aphthae
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
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.
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
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
Sjgrens Syndrome
Chronic autoimmune disorder Major clinical manifestations resulting from changes in exocrine glands
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
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
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
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.
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.
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.