auto immune disorder seminar

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AUTO IMMUNE DISORDERS


Contents:

IntroductionCausesContributing factorsOrgansToleranceDisorders


Autoimmunity Breakdown of mechanisms responsible for self tolerance and

induction of specific adaptive immune response against components of the self.

Condition in which structural or functional damage is produced by action of immunological component cells or antibodies against the normal components of the body


Earliest example by

Metalnikoff(1900)

Ehrlich (1901)- “horror autotoxicus”

Donath and landsteiner-circulating auto antibodies in paroxysomal cold hemaglobinema

This is first description of an auto immune disease in human beings.


Dameshek and schwartz(1938) established the autoimmune basis of acute hemolytic anemia

The term auto immune disease is to those where autoimmune process , humoral or cellular are shown to be responsible for pathogenesis.


Sequestered or Hidden antigens

Neo antigens

Cessation of ToleranceIt may result when tolerance to the self-Ag is aborted.

Causes of autoimmune diseases

Loss of Immunoregulation

Loss of Self tolerance - caused by over activity or lowered activity of T and B- cells


Cross reacting Antigens

A foreign Ag which resembles self a agMany species share organ specific Ags.

E.g. Ag of Human brain & Ag of sheep brain, Streptococcal M protein & Heart muscles, Nephritogenic strains of Streptococci Ags & Renal glomeruli shares similar epiotes.


Contributing Factors

Defects in the immune system

Influence of hormones

Environmental conditions


Immunity

The lymho reticular system is a complex organisation of cells of diverse morphology distrubuted widely in different organs and tissues of the body responsible for immunity

Lymphoreticular cells consists of

Lymhoid Reticuloendothelial component

Lymphoid cells-lymphocytes Plasma cells

Specific immune response


Reticuloendothelial system

Phagocytic cells- scavenger functions of eliminating effete cells and foreign particles Non specific immunity removal of microorganisms from

blood and tissues

The functional component of lymphoid system are

Humoral or antibody mediated immunity(AMI)

Cellular or cell mediated immunity(CMI)- sensitized lymphocytes


Humoral immunity-mediated by plasma cells

Lymphoid system lymphoid organs- central(primary)-thymus bone marrow

peripheral(secondary)-lymph nodes Spleen Lymphoid cells


Thymus


Digeorge syndrome- deficient cmi seen in congenital aplasia of thymus

T lymphocytes develop in thymus

B lympho cytes develop in bone marrow

RUNT disease-

Lymphopenia deficient graft rejection

neonatally thymectomised mice


Lymphoid cells appear in spleen in 20th week of gestation

Then fetus produces igM and igD

It receives maternal igG



Lymph node functions:

As a filter for lymph , each of nodes draining a specific part of body

Functions- Phagocytose foreign materials including microorganisms In proliferation and circulation of t and b cells


Spleen:


The resources such as iron hemoglobulin are recycled serving as strong case for renaming this as green pulp

Functions

its graveyard

Reserve tank and settling bed for blood and as a systemic filter for trapping circulating blood borne foreign particles

Primarly directed against blood borne antigens


Lympho-reticular system

According to their size-

Classified into

Small(5-8um)(numerous) Medium(8-12) Large(12-15)

Based on life span

Short lived-2 weeks Long lived-3 years or more


B lymphocyte T lymhocytes

B lymphocytes-

Differentiated by their synthesis and display of membrane bound immunoglobulin(antibody)which serves as recepter for antigen

During binding of antigen to anyibody cells divide rapidly into

Effector cells/plasma cells Memory b cells Plasma cells produce antibodies


T lymphocyte

During maturation t cells exhibit unique antigen antibody molecule called t cell receptor

T cell receptor only recognize the antigen that is bound to cell membrane called MHC

Proliferates and differentiate into effector t cellsMemory t cells


• Activate cells related to cell mediated immunity , marcophages, natural killer cells,Tc cells

T helper cells

• Destroys target cells on contactCytotoxic t

cells

• Regulates immune response and helps maintain tolerance

T regulatory cells




Immunological tolerance

tolerance

Central (thymic)

deletion Anergy

Indifference

ignorance

peripheral

Anergy Regula

tory cells

Indifference

ignorence



Diseases of auto immune origin usually exhibit the following features:

An elevated level of immunoglobulins Demonstrable autoantibodies Accumulation of lymphocytes and plasma cells at the site of

lesions The occurrence of more than one type of autoimmune lesion in

an individual A genetic predisposition towards autoimmunity Incidence higher among females Chronicity. Usually non reversible Benefit from corticosteroid or other immunosuppressive therapy


Sequestered AntigenPATHOPHYSIOLOGY

Organ damage

Hidden antigen released

Reaches blood stream

Encounters antigen sensitive cells

Stimulate auto immunity


Altered Antigen

Surface antigens on host altered by chemical, biological or physical means.

This new antigenic determinant may be recognized as foreign by the host.

Loss of immunoregulation

Loss of Self tolerance – caused by over activity or lowered activity of T and B- cells



Systemic Lupus Erythematosus

Autoimmune disease characterized by Autoantibodiesimmune complex formationimmune dysregulation resulting in damage to kidney, skin, blood cells and CNS.

Because of its protien manifestations lupus must be considered in the differential diagnosis of many problems.


Etiology

Specific etiology is unknownGeneticsHormones Environment

Greater production of auto antibodies

• Immune complex formation

Tissue damage


Produce autoantibodies against DNA Nuclear antigensRibosomesPlateletsErythrocytesLeucocytes Other tissue specific antigens


Clinical Manifestations

Serious cutaneous – systemic disorder with repeated remissions and exacerbations.

Females – 30 years Males – 40 years

Female to male ratio 2:1 Before and after puberty-4:1


Also involves neck upper arms shoulders fingers

The generalized manifestations involve various organs including kidney and heart.

Collagen diseases


Rheumatic fever Rheumatoid arthritis Polyarteritis nodosa Scleroderma Dermatomyositis

kidney – Fibrinoid thickening of Glomerular capillaries (wire loops)

Heart – Atypical Endocarditis and fibrinoid degeneration



Oral manifestations

Oral mucous membrane - 20-50% Bleeding Petechiae Superficial ulcerations –result of localized telangiectasie

Superimposed Oral Moniliasis Xerostomia are reported.


DIAGNOSIS

Anemia Leukopenia Thrombocytopenia Elevated sedimentation rate LE cell inclusion phenomenon Formation of gamma globulin of serum Elevation of ESR with normal C reactive protein levels Detection of antinuclear antibodies (anas)


Treatment

Carefull and frequent clinical and laboratory evaluation – corner stone of successful intervention.

Corticosteriods are Useful in controlling disease flares.

When symptomatic oral lesions present- potent topical steroids such as

Clobetasol Propionate gel – 0.05% Betamethasone dipropionate- 0.05% 2-3 times daily Fluticazzone propionate spray – 50 microgms


For severe : a pulse IV Cyclophosphamide

Other less toxic agents such as Mycophenolate mofetil (MMF) and Azathioprine has been shown to possess efficacy equivalent to that of quaterly Cyclophosphamide with fewer side effect.

NSAIDS are used for sympotomatic relief in arthritis.


A complete blood count(CBC) is obtained prior to treatment.

Elective oral surgical procedures with potential of Bacteremia is delayed.

Prophylactic antibiotics is often recommended if neutrophilic count falls below 500-1000cells/mm3.

Platelet transfusion recommended in surgical patients with platelet count <50000cells/mm3 .

Dental management


Systemic sclerosis

Scleroderma, Dermatosclerosis, Hidebound disease

Is a systemic connective tissue disease characterized by vasomotor disturbances

Fibrosis Subsequent atrophy of the skin Sub cutaneous tissue Muscle Internal organs including alimentary tract,heart , lungs, kidney,

gastrointestinal tract.


Etiology

Unclear etiology.

Genetic Environmental vascular factors

Human leukocyte antigens likeHLA-B8, HLA-DR5, HLA-DR3,HLA-DR52 and HLA-DQB2.


Apoptosis and generation of free radicals may be involved in pathogenesis

Increased collagen deposition in tissues is a characteristic feature of systemic sclerosis


Clinical features

begin in children or young adults.

30 and 50 years Females>males

Ultimate induration of the skin and fixation of the epidermis to the deeper subcutaneous tissues.


Usually begins on the face Hands or trunk simultaneously with the development of the

early typical indurated oedema of the skin Neuralgia Paresthesia Arthritis Pigmention of skin Erythema accompaines these cutaneous changes Skin takes on yellow,gray/ivory white waxy appearnce Deposition of calcium in affected areas is also found.


Involves many internal organs by fibrosis most frequently involving GIT, lungs, CVS, muscoskeletal system and CNS.

One variant of systemic sclerosis is crest syndrome.


Circumscribed scleroderma / morphea

Circumscribed scleroderma on sides of chest and thighs

Linear sclerodermaCoup de sabre

One or more slightly elevated Depressed cutaneous patches White or yellowish Surrounded by violaceous halo


Oral manifestations:

Tongue, soft palate and larynx are mostly involved. Early mild edema followed by atrophy and induration of

mucosa and muscular tissues

Microstomia , “mouse fascies”


•Gingival recession •Dysphagia •hypomobile (board like ) tongue•Reduced mouth opening and fixation of jaw•Xerostomia

Alarcon-segovia-sjorgen disease with Lymphocyte infiltration Duct cell proliferation Collagen infiltration

Weisman and calcatena-alterations in salivary gland functions-sicca syndrome


Radiographic findings

Extreme widening of periodontal ligament space

Bilateral bone resorption of the angle of mandibular ramus.

Partial or complete resorption of condyles or coronoid process.


Early diagnosis and treatment are advised.

Calcium channel blockers

D- penicillamine

Cyclophosphamide

Angiotensins

Treatment


Dental management

Most common problem is physical limitation of oral aperture.

Stretching Exercises Tongue Blades Bilateral Commissurotomy

Customized tooth brush handles should be provided for patients who cannot grip.


Rheumatoid Arthritis

Commonly begins in early adult life

Women>men 2:1 Hypersensitivity reaction to bacterial toxins

specifically streptococci Poly articular disease

Its symptoms include fatigue Weight loss Morning stiffness Low grade fevers Anemia.


Subtypes:

Juvenile rheumatoid arthritis children < 16 years Joint stiffness Decreased range of motion, Pain on range of motion Joint warmth for atleast 6 weeks without another cause.


Systemic (still’s disease): characterized by joint swelling, fever, rash, and organ involvement

Early stages may be manifested by slight fever, loss of weight and fatigability.

The joints affected are swollen.

Movement of the jaw as during mastication or talking causes pain and may be limited because of stiffness.

Clinical features


Severe cases ankylosis of tmj

Stills disease : class ii div i malocclusion, anterior open bite

Deformation of the mandible characterized by shortening of the body and reduction in the height of the ramus due to failure of growth center in the condylar area


Radiographic findings: flattening and stunting of condyle

Haziness about joint-periarticular fibrosis


Is a symmetrical polyarthritis often involving proximal inter phalangeal joints of the fingers and metacarpophalengeal joints of the hands: the wrists, elbows, knees and ankles also can be affected.


The treatment of causes oral manifestations, the long term use of Methotrexate and other anti rheumatic agents such as D- pencillamine and NSAIDS can cause Stomatitis.

Minocycline may cause hyperpigmentation intraorally,

Oral manifestations


Gingival overgrowth in patients taking Cyclosporine,

Prednisone and TNFa blocking therapy may predispose patient to development of opportunistic infections.


Dental management

When treating RA patient it is important to understand the Mechanism of action Side effects Drug interactions of the current medications


Sjogrens syndrome

Sicca syndrome/ gougerat-sjogren syndrome

Primary Sjogrens Syndrome – Dry eyes & Dry mouth Secondary Sjogrens Syndrome – SLE Polyareritis Nodosa Polymyositis Scleroderma Rheumatoid arthritis

Keratoconjunctivitis siccaXerostomiaRhuematoid Arthritis


Etiology

Genetic Hormonal Infectious immunological or combination of factors play a role in the

etiology of this condition.

Most consider an altered immunological response to be the main intrinsic factor which is responsible for the disease.

Primary form-HLA-DR3,HLA-B8 Hla-drw52 for both Sera anti salivary duct antibody


Clinical manifestations:

Predominantly in women over 40 years of age.

Female to male ratio is 10:1 Typical features are dryness of the mouth and eyes Various secretory glands of the nose, larynx, pharynx,

tracheobronchial tree are involved with this dryness Xerostomia Elevated levels of IgA,Potassium,sodium in saliva

80% primary Sjogrens syndrome have parotid enlargement

14% secondary Sjogrens syndrome have parotid enlargement Lymphadenopathy


Radiographic findings

Sialography may be of diagnostic value in Sjogrens syndrome.

They demonstrate ‘cherry blossom’ or ‘ branchless fruit laden tree’ effect.


Treatment

Most patients are treated symptomatically

Occular lubricants – methylcellulose – to treat keratoconjunctivitis sicca

Saliva substitutes – to treat xerostomia

Extensive dental caries and poor oral hygiene – frequent fluoride application.

Surgery and radiation therapy has been recommended to treat enlarged salivary glands.


A major complicating factor is development of the pseudolymphoma and malignant lymphoma.

The risk of lymphoma [non hodgkins] in sjogrens syndrome patients is 6.4 cases for 100 cases.


Reiter’s syndrome

Unknown etiology associated with urethritis Calanitis Conjuctivitis Mucocutaneous lesions

It is a complication of nonspecific urethritis and clinically mimics gonorrhea.

Pleura-pneumonia like organisms have been implicated and Mycoplasmal and Chlamydial species have also been suspected.

HLA-B27 Recent evidence suggests that this condition is also seen

frequently in HIV patients.


Clinical features

More prevalent in young adult men , usually between 20-30 years of age.

The male to female ratio is 9:1

Tetrad of manifestations Non Gonococcal urethritis Arthritis Conjunctivitis Mucocutaneous Lesions


Oral manifestations Lesions are painless, red , slightly elevated areas, sometimes

granular or even vesicular with a white circinate border on the buccal mucosa, lips,and gingiva.

Lesions on the tongue closely resemble Geographic tongue


Diagnosis Mild leucocytosis Elevated sedimentation rate pyuria

Treatment:

The disease may undergo spontaneous remission but has been treated by antibiotics and corticosteroids.


Oral Lichen Planus

lichen ruber planus It is a common mucocutaneous disease. Effects skin or mucosa or both

It can cause bilateral white striations, papules, or plaques on the buccal mucosa, tongue and gingiva.

The involvement of the oral mucous membrane is so frequent


Etiology:

T cell mediated autoimmune disease in which cytotoxic CD8+T cell trigger the apoptosis of oral epithelial cells.

The expression of the lichen planus antigen may be induced by drugs - Lichenoid Drug Reaction

Association of lichen planus, diabetes mellitus and vascular hypertension has been described as Grinspans Syndrome.


Clinical manifestationsFemale-male 1.4:1At 40 yearsSkin lesions-small AngularFlat toped papules few mm to cmEarly stages-red-reddish purpule or viloceous hueLater dirty brownish colour develops



Radiating white or gray velvety threadlike papules in a linear, annular or retiform arrangements forming typical lacy reticular patches , rings and streaks.

Tiny white elevated dot is frequently present at the intersection of white lines known as Wickhams Straie


These oral lesions produce no significant symptoms, although some patients complain of burning sensation.

Different forms are Plaque like, Bullous form Erosive form Atropic form – chronic desqumative gingivitis Hypertropic form

Oral manifestations occur weeks or months before the appearance of the skin lesions.


Differential diagnosis:

Lichenoid reaction Leukoplakia Candidiasis Pemphigus Cicatrial pemphigoidsyphilis Lupus erythematosus

Malignant transformation

Higher incidence of oral squamous cell carcinoma 0.3% to 3% Erosive and atropic forms mostly undergo malignant

transformation.


Treatment:

At present there is no cure,

Potential for malignant transformation is minimal, these patients kept on long term follow-up.

Principal aim is resolution of the painful symptoms, the lesion, reduction of risk of cancer, and maintenance of good oral hygiene.

Corticosteroids are recommended


Psoriasis

Noncontagious skin disorder Inflamed edematous skin lesions covered with a silvery white scale.

Most common type is plaque psoriasis Nails are pitted/thickened


The trigger event is unknown, but is an immunological event, significant evidence of autoimmunity is present.

Genetic predisposition

Lesions of psoriasis are associated with increased activity of T cells in underlying skin.

Perceived stress

Etiology


Clinical features: Of skin, is characterized by occurrence of small sharply defined

delineated dry papules each covered by a delicate silvery scale .

If the deep scale is removed , tiny bleeding point is disclosed a characterstic feature termed – Auspitz’s sign


Oral manifestations

Involvement of oral mucosa is rare.

A study by buchner found none with oral lesions of dermal psoriasis patients, however they did note 11%had angular cheliosis, 6% fissured tongue, 5% benign migratory glossitis.

They are yellowish-white plaques, as silvery white scaly lesions with erythematous base .Or as multiple papular eruptions which may be ulcerated


Psoriasiform lesions of oral mucosa-

Psoriasis Reiters syndrome Benign migratoey glossitis Ectopic geographic tongue


Treatment:

Lesions are benign but few cases are refractory to treatment.

Treatment include UV-light , Psoralen plus UV-A light(PUVA), Retinoids, methotrexate, cyclosporine.


Pemphigus vulgaris

Is an autoimmune intraepithelial blistering disease Skin and mucous membrane Mediated by circulating IgG autoantibodies directed against

keratinocyte cell surface.

Effects all races with equal gender prediction and mean age of onset is 50-60 years


Oral lesions – 1st sign of this disease

Characterized by rapid appearance of the vescicles and bullae, varying in diameter from milimetrs to several centimetres.

These lesions contain thin watery fluid shortly after development, but may soon become purulent

Nikolsky’s Sign

Clinical features


The disease involves mucosa in 50-70% of patients

Patients have ill defined irregularly shaped gingival buccal or palatine erosions which are painful and slow to heal.

Erosions extend peripherally with shedding of epithelium, and may spread to involve larynx with subsequent hoarseness.

Other mucosal surfaces may be involved including conjunctiva, oesohagus, cervix.

Oral manifestations



Diagnosis:

Tzanck cellsImmunofluroscense testing demonstrate IgG with combinations of C3IgM in intercellular spaces Differential diagnosis:

Dermatitis herprtiformisErythema multiformeBullous lichen planusBullous pemphigoid


Treatment:

Systemic Corticosteroids – main stay of treatment- 1-2mg/kg/day

Adjuvants – immunosuppresive drugs- mycofenolate mofetil, azathioprine, cyclophosphamide


WEGNER’ S GRANULOMATOSIS

Immunologically mediated multisystem disorder Vascular, renal and respiratory systems.

It involves nose paranasal air sinuses lower respiratory tract Gut Joints Nervous system and kidneys. Etiology:

It may be caused by an abnormal immune reaction secondary to a nonspecific infection or a hyper sensitivity reaction to an unknown antigen.


Clinical features

Classic type renal + respiratory lesions Limited type only respiratory lesions Superficial type only skin and mucosal lesions At any age 4th and 5th decades Male>females Rhinitis Sinusitis Otitis Occular symptoms

Straw berry gingivitis



Ulcerative Friable Granular lesions Simple enlargments of gingiva

Inflammation starts in interdental papilla,spreads to periodontal structure

Leads to bone loss and tooth mobility


Diagnosis:

Anemia Leucocytosis Elevated sedimentation rate hyperglobulinemia


Treatment

Majority of cases of wegners granulomatosis formerly terminated fatally.

However to prevent long term remissions cyclophosphamide and prednisolone are recommended.


CONCLUSION

An autoimmune disease develops when our immune system, which defends our body against disease, decides our healthy cells are foreign. As a result, our immune system attacks healthy cells.


Basics and clinical immunology-peakman,vergani-2nd edition

Kuby immunology-6th edition

Ananthanarayan and paniker text book of microbiology – 7th edition

Shafers textbook of oral patholgy -6th edition

Burkitts oral medicine -11th edition

References


Education

auto immune disorder seminar