auto immune disorder seminar

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Dr Nidesh mds pedodontics

AUTO IMMUNE DISORDERS

Contents:
Introduction
Causes
Contributing factors
Organs
Tolerance
Disorders

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 Tolerance
It 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 ag
Many 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 cells
Memory t cells

• Activate cells related to cell mediated
immunity , marcophages, natural
killer cells,Tc cells
T helper cells
• Destroys target cells on contact
Cytotoxic t
cells
• Regulates immune response and
helps maintain tolerance
T regulatory
cells

Immunological tolerance
tolerance
Central
(thymic)
deletion Anergy
Indifferenc
e
ignorance
peripheral
Anergy
Regulatory
cells
Indifferenc
e
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 Antigen
PATHOPHYSIOLOGY
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
Autoantibodies
immune complex formation
immune 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 unknown
Genetics
Hormones
Environment
Greater production of auto
antibodies
• Immune complex formation
Tissue damage

Produce autoantibodies against DNA
Nuclear antigens
Ribosomes
Platelets
Erythrocytes
Leucocytes
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 diseasesDr Nidesh mds pedodontics

 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 scleroderma
Coup de sabre
 One or more slightly elevated
 Depressed cutaneous patches
 White or yellowish
 Surrounded by violaceous haloDr Nidesh mds pedodontics

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 sicca
Xerostomia
Rhuematoid 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
 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 manifestations
Female-male 1.4:1
At 40 years
Skin lesions-small
Angular
Flat toped papules few mm to cm
Early stages-red-reddish purpule or viloceous hue
Later dirty brownish colour develops

Oral manifestations:
 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 cells
Immunofluroscense testing demonstrate IgG with
combinations of C3
IgM in intercellular spaces
Differential diagnosis:
Dermatitis herprtiformis
Erythema multiforme
Bullous lichen planus
Bullous 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

 Oral manifestations:
 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
 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

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