Auto-immune diseases

AUTOIMMUNE
DISEASES
By,By,
Dr. PriyankaSharmaDr. PriyankaSharma
22ndnd
year MDSyear MDS
Dept. Of Public Health DentistryDept. Of Public Health Dentistry
JSSDental College& HospitalJSSDental College& Hospital11

CONTENTSCONTENTS
IntroductionIntroduction
Definition & ClassificationDefinition & Classification
Affectsof autoimmunityAffectsof autoimmunity
Predisposing FactorsPredisposing Factors
PossibleCausesPossibleCauses
Mechanism of AutoimmunityMechanism of Autoimmunity
Organ specificAutoimmunediseasesOrgan specificAutoimmunediseases
Non-organ specificAutoimmunediseasesNon-organ specificAutoimmunediseases
Recent studiesabout AutoimmunediseasesRecent studiesabout Autoimmunediseases
ConclusionConclusion
References
22

INTRODUCTIONINTRODUCTION
Your immunesystem isthenetwork of cells
and tissuesthroughout your body that work
together to defend you from invasion and
infection.
When an intruder invadesyour body—likeaWhen an intruder invadesyour body—likea
cold virusor bacteriaon athorn that prickscold virusor bacteriaon athorn that pricks
your skin—your immunesystem protectsyou.your skin—your immunesystem protectsyou.
It triesto identify, kill, and eliminatetheIt triesto identify, kill, and eliminatethe
invadersthat might hurt you.invadersthat might hurt you. 33

Theorganism possessespowerfulTheorganism possessespowerful
mechanismsto avoid immuneautoaggression.mechanismsto avoid immuneautoaggression.
But sometimesproblemswith your immuneBut sometimesproblemswith your immune
system causeit to mistakeyour body’sownsystem causeit to mistakeyour body’sown
healthy cellsasinvadersand then repeatedlyhealthy cellsasinvadersand then repeatedly
attacksthem. Thisiscalled an autoimmuneattacksthem. Thisiscalled an autoimmune
disease. (“Autoimmune” meansimmunitydisease. (“Autoimmune” meansimmunity
against theself.)against theself.) 44

Human autoimmunediseases(AD) occur
frequently (affecting in aggregatemorethan
5%-7% of thepopulation worldwide), and
imposeasignificant burden of morbidity and
mortality on thehuman population.
Women aremoreaffected – 2/3rd of the
population.
Morethan 70 human diseasesautoimmunein
origin. 55

DEFINITION &DEFINITION &
CLASSIFICATIONCLASSIFICATION
IMMUNITY - In biology, IMMUNITY - In biology, immunityimmunity isthe isthe
stateof having sufficient biological defencesstateof having sufficient biological defences
to avoid infection, disease, or other unwantedto avoid infection, disease, or other unwanted
biological invasion. biological invasion.
66

Innate immunity, ornonspecific immunity
isthenatural resistanceswith which apersonisthenatural resistanceswith which aperson
isborn. isborn.
Adaptive immunity isoften sub-divided into isoften sub-divided into
two major typesdepending on how thetwo major typesdepending on how the
immunity wasintroduced.immunity wasintroduced.
Naturally acquired immunity occurs occurs
through contact with adiseasecausing agent,through contact with adiseasecausing agent,
when thecontact wasnot deliberate.when thecontact wasnot deliberate.
Artificially acquired immunity develops develops
only through deliberateactions such asonly through deliberateactions such as
vaccination.vaccination.
77

Passive immunity isacquired through
transfer of antibodiesor activated T-cellsfrom
an immunehost, and isshort lived—usually
lasting only afew months.
Active immunity isinduced in thehost itself
by antigen and lastsmuch longer, sometimes
lifelong.
88

According to cell involved
 Humoral immunity istheaspect of immunity that
ismediated by secreted antibodies.
Cell mediated immunity : theprotection provided
by involvesT-lymphocytesalone. 99

Humoral immunityHumoral immunity isis activeactive when thewhen the
organism generatesitsown antibodies, andorganism generatesitsown antibodies, and
passivepassive when antibodiesaretransferredwhen antibodiesaretransferred
between individuals. between individuals.
Cell mediated immunityCell mediated immunity isis activeactive when thewhen the
organisms’ own T-cellsarestimulated andorganisms’ own T-cellsarestimulated and
passivepassive when T cellscomefrom anotherwhen T cellscomefrom another
organism.organism.
1010

Autoimmunediseases-Autoimmunediseases- aretheresult ofaretheresult of
specific immuneresponsesdirected againstspecific immuneresponsesdirected against
structuresof theself (Burnet and Fenner,structuresof theself (Burnet and Fenner,
1949).1949).
ToleranceTolerance - Theacquired ability of the- Theacquired ability of the
immunesystem to avoid responsivenessto selfimmunesystem to avoid responsivenessto self
antigensisdefined as‘tolerance’, and isantigensisdefined as‘tolerance’, and is
obtained by thecooperativeeffortsofobtained by thecooperativeeffortsof central
andperipheralmechanisms, which allow a, which allow a
rapid and efficient removal of pathogens(e.g.rapid and efficient removal of pathogens(e.g.
virusesor bacteria) in theabsenceof self-virusesor bacteria) in theabsenceof self-
recognition.recognition. 1111

Autoimmunediseases, on theother hand,Autoimmunediseases, on theother hand,
originatefrom asustained and persistentoriginatefrom asustained and persistent
immuneresponseagainst self-constituents, andimmuneresponseagainst self-constituents, and
requirearequirea breakdo wn in to lerancebreakdo wn in to lerance ..
Themechanismsresponsiblefor thisThemechanismsresponsiblefor this
breakdown areso far poorly defined.breakdown areso far poorly defined.
1212

CLASSIFICATIONCLASSIFICATION
OFOF
AUTOIMMUNEDISEASESAUTOIMMUNEDISEASES
1313

 Hematological disordersHematological disorders
1)Red blood cells– autoimmunehemolytic anemia1)Red blood cells– autoimmunehemolytic anemia
2)Platelets– Idiopathic thrombocytopenic purpura2)Platelets– Idiopathic thrombocytopenic purpura
 Gastrointestinal diseasesGastrointestinal diseases
1) Stomach – Perniciousanemia1) Stomach – Perniciousanemia
2)Small bowel – Celiac sprue(gluten enteropathy)2)Small bowel – Celiac sprue(gluten enteropathy)
 Dermatologic diseasesDermatologic diseases
1)PemphigusVulgaris1)PemphigusVulgaris
2)Cicatrial Pemphigoid (CP) or mucousmembrane2)Cicatrial Pemphigoid (CP) or mucousmembrane
1616

3) Psoriasis
4) EpidermolysisBullosaAcquisita
5) Oral Lichen Planus(OLP)
6) ErythemaMultiforme
 Hormonal Disorders
1) Pancreatic islets– Type1 diabetes
2) Adrenal cells– Addison’sdisease
3) Thyroid – Hashimoto’sand Grave’sdisease 1717

 Other Organs
1) Muscles- Myastheniagravis1) Muscles- Myastheniagravis
2) Liver :2) Liver :
- Hepatocytes- Autoimmunehepatitis- Hepatocytes- Autoimmunehepatitis
- Bileduct cells– primary biliary cirrhosis- Bileduct cells– primary biliary cirrhosis
3)Heart – Rheumatic heart disease3)Heart – Rheumatic heart disease
4)Kidney/lung- Goodpasture’ssyndrome4)Kidney/lung- Goodpasture’ssyndrome
1818

Systemic auto immune diseases:Systemic auto immune diseases:
1)Ankylosing spondylitis1)Ankylosing spondylitis
2)Multiplesclerosis2)Multiplesclerosis
3)Rheumatoid arthritis3)Rheumatoid arthritis
4)Systemic lupuserythematosus4)Systemic lupuserythematosus
5)Scleroderma5)Scleroderma
6)Sjogren’ssyndrome6)Sjogren’ssyndrome
7)7) Reiter’sSyndromeReiter’sSyndrome
8)8) Behcet’sdiseaseBehcet’sdisease
9)9) Recurrent aphthousstomatitis(RAS)Recurrent aphthousstomatitis(RAS)
1919

TissuedestructionTissuedestruction
Antibodiesblock normal functionAntibodiesblock normal function
AntibodiesstimulateinappropriatefunctionAntibodiesstimulateinappropriatefunction
Antigen-antibody complexesaffect thenormalAntigen-antibody complexesaffect thenormal
functionsfunctions
AFFECTS OFAUTOIMMUNITYAFFECTS OFAUTOIMMUNITY
2020

PREDISPOSING FACTORSPREDISPOSING FACTORS
ADs
2121

POSSIBLE CAUSESPOSSIBLE CAUSES
Releaseof sequesteredAg (Smoking, injury orReleaseof sequesteredAg (Smoking, injury or
infection,surgery)infection,surgery)
Immunestimulation (Microbial infection )Immunestimulation (Microbial infection )
““ Self proteins” circulatewithout having been exposed toSelf proteins” circulatewithout having been exposed to
system (ex: sperm, eyelens, thyroid)system (ex: sperm, eyelens, thyroid)
Inefficient lymphocyteprogrammingInefficient lymphocyteprogramming
Potential Treatmentsgiven for control of inflammation(ex:Potential Treatmentsgiven for control of inflammation(ex:
diabetesmellitus)diabetesmellitus)
ImmunosuppressiveMedication (ex: corticosteriods,ImmunosuppressiveMedication (ex: corticosteriods,
cyclosporin, methotrexate)cyclosporin, methotrexate)
– TherapeuticAntibodiesagainst specific T cell molecules(withTherapeuticAntibodiesagainst specific T cell molecules(with
fewer sideeffects)fewer sideeffects)
2323

MECHANISMSOF
AUTOIMMUNITY
Ag released from hidden location.
Antigen generated by molecular changes.
Molecular mimicry.
Alteration inAg processing.
Infection.
Genetic factors. 2424

Lymphocytesabnormalities.
Failureof central tolerance.
Overcomeof peripheral tolerance.
Polyclonal lymphocytesactivation.
2525

Ag related from hidden location
 Many self Ag arefound in hidden location
eg. C N S,TESTES,EYE (CORNEA)
organ damage
Hidden Ag released
Reaches blood stream
Encounter Ag sensitivecells
Stimulateautoimmunity 2626

Antigen generated by molecular changesAntigen generated by molecular changes
Development of completely new epitopeson normalDevelopment of completely new epitopeson normal
protein. eg RF immuno conglutinine.protein. eg RF immuno conglutinine.
 Mechanism of formation of RF :Mechanism of formation of RF :
Ab + AgAb + Ag
New epitopesexposed on Fc region of AbNew epitopesexposed on Fc region of Ab
Stimulatetheformation of RfStimulatetheformation of Rf
Establishment of diseaselikerheumatiodEstablishment of diseaselikerheumatiod
artheritisand SLEartheritisand SLE
2727

Molecular mimicry
Sharing of epitopesbetween an infectiousagentSharing of epitopesbetween an infectiousagent
and itshost.and itshost.
Antibodiesdirected against theinfectiousAntibodiesdirected against theinfectious
agentsstartsreacting with normal self Ag.agentsstartsreacting with normal self Ag.
Triggersautoimmunity.Triggersautoimmunity.
2828

Alteration inAg processing
A T cell may fail to develop toleranceto
an self Ag simply because it isnot
efficiently procured.
If something happensto improvethe
processing, an autoimmunediseasemay
betriggered.
Thisusually happensat thesiteof
inflamation resulting in modifiedAb.
Eg. Thyrotoxicosis, diabetes.
2929

Infection
Hereautoimmunity isnot dueto infectiousHereautoimmunity isnot dueto infectious
agent itself ,but resultsfrom dis-regulation ofagent itself ,but resultsfrom dis-regulation of
host immuneresponseby themicrobes.host immuneresponseby themicrobes.
Thismay bedueto :Thismay bedueto :
Polyclonal lymphocyteactivation.Polyclonal lymphocyteactivation.
Enhanced stimulation of co-stimulator.Enhanced stimulation of co-stimulator.
Alteration of self Ag(crossreactiveneo-Ag)Alteration of self Ag(crossreactiveneo-Ag)
3030

Genetic Factors
Theimportant genesthat regulatethedevelopment of autoimmunityTheimportant genesthat regulatethedevelopment of autoimmunity
arelocated within MHC.arelocated within MHC.
MHC havegot critical rolein maturation of T cell & induction of IR .MHC havegot critical rolein maturation of T cell & induction of IR .
MHC genesaredirectly responsiblefor auto antigen processing andMHC genesaredirectly responsiblefor auto antigen processing and
presentation.presentation.
Thestructureof Ag binding groove will determine, if specificAgThestructureof Ag binding groove will determine, if specificAg
will trigger anAU response.will trigger anAU response.
Eg. Diabetesmellitusin dog: DLA-A3, A7, A10 and DLA-B4Eg. Diabetesmellitusin dog: DLA-A3, A7, A10 and DLA-B4
SLE: DLA- A7SLE: DLA- A7
POLYARTHRITIS: DLA- A7POLYARTHRITIS: DLA- A7
3131

Lymphocytesabnormalities
Primary abnormalitieseither in B cell or T cell.Primary abnormalitieseither in B cell or T cell.
Sincethesecellsarecritical regulatorsof all IR.Sincethesecellsarecritical regulatorsof all IR.
MHC presentation of all antigenic peptideto theseMHC presentation of all antigenic peptideto these
cellswill bedefective, in casethecellsarecellswill bedefective, in casethecellsare
abnormal.abnormal.
Abnormalitiesin lymphocytescould affect any oneAbnormalitiesin lymphocytescould affect any one
of themechanism that normally maintainsselfof themechanism that normally maintainsself
tolerance.
3232

Failureof central tolerence
Insideprimary lymphoid organ;
 Positiveselection
 Negativeselection (Deletion of self reacting T
cellsin thymuscausing apoptosis).
Failure of central tolerancestartsAU diseases.
3333

Polyclonal LymphocyteActivationPolyclonal LymphocyteActivation
Stimulation of non deleted self reactingStimulation of non deleted self reacting
lymphocytes. Theseareactivated by somelymphocytes. Theseareactivated by some
activators-activators-
LPS- POLYCLONAL B CELL ACTIVATORLPS- POLYCLONAL B CELL ACTIVATOR
BACTERIAL SUPERANTIGEN - POLYCLONALBACTERIAL SUPERANTIGEN - POLYCLONAL
T CELL ACTIVATORT CELL ACTIVATOR
3636

Damage to immunologically
privileged sites can lead to
autoimmunity
3737

AUTOIMMUNE HEMOLYTICAUTOIMMUNE HEMOLYTIC
ANEMIAANEMIA
Autoimmunehemolytic anemia(AHA) isAutoimmunehemolytic anemia(AHA) is
characterized by shortened red blood cellcharacterized by shortened red blood cell
(RBC) survival and thepresenceof(RBC) survival and thepresenceof
autoantibodiesdirected against autologousautoantibodiesdirected against autologous
RBCs.RBCs.
Due to formation of autoantibodies that attackDue to formation of autoantibodies that attack
patient’sown RBC’spatient’sown RBC’s 4040

Often associated with either lymphoOften associated with either lympho
proliferative disease or collagen vascularproliferative disease or collagen vascular
disease.disease.
It is an extravascular type of hemolyticIt is an extravascular type of hemolytic
anemia.anemia.
Two Types:Two Types:
1)1) Warm TypeWarm Type
2)2) Cold TypeCold Type
4141

1.Warm AIHemolysis:
– Can occursat all agegroupsCan occursat all agegroups
– F > MF > M
– Causes:Causes:
50% Idiopathic50% Idiopathic
Rest - secondary causes:Rest - secondary causes:
1.Lymphoid neoplasm: Lymphoma, Myeloma1.Lymphoid neoplasm: Lymphoma, Myeloma
2.Solid Tumors: Lung, Colon, Kidney, Ovary,2.Solid Tumors: Lung, Colon, Kidney, Ovary,
ThymomaThymoma
3.SLE,RA3.SLE,RA
4.Drugs: Alphamethyl DOPA, Penicillin ,4.Drugs: Alphamethyl DOPA, Penicillin ,
Quinine, ChloroquineQuinine, Chloroquine
5.Misc: HIV5.Misc: HIV
4242

Inv:Inv:
– hemolysis, MCVhemolysis, MCV
– PSmear: Microspherocytosis, n-RBCPSmear: Microspherocytosis, n-RBC
– Confirmation: Coomb’sTest / Antiglobulin testConfirmation: Coomb’sTest / Antiglobulin test
TreatmentTreatment
– Correct theunderlying causeCorrect theunderlying cause
– Prednisolone1mg/kg until Hb reaches10mg/dlPrednisolone1mg/kg until Hb reaches10mg/dl
then taper slowly and stopthen taper slowly and stop
– Transfusion: for lifethreatening problemsTransfusion: for lifethreatening problems
– If no responseto steroidsIf no responseto steroids  Spleenectomy or,Spleenectomy or,
– Immunosuppressive: Azathioprine,Immunosuppressive: Azathioprine,
CyclophosphamideCyclophosphamide
4343

2) Cold AIHemolysis
– Usually Ig MUsually Ig M
– Acuteor Chronic formAcuteor Chronic form
– Chronic:Chronic:
C/F:C/F:
– Elderly patientsElderly patients
– Cold , painful & often bluefingers, toes,Cold , painful & often bluefingers, toes,
ears, or nose( Acrocyanosis)ears, or nose( Acrocyanosis)
Inv:Inv:
– hemolysishemolysis
– PSmear: MicrospherocytosisPSmear: Microspherocytosis
– Ig MIg M
4444

Other causesof ColdAgglutination:Other causesof ColdAgglutination:
– Infection: Mycoplasmapneumonia, InfecInfection: Mycoplasmapneumonia, Infec
MononucleosisMononucleosis
– PCH : Rarecauseseen in children in associationPCH : Rarecauseseen in children in association
with viral infection.with viral infection.
– DemonstrableDONATH LANDSTEINERDemonstrableDONATH LANDSTEINER
ANTIBODYANTIBODY
Treatment:Treatment:
– Treatment of theunderlying causeTreatment of theunderlying cause
– Keep extremitieswarmKeep extremitieswarm
– SteroidstreatmentSteroidstreatment
– Blood transfusionBlood transfusion
4545

Idiopathic thrombocytopenicIdiopathic thrombocytopenic
purpurapurpura
Defined asisolated low platelet count (thrombocytopenia)Defined asisolated low platelet count (thrombocytopenia)
with normal bonemarrow and theabsenceof other causesofwith normal bonemarrow and theabsenceof other causesof
thrombocytopenia.thrombocytopenia.
Characteristic purpuric rash and an increased tendency toCharacteristic purpuric rash and an increased tendency to
bleed.bleed.
Acutecondition in children and achronic condition in adultsAcutecondition in children and achronic condition in adults
Diagnosed by alow platelet count in a completeblood count Diagnosed by alow platelet count in a completeblood count
Additional investigations(such asa bonemarrow biopsy)Additional investigations(such asa bonemarrow biopsy)
Altered Platelet Function asinASPIRIN (and other NSAID’s)Altered Platelet Function asinASPIRIN (and other NSAID’s)
4646

Treatment :Treatment :
 In mild cases:In mild cases:corticosteroids, intravenouscorticosteroids, intravenous
immunoglobulin, anti-D immunoglobulin, orimmunoglobulin, anti-D immunoglobulin, or
immunosuppressivedrugs.immunosuppressivedrugs.
 Refracto ry ITPRefracto ry ITP (not responsiveto conventional (not responsiveto conventional
treatment) may require splenectomy, thetreatment) may require splenectomy, the
surgical removal of thespleen.surgical removal of thespleen.
 Platelet transfusions may beused in severePlatelet transfusions may beused in severe
bleeding together with avery low count.bleeding together with avery low count.
4747

Oral manifestationsOf AutoimmuneOral manifestationsOf Autoimmune
Hematological DisordersHematological Disorders
Pallor (or) Jaundiceof oral mucosa.Pallor (or) Jaundiceof oral mucosa.
Paresthesiaof oral mucosa.Paresthesiaof oral mucosa.
Hyperplastic narrow spacesin maxilla,Hyperplastic narrow spacesin maxilla,
mandibleand facial bones.mandibleand facial bones.
Oral Bleeding -Oral Bleeding -
– Petechiae/ Easily Bruised (Ecchymoses)Petechiae/ Easily Bruised (Ecchymoses)
– BleedingAfter BrushingBleedingAfter Brushing
– SpontaneousGingival BleedingSpontaneousGingival Bleeding
– ProlongedAfter ExtractionsProlongedAfter Extractions
4848

Other Bleeding: Epistaxis, Hematemesis,Other Bleeding: Epistaxis, Hematemesis,
Hemoptysis, Hematuria, MelenaHemoptysis, Hematuria, Melena
Long Term Immunosuppression carriesLong Term Immunosuppression carries
increased Risk for Malignancy (Especiallyincreased Risk for Malignancy (Especially
lymphomaand leukemia)lymphomaand leukemia)
Oral Swelling &/or UlcerationOral Swelling &/or Ulceration
4949

Depapillation of tongue Ulceration
Petechiae Ecchymosis
5050

AUTOIMMUNEAUTOIMMUNE
GASTROINTESTINALGASTROINTESTINAL
DISORDERSDISORDERS
5151

PerniciousAnemiaPerniciousAnemia
Isoneof many typesof thelarger familyIsoneof many typesof thelarger family
of megaloblastic anemias.of megaloblastic anemias.
An atrophic gastritis, theautoimmuneAn atrophic gastritis, theautoimmune
desturction of parietal cells(and autoantibodydesturction of parietal cells(and autoantibody
inactivation of intrinsic factor) leadsto alackinactivation of intrinsic factor) leadsto alack
of intrinsic factor.of intrinsic factor.
Lossof intrinsic factor leadsto vitaminLossof intrinsic factor leadsto vitamin
BB1212 deficiency. deficiency.
5252

Clinical & Oral manifestationsClinical & Oral manifestations
Pallor – anemiaPallor – anemia
Glossitis– red, beefy, dry tongueGlossitis– red, beefy, dry tongue
NeuroabnormalitiesNeuroabnormalities
Gastrointestinal manifestations– diarrhoea,Gastrointestinal manifestations– diarrhoea,
anorexia, weight loss, dyspepsia.anorexia, weight loss, dyspepsia.
Congestiveheart failureCongestiveheart failure
Hemorrhagic manifestationsHemorrhagic manifestations
5353

TreatmentTreatment
Blood transfusionBlood transfusion
Marrow stimulating agaen( androgen) orally.Marrow stimulating agaen( androgen) orally.
Immunosuppresivetherapy with agentssuchImmunosuppresivetherapy with agentssuch
asanti-thrombocyteglobulin & anti-asanti-thrombocyteglobulin & anti-
lymphocyteserum or high doseoflymphocyteserum or high doseof
glucocorticoidsmay yield similar response.glucocorticoidsmay yield similar response.
Bonemarrow transplantation.Bonemarrow transplantation.
Replacement therapy with Vit B12.Replacement therapy with Vit B12.
5454

CELIAC SPRUECELIAC SPRUE
(GLUTEN ENTEROPATHY)(GLUTEN ENTEROPATHY)
Isan autoimmune disorder of the smallIsan autoimmune disorder of the small
intestine that occursin geneticallyintestine that occursin genetically
predisposed peopleof all agespredisposed peopleof all ages
Symptoms:Symptoms:
- Pain and discomfort in thedigestivetract,- Pain and discomfort in thedigestivetract,
- Chronic constipation and diarrhoea, - Chronic constipation and diarrhoea,
- Failureto thrive (in children)- Failureto thrive (in children)
- Anaemia and fatigue.- Anaemia and fatigue.
5555

DIAGNOSIS:DIAGNOSIS:
Serological blood tests Serological blood tests
endoscopy/gastroscopy and biopsyendoscopy/gastroscopy and biopsy
dual energy X-ray absorptiometry (DXA)dual energy X-ray absorptiometry (DXA)
scanningscanning
TREATMENT :TREATMENT :
- Lifelong gluten-freedietLifelong gluten-freediet
- Refractory Diseases:Refractory Diseases:
steroids or immunosuppressants (suchsteroids or immunosuppressants (such
as azathioprine)as azathioprine)
5656

AUTOIMMUNEAUTOIMMUNE
DERMATOLOGICAL DISEASESDERMATOLOGICAL DISEASES
5757

PemphigusVulgarisPemphigusVulgaris
Pemphigusvulgarisisthemost common formPemphigusvulgarisisthemost common form
of pemphigus.of pemphigus.
Oral lesionsusually precedetheskin blistersOral lesionsusually precedetheskin blisters
by weeksto months(80% present with oralby weeksto months(80% present with oral
lesionsfirst).lesionsfirst).
5858

Theetiology isfrom autoimmunity to theTheetiology isfrom autoimmunity to the
pemphigusvulgarisantigen (desmoglein 3) apemphigusvulgarisantigen (desmoglein 3) a
member of thecadherin family and anormalmember of thecadherin family and anormal
component of human keratinocytecellcomponent of human keratinocytecell
membranes.membranes.
5959

Theprimary lesion isaflaccid blister/bullaeTheprimary lesion isaflaccid blister/bullae
that easily ruptures, leaving erosionsandthat easily ruptures, leaving erosionsand
crusting, and eventual marked post-crusting, and eventual marked post-
inflammatory changes.inflammatory changes.
6060

In severecasestheoral epithelium isIn severecasestheoral epithelium is
completely denuded and isassociated withcompletely denuded and isassociated with
intraoral pain that isparticularly worsened byintraoral pain that isparticularly worsened by
eatingeating
Infrequently other mucousmembranesmaybeInfrequently other mucousmembranesmaybe
involved (ocular and genitourinary)involved (ocular and genitourinary)
6161

Nonpruritic skin blistersvarying in sizefrom 1Nonpruritic skin blistersvarying in sizefrom 1
to several cm’sgradually appear and maybeto several cm’sgradually appear and maybe
localized for aconsiderabletime.localized for aconsiderabletime.
Nikolsky'ssign (gentlelateral pressure) onNikolsky'ssign (gentlelateral pressure) on
unaffected mucosaor skin raisesabulla.unaffected mucosaor skin raisesabulla.
6262

Thelesionsbecomeinvariably moreThelesionsbecomeinvariably more
generalized if left untreated.generalized if left untreated.
It isusually most accentuated in theIt isusually most accentuated in the
intertriginousareas.intertriginousareas.
6363

DiagnosisDiagnosis
Clinical pictureClinical picture
Skin biopsy for light microscopySkin biopsy for light microscopy
Skin biopsy for direct IF studiesSkin biopsy for direct IF studies
Indirect IF studies(levelscorrelatewithIndirect IF studies(levelscorrelatewith
diseaseactivity)diseaseactivity)
6464

Treatment of P.VulgarisTreatment of P.Vulgaris
 Oralstero idsOralstero ids
 AzathioprineAzathioprine
 CyclosporineCyclosporine
 PlasmapheresisPlasmapheresis
 RituximabRituximab
6565

Cicatrial Pemphigoid (CP) or mucousCicatrial Pemphigoid (CP) or mucous
membranepemphigoid (MMP)membranepemphigoid (MMP)
Isararechronic autoimmunesubepithelialIsararechronic autoimmunesubepithelial
blistering diseaseblistering disease
Erosive skin lesions of themucousmembranesErosive skin lesions of themucousmembranes
and skin that resultsin scarringand skin that resultsin scarring
Sings& Symptoms:Sings& Symptoms:
lesionsin the gingiva or gumslesionsin the gingiva or gums
6666

Diagnostic techniques:Diagnostic techniques:
antibodies (IgG) precipitatescomplement (C3)antibodies (IgG) precipitatescomplement (C3)
in the laminalucida of thebasementin the laminalucida of thebasement
membrane.membrane.
Circulating auto-antibodiesto BP-1 antigenCirculating auto-antibodiesto BP-1 antigen
(located in hemidesmosome). 50% haveBP-2.(located in hemidesmosome). 50% haveBP-2.
Negative Nikolsky sign.Negative Nikolsky sign.
IgG, C3 deposition at BM creating smooth lineIgG, C3 deposition at BM creating smooth line
in immunofluorescent analysis.in immunofluorescent analysis.
6767

ManagementManagement
ConservativeConservative
Good oral hygiene- periodontal scalingGood oral hygiene- periodontal scaling
MedicationsMedications
Topical and intralesional (injected into theTopical and intralesional (injected into the
affected areas) corticosteroid drugs-affected areas) corticosteroid drugs-
fluocinonide, clobetasol fluocinonide, clobetasol
propionate or triamcinoloneacetonide.propionate or triamcinoloneacetonide.
Antimycotics such as miconazole gelAntimycotics such as miconazole gel
or chlorhexidine mouthwash areused toor chlorhexidine mouthwash areused to
prevent oral candidiasis.prevent oral candidiasis.
Topical ciclosporin issometimesused.Topical ciclosporin issometimesused. 6868

Dapsone issometimesused asa steroidDapsone issometimesused asa steroid
sparing agent. sparing agent.
Systemic steroidsSystemic steroids
Many other drugs-Many other drugs-
azathioprine, cyclophosphamide,methotrexateazathioprine, cyclophosphamide,methotrexate
OthertreatmentsOthertreatments
Plasmapheresis appearsto help somecases.Plasmapheresis appearsto help somecases.
Sometimessurgical proceduresarerequired toSometimessurgical proceduresarerequired to
repair scars, prevent complicationssuch asrepair scars, prevent complicationssuch as
blindness, upper airway stenosisor esophagealblindness, upper airway stenosisor esophageal
stricture.stricture.
6969

PSORIASISPSORIASIS
It isnon-contagiousskin disorderIt isnon-contagiousskin disorder
Inflammed , edematousskin lesionscoveredInflammed , edematousskin lesionscovered
with thesilvery whitescale.with thesilvery whitescale.
Etiology:Etiology: Associated with theincreasedAssociated with theincreased
activity of T cellsin underlying skin.activity of T cellsin underlying skin.
- Percieved stresscan causeexacerbation ofPercieved stresscan causeexacerbation of
psoriasis.psoriasis.
Auspitz’ signAuspitz’ sign : When thedeep scalesare: When thedeep scalesare
removed oneor moretiny bleeding pointsareremoved oneor moretiny bleeding pointsare
disclosed .disclosed . 7070

Oral manifestation of psoriasis:Oral manifestation of psoriasis:
- RareRare
- Gray/yellowish-whiteplaquesGray/yellowish-whiteplaques
- Silvery white, scaly lesionswith anSilvery white, scaly lesionswith an
erythematousbaseerythematousbase
- Papillary elevated lesionPapillary elevated lesion
Treatment of psoriasis:Treatment of psoriasis:
- UV-A lightUV-A light
- Psoralen plusUV-A light (PUVA)Psoralen plusUV-A light (PUVA)
- Retinoids( eg. Isotretinoin, acitretin)Retinoids( eg. Isotretinoin, acitretin)
- Methotrexate,cyclosporineand alefacept.Methotrexate,cyclosporineand alefacept.
7171

EpidermolysisbullosaaquisitaEpidermolysisbullosaaquisita
EpidermolysisbullosaacquisitaisrareinEpidermolysisbullosaacquisitaisrarein
humans.humans.
Epidermolysis bullosa acquisitaEpidermolysis bullosa acquisita isachronic isachronic
subepidermal blistering diseaseassociatedsubepidermal blistering diseaseassociated
with autoimmunity to typeVII collagenwith autoimmunity to typeVII collagenwithinwithin
anchoring fibril structuresthat arelocated atanchoring fibril structuresthat arelocated at
the dermo-epidermal junction.the dermo-epidermal junction.
EpidermolysisbullosaacquisitaisEpidermolysisbullosaacquisitais
characterized clinically by blisters, scars, andcharacterized clinically by blisters, scars, and
miliaprimarily at thetrauma-proneareas.miliaprimarily at thetrauma-proneareas. 7272

Patientswith epidermolysisbullosaacquisita(EBA) mayPatientswith epidermolysisbullosaacquisita(EBA) may
requiretherapy with oral corticosteroidsandrequiretherapy with oral corticosteroidsand
immunosuppressants.immunosuppressants.
For patientswho areon long-term systemic corticosteroidFor patientswho areon long-term systemic corticosteroid
treatment, daily calcium and vitamin D supplementsaretreatment, daily calcium and vitamin D supplementsare
essential for reducing steroid-induced osteoporosis.essential for reducing steroid-induced osteoporosis.
In addition, patientswho areon long-term systemicIn addition, patientswho areon long-term systemic
corticosteroid treatment should takebisphosphonate, aclassofcorticosteroid treatment should takebisphosphonate, aclassof
specific inhibitor of osteoclast-mediated boneresorption (eg,specific inhibitor of osteoclast-mediated boneresorption (eg,
alendronate[Fosamax]).alendronate[Fosamax]).
For patientswho do not respond to oral corticosteroidsandFor patientswho do not respond to oral corticosteroidsand
immunosuppressives, physicianscould also consider usingimmunosuppressives, physicianscould also consider using
someother newer, but not-yet-proven therapeutic options,someother newer, but not-yet-proven therapeutic options,
including intravenousimmunoglobulin and intravenousincluding intravenousimmunoglobulin and intravenous
infusion of anti-CD20 antibodies(rituximab).infusion of anti-CD20 antibodies(rituximab).
7373

Oral Lichen Planus (OLP)
OLPisacommon chronic immunologicOLPisacommon chronic immunologic
inflammatory mucocutaneousdisorder frominflammatory mucocutaneousdisorder from
keratotic (reticular/plaquelike) tokeratotic (reticular/plaquelike) to
erythematousor ulcerative.erythematousor ulcerative.
It isthought to betheresult ofIt isthought to betheresult of
an autoimmune processwith an unknownan autoimmune processwith an unknown
initial trigger.initial trigger.
Women>Men (3:2)Women>Men (3:2)
7474

Extra-oral features:Extra-oral features: 4 P’s4 P’s
Purple, polygonal, pruritic, papules–Purple, polygonal, pruritic, papules–
Characteristic cutaneouslesions.Characteristic cutaneouslesions.
Oral lesion:Oral lesion:
May betender or painful (mild casesmay notMay betender or painful (mild casesmay not
causeplain)causeplain)
Arelocated on thesidesof thetongue, insideArelocated on thesidesof thetongue, inside
of thecheek, or gumsof thecheek, or gums
Look likeblue-whitespotsLook likeblue-whitespots
Form linesin alacy network – Wicham striaeForm linesin alacy network – Wicham striae
Gradual increasein sizeof theaffected areaGradual increasein sizeof theaffected area
Sometimesform painful ulcersSometimesform painful ulcers 7575

Skin Lesions:
Areusually found on theinnerwrist, legs, torso,
orgenitals
Areitchy
Haveeven sides (symmetrical) and sharp borders
Occur in singlelesion or clusters, often at thesite of
skin injury
May be covered with thin white streaks or
scratch marks(called Wickham's striae)
Areshiny orscaly looking
Haveadark, reddish-purple color on theskinor
are gray-white in themouth
May develop blisters or ulcers 7777

Othermanifestations:Othermanifestations:
Dry mouthDry mouth
Hair lossHair loss
Metallic tastein themouthMetallic tastein themouth
Ridgesin thenailsRidgesin thenails
(nail abnormalities)(nail abnormalities)
7878

Treatments may include:
– AntihistaminesAntihistamines
– Medicinesthat calm down theimmunesystem, such asMedicinesthat calm down theimmunesystem, such as
cyclosporine(incyclosporine(in severesevere cases)cases)
– LidocaineLidocaine mouthwashestomouthwashesto numb the areanumb the area and makeand make
eating morecomfortable(for mouth sores)eating morecomfortable(for mouth sores)
– Topical corticosteroidsTopical corticosteroids (such asclobetasol) or oral(such asclobetasol) or oral
corticosteroids(such asprednisone)corticosteroids(such asprednisone) to reduce swellingto reduce swelling
andand lowerimmune responseslowerimmune responses
– Corticosteroids shotsCorticosteroids shots into asore into asore
– Vitamin A as a creamVitamin A as a cream (topical retinoic acid) or taken(topical retinoic acid) or taken
mouth (acitretin)mouth (acitretin)
– DressingsDressings placed over skin medicines placed over skin medicines to protect fromto protect from
scratchingscratching
– Ultraviolet light therapyUltraviolet light therapy for somecasesfor somecases 7979

Erythema MultimformeErythema Multimforme
Erythema– RednessErythema– Redness
Multiforme– PolymorphicMultiforme– Polymorphic
Acute, Recurrent, self-limiting CutaneousAcute, Recurrent, self-limiting Cutaneous
and/or Mucocutaneouseruptionscharacterisedand/or Mucocutaneouseruptionscharacterised
by target –shaped plaquescommonly overby target –shaped plaquescommonly over
extremitiesand face.extremitiesand face.
Assoc with HSV /Assoc with HSV / Myco plasma pneumo niaMyco plasma pneumo nia
infectionsinfections
Male: Female= 3:2Male: Female= 3:2
Occursin theyoung / adoloscentsOccursin theyoung / adoloscents 8080

Classification of ErythemaMultiformeClassification of ErythemaMultiforme
EM Minor : Cutaneouswithout MucousinvEM Minor : Cutaneouswithout Mucousinv
EM Major (EMM) : Cutaneous+ MucousinvEM Major (EMM) : Cutaneous+ Mucousinv
Mucosal EM : Fuch’sEctodermosisPluriorificialisMucosal EM : Fuch’sEctodermosisPluriorificialis
HAEMHAEM
MPAEMMPAEM
8181

Clinical Feature:Clinical Feature:
Prodromal FeaturesProdromal Features
PreviousAttack (30%)PreviousAttack (30%)
Preceding InfectionPreceding Infection
Fever (T>103.1 deg C)Fever (T>103.1 deg C)
 Cutaneouslesions:Cutaneouslesions:
Symmetrical, Acral, Centripetal RashSymmetrical, Acral, Centripetal Rash
Extensor aspect : Extremities> Face> Neck >Extensor aspect : Extremities> Face> Neck >
TrunkTrunk
8282

Predilection to Sun-ExposedAreas/Predilection to Sun-ExposedAreas/
KoebnerizationKoebnerization
Well-defined, circular, blanching papule/Well-defined, circular, blanching papule/
plaquethat persistsfor 01 week – Self-limitingplaquethat persistsfor 01 week – Self-limiting
in 04 weeks– Persistent / ContinuousEMin 04 weeks– Persistent / ContinuousEM
8383

Typical Target Lesion :-Typical Target Lesion :-
1. Dusky Central Disk / Bulla1. Dusky Central Disk / Bulla
(later Violaceous/ Purpuric)(later Violaceous/ Purpuric)
2. Infiltrated PaleRing2. Infiltrated PaleRing
3. Erythematousedematoushalo3. Erythematousedematoushalo
Larger lesionsshow CentralLarger lesionsshow Central
Bullaand Marginal ring of vesiclesBullaand Marginal ring of vesicles
-- Herpes Iris o f BatemanHerpes Iris o f Bateman
8484

Target LesionsTarget Lesions
8585

CutaneousLesionsCutaneousLesions
RaisedAtypical Target lesions/ Targetoid lesionsRaisedAtypical Target lesions/ Targetoid lesions
SJS-TEN lesions– mostly MacularSJS-TEN lesions– mostly Macular
8686

Mucosal LesionsMucosal Lesions
70% Cases70% Cases
Lips– CutaneousLips– Cutaneous
Target LesionsTarget Lesions
SerousCrustingSerousCrusting
8787

Mucosal LesionsMucosal Lesions
LIPS– Mucosal (Erosions/ Vesicles/ Bullae)LIPS– Mucosal (Erosions/ Vesicles/ Bullae)
GINGIVAL / Ventral TongueGINGIVAL / Ventral Tongue
Hard Palate– SparedHard Palate– Spared
Pharynx / Larynx / Trachea/ BronchiPharynx / Larynx / Trachea/ Bronchi
ConjunctivitisB/L with Vesicles/ ErosionsConjunctivitisB/L with Vesicles/ Erosions
Nasal / Urethral / Anal MucosaeNasal / Urethral / Anal Mucosae
2/3 Mucosal SitessansCutaneousinv2/3 Mucosal SitessansCutaneousinv
–– FUCH’sSYNDROMEFUCH’sSYNDROME
8888

Treatment of ErythemaMultiformaTreatment of ErythemaMultiforma
Treating underlying EtiologyTreating underlying Etiology
Reducing morbidity – Oral CSReducing morbidity – Oral CS
Macrolides/ Quinolonesfor MPAEMMacrolides/ Quinolonesfor MPAEM
Oral EM – Topical CS/ Anesthetics/ AntacidsOral EM – Topical CS/ Anesthetics/ Antacids
9191

Diseaseof MusclesDiseaseof Muscles
9292

MyastheniaGravisMyastheniaGravis
Myastheniagravis(MG) isacomplex, autoimmuneMyastheniagravis(MG) isacomplex, autoimmune
disorder in which antibodiesdestroy neuromusculardisorder in which antibodiesdestroy neuromuscular
connections.connections.
Morecommon in women younger than 40 and in menMorecommon in women younger than 40 and in men
older than 60.older than 60.
No curefor myastheniagravis, but treatment can helpNo curefor myastheniagravis, but treatment can help
relievesignsand symptoms.relievesignsand symptoms.
Types:Types:
1)1) CongenitalCongenital
2)2) Transient neonatalTransient neonatal
3)3) JuvenileJuvenile 9393

 Clinical Manifestations:Clinical Manifestations:
1)1) Eyemuscles:Eyemuscles:
In more than half the people who develop MG, theirIn more than half the people who develop MG, their
first signsand symptomsinvolveeyeproblems:first signsand symptomsinvolveeyeproblems:
 Drooping of oneor both eyelids(ptosis)Drooping of oneor both eyelids(ptosis)
 Double vision (diplopia), which may be horizontalDouble vision (diplopia), which may be horizontal
or verticalor vertical
 Blurred vision, which may comeand goBlurred vision, which may comeand go
9595

2) Face and throat muscles:2) Face and throat muscles:
 SpeakingSpeaking. The speech may be very soft or sound nasal,. The speech may be very soft or sound nasal,
depending upon which muscleshavebeen affected.depending upon which muscleshavebeen affected.
 SwallowingSwallowing. May choke very easily, which makes it difficult. May choke very easily, which makes it difficult
to eat, drink or take pills. In some cases, liquids may come outto eat, drink or take pills. In some cases, liquids may come out
of thenose.of thenose.
 ChewingChewing. The muscles used for chewing may wear out. The muscles used for chewing may wear out
halfway through ameal, particularly if eatinghalfway through ameal, particularly if eating
something hard to chew, such assugarcane.something hard to chew, such assugarcane.
 Facial expressionsFacial expressions. Family members may note "lost smile". Family members may note "lost smile"
if themusclesthat control facial expressionsareaffected.if themusclesthat control facial expressionsareaffected.
9696

Myastheniagraviscan causeweaknessin armsandMyastheniagraviscan causeweaknessin armsand
legs. If it affectslegs, may waddlewhen walking.legs. If it affectslegs, may waddlewhen walking.
Myasthenic crisisMyasthenic crisis: A life-threatening condition,: A life-threatening condition,
which occurswhen themusclesthat control breathingwhich occurswhen themusclesthat control breathing
becometoo weak to do their jobs. Emergencybecometoo weak to do their jobs. Emergency
treatment isneeded to providemechanical assistancetreatment isneeded to providemechanical assistance
with breathing. Medicationsand blood-filteringwith breathing. Medicationsand blood-filtering
therapieshelp peoplerecover from myasthenic crisis,therapieshelp peoplerecover from myasthenic crisis,
so they can again breatheon their own.so they can again breatheon their own.
9797

DiagnosisDiagnosis
Edrophonium test :It isconfirmed with aEdrophonium test :It isconfirmed with a
Tensilon test. With thistest, asmall amount ofTensilon test. With thistest, asmall amount of
medicine(Tensilon) isinjected into thechild,medicine(Tensilon) isinjected into thechild,
if thechild hasMG, an immediate, but brief,if thechild hasMG, an immediate, but brief,
increasein muscletoneisnoted.increasein muscletoneisnoted.
Blood testsBlood tests
Genetic testsGenetic tests
Electromyogram (EMG)Electromyogram (EMG)
MusclebiopsyMusclebiopsy
9898

Repetitivenervestimulation
Single-fiber electromyography (EMG)
Imaging scans
9999

1)1) Cholinesteraseinhibitors: pyridostigmineCholinesteraseinhibitors: pyridostigmine
(Mestinon)(Mestinon)
2)2) Corticosteroids.Corticosteroids.
3)3) ImmunosuppressantsImmunosuppressants
4)4) PlasmapheresisPlasmapheresis
5)5) IntravenousimmuneglobulinIntravenousimmuneglobulin
6)6) ThymectomyThymectomy 100100

Hormonal DiseasesHormonal Diseases
101101

TypeI DiabetesMellitusTypeI DiabetesMellitus
Also called Insulin dependent diabetesor Juvenile
diabetes.
Autoimmunedestruction of insulin-producing (beta
cells) of thepancreas
Resultsin total insulin deficiency.
Affects1 in 300 children and moreadults.
102102

BetaCells: secrete
insulin.
AlphaCells: secrete
glucagon
Autoimmunity occursin islet of Langerhans
against thebetacells...
103103

Symptoms
Hyperglycemia
Polyuria: Excessiveurine
Polydipsia: ExcessiveThirst
Lipidemia
Polyphagia:ExcessiveHunger
Glycosuria: Sugar in theurine
Lipidemia: Lack of insulin starvesbody of glucose, body begins
metabolizing fatty acidsasenergy source.
Ketoacidoses: Ketonesbuild up in blood, dropping Ph
Ketouria: Ketonesin urine
Macular degeneration
104104

DIAGNOSIS:
Fasting plasmaglucoselevels.
-Detection of antibodiesagainst islet antigens(insulin, beta
cells, etc.) in theserum. Detectsautoimmunity before
diabetesisclinical.
Hemoglobin A1c (glycolated
hemogolobin) test.
105105

TREATMENT:
Type1 diabetesisfatal if not treated with external insulin.
Insulin:
-fast acting and slow acting
Delivery:
- subcutaneousinjection
- insulin pump
106106

A FutureCure?A FutureCure?
Type-1 Diabetesiscurrently non-preventablebut…Type-1 Diabetesiscurrently non-preventablebut…
Drugs?Drugs?
Diet?Diet?
…… Mostly in experimental stages.Mostly in experimental stages.
FurtherFurther research isrequired.research isrequired.
Pancreastransplantation?Pancreastransplantation?
Islet cell transplantation?Islet cell transplantation? Somesuccessin miceSomesuccessin mice
107107

ADDISON’SDISEASEADDISON’SDISEASE
108108

Addison’sdiseaseisrareAddison’sdiseaseisrare
1/100,000 people1/100,000 people
Effectsall agegroups(Morecommon between ages30 – 50)Effectsall agegroups(Morecommon between ages30 – 50)
Moreprevalent in women but can effect men aswell.Moreprevalent in women but can effect men aswell.
CLINICALFINDINGS:CLINICALFINDINGS:
HyperpigmentationHyperpigmentation
HypotensionHypotension
HypoglycemiaHypoglycemia
HyperkalemiaHyperkalemia
VomitingVomiting
DiarrheaDiarrhea
Mouth lesionsMouth lesions
Decreasein body hairDecreasein body hair 109109

TREATMENT:
Fludrocortisone
– Aldosteronereplacement
– Oral corticosteroid
Hydrocortisone/Prednisone
– Cortisol replacement
– Oral or injection:
INJECTION given when patient isexperiencing N/V or during an
Addisonian Crisis
Hormonereplacement isused to correct theinsufficient levelsof steroids
theadrenal glandscan not produce.
Increase in sodium intake
Lifelong drug maintenance isrequired .
Patient EducationPatient Education
- Never skip adose. Thiscould lead to anAddisonian crisisNever skip adose. Thiscould lead to anAddisonian crisis
- Learn to recognizethesymptomsof anAddisonian crisis. Ex: pain in lower- Learn to recognizethesymptomsof anAddisonian crisis. Ex: pain in lower
back, severevomiting and diarrhea, extremeweakness, fainting. Contactback, severevomiting and diarrhea, extremeweakness, fainting. Contact
physician immediatelyphysician immediately
 Pertinent Nursing
112112

Auto-Immunity
NON-ORGANS
113113

MultiplesclerosisMultiplesclerosis
It isidiopathic inflammatory demyelinatingIt isidiopathic inflammatory demyelinating
diseaseof CNS.diseaseof CNS.
EtiologyEtiology:: human herpesvirus-6 orhuman herpesvirus-6 or ChlamydiaChlamydia
pneumo nieapneumo niea
Symptoms:Symptoms:
1) Occular disturbanceslikeretrobulbar neuritis,1) Occular disturbanceslikeretrobulbar neuritis,
nystagmusand diplopia.nystagmusand diplopia.
2) Fatiguability, weakness, stiffnessof2) Fatiguability, weakness, stiffnessof
extrimities, facial and jaw weakness.extrimities, facial and jaw weakness.
3) Superficial or deep paresthesia.3) Superficial or deep paresthesia. 114114

4)mood deviation4)mood deviation
5)rectal retention5)rectal retention
Charcot’s triadCharcot’s triad diagnostic characteristicsdiagnostic characteristics
-- Nystagmus
- Intention tremor
- Dysarthria
-- NoNo treatmenttreatment
- Remission occursfrequentlyRemission occursfrequently
- Ingravescent courseto death.Ingravescent courseto death.
117117

Betainterferon-1aBetainterferon-1a
 Avonex – administered weekly by an intramuscularlyAvonex – administered weekly by an intramuscularly
injection (2003)injection (2003)
 Rebif – administered subcutaneously threetimesaweekRebif – administered subcutaneously threetimesaweek
(2002)(2002)
Betainterferon-1bBetainterferon-1b
 Betaseron – administered subcutaneously every other dayBetaseron – administered subcutaneously every other day
(1993)(1993)
 Early and aggressivetreatment with immunestimulatingEarly and aggressivetreatment with immunestimulating
interferonscan delay diseaeprogression.interferonscan delay diseaeprogression.
 Preventscrippling symptomsof MSPreventscrippling symptomsof MS
118118

Animation showing dissemination
of brain lesionsin timeand space
asdemonstrated by monthly MRI
studiesalong ayear.
119119

Sjogren’ssyndrome
It’sacondition described by Henrik Sjogren inIt’sacondition described by Henrik Sjogren in
19331933
TriadTriad : kerato-conjuctivitissicca, xerostomia,: kerato-conjuctivitissicca, xerostomia,
rheumatoid arthritisrheumatoid arthritis
Types: PrimaryTypes: Primary
SecondarySecondary
EtiologyEtiology::
Genetic,hormonal,infectious,immunological,Genetic,hormonal,infectious,immunological,
combination of allcombination of all
Associated with HLA-DR3 & HLA-B8Associated with HLA-DR3 & HLA-B8 120120

Clinical symptoms:
Predominant in women above40yrs.Predominant in women above40yrs.
Painful burning sensation of oral mucosaPainful burning sensation of oral mucosa
Drying of secretory glandsof nose, larynx,Drying of secretory glandsof nose, larynx,
pharynx, tracheo-bronchial tree, vagina.pharynx, tracheo-bronchial tree, vagina.
80% patientshaveenlarged parotid gland in80% patientshaveenlarged parotid gland in
primary SJ,14% in secondary SJprimary SJ,14% in secondary SJ
Siccacomplex:Siccacomplex:
- Xerostomia+kerato-conjuctivitis- Xerostomia+kerato-conjuctivitis
121121

S.S Could be associated
with
Central &peripheral
manifestations :
Brain and spinal cord:
Pachymeningiti
s and
hypophysitis
Myelitis.
DEVIC’S
syndrome.
Brain and spinal cord:
Pachymeningiti
s and
hypophysitis
Myelitis.
DEVIC’S
syndrome.Peripheral
manifestations:
Autonomic
neuropathy
Trigeminal
neuralgia and
glossopharyngea
l neuralgia
Mononeuritis
multiplex.
Peripheral
manifestations:
Autonomic
neuropathy
Trigeminal
neuralgia and
glossopharyngea
l neuralgia
Mononeuritis
multiplex.
126126

Lab findings:
- Polyclonal hyperglobulinemia,
- Cryoglobulins,
- Multipleorgan or tissuespecific antibodiesarefound,
- Including antisalivary duct antibodies,
- Rheumatoid factors
- Antinuclear antibodies.
• Elevated ESR
• Anemia
 Schirmer test.
 Serum electrophoresis.
 Sialography and Scintigraph.
 Biopsy.
127127

Radiographic featuresRadiographic features::
 Sialograph shows formation of punctuate,Sialograph shows formation of punctuate,
cavitary defectswhich arefilled withcavitary defectswhich arefilled with
radiopaquecontrast media. These fillingradiopaquecontrast media. These filling
defectshavebeen said to produceacherrydefectshavebeen said to produceacherry
blossom or branchlessfruit-laden treeeffect.blossom or branchlessfruit-laden treeeffect.
128128

Pachymeningitis /pachy·men·in·gi·tis/(-men in-ji´tis)″
inflammation of the dura mater.
Pachymeningitis
Case.
Normal.
129129

Hypophysitis refersto an inflammation of thepituitary
gland. Hypophysitisisrareand not fully understood.
130130

Myelitis involvestheinfectionor theinflammationof
whitematter or gray matter of spinal cord.
131131

Devic's syndrome, isan autoimmune, inflammatory
disorder in which aperson'sown immunesystem attacks
theoptic nervesand spinal cord.
132132

Treatment and prognosis:Treatment and prognosis:
Treated symptomaticallyTreated symptomatically
Keratoconjuctivitis- instillation of ocularKeratoconjuctivitis- instillation of ocular
lubricantssuch asartificial tearscontaininglubricantssuch asartificial tearscontaining
methylcellulose.methylcellulose.
Xerostomia– salivasubstitutessuch asthoseXerostomia– salivasubstitutessuch asthose
used in treatment of person with xerostomiaused in treatment of person with xerostomia
secondary to radiation therapy.secondary to radiation therapy.
Majorcomplicating factorMajorcomplicating factor:developmenr of:developmenr of
pseudolymphoma&malignant lymphoma.pseudolymphoma&malignant lymphoma.
133133

BETCHET SYNDROMEBETCHET SYNDROME
Uncertain etiology, resemblesinfectiousdisease.Uncertain etiology, resemblesinfectiousdisease.
Cytokinesand heat shock protein-major factor inCytokinesand heat shock protein-major factor in
pathogenesis.pathogenesis.
136136

Spectrum Of Organ Involvement In Behçet’s
Disease.
137137

Clinical featureClinical feature::
11stst
manifestation isoral or genital lesionsmanifestation isoral or genital lesions
Painful oral lesionssimilar to reccurentPainful oral lesionssimilar to reccurent
apthousulcersapthousulcers
Occur in cropsat any intraoral sitesandOccur in cropsat any intraoral sitesand
consist of ulcersranging in sizefrom severalconsist of ulcersranging in sizefrom several
millimetersto centimeters.millimetersto centimeters.
Erythematousbordersof ulcersarecoveredErythematousbordersof ulcersarecovered
with gray or yellow exudate.with gray or yellow exudate.
138138

Cutaneous manifestations(58.6-97%)Cutaneous manifestations(58.6-97%)
A variety of skin lesionsmay appear,A variety of skin lesionsmay appear,
EgEg.-.-
Sweet syndrome–like
lesion.
Papulopustulareruptions
(55-83%, M>F)
Erythema nodosum–like
lesions (44-62%, F>M)
139139

Typical positive
pathergy reaction at
injection site
Anterior segment complicationsof
retinal vein occlusion: retinal
ischaemiawith secondary rubeosis
iridis.
140140

Ocular involvement showing
posterior uveitis.
HYPOPYON – pusin theanterior
chamber associated with uveitis
141141

Ocular lesions, beginning asphotophobiaandOcular lesions, beginning asphotophobiaand
irritation, may rangein severity from asimpleirritation, may rangein severity from asimple
conjuctivitisto uveitisand finaly hypopyon.conjuctivitisto uveitisand finaly hypopyon.
Theskin lesionsaresmall pustuleson trunk orTheskin lesionsaresmall pustuleson trunk or
limbsand around genitalia.limbsand around genitalia.
Apart from pyoderma, erythemanodosum andApart from pyoderma, erythemanodosum and
erythemamultiformeoccurerythemamultiformeoccur
Arthralgia, thrombophlebitisand CNS, cardiacArthralgia, thrombophlebitisand CNS, cardiac
and pulmonary involvement areoccational.and pulmonary involvement areoccational.
142142

Lab findingsLab findings::
- hyper-gammaglobulinemia, leukocytosiswith- hyper-gammaglobulinemia, leukocytosiswith
eosinophiliaand elevated sedimentation rate.eosinophiliaand elevated sedimentation rate.
TreatmentTreatment::
- Needsmultidisciplinary approach- Needsmultidisciplinary approach
- no specific treatment- no specific treatment
- supportivetreatment- supportivetreatment
143143

drug doses indication
Methylprednisolone 40 mg/every 3 wk
lM
Erythema nodosum (but not orogenital
ulcers)
Rebamipide 300 mg/day PO Oral ulcers
Colchicine 1-2 mg/day PO Erythema nodosum, arthritis, genital
Ulcer s (oral ulcer in female)
Dapsone 100 mg/day PO Orogenital ulcers, skin lesions, pathergy
Azathioprine 2.5 mg/kg/day Recent onset ocular disease
lnterferon-alfa-2a 6x106 lU/3x/wk SC Orogenital ulcers, papulopustular lesions
Thalidomide 100 mg/day Orogenital ulcers, Papulopustular lesions
CyclosporinA 10 mg/kg/day PO Ocular manifestations, skin lesions,
orogenital ulcers
Etanercept 25 mg/2 x/wk P0 Oral ulcers, papulopustular lesions
nodular lesions, (not pathergy test) 144144

Reiter syndromeReiter syndrome
Associated with urithritis, balanitis,Associated with urithritis, balanitis,
conjuctivitisand mucocutaneouslesion.conjuctivitisand mucocutaneouslesion.
Immuno-dysregulated conditionImmuno-dysregulated condition
HLA-B27 diseasesusceptibilty factorsHLA-B27 diseasesusceptibilty factors
Clinical featuresClinical features::
Prevalent in young 20-30yr menPrevalent in young 20-30yr men
Typical tetrad- Nongonococcol urethritis,Typical tetrad- Nongonococcol urethritis,
arthritis, conjuctivitis, mucocutaneouslesion.arthritis, conjuctivitis, mucocutaneouslesion.
11stst
sign- urithritissign- urithritis
145145

Painful urethral dischargewith burningPainful urethral dischargewith burning
sensationsensation
Arthritisisbilaterally symmetrical andArthritisisbilaterally symmetrical and
polyarticularpolyarticular
Lesionshavered or yellow keratotic maculesLesionshavered or yellow keratotic macules
or papuleswhich desquamate.or papuleswhich desquamate.
Oral manifestations:Oral manifestations:
Occur in 5 to 50% of patientsOccur in 5 to 50% of patients
Painless, red slightly elevated areas, granularPainless, red slightly elevated areas, granular
or even vesicular, with whitecircinateborderor even vesicular, with whitecircinateborder
on buccal mucosa,lips,gingiva.on buccal mucosa,lips,gingiva.
146146

Palatal lesionsaresmall, bright red, purpuric
spotswhich darken and coalesce, whilethe
lesion on tongueresemblegeographic tongue.
Histologic feature:
Parakeratosis, acanthosis,polymorphonuclear
leukocytesinfiltration of epithelium,
microabcess.
Lab findings:
- mild leukocytosis, elevated sedimentation rate
and pyuria.
Treatment: antibioticsand corticosteroids. 147147

Recurrent apthousstomatitisRecurrent apthousstomatitis
Common, painfull,recurring solitary orCommon, painfull,recurring solitary or
multipleulcerationsof oral mucosamultipleulcerationsof oral mucosa
Etiology: Immunological abnormalitiesEtiology: Immunological abnormalities
Classification:Classification:
- RA major- RA major
- RA minor- RA minor
- Recurent herpetiform ulcerationsRecurent herpetiform ulcerations
- Betchet syndromeBetchet syndrome
148148

Clinical featureClinical feature ::
 Onset isbetween 10-30 yrsOnset isbetween 10-30 yrs
 Familial tendencyFamilial tendency
 Frequency of outbreaksvariesFrequency of outbreaksvaries
 Generalized edema,Generalized edema,
 Burning sensation,Burning sensation,
 Paresthesia,Paresthesia,
 Malaise,Malaise,
 Low gradefever,Low gradefever,
 Localised lymphadenopathy,Localised lymphadenopathy,
 Vesiclelikelesionscontaining mucous.Vesiclelikelesionscontaining mucous.
149149

Minor ulcerMinor ulcer
Consists of 1-5 small,Consists of 1-5 small,
moderately painful ulcersmoderately painful ulcers
persisting for 4- 14 dayspersisting for 4- 14 days
Major ulcer
1-10 very painful ulcers, measuring
10-30 mm, persisting up to 6
weeks, and possibly leaving a scar
upon healing
Herpetiform ulcer
Recurrent crop of as many as 1000
small and painful ulcers
150150

Treatment :Treatment :
• mild diet, avoidanceof irritating agents,mild diet, avoidanceof irritating agents,
• Caustic solutionsCaustic solutions (silver nitrate, 1%-2%; tincturamyrrha, 5%-10%(silver nitrate, 1%-2%; tincturamyrrha, 5%-10%
weight/volume; H202,0.5%; methylviolet,0.5%) 1-2xldweight/volume; H202,0.5%; methylviolet,0.5%) 1-2xld
• Antiseptic and anti-inflammatory preparationsAntiseptic and anti-inflammatory preparations (amlexanox, 5% in(amlexanox, 5% in
oral paste; triclosan, 0.1% mouthwash solution and in toothpaste), 3%oral paste; triclosan, 0.1% mouthwash solution and in toothpaste), 3%
diclofenac in 2.5% hyaluronic acid, tetracyclinemouthwashdiclofenac in 2.5% hyaluronic acid, tetracyclinemouthwash
• CorticosteroidsCorticosteroids (triamcinolonemucosal ointment, dexamethasonemucosal(triamcinolonemucosal ointment, dexamethasonemucosal
paste, betamethasonepastilles) 4 x/day or during night (ointment / paste) orpaste, betamethasonepastilles) 4 x/day or during night (ointment / paste) or
intrafocal infiltrationswith triamcinolonesuspension 0.1-0.5 mL per lesionintrafocal infiltrationswith triamcinolonesuspension 0.1-0.5 mL per lesion
• AnaestheticsAnaesthetics (lidocaine- 2%-5%; mepivacaine- 1.5%, tetracaine- 0.5%-(lidocaine- 2%-5%; mepivacaine- 1.5%, tetracaine- 0.5%-
1% gelsor mucosal ointments) 2-3 x/day1% gelsor mucosal ointments) 2-3 x/day
• Sucralfate suspensionSucralfate suspension,, 5 mL x 4/day (for oral aphthous)5 mL x 4/day (for oral aphthous)
• Topical tacrolimus, nicotine patches, and topical G-CSFTopical tacrolimus, nicotine patches, and topical G-CSF
• Tetracyclin mouthwashTetracyclin mouthwash
151151

Systemic LupusErythematosusSystemic LupusErythematosus
Autoimmunediseasecharacterized byAutoimmunediseasecharacterized by
autoantibodies,immunecomplexautoantibodies,immunecomplex
formation,and immunedysregulation resultingformation,and immunedysregulation resulting
in damageto essentially any organ.in damageto essentially any organ.
EtiologyEtiology: undetermined: undetermined
Clinical features:Clinical features:
Peaks30yrsin femaleand 40yrsin malePeaks30yrsin femaleand 40yrsin male
Erythematouspatcheson facewhich coalesceErythematouspatcheson facewhich coalesce
to form roughly symmetrical pattern overto form roughly symmetrical pattern over
cheecksand acrossnosebridgeakabutterflycheecksand acrossnosebridgeakabutterfly
distribution.distribution. 152152

Also involvesneck,upper arms,shouldersandAlso involvesneck,upper arms,shouldersand
fingers,itching or burning sensation aswell asfingers,itching or burning sensation aswell as
areasof hyperpigmentation.areasof hyperpigmentation.
Oral manifestationsOral manifestations:: lesion similar to DLElesion similar to DLE
except hyperimia, edemaand extension ofexcept hyperimia, edemaand extension of
lesion ismorepronounced, greater tendencylesion ismorepronounced, greater tendency
for bleeding, petechiaand superficialfor bleeding, petechiaand superficial
ulcerationssurrounded by red halo.ulcerationssurrounded by red halo.
153153

154154
BUTTERFLY RASH
PHOTOSENSITIV
E ERYTHEMA
SUBACUTE CUTANEOUS
RASH
DISCOID LUPUS
ERYTHMATOUSBULLOUSLESIONS

Lab findingsLab findings::
- LE inclusion phenomenon (rosetteof- LE inclusion phenomenon (rosetteof
neutophilssurrounding palenuclear massneutophilssurrounding palenuclear mass
derived from lymphocytes.derived from lymphocytes.
-- careful and frequent clinical lab evaluation tocareful and frequent clinical lab evaluation to
tailor medical regimen.tailor medical regimen.
155155

Rheumatoid arthritisRheumatoid arthritis
Beginsin early adult lifeBeginsin early adult life
Affectswomen moreAffectswomen more
Distribution of joint involvement isnearlyDistribution of joint involvement isnearly
polyarticular and frequently symmetricallypolyarticular and frequently symmetrically
bilateralbilateral
Clinical featureClinical feature :joints:joints
swollen,pain,stiffness,involvement of TMJswollen,pain,stiffness,involvement of TMJ
Movement of jaw during mastication causesMovement of jaw during mastication causes
pain.pain.
156156

RA in kids:RA in kids: Still’s diseaseStill’s disease
Shortening of body, reduction in height ofShortening of body, reduction in height of
ramus.ramus.
- No- No specific treatmentspecific treatment
- Administration of ACTH or cortisone- Administration of ACTH or cortisone
- Surgical intervention- Surgical intervention
157157

RECENTSTUDIESRECENTSTUDIES
158158

AUTOIMMUNITY & LEFT-AUTOIMMUNITY & LEFT-
HANDEDNESSHANDEDNESS
Left handed individualsmoreaffected.Left handed individualsmoreaffected.
11% of left handed & 4% of right handed.11% of left handed & 4% of right handed.
Reasonsfor thisareobscure.Reasonsfor thisareobscure.
Left-handedness& immunemalfunction mayLeft-handedness& immunemalfunction may
both result from abnormal endocrinefunctionboth result from abnormal endocrinefunction
in fetal life.in fetal life.
159159

Where are We?Where are We?
Thehunt continues.Thehunt continues.
Handful of genesmight beoperative(or)Handful of genesmight beoperative(or)
ELUSIVE.ELUSIVE.
An environmental agent may be– STILLAn environmental agent may be– STILL
UNIDENTIFIED.UNIDENTIFIED.
ISIT AN INTERPLAY BETWEEN BOTH – AISIT AN INTERPLAY BETWEEN BOTH – A
PROBABLE YES.PROBABLE YES.
Wedo not know onemillionth of onepercent about anything –Wedo not know onemillionth of onepercent about anything –
ThomasEdisonThomasEdison165165

Over many yearsautoimmunediseasesOver many yearsautoimmunediseases
remained an unsolved puzzleand an enigma.remained an unsolved puzzleand an enigma.
Significant advanceshavebeen made,inSignificant advanceshavebeen made,in
immunopathology,categorisation ofimmunopathology,categorisation of
severity,diseasemodifying drugsand theirseverity,diseasemodifying drugsand their
usage.usage.
Research isstill on in finding theelusivegeneResearch isstill on in finding theelusivegene
or an environmental agent or both.or an environmental agent or both.
Despiteall theseadvancestwo thingsarestillDespiteall theseadvancestwo thingsarestill
unanswered – curativetherapy & theexactunanswered – curativetherapy & theexact
cause.cause.
166166

Asadentist acompleteknowledgeAsadentist acompleteknowledge
about themechanism of autoimmuneabout themechanism of autoimmune
diseasesisrequired to hencetreat anddiseasesisrequired to hencetreat and
prevent them from being alifeprevent them from being alife
threatening cause!!! …..threatening cause!!! …..
167167

REFERENCESREFERENCES
Shafer'S Shafer'S TextbookTextbook Of Of Oral PathologyOral Pathology -6Th -6Th
EditionEdition
OralOral and Maxillofacial and Maxillofacial PathologyPathology – Neville-– Neville-
3e 3e
Davidson'sDavidson's Principlesand Practice Principlesand Practice
of of MedicineMedicine, 22nd Edition, 22nd Edition
Textbook of theAutoimmuneDiseases- KelleyTextbook of theAutoimmuneDiseases- Kelley
– 1– 1stst
editionedition
168168

RECENT ADVANCESIN COELIACRECENT ADVANCESIN COELIAC
DISEASE,DISEASE,D A van Heel, JWest,D A van Heel, JWest, RecentRecent
advancesin clinical practice:Gutadvancesin clinical practice:Gut
2006;55:1037–1046.2006;55:1037–1046.
CommitteetoAdvisethePublic HealthCommitteetoAdvisethePublic Health
Serviceon Clinical PracticeGuidelines,Serviceon Clinical PracticeGuidelines,
Instituteof Medicine. Clinical PracticeInstituteof Medicine. Clinical Practice
Guidelines: Direction of aNew Program. FieldGuidelines: Direction of aNew Program. Field
MJ, Lohr KN, eds. Washington, DC: NationalMJ, Lohr KN, eds. Washington, DC: National
Academy Press; 1990.Academy Press; 1990.
Progressreport :Oral ulceration and Behget'sProgressreport :Oral ulceration and Behget's
syndrome:Gut, 1977, 18, 491-511.syndrome:Gut, 1977, 18, 491-511. 169169

Autoimmunity as a special case ofAutoimmunity as a special case of
immunity: removing threats from withinimmunity: removing threats from within,,
Uri Nevo et al: Jornal of trendsin molecularUri Nevo et al: Jornal of trendsin molecular
medicine, vol 9,Issue3, March 2003, Pagesmedicine, vol 9,Issue3, March 2003, Pages
88–93.88–93.
Prosand consof stem cell transplantation forProsand consof stem cell transplantation for
autoimmunedisease.ThomasED:TheJournalautoimmunedisease.ThomasED:TheJournal
of Rheumatology. Supplement [2007, 48:100-of Rheumatology. Supplement [2007, 48:100-
102].102].
Socioeconomic status. Therelationship withSocioeconomic status. Therelationship with
health and autoimmunediseases. Calixtohealth and autoimmunediseases. Calixto
OJ, AnayaJM: Autoimmunity Reviews [2014,OJ, AnayaJM: Autoimmunity Reviews [2014,
13(6):641-654]13(6):641-654] 170170

Autoimmunity as an immune defenseAutoimmunity as an immune defense
against degenerative processes: aagainst degenerative processes: a
primary mathematical model illustratingprimary mathematical model illustrating
the bright side of autoimmunity,the bright side of autoimmunity, Uri NevoUri Nevo
et al. Journal of Theoretical Biologyet al. Journal of Theoretical Biology VolumeVolume
227, Issue4, 21April 2004, Pages583–592.227, Issue4, 21April 2004, Pages583–592.
Protective autoimmunity against theProtective autoimmunity against the
enemy within,enemy within, Michal Schwartz et al.Michal Schwartz et al.
Journal of trendsin neurosciences.Journal of trendsin neurosciences.Volume26,Volume26,
Issue6, June2003, Pages297–302Issue6, June2003, Pages297–302
171171

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