jakarta aventis 3 feb 2001

8/17/2019 Jakarta Aventis 3 Feb 2001

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Fn: PatofisDiag RINAL Exp15’ Avt 3 Feb 2001

UNIER!I"A! PAD#AD#ARAN

$A%PU!

I&A $'E!'E%A !'E%AN"RI#ALAN DIPA"I U$UR 35 (ANDUN) IND'NE!IA


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By :

Iwin Sumarman

Faculty of Medicine Padjadjaran University

Dr. Hasan Sadikin General Hospital

Bandung !ndonesia

Pat"op"ysiology andPat"op"ysiology and

Diagnostic ProcedureDiagnostic Procedure

inin #llergic $"initis#llergic $"initis


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Chronic ongoing diseaseChronic ongoing disease Factors :Factors :

EnvironmentalEnvironmental (allergenic and or nonallergenic)(allergenic and or nonallergenic)

#llergic $"initis#llergic $"initis

GeneticsGenetics Immunity disturbancesImmunity disturbances

Suceptible to secunder infectionsSuceptible to secunder infections

!*+a,+an- Pat.op./sioog/ an Diagnosti P,oe*,e of Ae,gi R.initis


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Symptoms 1) 2) 3)

Stage 2+3+4 Stage 3+4

$"inor"ea %&'( ))'* &*'+ ,('&

Snee-ing %'/ )0'0 &'( ,/',1 2ongestion ,', 0*'* )+'0 ()'0

1 !tc"ing (&' +/' nd nd#dapted fro3:

(4 Su3ar3an et al. Hasan Sadikin Hosp. 5167PD patients 8Bandung' (%%+4

+4 Supri"ati et al 9aryadi Hosp. 5167PD patients 8Se3arang' (%&04

04 Haryanto Su3ar3an. 8Population of Bandung 2ity' (%%%4

Distribution of PAR symptoms Distribution of PAR symptoms

in Indonesiain Indonesia

!*+a,+an- Patop./sioog/ an Diagnosti P,oe*,e of Ae,gi R.initis


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History of Nasal & non nasal s/+pto+s

History of Fa+i/ Ae,g/

DIA)N'!"I P,oe*,e:

• Nasa 4 Non nasa inia signs• A*nt iagnosti



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".e potentia t,eat+ent +oaities of".e potentia t,eat+ent +oaities ofAe,gi R.initis +anage+ent:Ae,gi R.initis +anage+ent:

".,ee basi app,oa.:

1- Ae,gen avoiane

2- P.a,+aot.e,ap/

3- I++*not.e,ap/

6&7' Initiative ARIA 20008

'ptiona t.e,ap/:P.a,+aot.e,ap/ an9o, s*,ge,/ fo, o+piations



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5it"er diagnostic or5it"er diagnostic or

3anage3ent of allergic r"initis'3anage3ent of allergic r"initis'

present or future' needs a goodpresent or future' needs a goodunderstanding of allergic r"initisunderstanding of allergic r"initis

p"atop"ysiologyp"atop"ysiology



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8!*+a,+an- Pat.op./sioog/ an Diagnosti P,oe*,e of Ae,gi R.initis

1or3al i33une p"ysiology1or3al i33une p"ysiology

Ae,gi ,.initis infa++ato,/ es a*+*ation

&./

No,+a e;*iib,- of t.e i++*ne s/ste+

7*+o,a i++*nit/

Ativate %In*ing %I

". 26D


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Pathophysiology of Allergic InflammationPathophysiology of Allergic Inflammation

Three phases :

Sensiti-ation p"ase

5arly P"ase #llergic $eaction

;ate P"ase #llergic $eaction



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#llergic r"initis p"atop"ysiology#llergic r"initis p"atop"ysiology

!ensiti@ation p.ase of ae,gi ,.initis

7o

Dise;*iib,- of t.e i++*ne siste+

Un,est,ite

/to>ine p,ofie

". 0D


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Dise


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Ae,gi Infa++ationAe,gi Infa++ation

IgEBbea,ing (BesIgEBbea,ing (Bes

-

MH

C

Fragment

Th2

1. Sensitization 1. Sensitization !g5 production!g5 production

Adated from Creticos, 1998

IgE antibo/IgE antibo/

IgEIgE

IgEIgE



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-

MH

C

Fragment

Th2

!"inorea

#nee$ing

Congestion

Ae,gi Infa++ationAe,gi Infa++ation

!. Early "hase #llergic $eaction!. Early "hase #llergic $eaction 8$eaksi alergi fase cepac 8$#F248$eaksi alergi fase cepac 8$#F24



IgEIgE

IgEIgE


%astosit

IgEIgE

IgEIgE



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Ae,gi Infa++ation

0. ;ate p"ase #llergic $eaction0. ;ate p"ase #llergic $eaction


-

!"inorea

#nee$ing

Congestion

MHC

Fragment

Th2

%astosit



IgEIgE

IgEIgE


R.ino,ea!nee@ing

ongestion

7R'NI

INFLA%%A"I'N


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P,oinfa++ato,/ /to>ines an es invove in ai,a/P,oinfa++ato,/ /to>ines an es invove in ai,a/

ate p.ase ae,gi infa++ationate p.ase ae,gi infa++ation %Weiss. & A''ergy C'in (mm)no'*2000+105



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#d"esion 3olecules :

!33unoglo=ulin gene superfa3ily : ICAM-1, ICAM-2, VCAM-1

Selectin gene superfa3ilyE-selectin, P-selectin, L-selectin

!ntegrin fa3ily:

LFA-1, Mac-1, p150,5, VLA-!, VLA-", Act-1

Ahesion molecules functions :!"A#$1 %especially for &'S cells)

I"A#$1 an &$selectin

%for &'S( aso an *eutro cells)

7t"er i3portant 3olecular products7t"er i3portant 3olecular products duringduring5arly and ;ateP"ase #llergic $eactions :5arly and ;ateP"ase #llergic $eactions :



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#d"esion 3olecules functions on

recruit3ent of infla33atory cells :

1 ,olling%Ig superfammily an

integrin)

2 #argination

%Ig superfammily anintegrin)

Eos in ai,

avit/ Eos

in"iss*e

(oo vesse

(o.ne,C

1G


3 -iapeesis %.$selectin)

4 an / "hemota0is %Ig superfammily an integrin)


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%ast e H " e inte,ations- %ast e as p,esenting e fo, antigen to "Be-

%Adated from , e!ori and etcalfe, " Aller#y Clin Immunol 1999$1%'(19)



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!/+pto+s:

R*inorr*ea + nee-in#

+ Con#estion + Nasal Itc*y

1 . tri/ial $ 0 . mild$ . moderate$ . se/ere



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!nee@ing

P,eo+inant/ in EPR• 61B2 +in*tes afte, ae,gen expos*,e8

• Is assoiate it. +ast es eg,an*ation:

• 7ista+ine sti++*ation on H1 receptor onC fibre sensory ner/e endin#

• Peptide endotelin21

• 3eu!otrien Naclerio, 1999



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P,*,it*s

• Ex*sive/ in EPR

• Nasa it.ing an Paata i>ing

• 7ista+ine stimmulation on H1 receptor on C fibre

sensory ner/e endin#

• Prota#landin may also constribute Naclerio, 1999



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R.ino,,.ea

• 45cessi/e disc*ar#e from nasal mucous6 membrane• 7e#in min6, last for appro56 0% to % min6 after aler#en c*allen#e

•R.ino,,.ea 67ista+ine ,eease f,o+ %ast es8•P,eo+inant/ in EPRC an aso in LPR

Effet of :

• 7ista+ine on 71 ,eepto,:• 3ea! of plasma and lar#e molecular2ei#*t of proteins

•landular stimulation t*rou#* parasympat*etic ner/e• Aet/.oine• L"


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ongestion

!ensation of in,ease ,esistane to ai, fo it.in t.e nose

as*a, obst,*tive event 6iatation8 : non fi5 obstruction )'

Histamine2H12receptor2mediated2/asodilatation

(*tC 7ista+ine is a +ino, fato, an on/ *,ing EPR

%a/o, fato,s a,e:

PD0, 3;C, 3;D, PA< :/asodilatation mayor factors)

P)D2: 10 J .ista+ine effets (,a/>ininBb,a/>inin 2 ,eepto,

Ne*,opeptie 6!PC aitoninBgene ,eate peptie8

Naclerio, 1999



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Nasa s/+pto+s: 1- K!nee@e, an ,*nne,s 2- K(o>e,s :R*inorr*ea = nee-in# = Con#estion2 Nasal Itc*y)

7isto,/ of nonBnasa ae,gi s/+pto+s:p*aryn5, ear, eye, s!in, lun#)

History of Fa+i/ Ae,g/

DIA)N'!"I P,oe*,e:

Ro*tine tests:6ao,ing to &7' initiative ARIA 20008

• Exte,na Nasa 4 inte,na nasa inia signs

• Non nasa inia ae,gi signs



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(an*ng AR assifiation

Pe,enia ae,gi ,.initis'*pationa ae,gi ,.initis

!easona ae,gi ,.initis

!taging o, Ae,gi R.initis"ota nasa s/+pto+s so,e:

6fo, ,.ino,.eaC snee@ingC ongestionC nasa it.ing8

!tage I 6",ivia8 1 B 3

!tage II 6+i8 < B M

!tage III 6+oe,ate8 G B

!tage I 6seve,e8 10 B 12



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KInte,+itten : t.e s/+pto+s a,e p,esent:

• < a/s a ee>

• ', fo, ess t.an < ee>s

KPe,sistent : t.e s/+pto+s a,e p,esent:

• O < a/s a ee>

• An fo, +o,e t.an < ee>s


Ne assifiation of AR:6ao,ing to &7' iitiative ARIA 20008:


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6ao,ing to &7' initiative ARIA 20008:

K%i : t.at none of t.e fooing ite+s a,e p,esent:• !eep ist*,banes

• I+pai,+ent of ai/ ativit/C eis*,e an9o, spo,t• I+pai,+ent of s.oo o, o,>

• ",o*be so+e s/+pto+s

Ne AR s/+pto+s g,aing assifiation

K%oe,ate !eve,e : 'ne o, +o,e of t.e fooing ite+s a,e p,esent:

•!eep ist*,banes• I+pai,+ent of ai/ ativit/C eis*,e an9o, spo,t• I+pai,+ent of s.oo o, o,>

• ",o*be so+e s/+pto+s


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Aller#y tests + !in test and or

+ erum specific I#4)

4ndoscopy

+ ri#id or + fle5ible

.asa' se/retion %/yto'ogy .asa' /"a''enge % a''ergen 'ysin asirin

!adio'ogy %'ain radiogra"s and or C-s/an

DIA)N'!"I P,oe*,e:

Ro*tine tests:6ao,ing to &7' initiative ARIA 20008



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Nasal biopsy Nasal sab bacteriolo#y

!adio'ogy %RI

• %*oiia,/ f*ntion

• Nasa ai,a/ assess+ent• 'fation tests

• Nit,i oxie +eass*,e+ent

DIA)N'!"I P,oe*,e:

'ptiona tests:6ao,ing to &7' initiative ARIA 20008



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% Scratc" test% Patc" test

% !ntracutan test% Skin prick test% Skin endpoint titration 8S564

S k i n 6 e s t s


5ac" test "as o>n advantages and

disadvantages and specific indication


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% !ndonesian : 6es kulit tusuk

86es kulit cungkit4

% Si3ple' save' painless' and prefera=ly

% Single device 8good enoug" and c"eap4

% Multiple devices 8=etter =ut 3ore e?pensive4

% @olar region

% 6"e rick =e laced A 0 c3 a art

S k i n P r i c k 6 e s t



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%Standardi-ed e?tract

% 6"e =est set: / allergen' =ut can 3ore

% 1o prick =leeding 8in appropriate result4

% #sses3ent: dia3. >"eal and flare 8334

8*' (C' +C' 0C and ,C4 % False negative A positive

S k i n P r i c k 6 e s t



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Skin endpoint titration 8S564


% !ndications:

% !f SP6 negative !D test S56

% For deter3inining !6 allerg. starting dose

% 5?tract 3ite (:(** ot"er (:+* 8Standardi-ed e?tract4


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% Dilution ( : ) 8Mite E((:)** E)0(+.)**4

87t"er #lg: E((:(** E)/+.)**4

% Upper "and region' =e placed A ) c3 apart

% #sses3ent: dia3. >"eal 8334

>"eal * ,33

>"eal () ) 33 81egative resp4

>"eal () A ) 33 8Positive resp4


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S56 interpretation


* 3inute >"eal : , 33

() 3inutes >"eal:

E) E , E 0 E + E ( Dilution

1or3al response

) ) % 33

5ndpoint is E 0

6"e endpoint is t"e ne?t stronger dilution

>it" a A +33 larger >"eal positive response

#=nor3al response:

Flas" response Plateau response Hourglass response


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6"e ulti3ate o=jective of S56 are:

(. Safe initiate dose of i33unot"erapy 8!64

+. Decrease of interval of injection of !6

0. Usefull at prae seasonally or coseasonally !6

,. Safe testing and treat3ent on patient >it"

severe sy3pto3s


6" d t d di d t f i it t t


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6"e advantages and disadvantages of in vitro test


!3unoglo=ulin 5 8!g54% Does not 3ediate t"e allergic alone% sensiti-ed to 3iscellaneous antigens

8not specific4% !g5 $#S6 8*' (C' +C' 0C' ,C4

% !g5 3odified $#S6 8*' (C' +C' 0C' ,C4

% !peifi to one antigen9ae,gen

• (*t expensive


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1- Ae,gi ,.initis is IgE +eiate ./pe,sensitivit/Csta,ting b/ sensiti@ation p.aseC fooe b/

EPR an LPR

'NLU!I'N! :

2- D*,ing LPR : infa++ato,/ es a*+*ation

fooe b/ +eiato,sC /to>inesC .e+o>ines

,eease 6in*ing a.esion +oe*es an

.e+otati fato,s8

3- A.esion +oe*es pa/ an i+po,tant ,oe on ,oingan +a,ginationC iapeesisC an .e+otaxis of

infa++ato,/ es



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'NLU!I'N! :


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jakarta aventis 3 feb 2001

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