MED2 20101203 CT Diseases
Transcript of MED2 20101203 CT Diseases
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Connective Tissue Diseases
Emmanuel C. Perez, M.D., MPH, FPCP, FPRA
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Connective Tissue Diseases
Systemic lupus Erytematosus
Reumatoi! Artritis
Polymyositis / Dermatomyositis
Systemic Sclerosis
Sjogrens Syndrome Mixed Connective Tissue Disease
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Polymyositis "
Dermatomyositis
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Polymyositis "
Dermatomyositis #n$lammatory !isease o$ striate!
s%eletal muscle, some times &itcaracteristic s%in ras
'ccurs (et&een te )tto *t!eca!e o$
li$e &it a $emale prepon!erance
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Classification of Myositis
Dermatomyositis
Polymyositis
Myositis associate! &it CTD Myositis associate! &it mali+nancy
#nclusion (o!y myositis
Myositis !ue to in$ectious a+ents Dru+ an! To-inin!uce! myositis
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Pato+enesis
A((erations in te immune system tat +ives
rise to an increase! suscepti(ility to in$ectious
a+ents viruses an to-oplasma +on!ii/, an! tomo!i$ications o$ cellular immunity tat lea! to
te !evelopment o$ mononuclear cells
capa(le o$ in0urin+ muscle
Complement may play a role in tissue in0uryin !ermatomyositis
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Histopatolo+y
Inflammatory cellular infiltrate&it
associate! degeneration and necrosiso$
muscle $i(ers Regenerationo$ $i(ers an! perivascular
in$lammatory in$iltrate lea!in+ to interstitial
$i(rosis later on Calcinosis may(e seen especially in te
cil!oo! $orm
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Histopatolo+y
#n$iltrates in PM an! #1M contain mainly C23
Tlympocytes an! macropa+es, &ile 1
cells are more common in DM 4asculopaty may(e seen in te small
arteries o$ te muscle, s%in an! te
+astrointestinal tract
Eosinopilic inclusions in te sarcoplasm an
nucleus may(e seen in inclusion (o!y
myositis
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Dia+nostic Criteria $or PM" DM
Symmetric pro-imal muscle &ea%ness withor without dysphagia or respiratory muscle involvement/
Elevation o$ serum muscle enzymes creatinekinase, aldolase, LHD, AST/
Typical EM5 tria! Sort!uration, smallamplitu!e, polypasic motor unit
potentials
Pseu!omyotonic i+$re6uency pattern
Spontaneous $i(rillation an! 3/ sarp &aves sa& tootpattern/ in restin+ muscle
Typical istolo+y in muscle specimens
Caracteristic s%in ras o$ !ermatomyositis
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S%in Rases o$ Dermatomyositis
7ilac !iscoloration o$ te upper eyeli!s&it perior(ital e!ema Heliotrope ras/
Erytematous or atropic scalin+,
patcy or linear ras involvin+ tee-tensor sur$aces o$ te 0oints 5ottron8sras/, $ace, nec% an! (ac% Sa&l si+n/,
or te cest in a 4sape! pattern 4nec% si+n/
Erytematous scalin+ 5ottron8spapules/ over te MCP an P#P 0oints
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Clinical Features o$ #MDFeatures DM PM Myositis
&" CTD
Ras 9:; (-) :; :; >=; =:;
#nterstitial pneumonitis,cariomyopaty, eart
(loc%s
rare rare
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'ter Myositis
Myositis associate! &it mali+nancy? DM i+er association &it mali+nancy@ el!erly PMDM
patients )- li%ely to ave cancer
? Myositis prece!es mali+nancy (y an avera+e o$ > to :
years
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CREST Syn!rome
Telangiectasia
Calcinosis
&aynauds
phenomenon
*sophageal
dysmotility
Sclerodactyly
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Possi(le causes o$ Sclero!erma
5enetic $actors #n$ectious a+ents
? viral, e.+. CM4
? Imolecular mimicryJ
onin$ectious
environmental $actors? silica !ust
? petroleum(ase! solvents
? vinyl clori!e
? contaminate! rapesee! oil
? 7tryptopan
Dru+s? (leomycin
? pentazocin
? cocaine
Microcimerism no. o$ immunolo+ic
stem cell o$ $etal ori+in in
&omen &it sclero!erma
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Pato+enesis
patolo+ic allmar% pro+ressive$i(rosis o$ te s%in an! various internal
or+ans lun+s, eart, 5#T/ !isruption o$ te normal arcitecture o$
te a$$ecte! or+ans lea!in+ to teir!ys$unction an! $ailure
upre+ulation o$ colla+en +enee-pression in SSc $i(ro(lasts
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#mmunopato+enesis
S+SC*PT$%)* ,OST
E-o+enous tri++ers
1cell activation T-C*)) .CT$.T$O0 Activation o$ nonspeci$ic in$lammatory cells
Autoanti(o!ies, #+ #n$lammatory in$iltrates
Solu(le me!iators, cytoto-icity
F#1R'17ASTS ED'THE7#A7 CE77S
Activation, in0ury
#$%&OS$S $SC,*M$C .SC+)OP.T,1
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Difuse cutaneous SScLimited cutaneous SSc
Anti-DNA topoisomerase l
Pulmonary fbrosis
Peripheral vasculopathy
Anti-RNA polymerase l, ll , lllScleroderma kidney
Pulmonary fbrosis
NONE SKIN THICKNESS MAXIMUM
Anticentromere
calcinosis
telaniectasias
Pulmonary fbrosis
Antinuclear anti(o!ies in Sclero!erma
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Autoanti(o!ies
anti-topoisomerase-$ 'Scl-23(? speci$ic
? !i$$use sclero!erma
? interstitial lun+ $i(rosis? Kprotection8 $rom isolate! pulmonary
ypertension
? !i+ital pittin+ scars an! ma-imum s%in
tic%ness score? lcSSc more $re6uent an! more severe
0oint, s%in, an! lun+ involvement
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Autoanti(o!ies
anti-&0. polymerase $4 $$$? !i$$use sclero!erma
? more o$ten male an! ol!er at onset? i+er $re6uency o$ renal an! car!iac
!isease
anti-+5&0P 'fi6rillarin(? nonspeci$ic
? poor outcome in (lac% male patients &it!cSSc an! visceral involvement
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Autoanti(o!ies
anticentromere anti6odies? limite! sclero!erma
? increase! esopa+eal !isease
? possi(le increase! isolate! pulmonaryypertension
? Kprotection8 $rom pulmonary $i(rosis an!renal !isease
PM-Scl? sclero!ermapolymyositis overlap syn!rome
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5enetic mar%er
,).-D&78a
? interstitial lun+ $i(rosis
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Sclero!erma Facies
$ace is stretce!, an!
Imas%li%eJ or
Ie-pressionlessJ
pince! nose tin lips &it
!iminise! oral
aperture
ra!ial $issurin+ aroun!
te mout Imouseli%eJ $ace
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Cutaneous mani$estations
S%in involvement? inflammatory
edematous phase
pu$$iness, s&ellin+,
s%in $le-i(ility
? indurative phase
s%in tic%enin+, pu$$y
$in+ers, loss o$ normal(o!y creases an! s%in
appen!a+es
? atrophic phase
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Cutaneous mani$estations
&aynauds phenomenon
- closure of digital arteries inresponse to cold
- 5 color phases9 whitenessor pallor !ue to
vasoconstriction
cyanosis!ue to stasis an!
removal o$ o-y+en $rom te(loo!
redness!ue to vaso!ilatation
an! reactive yperemia
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Cutaneous mani$estations
periun+al telan+iectasia a(normal nail$ol!
capillary patterns
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Cutaneous mani$estations
ulcerations
telan+iectasias
calcinosis cutis 9;/
? calcium hydro(yapatite deposits
pi+mentary a(normalities
? )salt and pepper* pattern
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Muscle A(normalities
nonspeci$ic
muscle enzymes normal to >::L EM5 a(normalities
s%eletal muscle involvement ris% $or
si+ni$icant myocar!ial !ys$unction
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5astrointestinal Mani$estations
*sophagus
a(normal motility+astroesopa+eal re$lu-
1arrett8s esopa+us
a!enocarcinoma
in$ectious esopa+itis
pillin!uce! esopa+itis
Stomach
+astroparesis
telan+iectasias
Small intestine
pseu!oo(struction
(acterial over+ro&t
telan+iectasias
pneumatosis cystoi!es intestinalis
small (o&el !iverticula
Colon
&i!emout !iverticulacolonic inertia
$ecal"(arium impaction
me+acolon
per$oration
telan+iectasias.norectum
impaire! internal spincterrela-ation
anal spincter restin+ pressure
rectal compliancerectal prolapse
,epatic
primary (iliary cirrosis
!ru+in!uce! epatitis
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Pulmonary Mani$estations
#nterstitial in$lammation
an! $i(rosis
Pulmonary vascular
!isease
1ronciolectasis cysts/
Spontaneous
pneumotora- Pleural !isease
Aspiration pneumonia
Calcinosis
Mali+nancy Pneumoconiosis
silica/
Di$$use alveolar
emorra+e
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#nterstitial 7un+ Fi(rosis
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Ma0or Pulmonary Mani$estationsClinical Features Pulmonary
Hypertension
#nterstitial
Pulmonary Fi(rosisClinical su(set lcSSc lcSSc or !cSSc
Symptoms !yspnea, syncope !yspnea, cou+
Si+ns lou! P< crac%les, !i+italpittin+
PFT isolate! D7C' F4C, FE4>,D7C', FE4>"F4C,
T7CAA associations 3/ ACA, (ut notpre!ictive
3/ Scl:
=year survival N>:; $rom !ia+nosis )=; $rom initialPFTs
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Car!iac #nvolvement
myocar!ial $i(rosis? allmar% o$ car!iac involvement
? patcy
? systolic an!"or !iastolic !ys$unction
myositis
myocar!ial in$arction
con!uction a(normalities an! arrytmias pericar!ial !isease
valvular !isease
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Sclero!erma Renal Crisis
ne& onset o$ accelerate! arterialypertension an!"or rapi!ly pro+ressiveoli+uric renal $ailure !urin+ te course o$
systemic sclerosis primary process en!otelial cell in0ury
in >:; o$ all patients at +reatest ris% are
tose &it !i$$use sclero!erma
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ervous System #nvolvement
Central nervous system mo!i$ication o$ EE5
activity
psyciatricsymptomatolo+y
(ul(ar palsy
Peripheral nervous system
optic neuritis
tri+eminal neuropaty
(ul(ar palsy
t, 2t, 9t,>
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Mana+ement Strate+ies
4ascular terapy
#mmunomo!ulation
Anti$i(rotic !ru+s
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Raynau!8s penomenon
$on#pharmacologic therapy
stop smo%in+, avoi!ance o$ a++ravatin+
!ru+s e.+. (loc%ers/ central an! periperal &armt (o!y
&armers, mu$$s, +loves, etc./
even, am(ient temperature pysical e-ercises &irlin+ o$ te arms,
(io$ee!(ac% tecni6ues/
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Raynau!8s penomenon
Parmacolo+ic terapy Calcium cannel (loc%ers
? lon+ actin+ ni$e!ipine, nicar!ipine
Alpa (loc%ers? prazosin
ACE ini(itors
A+ents &ic a$$ect serotonin
? =y!ro-ytryptamine, %etanserin, SSR#s $luo-etine/ Topical terapy
? trans!ermal nitro+lycerin patces, topicalnitro+lycerin
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Raynau!8s penomenon
parenteral vaso!ilators? car(oprostacyclin #loprost/
+igley - et al., Ann Intern -ed /0012 /345/00
+reater re!uction in te no. o$ &ee%ly attac%s B9 vs.
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Raynau!8s penomenon
Sur+ical proce!ures
lum(ar sympatectomy ra!ical arteriolysis !i+ital sympatectomy/
!e(ri!ement, !i+ital amputation
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#mmunomo!ulation
Cyclopospami!e? uncertain
? primary role in com(ination &itcorticosteroi!s $or patients &it $i(rosin+
alveolitis &o !o not yet ave a!vance!$i(rosis
Corticosteroi!s
? restricte! to patients &it myositis, active$i(rosin+ alveolitis, symptomatic serositis,te early e!ematous pase o$ te s%in!isease, an! re$ractory artritis an!tenosynovitis
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#mmunomo!ulation
Cyclosporine? suppresses CM# an! re!uces colla+en
syntesis
? !iminise! s%in tic%enin+ (ut no can+e in
car!iac or pulmonary !isease? neproto-ic
Metotre-ate
? improve! s%in scores an! sense o$ &ell (ein+? o$ +reater (ene$it in localize! sclero!erma
immunoistocemical parameters/ Seyer !! et al", # $athol 2001
A%r& 193'():511-1*
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Anti$i(rotic Terapy
Dpenicillamine? a$$ects colla+en (iosyntesis an! te immune
system
? improve! cumulative $ive year survival 2:;/an! a lo&er rate o$ ne& visceral involvement
B patients on Dpenicillamine vs. )= patients on place(o
Steen + et al", Ann ntern !ed 1982& 9.:*52
=; improvement in s%in sclerosis in *9 patients treate!&it penicillamine $or * monts
#imene/ SA, et al", # Rheumatol 1991& 18:1(9*
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Anti$i(rotic Terapy
#nter$erons
? ini(it colla+en syntesis
? inter$eron more potent tan inter$eron Colcicine
? ini(its colla+en pro!uction (y !isruptin+
microtu(ule $ormation in $i(ro(lastcytos%eleton
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'ter a+ents
antitymocyte an! antilympocyte +lo(ulin? improvement o$ autoimmune emolytic
anemia, +lomerulonepritis, lun+ $i(rosis, s%in
an! 0oint involvements? in cases o$ severe autoimmune !iseases
unresponsive to re+ular immunosuppressive
treatment Scand 6 Rheumatol /00
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'ter a+ents
e-tracorporeal potoperesis? e$$ective treatment mo!ality in severe
sclero!erma particularly &en starte! early,
&it sta(ilization o$ te !isease course an!partial remission o$ te cutaneous $in!in+s,&ereas visceral involvement may rarelyimprove
>rasagakis > et al., Dermatology /008 /0=
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'ter a+ents
P4A potocemoterapy? $or localize! sclero!erma
Araane et al", # Cutan !ed Sur 2001!ar-A%r& 5'2):135-9
antitymocyte +lo(ulin 3 mycopenolate
mo$etil? $or recent onset !i$$use sclero!erma Stratton R# et al", Rheumatoloy 'ord) 2001
#an&(0'1): 8(-8
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e& Potential Terapies
#mmune
? Rapamycin (loc%s cyto%ine action in Tcell activation"proli$eration
? Mycopenolate mo$etil ini(its lympocyte proli$eration
? Stem cell terapy
? 'ral tolerance in!uces re+ulatory suppression o$ speci$ic immune
response trou+ oral a!ministration o$ smallamounts o$ anti+en
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e& Potential Terapies
Anti$i(rotic
? anticentromere anti(o!ies
(loc% me!iators o$ $i(ro(last activation
? enzyme anta+onists
lysyl an! prolyl y!ro-ylase ini(itors
? pretranslational ini(ition
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'r+an(ase! Terapy
S%in Disease Pruritus
? antiistamines
?lu(ricatin+ creams
Calcinosis? sur+ical removal
? anti(iotics i$ in$ecte!
? pro(eneci!, colcicine, &ar$arin not proven/
? !iltiazem
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'r+an(ase! Terapy
Musculos%eletal Symptoms
.rthritis? acetaminopen,
? SA#Ds
? lo& !ose steroi!s
Myopathy? muscle stren+tenin+ e-ercises 3 SA#Ds
? pysical terapy to limit contractures
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'r+an(ase! Terapy
Renal Disease .C* inhi6itors
? mainstay o$ treatment
? increase! antiypertensive e$$icacy
? associate! &it improve! survival
? (etter preservation o$ renal $unction
? +reater inci!ence o$ renal $unctional recovery Steen + et al", Arthritis Rheum 1998& (1:1*13
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'r+an(ase! Terapy
Renal Disease
Calcium channel 6loc"ers? a!!e! i$ response to ACE ini(itor is ina!e6uate
$ntravenous prostacyclin? at te onset
? anec!otal reports
? elp in te microvascular lesion
#ish oils? teoretically (ene$icial emo!ynamic an! antiplateletproperties
? e$$icacy unproven
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'r+an(ase! Terapy
Pulmonary Disease
0o evidence of lung disease? Reevaluate patient every * monts to permit early
!ia+nosis since :; o$ patients eventually !evelop
lun+ !isease
Symptoms e.+. !yspnea/
Pulmonary $unction tests inclu!in+ D7co
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Fi(rosin+ Alveolitis an!
#nterstitial 7un+ Disease :round glass opacification on ,&CT
? imme!iate terapy in!icate! since tis pattern almost
al&ays respon!s &it an improvement in lun+ $unctionan!"or te appearance on CT scan
? 7o& !ose pre!nisolone
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Fi(rosin+ Alveolitis an!
#nterstitial 7un+ Disease Predominantly reticular
pattern on ,&CT
? Fast clearance o$ isotope onDTPA scannin+ treat as
+roun! +lass +roup
? ormal DTPA clearance
monitor &itout speci$icterapy
P l 4 l Di !
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Pulmonary 4ascular Disease an!
Pulmonary Hypertension
0ifedipine? no !e$initive stu!ies &ic so& an improvement in survival
Chronic anticoagulation ;ith ;arfarin
? still unproven (ut may so& similar (ene$it to tose &it primarypulmonary ypertension #R
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'r+an(ase! Terapy
Car!iac Disease
pericar!itis SA#Ds, corticosteroi!s
pericar!ial
e$$usion
pericar!iocentesis,
pericar!iotomymyocar!ial $i(rosis none
myocar!itis corticosteroi!s
arrytmias o$ten no treatmentre6uire!
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'r+an(ase! Terapy
5astrointestinal Disease
:*&D? pro%inetic !ru+s, omeprazole, sur+ery
$ntestinal pseudoo6struction? pro%inetic !ru+s an! !ietary mo!i$ication $or te
early pase
? rotatin+ anti(iotics $or (acterial over+ro&t
Malnutrition? parenteral nutrition
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Summary
Pro+ressive $i(rosis o$ te s%in an! variousinternal or+ans is te patolo+ic allmar% o$sclero!erma.
E-cessive colla+en !eposition in a$$ecte! tissuesis responsi(le $or most o$ its clinicalmani$estations.
Oile supportive terapy is man!ate!,
parmacolo+ic manipulation o$ te multiple stepsinvolve! in te comple- pat&ay lea!in+ toe-a++erate! $i(ro+enesis o$$ers a potentiallysuccess$ul approac to treatment.
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S0o+ren8s Syn!rome
Cronic in$lammatory !isease
associate! &it lympocyte in$iltration
o$ e-ocrine +lan!s Classi$ication
? Primary
? Secon!ary &it associate! connectivetissue !isease/
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S0o+ren8s Syn!rome
De$ine! as te presence o$ t&o o$ te
$ollo&in+ $in!in+s
? eratocon0uctivitis sicca !ry eyes/? Lerostomia !ry mout/
?Any o$ CTD syn!romes
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S0o+ren8s Syn!rome
More common amon+ mi!!le a+e!
&omen ): years an! a(ove 9:;/
Se- ratio 9> #mmuno+enetic stu!ies !emostrate
H7A12, DRB an! DR&=:;/
? Sclero!erma =2;/
? Polymyositis
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Pato+enesis o$
S0o+ren8s Syn!rome
Caracterize! (y lympocytic Telper
"in!ucer/ in$iltation o$ e-ocrine +lan!s
an! 1lympocyte yperreactivity. Autoanti(o!ies !irecte! to
immuno+lo(ulins rheumatoid a4tor/
an! nuclear" cytoplasmic anti+ensRoSS-A, 6a SS-7/
A ti( ! A i ti i
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Anti(o!y Associations in
S0o+ren8s Syn!rome Earlier !isease onset
7on+er !isease !uration
Salivary +lan! enlar+ement Severe lympocytic in$iltration o$ minor
salivary +lan!s
E-tra+lan!ular mani$estations? lympa!enopaty
? purpura
? vasculitis
Clinical Mani$estations o$
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Clinical Mani$estations o$
S0o+ren8s Syn!rome
Lerostomia &it !ry, erytematous, stic%y oralmucosa
Decrease! lacrimal an! salivary +lan! $unctions
? Dyspa+ia &it (urnin+ sensation in te mout
? #na(ility to spea% continously
? #ncrease! !ental caries
? Paroti! +lan! enlar+ement
? Dry eyes &it san!y or +ritty sensation lea!in+ to eyeirritation, re!ness, itcin+ an! corneal ulcerations
E-tra+lan!ular Mani$estations
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E-tra+lan!ular Mani$estations
in S0o+ren8s Syn!rome
Artral+ias" onerosive artritis
Raynau!8s penomenon
7ympa!enopaty
7un+, i!ney, an! liver involvement
4asculitis
7ympoma
Splenome+aly Periperal neuropaty
Myositis
T t t
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Treatment
Symptomatic relie$ an! limit !ama+e o$-erostomia an! CS
Flui! replacement i.e. arti$icial tears
Avoi!ance o$ te $ollo&in+ me!ications
? Diuretics?Antiypertensives
?Anti!epressants
'ter me!ications
? Pilocarpine, (rome-ine
? Hyro-ycloro6uine
? steroi!s
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THA '
$or your %in! attention
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