SLE.kulah FKUMJ 2010 Fkkumj

7/23/2019 SLE.kulah FKUMJ 2010 Fkkumj

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SLE

J.Pudji Rahardjo. Sp.PD – kGH

Jakarta



SLE : Definition

• a chronic inflammatory disease of unknowncause

• that can affect the skin, joints, kidneys, lungs,

nervous system, serous membranes and/orother organs of the body.

• mmunologic abnormalities, es!ecially the!roduction of a number of antinuclear

antibodies, are another !rominent feature of thedisease.



SLE : "linical #anifestation

$he clinical course :

%ariable and

"haracteri&ed by !eriods of

remissions and chronic or acute rela!ses.'omen, es!ecially in

their ()s and *)s, are affected more

fre+uently than men.atients with SLE are subject to myriad

sym!toms, com!laints, and inflammatory

involvement that can affect virtually every



SLE :

$he most common !attern is a mi-ture ofconstitutional com!laints with skin,

musculoskeletal, mild

hematologic, serologic

involvement . Some !atients

have !redominately hematologic, renal, or

central nervous system manifestations.

$he !attern that dominates during the first fewyears of illness tends to !revail subse+uently



SLE : Diagnosis

Straightforward in a patient who presents

with several o!pati"le linial featuresand has supportive la"orator# studies.

E-am!le is a young woman who presents with complaints of fatigue,arthralgia, and pleuritic chest pain, who isfound to have hypertension, a malar rash,a pleural friction rub, several tenderand swollen joints, and mild peripheral

edema. .



SLE : Diagnosis



Laboratory testing may reveal leukopenia,

anemia, an elevated serum creatinine,hypoalbuminemia, proteinuria, an

active urinary sediment,hypocomplementemia, a positive

Coombs test, and positive tests forantinuclear antibodies, including those todouble stranded DNA and the SmithSm! antigen.



SLE : Diagnosis



Laboratory testing may reveal leukopenia,

anemia, an elevated serum creatinine,hypoalbuminemia, proteinuria, an

active urinary sediment,hypocomplementemia, a positive

Coombs test, and positive tests forantinuclear antibodies, including those todouble stranded DNA and the SmithSm! antigen.



SLE : Diagnosis

• Straightforward in a patient who presentswith several o!pati"le linial featuresand has supportive la"orator# studies..

SLE an also ause isolatedcytopenias or single organ involvementeg, nephritis or pericarditis!, or may firstbe manifested by an incidentallaboratory finding, such as a biologicfalse positive test for syphilis.

Such !atients may subse+uently develo!the characteristic multisystem features ofSLE over a !eriod of months or years.



Presenting linial !anifestations

$suall# SLE "egins with one or several of the following features %

• $ne&plained nonspeifi s#!pto!s suh as fever' fatigue' or weightloss.

• Photosensitive rash• (rthralgia or arthritis• Ra#naud pheno!enon• Serositis )pleuritis' periarditis' peritonitis*• +ephritis or nephroti s#ndro!e• +eurologi s#!pto!s suh as sei,ures or ps#hosis• (lopeia• Phle"itis• Reurrent !isarriage• (ne!ia

• SLE should also "e suspeted in #oung wo!en presenting withpurpura' eas# "ruising' diffuse adenopath#' hepatospleno!egal#'peripheral neuropath#' endoarditis' !#oarditis' interstitialpneu!onitis' or asepti !eningitis. ( positive -oo!"s test'h#poo!ple!ente!ia' and i!!une deposits at the der!alepider!al

juntion on skin "iops# are other findings suggestive of lupus.



La"orator# testing

La"orator# tests that !a# provide diagnostiall# useful infor!ation when SLEis suspeted inlude%

•-o!plete "lood ount and differential

• -o!prehensive !eta"oli profile• -reatine kinase• Er#thro#te sedi!entation rate and/or - reative protein• $rinal#sis• 01hour urine olletion for alulation of reatinine learane•

and 2uantitation of proteinuria or protein/reatinine ratios

(utoanti"od# testing is also indiated )see 3(utoanti"odies3 "elow*. 4hoseautoanti"odies that are routinel# assa#ed are%

• (ntinulear anti"odies )(+(*• (ntiphospholipid anti"odies•

(nti"odies to dou"le stranded D+(• (ntiS!ith )S!* anti"odies

5easure!ent of seru! o!ple!ent levels -6 and -1 !a# also "e helpful'sine h#poo!ple!ente!ia is a fre2uent finding in ative SLE.



La"orator# testing

La"orator# tests that !a# provide diagnostiall# useful infor!ationwhen SLE is suspeted inlude%

• -o!plete "lood ount and differential• -o!prehensive !eta"oli profile• -reatine kinase• Er#thro#te sedi!entation rate and/or - reative protein• $rinal#sis• 01hour urine olletion for alulation of reatinine learane• and 2uantitation of proteinuria or protein/reatinine ratios

(utoanti"od# testing is also indiated )see 3(utoanti"odies3 "elow*.4hose autoanti"odies that are routinel# assa#ed are%

• (ntinulear anti"odies )(+(*• (ntiphospholipid anti"odies• (nti"odies to dou"le stranded D+(• (ntiS!ith )S!* anti"odies

5easure!ent of seru! o!ple!ent levels -6 and -1 !a# also "e helpful'sine h#poo!ple!ente!ia is a fre2uent finding in ative SLE.



7!aging

Diagnosti i!aging !a# "e valua"le

"ut is not routinel# o"tained unlessindiated "# the presene ofs#!pto!s' linial findings' orla"orator# a"nor!alities. E&a!ples

inlude% –Plain radiographs of involved joints –Renal ultrasonograph# to assess kidne#

si,e and rule out urinar# trat

o"strution when there is evidene ofrenal i!pair!ent

–-hest radiograph#



7!aging

Diagnosti i!aging !a# "e valua"le "ut is notroutinel# o"tained unless indiated "# the

presene of s#!pto!s' linial findings' orla"orator# a"nor!alities. E&a!ples inlude% – Ehoardiograph# )eg' for suspeted periardial

involve!ent' to assess for a soure of e!"oli' ornoninvasive esti!ation of pul!onar# arter# pressure*

– -o!puted to!ograph# )-4* )eg' for a"do!inal pain'suspeted panreatitis*

– 5agneti resonane i!aging )eg' for foal neurologidefiits or ognitive d#sfuntion*

– -ontrast angiograph# !a# "e valua"le if vasulitisaffeting !ediu! si,ed arteries is suspeted )eg'!esenteri or li!"threatening ishe!ia*



8iops# 9 :ther tests

• 8iops# of an involved organ )eg' skin

or kidne#* is neessar# in so!e ases.

4here are t#pial histologi findings in

various organs in SLE to the partiularsites of involve!ent' suh as the

kidne#.



8iops# 9 :ther tests

• :ther tests that !a# "e neessar# are

t#piall# ditated "# the linial presentationand assoiated differential diagnosti

possi"ilities.

E&a!ples inlude% – "lectrocardiography in the assessment of chest

pain that may be due to pericarditis

– #ests to assess for pulmonary embolism in a

patient with pleuritic chest pain and dyspnea

– Diffusing capacity for carbon mono$ide D%C&! to

assess for suspected pulmonary hemorrhage and

estimate the severity of interstitial pneumonitis



Diagnostic criteria

• useful a!!roach to the detection of SLE and indifferentiating it from other systemic disordershas been the use of a +uestionnaire.

• f three or more +uestions are answered!ositively, SLE is a !ossibility and an test isindicated.

• $esting for antinuclear antibodies has re!lacedlooking for evidence of !hagocytosis of nuclearmaterial 0LE cells1 in a blood smear, but LE cellsmay still be noted incidentally in body fluids suchas !leural or !ericardial effusions.



;uestionnaire for the diagnosis of s#ste!i lupus

er#the!atosus

•

Have #ou ever had arthritis or rheu!atis! for !ore than 6 !onths<• Do #our fingers "eo!e pale' nu!"' or uno!forta"le in the old<• Have #ou had an# sores in #our !outh for !ore than 0 weeks<• Have #ou "een told that #ou have low "lood ounts )ane!ia' low

=8- ount' or low platelet ount*<• Have #ou ever had a pro!inent rash on #our heeks for !ore than

> !onth<• Does #our skin "reak out after #ou have "een in the sun )not

sun"urn*<• Has it ever "een painful to take a deep "reath for !ore than a few

da#s )pleuris#*<• Have #ou ever "een told that #ou have protein in #our urine<•

Have #ou ever had rapid loss of lots of hair<• Have #ou ever had a sei,ure' onvulsion' or fit<



(R( -riteria for diagnosis of SLE

-riterion Definition

5alar rash ?i&ed er#the!a' flat or raised' over the !alar e!inenes'tending to spare the nasola"ial folds

Disoid rash Er#the!atosus raised pathes with adherent keratotisaling and folliular plugging@ atrophi sarring !a#

our in older lesionsPhotosensitivit# Skin rash as a result of unusual reation to sunlight' "#

patient histor# or ph#siian o"servation:ral ulers :ral or nasophar#ngeal uleration' usuall# painless'o"served "# a ph#siian

(rthritis +onerosive arthritis involving 0 or !ore peripheral joints'harateri,ed "# tenderness' swelling' or effusion

Serositis Pleuritis onvining histor# of pleuriti pain or ru" heard "#a ph#siian or evidene of pleural effusion :R

Periarditis dou!ented "# EAG' ru" or evidene ofperiardial effusion

Renal disorder Persistent proteinuria greater than B.C gra!s per da# orgreater than 6 if 2uantitation not perfor!ed :R

-ellular asts !a# "e red ell' he!oglo"in' granular' tu"ular' or

!i&ed



(R( -riteria for diagnosis of SLE

-riterion Definition

+eurologi disorder Sei,ures :R ps#hosis in the a"sene of offendingdrugs or known !eta"oli derange!ents )ure!ia'

ketoaidosis' or eletrol#te i!"alane*He!atologi disorder He!ol#ti ane!ia with retiulo#tosis :R

Leukopenia less than 1'BBB/!!6 total on two or !ore

oasions :R

L#!phopenia less than >'CBB/!!6 on two or !oreoasions :R

4hro!"o#topenia less than >BB'BBB/!!6 in the a"sene

of offending drugs

7!!unologi disorders Positive antiphospholipid anti"od# :R

(ntiD+( anti"od# to native D+( in a"nor!al titer :R

(ntiS! presene of anti"od# to S! nulear antigen :R?alse positive serologi test for s#philis known to "e

positive for at least si& !onths and onfir!ed "# 4repone!a

pallidu! i!!o"ili,ation or fluoresent trepone!al anti"od#

a"sorption test

(ntinulear anti"od# (n a"nor!al titer of antinulear anti"od# "#

i!!unofluoresene or an e2uivalent assa# at an#point in ti!e and in the a"sene of drugs known to "eassoiated with dru indued lu us s ndro!e



Diagnosti riteria

• 5ost ph#siians rel# on diagnosti

riteria for lupus that were developed"# the (!erian Rheu!atis!(ssoiation )(R(' now the (!erian-ollege of Rheu!atolog# or (-R*

• 4hese riteria were developed for thelassifiation of SLE patients whenSLE was o!pared to other rheu!ati

diseases for stud# purposes.



Diagnosti riteria

•

=hether these riteria appl# to otherpopulations has not "eenesta"lished' although the# have "eenused to de!onstrate that thefre2uen# of SLE is higher a!ong(fro(!erians' (fro-ari""eans'(nglo(sians' and (!erian

Hispanis than in -auasians• SLE is virtuall# none&istent a!ong

8laks in (fria



Diagnosti riteria

• 4he diagnosis of SLE is !ade if four or!ore of the !anifestations are present'either seriall# or si!ultaneousl#' duringan# interval of o"servations.

•( positive LE ell test' used in the olderriteria' has "een replaed "# thepresene antiphospholipid anti"odies.

• =hen tested against other rheu!atidiseases' these riteria have a sensitivit#and speifiit# of appro&i!atel# Fperent.



Diagnosti riteria

• 2sing the analogy of the "3 criteria for the diagnosis of

rheumatoid arthritis, suggest that !atients be classified asfollows: – Classical S%" ' many criteria – Definite S%" ' four or more criteria – (ndifferentiated connective tissue disease

• 2ndifferentiated connective tissue disease 02"$D1 isdefined as a !atient with a !ositive serology and evidence ofinflammation on e-amination who does not meet the "3criteria for SLE any other autoimmune disorder.

• atients with 2"$D need to be followed carefully andencouraged to re!ort new sym!toms and to have !eriodiclaboratory testing to assess for the emergence of newclinical features or laboratory findings.



utoantibodies

•

$he test is the best diagnostic test forSLE and should be !erformed wheneverSLE is sus!ected

• $he is !ositive in significant titer

0usually 4:45) or higher1 in virtually all!atients with SLE.

• $he !robability of having SLE in a !o!ulationat variable risk for lu!us is less than ).46

!ercent if the test is negative.



utoantibodies

• (ntinulear anti"odies are alsopresent' usuall# in lower titer' in avariet# of other disorders %% – Sjgren3s s#ndro!e I perent –

Sleroder!a I 1B to KC perent)espeiall# with a spekledpattern of(+(s*

– Juvenile rheu!atoid arthritis I > perent

– Rheu!atoid arthritis I 0C to CB perent)espeiall# with a diffuse pattern of (+(s*



utoantibodies

• dsD and Sm antibodies – $here are two autoantibodies that are highly s!ecific

for SLE: anti7double7stranded D 0dsD1

antibodies8 and anti7Sm antibodies .

– $he sensitivity is much lower at about 9 and (

!ercent, res!ectively. – ;ne study, for e-am!le, evaluated seven commercial

ELS assays for anti7dsD antibodies8 the following

results were obtained <(=>:

•Sensitivity ' )) to *+ percent

• Specificity ' + to - percent

• /redictive value ' 0* to - percent



D7??ERE+47(L D7(G+:S7S

• Given the protean !anifestations of SLE' thedifferential diagnosis is orrespondingl# "road% –

Systemic sym!toms causes of chronic fatigue and weightloss should be considered. – olyarthritis/!olyarthralgia – 3enal disease – ;ther causes of im!aired renal function –

"utaneous lesions – #ucosal lesions – bdominal !ain – Liver disease – Lung disease –

"ardiovascular disease – "entral nervous system disease – ;!hthalmologic disease – ?ematologic abnormalities – Lym!hadeno!athy



SLE % PR:G+:S7S

• S#ste!i lupus er#the!atosus )SLE* is a

hroni' oasionall# life threatening'!ultis#ste! disorder.

• Patients suffer fro! a wide arra# of s#!pto!sand have a varia"le prognosis that depends

upon the severit# and t#pe of organinvolve!ent.

• Due to the unertain ourse' effetive treat!entre2uires ongoing patientdotor o!!uniation

to orretl# interpret la"orator# tests' alleviates#!pto!s' prevent and treat relapses' andlessen side effets related to drug therap#.

DE4ER57+(47:+ :? D7SE(SE (-4774M (+D



DE4ER57+(47:+ :? D7SE(SE (-4774M (+D

SEER74M

•

(n effetive therapeuti regi!en firstre2uires the aurate deter!ination of"oth disease ativit# and severit#

• Disease ativit# usuall# refers to the

degree of infla!!ation' while severit#i!plies that organ funtion and perhapsits underl#ing struture is 2uantitativel#i!paired.

•

4he degree of organ d#sfuntion has"een referred to as the da!age inde&.

DE4ER57+(47:+ :? D7SE(SE (-4774M (+D



DE4ER57+(47:+ :? D7SE(SE (-4774M (+D

SEER74M

•

4he presene of severe organd#sfuntion does not neessaril# i!pl#ongoing infla!!ation. (s an e&a!ple'!arked proteinuria and a dereasing

glo!erular filtration rate !a# result fro!either ative infla!!ation or inativesarring.

• 4he a"ilit# to differentiate "etween these

two possi"ilities is e&tre!el# i!portant'sine i!!unosuppressive therap# is notindiated in the latter setting.



-liniall# useful !arkers of ativit#

• Disease ativit# is assessed using a o!"ination of the linialhistor#' ph#sial e&a!ination' organ speifi funtional tests' and

serologi studiesE&a!ples inlude% – (tive SLE )partiularl# lupus nephritis* is often preeded "# a rise in

7gG antidou"lestranded D+( titers' a fall in o!ple!ent levels)espeiall# -HCB' -6 and -1*' and an elevation in o!ple!ent split andativation produts.

–

Persistentl# low seru! levels of o!ple!ent ->2 are assoiated withontinued ativit# of proliferative glo!erulonephritisN. – ?alling levels of antiD+( anti"odies !a# our in assoiation with

ative disease – 7nreases in the er#thro#te sedi!entation rate )ESR* and the seru! -

reative protein )-RP* onentration are also o!!onl# seen with inthis settingN' as well as in assoiation with a "road range of linial

features' ativit#' and organ da!age in one stud# O0N' "ut onl# withativit# )espeiall# onstitutional' e#e' pul!onar#' gastrointestinal' andneurologi*' "ut not with an inde& of organ da!age.

– 4here are onfliting data on the diagnosti value of a !arkedelevation of -RP in distinguishing ative lupus fro! infetion' "ut a!arkedl# elevated level of -RP in a patient with SLE should raise thesuspiion for infetion.



-liniall# useful !arkers of ativit#

• Disease activity is assessed using a combination of the

clinical history, !hysical e-amination, organ s!ecificfunctional tests, and serologic studies

• ?owever, not all !atients with these serologic markers haveactive disease and these markers do not necessarily !redict

disease e-acerbation.



?re2uen# of la"orator# testing

• #onitoring laboratory tests are tailored to each !atient, in

general, !atients with more active disease are monitoredmore fre+uently, while those with inactive disease re+uireless fre+uent monitoring.

s e-am!les: – !atient with active lu!us ne!hritis might have a battery of

tests done once weekly. – @or someone with a reduction in glomerular filtration ratewhose disease is stable and who is free of !roteinuria,testing every two to three months may be a!!ro!riate.

– !atient with !reviously active ne!hritis, a normalglomerular filtration rate and no !roteinuria, whose SLE is

otherwise +uiescent, may be tested every four to si-months.

– Someone with no history of renal involvement and+uiescent disease may be retested every 5 to 4( months



$he following laboratory tests are suggested for monitoring

in a !atient with a !revious history of renal involvement

who is currently free of !roteinuria and who has a normal

creatinine clearance.

• -o!plete "lood ount• Er#thro#te sedi!entation rate• -reative protein• $rinal#sis with e&a!ination of urinar# sedi!ent• Spot )unti!ed* urine protein and reatinine• Seru! reatinine and esti!ated glo!erular filtration rate

)eG?R*• Seru! al"u!in• (ntidsD+(•

-o!ple!ent )-HCB or -6 and -1*

?or patients without a histor# of lupus nephritis' the spot)unti!ed* urine protein and reatinine and seru! al"u!in areunneessar#.



GE+ER(L 4RE(45E+4

-:+S7DER(47:+S

• lthough organ involvement re+uires s!ecificdrug thera!y, a number of general issues area!!licable to every !atient with SLE.

•

Sun !rotection A void e-!osure to direct orreflected sunlight and other sources of ultravioletlight 0eg, fluorescent and halogen lights1. 2sesunscreens, !referably those that block both 2%7

and 2%7B, with a minimum skin !rotection

factor 0S@1 of *).



GE+ER(L 4RE(45E+4

-:+S7DER(47:+S

•

Diet and nutrition A Limited data e-ist concerning the effectof dietary modification in SLE. ;f two studies !erformed byone grou! of investigators, the largest trial randomlyassigned 5) !atients to either receive 4.C grams ofeicosa!entanoic acid 0E1 and 4.( grams ofdocosahe-anoic acid 0D?1 or !lacebo, daily, for (6 weeks.$hose on fish oil had a significantly greater reduction in aninde- of disease activity 0SL#731 and im!rovement inendothelial function as assessed by flow7mediated arterialdilation than did the !lacebo grou!. $hese findings awaitinde!endent confirmation: at !resent, we do not recommend

fish oil su!!lements in the treatment of SLE.

• conservative a!!roach is to recommend a balanced dietconsisting of carbohydrates, !roteins, and fats. ?owever,the diet should be modified based u!on disease activity and

the res!onse to thera!y



GE+ER(L 4RE(45E+4

-:+S7DER(47:+S

• %itamins are rarely needed when !atients eat a balanceddiet. ?owever, a daily multivitamin should be taken by!atients who are not able to obtain an ade+uate diet orwho are dieting to lose weight.

• $he majority of !atients with SLE have low serum levels

of (7hydro-yvitamin D 0calcidiol1 <6=>, !robably due atleast in !art to avoidance of sun e-!osure. atients withlow vitamin D levels should be treated with su!!lemental%itamin D.

• atients on long7term glucocorticoids and

!ostmeno!ausal women should ingest C)) units ofvitamin D !lus 4)) mg of calcium !er day and/or abis!hos!honate to minimi&e the degree of bone loss.

• ?erbs are of un!roven benefit, and may cause harm.



GE+ER(L 4RE(45E+4 -:+S7DER(47:+S

• E&erise I 7nativit# produed "# aute illness auses a rapidloss of !usle !ass and sta!ina resulting in a sense offatigue. 4his an usuall# "e treated with graded e&erise. 7nseleted refrator# ases' relief an "e o"tained withanti!alarial drugs.

• S!oking essation I -igarette s!oking !a# inrease the riskof developing SLE' and s!okers in general have !ore ativedisease. Patients should "e ounseled not to s!oke' or to 2uits!oking and provided with help to do so.

• 7!!uni,ations I 7t had "een previousl# thought thati!!uni,ation ould e&aer"ate SLE. However' influen,avaine and pneu!ooal vaines also safe "ut resultant

anti"od# titers are so!ewhat less in patients with SLE than inontrols. $se of gluoortioids' suh as prednisone' or otheri!!unosuppressive agents !a# ontri"ute to the "luntedanti"od# response.



GE+ER(L 4RE(45E+4 -:+S7DER(47:+S

• n contrast, it is inadvisable to immuni&e !otentially

immunosu!!ressed !atients 0including those treated withglucocorticoids alone at doses e+uivalent to () mg/dayof !rednisone for more than two weeks1 with livevaccines 0eg, measles, mum!s, rubella, !olio, varicella,and vaccinia <small!o->1

• 'hile the issue of efficacy of vaccination with he!atitis Bvaccine has not been com!letely resolved, the risks!osed by ?e!B vaccine to !atients with SLE must atmost be very small>.



GE+ER(L 4RE(45E+4

-:+S7DER(47:+S

• 3adiation thera!y A necdotal re!orts of increased to-icity following thera!euticioni&ing radiation have made radiation oncologists wary of treating !atients with SLEand other collagen vascular disorders <=>. atients with scleroderma may be atgreater risk. ?owever, if needed, radiation thera!y may be used in !atients with SLEto treat malignant disease. $wo observational series have included 4= !atients withSLE among those with collagen vascular diseases receiving radiation thera!y forcancer <5),54>. o unusually severe local reactions in the skin or subcutaneoustissues in the radiation !ortal were noted in those with lu!us. n contrast, in a study of49 !atients with SLE, four had a grade * or higher to-icity at to 4) years, es!eciallyin !atients with more severe disease, and more organ involvement <5(>. ;ther studies<5*> and a review <56> arrive at similar conclusions: that radiation thera!y can!robably be given to most !atients with SLE, e-ce!t for those with severe multi7organdisease, to whom radiation thera!y should be used with caution if at all.

• voidance of s!ecific medications A Some data suggest that sulfonamide7containingantibiotics 0eg, sulfadia&ine, trimetho!rim7sulfametho-a&ole, sulfiso-a&ole1 and!enicillin 0but not the semisynthetic !enicillins1 may cause e-acerbations and shouldtherefore be avoided <5>. $his im!ression with regard to sulfa7containing agents wassu!!orted by the following:

• F case7control study of 46 !atients with SLE and 4)6 controls8 adverse reactions

to sulfonamide7containing antibiotics were more than twice as fre+uent in those withSLE 0( versus 4= !ercent1 <55>.



GE+ER(L 4RE(45E+4

-:+S7DER(47:+S

• Radiation therap# I (nedotal reports of inreased to&iit#following therapeuti ioni,ing radiation have !ade radiationonologists war# of treating patients with SLE and otherollagen vasular disorders. Patients with sleroder!a !a# "eat greater risk. However' if needed' radiation therap# !a# "eused in patients with SLE to treat !alignant disease. 4wo

o"servational series have inluded >F patients with SLE a!ongthose with ollagen vasular diseases reeiving radiationtherap# for aner. +o unusuall# severe loal reations in theskin or su"utaneous tissues in the radiation portal were notedin those with lupus. 7n ontrast' in a stud# of >K patients withSLE' four had a grade 6 or higher to&iit# at C to >B #ears'espeiall# in patients with !ore severe disease' and !oreorgan involve!ent. :ther studies and a review arrive at si!ilaronlusions% that radiation therap# an pro"a"l# "e given to!ost patients with SLE' e&ept for those with severe !ultiorgan disease' to who! radiation therap# should "e used withaution if at all.



GE+ER(L 4RE(45E+4

-:+S7DER(47:+S

• (voidane of speifi !ediations I So!e data suggest thatsulfona!ideontaining anti"iotis )eg' sulfadia,ine'tri!ethopri!sulfa!etho&a,ole' sulfiso&a,ole* and peniillin)"ut not the se!is#ntheti peniillins* !a# ausee&aer"ations and should therefore "e avoided. 4hisi!pression with regard to sulfaontaining agents was

supported "# the following% – ( aseontrol stud# of >1C patients with SLE and >B1

ontrols@ adverse reations to sulfona!ideontaininganti"iotis were !ore than twie as fre2uent in those withSLE )C0 versus >F perent*.

– ( stud# of 1>K patients with SLE' a!ong who! >>1 had a

histor# of sulfona!ide allerg#.

• 7n ontrast' !ediations that ause drugindued lupus' suhas proaina!ide and h#drala,ine' do not ause e&aer"ationsof idiopathi SLE. 4his o"servation is a presu!ed refletion ofthe pathogeneti differenes "etween the two disorders



GE+ER(L 4RE(45E+4

-:+S7DER(47:+S

• Pregnan# and ontraeption I Pregnan# should "eavoided during ative disease )espeiall# withsignifiant organ i!pair!ent* due to the high risk of!isarriage and e&aer"ation of SLE. =o!en with SLEshould "e ounseled not to "eo!e pregnant until the

disease has "een 2uiesent for at least si& !onths.

• Pregnant patients with ative lupus are generall#!anaged with gluoortioids. :ther drugs used duringpregnan# inlude nonsteroidal antiinfla!!ator# drugs

and h#dro&#hloro2uine )pro"a"l# safe*.-#lophospha!ide and !ethotre&ate areontraindiated' while a,athioprine an "e autiousl#used.



GE+ER(L 4RE(45E+4

-:+S7DER(47:+S

• :ral ontraeptives ontaining high dose estrogens anause e&aer"ations of SLE. However' this o!pliationrarel# ours with the urrent use of lowdose estrogenor progesterone ontaining o!pounds. Patients with!igraine headahes' Ra#naud pheno!enon' a histor#

of phle"itis' or antiphospholipid anti"odies pro"a"l#should not "e treated with oral ontraeptives.Hor!one replae!ent therap# in post!enopausalwo!en !a# "e assoiated with a !odest inrease inthe rate of flares' and deisions a"out use of estrogen

for post!enopausal s#!pto!s !ust "e arefull#onsidered weighing the potential "enefits against risksof thro!"oti events' "reast and uterine aner.

4RE(45E+4 :? SPE-7?7- :RG(+



4RE(45E+4 :? SPE-7?7- :RG(+

7+:LE5E+4 I

• ( nu!"er of !ediations are o!!onl# used

in the treat!ent of SLE' inluding nonsteroidalantiinfla!!ator# drugs )+S(7Ds*' anti!alarials)pri!aril# h#dro&#hloro2uine*'gluoortioids' and i!!unosuppressiveagents )inluding #lophospha!ide'!ethotre&ate' a,athioprine' and!#ophenolate*.

• Patient o!pliane with reo!!endedtreat!ent is' as e&peted' assoiated with

"etter outo!es than nono!pliane.

4RE(45E+4 :? SPE-7?7- :RG(+



4RE(45E+4 :? SPE-7?7- :RG(+

7+:LE5E+4 I

• Drugs whih are preferred in seleted linial settings.

– 4opial therapies are often useful for loalpro"le!s and redue the risk of side effets thatare assoiated with s#ste!i use of +S(7Ds'gluoortioids' or i!!unosuppressants suh astaroli!us )Protopi*.

–+S(7Ds are generall# effetive for!usuloskeletal o!plaints and !ild serositis.-#loo&#genase )-:Q*0 seletive inhi"itors !a#also "e effetive in suh patients. :f the availa"le-:Q0 inhi"itors' eleo&i" ontains a

"en,enesulfona!ide !oiet# and should "e usedwith aution in those patients with a histor# ofallerg# to sulfona!ide ontaining anti"iotis.However' eleo&i" has "een used in SLEpatients' even those with sulfa allerg#' withoutpreipitating an# allergi response.

4RE(45E+4 :? SPE-7?7- :RG(+



4RE(45E+4 :? SPE-7?7- :RG(+

7+:LE5E+4 I

• (nti!alarials ae !ost useful for skin

!anifestations and for !usuloskeletalo!plaints that do not ade2uatel# respond to+S(7Ds.

• 7n addition' in longter! studies the use of

anti!alarials' suh as h#dro&#hloro2uine'prevented !ajor da!age to the kidne#s andentral nervous s#ste!.

• 4heir use !a# also redue the risk of diseaseflares@ though this is less lear for renal and

entral nervous s#ste! !anifestations @anti!alarials are not the drugs of hoie fordisease in these organ s#ste!s.

4RE(45E+4 :? SPE-7?7- :RG(+



4RE(45E+4 :? SPE-7?7- :RG(+

7+:LE5E+4 I

• S#ste!i gluoortioids )eg' high dosesof > to 0 !g/kg/da# of prednisone ore2uivalent or as inter!ittent intravenouspulses of !eth#lprednisolone* usedalone or in o!"ination withi!!unosuppressive agents are generall#reserved for patients with signifiantorgan involve!ent' partiularl# renal andentral nervous s#ste! disease. 4here

are a pauit# of data to support the use ofintravenous pulse versus dail# oralgluoortioids.

4RE(45E+4 :? SPE-7?7- :RG(+



4RE(45E+4 :? SPE-7?7- :RG(+

7+:LE5E+4 I

• 7!!unosuppressive agents suh as!#ophenolate or #lophospha!ide are givenwith gluoortioids to patients with !ore than!ild lupus nephritis' and #lophospha!ide tothose with alveolar he!orrhage' s#ste!i

vasulitis' and to !ost patients with signifiantentral nervous s#ste! involve!ent.• Lower doses of gluoortioids )eg' >B !g/da#

of prednisone* !a# "e used for s#!pto!atirelief of severe arthralgia' arthritis' or serositis

while awaiting a therapeuti effet fro! other!ediations.

4RE(45E+4 :? SPE-7?7- :RG(+



4RE(45E+4 :? SPE-7?7- :RG(+

7+:LE5E+4 I

• $reatment with !rednisone as soon as asignificant rise in anti7dsD occurs !reventedrela!ses in most cases in a study of 45!atients. s noted above, however, we followsuch !atients closely but do not treat titers in the

absence of clinical evidence of active disease.

• $reatment with immunosu!!ressive medicationsother than glucocorticoids 0eg, methotre-ate,cyclo!hos!hamide, a&athio!rine,myco!henolate, or ritu-imab1 is generallyreserved for !atients with significant organinvolvement, and/or !atients who have had aninade+uate res!onse to glucocorticoids.

RES7S4(+4 D7SE(SE (+D EQPER75E+4(L



RES7S4(+4 D7SE(SE (+D EQPER75E+4(L

4HER(PM

• Patients with severe organ involve!ent

who are resistant to

#lophospha!ide therap# generall#

do poorl#.• 4he opti!al approah to suh patients

is unertain.

PR:G+:S7S



PR:G+:S7S

• SLE an run a varied linial ourse' ranging

fro! a relativel# "enign illness to a rapidl#progressive disease with ful!inant organfailure and death. 5ost patients have arelapsing and re!itting ourse' whih !a# "eassoiated with the use of high dose steroids

during the treat!ent of severe flares.

PR:G+:S7S



PR:G+:S7S

• Patient survival A $he five7year survival rate in SLEhas dramatically increased over the last several decadesfrom a!!ro-imately 6) !ercent in the 4=)s to more than =)!ercent in studies beginning after 4=C), a trend that hascontinued into the early (4st century.

• $he likelihood of survival can be ranked on the basis oforgan involvement 0skin and musculoskeletal best, central

nervous system and kidney worst1 and on the number of merican "ollege of 3heumatology criteria for SLE. ;lderage, male se-, !overty, and a low com!lement may also be!oor !rognostic factors, as was noted in a cohort of orth

merican !atients. ?owever, increasing age was not a

!redictor of an increased mortality rate in one "hinesecohort of 66( !atients when com!ared to a age7adjusted!o!ulation mortality rate. #easures of disease activity andaccumulated organ damage may also be !redictive orincreased mortality while use of antimalarial drugs mayreduce mortality rates.

PR:G+:S7S



PR:G+:S7S

• $he im!rovement in !atient survival is !robably due tomulti!le factors. $hese include increased disease

recognition with more sensitive diagnostic tests , earlierdiagnosis or treatment, the inclusion of milder cases, andincreasingly judicious thera!y and !rom!t treatment ofcom!lications .

• n a ())( re!ort from the "enters for Disease "ontrol inthe 2nited States, deaths due to SLE varied amongdifferent !o!ulation grou!s. s e-am!les, the !ro!ortionof deaths due to SLE was more than five times higher inwomen than men, and more than three times higher in

black com!ared to white women. #ore than one7third ofdeaths due to lu!us occurred in !eo!le aged 4 to 66years.

- f d th



-auses of death

• $he major cause of death in the first few years of illness is activedisease 0eg, "S, renal, or cardiovascular disease1 or infection due

to immunosu!!ression, while late deaths are either caused by theillness 0eg, end7stage renal disease1, treatment com!lications0including infection and coronary disease1, non7?odgkin lym!homa,and lung cancer. – ;ne study evaluated the causes of death in 6)C !atients with SLE

followed over a mean !eriod of 44 years8 466 0* !ercent1 died<4**>. $he major causes of death were active lu!us 0*6 !ercent1,

infection 0(( !ercent1, cardiovascular disease 045 !ercent1, andcancer 05 !ercent1. Deaths that resulted directly from SLE andinfection were common among younger !atients8 the risk of deathdirectly due to SLE was highest in the first three years after

diagnosis.

• F nother !ros!ective study followed 4))) !atients for 4) years<4()>. $he most fre+uent causes of death were active SLE 0(5!ercent1, infection 0( !ercent1, and thromboses 0(5 !ercent1 <4()>.

• F n a cohort of 6969 Swedish !atients who were diagnosed withSLE between 4=56 and 4==, the !ro!ortion of deaths due tocardiovascular events, SLE, and malignant disease were 6(

-auses of death



-auses of death

• "auses of death A $he major cause of death in the first few years of illness is active disease 0eg, "S, renal, orcardiovascular disease1 or infection due to immunosu!!ression, while late deaths are either caused by the illness0eg, end7stage renal disease1, treatment com!lications 0including infection and coronary disease1, non7?odgkinlym!homa, and lung cancer <4(5,4(C74*(>. $he fre+uency of the different causes of death can be illustrated by

the following observations:

• F $he largest study to date included survival data and causes of death in a total of =69 !atients who werefollowed for an average of C.4 years <4*(>. Standardi&ed mortality rates 0S#31 of SLE !atient to e-!ected ratesfor a age and se- adjusted !o!ulation were noted for circulatory disease 0S#3 4.91, es!ecially heart disease0S#3 4.91, non7?odgkin lym!homa 0S#3 (.C1, lung cancer 0S#3 4=.61, infections 0S#3 =.)1, es!ecially!neumonia 0S#3 9.(1, and renal disease 0S#3 6.*1. $hose at !articular high risk for mortality were younger,female, and black, with a disease duration of less than one year.

• F ;ne study evaluated the causes of death in 6)C !atients with SLE followed over a mean !eriod of 44 years8 4660* !ercent1 died <4**>. $he major causes of death were active lu!us 0*6 !ercent1, infection 0(( !ercent1,cardiovascular disease 045 !ercent1, and cancer 05 !ercent1. Deaths that resulted directly from SLE and infectionwere common among younger !atients8 the risk of death directly due to SLE was highest in the first three yearsafter diagnosis.

• F nother !ros!ective study followed 4))) !atients for 4) years <4()>. $he most fre+uent causes of death wereactive SLE 0(5 !ercent1, infection 0( !ercent1, and thromboses 0(5 !ercent1 <4()>.

•

F n a cohort of 6969 Swedish !atients who were diagnosed with SLE between 4=56 and 4==, the !ro!ortion ofdeaths due to cardiovascular events, SLE, and malignant disease were 6( !ercent, (4 !ercent, and 4( !ercentres!ectively <4*6>.

• Serious infection is most often due to immunosu!!ressive thera!y. 0See Secondary immune deficiency due tomiscellaneous causes, section on GSystemic lu!us erythematosusG.1 atients at !articular risk are those treatedwith both glucocorticoids and cyclo!hos!hamide, es!ecially if the white blood cell count is less than *)))/HLand/or high7dose steroids are given <4*,4*5>. Lym!ho!enia 0I4)))/HL1 at !resentation, may be an inde!endentrisk factor <4*9>. 0See Jeneral to-icity of cyclo!hos!hamide and chlorambucil in inflammatory diseases and#ajor side effects of systemic glucocorticoids.1

SLE.kulah FKUMJ 2010 Fkkumj

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