sle tinjauan

8/19/2019 SLE Tinjauan

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CHAPTER II

LITERATURE REVIEW

2.1. Definition

Systemic lupus erythematosus (SLE) is a rheumatic disease characterized by

autoantibody directed against self-antigens, immune complex formation, and

immune deregulation, resulting in damage to essentially any organ. hildhood S

L E generally presents bet!een the ages of " and #$ years, !ith girls out

numbering boys "%# '. n #-*+ of SLE patients the diagnosis is made for thefirst time in childhood &*-'. he disease can affect any organ but the most

freuent are the /idneys, s/in, blood 0essels and cells, 1oints, heart and SLE

ner0ous system.

2.2. Epidemiology

2ediatric SLE (pSLE) represents approximately #$-* + of all SLE patients.

t is more common in females than in males, !ith a female to male ratio 0arying

from *.3%# to %#, depending on the study. he incidence of the disease 0aries

according to different ethnic groups. SLE is more common in 4frican-4merican

females. 5carty 67 etc. reported the annual incidence of SLE is t!o and half

times more in 4frican-4merican females than that in !hite females. 4lso in

8riental population in 9orth 4merica, the disease appears to be aggressi0e and is

associated !ith a higher mortality. 4ccording to a sur0ey conducted in t!o

decades ago in Shanghai, the pre0alence of the disease is around : per #,

people and ##3 per #, in female population. t is estimated that there are

one million patients in hina. ;oth genetic factors and sex hormone are

contributed to the de0eloping of the disease. f a family member has SLE, the

li/elihood of SLE increases !ith approximately 3 + for identical t!ins and $+

for other first-degree relati0es.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22McCarty+DJ%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22McCarty+DJ%22%5BAuthor%5Dhttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22McCarty+DJ%22%5BAuthor%5D


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2.3. Etiopatogene!i!

n SLE, there is mar/ed disturbance in immune regulation. hese

abnormalities may ha0e arisen from genetic, en0ironmental and hormonal factors.

he exact mechanism of interplay of these combined effects is still un/no!n.

"ig#$e 1. 9atural history of systemic lupus erythematosus. SL, Systemic Lupus

nternational ollaborating linics?, Salmon 7E, ;oumpas 6. herapeutic

opportunities in systemic lupus erythematosus% state of the art and prospects for the ne!

decade. Ann Rheum Dis *#@%#3A##.

#. >enetic factors

Siblings of SLE patients are approximately 3 times more li/ely to de0elop

SLE compared !ith indi0iduals !ithout an aff ected sibling. he rate of gene

disco0ery in SLE has increased during the past fe! years than/s to large genome-

!ide association studies (>B4S) using hundreds of thousands of single

nucleotide polymorphism (S92) mar/ers. >B4S in lupus ha0e confirmed the

importance of genes associated !ith immune response and inflammation (CL4-

6=, 229**, S4", =D$, ;L?, 8"L, D>=*4, ;49?#, S22#, =4?#,


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9D423, *, ", , 2?), 694 repairs (=E#), adherence of infl

ammatory cells to the endothelium (>45), and tissue response to in1ury

(?L?#, ?L?3). hese findings highlight the importance of oll-li/e receptor

(L=) and type # interferon (D9) signalling path!ays. Some of the genetic loci

may explain not only the susceptibility to disease but also its se0erity. Dor

instance, S4", a genetic ris/ factor for rheumatoid arthritis and SLE, is

associated !ith se0ere SLE. 8ne of the /ey components of these path!ays is

9D423, !hich has been implicated in at least six autoimmune disorders,

including SLE.

*. Epigenetic effects

he ris/ for SLE may be influenced by epigenetic effects such as 694

methylation and post-translational modifications of histones, !hich can be either

inherited or en0ironentally modified. Epigenetics refers to inherited changes in

gene expression caused by mechanisms other than 694 base seuence changes.

he most !ell understood type of epigenetic factor is 694 methylation, !hich

plays a role in a 0ariety of human processes, such as chromosome inacti0ation

and certain cancers. 2re0ious research has also implicated the importance of

694 methylation in SLE. 6ifferences in the methylation status of genes may

explain, at least in part, the discordance obser0ed in some identical t!ins that are

discordant for SLE. Epigenetic mechanisms may represent the missing lin/

bet!een genetic and en0ironmental ris/ factors.

3. En0ironmental factors

andidate en0ironmental triggers of SLE include ultra0iolet light,

demethylating drugs, and infectious or endogenous 0iruses or 0iral li/e elements.

Sunlight is the most ob0ious en0ironmental factor that may exacerbate SLE.

EpsteinA;arr 0irus (E;F) has been identified as a possible factor in the

de0elopment of lupus. E;F may reside in and interact !ith ; cells and promotes


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interferon a(D9a) production by plasmacytoid dendritic cells (p6s), suggesting

that ele0ated D9a in lupus may be at least in part due to aberrantly controlled

chronic 0iral infection. t is !ell established that certain drugs induce

autoantibodies in a significant number of patients, most of !hom do not de0elop

signs of an autoantibody associated disease. 80er # drugs ha0e been reported

to cause drug-induced lupus (6L), including a number of the ne!er biologics

and anti0iral agents. 4lthough the pathogenesis of 6L is not !ell understood, a

genetic predisposition may play a role in the case of certain drugs, particularly

those agents that are metabolised by acetylation such as procainamide and

hydralazine, !ith disease more li/ely to de0elop in patients !ho are slo!

acetylators. hese drugs may alter gene expression in 6" cells by inhibiting

694 methylation and induce o0erexpression of LD4-# antigen, thus promoting

autoreacti0ity.

". Cormonal factors

n murine models, addition of oestrogen or prolactin can lead to an

autoimmune phenotype !ith an increase in mature high affinity autoreacti0e ;

cells. 8ral contracepti0e use in the 9urses Cealth Study !as associated !ith a

slightly increased ris/ of de0eloping SLE (relati0e ris/ #. compared to ne0er

users). his poses important uestions pertaining to the use of oestrogens for oral

contraception or as hormone replacement therapy in postmenopausal !omen.

Bhile it is clear that hormones can influence autoimmune de0elopment in murine

models, the use of oral contracepti0es does not increase disease fl ares in !omen

!ith stable disease (Sanchez->uerrero et al *$). 2regnancy may cause in some

cases a lupus flare, but this is not due to an increase in oestradiol or progesterone@

infact, the le0els of these hormones are lo!er in the second and third trimester for

SLE patients in comparison !ith healthy pregnant !omen.

$. 6rug-nduced Lupus Erythematosus


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Se0eral medications can cause systemic and subacute or chronic cutaneous

lupus phenotypes in children. he cutaneous manifestations of systemic drug-

induced lupus (6L) include malar rash, purpura, erythema nodosum, urticaria,

and photosensiti0ity. Systemic symptoms include arthritis, oral ulcers, pleuritis,

hematologic manifestations, and less commonly renal disease. haracteristic

laboratory findings of 6L are positi0e 494 and antihistone antibodies. 6rugs

implicated are minocycline, anticon0ulsi0e drugs, hydralazine, procainamide, and

isoniazid. 5anagement of drug induced lupus is based on the !ithdra!al of the

offending drug. opical and


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be *+ to $+, but this ris/ may be increased by #-fold in !omen !ith a pre0ious

child !ith C;. 4 recent study suggests an o0erall recurrence rate of cardiac

9LE of #:+, independent of maternal health, antenatal use of steroids, antibody

status, se0erity of cardiac disease in the first affected child, or sex of the

subseuent child. n addition to heart bloc/, ne!borns !ith 9LE can present !ith

a characteristic 9LE rash, hepatic dysfunction, and hematologic abnormalities

including significant thrombocytopenia. ypically the 9LE rash is located around

the eyes but may present else!here on the body.

2.%. Patogene!i! and patopy!iology

mmune responses against endogenous nuclear antigens are characteristic of

SLE. 4utoantigens released by apoptotic cells are presented by dendritic cells to

cells leading to their acti0ation. 4cti0ated cells in turn help ; cells to produce

antibodies to these self constituents by secreting cyto/ines such as interleu/in #

(L#) and L*3 and by cell surface molecules such as 6"L and L4-". n

addition to this antigen-dri0en cell-dependent production of autoantibodies,

recent data support cell-independent mechanisms of ; cell stimulation 0ia

combined ; cell antigen receptor (;=) and L= signalling. h e pathogenesis

of SLE in0ol0es a multitude of cells and molecules that participate in apoptosis,

innate and adapti0e immune responses (table #). ncreased amounts of apoptosis

related endogenous nucleic acids stimulate the production of D9a and promote

autoimmunity by brea/ing self tolerance through acti0ation of antigen presenting

cells (figure 3). 8nce initiated, immune reactants such as immune complexes

amplify and sustain the inflammatory response.


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"ig#$e 2. n systemic lupus erythematosus all path!ays lead to endogenous nucleic acids-mediated production of interferon a (D9a). ncreased production of autoantigens during

apoptosis (JF-related and


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crosslin/ing. 6, dendritic cell, ;=, ; cell receptor, Dc=, Dc receptor, JF, ultra0iolet@

L=, toll-li/e receptor. =eprinted !ith permission from ;ertsias >?, Salmon 7E, ;oumpas6. herapeutic opportunities in systemic lupus erythematosus% state of the art and prospects

for the ne! decade. Ann Rheum Dis *#@%#3A##.

Ta&le 1 ?ey pathogenic processes, cells and molecules in systemic lupus

erythematosus

K Apopto!i!' a source of autoantigens and molecules !ith ad1u0ant


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##

Se0eral lupus-related genes encode proteins that mediate or regulate L= signals and are

associated !ith increased plasma D9a among patients !ith specifi c autoantibodies!hich may deli0er stimulatory nucleic acids to L=: or L= in their intracellular

compartments. 4cti0ation of the D9 path!ay has been associated !ith the presence of

autoantibodies specifi c for =94-associated proteins. =94-mediated acti0ation of L=

is an important mechanism contributing to production of D9a and other proinfl

ammatory cyto/ines. 4cti0ation of the D9 path!ay is associated !ith renal disease and

many measures of disease acti0ity.

K Complement' 4cti0ation of complement shapes the immune infl ammatory response

and facilitates clearance of apoptotic material.

K (e#t$opil!' n lupus a distinct subset of proinfl ammatory neutrophils (lo! density

granulocytes) induces 0ascular damage and produces D9a. 2athogenic 0ariants of 45

increase the binding to 45 and the adhesion leucocytes to acti0ated endothelial cells.

K Endotelial )ell!' n lupus, impaired 694 degradation as a result of a defect in repair

endonucleases (=E#) increases the accumulation of ss694 deri0ed from endogenous

retro-elements in endothelial cells and may acti0ate production of D9a by them. D9a in

turn propagates endothelial damage and impairs its repair.

Adaptie imm#nity

K T and / )ell!' nteractions bet!een co-stimulatory ligands and receptors on and ;

cells, inc6*I, inducible costimulator (8S) ligand !ith 8S, and 6" ligand !ith6", coantibody producing plasma cells. 4utoantibodies also facilitate the deli0ery of

stimand chemo/ines produced by and ; cells also shape the immune response and pr

K / lympo)yte !tim#lato$ */ly!+' h e soluble 9D family member ;lyS is a ; cell

surincreased in serum of many lupus patients@ inhibition of ;lys pre0ents lupus fl ares.

K Imm#ne )omple0e!' n healthy indi0iduals, immune complexes are cleared by Dc=

agenetic 0ariations in Dc= genes and the 3bi receptor gene (>45) may impair ththen

deposit and cause tissue in1ury at sites such as the s/in and /idney.

2.. Di!ea!e me)ani!m! and ti!!#e damage

mmune complexes and complement acti0ation path!ays mediate eff ector

function and tissue in1ury. n healthy indi0iduals, immune complexes are cleared

by Dc and complement receptors@ failure to clear immune complexes results in

tissue deposition and tissue in1ury at sites. issue damage is mediated by

recruitment of infl ammatory cells, reacti0e oxygen intermediates, production of

infl ammatory cyto/ines, and modulation of the coagulation cascade.


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#*

4utoantibody-mediated tissue in1ury has been implicated in neuropsychiatric SLE

(92SLE), !here antibodies reacting !ith both 694 and glutamate receptors on

neuronal cells can mediate excitotoxic neuronal cell death or dysfunction. Locally

produced cyto/ines, such as D9a and tumour necrosis factor (9D), contribute

to aff ected tissue in1ury and infl ammation. h ese mediators, together !ith the

cells producing them (macrophages, leucocytes, dendritic cells and lymphocytes),

are the sub1ect of in0estigation as potential therapeutic targets in lupus. =ecent

studies ha0e also highlighted the role of locally expressed factors for the

protection of tissues under immune attac/. Dor example, defects in /alli/reins

may 1eopardise the ability of lupus /idneys to protect themsel0es from in1ury,

26-#-ligand do!n-regulates the acti0ity of the infi ltrating lymphocytes, and

impaired regulation of complement amplifi es 0ascular in1ury. Fascular damage in

SLE has recei0ed increased attention in 0ie! of its relationship !ith accelerated

atherosclerosis. Comocysteine and proinflammatory cyto/ines, such as D9a,

impair endothelial function and decrease the a0ailability of endothelial precursor

cells to repair endothelial in1ury. 2ro-inflammatory high density lipoproteins

(C6L) and a dysfunction of C6L mediated by antibodies ha0e also been

implicated in defecti0e repair of endothelium. 5oreo0er, pathogenic 0ariants of

45 (immuno-tyrosine acti0ation motif ) alter its binding to 45-#

(intercellular adhesion molecule #) and may increase the adherence of leucocytes

to acti0ated endothelial cells. mpaired 694 degradation as a result of mutations

of the 3H repair exonuclease # (=E#), and increased accumulation of single

stranded 694 deri0ed from endogenous retroelements in endothelial cells, may

acti0ate the D9-stimulatory 694 response and direct immune mediated in1ury to

the 0asculature.

2.. Cla!!ifi)ation )$ite$ia

riteria for SLE classifi cation !ere de0eloped in #:#, re0ised in #I*, and


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#3

re0ised again in #: (table *) (Cochberg #:). hese criteria distinguish

patients !ith the disease in uestion from those !ithout the disease. he

4merican ollege of =heumatology (4=) classification criteria !ere de0eloped

for clinical studies of lupus to ensure that cases reported in the literature do in

fact ha0e the disease. n addition to the !ide 0ariety of manifestations, SLE runs

an unpredictable course. he dynamic nature of the disease often ma/es its

diagnosis challenging. 4lthough the 4= classification criteria may also be used

as a diagnostic aid, there are se0eral ca0eats in their use for diagnostic purposes.

hese criteria !ere de0eloped and 0alidated for the classification of patients !ith

a longstanding established disease and may exclude patients !ith early disease or

disease limited to a fe! organs. hus, in spite of their excellent sensiti0ity

(NI$+) and specifi city (N$+) for patients !ith established disease, their

sensiti0ity for patients early in the disease may be significantly lo!er. Some

systems are o0errepresented@ the mucocutaneous manifestations, for example, are

represented !ith four criteria (photosensiti0ity, malar rash, discoid lesions, and

oral ulcers). 4ll features included in the classifi cation criteria are contributing

eually !ithout any !eight based upon sensiti0ity and specifi city for each

indi0idual criterion. hus, studies ha0e sho!n and experience supports that

criteria such as ob1ecti0e e0idence of renal disease (significant proteinuria, acti0e

urine sediment or renal biopsy !ith e0idence of lupus nephritis), discoid rash, and

cytopenias are more useful in establishing the diagnosis of lupus than the other

criteria. ;ecause SLE is a disease !hose course is typified by periodic

in0ol0ement of one organ system after another, it is apparent that patients must

ha0e the disease for years before they fulfil the classification criteria. 4mong

patients referred for lupus to tertiary care centres, t!o thirds of patients fulfi l

4= criteria, approximately #+ ha0e clinical lupus but do not fulfil criteria, and

*$+ ha0e fibromyalgia li/e symptoms and positi0e antinuclear antibody (494)


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#"

but ne0er de0elop lupus.


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#$

Ta&le 2. he 4merican ollege of =heumatology re0ised classiO cation criteria

for systemic lupus erythematosusC$ite$ia Definition

5alar rash Dixed erythema, flat or raised, o0er the malar eminences, tending to spare the

nasolabial folds

6iscoid rash Erythematous raised patches !ith adherent /eratotic scaling and follicular

plugging@ atrophic scarring occurs in older lesions

2hotosensiti0ity S/in rash as a result of unusual reaction to sunlight, by patient history or

physician obser0ation

8ral ulcers 8ral or nasopharyngeal ulceration, usually painless, obser0ed by a physician

4rthritis 9on-erosi0e arthritis in0ol0ing t!o or more peripheral 1oints, characterised by

tenderness, s!elling or eff usion

Serositis a. Pleuritis% con0incing history of pleuritic pain or rub heard by a physician or

e0idence of pleural eff usion or

b. Pericarditis% documented by E> or rub or e0idence of pericardial eff usion

=enal disorder a. 2ersistent proteinuria N.$ g per day or N3 if uantitation is not performed

or

b. ellular casts% may be red cell, haemoglobin, granular tubular, or mixed

9eurological disorder a. Seizures% in the absence of off ending drugs or /no!n metabolic

derangements (eg, uraemia, acidosis, or electrolyte imbalance) or

b. 2sychosis% in the absence of off ending drugs or /no!n metabolic

derangements (eg, uraemia, acidosis, or electrolyte imbalance)

Caematologic disorder a. Caemolytic anaemia !ith reticulocytosis, or

b. Leucopenia% P"


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#

4ssessing disease acti0ity in SLE is crucial to the physician as it forms the

basis for treatment decisions. 6isease acti0ity needs to be distinguished from

damage as this has important implications for the long term prognosis and the

appropriate treatment. Se0eral 0alidated global and organ specific acti0ity indices

are !idely used in the e0aluation of SLE patients (Jro!itz and >ladman #I).

hese include the European onsensus Lupus 4cti0ity 5easure (EL45), the

;ritish sles Lupus 4ssessment >roup Scale (;L4>), the Lupus 4cti0ity ndex

(L4), the 9ational nstitutes of Cealth SLE ndex Score (SS), the Systemic

Lupus 4cti0ity 5easure (SL45), and the SLE 6isease 4cti0ity ndex

(SLE64). hese indices ha0e been de0eloped in the context of long term

obser0ational studies and ha0e been sho!n to be strong predictors of damage and

mortality, and reflect change in disease acti0ity. 5oreo0er, they ha0e been

0alidated against each other. Be recommend the use of at least one of these

indices for monitoring of disease acti0ity. n our experience the EL45 and the

SLE64 (table 3) are more con0enient for use in daily practice. omputerised

clinical charts that compute se0eral disease acti0ity indices simultaneously ha0e

been de0eloped. Existing disease acti0ity indices ha0e important limitations !hen

used in the context of clinical trials. Dor clinical trials, composite end points and

responder indices may be more useful, especially for studies in general lupus, as

compared to studies for lupus affecting single organs (eg, nephritis). o this end,

using composite index (SLE responder index, S=) in0estigators in the

;elimumab trial !ere able to sho! efficacy. he S= includes impro0ement in

SLE64 by at least " !ithout !orsening in ;L4> and 2>4. he S= could be

ad1usted to loo/ for larger treatment effects (for instance, more than : or #*

points difference in SLE64) similar to !hat is being used in rheumatoid arthritis

(4= *, and $, or EJL4= moderate and good response).


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#:

Ta&le 3 he Systemic Lupus Erythematosus 6isease 4cti0ity ndex (SLE64)


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#I


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#

2.. C$oni)ity and damage inde0

he Systemic Lupus nternational ollaborating linics< 4merican ollege

of =heumatology (SLladman et al #). 6amage

in SLE may be due to the disease itself or to drug therapy. he index records

damage in #* organs or systems (table "). here is no index to measure harms

caused by drugs in lupus at present. he change must ha0e been present for at

least months and is ascertained clinically or by simple in0estigations. Studies

ha0e sho!n that the early acuisition of damage is a sign of a poor prognosis.

Ta&le % he Systemic Lupus nternational ollaborating linics


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*


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*#

2.4. Clini)al feat#$e!

2.4.1. 5#)o)#taneo#! feat#$e!

5ucocutaneous in0ol0ement is almost uni0ersal in SLE !ith both lupus-

specifi c and non-specific lesions (table $). Lupus specific lesions can be further

classified as acute, subacute, and chronic lesions.

4. 4cute rashes-malar rash.

he classic lupus MbutterflyH rash presents acutely as an erythematous,

ele0ated lesion, pruritic or painful, in a malar distribution, commonly

precipitated by exposure to sunlight. he rash may last from days to

!ee/s and is commonly accompanied by other infl ammatory

manifestations of the disease. he acute butterfly rash should be

differentiated from other causes of facial erythema such as rosacea,

seborrhoeic, atopic, and contact dermatitis, and glucocorticoid induced

dermal atrophy and flushing. 8ther acute cutaneous lesions include

generalised erythema and bullous lesions. he rash of acute cutaneous

lupus erythematosus can be transient and heal !ithout scarring, although

persistently acti0e rashes may result in permanent telangiectasias.

;. Subacute rashes.

Subacute cutaneous lupus erythematosus (SLE) is not uniformly

associated !ith SLE. 4pproximately $+ of affected patients ha0e SLE

and about #+ of patients !ith SLE ha0e this type of s/in lesion. 2atients

!ith SLE may present !ith annular or psoriasi form s/in lesions, and

this is strongly associated !ith anti-=o (SS-4) and anti-La (SS-;)

antibodies. 2atients !ith SLE ha0e a high incidence of photosensiti0ity

and in rare instances can present !ith erythema multiforme-li/e lesions

(=o!ellHs syndrome). SLE lesions begin as small, erythematous, slightly

scaly papules that e0ol0e into either a psoriasiform (papulosuamous) or


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**

annular form. h e latter oft en coalesce to form polycyclic or fi gurati0e

patterns). he lesions typically ha0e erythematous, and sometimes

crusted, margins. ommonly aff ected areas are the shoulders, forearms,

nec/, and upper torso. he face is usually spared.

. hronic rashes.

6iscoid lupus erythematosus (6LE) lesions de0elop in up to *$+ of SLE

patients. 2atients !ith 6LE ha0e approximately a $A#+ ris/ of

de0eloping SLE !hich tends to be mild. =is/ is e0en higher !ith

numerous and !idespread s/in lesions. 6iscoid lesions are characterised

by discrete, erythematous, slightly infiltrated plaues co0ered by a !ell-

formed adherent scale that extends into dilated hair follicles (follicular

plugging). hey are oft en seen on the face, nec/, and scalp, but also

occur on the ears, and infreuently on the upper torso. hey slo!ly

expand !ith acti0e infl ammation at the periphery, and then heal, lea0ing

depressed central scars, atrophy, telangiectasias, and dyspigmentation

(hyper or hypopigmentation). he differential diagnosis includes

hypertrophic lichen planus, eczema, and actinic /eratosis@ some early and

scaly discoid lesions must also be diff erentiated from psoriasis.

6. 8ther rashes.

Lupus profundus presents as a firm nodular lesion !ith or !ithout an

o0erlying cutaneous lesion. he nodules are often painful and consist of

peri0ascular infi ltrates of mononuclear cells plus panniculitis, manifested

as hyaline fat necrosis !ith mononuclear cell infiltration and lymphocytic

0asculitis. hey usually appear on the scalp, face, arms, chest, bac/,

thighs, and buttoc/s@ ulcerations are uncommon and they usually resol0e

lea0ing a depressed area. Lupus tumidus, a rare 0ariant, is characterised

by photo distributed lesions !ith chronic pin/ indurated plaues or broad


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*3

lesions that are slo! to heal.

E. 4lopecia.

4lopecia defined as exaggerated hair loss occurs in most SLE patients. t

may in0ol0e the scalp, eyebro!s, eyelashes, beard, and body hair.

Scarring alopecia is a complication of discoid lupus that typically aff ects

the scalp. MLupus hairH is characterised by thin hair that easily fractures. t

usually occurs along the frontal hairline, is associated !ith disease

acti0ity, and gro!s bac/ normally as the disease subsides.D. 2hotosensiti0ity.

2hotosensiti0ity is defi ned as the de0elopment of a rash aft er exposure to

ultra0iolet (JF) ; radiation coming from sunlight or fl uorescent lights. t

occurs in A#+ of SLE patients. Some patients are also sensiti0e to

JF4 radiation (emitted from photocopiers or some light bulbs), and may

e0en be sensiti0e to the 0isible light spectrum. 9ot all photosensiti0e

indi0iduals ha0e lupus, nor are the t!o disorders causally lin/ed in all

SLE patients.


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*"

Ta&le lassiOcation of lupus erythematosus (LE) associated s/in lesions


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*$

2.4.2. 5#!)#lo!-eletal feat#$e!

he musculos/eletal system is aff ected in $3A$+ of SLE patients.

4. 4rthritiseneralised myalgia and muscle tenderness are common during disease

exacerbations. nfl ammatory myositis in0ol0ing the proximal muscles

has been reported in $A##+ of cases and may de0elop at any time during


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*

the course of the disease. 4 lo! serum creatine phospho/inase (2?)

0alue can be found in patients !ithconnecti0e tissue disease including

SLE@ thus a normal 2? 0alue in the presence of symptoms and signs of

myositis should not dissuade the physician from its diagnosis. h e s/in

lesions of dermatomyositis can also appear in patients !ith SLE.

. 40ascular bone necrosis.

40ascular necrosis (4F9) of bone is a ma1or cause of morbidity and

disability in SLE. Symptomatic 4F9 occurs in $A#*+. Cigher pre0alence

has been reported !hen magnetic resonance imaging (5=) is used for its

detection. 4cute 1oint pain presenting late in the course of SLE and

localised to a 0ery fe! areas, especially shoulders, hips, and /nees, may

indicate 4F9. Dactors that can induce bone ischaemia and necrosis

include =aynaudHs phenomenon, 0asculitis, fat emboli, corticosteroids,

and the antiphospholipid syndrome. 8steonecrosis oft en de0elops shortly

aft er the onset of high-dose corticosteroid therapy.

2.4.3 .Renal feat#$e!

=enal in0ol0ement occurs in "A:+ of all SLE patients and is a ma1or

cause of morbidity and hospital admissions. mmune complex formation<

deposition in the /idney results in intra glomerular inflammation !ith recruitment

of leucocytes and acti0ation and proliferation of resident renal cells (figure ).

2roteinuria of 0arious le0els is the dominant feature of lupus nephritis (L9) and

is usually accompanied by glomerular haematuria. Jrinalysis is the most

important and effecti0e method to detect and monitor disease renal acti0ity. o

assure its uality, se0eral steps ha0e to be ta/en. hese include expeditious

examination of a fresh, early morning, midstream, clean catch, non-refrigerated

urine specimen@ and flagging of specimens from patients at substantial ris/ of

de0eloping L9 to ensure careful examination at central laboratories. Caematuria


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*:

(usually microscopic, rarely macroscopic) indicates inflammatory glomerular or

tubulointerstitial disease. Erythrocytes are fragmented or misshaped

(dysmorphic). >ranular and fatty casts reflect proteinuric states !hile red blood

cell, !hite blood cell, and mixed cellular casts reflect nephritic states. ;road and

!axy casts reflect chronic renal failure. n se0ere proliferati0e disease, urine

sediment containing the full range of cells and casts can be found (Mtelescopic

urine sedimentH) as a result of se0ere glomerular and tubular ongoing disease

superimposed on chronic renal damage. =enal biopsy rarely helps the diagnosis

of lupus, but is the best !ay of documenting the renal pathology. n the absence

of renal abnormalities, renal biopsy has nothing to offer and should not be

performed.

2.4.%. (e$o#! !y!tem feat#$e!

SLE affects both the central ner0ous system (9S) and the peripheral

ner0ous system (29S) . 9er0ous system in0ol0ement in SLE remains one of the

ma1or causes of morbidity and mortality@ it is the least understood manifestation

of the disease, and remains a complex diagnostic entity as a result of its multiple

clinical presentations. h e 4= described case definitions and classifi cation

criteria for # 9S and 29S syndromes obser0ed in patients !ith SLE, !hich

collecti0ely are referred to as neuropsychiatric SLE (92SLE) syndromes. he

EJL4= tas/ force on SLE has critically re0ie!ed the literature on 92SLE in an

eff ort to pro0ide an e0idence and expert based response to common clinical

uestions encountered in the disease (;ertsias et al *#b).

2.4. Ca$dioa!)#la$ feat#$e!

2ericarditis may occur in approximately *$+ of SLE patients. 2ericardial

effusions may be asymptomatic and are usually mild to moderate. amponade is

rare. 5yocardial in0ol0ement is rare and typically occurs in the presence of


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*I

generalised lupus acti0ity. he patient may present !ith fe0er, dyspnoea,

tachycardia, and congesti0e heart failure. linical features of left 0entricular

dysfunction, non-specific S- !a0e changes, segmental !all motion

abnormalities, and decreased e1ection fraction are found in NI+ of patients.

5= has been used to detect both clinical and subclinical myocardial

in0ol0ement in SLE.

SLE patients ha0e substantially increased morbidity and mortality from

cardio0ascular disease (F6). his includes accelerated, premature

atherosclerosis and 0al0ular heart disease. Studies ha0e also demonstrated an

increased ris/ for myocardial infarction or stro/e compared to the healthy

population, and this ris/ cannot be fully explained by the traditional F6 ris/

factors. Fal0ular heart disease is common in SLE and has been lin/ed to the

presence of antiphospholipid antibodies. h e most common abnormality is diff

use thic/ening of the mitral and aortic 0al0es follo!ed by 0egetations, 0al0ular

regurgitation, and stenosis in decreasing order of freuency. he combined

incidence of stro/e, peripheral embolism, heart failure, infecti0e endocarditis, and

the need for 0al0e replacement is approximately threefold higher in those patients

!ith 0al0ular disease compared to those !ithout it. 2athologic studies ha0e

sho!n acti0e and healed 0al0ulitis, as !ell as acti0e Libman-Sac/s 0egetations

!ith acute thrombus, healed 0egetations !ith or !ithout hyalinised thrombus, or

both acti0e and healed 0egetations, in the same or diff erent 0al0es.

2.4.. Ple#$a and l#ng!

he most common pleuropulmonary manifestation of SLE is. 2leuritic pain

is present in "$A+ of patients and may occur !ith or !ithout a pleural eff

usion, !ith clinically apparent pleural effusions reported in up to $+. Eff usions

are usually bilateral and eually distributed bet!een the left and right

hemithoraces. he effusion is in0ariably exudati0e !ith higher glucose and lo!er


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*

lactate dehydrogenase le0els than those found in rheumatoid arthritis. linically

significant interstitial lung disease (L6) complicates SLE in 3A#3+ of patients,

but is rarely se0ere. 4cute lupus pneumonitis presenting as cough, dyspnoea,

pleuritic pain, hypoxaemia, and fe0er occurs in #A"+. hest radiographs re0eal

unilateral or bilateral infiltrates. 2ulmonary haemorrhage is a rare but potentially

catastrophic complication of SLE. linical features are nonspecific but diffuse

al0eolar infiltrates, hypoxaemia, dyspnoea, and anaemia are characteristic.

4l0eolar haemorrhage usually occurs in patients !ith a /no!n history of SLE,

high titres of anti-694 antibodies, and acti0e extrapulmonary disease. Dibreoptic

bronchoscopy !ith bronchoal0eolar la0age (;4L) and transbronchial lung

biopsies are usually needed to substantiate the diagnosis. he Mshrin/ing lung

syndromeH is characterised by progressi0e dyspnoea and small lung 0olumes on

chest radiographs, and is thought to be secondary to diaphragmatic dysfunction. t

can be diffi cult to differentiate from respiratory muscle !ea/ness, primary

parenchymal disease or pleural causes of lo! lung 0olumes !ithout the use of

in0asi0e studies. 2ulmonary hypertension (2C) is a rare but potentially life-

threatening complication. 6yspnoea is the most common presenting symptom

!hile up to $I+ of patients ha0e =aynaudHs phenomenon.

2.4.. Lympadenopaty and !plenomegaly

Lymphadenopathy occurs in approximately "+ of patients, usually at the

onset of disease or during disease fl ares. Lymph nodes are typically soft , non-

tender, discrete, and usually detected in the cer0ical, axillary, and inguinal area.

linically signifi cant lymphadenopathy that raises diagnostic issues is less

common. 2atients !ith lymphadenopathy are more li/ely to ha0e constitutional

symptoms. 4 lymph node biopsy may be !arranted !hen the degree of

lymphadenopathy is out of proportion to the acti0ity of the lupus. Splenomegaly

occurs in #A"$+ of patients, particularly during acti0e disease, and is not


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3

necessarily associated !ith cytopenias. Splenic atrophy and functional

hyposplenism ha0e also been reported in SLE and may predispose to se0ere

septic complications.

2.4.4. Haematologi) feat#$e!

Caematologic abnormalities are common and can be the presenting symptom

or sign in SLE. 5a1or clinical manifestations include anaemia, leucopenia,

thrombocytopenia, and the antiphospholipid syndrome.

4. 4naemia.4naemia in SLE is common and correlates !ith disease acti0ity. ts

pathogenesis includes anaemia of chronic disease, haemolysis

(autoimmune or microangiopathic), blood loss, renal insufficiency,

medications, infection, hypersplenism, myelodysplasia, myelofibrosis,

and aplastic anaemia. 4 freuent cause is suppressed erythropoiesis from

chronic inflammation. 80ert autoimmune haemolytic anaemia has been

reported in up to #+ of patients@ of note, SLE patients may ha0e a

positi0e oombs test !ithout o0ert haemolysis. ;lood loss, either from

the gastrointestinal (>) tract, usually secondary to medications (non-

steroidal anti-infl ammatory drugs (9S46s)), or due to excessi0e

menstrual bleeding, may cause an iron defi ciency anaemia. 4 rare cause

of iron deficiency anaemia in SLE may be lo! grade pulmonary

haemorrhage !ithout signs of haemoptysis. 4 microangiopathic

haemolytic anaemia !ith or !ithout the other features (fe0er,

thrombocytopenia, /idney in0ol0ement, neurologic symptoms) of

thrombotic thrombocytopenic purpura (2) has been described in SLE.

he presence of schistocytes in the peripheral blood smear and increased

lactate dehydrogenase (L6C) le0els are the hallmar/s of this disorder.

Bhen this occurs in the setting of generalised lupus acti0ity, !e prefer to


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3#

call it 2-li/e syndrome and use immunosuppressi0e therapy. n the

absence of generalised lupus acti0ity !e 0ie! it as a bona fi de 2. 4

similar syndrome can also occur in the presence of antiphospholipid

antibodies. =ed cell aplasia due to antibodies against erythrocyte

progenitors has been rarely reported in SLE patients.

;. Leucopenia.

Leucopenia is common in SLE@ it can be the presenting symptom and is

usually associated !ith disease acti0ity. 4 !hite blood cell count

P"$ in0ol0ement or eff ects of medications.


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3*

6yspepsia has been reported in ##A$+, and peptic ulcers (usually

gastric) in "A*#+.

;. 4bdominal pain.

4bdominal pain accompanied by nausea and 0omiting occurs in up to

3+ of SLE patients. Special consideration should be gi0en in conditions

such as peritonitis, mesenteric 0asculitis !ith intestinal infarction,

pancreatitis, and infl ammatory bo!el disease. =is/ factors for the

de0elopment of mesenteric 0asculitis include peripheral 0asculitis and

9S lupus. h e clinical presentation is usually !ith insidious symptoms

that may be intermittent for months before the de0elopment of an acute

abdomen !ith nausea, 0omiting, diarrhoea, > bleeding, and fe0er.

2atients !ith acute presentation may also ha0e mesenteric thrombosis and

infarction, oft en in association !ith antiphospholipid antibodies. h e

diagnosis of mesenteric 0asculitis may be diffi cult to establish. 2lain

radiographic studies may re0eal segmental bo!el dilatation, air-fl uid

le0els, Mthumb-printingH or narro!ing of the lumen, and pseudo-

obstruction. 4bdominal computed tomography () scan fi ndings

compatible !ith mesenteric 0asculitis include prominence of mesenteric

0essels !ith a comb-li/e appearance supplying dilated bo!el loops, small

bo!el thic/ening and ascites. Fasculitis generally in0ol0es small arteries,

!hich can lead to a negati0e arteriogram. 2ancreatitis due to lupus may

result from 0asculitis or thrombosis and occurs in as many as *AI+ of

patients. Ele0ated le0els of serum amylase ha0e been described in patients

!ith SLE !ithout pancreatitis and thus should be interpreted in light of

the o0erall clinical examination.

. Li0er disease.

Cepatic disease may be more common in SLE than initially thought.


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33

Co!e0er, clinically signifi cant hepatic disease is generally unusual. he

incidence of hepatomegaly is #*A*$+. Excessi0e fatty infiltration

(steatosis) is a common finding and may occur as part of the disease

process or may be secondary to corticosteroid treatment. Li0er chemistries

(aspartate aminotransferase (4S), alanine aminotransferase (4L), L6C,

al/aline phosphatase) may be abnormal in patients !ith acti0e disease or

those recei0ing 9S46s. he term Mlupoid hepatitisH !as formerly used to

describe autoimmune hepatitis because of clinical and serologic

similarities to SLE. 4utoantibodies may help to distinguish bet!een

autoimmune hepatitis and li0er disease associated !ith lupus. 494s can

be seen in both disorders, but antismooth muscle and anti-mitochondrial

4ntibodies are not common in SLE (P3+) and usually !hen found are

in lo! titres. n lupus-associated hepatitis histology rarely sho!s. he

periportal (interface) hepatitis !ith piecemeal necrosis haracteristic of

4utoimmune hepatitis, and li0er-associated chemistries tend to be lo!er

in lupus !ith only mild (usually up to three to four times normal)

ele0ation. h e absence of these antibodies and the presence of anti-

ribosomal 2 protein antibodies could be suggesti0e of lupus hepatitis.

6. 4scites

4scites is uncommon in SLE and, !hen detected, infectious causes and


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3"

2.4.18. 9ptalmi) feat#$e!Jp to I+ of SLE patients de0elop infl ammation of the retinal artery during

the course of their disease. 4n eual number of patients ha0e infarction of the

retinal 0asculature secondary to antiphospholipid antibodies. ;oth conditions can

lead to the presence of Mcotton !oolH spots in the retina 0isible on

ophthalmoscopy or fl uorescein angiography (!here peri0ascular exudates and

patches of dye lea/age along the 0essels are seen). otton !ool spots result from

focal ischaemia and are not pathognomonic for lupus. =etinal 0asculitis is usually

associated !ith generalised acti0e systemic disease and presents early in the

disease process. orneal and con1uncti0a in0ol0ement is usually part of S1GgrenHs

syndrome associated !ith SLE@ u0eitis and scleritis are extremely rare

manifestations in SLE, seen in P#+ of patients. 8ptic neuritis is rare and may be

associated !ith trans0erse myelitis.

*.. 6iagnosis and 6iagnostic ests

he diagnosis of pSLE is based on clinical findings, laboratory test results

including inflammatory mar/ers, complement le0els, mar/ers of organ

in0ol0ement, and specific autoantibodies. issue biopsies and imaging studies

can further support and


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3$

children !ith acti0e lupus, except for those presenting !ith serositis or concurrent

infections. 4n abnormal urinalysis including microscopic e0idence of casts

indicated renal in0ol0ement. =enal function impairment is best e0aluated by

serum creatinine, albumin, and urine proteinAto-creatinine ratio. Lupus

anticoagulant and specific lupus autoantibody testing including 494, ds694,

E94, and antiphospholipid antibodies is mandatory. 494 is found is almost

e0ery child !ith pSLE, !hile ds694 is detected in more than I+. 9o0el

antibodies ha0e been proposed and reuire prospecti0e 0alidation n pSLE.

hildren may ha0e fran/ hypothyroidism or hyperthyroidism or solely raised

titers of thyroid antibodies.

2.18. Pa$ma)ologi) te$apie!

he choice of immunosuppressi0e therapy in children and adolescents

depends on the patientHs specific disease manifestations. Jnfortunately, the

medical literature pro0ides little e0idence-based guidance on !hich to base

therapeutic decisions in the pediatric population. he limited a0ailable data are

often from retro specti0e or noncontrolled studies in children and adolescents or

inferred from adult studies. n children, selecting a medication also reuires

consideration of con0enience(e.g. thrice-daily dosing reuires gi0ing a dose at

school) and discomfort (e.g. oral 0ersus parenteral administra tion).

1. 7l#)o)o$ti)oid!

>lucocorticoids remain the mainstay for initial treatment of significant organ-

system in0ol0ement in pediatric SLE. he numerous toxicities associated !ith

chronic glucocorticoid therapy mandate careful use, and the best approach for

reducing toxicity is the use of steroid-sparing agents to minimize total

glucocorticoid exposure. n children, particularly important concerns include

effects on gro!th and body image, bone toxicity (loss or inadeuate accrual of

bone mass and a0ascular necrosis), and ris/ of mood disorders. =apid tapering of


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3

the glucocorticoid dose can result in disease flares. Jse of alternate-day dosing of

prednisone in stable SLE is a freuent practice, but no clinical trial data pro0es

that it is superior or eual to daily dosing of pred nisone. Small studies ha0e

sho!n that glucocorticoids reduce dendritic cell numbers and interferon

expression in patients !ith SLE intra0enous glucocorticoid pulse therapy appears

to enhance this effect (F 2ascual, personal communication). he safest dose,

route, freuency, and duration of glucocorticoid therapy remain un/no!n.

2. Hyd$o0y)lo$o:#ine

t is standard practice in the pediatric rheumatology community to maintain

children and adolescents !ith SLE on hydroxychlorouine. Bhile no studies ha0e

been performed in the pediatric population, a double-blind, placebocontrolled

!ithdra!al study in adults !ith SLE sho!ed a lo!er disease-flare rate in those

ta/ing hydroxychlorouine compared !ith those on placebo.

Cydroxychlorouine impro0es lipid profiles in adults !ith SLE, especially those

ta/ing glucocorticoids. he drug appears to be safe during pregnancy le0els of

hydroxychlorouine are lo! in breast mil/, suggesting that use during lactation

might be safe, although further Study is !arranted.

3. (on!te$oidal anti,inflammato$y d$#g!

9onsteroidal anti-inflammatory drugs (9S46s) are used in pediatric SLE

primarily to treat musculos/eletal symptoms. =ecent data ha0e highlighted the

potential cardio0ascular ris/ associated !ith chronic use of cyclo-oxygenase *

(8*)-specific inhibitors in adults, but it is not clear !hether this ris/ is

specific to 8* inhibitors or applicable to all 9S46s. he longterm

cardio0ascular conseuences of chronic 9S46 use in childhood remain

un/no!n and are particularly !orrisome in a population predisposed to

premature atherosclerosis. 4 hildhood 4rthritis and =heumatology =esearch

4lliance sur0ey of $ pediatric rheumatologists !ith #,$" years of cumulati0e


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3:

clinical experience reported only one cardio0ascular e0ent (pulmonary embolism

in a child !ith multiple =is/ factors for thrombophilia) in 9S46-treated

rheumatology patients ( Sandborg, personal communication). Lo!-dose,

prophylactic aspirin is commonly prescribed for adult and pediatric SLE patients

!ith 492C8S2C8L26 49;86ES but no history of thrombotic e0ents.

9o large-scale trials ha0e addressed the safety or efficacy of this practice.

%. 5etot$e0ate

Bee/ly oral or subcutaneous methotrexate is prescribed to treat

mucocutaneous and articular manifestations refractory to hydroxychlorouine or

9S46s. 6ata e0aluating methotrexateHs efficacy in pediatric SLE are limited

and mixed. Bhile an open-label study of # children sho!ed impro0ement in

disease acti0ity and decreased use of glucocorticoid in eight sub1ects, a

retrospecti0e assessment of ## patients !ith refractory pediatric SLE (se0en of

!hom also had nephritis) demonstrated only transient impro0ement.

5ethotrexate impro0es cutaneous and articular disease and reduces steroid

exposure in adults.

. A;atiop$ine

4zathioprine is often used as a steroid-sparing therapy in pediatric SLE@

ho!e0er, no controlled clinical trials ha0e assessed the efficacy of aza thioprine

in this population. 4zathioprine can be helpful in managing hematologic

manifestations of SLE, cutaneous disease refractory to hydroxychlorouine and

methotrexate, stable pneumonitis, or pleuritis and follo!ing standard

cyclophosphamide therapy for diffuse proliferati0e glomerulonephritis. Some

ad0ocate its use as first-line therapy in diffuse proliferati0e glomerulonephritis,

although this remains contro0ersial.

. 5y)openolate mofetil

5ycophenolate mofetil (55D) has recently gained popularity as a therapy


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3I

for lupus nephritis. Studies in adults !ith lupus nephritis suggest that 55D, !hen

used as induction or maintenance therapy, has short-term efficacy and safety at

least eual to cyclo phosphamide. 4 noncontrolled trial in0ol0ing ## children

!ith SLE sho!ed 55D (a0erage dose ** mg


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3

li/ely to de0elop permanent gonadal failure than their older counterparts@

ho!e0er, the ris/ is still #:+. n adult !omen !ith SLE !ho !ere recei0ing

cyclophosphamide treatment, gonadotropin-releasing hormone (>n=C) agonists

educed the incidence of o0arian failure. 2otential side effects of >n=C therapy

include menopausal symptoms, loss of bone mass, depression, and delay of

pubertal de0elopment. 9o studies ha0e assessed the safety and efficacy of >n=C

agonists in pediatric SLE, but a double-blind, placebo-controlled trial of

triptorelin in girls !ith SLE !ho are recei0ing cyclophosphamide therapy is

currently under!ay.n males, sperm ban/ing is a reliable option for reser0ing

child-bearing potential, but the issue must be discussed !ith sensiti0ity,

especially in younger boys. 8ther, more contro0ersial, options for preser0ing

fertility include in-0itro fertilization !ith embryo preser0ation and in0estigational

cryopreser0ation of oocytes or o0arian tissue. 2reser0ation of o0arian tissue,

oocytes, or sperm in inors raises ethical issues, including insurance co0erage and

o!nership in e0ent of a childHs death. ;efore starting cyclophosphamide therapy

in boys and girls !ith SLE, consultation !ith a reproducti0e endo crinologist is

strongly recommended.

4. Rit#0ima&

=ituximab, a ;-cell-depleting therapy, seems an attracti0e therapy for SLE, a

disease character ized by the presence of autoantibodies. 4 phase


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"

n noncontrolled trials, cyclosporin has sho!n some promise for treatment of

SLE@ ho!e0er, concerns about toxicity, including hirsutism, hypertension, renal

toxicity, and dyslipidemia, limit its use. Leflunomide, intra0enous immuno

globulin, plasma exchange, and stem-cell transplantation ha0e been sho!n to be

effecti0e in SLE in case reports or small studies, but none of these therapies has

yet gained !idespread acceptance as standard treatment in pediatric SLE.

hronic anticoagulation !ith !arfarin or heparin is indicated for children and

adolescents !ith antiphospholipid antibody syndrome.


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"#

2.11. Diffe$ential Diagno!i!

6ifferential diagnosis of childhood-onset Systemic Lupus Erythematosus.

2.12.

P$ogno!i!

4lthough current treatment of lupus has impro0ed sur0i0al dramatically,

prolonged and complete remission defined as $ years !ithout clinical and

laboratory e0idence of acti0e disease and on no treatment has remained


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"*

elusi0e for most patients. he incidence of flare is estimated to .$ per

patient-year of follo!-up. 5oreo0er, a significant number of patients (#A

*+ in tertiary referral centres) do not respond adeuately to

immunosuppressi0e therapies.


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"3

CHAPTER III

4SE =E28=

3.1. Patient Identity

9ame % =9

4ge % #" years old

>ender % Demale

4ddress % Lumban Sitahua/ apanuli Jtara

=eligion % hristian

=ace % 4sian

5arital status % Single

2e/er1aan % Student

Ceight % #$$ cm

Beight % 3 /g=5 number % .$.*.#"

3.2. Objective

he ob1ecti0e of this paper is to report a case of a #" years old girl !ith a diagnosis of

systemic lupus erythematosus

3.3.Case

=9, a #"-year-old girl presented to the adam mali/ hospital !ith a complaint

continue chemotherapy. he patient has been enrolled in the di0ision of allergy

immunology 4dam 5ali/ hospital !ith the diagnosis of systemic lupus

ertematosus. Cistory of pre0ious illness, patients come first in September !ith a

history of 1oint pain and s!elling in the hands, /nees, and an/les. 2ain is felt

already for # !ee/ . 2ain of the 1oints getting !orse in the morning, especially on


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""

!a/ing. =eddish rash experienced by the patient in simultaneously !ith pain. he

rash felt heat and itching. he rash initially patchy reddish spots alone and

increasingly spread on both sides of the chee/s. =ash !orsens !hen exposed to

sunlight. patients experienced hair loss since * !ee/s. Jrination abnormalities

denied. omplaints of pale and yello! body denied. 2resent seizures denied.

2re0ious history of seizures experienced by patients until there is a decrease of

consciousness.

Cistory of disease% Systemic lupus erythematosus

Cistory of medication %5ethylprednisolone in1ection, 24 in1ection,

methylprednisolone tablet.

Cistory of family % 9one

Cistory of parentHs medication % 9one

Cistory of pregnancy % he age of the patientHs mother !as * during

pregancy. he gestation age !as Q months.

Cistory of birth % ;irth !as assisted by traditional mid!ife. he

patient !as born per0aginam and cried

immediately after birth. ;ody !eight at birth !as

unclear, body length at birth !as unclear and head

circumference !as unclear. yanosis (-), 7aundice

(-).

Cistory of feeding % exclusi0ely breast feeding, formula feeding (-#I

months), porridge mil/ (since #* months),

porridge rice (since #* months), family food (since

#I months).

Cistory of immunization % Jnclear

Cistory of gro!th and de0elopment % 2atientHs mother reported that patient gre!


43/52

"$

normally. he patient had de0eloped tal/ing,

cra!ling, and !al/ing s/ills on time.

2hysical Examination%

P$e!ent !tat#!'

Sensorium %compos mentis ;ody temperature% 3:.R

C=% I bpm ==% **bpm

;B% 3/g ;C% #$$ cm

anemic (-), icteric (-), dyspnea (-), cyanosis (-), edema (-).

Localized status%

• Head :

Hair and scalp :alopesia

Face : edema (-), malar rash (), discoid rash ()

Eye : endofthalmus (-), eofthalmus (-), li!ht

re"e (#$#), isochoric pupil, palpebral

conjunctiva pale (-$-),sclerai%eri% (-$-),

normal vision

Ears % both ear lobe in normal morphologic, ear discharge (-


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"

'arrel chest (-), i!eon chest (-), Funnel

chest(-), /ymmetrical fusiform, retraction (-)

alpation : stem fremitus left0ri!ht, normal

condition 1ithin both lun!s2

ercussion :

un!s :sonor on both lun!s2

Heart :

3pper barrier : .C/ ... sinistra

4i!ht barrier : .C/ + /5 detra

eft barrier6 .C/ + 7 cm medial 8C/

9uscultaion:

un!s :

'reathin! sound :vesi%uler

9dditional sound:ron%i(-$-), 1heein! (-$-)

Heart : /7,/; (#), /


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":

Bor/ing diagnosis % Systemic lupus erithematosus

Laboratory finding%

omplete blood analysis

est =esult Jnit =eferences

Cemoglobin ##,$ g+ ##.3-#".#

Erythrocyte 3.$ #


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"I

2otassium 3. mE


47/52

"

CHAPTER IV

"9LL9W UP

6ate S 8 4 2

herapy 6iagnostic

#*


48/52

$

A

#"


49/52

$#

murmur (-) == % *"x


50/52

$*

CHAPTER V

DIenetic factor

3. Epigenetic effect

". Cormonal factor

$. 6rug. nduced Lupus Erythematous

. 9eonatal Lupus Erythematous

diopatic

CLI(ICAL 5A(I"E

CLA


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$3

72 4ntinuclear antibodies (494)

772 mmunologic disorder%

anti-694 antibody, anti-Sm

antibody, or antiphospholipid

antibodies

LA/ DIA7(9


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$"

sle tinjauan

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