HMS-Arthritis in Systemic Lupus Erythematosus

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Arthritis in Systemic Lupus

ErythematosusProf. Hermansyah

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History

• 1948 – Malcolm Hargra es !isco ers thelupus erythematosus "LE# cell.

• 19$% – &he 'rst anti()*A anti+o!y isi!enti'e!.

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Systemic Lupus Erythematosus

• ,n-ammatory autoimmune !iseaseof un no/n etiology

• Mor+i!ity – )isease associate! – 0orticosteroi! associate!

• 0orticosteroi! use as high as 89 1(2

• Mortality $(13 at 13 years – Early ( acti e !isease an! infections – Late ( atherosclerosis1. onana(*acach et al .5 2333 2. 6ro/it7 et al .5 A0 meeting 2333

"A+stract#

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• Michael ac son has +een !iagnose!/ith lupus5 :o; *e/s is reporting <

=Systemic lupus erythematosus "SLEor lupus# is a chronic

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)amage /ithin SLESL,00>A0 )amage ,n!e; 1

Damage Index Domain N %

Musculoskeletal 121 22%Neuropsychiatric 110 20%Renal 79 1 %

!cular "# 1$%ardio&ascular '7 9%

(ulmonary $9 7%)kin ' #%(eripheral &ascular $' "%Dia*etes mellitus $0 "%

+astrointestinal 19 '%Malignancy 1' $%(remature gonadal ,ailure 12 2%1- .onana/Nacach et al - 2000

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? er ie/ of 0linical &rial )esignProcess

• 0olla+orati e process +et/een@enela+s5 :)A an! 0onsultants

• 199$ Arthritis A! isory0ommittee – &/o e cacy per(patient en!points

• steroi! re!uction

• impro e! !isease acti ity• 1999 Arthritis A! isory

0ommittee – 0linical trial en!points !iscusse!

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Primary E cacy En!point " espon!er#

Sustaine! pre!nisonere!uction < – Pre!nisone !ecrease! to ≤ %.$

mg>!ay• :or ≥ 2 consecuti e months

• ,nclu!ing last isit

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1# e!uction in 0orticosteroi!eBuirements

• ,f SLE)A, /as sta+le or impro e!5an algorithm !ictate! steroi! taper

2# ,mpro ement or Sta+ili7ation of SLE• Case! upon impro ement or

sta+ili7ation in each of SLE)A,5SLAM5 D:SS an! Patient AS5/ithout clinical !eterioration

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@enetic Associations

• HLAFs are loci on genes that co!e forcertain G chain on the MH0 comple;

• HLA() 2• HLA()• HLA()IC1 – ,n ol e! in me!iating

pro!uction of anti+o!ies to !s()*A

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Cur!en of )isease

• Most patients ha e either recurrent-ares or continuously acti e !isease 1

• :lares remain common in esta+lishe!!isease 2

• Mor+i!ity also associate! /ithcorticosteroi! use

1. Carr et al .5 1999 J 2. Petri et al .5 1991J . onana(*acach5 et al .5 2333

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Symptoms

• *on(speci'c< – :atigue – Keight loss

– Malaise generally feeling ill – :e er – Anore;ia "o er time# – Arthritis

• 93 of patients e;perience arthritic symptoms• Symmetrical• Appears in han!s5 /rists5 an! nees mainly

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S in Manifestations• Malar or

Cutter-y ash• )iscoi! ash –

Stimulate! +y6 light• S in

manifestations

only appear in3(43 of lupuspatients.

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enal "Di!ney#Manifestations

• $3(%3 of all lupuspatients e;perience renal!e elopments.

• Most )angerous< – @lomerulonephritis

/here at least $3 ofthe glomeruli ha ecellular proliferation

• @lomeruli – capillary+e!s in the i!neythat 'lter the +loo!.

• enal :ailure +ecause of@lomerulonephritis is thelea!ing cause of !eathamong lupus patients.

Normal

Glomerulonephritis16/09/11 18


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?ther Manifestations

• 0ar!iac• 0entral *er ous System

• Hematological

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Main Pathology

• &he plasma cells are pro!ucing anti+o!iesthat are speci'c for self proteins5 namely!s()*A

• ? eracti e C(cells• Suppresse! regulatory function in &(cells• Lac of &(cells

• Acti ation of the 0omplement system

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? eracti e C(cells

• Estrogen is a stimulator of C(cell acti ity – Lupus is much more pre alent in females of

ages 1$(4$• Height of Estrogen pro!uction

• ,L(135 also a C(cell stimulator is in highconcentration in lupus patient serum. – High concentration lin e! to cell !amage

cause! +y in-ammation

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&(cell Malfunctions

• :c region s/itch – NO – Lea!s to malfunction in signaling an!

!ecrease! ,L(2 pro!uction• ,ncrease! le els of 0a 2

– Lea!s to spontaneous apoptosis

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Acti ation of 0omplement System

• 0omplement system is acti ate! +ythe +in!ing of anti+o!ies to foreign!e+ris. – ,n this case its o er acti ation

• C0s lac 0 1 receptor – )ecreasing the aQecti e remo al of

comple;es

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,g@ Pathogen

• ,g@ is the most Rpathogenic+ecause it forms interme!iate si7e!comple;es that can get to the smallplaces an! +loc them.

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&esting

• ES• 6rinalysis• 0omplement &est

– &ests le els of 0 5 045 0H$3 – Lo/ le els in!icates possi+le presence of

!isease• :A*A – :luorescent antinuclear anti+o!y• ?uchterlony &est – sho/s interactions

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:A*A• EL,SA &est

– @enerally test for<• !s()*A

anti+o!ies

• Antihistoneanti+o!ies – Cin!s to )*A5

maTorconstituent of

chromatin• )eo;yri+onucleop

rotein ")*P#

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?uchterlony &est• 6se! to !etermine

immunologicalspeci'city

• ules out a falsepositi e

• Sho/s the serum!oes or !oes notha e antinuclearanti+o!ies

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HMS-Arthritis in Systemic Lupus Erythematosus

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