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Lupus Eritematosus

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  • PENDAHULUANLupus Eritematosus Sistemik/LES merupakan penyakit sistemik evolutif yg mengenai satu atau beberapa organ tubuh, ditandai oleh inflamasi luas pada pembuluh darah dan jaringan ikat, bersifat episodik yang diselingi oleh periode remisi.Manifestasi klinis LES sangat bervariasi dgn perjalanan penyakit yg sulit diduga, tidak dapat diobati, dan sering berakhir dengan kematian

  • Karena gambaran klinisnya bervariasi dan penampilan awalnya tidak selalu menunjukkan keterlibatan multi organ, maka sering kali gejala awal sudah timbul lama, bahkan bertahun tahun sebelum didiagnosis SLE ditegakkan. Kadang pada waktu SLE ditegakkan, kelainan ginjal sudah ditemukan

  • INTRODUCTIONSystemic lupus erythematosus (SLE) is a chronic autoimmune disease that can be fatal; however, with recent medical advances, fatalities are becoming increasingly rare. The immune system attacks the bodys cells and tissue, resulting in inflammation and tissue damage. SLE can affect any part of the body, but most often harms the heart, joints, skin, lungs, blood vessels, liver, kidneys, and nervous system. Lupus can occur at any age, and is most common in women, particularly of non-European descent.

  • ETIOLOGI1. Faktor GENETIK2. Faktor ENDOKRIN3. Faktor OBAT4. Faktor INFEKSI

  • Etiophathogenesis = Cellular LevelT-Cell dysfunctionB-Cell activationAbnormal Cytokine productionBottom line:(the above factorsand other immune dysregulation culminates in an) abnormal abundance ofautoantibodies and reduced reaction to pathogens

  • T-Cell DysfunctionDecreased Th1 activity--> normally regulate other TcellsDecreased IL-2, TNF-alpha, INF-gammaIncreased Th2 activity--> normally regulate B cell growthIL-4,5,6,10antigen binds here

  • B-Cell Activation

  • Abnormal Cytokine ProductionIncreased Th2--> Increased IL-10--l IL-1,2 (spontaneous in ppl w/ SLE)IL-10 --> Th2 cytokines that activate B cells and deactivate macrophages... viscious cycle...

  • PATOFISIOLOGILES timbul sebagai ekspresi klinis suatu mekanisme sekuensial, yang awalnya merupakan berbagai faktor etiologi yang masih belum diketahui dengan jelas.Secara ringkas LES berawal dari ketidak mampuan sistem imun tubuh untuk mengebnal struktur antigen diri sehingga terjadi mekanisme autoimun.Autoantibodi yg terbentuk akan berikatan dgn autoantigen membentuk kompleks imun yang mengendap berupa depot dalam jaringan.Akibatnya akan terjadi aktivasi komplemen sehingga terjadi reaksi inflamasi yang menimbulkan lesi ditempat tersebut.

  • House is wrong

    This time...House is wrong...

  • Systemic Lupus ErythematosusA chronic inflammatory systemic autoimmune disease of unknown etiology characterized by polyclonal B-cell activation and abnormal autoantibodies

  • MANIFESTASI KLINISGejala yang timbul merupakan manifestasi aktivitas autoantibodi dan /atau depot kompleks imun dgn vaskulitis.Semua organ tubuh dapat terserang pada suatu saat, atau pada tahap evolusi penyakit yang berbeda.Pada awal perjalanan penyakit, gejala klinis yang muncul sangat terbatas hingga diagnosis sulit ditegakkan.Pada perjalanan penyakit selanjutnya gejala klinis tersebut akan lebih kerap ditemukan.Bila gejala tsb muncul berulang atau disertai gejala lain sehingga menjadi lengkap, maka diagnosis dapat lebih mudah ditegakkan

  • Gambaran klinis LESLESSSP20%Hepotomepali/Splenomegali20%Sal cerna18%Paru38%Hematologi50%Jantung 48%VaskulitisGinjal50%Limphadenopati12-50%Kelelahan90%Panas lama80-82%BB turun60%Artritis/Artralgia90% Kulit50-58%

  • SYMPTOMS

    SYMPTOMSPERCENTAGE (%)Achy joints / arthralgia95 Fever of more than 100 degrees F / 38 degrees C 90Arthritis / swollen joints 90Prolonged or extreme fatigue 81Skin Rashes 74Anemia71Kidney Involvement 50Pain in the chest on deep breathing / pleurisy45Butterfly-shaped rash across the cheeks and nose 42Sun or light sensitivity / photosensitivity 30Hair loss 27Abnormal blood clotting problems20Fingers turning white and/or blue in the cold17Mouth or nose ulcers12

  • Systemic Lupus Erythematosusbutterfly rashFinger turns blue

    Skin rashes

  • ImmunogeneticsIncreased Risk for SLE in:HLA-DR2 (anti-DNA Abs)HLA-DR3 (anti-Ro Abs)Null alleles at C2 and C4 lociSLE may be transmitted in an autosomal dominant pattern (family studies)

  • SLE Genetic Susceptibility MHC RelatedHLA-DR1, 2, 3, 4Alleles of HLA-DRB1, IRF5, and STAT4 C2 - C4 deficiencyTNF- polymorphisms

    Not MHC RelatedC1q deficiency (rare but highest risk)Chromosome 1 region 1q41-43 (PARP), region 1q23 (FcRIIA, FcRIIIA)IL-10, IL-6 and MBL polymorphismsChromosome 8.p23.1: reduced expression of BLK and increased expression of C8orf13 (B cell tyrosine kinase), chromosome 16p11.22: integrin genes IGAM-ITGAXB cell gene BANK1X chromosome-linked gene IRAK1

  • DIAGNOSIS

    CriterionDefinitionMalar RashRash over the cheeksDiscoid RashRed raised patchesPhotosensitivityReaction to sunlight, resulting in the development of or increase in skin rashOral UlcersUlcers in the nose or mouth, usually painlessArthritisNonerosive arthritis involving two or more peripheral joints (arthritis in which the bones around the joints do not become destroyed)SerositisPleuritis or pericarditis (inflammation of the lining of the lung or heart)Renal DisorderExcessive protein in the urine (greater than 0.5 gm/day or 3+ on test sticks) and/or cellular casts (abnormal elements the urine, derived from red and/or white cells and/or kidney tubule cells)

  • DIAGNOSISAdapted from: Tan, E.M., et. al. The 1982 Revised Criteria for the Classification of SLE. Arth Rheum 25: 1271-1277.

    CriterionDefinitionNeurologic DisorderSeizures (convulsions) and/or psychosis in the absence of drugs or metabolic disturbances which are known to cause such effectsHematologic DisorderHemolytic anemia , leukopenia , lymphopenia or thrombocytopenia. The leukopenia and lymphopenia must be detected on two or more occasions. The thrombocytopenia must be detected in the absence of drugs known to induce it.Antinuclear AntibodyPositive test for antinuclear antibodies (ANA) in the absence of drugs known to induce it.Immunologic DisorderPositive anti-double stranded anti-DNA test, positive anti-Sm test, positive antiphospholipid antibody such as anticardiolipin, or false positive syphilis test (VDRL).

  • 1982 ACR (Revised 1997) SLE Classification Criteria

    Malar (butterfly) rashDiscoid lesionsPhotosensitivityOral ulcersNon-deforming arthritis (non-erosive for the most part)Serositis: pleuropericarditis, aseptic peritonitisRenal: persistent proteinuria 0.5 g/d or 3+ or cellular castsNeurologic disorders: seizures, psychosisHeme: hemolytic anemia; leukopenia, thrombocytopeniaImmune: anti-DNA, or anti-Sm, or APS (ACA IgG, IgM), or lupus anticoagulant (standard) or false + RPRPositive FANA (fluorescent antinuclear antibody) Definite SLE = 4 or more positive criteria

  • Lupus Diagnostic Criteria (need 4)1. Malar Rash: Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds

    2. Discoid rash: Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions

    3. Photosensitivity: Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation

    4. Oral ulcers: Oral or nasopharyngeal ulceration, usually painless, observed by physician

    From http://www.rheumatology.org/publications/classification/SLE/1997UpdateOf1982RevisedCriteriaClassificationSLE.asp?aud=pat

  • Gambar Rash berbentuk KUPU KUPUseperti kupu-kupu pada penderita SLE

  • Malarrash

  • Arthritis (with swelling)

  • Joint involvement in lupus mimics rheumatoid arthritis (RA) but milder

  • Arthritis (Jaccouds)

  • Photosensitivity

  • SLE-Clinical and Laboratory FeaturesMusculoskeletal 90%Skin80%Renal50%CNS15%Severe thrombocytopenia 5-10%Positive ANA 95+%

    Also, cardiopulmonary involvement, thrombotic tendency (APS), and premature or accelerated atherosclerosis!

  • SLE Pathogenetic MechanismsImmune complex-mediated damage: glomerulonephritis

    Direct autoantibody-induced damage: thrombocytopenia and hemolytic anemia

    Antiphospholipid antibody-induced thrombosis

    Complement-mediated inflammation: CNS lupus (C3a), hypoxemia, and also anti-phospholipid mediated fetal loss

    Either failure of or abnormal response to normal apoptosis

  • Immune-complex Injury in SLEDNA + Anti-DNA = DNA - Anti-DNA complex C3 C4

    Tissue Injury

    SLE: Anti-DNA, C3, C4

  • SLE THE USE OF POSITIVE ANAS A positive ANA alone is not enough to diagnose SLE! Are there other autoantibodies present, e.g., anti-DNA, anti- Sm, anti-Ro? What are the patients clinical features that suggest lupus? Photosensitivity, serositis, thrombocytopenia, proteinuria, skin rashes?

    An ANA should only be ordered if the clinical picture warrants it! About 6-10% of people in the general population are ANA (+)

  • SLE Cardiac DiseasePericarditisInflammatory fluid Rarely tamponadeMyocarditisCoronary vasculitis RareLibmann-Sachs endocarditisPremature or accelerated atherosclerotic disease

  • Causes of Cardiovascular Complications in Lupus

    Procoagulant State (multifactorial, APS)

    Strokes PVD

    Premature or Accelerated Atherosclerosis

    MIs

  • CV SystemPericarditis 6-45% of patients: low likelihood of tamponade or constrictive t

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