Diagnosis dan Penatalaksanaan Lupus Natsir Akil RS Kanujoso Djatiwibowo Balikpapan

Pendahuluan Lupus dengan berbagai julukan : Penyakit seribu wajah (The Disease with a Thousand Faces). Peniru ulung (The Great Imitator). Penyakit misterius (The Mysterious Disease).

Pendahuluan Lupus Salah satu dari penyakit autoimmune (AI) Etiologi belum diketahui dengan pasti Menyerang wanita muda. Angka kematian cukup tinggi. Pengobatan belum memberi hasil yg memuaskan Efek samping pengobatan

The immune system The immune system is a network of organs, cells and molecules that work together to defend the body against attacks by foreign (not of the body) invaders such as germs, bacteria, viruses, parasites and fungi. We will focus on adaptive responses. All these feature of an adaptive response require very specific interactions of molecules. Will describe B and T cells and their roles. Immunological memory - vaccination

The immune system Anatomic barriers (Skin,mucous membranes) Innate (non-specific) immunity Adaptive (specific) immunity Anatomic barriers (Skin,mucous membranes) Physological barriers (temperature, pH) Phagocytic Barriers (cells that eat invaders) Inflammatory barriers (redness, swelling, heat and pain) Antigen specificity Diversity Immunological memory Self/nonself recognition We will focus on adaptive responses. All these feature of an adaptive response require very specific interactions of molecules. Will describe B and T cells and their roles. Immunological memory - vaccination

Autotolerance Unresponsiveness to self antigens is known as autotolerance Both B-cells and T-cells participate in tolerence but T-cells play the primary role Yamamoto K. JMAJ 2004; 47(9): 403–406.

HEALTHY PERSON Autotolerance AUTOIMMUNITY SUCCES HEALTHY PERSON Autotolerance FAIL AUTOIMMUNITY AUTOIMMUNE DISEASE

Faktor predisposisi lupus Genetics Hormones Environment

Patogenesis lupus

Type-III Hypersensitivity: Immune Complex Animation: Large quantities of soluble antigen-antibody complexes form in the blood and are not completely removed by macrophages. These antigen-antibody complexes lodge in the capillaries between the endothelial cells and the basement membrane. The antigen-antibody complexes activate the classical complement pathway and complement proteins and antigen-antibody complexes attract leukocytes to the area. The leukocytes then discharge their killing agents and promote massive inflammation. This leads to tissue death and hemorrhage

Type-II Hypersensitivity: ADCC Host cell

Type-II Hypersensitivity: ADCC Host cell

Diagnosis lupus Pada beberapa kasus sulit, terutama fase dini. Menyerupai banyak penyakit non autoimun. Antara satu penyakit autoimun dengan yg lain juga kadang2 sulit membedakan. Tidak ada pemeriksaan tunggal yg dpt menentukan lupus. Pada seseorang individu bisa ditemukan bbrp penyakit AI.

Kewaspadaan akan Lupus Kecurigaan akan lupus perlu dipikirkan jika dijumpai 2 atau lebih kriteria dibawah 1. Wanita dengan keterlibatan 2 organ atau lebih 2. Gejala konstitusional : kelelahan, demam (tanpa bukti infeksi) dan penurunan BB 3. Muskuloskeletal : artritis, atralgia, dan miositis 4. Kulit : ruam kupu-kupu (butterfly atau malar rash), fotosensitivitas, lesi membrane mukosa, alopesia, fenomena Raynaud, purpura, urtikaria, vasculitis. 5. Ginjal : hematuria, proteinuria, silinderuria, sindroma nefrotik 6. Gastrointestinal : mual, muntah, dan nyeri abdomen 7. Paru-paru : pleurisy, hipertensi pulmonal, lesi parenkim paru. 8. Jantung : pericarditis, endocarditis, miokarditis 9. Retikulo-endotel : organomegali (limfadenopati, splenomegaly, hepatomegaly) 10. Hematologi : anemia, leukopenia, dan trombositopenia 11. Neuropsikiatri : psikosis, kejang, sindroma otak organic, myelitis transversus, gangguan kognitif neuropati kranial dan perifer

ACR 1997 CRITERIA FOR SLE Neurologic Malar rash Pleuritis or pericarditis Cytopenia Positive immunoserology - Anti-dsDNA - Anti-sm - Anti-phospholipid antibodies 11. ANA positive Malar rash Discoid rash Photosensitivity Oral or nasal ulcers Non erosive arthritis Nephritis - Proteinuria >0.5 gm/day - Cellular casts aa Diagnosis SLE ditegakkan jika ditemukan 4 atau lebih dari 11 kriteria

SLICC Classification Criteria for Systemic Lupus erythematosus Requirements : > 4 criteria (at least 1 clinical and 1 laboratory criteria) OR biospy-proven lupus nephritis with positive ANA or Anti-DNA Clinical Criteria Immunologic Criteria Acute Cutaneus Lupus Chronic Cutaneus Lupus Oral or nasal ulcers Non-scarring alopecia Synovitis Serositis Renal Neurologic Hemolytic anemia Leukopenia (<4000) or Lymphopenia (<1000) Thrombocytopenia (<100.000/mm3) ANA Anti-DNA Anti-Sm Antiphospholipid Ab Low complement (C3,C4,CH50) Direct Coombs’ test (do not count in the presence of hemolytic anemia) Inflammatory synovitis with physician-observed swelling of two or more joints OR tender joints with morning stiffness. Renal : urine protein/creatinine (or 24 hr urine protein) representing at least 500 mg of protein/24 hr or red blood cell casts. Neurologic : seizures, psychosis, mononeuritis multiplex, myelitis, peripheral or cranial neuropathy, cerebritis (cute confusional state). Antiphospholipis antibody : lupus anticoagulant, false-positive test for syphilis, anticardiolipin-at least twice normal or medium-high titer, anti-β2 glycoprotein 1 SLICC : Systemic Lupus International Collaborating Clinics Petri M, et al. Arthritis and Rheumatism. Aug 2012

Prinsip pengobatan lupus Menekan aktifitas sistim imun Menggunakan steroid, obat-obatan imunosupressan, dan Agen Biologik. Mencari keseimbangan antara efikasi dari obat2an dan efek samping pengobatan yang mungkin timbul Mengobati komorbiditas Tindakan non farmakologis

Obat-obatan imunosupressan Steroid Klorokuin/hidroksiklorokuin Methotrexate (MTX) Azathioprine (Imuran) Siklosporin (Sandimun) Cellcept/Myfortic Cyclophosphamide IV IG Biologic agents

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