Lupus

Sigit Widyatmoko Fakultas Kedokteran UMS

Pendahuluan

Beberapa dekade yang lalu SLE merupakan penyakit yang progresif dan fatal Saat ini lebih sering dijumpai SLE kronik, di antara episode aktif terdapat masa remisi sempurna Jalur kematian: vaskulitis ginjal, SSP Sebagian penderita lain kematian akibat infeksi sekunder Merupakan prototip penyakit autoimun multisistem berbeda dengan penyakit autoimun lain yang organ-specific (DM tipe 1, miastenia gravis, penyakit graves)

What is Lupus

Found in 1851, in Ancient Greece, Lupus is Latin for wolf, relating to the butterfly rash that may appear on the cheeks of many Lupus patients, referring to the facial marking of a wolf bite. Lupus, known as lupus erythematosus or systemic lupus erthematosus, it is an auto-immune disease, in which the bodies healthy tissues and organs are attacked by an increased amount of antibodies .

Lupus causes the body to become allergic to itself, and produce too many antibodies
These antibodies start attacking tissues and organs all throughout the body, causing inflammation in certain parts of the body where the attack is taking place The inflamed areas of the body are usually reddish in color, tender, and often painful

There Are 3 Types of Lupus!

Systemic Lupus Erythematosus, or (SLE), which involves many parts of the body including the heart , the kidneys, and brain. Discoid Lupus Erythematosus mainly affects the skin. Red rashes may occur on the face or stomach.

3 Types Of Lupuscontinued

Drug-Induced Lupus this one is triggered by few medicines. Similar to SLE, but goes away when medicine is stopped. Drugs that cause it are hydralazine and procainamide.

Who is at risk?

1.5- 2 million American are affected 90% are women More common in African American, Latinos, Asian, and Native Americans than in Caucasian

Prevalence

90% of Lupus patients are women ages 15-45. Estimated that 500,000 to 4 million people have Lupus.

Women are five times more likely to die than men.

There has been a 70% increase in the number of African-American women dying from Lupus.

Possible Causes

Speculations of environmental factors

Viral or bacterial infections. UV light. Prescription heart medication. Antipsychotic drugs. Epstein-Barr virus. Mononucleosis. Lyme disease. Anti-DNA antibodies. Genetic predisposition (Journal of American Medical News)

Possible Causes such as:

PatogenesisLupus

Etiopatologi SLE belum diketahui secara pasti melibatkan interaksi yang komplek dan multifaktorial antara variasi genetik dan faktor lingkungan Faktor genetik: elemen genetik yang berkontribusi terhadap SLE adalah gen dari MHC melibatkan polimorfisme gen HLA Contoh:

kejadian SLE lebih tinggi pada kembar monozigotik (25%) dibandingkan dizigotik (3%) Frekuensi pada keluarga penderita & etnik tertentu

Faktor hormonal

Faktor Sex:

Perempuan > laki-laki. Serangan pertama jarang terjadi pada prepubertas dan postmenipause Data: kadar estrogen , sedang androgen, testosteron,dihidrotestosteron,dehidroepiansosteron Estrogen berlebihan dan hormon androgen yang tidak adekuat bertanggungjawab terhadap perubahan respon Estrogen memperburuk SLE dengan memperpanjag hidup sel autoimun, meningkatkan produksi sel T helper2, dan menstimulasi produksi autoantibodi oleh sel B

Hormon lain: prolaktin kadar meningkat pada SLE Efek menyerupai sitokin, yang mempunyai aktivitas endokrin, parakrin, dan autokrin Prolaktin merupakan promotor aktivitas klinik dan keparahan penyakit Supresi prolaktin dengan bromokriptin mampu menurunkan aktivitas penyakit

Hormon Sel Lemak

Hormon sel lemak yang diduga terlibat dalam patogenesis SLE adalah leptin kadar leptin meningkat Leptin merupakan hormon yang disintesis oleh jaringan lemak dan berikatan dengan reseptor sitokin kelas 1 Leptin adalah hormon yang menyerupai sitokin dengan aksi pleiotropik dalam memodulasi respon imun

Disfungsi Imun

Autoantibodi:

Gangguan imunologis utama adalah produksi autoantibodi Antibodi ini ditujukan kepada self molecules yang terdapat pada nukleus, sitoplasma, dan permukaan sel ANA paling banyak ditemukan pada SLE (>95%) Anti double stranded DNA (anti dsDNA) dan anti Sm antibodi merupakan antibodi yang spesifik

Manifestasi Klinik

Keterlibatan organ non vital:

Kelainan dermatologis Artritis Serositis ringan

Keterlibatan organ vital:

Nefritis Serebritis Serositis berat

Gejala klinik

Symptoms

Symptoms may be unpredictable and transient, differing for each patient.

May include: Persistent profound fatigue. Joint pain and inflammation. Skin rashes. Extreme sensitivity to sunlight. Mental confusion. Chronic low-grade fever. Raynauds like extremities. Mouth ulcers and hair loss (Journal of American Medical News).

Symptoms

Skin: butterfly rash across the check, ulcers in the mouth, hair loss, discoid lesions, photosensitive Joint: pain , redness, swelling. Intermittent polyarthritis, varying from mild to disabling. Most commonly in hands, wrists, and knees Kidney: Nephritis asymptomatic: abnormal urinalysis (microscopic hematuria), excessive protein in the urine (> 500 mg/24h) Inflammation in the lining of the lungs, heart, and / or around the heart

Blood: RBC are destroyed by autoantibodies (normochromic normocytic), low WBC count, low number of platelets. Platelet count < 40,000 & abnormal bleeding (-): therapy may not be required Lungs: infiltrates (difficult to distunguish from infection on imaging), pleuritis with or without effusion mild: may respon with NSAID, severe: glucocorticoid therapy Cardiac: pericarditis (respond to steroid & infrequently leads to tamponade), myocarditis, endocarditis (leads to valvular insufficient).

Nervous system: in some cases these are the major cause of morbidity and mortality seizures, cognitive dysfunction (most common manifestation of diffuse SLE), headache. Psychosis must be distinguished from glucocorticoid-induced psychosis. Vascular occlusion: prevalence of TIA, stroke, and myocardial infarct is increased caused by focal occlusion (either noninflammatory or associated with vasculitis) or by embolization

Photosensitivity: exposure to ultraviolet light causes rash Oral ulcers: include oral and nasopharyngeal ulcers Serositis: pleuritis or pericarditis documented by ECG or rub or evidence of effusion

Laboratory Test

Anti-nuclear test (ANA): positive in > 95% of patients, usually at the onset of symptomps best screening test, repeated negative tests make SLE unlikely Anti-DNA antibody test: positive in 70% high titers are SLE specific and correlate with disease activity, nephritis, vasculitis Anti-Sm antibody test: positive in 25% specific for SLE: no definite clinical correlation

Diagnosis

There is no single test for Lupus, the FDA just approved a new screening tool used for testing. 50% of lupus patients see at least three doctors before being diagnosed (Journal of American Medical News). May take an average of up to eight years to diagnosis Lupus (Phillips, 21). A complete blood count. Liver and kidney screening panels. Laboratory tests for specific auto-antibodies. Antinuclear antibodies ANA, a syphilis test. Urinalysis. Blood chemistries. Erythrocyte sedimentation rate (Journal of American Medical News).

Initial screening includes:

Sensitivity is 75%, specifity is 95%

Renal Manifestations

50-70% of all lupus patients experience renal developments. Most Dangerous:

Glomerulonephritis where at least 50% of the glomeruli have cellular proliferation

Glomeruli capillary beds in the kidney that filter the blood.

Normal

Renal Failure because of Glomerulonephritis is the leading cause of death among lupus patients.
Glomerulonephritis

Pictures of Lupus & Diagram

Leg

Arm

Hands

Head

Nose

Malar Rash

Fixed erythema, flat or raised, over the malar eminences Treatment consists primarily of local glucocorticoids and

systemic antimalarials

Acute Cutaneous: Malar Rash Note Sparing of Nasolabial Folds

Chronic Cutaneous:Discoid Note Scarring, Hyperpigmentation

Diskoid Rash

Erythematous circular raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur Only 5% of people with DLE have SLE (although half have positive ANA)

Arthritis

Nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion

Erosions on joint x rays are rare

The prevalence of ischemic necrosis of bone is increased especially in patient treated with systemic glucocorticoid

Jaccouds Arthopathy: Nonerosive, Reducible Deformities

Subacute Cutaneous Lupus

Follicular Plugging

Livedo Reticularis

ACR

LE Cell
Now is more historic than diagnostic interest Results from the presence in the blood of IgG antibody, reacts with nuclei from many tissues, small amount of complement are required for the reaction Present in 70-80% of SLE, compared with ANA is less sensitive Do not differentiate drug and discoid LE from SLE Found in 10 % patient of RA, which is association with sjogrens syndrome

LE Cell

The LE cell is a neutrophil that has engulfed the antibody-coated nucleus of another neutrophil. LE cells may appear in rosettes where there are several neutrophils vying for an individual complement covered protein.

TREATMENT

There is no cure for SLE and complete sustained remission are rare Therapeutic choice depend on:

Whether disease manifestation are life threatening or likely to cause organ damage, justifying aggresive therapies Whether manifestations are potentially reversible The best approaches to preventing complications of disease and its treatment

Edukasi

Mencakup pemberian informasi mengenai penyakit, faktor yang dapat menyebabkan kekambuhan seperti terlalu lelah, paparan berlebihan sinar matahari Pencegahan osteoporosis baik karena obat atau aktivitas penyakit

Penatalaksanaan Lupus

Menghindarkan faktor pencetus Penekanan sistem imun secara non selektif Terapi simtomatik dan suportif imunomodulasi Memperbaiki toleransi tubuh secara selektif. Modulasi hormonal. Radioterapi

Menghindarkan Faktor Pencetus

Radiasi sinar ultra violet Obat-obatan yang digunakan sehari-hari drug induced LE Infeksi mikroorganisme yang memproduksi endotoksin Trauma Stress psikologis Penderita pasca bedah

Penekanan Sistem Imun Non Selektif

OAINS

Bekerja dengan menghambat produksi prostaglandin melalui jalur siklooksigenase dari metabolisme asam arakidonat Berguna untuk mengatasi manifestasi sistemik seperti demam, artritis, serositis Perlu diberikan terlebih dahulu pada penderita yang tidak ada manifestasi pada organ vital Terbukti dapat mengurangi kebutuhan dosis steroid

Anti Malaria

Bermanfaat untuk mengatasi kelainan kulit seperti ruam kulit dan alopesia Bekerja secara sinergistik dengan OAINS dan steroid Memungkinkan penggunaan steroid dosis lebih rendah SLE dengan kelainan sendi dan kulit yang ringan cukup dengan OAINS dan antimalaria Gejala sistemik berat dengan manifestasi kulit jelas: kortikosteroid tanpa OAINS + antimalaria Klorokuin: 1 X 250, hidroksiklorokuin: 1 X 400 Efek samping: toksik terhadap retina

Kortikosteroid

SLE ringan tidak diperbolehkan diberikan kortikosteroid berlebihan Kortikosteroid dosis tinggi, indikasi:
Serositis berat Kelainan hematologis (trombositopenia & anemia hemolitik) Kelainan ginjal

Oral: prednison, dosis rendah (5-15 mg/hari), dosis tinggi (60-80 mg/hari) Kortikosteroid i.v.:metilprednisolon 100 mg setiap 6 atau 8 jam

Terapi SLE Ringan

Lesi mengenai mukokutan dan artritis Edukasi dan penatalaksanaan umum Medikamentosa: parasetamol atau OAINS Steroid topikal dipakai untuk ruam kulit Jika aktivitas penyakit tidak dapat dikendalikan: klorokuin dan steroid oral dosis kecil

Life Threatening SLE

Systemic Glucocorticoid (0.5 to 2 mg/kg per day orally or 1000 mg of methylprednisolon sodium succinate i.v. daily for 3 days followed by 0,5-1 mg/kg of daily prednisone or equivalent) High doses are recommended for 4 to 6 weeks, tapered as rapidly. Maintenance dose varying from 5 to 10 mg prednisone, prednisolone, or equivalent per day or 10 to 20 mg every other day.

Imunosupresan

Contoh: azatriopin, siklofosfamid, metroteksat, klorambusil, siklosporin, dan nitrogen mustard Pilihan obat tergantung berat ringan penyakit, organ yang terlibat, adanya bukti ilmiah Nefritis lupus: siklofosfamid (oral/iv), azatriopin, micofenolat mofetil Artritis: metroteksat Kombinasi dengan steroid dosis tinggi dapat dibenarkan pada kasus SLE berat yang mengancam jiwa

Prognosis

Can not be cured. Medication can be taken to ease pain, etc. Adjustment of general life-style, changing behaviors and activities. Coping with emotional reactions, control stress and negative emotions Proper medication, helps suppress symptoms. Attention to diet and nutritional needs

Survival

Survival in patients with SLE is 90-95% at 2 years, 82-90% at 5 years, 71-80% at 10 years, 63-75% at 20 years Poor prognosis (50% mortality in 10 years is associated with (at the time of diagnosis):

High serum creatinine (>1.4) Hypertension Nephrotic syndrome Hypoalbuminemia hypocomplementemia

Comparison of annual number of deaths from 1979 to 1989

1600 1400 1200 1000 800 600 400 200 0 1979 1989 Annual number of deaths

Source: Journal of American Medical Association, 2002, 20:1-4