CURRICULUM VITAE Name : Dr.

Nanang Sukmana, SpPD-KAI Sex : Male Place of Birth : Pegaden (Subang, West Java, Indonesia) Date of Birth : August, 3rd 1948 Marital Status : Married Nationality : Indonesian Residence : Jl. Gambang No. 5 Kelapa Gading Bangun Cipta Sarana Jakarta 14250 Education University of Indonesia, Faculty of Medicine Awarded the degree of Medical Doctor, 1974 University of Indonesia, Faculty of Medicine Awarded the degree of Internal Medicine, 1987 University of Indonesia, Faculty of Medicine Department of Internal Medicine

Systemic Lupus Eritematosus

Diagnosis dini dan tata laksana
Nanang Sukmana Divisi Alergi Imunologi Klinik, Departemen IPD FK Universitas Indonesia/ RS Dr Cipto Mangunkusumo

Lupus eritematosus sistemik (LES)

Penyakit autoimun yang melibatkan berbagai organ dengan manifestasi klinis yang bervariasi dari yang ringan sampai berat . Pada keadaan awal, sering sekali sukar dikenal sebagai LES, karena manifestasinya sering tidak terjadi bersamaan. Sampai saat ini penyebab LES belum diketahui ada dugaan faktor genetik, infeksi dan lingkungan ikut berperan pada patofisiologi LES

Introduction
Systemic Lupus Erythematosus (SLE) is chronic, often life long, autoimmune disease It can be mild to severe Affects mostly women
Systemic is used because the disease can affect organs and tissue throughout the body

Lupus is Latin for wolf

Erythematosus is from Greek for red

Wanita > laki-laki

Genetic Defects
Researchers estimated that 20-100 different genetic factors may be involved in the alterations of the immune systems

Enviromental factors that may be relevant in the pathogenesis of systemic lupus erythematosus
Chemical/physical factors Aromatic amines Hydrazines Drugs (procainamide, hydralazine, chlorpromazine, isoniazid, phenytoin, penicillamine) Tobacco smoke Hair dyes Ultraviolet light Dietary factors L-canavanine (alfalfa sprouts) High intake of saturated fats Infectious agents ?Bacterial DNA/endotoxins ?Retroviruses Hormones and environmental oestrogens Hormonal replacement therapy, oral contraceptive pills Prenatal exposure to oestrogens
Mok CC, Lau CS. Pathogenesis of Systemic Lupus Erythematosus. J. Clin Pathol 2003;56:481-490

Gambaran klinis LES

Limphadenopati 12-50% SSP 20% Hepotomepali/ Splenomegali 20% Sal cerna 18% Paru 38% Hematologi 50% Jantung 48% Vaskulitis Kelelahan 90% Panas lama 80-82% BB turun 60% Artritis/Artralgia 90% Kulit 50-58% Ginjal 50%

LES

Constitutional Symptoms

Fatigue Weight changes Myalgia Fever

Weight changes
Decrease appetite The side effects of medications Gastrointestinal disease Loss of excess fluid due to use of diuretic medications

Fever
Fever is seen in most patients with SLE
Fever active SLE or infection Reflect central nervous or adverse effect of a drug

Faktor pencetus/eksaserbasi
Obat :

Procainamid Hidralazin Metildopa CPZ

Sinar UV (320-400 nm)

Keguguran

LES

Infeksi

Kehamilan

Tindakan pembedahan

The 1997 Revised Criteria for the Classification of SLE

(MD SOAP BRAIN)

1. Malar rash
2. Discoid rash 3. Serositis a. Pericarditis b. Pleuritis 4. Oral ulcer 5. Arthritis 6. Photosensitivity

7.

The 1997 Revised Criteria for the Classification of SLE Blood / Hematologic disorder
a. Hemolytic anemia OR b. Leukopenia (< 4000/ ml) OR c. Lymphopenia (<1500/ ml) OR d. Thrombocytopenia (<100.000)

8.

Renal disorder
a. Persistent Proteinuria (>0.5 gr/d) b. Cellular cast or any tipe

ANA 10. Immunologic disorder

9.
a. Anti ds DNA OR b. Anti Sm OR c. Antiphospholipid ab

11. Neurological disorder

Laboratorium
Blood Low white blood counts Anemia Low platelet counts

www-medlib.med.utah.edu

Cutaneous vasculitis rash in a patient with SLE

Oral Ulcers

Photosensitivity

Discoid Lupus

Discoid Lupus

Erythematous Rash

AUTOANTIBODIES PRECEDE DISEASE BY YEARS

Some Auto Ab before Dx: 80%

ANA: 3 yrs (9) Anti-Ro/La

Anti-DNA: 2 yrs (9) Anti-PL: (7)

Anti-Sm: 1 yr (7) Anti-RNP

General information
Exercise
To prevent a rapid loss of muscle & stamina

Immunization

Influenza and pneumococcal vaccines are safe

Pregnancy

Should avoid during periods of active disease

Diet and nutrition

Condition of Patients Steroids, increase appetite weight gain Hyperlipidemia Vitamins are rarely needed in people who eat a balanced diet Take 1000 to 1500 mg of calcium per day A supplement with 400 to 800 units of vitamin D is recommended every day

Dehidroepiandrosterone (DHEA)
DHEA are major circulating androgens Use of DHEA or DHEA sulfate supplements are not recommended

Crosbie D, Black C, McIntyre L, et al. Dehydroepiandrosterone for systemic lupus erythematosus. Cochrane Database Syst Rev 2007; CD 005114

Lannys

Laboratory aids in distinguishing preeclampsia from lupus nephritis

LUPUS NEPHRITIS Urinalysis C3, anti dsDNA PREECLAMPSIA

proteinuria and/or an active Proteinuria only urine sediment (red and white cells and cellular casts) Low C3, increased anti ds DNA High C3

Sign of SLE activities

Thrombocytopenia, elevated serum levels of liver enzymes and uric acid, and decreased urinary excretion of calcium

Drugs In Pregnancy and Lactation

Pregnancy NSAIDs Antimalarials Corticosteroids Azathioprine Mycophenolate Methotrexate Cyclophosphamide Anti-TNF Warfarin Yes (avoid after 32 weeks) Yes Yes Yes No No No No No (with caution after first trimester) Lactation Yes Yes Yes Yes? No No No No Yes

Heparin AAS (low dose)

Yes Yes

Yes Yes

NSAIDS, non-steroidal anti-inflammatory drugs; AAS, aspirin

Lupus and Pregnancy : ten questions and some answers. Gruiz-Irastorza and MA Khamashta. Lupus (2008)17, 416-420

Treatment of specific organ involvement

NSAIDs
Antimalarials Steroid and Immunosuppressive Other options
Stem cell transplantation (bone marrow transplantation) Anti-B cell antibodies

Treating mild SLE

Cream and Sunbloks

Rashes

NSAIDs

Fever Arthritis Headache Pleurisy Mild kidney involvement Inflammation of the tissue surrounding the heart

Antimalaria drugs

Treating severe SLE

Hemolytic anemia

Low platelet count with an accompanying rash (thrombocytopenia purpura) Major involvement in the lungs or heart Significant kidney damage Acute inflammation of the small blood vessels in the extremities or gastrointestinal tract Severe central nervous system symptoms

Suppress the immune factors, most often first with corticosteroids and other immunosuppressant drugs

Is cancer risk increased?

The relation of SLE to malignancy is unclear because conflicting data have been reported

Bernatsky S, Clarke A, Ramsey-Goldman R. Malignancy and systemic lupus erythematosus. Curr Rheumatol Rep 2002;4:351

Prognostic factors
Poor prognostic factors for survival in SLE include: Renal disease Hypertension Male sex Young age Older age at presentation Poor socioeconomic status Black race (reflect low socioeconomic status) Presence of antiphospholipid antibodies Antiphospholipid syndrome High overall disease activity

AVN Femoral Head

Causes of death
The major cause of death in the first few years of illness is active disease (eg, CNS, renal or cardiovascular disease) or infection due to immunosuppresion, while late deaths are either caused by the illness (eg, endstage renal disease), treatment complications (including infection and coronary disease)
Ward MM< Pyun E, Studenski S. Mortality risks associated with specific clinical manifestations of SLE. Arch Intern Med 1996;157;1337

Clinical Pearls
SLE is a systemic disease with the potential to affect any organ system The differential diagnosis of a lupus flare mandates consideration of infection, drug toxicities, or other etiologies In the absence of data from randomized trials, use of aggressive treatment must be balanced against associated toxicity SLE patients are at high risk of developing atherosclerotic disease, osteoporosis, malignancy, diabetes mellitus and hypertension (HTN); screening for and reduction of modifiable risk factor are essential Appropriate vaccinations are advisable
Antony Rosen. Mechanism of autoimmunity. Clinical Immunology Principles and Practice 3rd ed. 2008.

Thank You

Treating specific complication

The major complications of the disease must be treated as separate problems, keeping in mind the specific aspect of SLE

Treatment
Only three drugs are FDA-approved Prednisone Aspirin Hydrochloroquine

Cytokines
Infections Injuries Tissue repair Blood clotting Other aspects of healing

Specific organ symptoms1

Joint pain and stiffness Skin changes
Photosensitivity

Kidneys Gastrointestinal tract Pulmonary

Pleurisy Shortness of breath

Treating specific complication

The major complications of the disease must be treated as separate problems, keeping in mind the specific aspect of SLE

Small Vessel Vasculitis

Frequency of symptoms of systemic lupus erythematosus1

Symptoms Percent at onset Percent at anytime

Fatigue
Fever Weight loss Arthritis or arthralgia Skin Butterfly rash Photosensitivity Mucous membrane lesion Alopecia Raynauds phenomenon Purpura Urticaria Renal Nephrosis

50
36 21 62-67 73 28-38 29 10-21 32 17-33 10 1 16-38 5

74-100
40-80+ 44-60+ 83-95 80-91 48-54 41-60 27-52 18-71 22-71 15-34 4-8 15-34 4-8

Von Feldt, JM, Postgrad Med 1995; 97:79

Frequency of symptoms of systemic lupus erythematosus2

Symptoms
Gastrointestinal Pulmonary Pleurisy Effusion Pneumonia Cardiac Pericarditis Murmurs ECG changes

Percent at onset
18 2-12 17

Percent at anytime
38-44 24-98 30-45 24 29 20-46 8-48 23 34-70 21-50 9-20

15 8

Lymphadenopathy Splenomegaly

7-16 5

Hepatomegaly
Central nervous system Functional Psychosis Convulsions

2
12-21 1 0,5

7-25
25-75 Most 5-52 2-20

Von Feldt, JM, Postgrad Med 1995; 97:79

Symptoms
Fatigue Loss of appetite, nausea and weight loss Chest pain Bruising Menstrual irregularities Thought and concentration disturbances Personality changes Sleep disorders: restless legs syndrome sleep apnea Dryness of the eyes and mouth Brittle hair or hair loss

Gambaran klinis LES

Limphadenopati 12-50% SSP 20% Hepotomepali/ Splenomegali 20% Sal cerna 18% Paru 38% Hematologi 50% Jantung 48% Vaskulitis Kelelahan 90% Panas lama 80-82% BB turun 60% Artritis/Artralgia 90% Kulit 50-58% Ginjal 50%

LES

Faktor pencetus/eksaserbasi
Obat :

Procainamid Hidralazin Metildopa CPZ

Sinar UV (320-400 nm)

Keguguran

LES

Infeksi

Kehamilan

Tindakan pembedahan

Lannys

Laboratory aids in distinguishing preeclampsia from lupus nephritis

LUPUS NEPHRITIS urinalysis C3, anti dsDNA
proteinuria and/or an active urine sediment (red and white cells and cellular casts)

PREECLAMPSIA
Proteinuria only

Low C3, increased anti ds DNA

Sign of SLE activities

High C3

Thrombocytopenia, elevated serum levels of liver enzymes and uric acid, and decreased urinary excretion of calcium

The 1997 Revised Criteria for the Classification of SLE

(MD SOAP BRAIN)

1. Malar rash
2. Discoid rash 3. Serositis a. Pericarditis b. Pleuritis 4. Oral ulcer 5. Arthritis 6. Photosensitivity

Steps in Pathogenesis of SLE

1. 2. 3. 4. 5. 6. 7. Genetic factors/immune dysfunction Environmental/endogenous trigger Inflammation Development of Autoimmune Accelerated of Antigen Tissue Damage Clinical Disease

Autoantibodies
Anti-ds DNA Anti-Sm antibodies Anti-Ro (SSA) and Anti-La (SSB) Antiphospholipid antibodies

AUTOANTIBODIES PRECEDE DISEASE BY YEARS

Some Auto Ab before Dx: 80%

ANA: 3 yrs (9) Anti-Ro/La

Anti-DNA: 2 yrs (9) Anti-PL: (7)

Anti-Sm: 1 yr (7) Anti-RNP