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CURRICULUM VITAE

Name : Dr. Nanang Sukmana, SpPD-KAI

Sex : MalePlace of Birth : Pegaden (Subang, West Java, Indonesia)

Date of Birth : August, 3rd 1948

Marital Status : Married

Nationality : IndonesianResidence : 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 MedicineDe artment of Internal Medicine

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Systemic LupusEritematosus

Diagnosis dini dan tata laksana

Nanang Sukmana

Divisi Alergi Imunologi Klinik, Departemen IPD

FK Universitas Indonesia/ RS Dr Cipto Mangunkusumo

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Lupus eritematosus sistemik (LES)

Penyakit autoimun yang melibatkan berbagai organ

dengan manifestasi klinis yang bervariasi dari yang

ringan sampai berat . Pada keadaan awal, seringsekali 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

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Introduction

Systemic Lupus Erythematosus (SLE) is

chronic, often life long, autoimmune disease

It can be mild to severe

Affects mostly women

Systemic is usedbecause the disease

can affect organsand tissue

throughout the body

Lupus is Latinfor wolf

Erythematosus isfrom Greek for red

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Wanita > laki-laki

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Genetic DefectsResearchers estimated that20-100

different genetic factors may be

involved in the alterations of the

immune systems

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Enviromental factors that may be relevant in thepathogenesis of systemic lupus erythematosusChemical/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

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Gambaran klinis LES

LES

SSP

20%

Hepotomepali/

Splenomegali

20%

Sal cerna

18%

Paru

38%

Hematologi

50% Jantung

48%

Vaskulitis

Ginjal

50%

Limphadenopati12-50%

Kelelahan90%

Panas lama

80-82%

BB turun60%

Artritis/Artralgia

90%

Kulit

50-58%

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Constitutional Symptoms

Fatigue

Weight changes

Myalgia

Fever

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Weight changes

Decrease appetite

The side effects of medications

Gastrointestinal disease

Loss of excess fluid due to use of diuretic

medications

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Fever

Fever is seen in most patients with SLE

Fever active SLE or infection

Reflect central nervous or adverse effect of a drug

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Faktor pencetus/eksaserbasi

LES

Obat :

Keguguran

KehamilanTindakan

pembedahan

Infeksi

Sinar UV(320-400 nm)

ProcainamidHidralazin

Metildopa

CPZ

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The 1997 Revised Criteria for

the Classification of SLE

1.Malar rash

2.Discoid rash

3.Serositisa. Pericarditis

b. Pleuritis

4.Oral ulcer

5.Arthritis

6.Photosensitivity

(MD SOAP BRAIN)

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The 1997 Revised Criteria forthe Classification of SLE

7. Blood / Hematologic disordera. Hemolytic anemia ORb. Leukopenia (< 4000/ ml) ORc. Lymphopenia (

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Laboratorium

Blood

Low white blood counts Anemia

Low platelet counts

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www-medlib.med.utah.edu

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Cutaneous vasculitis rash in a patient with SLE

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Oral Ulcers

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Photosensitivity

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Discoid Lupus

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Discoid Lupus

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Erythematous Rash

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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

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General information

To prevent a rapid loss of

muscle & stamina

Influenza and pneumococcalvaccines are safe

Should avoid during periods of

active disease

Exercise

Immunization

Pregnancy

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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 calciumper day A supplement with 400 to 800 units of vitamin D

is recommended every day

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Dehidroepiandrosterone (DHEA)

DHEA are major circulating androgens

Use ofDHEA or DHEA sulfate supplements are

not recommended

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

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Lannys

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Lanny s

Laboratory aids in distinguishing pre-

eclampsia from lupus nephritis

LUPUS

NEPHRITIS

PRE-

ECLAMPSIA

Urinalysis proteinuria and/or an active

urine sediment (red andwhite cells and cellular

casts)

Proteinuria only

C3, anti

dsDNA

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

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Drugs In Pregnancy and Lactation

Pregnancy Lactation

NSAIDs Yes (avoid after 32 weeks) Yes

Antimalarials Yes Yes

Corticosteroids Yes Yes

Azathioprine Yes Yes?

Mycophenolate No No

Methotrexate No No

Cyclophosphamide No No

Anti-TNF No No

Warfarin No (with caution after first trimester) Yes

Heparin Yes Yes

AAS (low dose) Yes Yes

NSAIDS, non-steroidal anti-inflammatory drugs; AAS, aspirinLupus and Pregnancy : ten questions and some answers. Gruiz-Irastorza and MA Khamashta. Lupus (2008)17, 416-420

T f ifi

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Treatment of specific organ

involvement

NSAIDs

Antimalarials

Steroid and Immunosuppressive

Other options Stem cell transplantation(bone marrow transplantation)

Anti-B cell antibodies

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Treating mild SLE

Rashes

Fever

Arthritis

Headache

Pleurisy

Mild kidney involvement

Inflammation of the tissue

surrounding the heart

Cream and Sunbloks

NSAIDs

Antimalaria drugs

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Treating severe SLE

Suppress the immune factors, most often first with

corticosteroids and otherimmunosuppressant drugs

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

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Is cancer risk increased?

The relation ofSLE to malignancy is unclear

because conflicting data have been reported

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

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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

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AVN Femoral Head

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Causes of death

The major cause of death in the first few years of illness

is active disease (eg, CNS, renal or cardiovasculardisease) or infection due to immunosuppresion, while

late deaths are either caused by the illness (eg, end-

stage 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

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Clinical Pearls

SLE is a systemic disease with the potential to affect any organsystem

The differential diagnosis ofa lupus flare mandates

consideration ofinfection, drug toxicities, or other etiologies

In the absence of data from randomized trials, use ofaggressivetreatment must be balanced against associated toxicity

SLE patients are at high riskof developing atherosclerotic

disease, osteoporosis, malignancy, diabetes mellitus and

hypertension (HTN); screening for and reduction of modifiablerisk factor are essential

Appropriate vaccinations are advisable

Antony Rosen. Mechanism of autoimmunity. Clinical Immunology Principles and Practice 3rd ed. 2008.

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Treating specific complication

The major complications of the disease must be

treated as separate problems,keeping in mind the specific aspect of SLE

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Treatment

Only three drugs are FDA-approved

Prednisone

Aspirin Hydrochloroquine

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Cytokines

Infections

Injuries

Tissue repair Blood clotting

Other aspects of healing

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Specific organ symptoms1

Joint pain and stiffness

Skin changes

Photosensitivity

Kidneys

Gastrointestinal tract

Pulmonary Pleurisy

Shortness of breath

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Treating specific complication

The major complications of the disease must be

treated as separate problems,keeping in mind the specific aspect of SLE

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Small Vessel

Vasculitis

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Frequency of symptoms of systemic lupus erythematosus1

Symptoms Percent at onset Percent at anytime

Fatigue 50 74-100

Fever 36 40-80+

Weight loss 21 44-60+

Arthritis or arthralgia 62-67 83-95

Skin 73 80-91

Butterfly rash Photosensitivity

Mucous membrane

lesion

Alopecia

Raynauds phenomenon

Purpura

Urticaria

28-3829

10-21

32

17-33

10

1

48-5441-60

27-52

18-71

22-71

15-34

4-8

Renal 16-38 15-34

Nephrosis 5 4-8

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

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Symptoms Percent at onset Percent at anytime

Gastrointestinal 18 38-44

Pulmonary 2-12 24-98

Pleurisy

Effusion

Pneumonia

17 30-45

24

29

Cardiac 15 20-46

Pericarditis

Murmurs

ECG changes

8 8-48

23

34-70

Lymphadenopathy 7-16 21-50

Splenomegaly 5 9-20

Hepatomegaly 2 7-25

Central nervous system 12-21 25-75

Functional

Psychosis

Convulsions

1

0,5

Most

5-52

2-20

Frequency of symptoms of systemic lupus erythematosus2

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

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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

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b kli i

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Gambaran klinis LES

LES

SSP

20%

Hepotomepali/

Splenomegali

20%

Sal cerna

18%

Paru38%

Hematologi

50% Jantung

48%

Vaskulitis

Ginjal

50%

Limphadenopati12-50% Kelelahan90%

Panas lama

80-82%

BB turun

60%

Artritis/Artralgia

90%

Kulit

50-58%

/ i

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Faktor pencetus/eksaserbasi

LES

Obat :

Keguguran

KehamilanTindakan

pembedahan

Infeksi

Sinar UV(320-400 nm)

ProcainamidHidralazin

Metildopa

CPZ

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Lannys

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Laboratory aids in distinguishing pre-

eclampsia from lupus nephritis

LUPUS

NEPHRITIS

PRE-

ECLAMPSIA

urinalysis proteinuria and/or an activeurine sediment (red and white

cells and cellular casts)

Proteinuria only

C3, anti

dsDNA

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

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The 1997 Revised Criteria forthe Classification of SLE

1.Malar rash

2.Discoid rash

3.Serositisa. Pericarditis

b. Pleuritis

4.Oral ulcer

5.Arthritis

6.Photosensitivity

(MD SOAP BRAIN)

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Steps in Pathogenesis of SLE

1. Genetic factors/immune dysfunction

2. Environmental/endogenous trigger

3. Inflammation

4. Development of Autoimmune

5. Accelerated of Antigen

6. Tissue Damage7. Clinical Disease

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Autoantibodies

Anti-ds DNA

Anti-Sm antibodies Anti-Ro (SSA) and Anti-La (SSB)

Antiphospholipid antibodies

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AUTOANTIBODIES PRECEDE

DISEASE BY YEARSSome 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