PATHOFISIOLOGI dan

ASPEK KLINIS SYSTEMIC

LUPUS ERYTHEMATOSUS

1
Autoimmune diseases: pts 803
Disease classification
MULTIPLE SCLEROSIS 281 VASCULITIS 28
Behcets 6
CONNECTIVE TISSUE D. 232 Wegeners 7
SSc 136 Takayasu 2
SLE 78 Microscopic polyarteritis nodosa 2
PM/DM 8 Classical polyarteritis nodosa 1
Sjoegren 1 Churg-Strauss 1
Other/Unknown 12 Other 9

ARTHRITIS 147 OTHER NEUROLOGICAL 15

Rheumatoid arthritis 93 Myasthenia gravis 2
Juvenile chronic arthritis : Other 13
- Systemic JIA 32
- Other JIA 12
- Polyarticular JIA 5 INFLAMMATORY BOWEL 12
Psoriatic arthritis 2 Crohn's disease 6
Other 3 Ulcerative colitis 2
Other 4
HAEMATOLOGICAL 54
ITP 18 OTHER AD/AutoDise
AIHA 10 21
Evans 8
Pure Red Cell 6
Pure White Cell 2
Other 10

Lyon, March 2007

 TYPES OF LUPUS
ERYTHEMATOSUS
Systemic lupus erythematosus (SLE)

Discoid lupus erythematosus (DLE)

Drug-induced lupus erythematosus (DILE)

Neonatal lupus erythematosus (NLE)

INTRODUCTION
Systemic 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.

4
 INTRODUCTION

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,

5
 Pathophysiology of Lupus
Autoimmune: Exact Mechanism Unknown
Viruses
Environmental chemicals
Genetic
Antibodies attack healthy tissue
Causes inflammation to the organ or to the
vessels supplying blood to the organ
Deprives /mmbuang organs of arterial blood
supply

6
 Connective Tissue Diseases

Disease Autoantibody
Systemic Lupus Erythematosus Anti-dsDNA, Anti-SM
Rheumatoid Arthritis RF, Anti-RA33
Sjogrens Syndrome Anti-Ro(SS-A),Anti-La(SS-B)
Systemic Sclerosis Anti-Scl-70, Anti-centromere
Polymyositis/Dermatomyositis Anti-Jo-1
Mixed Connective Tissue Disease Anti-U1-RNP
Wegeners Granulomatosus c-ANCA

7
Connective Tissue
Diseases
Histopathology: Connective tissue and
blood vessel inflammation and abundant
fibrinoid deposits
Varying tissue distribution and pattern of
organ involvement
Symptoms nonspecific and overlapping
Difficult to diagnose
Systemic Lupus
Erythematosus
General
autoimmune multisystem disease
prevalence 1 in 2,000
female
peak age 15-25
immune complex deposition
photosensitive skin eruptions,
serositis/inflam.memb.serosa,
pneumonitis, myocarditis, nephritis, CNS
9
involvement
CLINICAL MANIFESTATIONS OF SLE
General (Constitutional)
Fever, chills, headache, fatigue, malaise and
weight loss

Renal
Hematuria, proteinuria

Skin
Malar Butterfly rash
Photosensitivity rash

Cardiac
Myocarditis, pericarditis, endocarditis
Athrosclerosis
CLINICAL MANIFESTATIONS OF
SLE

Central nervous system

Cognitive dysfunction
Pulmonary
Pleurisy
Musculoskeletal
Myalgias, arthralgias and arthritis
Hematologic
Anemia, leukemia, thrombocytopenia
Lymphatic system
Lymphadenopathy
 AMERICAN COLLEGE OF
RHEUMATOLOGY (ACR) CRITERIA
FOR DIAGNOSIS OF SLE
Serositis (Pleurisy, pericarditis)
Oral ulcers
Arthritis
Photosensitivity
Blood disorders (Leukopenia, thrombocytopenia)
Renal involvement
Antinuclear antibodies (ANA)
Immunologic phenomena [false-positive Rapid Plasma
Reagin (RPR)]
Neurologic disorder
Malar rash
Discoid rash
ETIOLOGY
The cause(s) of lupus is currently unknown, but
there are environmental and genetic factors
involved.
Some environmental factors which may trigger
the disease include :
Infections
antibiotics (especially those in the sulfa
and penicillin groups)
ultraviolet light
Certain/pasti drugs
hormones.

13
Patogenesia SLE
Faktor genetik/virus peran penting
terjadinya SLE.
Perbedaan distribusi SLE pd berbagai ras
berdasar atas perbedaan genetik(beda HL-
A)Jenis HL-A tertentu lbh mudah terjadi
mengalami infeksi virus.
Faktor lain yg berperan tejadinya SLE
adalah kekebalan seluler.
SLE dpt terjadi ok infeksi virus kronik,yg
telah terjadi ggn fungsi sel T,dpt juga ok
kelainan kongenital.
Virus yg msk dlm sel berintegrasi dg
genome sel,berakibat rangsangan tubuh
membentuk autoantibodi,thdp komponen
inti sel,mis DNA,RNA,nukeoprotein dsb.
14
Patogenesia SLE
Anti bodi ini bersama-sama dsbt ANA(Anti-
Nuclear Antibody).
Dengan antigen spesifik ANA membentuk
kompleks imun,beredar dalam
sirkulasi,akan mengendap pd berbagai
macam organ,fiksasi komplemen pd organ
tsb.terjadi radang.
Reaksi radang inilah yg menyebabkan
timbulnya keluhan pd tempat
bersangkutan(ginjal,sendi,pleura,kulit dsb.

15
Types of Lupus
SLE Systemic
Chronic, progressive, inflammatory
connective tissue disorder that
causes organ failure; potentially
fatal with a 5-year survival rate of
85%
Drug Induced Lupus
Procainamide
Hydralazine
INH
DLE Discoid
Affects only the skin 16
Systemic Lupus Erythematosus
Systemic Lupus
Erythematosus

Discoid Lupus: Cutaneous

manifestations
Scar upon healing
SYSTEMIC LUPUS
ERYTHEMATOSUS

butterfly rash

Skin rashes

Finger turns blue

19
 Skin Manifestations
Malar or Butterfly
Rash
Discoid Rash
Stimulated by UV
light
Skin manifestations
only appear in 30-
40% of lupus
patients.

20
Clinical Features of Systemic
Lupus Erythematosus

21
 Systemic Lupus
Erythematosus
Clinical Features on Presentation in SLE

Arthritis or Arthralgia 55%

Skin Involvement 20%
Nephritis 5%
Fever 5%
Other 15%

22
 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
/brsain for an individual
complement covered
protein.

23
 Serological Tests to Aid
Diagnosis of SLE
Test % positive in SLE
ANA 95%
Anti-nDNA 60%
Anti-nRNP 80%
Anti-Sm 20%
Anti-Ro 30%
Anti-La 10%
25
Clinical Manifestations

Fig 65-9
 Signs and Symptoms of Lupus
Skin:
Dry, scaly/bersisik, raised
rash on face
Appears to be in butterfly
patternthe Bite of the
Wolf.
Individual round lesions

Hair
Hair loss

Change in texture/ssnan jar. 27

 Signs and Symptoms of Lupus
Musculoskeletal
Joints are affected
causing painful mobility
(Polyarthritis in 90% of
SLE patients).
Joint inflammation

Avascular necrosis after

5 years of diagnosis
Muscle atrophy (results
from autoimmune
complex invasionleading
to Myositis).
Muscle pain 28
 Sign and Symptoms of Lupus
Renal
Lupus nephritis

Changes in the glomeruli

Decreased urinary
output
Proteinuria

Hematuria

Fluid retention

Leading cause of death

50% of all lupus pts

have this
29
Renal (Kidney) 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.
Renal Failure because of Normal
Glomerulonephritis is the
leading cause of death among
lupus patients.

Glomerulonephritis 30
Signs and Symptoms of Lupus
Respiratory
Pleural effusions

Results in restrictive and obstructive

changes
Dyspnea

Hypoventilation

31
 Signs and Symptoms of Lupus
Cardiac
Pericarditis Raynauds Disease
Tachycardia Lack of circulation
Pain to hands and feet
Myocardial ischemia

Chest Pain

Cardiac Dysrrhythmias

32
Signs and Symptoms of Lupus
Neurological
Psychoses

Paresis

Seizures

Headaches

Strokes

Peripheral neuropathies
http://www.mtio.com/lupus/lal_7.htm
33
 Signs and Symptoms of Lupus
GI Tract Psychosocial
Abdominal pain Dealing with illness

Mesenteric arteritis Fear of death chronic

Pancreatitis Lack of socialization

Ulcers Body image changes

Liver enlargement Rash

Spleenomegaly Medication related

Sexual Dysfunction Systemic

Pain Fever

Fatigue/weakness Generalized weakness

Self esteem Fatigue

Decreased desire Anorexia

Weight loss

34
 Brain

Salivary, Parotid glands

Thyroid
Heart, Lungs
Kidneys Serous linings of Heart, Lungs, GI tract
Special Complications of Pregnancy

Skin Organ-threatening

Non organ-threatening
Joints
Blood Vessels
And Blood Cells
Wallace in Arthritis and Allied Conditions, 13th Ed V2, p1319,
Koopman, ed 35
 Brain
Salivary, Parotid glands
Thyroid
Heart, Lungs
Kidneys Serous linings of Heart, Lungs, GI tract
Special Complications of Pregnancy

Skin
Inflammation vs
Coagulation vs
Joints Both
Blood Vessels
And Blood Proteins
 Systemic therapies for nonorgan-threatening
lupus
Nonsteroidal anti-inflammatory drugs
Antimalarials
Thalidomide
Hormonal interventions:
dehydroepiandrosterone, testosterone patches,
bromocriptine, prolactin
Immunosuppressive therapies: azathioprine,
methotrexate, leflunomide

37
The management of organ-threatening lupus

Existing immunosuppressive therapies: cyclophosphamide,

mycophenolate mofetil, cyclosporine A, fludarabine, cladribine
(2-CDA)
Intravenous immunoglobulin
Various biologic agents: BlyS inhibitor, CTLA-4Ig, LL2IgG
Stem cell transplantation

38
 Systemic Lupus Erythematosus
Treatment: Rheumatologist involvement
Avoidance of sun
Use of sunscreens
NSAIDS, topical and low dose steroids, antimalarials
Low dose methotrexate instead of steroids
Azothioprine, cyclophosphamide, high dose steroids
for serious visceral involvement
Symptomatic: Salivary substitutes, Klacks solution,
postprandial rinses of 1: 1 H2O2:H2O

39
Diagnostics
DLE = skin biopsy
Serum ANA, ESR, protein
electrophoresis,
complement, immunoglobins
Lupus cell prep (LE prep)
CBC
Electrolytes
Liver and cardiac enzymes
Coag studies
Anticardiolipin Antibodies

40
Systemic Lupus Erythematosus
Criteria (4 or more)
1. Butterfly rash 7. Neurologic dis
2. Discoid lupus 8. Hematologic dis
3. Photosensitivity 9. Renal disorder
4. Oral ulcers 10. Immunologic dis:
5. Arthritis LE cell, anti-DNA,
6. Serositis anti-Sm, false pos
STS
11. Anti-nuclear
antibody
41
 Rheumatoid Arthritis: Diagnostic Criteria
1. Morning stiffness (>1h)
2. Swelling of three or more joints
3. Swelling of hand joints (prox interphalangeal,
metacarpophalyngeal, or wrist)
4. Symmetric joint swelling
5. Subcutaneous nodules
6. Serum Rheumatoid Factor
7. Radiographic evidence of erosions or periarticular osteopenia in
hand or wrists

Criteria 1-4 must have been present continuously for 6 weeks or longer and must be
observed by a physician. A diagnosis of rheumatoid arthritis requires that 4 of the 7
criteria are fulfilled.

42
 Rheumatoid Arthritis
Head and Neck Manifestations
cricoarytenoid joint
most common cause of cricoarytenoid arthritis
30% patients hoarse
86% pathologic involvement
exertional dyspnea, ear pain, globus
hoarseness
rheumatoid nodules, recurrent nerve involvement
stridor
local/systemic steroids
poss. Tracheotomy
Rheumatoid Arthritis
 Rheumatoid Arthritis

Treatment
physical therapy, daily exercise, splinting, joint
protection
salicylates, NSAIDS, gold salts, penicillamine,
hydroxychloroquine, immunosuppressive agents
Cyclosporin-A
prognosis
10-15 yrs of disease
50% fully employed
10% incapacitated
10-20% remission
BLOOD TESTS IN THE DIAGNOSIS
OF SLE
The anti-nuclear antibody test (ANA) to
determine if autoantibodies to cell nuclei are
present in the blood.
The anti-DNA antibody test to determine if
there are antibodies to the genetic material in
the cell .

46
Rubgsok

47
Rheumatoid Arthritis

A symmetrical
peripheral
polyarthritis of
unknown aetiology
that leads to joint
deformity &
destruction due to
erosion of
cartilage & bone

48
 RA
The
inflammatory
process
results in
damage to
cartilage &
bone

NEJM 2001; 344 (12):

907 916.
49
Osteoarthritis

50
 Indications of high dose corticosteroid
therapy in lupus patients
Severe lupus nephritis
CNS lupus with severe manifestations
Autoimmune thrombocytopenia with extremely low
platelet counts (e.g.<30000/mm3)
Autoimmune hemolytic anemia
Acute pneumonitis caused by SLE.
Others: severe vasculitis with visceral organ
involvement, serious complications from serositis
(pleuritis, pericarditis, or peritonitis)

51
 Life-Threatening Manifestations of SLE:
Responses to glucocorticoids(1)

Manifestations often responsive to glucocorticoids

Vasculitis
Severe dermatitis of subacute cutaneous lupus erythematosus
or SLE
Polyarthritis
Polyserositispericarditis, pleurisy, peritonitis
Myocarditis
Lupus pneumonitis

52
Life-Threatening Manifestations of SLE:
Responses to glucocorticoids(2)
~(continue)
Glomerulonephritisproliferative forms
Hemolytic anemia
Thrombocytopenia
Diffuse CNS syndromeacute confusional state,
demyelinating syndromes, intractable headache
Serious cognitive defects
Myelopathies
Peripheral neuropathies
Lupus crisishigh fever and prostration

53
 Life-Threatening Manifestations of SLE:
Responses to glucocorticoids(3)

Manifestations not often responsive to

glucocorticoids
Thrombosisincludes strokes
Glomerulonephritisscarred end-stage renal disease,
pure membranous glomerulonephritis
Resistant thrombocytopenia or hemolytic anemia
occurs in a minority of patients; consider splenectomy,
cytotoxics, danazol, or cyclosporine/neoral therapies
Psychosis related to conditions other than SLE, such as
glucocorticoid therapy

54
 TREATMENTS

Drug therapy
nonsteroidal anti-inflammatory drugs and
antimalarials
Disease-modifying antirheumatic drugs
(DMARDs)
Immunomodulating Drugs
Anticoagulants

55
 TREATMENTS
Lifestyle changes
avoiding direct sunlight, covering up with sun-
protective clothing, and using strong UVA/UVB
sunblock lotion can also be effective in preventing
photosensitivity problems.
Weight loss is also recommended in overweight and
obese patients to alleviate some of the effects of the
disease, especially where joint involvement is
significant.
56
 Therapies for lupus patients with skin
lesions(1)
General
Avoid sun: clothing, sunscreens, avoid hot part of day with
most UV-B light, camouflage cosmetics
Stop smoking (so antimalarials works better)
Thiazides and sulfonylureals may exacerbate skin disease

57
Acute Cutaneous: Malar Rash Chronic Cutaneous:Discoid
Note Sparing of Nasolabial Folds Note Scarring, Hyperpigmentation

58
Subacute Cutaneous Lupus

59
 Therapies for lupus patients with skin
lesions(2)
Routine therapy
Topical steroids, intralesional steroids
Hydroxychloroquine
Oral corticosteroids
Dapsone for bullous lesions

60
 Therapies for lupus patients with skin
lesions(3)
Advanced therapy for resistant causes
Subacute cutaneous lupus: mycophenylate mofetil,
retinoids, or cyclosporine
Discoid lesions: chloroquine, clofazimine,
thalidomide, or cyclosporine
Lupus profundus: dapsone
Chronic lesions over 50% of body: topical nitrogen
mustard, BCNU, or tacrolimus
Vasculitis: may need immunosuppressives

61
 The treatment in lupus patients with
autoimmune thrombocytopenia
Splenectomy
Danazol
Immunosuppressive or cytotoxic drugs:
azathioprine, cyclophosphamide
Intravenous immunoglobulin(IVIG)

62
Other management principles in the treatment
of lupus patients(1)

Thrombosis
-Anticoagulation
Recurrent fetal loss with antiphospholipid
-Heparin in low dose or low-molecular-weight heparin with
or without aspirin
-If heparin ineffective or not tolerated, use low-dose aspirin
alone
-Glucocorticoids plus aspirin in moderate to high dose may
be used but is controversial
Thrombocytopenia or hemolytic anemia
-Intravenous gamma globulin, splenectomy, danazol,
cyclosporine, cytotoxic drugs 63
 Other management principles in the
treatment of lupus patients(2)
Seizures/srngan without other serious manifestations
-Anticonvulsants
Behavior disorders or psychosis without other serious
manifestations:
-Psychoactive drugs, neuroleptics
Pure membranous glomerulonephritis:
-Limited trials of immunosuppressives or no specific treatment

64
 Prognosis
Potentially fatal disorder
Increase in survival rate in last 20 years
Now 85% of clients survive at least 5 years
Leading cause of death are related to infection

65
 Summary
Lupus = Autoimmunity
Systemic and affects connective tissue
Caused by malfunctions of:
T-cells
B-cells
Complement System
Signal Transduction
Can be lethal or not
Unique to each individual

66
 Systemic Lupus:of
Review Summary
SLE
Polygenic, Heterogenous Immune
Disorder
Early, Aggressive Treatment for Organ or
Life-Threatening Manifestations is
Warranted
The Most Risk Comes From:
Early: Organ (esp Renal) Disease
Throughout the Course: Infection
Late: Atherosclerosis
THE END
67
68