Autoimmun

PATHOFISIOLOGI dan
ASPEK KLINIS SYSTEMIC
LUPUS ERYTHEMATOSUS

1
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 body’s
cells and tissue, resulting in
inflammation and tissue damage.

2
 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.

3
 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

4
 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
Wegener’s Granulomatosus c-ANCA

5
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 multisys
• tem disease
• prevalence 1 in 2,000
• female to male (1 in 700)
• peak age 15-25
• immune complex deposition
• photosensitive skin eruptions, serositis,
pneumonitis, myocarditis, nephritis, CNS
involvement
7
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/viral
 antibiotics (especially those in the sulfa
and penicillin groups)
 ultraviolet light
 certain drugs
 hormones.

8
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 kompnen inti sel,mis
DNA,RNA,nukeoprotein dsb.

9
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.

10
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
11
Systemic Lupus Erythematosus
Systemic Lupus
Erythematosus

• Discoid Lupus: Cutaneous

manifestations
• Scar upon healing
SYSTEMIC LUPUS
ERYTHEMATOSUS

butterfly rash

Skin rashes

Finger turns blue

14
 Skin Manifestations
• Malar or Butterfly
Rash
• Discoid Rash –
Stimulated by UV light
• Skin manifestations
only appear in 30-
40% of lupus
patients.

15
Clinical Features of Systemic
Lupus Erythematosus

16
 Systemic Lupus
Erythematosus
• Clinical Features on Presentation in SLE

– Arthritis or Arthralgia 55%

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

17
 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.

18
 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%
19
 Signs and Symptoms of Lupus
 Skin:
 Dry, raised rash on face

 Appears to be in butterfly

pattern—the “Bite of the Wolf.”

 Individual round lesions

 Hair
 Hair loss

 Change in texture

20
 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

invasion—leading to
Myositis).
 Muscle pain

21
 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

22
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 23
Signs and Symptoms of Lupus
 Respiratory
 Pleural effusions

 Results in restrictive and obstructive

changes
 Dyspnea

 Hypoventilation

24
 Signs and Symptoms of Lupus
 Cardiac
Pericarditis
 Myocardial ischemia

Chest Pain

Cardiac Dysrrhythmias

25
Signs and Symptoms of Lupus
 Neurological
 Psychoses

 Paresis

 Seizures/srngan tiba2

 Headaches

 Strokes

 Peripheral neuropathies
 http://www.mtio.com/lupus/lal_7.htm
26
 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/phargaan  Fatigue

 Decreased desire/hasrat  Anorexia

 Weight loss

27
 Brain

Salivary, Parotid glands

Thyroid
Heart, Lungs
Serous linings of Heart, Lungs, GI tract
Kidneys
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 28
 Systemic therapies for nonorgan-
threatening lupus
• Nonsteroidal anti-inflammatory drugs
• Antimalarials
• Thalidomide
• Hormonal interventions:
dehydroepiandrosterone, testosterone
patches, bromocriptine, prolactin
• Immunosuppressive therapies:
azathioprine, methotrexate, leflunomide

29
 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

30
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, Klack’s
solution, postprandial rinses of 1: 1
H2O2:H2O

31
 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

32
 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: LE cell, anti-
5. Arthritis
DNA, anti-Sm,
6. Serositis false pos STS
11. Anti-nuclear
antibody

33
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 .

34
 Indications of high dose
corticosteroid therapy in lupus
• Severe lupus nephritis
patients
• 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)
35
 Life-Threatening Manifestations
of SLE: Responses to
• Manifestations often responsive to
glucocorticoids(1)
glucocorticoids
– Vasculitis
– Severe dermatitis of subacute cutaneous lupus
erythematosus or SLE
– Polyarthritis
– Polyserositis—pericarditis, pleurisy, peritonitis
– Myocarditis
– Lupus pneumonitis

36
Life-Threatening Manifestations
of SLE: Responses to
glucocorticoids(2)
~(continue)
– Glomerulonephritis—proliferative forms
– Hemolytic anemia
– Thrombocytopenia
– Diffuse CNS syndrome—acute confusional
state, demyelinating syndromes, intractable
headache
– Serious cognitive defects
– Myelopathies
– Peripheral neuropathies
– Lupus crisis—high fever and prostration

37
Life-Threatening Manifestations of
SLE: Responses to
glucocorticoids(3)
• Manifestations not often responsive to
glucocorticoids
– Thrombosis—includes strokes
– Glomerulonephritis—scarred 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

38
 TREATMENTS
• Drug therapy
– nonsteroidal anti-inflammatory drugs and
antimalarials
– Disease-modifying antirheumatic drugs
(DMARDs)
– Immunomodulating Drugs
– Anticoagulants

39
 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.

40
 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

41
Acute Cutaneous: Malar Rash Chronic Cutaneous:Discoid
Note Sparing of Nasolabial Folds Note Scarring, Hyperpigmentation

42
Subacute Cutaneous Lupus

43
 Therapies for lupus patients
with skin lesions(2)
• Routine therapy
– Topical steroids, intralesional steroids
– Hydroxychloroquine
– Oral corticosteroids
– Dapsone for bullous lesions

44
 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

45
 The treatment in lupus patients
with autoimmune
thrombocytopenia
• Splenectomy
• Danazol
• Immunosuppressive or cytotoxic
drugs: azathioprine,
cyclophosphamide
• Intravenous immunoglobulin(IVIG)

46
 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

47
 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

48
 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

49
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
Wegener’s Granulomatosus c-ANCA

50
 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.

51
 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
Rubgsok

55
Rheumatoid Arthritis

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

56
 RA
• The
inflammatory
process
results in
damage to
cartilage &
bone

NEJM 2001; 344 (12):

907 – 916.
57
Osteoarthritis

58
 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

59
 Systemic Lupus: Summary
Review of 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
60
61