an overview of Lupus for journalist Lupus has a wide spectrum of manifestation. Some mild but in most cases it has a high impact of life and quality of life

1. Lahir di Garut, 16-1-1955Lahir di Garut, 16-1-1955
SD-SMA : GarutSD-SMA : Garut
Dokter umum: FK UNSRI PalembangDokter umum: FK UNSRI Palembang
Internist: FK UNPAD BandungInternist: FK UNPAD Bandung
Clinical Rheumatology & OsteoporosisClinical Rheumatology & Osteoporosis TrainingTraining::
Arthritis Foundation of WA PerthArthritis Foundation of WA Perth
Konsultan Reumatologi : FKUIKonsultan Reumatologi : FKUI JakartaJakarta
DivisiDivisi ReumatologiReumatologi
RS Dr Hasan SadikinRS Dr Hasan Sadikin
IRA, PAPDI, PEROSI, PERALMUNI, APLAR, IASP,IRA, PAPDI, PEROSI, PERALMUNI, APLAR, IASP,
OARSIOARSI

2. An overview for Journalist

3.  Infection  autoimmunity
 Autoimmune disease  infection
08/04/1

4. Source: http://www.biologymad.com/

5.  Classical systemic autoimmune disease (12)
 Systemic vasculitis (16)
 Idiopathic inflammatory myopathies (8)
 0ther immune mediated systemic diseases (4)
 Endocrine and reproductive autoimmune diseases (13)
 Hepatobillary and pancreatic autoimmune diseases (5)
 Gasrointestinal autoimmune disease (4)
 Cutaneous autoimmune diseases (4)
 Cardiovascular and pulmonary autoimmune diseases (6)
 Neurological autoimmune disease (11)
 Ocular autoimune diseases (4)
 Renal autoimmune diseases (5)
 Hematologic autoimmune diseases (11) 08/04/15

6.  Organ-specific diseases
Damage is confined to the organ
against which the immune
response is mounted
 Non-organ-specific diseases
Immune response against
antigens which are not
associated with the organ
involved
 Organ-specific diseases
Damage is confined to the organ
against which the immune
response is mounted
 Non-organ-specific diseases
Immune response against
antigens which are not
associated with the organ
involved

9. Systemic lupus erythematosus (SLE ) is a chronic
autoimmune connective tissue disease that can affect
any part of the body.
 SLE most often harms the heart, joints, skin, lungs,
blood vessels, liver, kidneys, and nervous system.
 The course of the disease is unpredictable, with
periods of illness (called flares) alternating with
remissions.
 The disease occurs nine times more often in women
than in men, especially between the ages of 15 and 50.

10.  SLE is treatable through addressing its symptoms,
mainly with corticosteroids and
immunosuppressants; there is currently no cure.
 SLE can be fatal, although with recent medical
advances, fatalities are becoming increasingly
rare.
 Survival for people with SLE in the United States,
Canada, and Europe is approximately 95%
at five years, 90% at 10 years, and 78% at 20
years.

11.  There are several types of lupus; in general,
when the word lupus alone is used, reference is to
systemic lupus erythematosus,
 Other types include:
1-Discoid lupus E ;
chronic cutaneous lupus, lead to skin disorder in which
there is red, raised rash on the face or scalp. limited to
the skin and diagnosed by skin biopsy.
2-Drug-induced lupus
(procainamide,hydralazin,quinidine,phenytoin)
3-Lupus nephritis:an inflammation of kidneys, caused
by SLE.

12. The principal fate
of lymphocytes that
recognize self antigens
in the generative organs
is death (deletion), BUT:
Some B cells may change
their specificity (called
“receptor editing”(
Some CD4 T cells may
differentiate into
regulatory (suppressive(
T lymphocytes
Central and peripheral tolerance
From Abbas, Lichtman and Pillai. Cellular and Molecular Immunology 6th ed, 2007

13. Consequences of self antigen recognition in thymus
From: Abbas & Lichtman, Cellular & Molecular Immunology 5th ed 2003

15. 08/04/1
 Age
 Gender *
 Genotype*
 Life style choices
 Stress

16. Skin cell
T cell T cell
B cell
APC
APC
Defective IC
clearance
UV light Infectio
n
External AgSelf
Ag
Ab
IC
Target
Geneticsusceptibility

17.  Common initial and chronic complaints are fever,
malaise, joint pains, myalgias, fatigue, and
temporary loss of cognitive abilities.
 Because they are so often seen with other
diseases, these signs and symptoms are not part
of the diagnostic criteria for SLE.
 When occurring in conjunction with other signs
and symptoms, however, they are considered
suggestive.

18.  30% to 50% suffering from the classic malar rash
(or butterfly rash) associated with the disease.
 Alopecia;
mouth, nasal, and vaginal ulcers.
Musculoskeletal manifestations
 The most commonly sought medical attention is
for joint pain, with the small joints of the hand and
wrist usually affected, although all joints are at
risk.

19.  Malar rash: This is
a "butterfly-shaped"
red rash over the
cheeks below the
eyes and across the
bridge of the nose.
It may be a flat or a
raised rash.
The rashes are
made worse by sun
exposure.

20.  Maculopapular
eruption

21.  Discoid lupus
These are red,
raised patches with
scaling of the
overlying skin.

22.  Vasculitic skin
lesin

23.  Alopecia

24.  Oral ulcer: Painless
sores in the nose or
mouth need to be
observed and
documented by a
doctor.

25.  Unlike rheumatoid arthritis, lupus arthritis is less
disabling and usually does not cause severe
destruction of the joints. Fewer than ten percent of
people with lupus arthritis will develop deformities
of the hands and feet.
 SLE patients are at particular risk of developing
osteoarticular tuberculosis.

26. Hematological manifestations
 Anemia usually present in up to 50% of cases. Low
platelet and white blood cell counts may be due to the
disease or a side-effect of pharmacological treatment.
 People with SLE may have an association with
antiphospholipid antibody syndrome,
(thrombotic
disorder), wherein autoantibodies to phospholipids are
present in their serum.
 Abnormalities associated with antiphospholipid
antibody syndrome usually present ,and a positive test
for antiphospholipid antibodies; lupus anticoagulant-
positive. Another autoantibody is the
anticardiolipin antibody.

27.  Deep venous
thrombosis (blood clot).
Notice the contrast
between the involved
left leg and the normal
right leg. Redness,
swelling, and warmth
combined with
discomfort in the
involved leg are
cardinal manifestations
of a deep venous
thrombosis.

28. Cardiac manifestations
 A person with SLE may have inflammation of various
parts of the heart, such as pericarditis, myocarditis,
and endocarditis.
 The endocarditis of SLE is characteristically
noninfective (Libman-Sacks endocarditis),
and involves either the mitral valve or the
tricuspid valve.
 Atherosclerosis also tends to occur more often and
advances more rapidly than in the general population.
 Vasculitis may produce myocardial infarction, and
Raynaud’s phenomenon.

29.  Pericarditis

30.  SLE can be
associated with
endocarditis. Shown
here is Libman-
Sacks endocarditis
in which there are
many flat, reddish-
tan vegetations
spreading over the
mitral valve and
chordae.

31. Pulmonary manifestations
 Lung and pleura inflammation can cause pleuritis,
pleural effusion, lupus pneumonitis, chronic
diffuse interstitial lung disease,
pulmonary hypertension, pulmonary emboli,
pulmonary hemorrhage.

32.  Renal involvement
 Painless hematuria or proteinuria may often be
the only presenting renal symptom.
 Acute or chronic renal impairment may develop
with lupus nephritis, leading to acute or end-stage
renal failure.
 A histological hallmark of SLE is membranous
glomerulonephritis.
 This finding is due to immune complex deposition
along the glomerular basement membrane.

33. Neuropsychiatric syndromes
 can result when SLE affects the central or
peripheral nervous system.
 The most common neuropsychiatric
disorder people with SLE have is headache.
 Other common neuropsychiatric
manifestation of SLE include
cognitive dysfunction, mood disorder,
cerebrovascular disease, seizures,
polyneuropathy, anxiety disorder, and
psychosis.

34. Systemic manifestations
 Fatigue in SLE is probably multifactorial and has
been related not only to disease activity or
complications such as anemia ,but also to pain,
depression, poor sleep quality, and poor
physical fitness.

36. 1.Malar rash: Fixed erythema over malar areas, sparing nasolabial folds
2.Discoid rash: Erythematous raised patches with keratotic scaling and follicular plugging
3.Photosensitivity: Skin rash after exposure to sunlight, history or physical exam
4.Oral ulcers: Oral or nasopharyngeal, painless, by physical exam
5.Arthritis:Tenderness, swelling, effusion in 2 or more peripheral joints
6.Serositis: A) pleuritis or B) pericarditis
7.Renal disorder A) proteinuria>0.5g/24hour or 3+ or B) cellular casts
8.Neurological disorder: A) seizures or B) psychiatric disorder (having
excluded other causes, e.g. drigs(
9.Haematological disorder: A) haemolytic anaemia or B) leucopenia or C)
thrombocytopenia
10.Immunologic disorder: A) positive LE cells or B) raised anti-native DNA
antibdy binding or C) anti-Sm antibody or D) false positive serological test for
syphilis.
11.Positive antinuclear antibody:
Criteria of the ARA for the classification of SLE

37.  Investigations
 ■ Blood:
 ■ A full blood count may show a leucopenia,
lymphopenia and/or thrombocytopenia. Anaemia of
chronic disease or autoimmune haemolytic anaemia
also occurs. The ESR is raised in proportion to the
disease activity. In contrast, the CRP is usually
normal but may be high when the patient has lupus
pleuritis or arthritis or a coexistent infection.
 ■ Urea and creatinine only rise when renal disease is
advanced. Low serum albumin or high urine protein/
creatinine ratio are earlier indicators of lupus
nephritis.

38. Autoantibodies – many different autoantibodies may
be present in SLE but the most significant are ANA,
anti-dsDNA, anti-Ro, anti-Sm and anti-La .
Antiphospholipid antibodies are present in
25–40% of cases but not all of these patients
develop antiphospholipid syndrome .
 ■ Serum complement C3 and C4 levels are often
reduced during active disease. The combination of
high ESR, high anti-dsDNA and low C3 may herald
a flare of disease. All these markers tend to return
towards normal as the flare improves

39.  The lupus
erythematosus (LE( cell
it has been
superseded by the ANA
and anti-dsDNA
techniques.
 ANA is a screening test
anti-Sm, anti-dsDNA
antibodies are lupus
specific antoantibodies.

40.  This homogenous
pattern of diffuse bright
green staining of nuclei
seen by
immunofluorescence
microscopy with a Hep2
cell substrate is called
homogenous, and is the
most common pattern
with autoimmune
diseases overall.

41.  This rim (peripheral (
pattern of linear bright
green staining around
the peripheral of nuclei
seen by
immunofluorescence
microscopy with a
Hep2 cell substrate .
 dsDNA

42.  Nucleolar pattern

43.  Speckled pattern
Scl70, SSA, SSB,
Sm

44.  These little Crithidia
organisms have a small
kinetoplast between the
nucleus and the flagella
which glows bright
green under
immunofluorescence
microscopy, and is
indicative of anti-native
DNA antibody that is
very specific for SLE.

45.  Immu-blotting
method to detect
anti-Sm, RNP,
SSA, SSB, Jo1,
Scl70 and
ribosomal P.

46.  Immunofluorescence of skin
with antibody to IgG
demonstrates a band-like
deposition of immune
complexes that is bright green
at the dermal epidermal
junction in this skin biopsy
taken from an area with a
visible rash. With SLE such
deposition can be found in skin
uninvolved by a rash, whereas
with DLE the immune
complexes are found only in
involved skin.

47.  Vasculitis in arteries
throughout the body
can account for signs
and symptoms from a
variety of organ
involvements. Seen
here is an artery with
extensive vasculitis with
chronic inflammatory
cells.

48.  SLE is
associated with a
peculiar
periarteriolar
fibrosis in the
spleen, as shown
here.

49.  WHO classification of lupus nephritis is
based on light, immunofluorescence, and
electron microscopic findings.

50. Treatment
 Being a chronic disease with no known cure, the
treatment of SLE is symptomatic. ,this involves
preventing flares and reducing their severity and
duration when they occur. Currently, medication is the
main form of treatment.
 Medications
 Due to the variety of symptoms and organ system
involvement with SLE, its severity in an individual must
be assessed in order to successfully treat SLE.
 Mild or remittant disease can sometimes be safely left
untreated. If required,
nonsteroidal anti-inflammatory drugs and antimalarials
may be used.

51. Disease-modifying antirheumatic drugs
 Disease-modifying antirheumatic drugs (DMARDs( are
used preventively to reduce the incidence of flares, the
process of the disease, and lower the need for steroid use;
when flares occur, they are treated with corticosteroids.
 DMARDs commonly in use are antimalarials and
immunosuppressants (e.g. methotrexate and azathioprine(.
 Hydroxychloroquine is an FDA-approved antimalarial used
for constitutional, cutaneous, and articular manifestations,
 whereas cyclophosphamide is used for severe
glomerulonephritis or other organ-damaging complications.

52. Clinical featureinitial dose of
prenisolone
Arthritis (poorly responding to NSAIDs) 20-30mg/d,
reducing
pleuritis by about
5mg/wk if
Pericarditis symptoms
abate
Haemolytic anemia 1mg/kg/d for
about 1M
Thrombocytopenia reduce by
10mg/d if
blood tests
improve
Nephritis 1mg/kg/d for
about 1M
Neuropsychiatric controversal!
1-2mg/kg/d,
0.5-1g/d
methylprednisolone

53.  Plasma exchange
 Intravenous Immunoglobulin
 Stem cell transplantation
 Immune therapy ( anti-IL10, anti-CD20,
and immune tolerance therapy)

54.  SLE has been stable for more than 1 year.
 Prednisone is no more than 10mg/d, and
cytotoxic drug has been stopped for more
than 6 moth.
SLE patients can plan to have a baby.

55.  Depending on the dosage, people that require
steroids may develop side-effects such as
central obesity, puffy round face, diabetes
mellitus, increased appetite, difficulty sleeping and
osteoporosis. Those side-effects can subside if
and when the large initial dosage is reduced, but
long-term use of even low doses can cause
elevated blood pressure and cataracts.

56.  Lifestyle changes
 Avoiding sunlight is the primary change to the
lifestyle of SLE sufferers, as sunlight is known to
exacerbate the disease. Drugs unrelated to SLE
should be prescribed only when known not to
exacerbate the disease

57. Prognosis
.
High serum creatinine, hypertension,
nephrotic syndrome, anemia and
hypoalbuminemia are poor prognostic factors.
The ANA is the most sensitive screening test for
evaluation, whereas anti-Sm (anti-Smith) is the
most specific.
The dsDNA (double-stranded DNA) antibody is
also fairly specific and often fluctuates with
disease activity; as such, the dsDNA titer is
sometimes useful to monitor disease flares or
response to treatment.

66. Thank you