1. Systemic Lupus Erythematosus
Prof DR Dr Ariyanto Harsono SpA(K)
Dept Pediatrics, Airlangga University, Surabaya, Indonesia.

2. Definition:
SLE is A disease of unknown cause, is
characterized by auto antibodies directed
against self-antigen and resulting in
inflammatory damage including the
kidney, heart, blood cells and the CNS
2Prof DR Dr Ariyanto Harsono SpA(K)

3. The diverse presentations of lupus range from
rash and arthritis through anaemia and
thrombocytopenia to
serositis, nephritis, seizures, and psychosis.
Lupus should be part of the differential
diagnosis in virtually any patient presenting
with one of these clinical problems, especially
in female patients between 15 and 50 years of
age.
Prof DR Dr Ariyanto Harsono SpA(K)

4. Genetic and Environmental Factors
 Since 90% of patients with lupus are female, an
important role for female hormones seems likely, but a
protective role for male hormones or an effect of genes
on the X chromosome is also possible. In a
blinded, randomized, controlled trial, menopausal
women with lupus who received hormone-
replacement therapy containingconjugated estrogens
and progesterone had a risk of a mild-to-moderate
disease flare that was 1.34 times the risk among
women who receivedplacebo (P=0.01). However, trials
of hormonal treatments for lupus, such as dehydro
epiandrosterone, have been disappointing.It is unclear
how sex hormones could promote lupus.
Prof DR Dr Ariyanto Harsono SpA(K)

5.  Many drugs cause a variant of lupus called drug-induced lupus.
The best known of these drugs are
procainamide, hydralazine, isoniazid and quinidine. Patients with
drug-induced lupus usually present with skin and joint
manifestations; renal and neurologic features are very rare.
 An antecedent viral-like illness may occur at the onset of lupus or
immediately before a flare. Identifying a particular causative virus
has proved challenging. Epstein–Barrvirus (EBV) may be
important, since a temporal association between the onset of
lupus and the occurrence of EBV infection has been reported. A
case–control study involving children and young adults showed
that anti-EBV antibodies were present in 99% and EBV DNA was
present in 100% of patients with lupus — much higher
proportions than those in the control group.
 Ultravioletradiation is the most obvious environmental factor
linked tolupus.
Prof DR Dr Ariyanto Harsono SpA(K)

6. 6Prof DR Dr Ariyanto Harsono SpA(K)

7. Prof DR Dr Ariyanto Harsono SpA(K) 7
Prof DR Dr Ariyanto Harsono SpA(K)

8. Pathogenesis
Auto antibodies in Lupus
 The affected organs in lupus that have been studied
most intensivelyare the kidneys and the skin. In both
cases, there is inflammation and the deposition of
antibodies and complement. In 1967, kidneys from
patients with lupus nephritis were shown to contain
antibodiesthat bound native, double-stranded DNA.
These antibodies areauto antibodies; that is, they bind
a normal constituent , double-stranded DNA — of the
patient's cellsand tissues. The importance of anti–
double-stranded DNA antibodies in the pathogenesis of
lupus has been confirmed.
Prof DR Dr Ariyanto Harsono SpA(K)

9.  Anti–double-stranded DNA antibodies are highly
specificfor lupus; they are present in 70% of patients
with lupus butin less than 0.5% of healthy people or
patients with other autoimmunediseases such as
rheumatoid arthritis. Levels of anti–ds-DNA antibodies
in serum tend to reflect disease activity, but not in all
patients. Among patients who have both elevated
levels of anti–double-stranded DNA auto antibodies
andclinically quiescent disease, 80% have disease that
becomesclinically active within 5 years after the
detection of elevatedlevels of these antibodies.

10.  In a study of renal-biopsy specimens obtained from patients with
lupus at autopsy, detected IgG that bound to a number of non-DNA
antigens, including Ro (a ribonucleoprotein complex), La (an RNA-
binding protein), C1q (a subunit of the C1 complement
component), and Sm (nuclear particles consisting of several different
polypeptides). The detection of antibodies to these antigens in
autopsy specimens does not prove that they play a role in the
development of lupus nephritis. Rather than cause the
inflammation, these auto-antibodies may establish themselves in
tissue only after the apoptosis of cells in inflamed kidney tissue
exposes nuclear antigens. The strongest evidence concerning the
mechanism of lupus nephritis relates to anti–double-stranded
DNA, anti-nucleosome, and anti– -actinin antibodies.
 Although anti–double-stranded DNA antibodies are the most
extensively studied auto-antibodies in lupus, others play a rolein
clinical manifestations, particularly in autoimmune haemolytic
anaemia, thrombocytopenia, skin disease, and neonatal lupus.

11. Tissue Damage by Auto antibodies in Lupus
Most studies of autoantibody-mediated tissue damage in patients
with lupus have focused on the role of anti–ds-DNA antibodies in
patients with lupus nephritis. There are two main theories; both
stress that the binding of antibodies to double-stranded DNA itself
is probably not the most criticaldeterminant of tissue damage.
Extracellular double-stranded DNA occurs mainly in the form of
nucleosomes, which are fragments of chromatin that cells release
when they undergo apoptosis. Pathogenic anti–ds-DNA auto
antibodies in patients with lupus bind to nucleosomes that have
entered the bloodstream; in turn, these antibody–nucleosome
complexes settle in the renal glomerular basement membrane.
Prof DR Dr Ariyanto Harsono SpA(K)

12. These immune complexes activate
complement, which initiates the
glomerulonephritis. This series of events has been
demonstrated in animal models. Furthermore, IgG
antibodies have been shown, by means of
electron microscopy, to co-localize with
extracellularchromatin in lupus nephritis in
humans and mice. Also relevantis the detection
of anti-nucleosome antibodies in the blood and
inflamed tissues of patients with lupus.
Prof DR Dr Ariyanto Harsono SpA(K)

13. The second model proposes that anti–ds DNA, anti-nucleosome
antibodies, or both cross-react with proteins in the kidney;
thus, they have a direct pathogenic effect on renal cells. This is an
example of polyreactivity, whereby the same antibody can bind to
antigens with different structuresbecause they have similar surface
shapes (so-called shared epitopes) or areas of similar charge.
Among possible target antigens in the kidney, attention is currently
focused on actinin. This protein is critical for maintaining the
function of renal podocytes,which are constituents of the
glomerular filtration barrier.Two studies have shown that mouse
monoclonal anti-DNA antibodies that cross-reacted with actinin (a
protein that cross-linksactin, a component of the cytoskeleton)
were pathogenic, whereas monoclonal anti-DNA antibodies that did
not cross-react with -actinin were non pathogenic
Prof DR Dr Ariyanto Harsono SpA(K)

14. Pathogenicity was judged accordingto whether
the antibodies caused proteinuria and histologic
changes of glomerulonephritis after passive
transfer into recipientmice. Although anti -
actinin antibodies are not specificfor lupus, these
antibodies, when present in the serum of
patientswith lupus, can serve as a marker of
renal involvement.The detection of anti- -actinin
antibodies has not been reported in specimens
obtained from renal biopsies in patients with
lupus.
Prof DR Dr Ariyanto Harsono SpA(K)

15. 15Prof DR Dr Ariyanto Harsono SpA(K)
Immune Response in SLE

16. Source of the Autoantigens in Lupus
The obvious source of nucleosomes is the cellular
debris released as a result of apoptosis. During
apoptosis, blebs of cellular material form on the
surface of the dying cell. Antigens thatare normally
buried within the cells are exposed on the surface
of these blebs, and they may trigger an immune
response. These exposed antigens include
nucleosomes, Ro 62, Ro 50, La, and anionic
phospholipids. Antibodies to these antigens occur
commonly in patients with lupus.
Prof DR Dr Ariyanto Harsono SpA(K)

17. 17Prof DR Dr Ariyanto Harsono SpA(K)

18. Prof DR Dr Ariyanto Harsono SpA(K) 18
Prof DR Dr Ariyanto Harsono SpA(K)

19. Diagnosis

20. DIAGNOSIS of SLE
ACR cRITERIA
Skin:
 Malar Rash
 Discoid rash
 Oral ulcers
 Photo sensitive rash
Systemic Criteria
 Arthritis
 Serositis
 Kidney Disorder
 Neurologic Disorder
 Hematolic Disorder
Laboratory Criteria
 Immunologic Disorder
 Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 20

21. DIAGNOSIS of SLE
ACR cRITERIA
Skin:
 Malar Rash
 Discoid rash
 Oral ulcers
 Photo sensitive rash
Systemic Criteria
 Arthritis
 Serositis
 Kidney Disorder
 Neurologic Disorder
 Hematolic Disorder
Laboratory Criteria
 Immunologic Disorder
 Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 21

22. DIAGNOSIS of SLE
ACR cRITERIA
Skin:
 Malar Rash
 Discoid rash
 Oral ulcers
 Photo sensitive rash
Systemic Criteria
 Arthritis
 Serositis
 Kidney Disorder
 Neurologic Disorder
 Hematolic Disorder
Laboratory Criteria
 Immunologic Disorder
 Positive ANA Test 22Prof DR Dr Ariyanto Harsono SpA(K)

23. DIAGNOSIS of SLE
ACR cRITERIA
Skin:
 Malar Rash
 Discoid rash
 Oral ulcers
 Photo sensitive rash
Systemic Criteria
 Arthritis
 Serositis
 Kidney Disorder
 Neurologic Disorder
 Hematolic Disorder
Laboratory Criteria
 Immunologic Disorder
 Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 23

24. DIAGNOSIS of SLE
ACR cRITERIA
Skin:
 Malar Rash
 Discoid rash
 Oral ulcers
 Photo sensitive rash
Systemic Criteria
 Arthritis
 Serositis
 Kidney Disorder
 Neurologic Disorder
 Hematolic Disorder
Laboratory Criteria
 Immunologic Disorder
 Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 24

25. DIAGNOSIS of SLE
ACR cRITERIA
Skin:
 Malar Rash
 Discoid rash
 Oral ulcers
 Photo sensitive rash
Systemic Criteria
 Arthritis
 Serositis
 Kidney Disorder
 Neurologic Disorder
 Hematolic Disorder
Laboratory Criteria
 Immunologic Disorder
 Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 25

26. DIAGNOSIS of SLE
ACR cRITERIA
Skin:
 Malar Rash
 Discoid rash
 Oral ulcers
 Photo sensitive rash
Systemic Criteria
 Arthritis
 Serositis
 Kidney Disorder
 Neurologic Disorder
 Hematolic Disorder
Laboratory Criteria
 Immunologic Disorder
 Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 26

27. DIAGNOSIS of SLE
ACR cRITERIA
Skin:
 Malar Rash
 Discoid rash
 Oral ulcers
 Photo sensitive rash
Systemic Criteria
 Arthritis
 Serositis
 Kidney Disorder
 Neurologic Disorder
 Hematolic Disorder
Laboratory Criteria
 Immunologic Disorder
 Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 27

28. DIAGNOSIS of SLE
ACR cRITERIA
Skin:
 Malar Rash
 Discoid rash
 Oral ulcers
 Photo sensitive rash
Systemic Criteria
 Arthritis
 Serositis
 Kidney Disorder
 Neurologic Disorder
 Hematolic Disorder
Laboratory Criteria
 Immunologic Disorder
 Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 28

29. DIAGNOSIS of SLE
ACR cRITERIA
Skin:
 Malar Rash
 Discoid rash
 Oral ulcers
 Photo sensitive rash
Systemic Criteria
 Arthritis
 Serositis
 Kidney Disorder
 Neurologic Disorder
 Hematolic Disorder
Laboratory Criteria
 Immunologic Disorder
 Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 29

30. DIAGNOSIS of SLE
ACR cRITERIA
Skin:
 Malar Rash
 Discoid rash
 Oral ulcers
 Photo sensitive rash
Systemic Criteria
 Arthritis
 Serositis
 Kidney Disorder
 Neurologic Disorder
 Hematolic Disorder
Laboratory Criteria
 Immunologic Disorder
 Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 30
• Haemolytic Anemia
• Low white blood cells
count
• Low thrombcyte count

31. DIAGNOSIS of SLE
ACR cRITERIA
Skin:
 Malar Rash
 Discoid rash
 Oral ulcers
 Photo sensitive rash
Systemic Criteria
 Arthritis
 Serositis
 Kidney Disorder
 Neurologic Disorder
 Hematolic Disorder
Laboratory Criteria
 Immunologic Disorder
 Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 31
LE Cell
Prof DR Dr Ariyanto Harsono SpA(K)

32. DIAGNOSIS of SLE
ACR cRITERIA
Skin:
 Malar Rash
 Discoid rash
 Oral ulcers
 Photo sensitive rash
Systemic Criteria
 Arthritis
 Serositis
 Kidney Disorder
 Neurologic Disorder
 Hematolic Disorder
Laboratory Criteria
 Immunologic Disorder
 Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 32
LE Cell

33. DIAGNOSIS of SLE
ACR cRITERIA
Skin:
 Malar Rash
 Discoid rash
 Oral ulcers
 Photo sensitive rash
Systemic Criteria
 Arthritis
 Serositis
 Kidney Disorder
 Neurologic Disorder
 Hematolic Disorder
Laboratory Criteria
 Immunologic Disorder
 Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 33
LE CellAnti ds-DNA

34. DIAGNOSIS of SLE
ACR cRITERIA
Skin:
 Malar Rash
 Discoid rash
 Oral ulcers
 Photo sensitive rash
Systemic Criteria
 Arthritis
 Serositis
 Kidney Disorder
 Neurologic Disorder
 Hematolic Disorder
Laboratory Criteria
 Immunologic Disorder
 Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 34Anti Ro

35. DIAGNOSIS of SLE
ACR cRITERIA
Skin:
 Malar Rash
 Discoid rash
 Oral ulcers
 Photo sensitive rash
Systemic Criteria
 Arthritis
 Serositis
 Kidney Disorder
 Neurologic Disorder
 Hematolic Disorder
Laboratory Criteria
 Immunologic Disorder
 Positive ANA Test Prof Ariyanto Harsono MD PhD SpA(K) 35
Anti Nuclesr Antibody

36. Prof DR Dr Ariyanto Harsono SpA(K) 36

37. Prof Ariyanto Harsono MD PhD SpA(K) 37

38. 38Prof Ariyanto Harsono MD PhD SpA(K)

39. 39Prof DR Dr Ariyanto Harsono SpA(K)
Anti Nuclear Antibody

40. 40Prof DR Dr Ariyanto Harsono SpA(K)
Anti ds_DNA

41. 41Prof DR Dr Ariyanto Harsono SpA(K)
Anti Ro

42. Skin Biopsy
42Prof DR Dr Ariyanto Harsono SpA(K)
Superficial and deep perivascular lymphocyte
infiltrate with increased mucin deposition in
the dermis.

43. Fig. 9-1-3-Autoimmune hepatitis.
Lobular inflammation and focal necrosis. 43
Prof DR Dr Ariyanto Harsono SpA(K)
Prof DR Dr Ariyanto Harsono SpA(K)

44. Giant multinucleated hepatocytes.
Inflammatory infiltration in the lobule
44

45. Cerebral Lupus
45
Cerebral ischemia

46. Clinical Manifestation by Target Organ
46Prof DR Dr Ariyanto Harsono SpA(K)

47. 47Prof DR Dr Ariyanto Harsono SpA(K)

48. 48Prof DR Dr Ariyanto Harsono SpA(K)

49. Bulous Eruption
49Prof DR Dr Ariyanto Harsono SpA(K)

50. Mouth Ulcer
50

51. disseminated lupus
51Prof DR Dr Ariyanto Harsono SpA(K)

52. Malar Rash
52Prof DR Dr Ariyanto Harsono SpA(K)
Malar Rash
Prof DR Dr Ariyanto Harsono SpA(K)

53. Alopecia
53Prof DR Dr Ariyanto Harsono SpA(K)
Alopecia
Prof DR Dr Ariyanto Harsono SpA(K)

54. 54Prof DR Dr Ariyanto Harsono SpA(K)

55. Prof DR Dr Ariyanto Harsono SpA(K) 55Prof DR Dr Ariyanto Harsono SpA(K)

56. Deep venous thrombosis. 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.
Prof DR Dr Ariyanto Harsono SpA(K) 56Prof DR Dr Ariyanto Harsono SpA(K)

57. Subacute cutaneous lupus erythematosus
Lesions, most prominent in sun-damaged
skin, consist of non-scarring
papulosquamous lesions which are
often polycyclic. Classic DLE lesions
though may be found in some patients.
Some criteria of SLE may also be
present.
Unlike discoid lupus
erythematosus, follicular plugging is not
a prominent feature.
Arthritis is a common feature.
Anti-Ro and anti-La are frequently
positive.
SCLE may be triggered by drugs such as
hydrochlorothiazide and griseofulvin.
Children born to mothers with SCLE may
have neonatal LE.
Prof DR Dr Ariyanto Harsono SpA(K) 57

58. Discoid Lupus
58Prof DR Dr Ariyanto Harsono SpA(K)
Discoid rash

59. Raynaud Phenomena
59Prof DR Dr Ariyanto Harsono SpA(K)

60. Vasculitis
60Prof DR Dr Ariyanto Harsono SpA(K)

61. Lupus profundus
61Prof DR Dr Ariyanto Harsono SpA(K)

62. Photosensitive rash
62Prof DR Dr Ariyanto Harsono SpA(K)

63. Necrotizing Sleritis, is rare inSLE Retinal involvement in SLE is the second
most common ocular manifestation
63Prof DR Dr Ariyanto Harsono SpA(K)

64. Retinopathy
64Prof DR Dr Ariyanto Harsono SpA(K)

65. Serositis
65Prof DR Dr Ariyanto Harsono SpA(K)
serositis

66. IgA Nephropathy Lupus nephritis
66Prof DR Dr Ariyanto Harsono SpA(K)

67. Thrombotic microangiopathy
67Prof DR Dr Ariyanto Harsono SpA(K)

68. 68

69. lymphadenitis
69Prof DR Dr Ariyanto Harsono SpA(K)

70. 70Prof DR Dr Ariyanto Harsono SpA(K)

71. 71

72. Two trials have shown that a strategy of increasing doses
of corticosteroids in response to a specified increase in
levels of anti–double-stranded DNA antibodies leads to
lower mean levels of such antibodies and reduced
frequency of severe flares of disease, but one study
indicated that the side effects of corticosteroids were a
problem. Rituximab and abetimus sodium have been used
as specific methods of reducing levels of anti–double-
stranded DNA. Rituximab is nonspecific; that is, it is an
antibody against CD20, which is found on the surface of all
mature B cells.
Prof DR Dr Ariyanto Harsono SpA(K)

73. Abetimussodium is designed to deplete only B lymphocytes that
produceanti–double-stranded DNA antibodies because its four
surfaceoligonucleotides can engage surface anti–double-stranded
DNA antibodies on those cells, but it has no epitopes to allow
binding of helper T cells. The B cells therefore undergo apoptosis
rather than proliferation, but it is not clear whether this depleting
mechanism occurs in patients. Abetimus sodium mayalso work by
forming complexes with anti–double-stranded DNA
antibodies, which are then cleared from the circulation.
Prof DR Dr Ariyanto Harsono SpA(K)

74. 74