1. Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect multiple organ systems. 2. SLE is characterized by the production of autoantibodies directed against cell nuclei. 3. Treatment of lupus nephritis involves induction therapy with corticosteroids and cytotoxic agents to control disease activity, followed by long-term maintenance treatment to prevent flares and preserve renal function.

1. Systemic Lupus
Erythematosus
Mohammad Ilyas, M.D.
Assistant Clinical Professor
University of Florida /Health Sciences Center
Jacksonville, Florida USA

2. QUIZ
THE LUPUS IS A LATIN WORD MEAN
A.Crocodile
B.Wolf
C.Sheep
D.Snake

3. INTRODUCTION
Systemic lupus erythematosus (SLE) is
the prototypic multisystem autoimmune
disorder with a broad spectrum of clinical
presentations encompassing almost all
organs and tissues.
The extreme heterogeneity of the disease
has led some investigators to propose
that SLE represents a syndrome rather
than a single disease.

4. HISTORY
1. The term ‘lupus’ (Latin for ‘wolf’) was first used during the Middle Ages
to describe erosive skin lesions evocative of a ‘wolf’s bite’.
2. The butterfly metaphor - Viennese physician Ferdinand von Hebra
1846
3. “Lupus erythematosus - Atlas of Skin Diseases in 1856.
4. Systemic disease with visceral manifestations by Moriz Kaposi (1837–
1902).
5. False positive test for syphilis in SLE by Reinhart and Hauck (1909);
6. Endocarditis lesions in SLE by Libman and Sacks in New York (1923);
7. Glomerular changes by Baehr (1935),
8. ‘Diff use connective tissue disease’ by Klemperer, Pollack and Baehr
(1941).
9. The ‘LE’ cell by Hargraves, Richmond and Morton at the Mayo Clinic in
1948.

5. DEFINITION
Inflammatory autoimmune disorder
affecting multiple organ systems
characterized by the production of
autoantibodies directed against cell
nuclei”

6. Natural History and
Course

7. Etiology
Genetic (HLA DR3 association)
Abnormal immune response
Environmental
UV
Hormones (Estrogen, Prolactin)
Demethylating drugs (Biologic, antiviral..)
Infectious
Endogenous viruses or viral-like elements

8. EPIDEMIOLOGY
Prevalence influenced by age, gender, race,
and genetics
Prevalence: 1:2000
Peak incidence 16-55 years (Tripled last 40 yrs)
Black > White (4:1)
Urban > Rural
Female predominance 9:1
HLA DR3 association, Family History
Severity is equal in male and female

9. PATHOPHYSIOLOGY
Increased amounts of apoptosis-related
endogenous nucleic acids stimulate the
production of IFNα and promote
autoimmunity by breaking self-tolerance
through activation of antigen-presenting
cells.
Once initiated, immune reactants such as
immune complexes amplify and sustain
the inflammatory response.

10. Pathogenesis

11. Lupus criteria
For the purpose of identifying patients
in clinical studies, a person has SLE if
4 or more of the 11 criteria are present,
serially or simultaneously, during any
interval of observation.
It is important to remember that a
patient may have SLE and not have 4
criteria.

12. CLINICAL FEATURES:
Mucocutaneous
 Malar Rash (butterfly erythema)
 Discoid rash
 Photosensitive rash
 Subacute cutaneous LE
 Livedo reticularis
 Alopecia
 Raynaud’s
Vasculitic ulceration
Oral ulceration
Nasal septal perforation
Nailfold capillary
changes

13. Lupus criteria
(pneumonic)
M D S O A P B R A I N

14. Lupus criteria
(pneumonic)
Malar rash
Discoid lupus
Serositis
Oral ulcers
Arthritis
Photosensitivity
Blood
abnormalities
Renal
ANA
Immune
Neurologic

15. Malar
rash
M
D
S
O
A
P

16. Malar
rash

17. Discoid
rash
M
D
S
O
A
P

18. Discoid
rash

19. Discoid
rash

20. Vasculitis

21. Alopecia

22. Lupus criteria
(pneumonic)
Serositis
Pleuritis, pleural
effusion
Pericarditis, pericardial
effusion
Ascites
M
D
S
O
A
P

23. Oral
ulcer
s
M
D
S
O
A
P

24. Arthritis (with
swelling)
M
D
S
O
A
P

25. Arthritis (Jaccoud’s)

26. Photosensitivit
y
M
D
S
O
A
P

27. Blood abnormalities
Leukocytopenia (< 4000 on 2 + occasions)
Lymphopenia (< 1500 on 2 + occasions)
Hemolytic anemia
Thrombocytopenia (<100, 000)
B
R
A
I
N

28. B
R
A
I
N
Renal:
A) Proteinuria (>500
mg/24hrs)
B) Cellular casts

29. Pathogenesis
Immune aggregates are present at sites of
injury in glomeruli, and in the tubules also in
about two-thirds of renal biopsies, as are
complement components.
Whether these are derived from circulating
complexes or from in situ combination of
antigen and antibody is still unclear.

30. Pathogenesis
The effector mechanisms of renal
damage (complement, polymorphs,
monocytes, cytokines, eicosanoids,
etc.) are similar in lupus and primary
glomerulonephritis, but the interstitial
cellular infiltrates in lupus often show an
excess of CD8+
cytotoxic T lymphocytes
over CD4+

31. Renal Manifestations
of Lupus

32. Anti-nuclear
antibodies (ANA)
Rim
Nucleolar
Diffuse
Speckled
B
R
A
I
N

33. Immune
abnormalities
Smith antibody
Anti-ds DNA antibody
Anti-phospholipid antibody (1997
modification)
 Anti-cardiolipin antibody (IgG or IgM)
 Biologic false positive VDRL (> 6 months)
 Lupus anticoagulant
B
R
A
I
N

34. Neurologic: A)
Seizure
B)
Psychosis
B
R
A
I
N

35. Extrarenal
Manifestations
Constitutional
Musculoskeletal 80%
Mucocutaneous 33%
Serositis
Hematological
Neuro-psychiatric
System 30-45%
Lung 75%
Secondary
Antiphospholipid
Antibody Syndrome
Ocular
Cardiac
Gastrointestinal

36. Laboratory
Investigations
Antinuclear Antibodies
Hematology
Antiphospholipid Antibodies
Compliments C3 – C4
ESR, CRP

37. Antinuclear
Antibodies

38. Differential diagnosis
Rheumatic fever
Rheumatoid arthritis
Hemolytic anemia
Mixed connective tissue disease (MCTD)
Henoch-Scho¨nlein purpura (HSP)
IgA Nephropathy

39. Diagnosis
High index of suspicion
Immunologic Tests
Crithedia lucilae kinetoplast test
Hypocomplementemia
Abnormal urine and/or
Reduced renal function

40. Renal Histologic
Findings
Glomerular Appearances

43. Mesangial type lupus nephritis,
WHO class II.

44. WHO class IV lupus
nephritis.

46. Outcome and Mortality

47. Treatment of Lupus Nephritis
The Acute Phase: Induction Treatment
Corticosteroids.
Cytotoxic Agents.
Plasma Exchange.
Rituximab (Humanized monoclonal
antibody)

49. IV Cyclophosphamide
For Lupus Nephritis
Pulsed intravenous cyclophosphamide
therapy in conjunction with low dose
prednisone
Seven (7) total doses of monthly i.v.
cyclophosphamide beginning with 500 mg/m2
body surface area and increasing to 750 and
then 1000 mg/m2
as tolerated.
Good clinical response - Patient begins every
3 month cyclophosphamide until a total of 36
months have elapsed.

50. Inclusion Criteria
1. Decline in creatinine clearance < 75
ml/min/1.73m2
OR
2. Renal biopsy evidence of active disease- as
determined by WHO classification (levels III,
IV, V, or VI) OR
3. If failing' to improve in renal function after 6
months of high dose prednisolone

51. Clinical
Manifestations
Pre Post
% %
Constitutional 86 18
Mucocutanous rash 68 36
Alopecia 50 4.5
Arthralgia/arthritis 81.8 31.8
Raynaud’s phe. 4.5 0
Pericardial effusion 27 4.5
Lymphadenopathy 31.8 0
Hematological 63.6 27
Neuropsychiatric 13.6 9
Hematuria 54.5 31.8
Proteinuria 90.9 50
NS 63.6 31.8
Hypertension 31.8 31.8
Renal insufficiency 9 9

52. Chemical Pre Post Normal
BUN 17.4 13.95 <18
Cr 0.8 0.7 <1
WBC 5.45 6.05 4-10.5
Hct 29.95 36.09 36-48
Plts 257.46 283.55 140-440
CRP 3.68 1.86 <0.8
ESR 71.06 29.6 1-20
C3 50.27 92.92 >85
C4 7.7 14.015 >14
dsDNA 973.6 468.96 <25
U-Protein 1329.7 752.8 10-150
Creatinine Clearanc 107.86 122.6 >80

53. Renal biopsies pre & post Tx
Biopsy Pre Post
WHO Class
5 9.5% 63.6%
4 66.7% 0%
3 0% 36.4%
2 0% 18.2%
Activity
Severe 42.8% 0%
Moderate 71.4% 0%
Mild 28.6% 37.5%
No 0% 62.5%
Chronicity
Severe 0% 0%
Moderate 0% 0%
Mild 28.6% 44.4%
No 71.4% 55.5%

54. The Chronic Phase:
Maintenance Treatment
Corticosteroids.
Cytotoxic Agents.
Cyclosporine.
Intravenous Gamma Globulin.
Total lymphoid irradiation
Nonsteroidal anti-inflammatory
Thromboxane synthetase inhibitors
Fish Oil and Dietary Fat

55. When Can We Stop Treatment
in Lupus Nephritis?
Goal: suppression of disease with minimum
side effects
Repeat renal biopsies
Stable renal function,
Lack of proteinuria, and normal
immunologic tests are signs of success.