1. No history of arthritis Significant cardiomegaly on chest x-ray
** You are asked to see a 24 y/o female with fatigue, myalgias, and a positive ANA. Which of the following would NOT be consistent with SLE?
The positive ANA confirms the diagnosis so no further evaluation is necessary
Pancytopenia
A history of a transient episode of confusion followed by numbness and tingling in the right arm
No history of arthritis
Significant cardiomegaly on chest x-ray

2. Immune Mediated Disease
Etiology - unknown
Multiple organ system involvement
Immune complexes
ANA
Complement
Other antibodies
Treatment - usually corticosteroids

3. Facial rash

6. Systemic Lupus Erythematosus
Multisystem disease - young female
Antigen-antibody complexes
positive ANA, dsDNA, complement
Common problems
Arthritis, dermatitis, hematologic, renal, polyserositis, CNS, splenomegaly
Treatment - corticosteroids

7. Lupus Demographics young women 5:1 over men ages - 15 - 40
Relatively uncommon – 50/100,000 individuals % population
Males, Afro-Americans (increased Sm/RNP), Hispanics have worse prognosis
Genetic factors – variable
High prevalence among twins
5-12% cumulative incidence among first-degree relatives
HLA Class II (multiple associations) and C4a null alleles

8. Typical findings
Skin - butterfly rash, alopecia, photosensitivity, mucosal ulcerations
Arthritis - 90%, symmetrical
CNS %
focal vs. general, headache most common
Serositis - pericardial, pleural, peritoneal
CV – Increased incidence of atherosclerotic plaques
Splenomegaly

9. Vasculitis of fingers

10. Chest xray

11. Atherosclerotic plaque (controls vs. SLE patients)
(controlled for corticosteroid use)
NEJM 349:2003,

12. Immunofluorescence of glomerulus

13. SLE - Renal Disease – 50% (acute vs chronic)
Normal - I
Minimal change - IIA
Mesangial - IIB
Focal Proliferative - III
Diffuse Proliferative - IV
Membranous - V
Sclerosis - VI
WHO Classification

14. Diffuse Proliferative
Focal Proliferative
Membranous
Mesangial

15. SLE - Classification criteria (4 of 11 criteria should be present)
Malar rash
Discoid rash
Photosensitivity
Oral Ulcers
Arthritis
Serositis
Renal disorder
Neurologic disorder
Hematologic disorder
Immunologic disorder
ANA positive
1997 update of the 1982 revision of the ACR classification criteria for SLE

16. or
APL antibody
MS Core

19. Systemic Lupus - Laboratory Findings
Serology
ANA - 95% (nDNA 50%, Sm 50%)
Rheumatoid factor %
Complement %
CBC
Leukopenia - 50%
Anemia %
Thrombocytopenia %

20. Autoantibodies in Rheumatic Diseases
SLE
DS DNA, Sm
Drug induced SLE
Histone
SCLE
Anti Ro (SS-A)
MCTD
RNP
Scleroderma
Scl-70
CRST
Centromere
Polymyositis/Dermatomyositis
Jo-1 (histadyl tRNA synthetase)
Sjogren’s Syndrome
SS-A, SS-B
Wegener’s Granulomatosis
cANCA (Proteinase 3)
See appendix for more information

21. Outdated
ANA – four types

22. Lupus Erythematosus - Subtypes
SLE - systemic
Discoid – relatively benign (skin and joints)
SCLE - subacute cutaneous
anti-Ro antibody positive
neonatal lupus / congenital heart block
Drug induced – anti-histone antibody
Anti-phospholipid antibody syndrome

23. Discoid lupus rash

27. Drug-Induced Lupus Major drug associations Less common associations
Hydralazine
Procainamide
Less common associations
Alpha methyldopa, Diphenylhydantoin, PTU, PCN, Sulfa, INH, BCP, Minocycline, anti-TNF
Antibody association
Anti-histone antibody

28. Anti-phospholipid Syndrome - lupus anticoagulant / anticardiolipin antibody
Increased clotting
Screening PTT, False + VDRL
Associated with SLE - 30% of cases
Anti-cardiolipin antibody may be present
Treatment - anticoagulation

29. Anti-phospholipid Syndrome Classification criteria
One clinical and one lab criteria must be found
Clinical (either of following)
Vascular thrombosis – one or more episodes of arterial, venous, or small vessel thrombosis
Pregnancy morbidity
Late term (>10 wk) abortion (normal fetus)
Premature birth (<34 week) with preeclampsia, eclampsia, or placental insufficiency
Three or more spontaneous abortions (<10 weeks) without other explanation
Abnormal lab (either test)
Anticardiolipin antibody (IgG or IgM) X2 twelve weeks apart and not more than 5 years previously (must be moderate or high titer)
Anti-β2 glycoprotein (IgM or IgG) - >99%ile
Lupus anticoagulant (prolonged PTT with failure to correct) x2 twelve weeks apart

31. Infarcts of pinna

33. SLE - treatment Nonsteroidals
Corticosteroids - major organ dysfunction
Antimalarials - Hydroxychloroquine skin and joint manifestations (minor organ systems)
Cytotoxics (CTX) - major renal involvement
high dose monthly IV ( mg/m2) OR
Daily oral ( mg/d)
Mycophenolate mofetil

34. Mycophenolate Mofetil (MMF)
Inhibits lymphocyte proliferation (both B and T cells)
Inhibits glycosylation of adhesion molecules
Relatively non toxic

35. Prognosis SLE
95% 10 year survival

36. No history of arthritis Significant cardiomegaly on chest x-ray
You are asked to see a 24 y/o female with fatigue, myalgias, and a positive ANA. Which of the following would NOT be consistent with SLE?
The positive ANA confirms the diagnosis so no further evaluation is necessary
Pancytopenia
A history of a transient episode of confusion followed by numbness and tingling in the right arm
No history of arthritis
Significant cardiomegaly on chest x-ray

37. Positive VDRL test for syphilis History of previous miscarriage
A 18 y/o female presents with a five month history of joint complaints, easy bruisibility, pain with breathing on the left side, and occasional weakness in the left hand and right foot. Which of the following would you NOT expect to find on further evaluation?
Positive VDRL test for syphilis
History of previous miscarriage
Recurrent oral ulcerations
3+ proteinuria on UA
History of allergy to multiple medications