1. ANA Testing
Carrie Marshall
1/18/08 1

2. Systemic Lupus Erythematosus Azami Ahad.MD Rheumatologist 92/9/30

3. What is SLE?
Prototypic autoimmune disease- loss of immune distinction between self and foreign
Combination of a genetically susceptible individual exposed to an environmental trigger
Tissue damage occurs by the deposition of autoantibodies in target tissues triggering inflammation.

4. Demographics of SLE 10/1 prevalence in females versus males
3-4/1 prevalence in African Americans and Hispanics compared to Caucasians
Occurs in up to 1% of young black women and is one of the leading causes of natural death in this group
Incidence has more than doubled in the last 20 years
Morbidity and mortality is markedly higher in African Americans and Hispanics compared to Caucasians

5. Immune system alterations in SLE
T cell abnormalities
B cell abnormalities and autoantibody production
Monocyte and macrophage abnormalities
Defect in immune regulation
Abnormality in apoptosis

8. SLE IMMUNOLOGY
Anti-DNA
Anti-
SSA
Anti-SSB
Anti-RNP
Anti-
DNA

9. PATHOPHYSIOLOGY Prototype multi-system autoimmune disease
Immune complexes & auto-antibodies
Always consider drug induced lupus:
hydralazine
phenytoin  anti-histone antibodies
minocycline
Spectrum:
arthralgias, rash, ANA  multisystem dysfunction
Fluctuating course with periods of quiescence
Spontaneous remission in 20%

10. Wallace in Arthritis and Allied Conditions, 13th Ed V2, p1319,
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

11. SCENARIOS “The Dwindles”: fatigue, muscle/joint pain
Unexplained single organ disease
Skin disease:
Discoid lupus
Subacute cutaneous lupus (anti-Ro/SSA antibody)
Pleural/pericardial effusion
Young stroke
Nephrotic syndrome  ARF  CRF
Complicated pregnancy:
Multiple miscarriages
Intra-uterine growth retardation (IUGR)
Pregnancy induced hypertension/eclampsia

12. SCENARIOS Unexplained multi-organ disease
Fever of Unknown Origin (FUO)
Pulmonary renal syndrome
Multi-organ dysfunction/failure
Unexplained laboratory abnormalities
Hemolysis
Leuko-/lymphopenia
Thrombocytopenia
Hypoalbuminemia
ANA +

14. Malar rash- note nasolabial sparing

15. Malar rash with discoid features

16. Malar rash again with nasolabial sparing

17. Lupus rash in sun exposed areas (photosensitivity)

18. Lupus alopecia

19. Vasculitic rash of the hand in lupus

20. Subacute cutaneous lupus associated with anti-Ro antibodies

21. Rash in neonatal lupus- will fade as mom’s antibodies are cleared

22. Vesicular rash from lupus- lupus can do anything in the skin

23. Lupus band test- IgG deposition at the dermal/epidermal interface

24. Oral ulcers in a patient with lupus- note hard palate location

26. Jaccoud’s arthropathy in lupus- joint deformities are reducible-no erosions

27. Libman Sachs endocarditis in lupus- sterile deposits usually mitral valve

28. Systemic Lupus Erythematosus: Renal Histology
Normal Light Microscopy, but Immunoglobin or Complement Protein Deposits Present
Mesangial Lupus Nephritis
Mild Focal Glomerulonephritis
Diffuse Proliferative Glomerulonephritis
Membranous Glomerulonephritis
Interstitial and Tubular Nephritis
ACR

29. Renal Disease in Lupus
Renal disease is the leading determinant of morbidity and mortality in SLE
Vast majority of renal disease is WHO Class III or IV proliferative nephritis
African Americans with lupus nephritis have a 5-10 fold increased risk of renal failure compared to age/sex matched Caucasians despite similar treatment

30. Glomerular staining with anti-IgG indicating immune complexes

31. SLE: Nervous System Disorders
Seizures Ataxia
Headache Rigidity, Tremor
Stroke Syndromes Chorea
Transverse Myelitis Aseptic Meningitis
Coma Psychiatric Disorders
Dementia
ACR

32. Choroid bodies in a patient with SLE

33. Retinal vasculitis with hemorrhage- associated with CNS lupus

34. Large infarct in a patient with CNS lupus

35. LE cells are dropped and anti-phospholipid antibodies added

36. Review of antibody structure- emphasize importance of Fc complement fixation and Fc
Receptor binding

38. Laboratory Evaluation of SLE
Screening test is the ANA (antinuclear antibody) which is positive in >95% of patients with SLE
Four patterns- speckled, homogeneous, rim and nucleolar (seen in scleroderma)
The speckled pattern is associated with antibodies to Sm, RNP, Ro and La
The rim pattern is associated with antibodies to double stranded DNA

39. Laboratory (continued)
Antibodies to Sm are felt to be specific for SLE- if you have them you have lupus
Anti-RNP antibodies are seen in lupus and mixed connective tissue disease
Anti-Ro and La antibodies are seen in SLE and in Sjogrens syndrome

40. Laboratory Monitoring of Disease Activity
The serum tests useful for following lupus disease activity are anti-dsDNA antibodies and complement levels (C3-C4 or CH50).
In some patients anti-dsDNA antibody levels parallel disease activity
With active disease complement proteins are consumed thus serum C3, C4 and CH50 decrease

41. Laboratory Monitoring (Continued)
CBCs are useful to monitor for development of Coombs positive hemolytic anemia as well as immune neutropenia and immune mediated thrombocytopenia
Urine analysis will demonstrate increased proteinuria and an active sediment (RBCs, WBCs and casts) with active lupus nephritis
All of these measures should improve with therapy