1. SYSTEMIC LUPUS ERYTHEMATOSUS

2. OUTLINE Definition Epidemiology Pathophysiology
Classification and diagnosis
Clinical Features
Lupus related syndromes
Treatment
Prognosis

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

4. EPIDEMIOLOGY Prevalence influenced by age, gender, race, and genetics
Peak incidence years
Black > White (1:250 vs. 1:1000)
Female predominance 10:1
HLA DR3 association, Family History
Severity is equal in male and female

5. Etiology Genetic (HLA DR3 association) Environmental
Abnormal immune response
Environmental UV
Viruses
Hormones (Estrogen)

6. PATHOPHYSIOLOGY

7. 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

8. MALAR RASH Fixed erythema, flat or raised, over the malar eminences
Tending to spare the nasolabial folds

10. DISCOID RASH
Erythematous raised patches with adherent keratotic scaling and follicular plugging;
Atrophic scarring may occur in older lesions

11. Alopecia

12. Subacute Cutaneous Lupus

14. Acute Cutaneous: Malar Rash
Note Sparing of Nasolabial Folds
Chronic Cutaneous:Discoid
Note Scarring, Hyperpigmentation

15. Follicular Plugging Livedo Reticularis
ACR

16. ORAL ULCERS Oral or nasopharyngeal ulceration
Usually painless, observed by a physician

17. SLE - VASCULOPATHY Small vessel vasculitis Raynaud’s phenomenon
Antiphospholipid antibody syndrome

18. CLINICAL FEATURES: Musculoskeletal
Arthritis is NONEROSIVE, transient, symmetrical, affecting small joints, seldom deforming, less severe than RA
Most common presenting feature of SLE

19. Jaccoud’s Arthopathy: Nonerosive, Reducible Deformities

20. CLINICAL FEATURES: Musculoskeletal
Synovitis-90% patients, often the earliest sign
Osteoporosis
From SLE itself and therapy (usually steroids)
Osteonecrosis (avascular necrosis)
Can occur with & without history of steroid therapy

22. CLINICAL FEATURES: Ocular
Conjunctivitis
Photophobia
Monocular blindness-transient or permanent
Blurred vision
Cotton-Wool spots on retina-degeneration nerves fibers due to occlusion retinal blood vessels

23. CLINICAL FEATURES: PLEUROPULMONAR
Pleuritis/Pleural effusion
Infiltrates/ Discoid Atelectasis
Acute lupus pneumonitis
Pulmonary hemorrhage
“Shrinking lung” - diaphragm dysfunction
Restrictive lung disease

24. CLINICAL FEATURES: Cardiac
Pericarditis –in majority of patients
Libman Sacks endocarditis
Cardiac failure
Cardiac Arrythmias-common
Valvular heart disease
Coronary Artery Disease

25. Lupus - Endocarditis
Noninfective thrombotic endocarditis involving mitral valve in SLE.
Note nodular vegetations along line of closure and extending onto chordae tendineae.

26. CLINICAL FEATURES: HEMATOLOGIC DISORDER
A) Hemolytic anemia - with reticulocytosis OR
B) Leukopenia - less than 4,000/mm3 total on 2 or more occasions
C) Lymphopenia - less than 1,500/mm3 on 2 or more occasions
D) Thrombocytopenia - less than 100,000/mm3 in the absence of offending drugs

27. CLINICAL FEATURES: Neurologic
Behavior/Personality changes, depression
Cognitive dysfunction
Psychosis
Seizures
Stroke
Chorea
Pseudotumor cerebri
Transverse myelitis
Peripheral neuropathy
Total of 19 manifestations described
May be difficult to distinguish from steroid psychosis or primary psychiatric disease

28. CLINICAL FEATURES: Renal (Lupus Nephritis)
Develops in up to 50% of patients
10% SLE patients go to dialysis or transplant
Hallmark clinical finding is proteinuria
Advancing renal failure complicates assessment of SLE disease activity
Nephritis remains the most frequent cause of disease-related death.

29. CLINICAL FEATURES: Renal (Lupus Nephritis)
Usually asymptomatic
Gross hematuria
Nephrotic syndrome
Acute renal failure
Hypertension
End stage renal failure

30. WHO CLASSIFICATION OF LUPUS NEPHRITIS
Class I Normal
Class II Mesangial
IIA Minimal alteration
IIB Mesangial glomerulitis
Class III Focal and segmental proliferative glomerulonephritis
Class IV Diffuse proliferative glomerulonephritis
Class V Membranous glomerulonephritis
Class VI Glomerular sclerosis

31. CLINICAL FEATURES: Gastrointestinal & Hepatic
Uncommon SLE manifestations
Severe abdominal pain syndromes in SLE often indicate mesenteric vasculitis, resembling medium vessel vasculitis (PAN)
Diverticulitis may be masked by steroids
Hepatic abnormalities more often due to therapy than to SLE itself

32. Laboratory Findings Complete blood count Urine Analysis Anemia
Leukopenia
Lymphopenia
Thrombocytopenia
Urine Analysis
Hematuria
Proteinuria
Granular casts

33. Immunological findings
ANA %-sensitive but not specific for SLE
Anti -ds DNA-specific(60%)-specific for SLE, but positive to other non lupus conditions
4 RNA associated antibodies
Anti-Sm (Smith)
Anti Ro/SSA-antibody
Anti La/SSB-antibody
Anti-RNP
Antiphospholipid antibody
Biologic false + RPR
Lupus anticoagulant-antibodies tocoagulation factors. risk factor for venous and arterial thrombosis and miscarriage. Prolonged aPTT
Anti-cardiolipin
Depressed serum complement
Anti hystones antibodies

34. THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLE
1. Malar rash
2. Discoid rash
3. Photosensitivity
4. Oral ulcers
5. Arthritis
6. Serositis
7. Renal disease.
> 0.5 g/d proteinuria
≥ 3+ dipstick proteinuria
Cellular casts
8. Neurologic disease.
Seizures
Psychosis (without other cause)
9. Hematologic disorders.
Hemolytic anemia
Leukopenia (< 4000/uL)
Lymphopenia (< 1500/uL)
Thrombocytopenia
(< 100,000/uL)
10. Immunologic abnormalities.
Positive LE cell
Anti-ds- DNA
Anti- Sm
Any antiphospholipid
11. Positive ANA ( % )

35. CLASSIFICATION CRITERIA
Must have 4 of 11 for Classification
Sensitivity 96%
Specificity 96%
Like RA, diagnosis is ultimately clinical
Not all “Lupus” is SLE
Discoid Lupus
Overlap syndrome
Drug induced lupus
Subacute Cutaneous Lupus

36. DIFFERENTIAL DIAGNOSIS
Almost too broad to consider given number of clinical manifestations
Rheumatic: RA, Sjogren’s syndrome, systemic sclerosis, dermatomyositis
Nonrheumatic: HIV, endocarditis, viral infections, hematologic malignancies, vasculitis, ITP, other causes of nephritis
“Overlap Syndrome” (UCTD, MCTD)

37. LUPUS RELATED SYNDROMES
Drug Induced Lupus
Classically associated with hydralazine, isoniazid, procainamide
Male:Female ratio is equal
Nephritis and CNS abnormalities rare
Normal complement and no anti-DNA antibodies
Symptoms usually resolve with stopping drug

38. LUPUS RELATED SYNDROMES
Antiphospholipid Syndrome (APS)
Hypercoagulability with recurrent thrombosis of either venous or arterial circulation
Thrombocytopenia-common
Pregnancy complication-miscarriage in first trimester
Lifelong anticoagulation warfarin is currently recommended for patients with serious complications due to common recurrence of thrombosis
Antiphospholipid Antibodies
Primary when present without other SLE feature.
Secondary when usual SLE features present

39. LUPUS RELATED SYNDROMES
Raynaud’s Syndrome:
-Not part of the diagnostic criteria for SLE
- Does NOT warrant ANA if no other clinical evidence to suggest autoimmune disease

40. SLE – treatment I.
Mild cases (mild skin or joint involvement): NSAID, local treatment, hydroxy-chloroquin
Cases of intermediate severity (serositis, cytopenia, marked skin or joint involvement): corticosteroid (12-64 mg methylprednisolon), azathioprin, methotrexat

41. SLE – treatment II.
Severe, life-threatening organ involvements (carditis, nephritis, systemic vasculitis, cerebral manifestations): high-dose intravenous corticosteroid + iv. cyclophosphamide + in some cases: plasmapheresis or iv. immunoglobulin, or, instead of cyclophosphamide: mycophenolate mofetil (not registered in the EU)
Some cases of nephritis (especially membranous), myositis, thrombocytopenia: cyclosporine

43. TREATMENT Antiphospholipid Syndrome Lupus and Pregnancy
Anticoagulation with warfarin (teratogenic)
subcutaneous heparin and aspirin is usual approach in pregnancy
Lupus and Pregnancy
No longer “contraindicated”
No changes in therapy other than avoiding fetal toxic drugs
Complications related to renal failure, antiphospholipid antibodies, SSA/SSB

44. TREATMENT
ESR, CRP probably useful as general markers of disease activity
Complement and anti-DNA antibodies may correlate to disease activity but often impractical turnaround time from lab
Patient history

45. PROGNOSIS Unpredictable course 10 year survival rates exceed 85%
Most SLE patients die from infection, probably related to therapy which suppresses immune system
Recommend smoking cessation, yearly flu shots, pneumovax q5years, and preventive cancer screening recommendations