SYSTEMIC LUPUS ERYTHEMATOSUS

OUTLINE

Definition
Epidemiology
Pathophysiology
Classification and diagnosis
Clinical Features
Lupus related syndromes
Treatment
Prognosis
DEFINITION

Inflammatory autoimmune disorder affecting

multiple organ systems characterized by the
production of autoantibodies directed against
cell nuclei
EPIDEMIOLOGY

Prevalence influenced by age, gender, race,

and genetics
Prevalence: 1:2000
Peak incidence 14-45 years
Black > White (1:250 vs. 1:1000)
Female predominance 10:1
HLA DR3 association, Family History
Severity is equal in male and female
Etiology

Genetic (HLA DR3 association)

Abnormal immune response
Environmental
UV
Viruses
Hormones (Estrogen)
PATHOPHYSIOLOGY
CLINICAL FEATURES: Mucocutaneous

Malar Rash (butterfly erythema) Vasculitic ulceration

Discoid rash Oral ulceration
Photosensitive rash
Nasal septal perforation
Subacute cutaneous LE
Livedo reticularis
Nailfold capillary
Alopecia
changes
Raynauds
MALAR RASH

Fixed erythema, flat or raised, over the

malar eminences
Tending to spare the nasolabial folds
 DISCOID RASH

Erythematous raised
patches with adherent
keratotic scaling and
follicular plugging;
Atrophic scarring may
occur in older lesions
Alopecia
Subacute Cutaneous Lupus
Acute Cutaneous: Malar Rash Chronic Cutaneous:Discoid
Note Sparing of Nasolabial Folds Note Scarring, Hyperpigmentation
Follicular Plugging Livedo Reticularis

ACR
 ORAL ULCERS

Oral or nasopharyngeal
ulceration
Usually painless,
observed by a physician
 SLE - VASCULOPATHY

Small vessel
vasculitis
Raynauds
phenomenon
Antiphospholipid
antibody syndrome
CLINICAL FEATURES: Musculoskeletal

Arthritis is NONEROSIVE, transient,

symmetrical, affecting small joints, seldom
deforming, less severe than RA

Most common presenting feature of SLE

Jaccouds Arthopathy: Nonerosive, Reducible Deformities
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
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
CLINICAL FEATURES: PLEUROPULMONAR

Pleuritis/Pleural effusion
Infiltrates/ Discoid Atelectasis
Acute lupus pneumonitis
Pulmonary hemorrhage
Shrinking lung - diaphragm dysfunction
Restrictive lung disease
CLINICAL FEATURES: Cardiac

Pericarditis in majority of patients

Libman Sacks endocarditis
Cardiac failure
Cardiac Arrythmias-common
Valvular heart disease
Coronary Artery Disease
 Lupus - Endocarditis

Noninfective thrombotic endocarditis involving mitral valve in SLE.

Note nodular vegetations along line of closure and extending onto chordae tendineae.
CLINICAL FEATURES: HEMATOLOGIC
DISORDER

A) Hemolytic anemia - with reticulocytosis

OR
B) Leukopenia - less than 4,000/mm3 total on 2 or more
occasions
OR
C) Lymphopenia - less than 1,500/mm3 on 2 or more
occasions
OR
D) Thrombocytopenia - less than 100,000/mm 3 in the
absence of offending drugs
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
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.
CLINICAL FEATURES: Renal (Lupus Nephritis)

Usually asymptomatic
Gross hematuria
Nephrotic syndrome
Acute renal failure
Hypertension
End stage renal failure
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
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
Laboratory Findings

Complete blood count

Anemia
Leukopenia
Lymphopenia
Thrombocytopenia

Urine Analysis
Hematuria
Proteinuria
Granular casts
Immunological findings

ANA - 95-100%-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
 CLASSIFICATION

THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLE

1. Malar rash 9. Hematologic disorders.

2. Discoid rash Hemolytic anemia
3. Photosensitivity Leukopenia (< 4000/uL)
4. Oral ulcers Lymphopenia (< 1500/uL)
5. Arthritis Thrombocytopenia
6. Serositis (< 100,000/uL)
7. Renal disease. 10. Immunologic abnormalities.
> 0.5 g/d proteinuria Positive LE cell
3+ dipstick proteinuria Anti-ds- DNA
Cellular casts Anti- Sm
8. Neurologic disease. Any antiphospholipid
Seizures 11. Positive ANA ( 95-100% )
Psychosis (without other cause)
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
DIFFERENTIAL DIAGNOSIS

Almost too broad to consider given number of

clinical manifestations
Rheumatic: RA, Sjogrens syndrome, systemic
sclerosis, dermatomyositis
Nonrheumatic: HIV, endocarditis, viral infections,
hematologic malignancies, vasculitis, ITP, other
causes of nephritis
Overlap Syndrome (UCTD, MCTD)
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
 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
LUPUS RELATED SYNDROMES

Raynauds Syndrome:
-Not part of the diagnostic criteria for SLE
- Does NOT warrant ANA if no other clinical
evidence to suggest autoimmune disease
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
 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
 TREATMENT

Antiphospholipid Syndrome
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
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
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