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)

• Discoid rash

• Photosensitive rash

• Subacute cutaneous LE

• Livedo reticularis

• Alopecia

• Raynaud’s

• Vasculitic ulceration

• Oral ulceration

• Nasal septal perforation

• Nailfold capillary changes

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 RashNote Sparing of Nasolabial Folds

Chronic Cutaneous:DiscoidNote Scarring, Hyperpigmentation

Follicular Plugging Livedo Reticularis

ACR

ORAL ULCERS

• Oral or nasopharyngeal ulceration

• Usually painless, observed by a physician

SLE - VASCULOPATHY

• Small vessel vasculitis

• Raynaud’s 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

Jaccoud’s 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 reticulocytosisOR

B) Leukopenia - less than 4,000/mm3 total on 2 or more occasions

ORC) Lymphopenia - less than 1,500/mm3 on 2 or more

occasionsOR

D) Thrombocytopenia - less than 100,000/mm3 in the absence of offending drugs

Behavior/Personality changes, depressionCognitive dysfunctionPsychosisSeizuresStrokeChoreaPseudotumor cerebriTransverse myelitisPeripheral neuropathyTotal of 19 manifestations describedTotal of 19 manifestations described

May be difficult to distinguish from steroid psychosis or primary psychiatric disease

CLINICAL FEATURES: Neurologic

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.

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

CLINICAL FEATURES: Renal (Lupus Nephritis)

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

1. Malar rash 2. Discoid rash3. Photosensitivity4. Oral ulcers5. Arthritis6. Serositis7. Renal disease.

> 0.5 g/d proteinuria ≥ 3+ dipstick proteinuria Cellular casts

8. Neurologic disease. SeizuresPsychosis (without other cause)

9. Hematologic disorders. Hemolytic anemiaLeukopenia (< 4000/uL) Lymphopenia (< 1500/uL) Thrombocytopenia (< 100,000/uL)

10. Immunologic abnormalities. Positive LE cell Anti-ds- DNAAnti- SmAny antiphospholipid

11. Positive ANA ( 95-100% )

THE 1982 REVISED CRITERIA FOR CLASSIFICATION OF SLE

CLASSIFICATION CRITERIA

• Must have 4 of 11 for Classification• Sensitivity 96%Sensitivity 96%

• Specificity 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, Sjogren’s 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

Raynaud’s 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