SYSTEMIC LUPUS ERYTHEMATOSUS

Manal Al Mashaleh

SYSTEMIC LUPUS ERYTHEMATOSUS

Autoimmune multisystem disease characterized by widespread inflammation and production of autoantibodies

This means wide spectrum of presentations

EPIDEMIOLOGY

Age:peak 15-40 years but any age can be affected

Sex :more women affected ,10:1 during childbearing age

Clinical features

General Severe fatigue Fever Weight loss Anorexia Lymphadenopathy

Dermatological features

MALAR RASH

Fixed erythema, flat or raised, over the malar eminences

Tending to spare the nasolabial folds

30-60 %

MALAR RASH

Photosensitivity

Rash over the sun exposed areas.Face,neck and V shaped area of chest.See rash varies in severity depending on exposure.Less under the orbit protected areas.

Discoid lupus

Erythematous hyper pigmented margins and flat scarred hypo pigmented centers

This can be seen in SLE and pure cutaneous lupus

DISCOID RASH

Erythematous raised patches with adherent keratotic scaling and follicular plugging

Atrophic scarring may occur in older lesions

Subacute Cutaneous Lupus

Acute Cutaneous: Malar RashNote Sparing of Nasolabial Folds

Chronic Cutaneous:DiscoidNote Scarring, Hyperpigmentation

Livedo Reticularis

SLE - VASCULOPATHY

Small vessel vasculitis

Raynaud’s phenomenon

Antiphospholipid antibody syndrome

Alopecia

Oral lesions of SLE

Erythema of hard and soft palate, papules ,vesicles and petechiae

Erythematous rash of the tongue.

Oral Ulcers

Oral or nasopharyngeal ulceration, usually painless, observed by physician

SLE ARTHROPATHY

Non erosive arthritis Hand may show

diffuse soft tissue swelling,ulnar deviation,swan neck deformity,MCP subluxation.

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

Ocular

ConjunctivitisPhotophobiaMonocular blindness transient or permanentBlurred visionCotton-Wool spots on retina due to occlusion retinal blood vessels

Serositis

Pleuritis : convincing history of pleuritic pain ,pleural

rub heard by a physician or evidence of pleural effusion or

Pericarditis: documented by ECG ,pericardial rub or

evidence of pericardial effusion

Pulmonary

Pleuritis the most common 30% in life time of SLE patient

Peumonitis, pulmonary embolism, pulmonary hypertension

Pulmonary hemorrhage: 50 % mortality with treatment

Cardiovascular

Pericarditis the most common Aortic insufficiency the most common

valvular lesion Endocarditis antibiotic prophylaxis indicated for

dental and surgical procedures Accelerated atherosclerosis with 10

times higher mortality from myocardial infarction from age and sex matched

Lupus - Endocarditis

Noninfective thrombotic endocarditis involving mitral valve in SLE.

Note nodular vegetations along line of closure and extending onto chordae tendineae

(libman_sacks syndrome).

Renal

50% of all lupus patients will have kidney involvement during their life

of these, 50 % will have serious kidney disease

Persistent proteinuria greater than 0.5 grams per day or greater than 3+

Cellular casts--may be red cell, hemoglobin, granular, tubular, or mixed

Impaired kidney function Lupus nephritis predict out come

(prognosis) Major cause of mortality

How does lupus damage the kidneys?

Autoantibodies are formed against antigens in the glomerulus basement membrane

Circulating immune complexes bind to the basement membrane of the glomeruli

These result in inflammation of the glomeruli (glomerulonephritis)

How does lupus damage the kidneys?

The basement membrane is damaged by the inflammation

Appearance of protein, white and red blood cells and ‘casts’ in the urine

Low albumin levels in the blood resulting in leakage of fluid from the vessels into the tissues (edema)

Accumulation of waste proteins (uremia) Hypertension

Do I really need a biopsy?

Most likely - YES

Kidney biopsies are important to dictate how to treat predict how long to treat predict the chance for kidney function recovery

The biopsy helps determine treatment

Inflammation can occur: Diffuse Focal

Types of Lupus Nephritis

6 classes based on a WHO classification

Class I (normal) mild

Class II (mesangial) mild

Class III (focal proliferative glomerulonephritis) moderately severe

Class IV (diffuse proliferative glomerulonephritis) severe Class V (membranous glomerulonephritis) Class VI (glomerulosclerosis) irreversible changes

Neurological

Seizures & Psychosis

in the absence of offending drugs or known metabolic derangements; e.g., uremia, ketoacidosis, or electrolyte imbalance

Cranial nerve lesions

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

Complete blood count

Hemolytic anemia--with reticulocytosis Leukopenia :less than 4,000/mm total on 2

or more occasions

Lymphopenia: less than 1,500/mm on 2 or more occasions

Thrombocytopenia: less than 100,000/mm, in the absence of offending drugs

Immunological findings

ANA - 95-100%-sensitive but not specific for SLE

Anti -ds DNA-specific(60%) 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 Lupus anticoagulant Anti-B2 glycoprotein 1 AB Anti-cardiolipin

Depressed serum complement ESR , CRP

CXR

Pleural effusion and pleural thickening Pericardial effusion,cardiomegaly Lung infiltrate from infection,pulmonary

embolism,Peumonitis,Interstitial lung disease or hemorrhage

CLASSIFICATION

1. Malar rash 2. Discoid rash3. Photosensitivity4. Oral ulcers5. Arthritis6. Serositis7. Renal disease. 8. Neurologic disease.

9. Hematologic disorders: -Hemolytic anemia -Leukopenia (Lymphopenia) -Thrombocytopenia 10. Immunologic

abnormalities: -Anti-ds- DNA -Anti- Sm -Antiphospholipid -False +ve VDRL

11. Positive ANA

CRITERIA FOR CLASSIFICATION OF SLE

CLASSIFICATION CRITERIA

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

Not all “Lupus” is SLE Discoid Lupus Drug induced lupus Subacute Cutaneous Lupus

DIFFERENTIAL DIAGNOSIS

Rheumatic: RA, Sjogren’s syndrome, systemic sclerosis, dermatomyositis

Nonrheumatic: HIV, endocarditis, viral infections, hematologic malignancies, vasculitis, ITP, other causes of nephritis

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

SLE – treatment I.

Mild cases (mild skin or joint involvement): NSAID, local treatment, hydroxy-chloroquine

Cases of intermediate severity (serositis, cytopenia, marked skin or joint involvement):

corticosteroid , azathioprine, methotrexate

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

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

TREATMENT

ESR, CRP probably useful as general markers of disease activity

Complement and anti-DNA antibodies may correlate to disease activity

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