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Systemic Lupus Erythematosus

Joko AnggoroBagian Ilmu Penyakit DalamFK Unram/RSUP NTB

WHAT IS LUPUS?

Lupus or SLE is inflammatory autoimmune disease that can affect the skin, joints, kidneys, lungs, nervous system, and other organs of the body.

Lupus is Latin for wolf, and "erythro" is derived from ερυθρός, Greek for "red." All explanations originate with the reddish, butterfly-shaped malar rash that the disease classically exhibits across the nose and cheeks.

Systemic Lupus Erythematosus (SLE)

Inflammatory autoimmune disease of unknown etiology

Morbidity Disease associated Corticosteroid associated

• Corticosteroid use as high as 89% 1-2

Mortality 5-10% at 10 years Early - active disease and infections Late - atherosclerosis1. Zonana-Nacach et al., 2000 2. Urowitz et al., ACR meeting 2000 (Abstract)

Background

Lupus affects 10 times as

many women as men.

Treatment depends on the

symptoms and their severity.

Because it is a complex

disease, lupus requires

treatment by a rheumatologist

and the patient’s active

participation in working

towards good health.

Several kinds of lupus

1. Systemic lupus erythematosus (SLE). The word “systemic”

means the disease can affect many parts of the body.

2. Discoid lupus erythematosus is a chronic skin disorder in which a

red, raised rash appears on the face, scalp, or elsewhere.

3. Subacute cutaneous lupus erythematosus refers to skin lesions

that appear on parts of the body exposed to sun.

4. Drug-induced lupus is a form of lupus caused by medications.

5. Neonatal lupus is a rare disease that can occur in newborn babies

of women with SLE, Sjögren’s syndrome, or no disease at all.

Aetiology

The cause is unknown but there are several predisposing factors:- Heredity

- Genetics - Complement - Sex hormone status

Premenopausal women are most frequently affected.

- Immunological factors Loss of ‘self-tolerance has several consequences

- Environmental tiggers

Immunological factors

B cell activation results in increased autoantibody (mainly IgG) production to a variety (up to 2000) of antigens (nuclear, cytoplasmic and plasma menbrane), e.g. ANA, anti-dsDNA.

Development of and failure to remove immune complexes from the circulation leads to deposition of complexes in the tissue, causing vasculitis and disease (e.g. glomerulonephritis).

There is impaired T cell regulation of the immune response.

There is abnormal cytokine production (IL-1 and IL-2), although its exact role in the pathogenesis is unknown. IL-6 and IL-10 levels are often reised.

TNF-α promoters have also been linked to SLE.

Environmental triggers

Drugs such as hydralazine, methyldopa, isoniazid, D-penicillamine and minocycline can induce lupus not associated with anti-dsDNA. Flare-ups can be induced by the contraceptive pill and hormone replacement therapy (HRT).

Ultraviolet light is another well-recognized trigger.

Model of SLE pathogenesis

Common Symptoms of Lupus Painful or swollen joints and muscle pain Unexplained fever Red rashes, most commonly on the face Chest pain upon deep breathing Unusual loss of hair Pale or purple fingers or toes from cold or stress (Raynaud’s

phenomenon) Sensitivity to the sun Swelling (edema) in legs or around eyes Mouth Ulcers Swollen glands Extreme fatigue

The 1997 Update of the 1982 American College of Rheumatology Revised Criteria for Classification of Systemic Lupus Erythematosus

Criterion Definition1. Malar Rash Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds

2. Discoid rash Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions3. Photosensitivity Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation

4. Oral ulcers Oral or nasopharyngeal ulceration, usually painless, observed by physician5. Nonerosive Arthritis Involving 2 or more peripheral joints, characterized by tenderness, swelling, or effusion6. Pleuritis or Pericarditis a) Pleuritis--convincing history of pleuritic pain or rubbing heard by a physician or evidence of pleural effusion

OR b) Pericarditis--documented by electrocardigram or rub or evidence of pericardial effusion

7. Renal Disorder a) Persistent proteinuria > 0.5 grams per day or > than 3+ if quantitation not performed OR b) Cellular casts--may be red cell, hemoglobin, granular, tubular, or mixed

8. Neurologic Disorder a) Seizures--in the absence of offending drugs or known metabolic derangements; e.g., uremia, ketoacidosis, or electrolyte imbalance

OR b) Psychosis--in the absence of offending drugs or known metabolic derangements, e.g., uremia, ketoacidosis, or electrolyte

imbalance

9. Hematologic Disorder a) Hemolytic anemia--with reticulocytosis OR b) Leukopenia--< 4,000/mm3 on ≥ 2 occasions OR c) Lymphopenia--< 1,500/ mm3 on ≥ 2 occasions OR d) Thrombocytopenia--<100,000/ mm3 in the absence of offending drugs

10. Immunologic Disorder a) Anti-DNA: antibody to native DNA in abnormal titer OR b) Anti-Sm: presence of antibody to Sm nuclear antigen OR c) Positive finding of antiphospholipid antibodies on: 1. an abnormal serum level of IgG or IgM anticardiolipin antibodies,2. a positive test result for lupus anticoagulant using a standard method, or3 a false-positive test result for at least 6 months confirmed by Treponema pallidum immobilization or fluorescent treponemal antibody absorption test

11. Positive Antinuclear Antibody An abnormal titer of antinuclear antibody by immunofluorescence or an equivalent assay at any point in time and in the absence of drugs

2009 American College of Rheumatology

Investigations

CBC Antinuclear antibody (ANA) (90%)sensitive Anti-double strand (ds) DNAspecific Antiphospholipid antibodies Anti-Smith antibodies Rheumatoid factor (25%) Serum complement levels are reduced during active disease Anticardiolipin antibodies (35-45%) Serological tests for syphilis (30%) Immunoglobulins are raised (usually IgG and IgM) Creatinine and BUN

Management

The disease and its management should be discussed, pointing out that the prognosis is much improved though patients are advised to avoid excessive exposure to sunlight and should reduce cardiovascular risk factors.

Summary – Key treatment

NSAIDs Antimalaria: chloroquine or

hydroxychloroquine: ↓ IL- 1β, IL-6, IL-18 and TNF-α serum levels after 3 months

Corticosteroids: prednisone Immunosuppressive drugs: methotrexate

(MTX), azathioprine, cyclophosphamide, mycophenolate mofetil.

Anti CD-20 antibody (Rituximab)

Lupus May 2006 vol. 15 no. 5 268-275

Course and prognosis

An episodic course is characteristic, with exacerbations and complete remissions that may last for long periods.

A chronic course is occasionally seen. Earlier estimates of the mortality in SLE were exaggerated; 10-year survival rate is about 90%.

Cause of death : vasculitis, infection, renal failure

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