Systemic Lupus Erythematosus

Isbandiyah, dr, SpPD

Etiology and Pathogenesis of SLE
 1. Genetic factor
• Many studies have described familial aggregation
of SLE. 5-13% of lupus have at least one first or
second degree relative with lupus
• It was found a 24-58% concordance in
monozygotic twins.
• 2-5% concordance in dizygotic twins or siblings..
• The risk of a child developing lupus born from a
mother (or father) with lupus is calculated to be 3-
4% at worst.
 2. Environmental factors

1. UV light, especially UVB

2. Drug-induced lupus. Drugs ( hydralazine, procainamide,
beta-blokers, isoniazid, penicillamine) can induce lupus.

3. Allergy.
4. Infection.
 3. Sex hormones
• Female : Male=9:1
• The sex difference is most prominent
during the female reproductive years.
• In mice, castrating females and /or
providing androgens or antiestrogens
protects from disease,whereas castrating
males and providing estrogens accelerates
and worsens SLE.
 4. Abnormal immune system
• Sustained presence of autoantigens: increased
apoptosis , impaired clearance of apoptosis
• Hyperactivity in B and T lymphocyte.
• Increased expression of surface molecules participating
in cell activation in both B- and T-cell.
• Overproduction of IL-6 and IL-10
• Defective regulatory mechanism.
• Autoantibodies to DNA, RNA, and a host of other cell
nucleus antigens.
• Circulating immune complexes
Clinical manifestations of SLE
 General symptoms
The most common symptoms listed as initial
complaints are fatigue, fever, and weight loss.
• Fever: fever secondary to active disease was
recorded from 50% to 86%.
• Fatigue is common in patients with SLE, especially
during periods of disease activity
 Dermatological involvement
• Up to 85% of SLE
• Butterfly rash
• Maculopapular eruption
• Discoid lupus
• Relapsing nodular non-suppurative panniculitis
• Vasculitic skin lesin
• Livedo reticularis
• Purpuric lesions
• Alopecia
• Oral ulcer
• Malar rash: This is a
"butterfly-shaped" red
rash over the cheeks
below the eyes and
across the bridge of the
nose. It may be a flat or a
raised rash.
The rashes are made
worse by sun exposure.
• Maculopapular
eruption
• Discoid lupus
These are red, raised
patches with scaling of
the overlying skin.
• Vasculitic skin lesin
• Alopecia
• Oral ulcer: Painless sores
in the nose or mouth
need to be observed and
documented by a doctor.
 Musculoskeletal system
• The arthritis of lupus is usually found on both
sides of the body and does not cause deformity of
the joints. Swelling and tenderness must be
present.
• The most frequently involved joints are those of
the hand, knees, and wrists.
• People with lupus can suffer from a certain type of
low blood flow injury to a joint causing death of
the bone in the joint.
 Kidney system
• Haematuria
• Proteinure (>0.5g protein/d or 3+ )
• Cast
 Nervous system
• The brain , nerve problems and psychiatric syndromes are
common in lupus affecting up to two-thirds of people.
• Potential disorders include seizures, nerve paralysis, severe
depression, and even psychosis.
• Spinal cord involvement in lupus is rare
 Hematological abnormalities
• Red blood cells
a normochromic, normocytic anemia is frequently found in SLE.
haemolytic anemia as detected by the Coombs’ test is the
feature of SLE.
• Platelets.
thrombocytopenia (<100*109/L) appears to be mediated by anti-
platelet antibodies or/and anti-phospholipid antibodies
• White blood cell
leucopenia (<4.0*109/L), its cause is probably a combination of
destruction of white cells by autoantibodies, decreased
marrow production
• Lymphopenia - less than 1,500/mm3
 Pulmonary manifestations
• Pleurisy
it is the most common manifestation of pulmonary
involvement of SLE. The volume of pleural effusions
usually is small to moderate and maybe unilateral
or bilateral. Large pleural effusion are uncommon.
It usually exudative in character.
Pleural effusions may also occur in SLE patients with
nephrotic syndrome, infection, cardiac failure.
• Lung
1) acute lupus pneumonitis: fever, dyspnea,
cough with scanty sputum, hemoptysis,
tachypnea and pleuritic chest pain.
2) pulmonary hemorrhage
3) chronic diffuse interstitial lung disease.
the diagnosis should not be made until infectious
processes such as viral pneumonia, tuberculosis, and
other bacterial, fungal and pneumocystis carinii infection
have been completely excluded.
 Cardiovascular manifestations
• Pericarditis is the most common cardiac
manifestation of SLE.
• Myocarditis (the clinical features of lupus
myocarditis resembles that of viral myocarditis)
• Endocarditis and valvular disease
• Hypertension, cardiac failure
 Gastrointestinal and hepatic manifestation

• Esophagitis, dysphagia, nausea, vomiting: (drug

related in most cases)
• Chronic intestinal pseudo-obstruction, mesenteric
vasculitis, protein-losing enteropathy
• Pancreatitis
• Lupus hepatitis
Laboratory investigation
 Autoantibodies in SLE
• Antibodies to cell nucleus component
ANA, anti-dsDNA, antibodies to extracellular nuclear antigen
(ENA, anti-Sm, anti-RNP, anti-Jo1)
• Antibodies to cytoplasmic antigens
anti-SSA, anti-SSB
• Cell-specific autoantibodies
lymphocytotoxic antibodies, anti-neurone antibodies, anti-
erythrocyte antibodies, anti-platelet antibodies
• Antibodies to serum components
antiphospholipid antibody
anticoagulants antiglobulin (rheumatoid factor)
Diagnosis
 Criteria of the ARA for the classification of SLE

1. Malar rash: Fixed erythema over malar areas, sparing nasolabial folds

2. Discoid rash: Erythematous raised patches with keratotic scaling and follicular plugging
3. Photosensitivity: Skin rash after exposure to sunlight, history or physical exam
4. Oral ulcers: Oral or nasopharyngeal, painless, by physical exam
5. Arthritis:Tenderness, swelling, effusion in 2 or more peripheral joints
6. Serositis: A) pleuritis or B) pericarditis
7. Renal disorder A) proteinuria>0.5g/24hour or 3+ or B) cellular casts
8. Neurological disorder: A) seizures or B) psychiatric disorder (having excluded other
causes, e.g. drigs)
9. Haematological disorder: A) haemolytic anaemia or B) leucopenia or C)
thrombocytopenia
10. Immunologic disorder: A) positive LE cells or B) raised anti-native DNA antibdy binding
or C) anti-Sm antibody or D) false positive serological test for syphilis.
11. Positive antinuclear antibody:
Management and treatment
 Grading clinical activity
SLE disease activity index (SLEDAI)
Clinical feature score
seizure , psychosis , organ brain syndrome 8
visual disturbance, cranial nerve disorder 8
lupus headache, cerebrovascular accidents, 8
vasculitis 8
arthritis 4
myositis 4
urinary casts, hematuria, proteinure, pyuria 4
rash, alopecia, mucosal ulcers, 2
pleurisy, pericarditis 2
low complement, increased DNA binding 2
fever 1
thrombocytopenia, leucopenia 1
 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
 Use of corticosteriod to treat various lupus manifestation
Clinical featureinitial dose of prednisolone

Arthritis (poorly responding to NSAIDs) 20-30mg/d, reducing

pleuritis by about 5mg/wk if
Pericarditis symptoms abate

Haemolytic anemia 1mg/kg/d for about 1M

Thrombocytopenia reduce by 10mg/d if
blood tests improve

Nephritis 1mg/kg/d for about 1M

Neuropsychiatric controversal!
1-2mg/kg/d,
0.5-1g/d methylprednisolone
 Other therapy
• Plasma exchange
• Intravenous Immunoglobulin
• Stem cell transplantation
• Immune therapy ( anti-IL10, anti-CD20, and
immune tolerance therapy)
 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
 PROGNOSIS

• Unpredictable course
• 10 year survival rates exceed 85%
• Most SLE patients die from infection,
probably related to therapy which
suppresses immune system