This document provides information about systemic lupus erythematosus (SLE), a multi-system connective tissue disease of unknown cause characterized by damage to tissues and cells by autoantibodies and immune complexes. It is more common in women of childbearing age. The document discusses the etiology and pathogenesis of SLE, diagnostic criteria including clinical features and tests, classifications of lupus nephritis, investigations, clinical manifestations, management, and prognosis.

1. KOLOWA K. M.
GROUP ML 608.
TOPIC:SLE.
22/05/2015

2. Systemic Lupus
Erythematosus (SLE)
IT IS A MULTISYSTEM CONNECTIVE TISSUE DISEASE OF UNKNOWN CAUSE IN
WHICH TISSUES AND CELLS ARE DAMAGED BY PATHOGENIC
AUTOANTIBODIES AND IMMUNE COMPLEXES.IT IS MORE COMMON IN
WOMEN OF CHILD BEARING AGE (MALE: FEMALE IS 1 : 9).
AETIOLOGY AND PATHOGENESIS
1. THERE IS DISTURBANCE OF IMMUNE REGULATION.
2. GENETIC FACTORS ARE INVOLVED (HLA-B8 AND DR3)
3. INVOLVEMENT OF ENVIRONMENTAL FACTORS (SUNLIGHT).
4. DRUGS: OESTROGENS, ORAL CONTRACEPTIVES, QUINIDINE,INH,
HYDRALAZINE, CHLORPROMAZINE, PRACTOLOL,METHYLDOPA,
PHENYTOIN, A INTERFERON AND PROCAINAMIDE (MOST FREQUENT).

3. 5. Infection is thought to be one of the aetiological
factors- EB virus.
6. Immunologically-mediated tissue damage, also
results.
7. Miscellaneous: Ingested alfalfa sprout and chemicals
like hydrazines, hairdyes are also implicated.
Criteria for the Diagnosis of SLE
1. Malar rash
2. Photosensitivity
3. Oral/nasopharyngeal ulcers
4. Arthritis involving >2 peripheral joints
5. Serositis – pleura/pericardium
6. Renal involvement

4. 8. Haematological disorders
 Leucopenia - < 4000/μL
 Lymphopenia - < 1500/μL
 Thrombocytopenia - < 1,00,000/μL
9. Immunological markers
 Antinuclear/antiphospholipid/Anti ds DNA/
 Anti Sm
For diagnosis 4 or more criteria should be present either
serially or simultaneously.

5. WHO - Classification of Lupus Nephritis
Grade Histological changes
I No histological changes
II Proliferative changes confined to the mesangium
III Proliferative changes 10-50% of glomeruli
IV Proliferative glomerulonephritis >50% of glomeruli
V Membranous changes with various degree of
proliferation
VI End stage scarred glomeruli

6. Investigations
1. Elevated ESR
2. Peripheral smear: normocytic, normochromic
anaemia
of chronic disease, leucopenia and
thrombocytopenia.
3. Coombs’ test may be positive (haemolytic
anaemia)
4. Anti-nuclear antibodies (ANA): Detection of
ANA is more sensitive for diagnosing SLE. They can

7. a. SLE
b. Polymyositis
c. Rheumatoid arthritis
d. Scleroderma
e. Sjögren’s syndrome
f. Myasthenia gravis
g. Fibrosing alveolitis
h. Chronic liver disease
i. Polyarteritis
j. Leukaemia.

8. 5. Antibodies to double stranded DNA (anti-dsDNA): These
are more specific for the diagnosis of SLE and can be
detected by radioimmunoassay.A recent increase in anti-DNA
double strand (ds
DNA) antibodies indicates a flare. Antibodies to Sm are also
specific for SLE and assist in diagnosis and Sm antibodies do not
usually correlate with disease
activity.
6. Evidence of activation of classical complement pathway
(High levels of anti-DNA antibodies, low C3 and C4)
are seen.

9. 7. Organ biopsies and lupus band test
(immunofluorescence at the dermoepidermal junction of
normal skin due to the presence of immune
complexes,complement components and
immunoglobulins) are also diagnostic.
8. Lupus anticoagulants: This is an anticardiolipin antibody
detected either by a prolongation of the partial
thromboplastin time which is not correctable by the
addition of normal plasma, or by a prolongation of dilute
prothrombin time. These are detected by ELISA also and
are responsible for
thrombocytopenia and recurrent abortions especially in
the first trimester.

10. Clinical Features
1. Skin .Fixed, erythematous rash over malar regions (Butterfly rash), discoid rash,
alopecia, diffuse
maculopapular rash, urticaria, erythema multiforme, lichen planus like lesions,
photosensitivity, psori form
lesions (subacute cutaneous lupus), oral ulcers, vasculitis
2. Renal .Proteinuria, nephrotic syndrome, focal, proliferative glomerulonephritis,
hypocomplementemia and renal failure.
3. Nervous system. Meninges, spinal cord, cranial and peripheral nerves are
involved. Patients can have cognitive dysfunction,
organic brain syndromes (psychosis, neurosis), pseudotumour cerebri,
extrapyramidal and cerebellar involvement. Hypothalamic dysfunction causes
inappropriate ADH secretion.
4. Vascular .Thrombosis can occur due to vasculitis, antibodies against
phospholipids (lupus anticoagulant, anti cardiolipin antibodies), and immune
complex mediated destruction.

11. 6. Cardiopulmonary.Pericarditis, pericardial effusion, constrictive pericarditis,
myocarditis (arrhythmias, CCF) sudden death due
to MI, and Libman-Sachs’ endocarditis causing MR or AR.
Pleurisy and pleural effusion are common. Lupus pneumonia, interstitial fibrosis,
pulmonary hypertension
and ARDS can occur.
7. Gastrointestinal. Nausea, diarrhoea, vague discomfort, lupus peritonitis, vasculitis of
intestine, intestinal perforation, GI
motility disorders and intestinal pseudo obstruction.
8. Ocular. Retinal vasculitis, conjunctivitis, episcleritis and blindness can occur (fundus
shows sheathed, narrow retinal
arterioles and cystoid bodies).
9. Musculoskeletal system. Myopathy, myositis and ischaemic bone necrosis are
common; Arthritis, arthralgia which can be transient or
persistent leading to chronic inflammatory arthritis and tenosynovitis causing
deformities and contractures.
10. Systemic. Fatigue, malaise, fever, anorexia, and weight loss can occur.

12. Butterfly rash in SLE and SLE—Sclerokeratitis

13. Retinal vasculitis in SLE

14. Tests that can Confirm Clinical Diagnosis and Predict
Severity
Specific for SLE
 Anti-dsDNA
 Anti-sm.
Nonspecific
ANA (most sensitive)
Anti-Ro
Direct Coombs’ test
VDRL (due to anti-cardiolipin antibodies)
PTT
Anticardiolipin
Hematocrit
WBC count
Platelet count
Urinalysis
Serum creatinine.

15. Test Helpful in Following the Clinical Course
 Titre of anti-ds DNA
 Serum complement levels
 ESR
 Haematocrit
 WBC count
 Platelet count
 Urinalysis
 Serum creatinine.

16. Management
1. For acute, life-threatening manifestations, prednisolone 40–80
mg/day can be g iven (1–2 mg/kg/day and maintained with a dose
of 15 mg/day).
2. Pulse therapy with methylprednisolone (1 gm IV on 3 consecutive
days) can be tried for patients with proliferative glomerulonephritis
and deteriorating renal function.
3. NSAIDs are used for joint manifestations.
4. Antimalarials like hydroxychloroquine in a dose of 400 mg/day are
useful in skin and joint manifestations.It can be given for a few weeks
and routine ophthalmic checkup is mandatory.

17. Indications for immunosuppressive therapy.
a. Life-threatening manifestations of SLE like
glomerulonephritis, CNS involvement, thrombocytopenia
and haemolytic anaemia.
b. Inability to reduce corticosteroid dosage or severe
corticosteroid side effects.
Azathioprine, (in a dose of 2–3 mg/kg orally) or
cyclophosphamide (10–15 mg/kg once a month as a
pulse dose or 1.5–2.5 mg/day IV) or chlorambucil
can be used.

18. 6. Anticoagulation should be given to prevent clotting when needed. Chronic
warfarin therapy to prevent.venous clotting can be given along with
plasmapheresis.
7. Antibodies to T lymphocyte, total lymph node irradiation,IV gammaglobulin,
cyclosporine and fish oil have been tried experimentally.
8. Mycophenolate mofetil and rituximab have also been used in severe SLE.
Prognosis
Five-year survival rate is more than 90%. Patients with
severe renal, pulmonary and neurological involvement
have worst prognosis. Infection as a result of immunosuppression
is an important cause of morbidity.
Pregnancy is not contraindicated when the patient is in
remission especially when other organ systems are not
involved.