Anagha.
A
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INTRODUCTION
• Systemic lupus erythematosus (SLE) is a chronic, multisystemic
autoimmune disease that results from immune system-mediated
tissue damage and is characterized by the presence of broad
spectrum of autoantibodies.
• Arthralgia and rashes are the most common clinical features,
whereas cerebral and renal diseases constitute most serious
problems.
• Age: It usually occurs in young women between 20 to 30 years,
but may manifest at any age.
• Sex: It predominantly affects women, with female-to-male ratio
of 9:1.
ETIOLOGY
Genetic Factors
Hormones
Environmental factors
GENETIC FACTORS
• Familial association:
Family members of SLE patients have an increased risk of SLE.
About 20% of unaffected first-degree relatives may show
autoantibodies.
High rate of concordance (>25%) in monozygotic twins when
compared with dizygotic twins (1–3%)
• HLA Association:
Risk is more with HLA-DR2 or HLA-DR3
ENVIRONMENTAL FACTORS
• UV radiation
• Cigerette smoking
• Infections (eg: EBV)
• Drugs (eg: hydralazine, procainamide)
HORMONAL FACTORS
• SLE is more common in women of reproductive age
• Estrogen play role in modulating immune response
PATHOGENESIS
CLINICAL FEATURES
Musculoskeletal Features
• Arthralgia and nonerosive arthritis are most common (>85%).
Commonly involves proximal interphalangeal and
metacarpophalangeal joints of the hand, along with the knees
and wrists.
• In about 10% of patients, deformities result from damage to
periarticular tissue, a condition termed Jaccoud’s
arthropathy.
Cutaneous Features
• Classic malar rash consists of erythematous (flat or raised)
facial rash with a butterfly distribution across the malar and
nasal prominences and sparing of the nasolabial
folds and is seen in 30–60% of patients.
• Butterfly rash is often triggered by sun exposure.
• Discoid rash (erythematous, raised patches with adherent
keratotic scaling and follicular plugging).
• Presence of only discoid rash without any systemic features
occurs in discoid lupus erythematosus. The rash is primarily
on the face, but can occur on any part of the body.
• Only 5% of people with DLE have SLE
• Generalised photosensitivity and Alopecia.
Renal Features
• Kidney may be involved in 30–50% of SLE patients
and is one of the most important organs involved.
• Often asymptomatic in most lupus patients,
particularly initially. Hence, urinalysis should be done
in any person suspected of having SLE followed by
regular urinalysis and blood pressure monitoring.
• Characterized by proteinuria (>500 mg/24 hours)
and/or cellular (red cell) casts.
Neuropsychiatric Features
• Nervous system involvement in SLE produces both
neurologic and psychiatric manifestations.
• Clinical features include cognitive dysfunction, headache and
seizures, psychiatric features including depression and
psychosis.
• Peripheral nervous system involvement can cause neuropathy.
Cranial nerve and ocular involvement due to vasculopathy.
Cardiac Features
• Pericarditis most frequent; serious manifestations are
myocarditis and Libman-Sack (noninfective endocarditis
involving the mitral valve) endocarditis.
• Increased risk for myocardial infarction, usually due to
accelerated atherosclerosis and vasculitis.
Pulmonary Features
• Pleural lesions: Pleurisy with or without pleural effusion—
most common pulmonary manifestation.
• Pleural effusion is exudative with low C3 and ANA test positive
in the pleural fluid.
• Lung lesions: Pneumonitis, shrinking lung syndrome,
interstitial inflammation leading to fibrosis and intra-alveolar
hemorrhage.
Gastrointestinal Features
• Non-specific diffuse abdominal pain (caused by autoimmune
peritonitis and/or intestinal vasculitis) and dyspepsia.
• Nausea with vomiting and diarrhea.
• Increases in serum aspartate aminotransferase (AST) and
alanine aminotransferase (ALT).
• Mesenteric vasculitis can cause infarction or perforation of
small intestine
Hematological Features
• Normocytic normochromic anaemia
• Coombs positive haemolytic anaemia.
• Leucopenia.
• Thrombocytopenia
Causes of Death
• Infections and renal failure are the leading causes of
death in the first decade of disease, whereas
thromboembolic events are frequently the cause of
death in the second and later decades.
• Atherosclerosis occurs prematurely in patients with SLE
and is an risk factor for cardiovascular causes
of death.
INVESTIGATIONS
• Immunological abnormalities
• ANA is the best screening test. Antinuclear antibodies (ANA)
are antibodies that bind to various nuclear antigens. These are
generally detected using indirect immunofluorescence More
than 90% of the patients have a positive test
• Anti-double-stranded DNA (Anti-dsDNA) and anti-Sm are
relatively specific for SLE.
• Rising levels of anti-dsDNA and low levels of complement (C3
and C4) are usually reflect disease activity.
Other Tests
• CBC: anemia, leucopenia, lymphopenia, thrombocytopenia
• ESR: elevated
• CRP: elevated if there is accompanying infection or arthritis
• Low c3 levels
• Urinanalysis: When there is active nephritis, urinalysis shows
proteinuria, hematuria and cellular or granular casts.
Blood urea nitrogen and serum creatinine are elevated in
acute kidney injury.
If there is proteinuria, urine albumin/creatinine ratio should
be measured.
• Renal biopsy confirms renal involvement.
IMAGING
• Chest X-ray: To exclude other pathology, for
pulmonary and cardiac pathology.
• High resolution CT: To demonstrate fibrotic lung.
• Magnetic resonance imaging (MRI) of brain or spinal
cord in cases with central nervous system disease
involvement.
• Echocardiography to diagnose pericardial and
endocardial involvement.
Diagnostic Criteria for SLE
• 2019 EULAR/ACR Classification Criteria for SLE
1) Entry Criterion (Must be met first):
• Positive ANA (antinuclear antibody) at a titer of ≥1:80 on
HEp-2 cells or equivalent.
If ANA is negative, SLE cannot be classified using these criteria.
2)Additive Criteria (After ANA+ is confirmed)
Points are assigned to clinical and immunologic domains. Only
the highest-scoring criterion in each domain is counted.
• Clinical Domains
• Immunologic Domains
A total score of ≥10 points classifies the patient as
having SLE.
MANAGEMENT
Goals of therapy
• Control disease manifestations
• To avoid disease exacerbations
• Prevent organ damage
I. CORTICOSTEROIDS
1. Oral Corticosteroids
• Patients with mild SLE do not normally require use of systemic
corticosteroids
• High-dose corticosteroids are necessary for severe organ
systems' manifestations especially CNS, renal & hematologic
manifestations
• Decreases inflammation by suppression of the immune
system
2. Topical Corticosteroids
• Helpful for discoid lesions especially on the scalp
3. Parenteral Corticosteroids
• Pulse therapy with IV corticosteroids in combination with
immunosuppressive therapy is recommended for Class III and
IV SLE patients with confirmed glomerulonephritis
- Acutely ill patients and patients with active proliferative
glomerulonephritis may be treated with prednisone at 60 mg
daily or 1 g of intravenous methylprednisolone administered
daily for 3 days
II. HYDROXYCHLOROQUINE
• Used for skin & joint manifestations
• Also used for preventing flares & other constitutional symptoms
• Inhibits chemotaxis of eosinophils & locomotion of neutrophils &
impairs complement-dependent antigen-antibody reactions
• Recommended as background treatment for Class III and Class IV
SLE patients with nephritis
III. IMMUNOSUPPRESSANTS
• These agents act as immunosuppressive, cytotoxic & anti-
inflammatory agents
• In the treatment of severe CNS & severe glomerulonephritis,
thrombocytopenia & hemolytic anemia, high dose
glucocorticoids & Immunosuppressants are used
1. Azathioprine
2. Cyclophosphamide
3. Methotrexate
4. Mycophenolate mofetil (MMF)
IV. NSAIDS
• provide symptomatic relief of fever, arthritis
• Inhibit inflammatory reactions & pain by decreasing
prostaglandin synthesis
V. SUNSCREEN
• prevent dermal or systemic disease flares upon exposure to
ultraviolet light
THANKS