Systemic
Lupus
Erythematosus
(SLE)
Introduction
• SLE is an autoimmune connective tissue disease characterised by
dysregulation of immune responses with autoantibody production often
directed at components of cell nucleus and tissue damage
• More prevalence among Europeans and African Caribbean origin(0.2%)
• 90% of affected patients are females
• Peak age of onset between 20 to 30 yrs
Etiology
• Genetic factors: Risk is more in monozygotic twins, those with HLA-B8,
HLA-DR2, HLA-DR3
• Hormonal factors: Females are more prone, usage of estero gen
contraceptives and high prolactin levels predisposes risk of developing SLE
• Environmental factors: Viruses, ultraviolet rays ,silica dust, increased
oxidative stress- high chances of developing SLE
• Drug induced: Minocycline, Procainamide, Methyldopa,
Hydralazine,Quinidine can also lead to development of SLE
Pathophysiology
• SLE is associated with inherited mutations in complement components C1q, C2 ,C4
in immunoglobulin receptor FcRIIIb, and DNA exonuclease TREX
• Autoantibody production against intercellular and intranuclear components
• Defects in apoptosis or clearance of apoptotic cells
• Inappropriate exposure of intracellular antigens
• Leading to polyclonal B and T cell activation
• Tissue damage and organ failure
Clinical features
Constitutional symptoms
• Fever, fatigue, weightloss, lymphadenopathy
Raynaud’s phenomenon
• Vasoconstriction of small vessels of hand and feet in response to cold
followed by cyanosis of affected digits followed by vasodilation causing
affected digits to turn red
• Examination of capillary nail fold loops show loss of normal loop
pattern ,capillary fallout and dilatation
• This is used to differentiate from primary RP
Skin
• Classic malar facial rash- erythematous, raised
and itchy over cheeks sparing nasolabial folds
• Discoid rash- hyperkeratosis and follicular
plugging, scarring alopecia if it occurs on scalp
• Non scarring alopecia
• Urticarial eruptions
• Livido reticularis
Kidney
• Typical renal lesion is proliferative glomerulonephritis
• Heavy hematuria, proteinuria and casts on urine microscopy
• Regular BP monitoring and urine analysis
• Histologically, lupus nephritis is classified as:
◦ Class I — Minimal mesangial lupus nephritis.
◦ Class II — Mesangial proliferative lupus nephritis.
◦ Class III — Focal lupus nephritis.
◦ Class IV — Diffuse lupus nephritis.
◦ Class V — Membranous lupus nephritis.
◦ Class VI — Advanced sclerosing lupus nephritis (>90% globally sclerosed
glomeruli without residual activity).
Cardiovascular
• Myocarditis and pericarditis.
• Endocarditis (Libman–Sacks endocarditis).
• A higher risk of coronary artery disease compared to general population due to increased risk of
atherosclerosis and vasculitis.
Lung
• Serositis
• Pleural effusion
• Reduced lung volume
• Pulmonary fibrosis
• Thromboembolism
Neuropsychiatric
• Fatigue , headache, poor concentration
• Visual hallucinations, chorea, organic psychosis, transverse myelitis,
lymphocytic meningitis
• Seizures
Gastrointestinal
• Non specific abdominal pain
• Mesentric vasculitis
• Pancreatitis, peritonitis , colitis
• Hepatonsplenomegaly
• Mouth ulcers
Haematological
• Neutropenia, lymphopenia, thrombocytopenia, hemolytic
anaemia
Bone
• Arthralgia, tensosynovitis
• Classical Jaccouds arthropathy
Paediatric
• Renal and cutaneous manifestations are more
• An adult has SLE if 4 of 11
features are present
• The above is the diagnostic criteria
for SLE by American college of
Rhemautology(ACR)
Investigations
• Complete blood count and differential count: Anemia or pancytopenia is seen.
• Serum creatinine, urine analysis with microscopy, and 24-hour urinary protein excretion to rule out
renal involvement.
• ESR, CRP are elevated and complement levels (C3, C4) are decreased.
• Autoantibody testing:
◦ ANA (antinuclear antibody)
◦ Antiphospholipid antibodies
◦ Anti-dsDNA and Anti-Smith (Sm) antibodies (highly specific for SLE)
◦ Others: Anti-ssDNA, anti-RNP, anti-Ro (SS-A), anti-La (SS-B)
◦ Note: ANA is very sensitive but not specific for SLE (positive in Sjögren’s, scleroderma, RA also).
• Chest X-ray: pneumonitis, interstitial lung disease.
• CT/MRI brain: for seizures/neurological involvement.
• Biopsy (skin or kidney) when organ involvement suspected.
Autoantibodies in SLE
• ANA (antinuclear antibody):
◦ Screening test for connective tissue diseases.
◦ Positive in high titer (≥1:160) in almost all SLE patients.
◦ Not specific (can be positive in Sjögren’s, scleroderma, RA).
◦ Subtypes include anti-dsDNA, anti-Sm, anti-SSA, anti-SSB, anti-ribosomal P, anti-RNP.
• Anti-dsDNA (double-stranded DNA):
◦ High specificity for SLE, sensitivity ~70%.
◦ Levels correlate with disease activity.
◦ High levels more active lupus.
• Anti-Sm (Smith):
◦ Most specific antibody for SLE, but sensitivity only 30–40%.
◦ Associated with CNS involvement, kidney disease, lung fibrosis, pericarditis.
◦ Not correlated with disease activity.
Autoantibodies in SLE
• Anti-SSA (Sjogren’s A) / Anti-SSB (Sjogren’s B):
◦ Seen in ~15% of SLE.
◦ Also present in Sjögren’s syndrome & other connective tissue diseases.
• Anti-ribosomal P:
◦ Rare antibody.
◦ May correlate with CNS disease risk (especially lupus psychosis).
• Anti-RNP (ribonucleic protein):
◦ Suggests mixed connective tissue disease with overlap (SLE, scleroderma, myositis).
• Anticardiolipin (IgG/IgM):
◦ Antiphospholipid antibody (APLA).
◦ Used to screen for APLA syndrome in SLE.
Autoantibodies in SLE
• Lupus anticoagulant (LA):
◦ Tested with anticardiolipin antibody for APLA diagnosis.
◦ Despite name, it is a prothrombotic antibody.
• Direct Coombs’ test:
◦ Positive in autoimmune hemolysis (antibodies against RBCs).
• Anti-histone:
◦ Common in drug-induced lupus (e.g., procainamide, hydralazine).
◦ p-ANCA positive in minocycline-induced lupus.
Management
• General measures
❖ Avoid sun exposure ,use sun protection
❖ Avoid smoking, lifestyle modifications
❖ Regular monitoring of disease activity and lab parameters
Management
• Mild–Moderate disease (skin/joint involvement):
◦ NSAIDs for arthralgia/arthritis.
◦ Hydroxychloroquine (HCQ): long-term (cornerstone).
◦ Prednisolone (low dose): 5–20 mg/day if needed.
◦ Immunosuppressants (if resistant):
▪ Methotrexate (MTX) 10–25 mg/week
▪ Azathioprine 2–2.5 mg/kg/day
▪ Mycophenolate mofetil (MMF) 2–3 g/day
◦ Belimumab (biologic) if refractory.
Management
• Severe / Life-threatening disease (renal, CNS, cardiac):
◦ IV Methylprednisolone: 10 mg/kg/day × 3 days, then oral
taper.
◦ Cyclophosphamide (CYC): 15 mg/kg IV every 2–3 weeks × 6
cycles.
◦ Alternative: MMF (esp. lupus nephritis).
◦ Rituximab (anti-CD20): for resistant cases.
Management
• Maintenance therapy:
◦ Taper steroids to ≤10–15 mg/day (aim to stop ≤3 months).
◦ Continue HCQ in all patients (unless contraindicated).
◦ Immunosuppressants for relapse prevention:
▪ MTX 10–25 mg/week
▪ Azathioprine 2–2.5 mg/kg/day
▪ MMF 2–3 g/day
◦ Prevent complications: calcium + vitamin D, DEXA scan, CV risk control.