Systemic Lupus Erythematosus

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SLE Introduction & Pathophysiology - The Immune Betrayal

  • Definition: Chronic, multisystem autoimmune inflammatory disease.
  • Epidemiology: F:M ratio ~9:1; peak onset 15-45 years.
  • Predisposition: Genetic (HLA-DR2, HLA-DR3), environmental triggers (UV, drugs, infections).
  • Pathophysiology: Autoimmunity due to loss of self-tolerance.
    • Autoantibody production: ANA (screening), anti-dsDNA & anti-Sm (specific).
    • Immune complex deposition (Type III hypersensitivity) & Type II cytotoxic reactions.
    • Complement activation leading to tissue inflammation & damage. image

⭐ SLE is characterized by the loss of self-tolerance and production of autoantibodies against nuclear antigens.

SLE Clinical Spectrum - Rash to Renal

  • Constitutional: Fever, fatigue, weight loss.
  • Mucocutaneous:
    • Malar rash (spares nasolabial folds).
    • Discoid lupus.
    • Photosensitivity.
    • Oral ulcers (painless).
    • Alopecia (non-scarring).
  • Musculoskeletal: Non-erosive arthritis (Jaccoud's arthropathy), arthralgia, myalgia.
  • Serositis: Pleuritis, pericarditis.
  • Hematological: Anemia (of chronic disease, hemolytic), leukopenia, lymphopenia, thrombocytopenia.
  • Renal (Lupus Nephritis): Proteinuria, hematuria. Classes I-VI (biopsy-based).
    • Class I: Minimal mesangial LN
    • Class II: Mesangial proliferative LN
    • Class III: Focal LN (<50% glomeruli)
    • Class IV: Diffuse LN (>50% glomeruli) - most common & severe
    • Class V: Membranous LN
    • Class VI: Advanced sclerosing LN (>90% sclerosed glomeruli)
  • Neuropsychiatric (NPSLE): Seizures, psychosis, cognitive dysfunction, stroke.
  • Cardiovascular: Libman-Sacks endocarditis (verrucous, non-bacterial, on mitral/aortic valves).

⭐ Malar rash (butterfly rash) characteristically spares the nasolabial folds.

Lupus Nephritis kidney biopsy micrograph

📌 SOAP BRAIN MD (Mnemonic for SLE criteria - not exhaustive for clinical spectrum but helpful)

  • Serositis
  • Oral ulcers
  • Arthritis
  • Photosensitivity
  • Blood disorders
  • Renal disorder
  • ANA positive
  • Immunologic disorder (anti-dsDNA, anti-Sm, antiphospholipid Ab)
  • Neurologic disorder
  • Malar rash
  • Discoid rash

SLE Diagnosis & Labs - Unmasking SLE

  • 2019 EULAR/ACR Classification Criteria:
    • Entry criterion: ANA $\ge$ 1:80.
    • Additive weighted criteria from clinical & immunological domains; score $>$ 10 points needed for classification.

Key Autoantibodies in SLE:

AntibodySignificanceAssociation(s)
ANAScreening (entry criterion)Sensitive, not specific
Anti-dsDNASpecific, monitors activity, lupus nephritisLupus nephritis, disease activity
Anti-SmHighly specificDiagnostic marker
Anti-Ro (SSA)Neonatal lupus, Sjogren's, photosensitivitySCLE, congenital heart block, Sjogren's
Anti-La (SSB)Neonatal lupus, Sjogren'sSjogren's, less common than Anti-Ro
Antiphospholipid AbsThrombosis, pregnancy morbidityAntiphospholipid Syndrome (APS)
*   ↓C3, ↓C4 (complement consumption, active disease)
*   ↑ESR (inflammation, non-specific)

⭐ Anti-Sm antibody is the most specific antibody for SLE.

SLE Management & Complications - Calming the Storm

Goals: Achieve remission, prevent flares & organ damage.

  • General Measures: Sun protection, lifestyle. HCQ for ALL (unless contraindicated).

    ⭐ Hydroxychloroquine (HCQ) is recommended for all SLE patients unless contraindicated, as it reduces flares and improves survival.

  • Pharmacological Therapy (Severity-based):
    • Mild: NSAIDs, low-dose corticosteroids.
    • Moderate/Severe: Corticosteroids (high-dose/pulse), Immunosuppressants (Mycophenolate Mofetil - MMF, Azathioprine - AZA, Cyclophosphamide - CYC), Biologics (Belimumab for refractory).
  • Lupus Nephritis Management:
    • Induction: MMF or CYC + high-dose steroids.
    • Maintenance: MMF or AZA.
  • Drug-Induced Lupus: 📌 Hydralazine, Procainamide, Isoniazid (HPI). Anti-histone Abs characteristic.
  • SLE & Pregnancy: HCQ safe. Plan conception during remission (≥6 months).
  • Key Complications: Lupus Nephritis, accelerated atherosclerosis, infections, osteoporosis, AVN.

Treatment Algorithm:

High-Yield Points - ⚡ Biggest Takeaways

  • SLE is a multisystem autoimmune disease predominantly affecting young females.
  • ANA is a sensitive screening test; anti-dsDNA and anti-Sm antibodies are highly specific.
  • Characteristic skin manifestations include malar rash (butterfly rash) and discoid rash.
  • Lupus nephritis is a major cause of morbidity; renal biopsy is crucial for prognosis and management.
  • Drug-induced lupus (e.g., hydralazine, procainamide) is often associated with anti-histone antibodies.
  • Coexisting Antiphospholipid Syndrome (APS) significantly ↑ risk of thrombosis and recurrent fetal loss.
  • Hydroxychloroquine (HCQ) is a cornerstone for long-term management in most patients.

Practice Questions: Systemic Lupus Erythematosus

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Which of the following cannot be diagnosed without positive ANA?

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Flashcards: Systemic Lupus Erythematosus

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_____ criteria is used for the diagnosis of Rheumatoid arthritis

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_____ criteria is used for the diagnosis of Rheumatoid arthritis

EULAR

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