Systemic Lupus Erythematosus

Rheumatology

Illness script · Rheumatology

Systemic Lupus Erythematosus

Systemic autoimmune disease causing multi-organ inflammation via autoantibodies and immune complex deposition, with relapsing-remitting course.

This illness script for Systemic Lupus Erythematosus covers predisposing factors, classic presentation, mechanism, workup, management, and the clinical pivots that separate it from look-alikes—written for USMLE Step 1 and clerkship reasoning.

Updated Jul 19, 2026All scripts

01

Predisposing factors

  • Women of childbearing age (9:1 female-to-male ratio)
  • African American, Hispanic, Asian women disproportionately affected
  • Peak onset ages 15–45
  • Drug-induced SLE: hydralazine, procainamide, isoniazid (anti-histone Ab)
  • UV light exposure triggers flares
  • Genetic: HLA-DR2, HLA-DR3, C1q/C4 complement deficiencies

02

Presentation

  • Malar (butterfly) rash: fixed erythema over cheeks sparing nasolabial folds
  • Photosensitivity, discoid rash, painless oral ulcers
  • Arthritis: non-erosive, symmetric, small joints (Jaccoud arthropathy)
  • Serositis: pleuritis or pericarditis (sharp chest pain, positional)
  • Nephritis: hematuria, proteinuria, hypertension — major mortality driver
  • Neuropsychiatric SLE: psychosis, seizures; cytopenias (hemolytic anemia, thrombocytopenia, lymphopenia)

03

Pathophysiology

  • Defective clearance of apoptotic cells → nuclear antigen exposure
  • Autoreactive B and T cells generate pathogenic autoantibodies (anti-dsDNA, anti-Sm)
  • Immune complex deposition (type III hypersensitivity) → complement activation → tissue inflammation
  • Anti-dsDNA titers correlate with disease activity; low complement (C3/C4) during flares

04

Diagnostics

  • ANA: highly sensitive (~99%) but not specific — best screening test
  • Anti-dsDNA: highly specific (~70%), tracks disease activity, correlates with nephritis
  • Anti-Smith (anti-Sm): most specific (~99%) but low sensitivity (~30%)
  • Anti-Ro/SSA, anti-La/SSB: associated with neonatal lupus and congenital heart block
  • Urinalysis + urine protein:creatinine ratio to screen for nephritis; renal biopsy for class staging
  • Complement levels (C3, C4) drop during active disease — useful to monitor flares

05

Management

  • Hydroxychloroquine (HCQ): first-line for all SLE patients; reduces flares and mortality
  • NSAIDs and low-dose corticosteroids for mild-to-moderate disease (arthritis, serositis)
  • Moderate-to-severe disease (nephritis, CNS): high-dose corticosteroids + mycophenolate or cyclophosphamide
  • Belimumab (anti-BLYS): approved add-on for active serologic disease
  • Strict sun protection; avoid estrogen-containing OCP in antiphospholipid antibody-positive patients
  • Monitor for hydroxychloroquine retinal toxicity with annual ophthalmology exam

06

Clinical pivots

How to separate this script from the look-alikes that show up on exams and on the wards.

  • Rheumatoid Arthritis

    RA causes erosive joint disease with positive RF/anti-CCP; SLE arthritis is non-erosive with positive ANA/anti-dsDNA

  • Drug-Induced Lupus

    Drug-induced SLE spares kidneys/CNS, is anti-histone Ab positive (not anti-dsDNA), and resolves with drug discontinuation

  • Dermatomyositis

    Dermatomyositis features proximal muscle weakness, elevated CK, heliotrope rash, and Gottron's papules — not malar rash

  • Antiphospholipid Antibody Syndrome

    APS causes thrombosis and recurrent pregnancy loss without the multi-system inflammation; can co-exist with SLE (secondary APS)

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Educational use only. This illness script is a study framework, not medical advice. Confirm decisions with current guidelines and your clinical supervisors.