Multisystem autoimmune disease with autoantibodies against nuclear antigens and immune-complex tissue injury.
Also known as: SLE, lupus, systemic lupus
Overview
Chronic relapsing-remitting autoimmune disease characterized by loss of tolerance to nuclear self-antigens, production of autoantibodies (notably ANA, anti-dsDNA, anti-Smith), and immune-complex deposition that drives inflammation across skin, joints, kidneys, blood, serosa, and the central nervous system.
Epidemiology
Female-to-male ratio ~9:1; peak onset 15-44 years. More common and more severe in Black, Hispanic, and Asian populations. Lupus nephritis is the strongest predictor of morbidity.
Try two board-style Systemic Lupus Erythematosus questions
Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.
Question 1MusculoskeletalMedium
A 28-year-old woman has fatigue, a malar rash, photosensitivity, oral ulcers, pleuritic chest pain, and 2+ proteinuria. Antinuclear antibody (ANA) titer is 1:640. Which of the following additional antibodies is most specific for her diagnosis?
AAnti-Smith
BAnti-centromere
CAnti-Ro/SSA
DAnti-histone
EAnti-Jo-1
Reveal answer & full explanation
Correct answer: A — Anti-Smith
AAnti-Smith✓
BAnti-centromere
CAnti-Ro/SSA
DAnti-histone
EAnti-Jo-1
Why Anti-Smith is correct
The malar rash, photosensitivity, oral ulcers, serositis (pleuritic chest pain), and proteinuria with a high-titer ANA point to systemic lupus erythematosus (SLE).
Anti-Smith antibody has roughly 99% specificity for SLE, making it the most specific of the listed antibodies, although its sensitivity is only about 30%.
Anti-double-stranded DNA is also highly specific and additionally tracks disease activity and lupus nephritis.
Why the others are wrong
Anti-Jo-1 — marks antisynthetase syndrome (polymyositis with interstitial lung disease), not SLE; a buzzword-matching trap for myositis.
Anti-Ro/SSA — seen in Sjogren syndrome and neonatal lupus and is not specific for SLE, so it cannot confirm the diagnosis (confused-with sensitive-but-nonspecific marker).
Anti-centromere — associated with limited cutaneous systemic sclerosis (CREST), not SLE (premature closure on another connective-tissue disease).
Anti-histone — the lupus picture invites the antibody linked to drug-induced lupus, but anti-histone antibodies also occur in many patients with idiopathic SLE and in other rheumatic diseases, so they are not specific for SLE, and no implicated drug such as hydralazine or procainamide is reported (drug-induced lupus look-alike trap).
Question 2MusculoskeletalMedium
A 31-year-old woman has photosensitive rash, oral ulcers, arthritis, and proteinuria. Which of the following tests is most specific for the suspected disease?
AAnti-Ro (SSA) antibody panel
BAntinuclear antibody titer level
CRheumatoid factor antibody level
DAnti-histone antibody assay
EAnti-double-stranded DNA antibody
Reveal answer & full explanation
Correct answer: E — Anti-double-stranded DNA antibody
AAnti-Ro (SSA) antibody panel
BAntinuclear antibody titer level
CRheumatoid factor antibody level
DAnti-histone antibody assay
EAnti-double-stranded DNA antibody✓
Why Anti-double-stranded DNA antibody is correct
Photosensitivity, oral ulcers, arthritis, and proteinuria fit systemic lupus erythematosus.
Anti-dsDNA is highly specific for SLE and titers track lupus nephritis activity.
It is the antibody used to confirm SLE once a positive ANA raises suspicion.
Why the others are wrong
Antinuclear antibody titer level — ANA is the screening test: nearly always positive in SLE but also positive in many non-lupus conditions, so it is sensitive, not specific (sensitivity-for-specificity trap).
Anti-Ro (SSA) antibody panel — Anti-Ro occurs in SLE but is more characteristic of Sjögren syndrome and subacute cutaneous/neonatal lupus, so it is not the most specific marker for SLE itself.
Rheumatoid factor antibody level — RF is nonspecific and points toward rheumatoid arthritis; it would not confirm a photosensitive, renal autoimmune disease (joint-overlap anchoring trap).
Anti-histone antibody assay — anti-histone antibodies are the classic marker of drug-induced lupus (hydralazine, procainamide, isoniazid) but also occur in many patients with idiopathic SLE, so they are not specific, and drug-induced lupus uncommonly involves the kidneys (drug-induced-lupus trap).
That's 2. Get 7,700+ more.
Unlock the full FirstPassPA bank: 7,700+ board-style questions, flashcards, and an AI tutor that explains every answer. Your 7-day free trial includes everything, and there's no credit card required.
You've read your 2 free diagnosis previews. Create your free account to unlock the full Systemic Lupus Erythematosus (SLE) outline — plus all 514 diagnoses, 7,700+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.
Defective clearance of apoptotic debris exposes nuclear antigens that bind self-reactive B and T cells. Autoantibodies form immune complexes that deposit in glomeruli, skin, and serosa, activating complement (low C3, C4) and recruiting neutrophils. Tissue injury results from immune-complex deposition, type I interferon overactivation, and direct cytotoxic mechanisms.
Clinical presentation
Symptoms
Constitutional: fatigue, low-grade fever, weight loss
Sun protection and smoking cessation for all patients
Hydroxychloroquine ≤5 mg/kg actual body weight/day (usually 200-400 mg/day) — foundational for all SLE; reduces flares, organ damage, and mortality (baseline eye exam, annually after 5 years)
NSAIDs — ibuprofen, naproxen — for mild musculoskeletal or serositis symptoms (caution with renal disease)
Glucocorticoids as short-term bridging therapy for activity, with maintenance minimized to prednisone ≤5 mg/day and withdrawn when possible; higher doses or pulse methylprednisolone for major organ flares
ANA-negative SLE is rare; if ANA is negative, the diagnosis becomes very unlikely.
Anti-dsDNA titer and complement levels often track with disease activity — particularly useful in lupus nephritis follow-up.
CRP normal in active SLE; elevated CRP should raise concern for infection or serositis.
Hydroxychloroquine retinopathy risk rises after 5 years; get a baseline eye exam, then annual screening after 5 years (sooner with renal impairment, tamoxifen, or dose >5 mg/kg/day).
Avoid sulfa antibiotics — may precipitate flares.
References
EULAR/ACR 2019 — 2019 EULAR/ACR Classification Criteria for SLE (Aringer et al., Ann Rheum Dis 2019)
EULAR 2023 — EULAR Recommendations for the Management of SLE (Fanouriakis et al., Ann Rheum Dis 2024)
ACR 2024 — 2024 ACR Guideline for the Screening, Treatment, and Management of Lupus Nephritis (Sammaritano LR et al., Arthritis Rheumatol 2025;77(9):1115-1135)
ACR 2025 — 2025 ACR Guideline for the Treatment of Systemic Lupus Erythematosus (Sammaritano LR et al., Arthritis Rheumatol 2026;78(7):1361-1386)
Practice Musculoskeletal questions on FirstPassPA
Turn this outline into retention. 7,700+ board-style questions with an AI tutor that explains every answer — free to start, no card required.
Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.