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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- ANA is sensitive but nonspecific
- Anti-dsDNA and anti-Smith are highly specific
- Low C3/C4 and rising anti-dsDNA suggest active immune complex disease
- Hydroxychloroquine is baseline therapy for most patients
- Proteinuria, hematuria, casts, rising creatinine, CNS disease, or severe cytopenias are red flags
Overview
SLE is a chronic autoimmune disease with autoantibodies to nuclear antigens, immune complex deposition, and multisystem inflammation involving skin, joints, kidneys, blood, nervous system, and serosa.
Epidemiology
SLE predominantly affects women of reproductive age and is more common/severe in Black, Hispanic, Asian, and Native American populations.
Clinical Features
Symptoms
Fatigue, fever, malaise, and weight loss during flares
Photosensitive rash, malar rash sparing nasolabial folds, discoid lesions, or alopecia
Nonerosive inflammatory arthritis
Pleuritic or pericarditic chest pain
Foamy urine, edema, hypertension, or hematuria suggesting nephritis
Seizures, psychosis, stroke, or focal neurologic deficits
Signs
Malar rash, oral/nasal ulcers, photosensitive dermatitis
Nonerosive synovitis or Jaccoud arthropathy
Raynaud phenomenon or livedo reticularis
Pericardial or pleural friction rub
Edema, hypertension, or active urine sediment
Thrombosis or recurrent pregnancy loss suggesting APS
Investigations
First-line
ANAHighly sensitive; negative ANA makes SLE unlikely
Anti-dsDNA and anti-SmithHighly specific; anti-dsDNA often correlates with nephritis
C3/C4, CBC, CMP, urinalysis, urine protein/creatinineAssess disease activity, cytopenias, kidney disease, and proteinuria
Second-line
Antiphospholipid antibodiesIf thrombosis, pregnancy loss, livedo, or prolonged PTT
ENA panelAnti-Ro/SSA, anti-La/SSB, anti-RNP for subphenotypes
ESR/CRPMarked CRP elevation should prompt infection consideration
Specialist
Kidney biopsyFor significant proteinuria, active sediment, or unexplained renal dysfunction
1
General management
- Hydroxychloroquine for most patients unless contraindicated
- Sun protection, smoking cessation, vaccination, pregnancy planning, and cardiovascular risk control
- Use the lowest effective glucocorticoid dose and taper when possible
2
Mild-to-moderate disease
- Cutaneous disease: photoprotection, topical therapy, hydroxychloroquine
- Arthritis: hydroxychloroquine, NSAIDs if safe, short steroids, methotrexate or azathioprine if persistent
- Serositis: NSAID/colchicine or glucocorticoid if severe
3
Organ-threatening disease
- Lupus nephritis: biopsy-guided high-dose glucocorticoids plus mycophenolate or cyclophosphamide-based therapy
- Severe CNS, pulmonary hemorrhage, hemolytic anemia, or thrombocytopenia needs urgent specialist immunosuppression
- APS with thrombosis usually requires warfarin in high-risk disease
Complications
- Lupus nephritis: Proteinuria, active sediment, hypertension, CKD, ESRD
- Antiphospholipid syndrome: Venous/arterial thrombosis and pregnancy morbidity
- Neuropsychiatric lupus: Seizures, psychosis, stroke, transverse myelitis
- Infection: Disease and immunosuppression both increase risk
USMLE Step 2 CK Exam Tips
- 1ANA is sensitive, not specific
- 2Anti-dsDNA and anti-Smith are specific
- 3Low complement + anti-dsDNA + proteinuria = lupus nephritis
- 4Drug-induced lupus has antihistone antibodies and usually spares kidney/CNS
- 5Hydroxychloroquine needs retinal screening
- 6Recurrent pregnancy loss + prolonged PTT = APS
- 7Anti-Ro/SSA can cause neonatal lupus/congenital heart block
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