Rheumatology · Connective Tissue Disease
The facts most likely to be tested
The ANA (antinuclear antibody) test is the most sensitive initial screening test for SLE, while anti-dsDNA and anti-Smith antibodies are the most specific markers.
Patients with SLE classically present with a malar rash (butterfly rash) that spares the nasolabial folds and is exacerbated by sunlight exposure.
Lupus nephritis is a major cause of morbidity, characterized by proteinuria, hematuria, and red blood cell casts on urinalysis, requiring a renal biopsy for definitive classification.
Hydroxychloroquine is the foundational therapy for all patients with SLE to reduce flares, prevent organ damage, and improve long-term survival.
Libman-Sacks endocarditis is a form of sterile, verrucous vegetations on both sides of the heart valves that can lead to embolic events.
Drug-induced lupus is most commonly associated with hydralazine, procainamide, and isoniazid, and is characterized by anti-histone antibodies.
SLE patients are at high risk for antiphospholipid syndrome, which presents with recurrent venous or arterial thrombosis and recurrent pregnancy loss.
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A 28-year-old woman presents to the clinic with a three-month history of joint pain in her hands and knees, fatigue, and a photosensitive rash on her cheeks that spares the nasolabial folds. Laboratory evaluation reveals a positive ANA, low C3 and C4 complement levels, and proteinuria on urinalysis. She has no history of medication use other than oral contraceptives. Physical examination is notable for oral ulcers and mild synovitis of the MCP joints.
Which of the following antibodies is most specific for the diagnosis of this patient's condition?
Anti-Smith antibody
The patient meets the clinical criteria for SLE, and while the ANA is the sensitive screening test, the anti-Smith antibody is highly specific for the diagnosis.
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Etiology / Epidemiology
Primarily affects women of childbearing age (15-45) with a strong genetic predisposition (HLA-DR2/DR3).
Clinical Manifestations
Malar rash (sparing nasolabial folds) and Libman-Sacks endocarditis are classic board findings.
Diagnosis
ANA is the best initial screening test; Anti-dsDNA and Anti-Smith are highly specific.
Treatment
Hydroxychloroquine is indicated for all patients; retinopathy requires annual eye exams.
Prognosis
Lupus nephritis is the leading cause of morbidity; monitor creatinine and proteinuria.
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Epidemiology & Etiology
Prevalence is highest in African American, Hispanic, and Asian women. Environmental triggers include UV light exposure, smoking, and certain medications (e.g., hydralazine, procainamide).
Pertinent Anatomy
Systemic involvement targets the kidneys (glomeruli), skin (dermal-epidermal junction), and serosal membranes (pleura/pericardium).
Pathophysiology
Type III hypersensitivity reaction involving immune complex deposition in tissues. Defective clearance of apoptotic debris leads to persistent autoantibody production. Complement activation (C3/C4 consumption) drives systemic inflammation.
Clinical Manifestations
Classic presentation includes malar rash, discoid rash, and non-erosive arthritis. Red flags include nephritic syndrome (hematuria, hypertension) and CNS lupus (seizures, psychosis).
Diagnosis
Screen with ANA (high sensitivity). Confirm with Anti-dsDNA (correlates with disease activity) or Anti-Smith (most specific). Low C3/C4 levels indicate active disease.
Treatment
Hydroxychloroquine is the cornerstone for all patients to prevent flares. Use NSAIDs for arthritis and prednisone for acute flares. Cyclophosphamide is reserved for severe organ-threatening disease due to hemorrhagic cystitis and infertility.
Prognosis
Major mortality drivers are cardiovascular disease and renal failure. Patients require lifelong monitoring of urinalysis and blood pressure.
Differential Diagnosis
Drug-induced lupus: Anti-histone antibodies positive
Rheumatoid arthritis: Erosive joint disease
Scleroderma: CREST syndrome features
Dermatomyositis: Gottron papules and heliotrope rash
Mixed Connective Tissue Disease: Anti-U1 RNP positive