SLE

Question 1

Demographics

Answer 1

Women in childbearing years

Black > white

Question 2

Presentation

Answer 2

Can be single or multiple organ involvement

• Constitutional - malaise, fatigue, fever, wt loss
• Mucocutaneous - oral ulcers, rashes (malar - photosensitive), palpable purpura, livedo reticularis, Raynaud
• Neuro - seizures, headaches, confusion
• Cardio - pericarditis, myocarditis, accelerates atherosclerosis
• Lungs - alveolar hemorrhage, pleuritis
• MSK - symmetric inflammatory arthritis (non-erosive), reducible arthropathy (can get joints to return to normal shape w/ pressure
• Heme - leukopenia, anemia, thrombocytopenia, hyper-coaguable, vasculitis
• Renal - glomerulonephritis (proteinuria, hematuria, inc creatinine, HTN)

Question 3

4 Other Things on Your Differential

Answer 3

• Viral infections (same symptoms and can trigger auto-antibodies - parvovirus, EBV, CMV)
• Non-Hodgkin’s Lymphoma (same constitutional and heme symptoms + ANA)
• Other auto-immune diseases (RA, dermatomyositis, MCTD)
• Drug-induced lupus (minocycline, procainamide, hydralazine, anti-TNF agents used for RA)

Question 4

Pathogenesis

Answer 4

• Genetics
• Auto-antibody production and immune complex deposition
  
  • Immune complex = auto-antibody + antigen
  • Deposition –> APCs take up Fc –> humoral/complement activation –> C3a and C5a which cause phag chemotaxis AND platelet activation which cause micro thrombi
  • Net effect is tissue damage (vasculitis, skin damage, deposition in kidney)
• B cell hyperactivity –> excessive autoantibody prod
• Abnormal T cell signaling –> lower threshold for activation and cytokine prod

Question 5

Autoantibodies + which correspond to disease activity?

Answer 5

• ANA (in 95%) but non-specific (only for dx not activity)
• dsDNA (less frequent) but more specific; associated w/ nephritis; predicts disease flare so followed in SLE pts
  
  • AKA coincides w/ disease activity
• Anti-phospholipid - associated w/ hypercoaguability

ALL OTHER DO NOT CORRESPOND

• Anti-Sm - high specificity, low sensitivity
• Anti-RNP - overlaps w/ scleroderma and MCTD
• Anti-SSA /SSB- neonatal lupus

Question 6

Labs for Monitoring Disease Activity

Answer 6

• Inflammatory markers (CRP, ESR)
• Complement - C3/C4 in flares
• dsDNA
• Urinalysis and creatinine to screen for glomerulonephritis

Question 7

Treatment

Answer 7

• Topical - rashes
• NSAIDs - for fever, myalgias, joint pain (AVOID IF RENAL PROB)
• Hydroxychloroquine (anti-malarial) - MOST COMMON BACKGROUND DRUG GIVEN - for cutaneous, MSK and constitutional symptoms
  
  • Slow onset, make take 3-4 mo to reach peak
• Glucocorticoids - decide dose based on level of symptoms
• Steroid-sparing Meds - methotrexate, mycophenolate mofetil, azathioprine, cyclophosphamide

Question 8

Prognosis

Answer 8

• Improved recently - better dx, more therapies
• Early death from renal, CNS, infection and later death from MI, end stage organ involvement, malignancy
  • 50X inc risk MI b/c early atherosclerosis