Thirty One Flashcards
What is systemic lupus erythematosus? Pathophys? Epidemiology?
A. Systemic autoimmune disease
Flares and remissions common
1 . Antigen antibody complexes damage multiple tissues
a. Poorly controlled apoptotic debris (from UV damage) activates self reactive lymphocytes, which produces antibodies to host nuclear antigens
b. complexes generated at low levels and taken into dendritic cells, where they activate TLRs which amplifies the immune response (IFN-alpha)
c. Complexes generate at a greater rate causing more disease.
d. Defeciency of early complement proteins (C1Q, C2, C4) is associated with SLE
- More commo n in middle aged women, especially African Americans and hispanics, though does arise in children and older adults with less of a gender bias.
What are some non-specific symptoms of SLE that don’t help with diagnostic criteria?
myalgias, fevers, fatigue,
Raynaud’s, alopecia, weight loss, LAD
What are some diagnostic symptoms of SLE? How many are needed? What is libman sacks?
4 symptoms needed for diagnosis
- Malar ‘butterfly’ rash (I) (Fig, 2.4), especially upon exposure to sunlight
- Discoid Rash
- Oral or nasopharyngeal ulcers
3 . Arthritis - Pleuritis and pericarditis (involvement of serosal surfaces)
i. Libman-Sacks endocarditis is a classic finding and is characterized by small, sterile deposits on both sides of the mitral valve. - CNS psychosis and seizures
- Renal damage—Diffus e proliferative glomerulonephritis (blood) OR membranous nephropathy (protein)
- Anemia (hemolytic), thrombocytopenia, or leukopenia (due to autoantibodies against cell surface proteins)
- ANA
- Anti-dsDNA or Anti-Sm or Antiphospholipid
What are some common causes of death in SLE? Initially? Eventually?
- Renal failure and infection are commo n causes of death
- Accelerated coronary artery sclerosis leads to death later on.
90% 5 year survival.
What is antiphospholipid antibody syndrome?
E. Antiphospholipid antibody syndrome is associated with SLE (30% of cases). More commonly a primary disorder.
1 . Characterized by autoantibody against proteins bound to phospholipids leading to a hypercoagulable state
2. Anticardiolipin and lupus anticoagulant are the most commo n antibodies,
i. Lead to false-positive syphilis test and falsely-elevated P T T lab studies, respectively
a. Also Anti-beta 2 glycoprotein I
3 . Results in arterial and venous thrombosis including deep venous thrombosis, hepatic vein thrombosis, placental thrombosis (recurrent pregnancy loss), and stroke
4. Requires lifelong anticoagulation
What antibody is positive in drug induced SLE? What drugs are commonly the cause? Treatment?
D. Antihistone antibody is characteristic of drug-induced SLE.
1 . Hydralazine, procainamide, and isoniazid are commo n causes,
2. Removal of drug usually results in remission.
3. ANA also positive.
4. CNS and renal involvedment rare.
What are treatment goals in SLE?
- There is no cure
- Aim for remission
- Minimizing adverse outcomes
o Monitor frequently for signs of infection, especially if on
o Monitor for drug toxicity
o Blood pressure control
o Electrolyte monitoring
o Osteoporosis (prevalence about
o Monitor for hyperlipidemia
immunosuppressive therapy
What is the pathophys of neonatal lupus? What are the symptoms? Progression?
• Presence of anti-SSA or anti-SSB in mother places fetus at risk for neonatal lupus
as these autoantibodies can transfer across the placenta
- Can be development of congenital heart block (CHB) or neonatal lupus syndrome with rash, cytopenias, or hepatic abnormalities
- Congenital heart block does not resolve but the other organ system manifestations usually disappear with the clearance of maternal antibodies - 6-8 month postnatal
- Neonatal lupus rash - lasts average of 17 weeks
- Hematologic or hepatic abnormalities less common
- Risk of developing congenital heart block is about 1-2% but if a previous child
was affected, the risk goes up to 18-20%
• If congenital heart block is diagnosed in a baby without structural abnormalities, studies have found that in >85% of cases, the mother had +anti-SSA or +anti-
SSB, regardless of whether she had lupus, Sjogren’s or was asymptomatic
• Of interest, in >50% of cases of congenital heart block, the mother was
asymptomatic and had no definite autoimmune disease but was +anti-SSA or
+anti-SSB
How is SLE managed? First line?
• Wide range of therapies available and is dependent upon what organ systems are
involved
- Try to treat by what the worst organ involvement is
- Many therapies are immunosuppressants
- Hydroxychloroquine
o Antimalarial medication
o First line agent typically used in SLE
o Beneficial for constitutional, musculoskeletal, and cutaneous
o Monitor for potential retinal toxicity with regular eye exam every 6-12
manifestations
months
• Fatigue
o Stress reduction, sleep hygiene and rest, steroids
• Serositis
o Salicylates, anti-inflammatories, low dose steroids (less than 15mg/day)
• Arthritis, Arthralgia, and Myalgia
o NSAIDs, salicylates, steroids
o Hydroxychloroquine
o Methotrexate
o Newest agent - belimumab -inhibits B-lymphocytic stimulator (Blys)
binding to B cells which inhibits B-cell survival, including autoreactive B
cells, and decreases B cell differentiation into immunoglobulin producing
plasma cells
• Try to treat by the most severe organ involvement with immunomodulators
o Azathioprine
o Cyclophosphamide
o Mycophenolate mofetil
o Methotrexate
o Belimumab
o Immunoglobulin
o Rituximab
Describe the role of complement in SLE.
Complement
• Complement cascade is regulated complex of proteins, proenzymes, and cell-
surface receptors that mediate the humoral and cellular immune response.
Role of Complement
- Opsonize particles for phagocytosis
- Activate leukocytes
- Assembly membrane attack complex
- In SLE, classical pathway is especially important as immune complexes stimulate
it
• In active disease, hypocomplementemia occurs – measure C3 and C4 which can
be markers of disease activity
• Complement deficiency predispose to SLE (C1q, C1s, C4, C2, C5, C7, C8, and
partial C4 deficiency – C4A)
