SLE Flashcards
Is there a genetic component to SLE?
Yes, the risk of SLE with a positive SLE sibling jumps to 5% from the normal 1:2000 (more common in monozygotes than dizygotes)
smoking not really a cause
What genes make one susceptible to SLE?
HLA-DR2, DR-3 (both weakly associated), complement deficiency (e.g. C4A)
What races/ethnicities are susceptible to SLE?
–more common in African American (3-6x), Hispanic and Native American (2-3x) and Asian (2x) populations than Caucasian Americans.
The typical patient for SLE: AA/Hispanic woman of child-bearing age. But can present at ANY age
Symptoms in SLE can be diverse. How do they characteristically present?
Periods of flare (increased disease activity) and remission or low-level disease activity
What are some predictors of flare (in some cases but not all) in SLE?
–New evidence of complement consumption (C3 and C4)
–Rising anti-dsDNA titers (can even precede flare)
–Increased ESR
–New lymphopenia
What patient populations typically have more severe disease?
Ethnic males of lower socioeconomic status with a younger age of disease onset (and abrupt onset of symptoms)
What are the leading causes of mortality in SLE?
heart disease, malignancy, and infection
What are some other factors assoicated with increased mortality in SLE?
You see increased mortality EARLY ON in disease duration, younger age at diagnosis, ethnic, poor, males, and high disease severity at onset
BUT, right now the likelihood of survival is almost 90%!
Symptoms of SLE?
extremely diverse and rarely the same for different patients
RASH OR PAIN (along with constitutional symptoms-most common)
Rash (malar or discoid)-80-90%
Arthritis (nonerosive)
Serositis- 50-70%
Heme disorders (e.g. cytopenias)
Oral/nasopharyngeal ulcers
Renal Disease- 40-60%
Photosensitivity
ANAs
Immune Disorders (anti-dsDNA, anti-Sm, antiphospholipid)- 20-30%
Neurologic (seizures, psychosis)- 40-60%
What are ANAs? How can you detect them?
Autoantibodies against various components of the cell nucleus; sensitive but not specific for SLE (thus, a negative ANA makes it unlikely that a patient has SLE even if clinical picture suggests lupus)
find via immuoflourescence (most reliable)
What percentage of SLE patients have a positive ANA?
95-99% (very sensitive, not specific)- this should ALWAYS be part of a workup
What are some other disease a positive ANA is seen in?
- normal people (3-4%), increases with age
- Scleroderma (95%)
- Sjogrens
- Hashimoto’s Thyroiditis (50%)
- IPF (50%)
What are two highly specific antibodies for SLE? Clinical Assocaition?
Anti-dsDNA (nephritis) and Anti-Sm (nonspecific)
Other Abs seen in SLE and their clinical association?
- Anti-RNP (low specificity)- arthritis, myositis, lung disease
- Anti-SSA and Anti-SSB (low specificity)- dry eyes/mouth, subacute cutaneous lupus eryhtematosus (SCLE), photosensitivity, neonatal lupus
- Antiphospholipid (intermediate specificity)- clotting diathesis, fetal wasting
These presentations would be most associated with what antibodies?
Pathogenic Autoantibodies—
Anti-SSA and Anti-SSB
What disease can you see this in?
Can be RA but this is SLE (Jaccoud’s-like arthropathy)
These hand deformities resemble those that develop in patients with a history of rheumatic fever and are caused by ligamentous and/or joint capsule laxity. Deformities in the hands, such as ulnar drift at the metacarpophalangeal joints, swan neck and boutonnière deformities, and hyperextension at the interphalangeal joint of the thumb, closely resemble the deformities seen in rheumatoid arthritis.
ABSCENCE of erosions on radiographs and their reducibility distinguish this condition from the deforming arthritis of rheumatoid arthritis.
THIS ARE REDUCABLE (not cartilage destruction)
What are the serositis manifestations of SLE?
•Pleura
–Pleuritic chest pain
–Pleural effusion
•Pericardium
–Chest pain
–Pericardial effusion
•Peritoneal cavity
–Abdominal pain
–Fluid accumulations usually subclinical
What is this?
Serositis in SLE (pleural effusion)
Renal involvement in SLE is atrtibuted to what antibodies? What part of the renal system is usually invovled?
Anti-DNA ABs (affects up to half of SLE patients). Note that
•Any renal structure can be affected
–Glomerulus (most common)
–Tubules and interstitium
–Vasculature
via immune complexes being deposited or forming in-situ
look for proteinuira and HTN
What are some of the potential physciatric manifestations of SLE? Neurologic?
–Depression, Psychosis, Cognitive abnormalities
Neurologically, seizures, strokes, MS like disease and peripheral neuropathy can be seen (hard to diagnose)
What are the GI manifestations of SLE?
The GI is less commonly affected in SLE but the most common symptom is abdominal pain, but other manifestations can occur including autoimmune hepatitis, elevated LFTS, bowel perforation, etc.
azathioprine can also cause pancreatitis
What is going on here?
Obstetrical involvment in SLE (neonatal lupus) - usually fertility is not affected by SLE, but infants are typically small for gestational age
How does neonatal lupus present?
- rash, leukopenia
- heart block
due to a transplacental transfer for autoantibodies
Cardiovascular invovlement in SLE can also be diverse and diffuse. Note that pericarditis, myocarditis, and endocarditis (Libman-Sacks) can be seen in SLE. What other CV manifestation is seen in SLE?
Libman-Sacks Endocarditis (LSE in SLE)
Coronary artery disease (corticosteroids can contribute)
Libman-Sacks (shown in picture)
What is going on here?
Vasculitus causing infarction of the digit (Raynaud’s can also be seen in SLE)
Joint are not a typical pathology specimen for SLE patients. We see skin and renal biopsies more frequently. What do SLE skin biopsies typically show?
Skin shows superficial and deep perivascular inflammation and mucin in the reticular dermis.
Skin Biopsies in SLE
What is Class I lupus Nephritis?
normal histology
What is Class II Lupus Nephritis characterized by?
mesangial proliferation
What is Class III Lupus Nephritis characterized by?
focal proliferative GN (less than 50% of glomeruli)
What is Class IV Lupus Nephritis characterized by?
diffuse proliferative GN (>50% of glomeruli)- This is the most common type. Note the marked increase in cellularity throughout the glomerulus (H&E stain).
Which class of Lupus shows wire looping?
Class IV
What are classes V and VI lupus nephritis characterized by?
V- membranous pattern
VI- advanced sclerosing glomerulopathy
How does Lupus Nephritis show on immunoflourescence?
IgG antibody in a granular pattern
Big picture pathology of lupus
some genetic (multigenic) with an intiiation event (probably environment exposure) causing B and T cell dysfunction (and dendritic cells) that produce autoantibodies (forming immune complexes- can **activate complement**) and proinflammatory molecules leading to tissue injury
What lupus nephritis pattern is this?
III- focal proliferative glomerulonephritis
What are these?
LE bodies (hematoxylin bodies)-denatured nuclei following Ab attack; when mixed when phagocytic cells which engulf them, form LE cells
LE cell test positive in 70+% of SLE
