Lupus I Flashcards
Characteristic marker of SLE
Anti-nucleic acid autoantibodies (ANAs)
Rates of SLE have ___ in the past 40 years
Rates of SLE have more than tripled in the past 40 years
The gender ratio for SLE is __:__ female:male
The gender ratio for SLE is 9:1 female:male
Suggested reasons for gender preference in SLE
- Role of estrogen in disease
- X-linked genes associated with risk
Onset of lupus
Anywhere from ~10 to 55 years, mean age in 30’s
Common causes of mortality in Lupus patients
- Cardiovascular disease
- Renal failure
- Infection
Typical treatments for Lupus
- Corticosteroids
- Other immunosuppressants (cyclophosphamide, etc)
- Antimalarials
- Appropriate treatment of comorbidities
__ of __ criteria are needed for the diagnosis of SLE.
4 of 11 criteria are needed for the diagnosis of SLE.
Genes which predispose to SLE
- C1q and C4 (complement)
- Lack of C4 functionality leads to decreased elimination of autoimmune B cells
- Lack of C1q functionality leads to decreased clearance of necrotic debris
- CD40 (necessary for B cell longevity and class-switching)
- Fc receptors (variants which bind to Igs poorly and make ICs harder to clear)
- Type I IFN variants
Criterion table for SLE
SLE patients have very high baseline levels of serum ___.
SLE patients have very high baseline levels of serum Type I IFNs.
Although the spectrum of autoantibody specificities in SLE is ___, only a few have ___.
Although the spectrum of autoantibody specificities in SLE is extensive, only a few have been shown to contribute to disease-related tissue injury.
Anti-CD3 and Anti-TCR
- Suppress IL-2 production
- Poor T cell proliferation results
Anti-DNA, anti-histone, and anti-chromatin
- Main drivers of immune complex formation in SLE
- Result commonly in kidney disease and neuropathy
Anti-Ro antibodies
- Alter function of myocytes and cells in the conduction system of the heart
- Linked to neonatal Lupus and congenital heart block
Anti-NMDAR antibodies
- Often a result of cross-reactivity due to NMDAR and DNA similarities
- NMDAR is expressed on CNS neurons, and so this antibody in CSF may lead to CNS neuropathy and cognitive deficits
- Resulting inflammation also compromises the blood-brain barrier
Antiphospholipid antibodies
- Interfere with coagulation system and endothelial cell function
- Induce chronic expression of adhesion molecules and tissue factor, promoting thrombosis
- May also cross-link platelets into larger aggregates
Antibody therapies for SLE
- Rituximab (B cell depletion)
- Belimumab (Anti-B-lymphocyte-stimulator, important B cell growth/survival factor)
The pathogenesis of SLE hinges on ___ and ___
The pathogenesis of SLE hinges on loss of tolerance and sustained autoantibody production
Circulating apoptotic microparticles that cause SLE also . . .
. . . trigger neutrophil NETosis! This provides even more fodder for SLE autoantibody development
Current pathogenesis model for SLE
SLE diagram
Podocytes
Cells of Bowman’s capsule with appendages that make contact with the endothelium of the glomerulus across the basement membrane.
Tubule cells
Surround podocytes in Bowman’s capsule and make up the rest of the capsule.
__% of SLE patients have positive ANA titers.
95-99% of SLE patients have positive ANA titers.
SLE “specific” antibodies
- Anti-ssDNA
- Anti-dsDNA
- Anti-Sm (nucleoplasmic protein)
SLE “nonspecific” antibodies
- Anti-histone
- Anti-Ro
- Anti-LA
- Anti-U1RNP
- Rheumatoid factor
One of the most difficult aspects of lupus is knowing whether. . .
. . . the patients are having a flare, an infection, or a drug eruption
They require completely different modes of treatment
Malar rash
How to avoid confusing malar rash and rosacea
- Malar rashes never have papules or pustules
- Malar rashes never have telangectasias
- Malar rashes always spare the orolabial and nasolabial folds
Patients with lupus describe sunlight as. . .
. . . worsening their rashes and making them feel fatigued or ill
Discoid rash
Characteristics of discoid rash
- Areas of hypopigmentation with hyperpigmented borders
- Raised/elevated
- Occurs frequently on the scalp, face, and neck
- Result of chronic inflammation in Lupus
Oral and nasal rashes in Lupus
- Often non-painful, as opposed to Herpes
- Often unreported and must be observed on HEENT exam
Serositis
- Inflammation of lining of body cavities (pleura, pericardium, peritoneum)
- Extremely painful
- Causes buildup of inflammatory cells and fluid
- Pericarditis may lead to tampanade (hydrostatic pressure resiting blood pumping)
- Pleuritis may lead to shortness of breath with decreased sounds in lower lung fields
____ nephritis in Lupus requires immediate attention
Class III or above nephritis in Lupus requires immediate attention
Jaccoud’s arthropathy
Finding of chronic lupus arthritis. Substantial ulnar deviation in the absence of bone erosion.
Lupus may lead to ___ by several different mechanisms
These include:
Lupus may lead to anemia by several different mechanisms
These include:
- Hemoltyic anemia
- Iron deficiency anemia
- Anemia of chronic disease
Even if platelet counts are low in patients with Lupus. . .
. . . they are still at risk for thrombosis! This is due to the effects of autoantibodies against thrombocytes
Neurological symptoms in Lupus may include
- Stroke
- Seizure
- Psychosis
- Worsening depression
- Worsening executive functioning
- Other neurological dysfunction
While not required or specific, Lupus patients often display ___.
While not required or specific, Lupus patients often display Reynaud’s phenomenon
Libman-Sack’s Endocarditis
- Formation of clotts and thrombosis on heart valves
- Posterior leaflets of aortic and mitral valves involved
- NOT infectious
- May be a source of emboli
