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111 Cards in this Set

  • Front
  • Back
Which genetic marker has the highest correlation with developing SLE?
Complement C1q deficiency - 90% develop SLE

C4 deficiency leads to SLE in 75%
C1r/C1s deficiency leads to SLE in 55%
What epigenetic phenomenon is associated with SLE?
DNA hypomethylation

Hydralazine and procainamide interfere with DNA methylation
Why is EBV thought to be linked with SLE?
High number of SLE have EBV infection, and during flares, EBV copies rise
Why are women thought to develop SLE in greater proportion than men?
Estradiol/progesterone exposure
What environmental exposure leads to SLE flares in most patients?
UV light
What subtype of antibody is implicated in most SLE, and what is the antigen?
IgG, directed at nuclear components
What process is believed to cause SLE patients' antibodies to gain exposure to nuclear components?
Inefficient apoptosis / phagocytosis deficiency
What inflammatory marker is released in larger amounts in SLE that enables anti-nuclear activity
human neutrophil peptide, which circulates with LL-37
What inflammatory agent is overexpressed in 70% of SLE patients?
What cytokine in SLE stimulates the release of inflammatory IL-6 and TNFalpha?
Name the clinical outcome associated with each antibody:

Anti-ribosomal P
Anti-cardiolipin, anti-β2 glycoprotein

Neuropsychiatric sx, renal impairment, photosensitive rash/congenital heart block in offspring, thrombosis
Anti-SSA/anti-RO - photosensitive rash/ congenital heart block in offspring
Anti-dsDNA - impairment renal
Anti-ribosomal P - neuropsych
Anti-cardiolipin, anti-β2 glycoprotein - thrombosis
Which SLE-associated markers are not associated with a specific clinical presentation?
Anti-Smith, ANA
Name the SLE components in MDSOAPBRAIN
Malar rash
Discoid rash
Oral ulcers
Blood abnl (thrombo- lympho-leukocytopenia, hemolytic anemia)
Renal (casts / proteinuria)
Immune abnl (Anti-smith, Anti-ds, APA)
Neurologic (sz, psychosis)
Which ethnicities have more severe SLE phenotypes?
Hispanics / Af-Amers
What is the 10-yr prognosis of SLE?
70% survival at 10 years
What is the difference between Jaccoud's symmetric polyarthritis of SLE and that of RA?
SLE is NON-erosive
What is the likely rheumatologic cause of a Libman-Sacks endocarditis (non-bacterial thrombosed valve)? Name the serologic marker associated.
SLE - anti-cardiolipin, anti-B2 glycoprotein
What cardiac abnormalities are SLE likeliest to die of?
The common ones, unrelated to their SLE:
CAD, premature atherosclerosis
What pathogenic marker in SLE is responsible for the serositis presentations? (Pleural effusion, ascites, pericarditis)
Immune complexes
What three mechanisms might be responsible for anemia in SLE?
Aplastic anemia (Parietal cell Ig)
Hemolytic anemia (Anti-phospholipid Ig)
Chronic disease anemia (TNFalpha, IL-6)
How does presentation of RA differ from OA?
RA: squishy nodes, in MCP and PIP joints
OA: Hard nodes (Heberden's, Bouchard's), in DIP joints
Where are RA nodules likeliest to form?
Over pressure points (finger joints, elbow)
Felty's Syndrome of RA (splenomegaly, leukopenia, freq infections) is associated most with which HLA subgroup?
HLA-DR4 (recognizes Beta-1 chain products)
Which antibodies might you expect to be positive in a person with Sjogren's syndrome?
Anti-SS-A (Ro), Anti-SS-B (La)
Rheumatoid Factor
What cancers are more likely in Sjogren's patients?
Lymphomas occur in 5-8% (44X higher than non Sjogren's):
B cell
Match the synoviocyte with the cell is acts most like:

Type A, Type B

Macrophage, fibroblast
Type A: Mac-like
Type B: Fibroblast-like
Describe a rheumatoid pannus.
Hypertrophied synovium infiltrated with T, B, and lymphocytes and blood vessels. Erodes adjacent cartilage and bone.
Describe the actions of rheumatoid factor (RF).
RF is an IgM pentamer or IgG antibody that has Fab portions that bind the Fc portions of other molecules.
How strong a predictor of clinical presentation is rheumatoid factor?
Not great. RF is in 80% of RA, but not specific(also in chronic bacterial, viral inflammatory states).

RF is associated with more severe disease and nodules.
What are antibodies to cyclic citrullinated peptides (CCP) predictive of in rheumatoid arthritis?
Earlier stage of disease, severity of extra-articular sx(maybe)
What serologic factor, when combined with smoking, is associated with 35X increase in risk of developing RA?
What are T/B cells infiltrating in early RA?
The synovial membrane on the inner joint capsule. This eventually stimulates angiogenesis, and extends to the articular cartilage, forming a pannus.
What cytokines are most associated with the effects of RA?
TNFalpha, IL-1beta, IL-6
What endogenous immunoglobulin acts as a natural CD80/86 (APC/T cell co-stimulator) antagonist?
What endogenous agent inhibits the binding of IL-1beta to IL-1receptor in rheumatoid arthritis?
Why is rituximab indicated for RA?
Anti-B cell action is helpful in lowering production of IgRF
Why is tocilizumab indicated for RA?
Anti-IL-6 antibody
What is the latest intercellular target of RA therapy?
JAK-STAT pathway of activated immune cells
Which joints are implied by Bouchard's and Heberden's nodes?
Bouchard's = PIP
Heberden's = DIP
What is the primary form of collagen in cartilage?
Type II
What is the major component of articular cartilage apart from chondrocytes?
Water (60-80%)
What are keratin sulfate and chondroitin sulfate components of?
proteoglycan of articular cartilage (attached to hyaluronic acid)
What aspect of articular cartilage is made up of N-acetylglucosamine and glucuronic acid?
Hyaluronic acid
What aspect of articular cartilage is responsible for it's compressive stiffness, and may be decreased in OA?
What are the changes in proteoglycans and H20 content responsible for OA stiffness and joint permeability?
Decreased proteoglycans
Increased H20
Describe the changes in levels of matrix metalloproteinases (MMPs)and TIMPs in OA?
Increased MMPs
Decreased TIMPs
favor destruction of collagen, which stimulates chondrocytes to try to repair (they do this badly and create spurs)
What do IL-1, TNFalpha, and NO cause in terms of proteinases?
Stimulate proteinase production and activity. IL-1 suppresses chondrocyte activity
What factors can block the destructive effects of IL-1 and TNF-alpha?
IL-1ra (receptor antagonist), TIMP
What growth factors promote cartilage repair in OA?
IGF1, TGFbeta
What directly injected agent can be used to inhibit release of AA, and IL-1 induced PGE2 synthesis by synoviocytes?
Hyaluronic acid. Injecting stimulates production of endogenous HA.
At what serum level (normal 2-3mg/dL) is a patient hyperuricemic?
How can you differentiate between a gout tophi and a RA nodule
Perform arthrocentesis, inspect aspirate under polarized light
Following an arthrocentesis, what color will the uric acid crystals in a gout patient appear when parallel to the polarizer?
What does a partial HGPRT deficiency lead to rheumatologically?
Gout, UA calculi (overproduction of UA)
What does a complete HGPRT deficiency lead to?
Lesch-Nyhan syndrome, overproduction of UA (self-mutilation, mental retardation, hyperuricemia, uric acid crystaluria
What does the disorder PRPP (phosphoribosyl pyrophosphate) synthetase overactivity cause rheumatologically, and how is it inherited?
gout, deafness, developmental defects from overproduction of UA

What kidney ion-channel/exchangers are mutated in hyperuricemia patients who have decreased clearance?
Which inflammatory mediators are attracted to urate crystals, and what is their effect?
IgG - increases phagocytosis
ApoE/B - decreases phagocytosis
What does TLR2/4 on synovial macrophages / chondrocytes stimulate?
UA crystal formation
Which interleukin is particularly implicated in gout?
What is the mechanism of action for Anakinra in gout?
What is the mechanism of action for febuxostat and allopurinol in gout?
Inhibit xanthine oxidase, preventing formation of uric acid
What is the mechanism of action for PEG-uricase in gout?
enhances breakdown of uric acid
What is the mechanism of action for colchicine in gout?
Inhibits PMN adhesion and motility
Inhibits Il-1 / IL-8
What drugs inhibit PGE2 for gout?
NSAIDS and steroids
How does Probenecid work for gout?
Inhibits URAT1, increasing uricosuria
What is the prototypical collagen-vascular disease?
Systemic sclerosis
Which systemic sclerosis is associated with the following (diffuse or limited cutaneous)

anti-topoisomerase I ABs
late pulm HTN
poorer prognosis
anti-centromere ABs
Raynaud's for years
anti-topo: diffuse
late pulm HTN: limited
poorer prognosis: diffuse
anti-centromere: limited
Raynauds for years: limited
What causes women to develop Raynaud's more frequently than men?
Estrogen is linked with more a-adrenergic receptors in periphery. These respond to stimuli with vasoconstriction
What rheumatologic disease can be secondary to use of vibrating tools?
What is TH2 release IL-4, causing release of TGF-b and fibroblast mitogen associated with?
Fibroblast stimulation: Systemic sclerosis
What does IL-1 release of platelet-derived growth factor from fibroblasts cause?
collagen deposition - systemic sclerosis
What abnormalities are responsible for IPF in SS?
vascular defects = excess of endothelin causing smooth muscle contraction
Describe whether each of the following is pro-inflammatory or anti-inflammatory:

anti-inflammatory (profibrotic)

pro-inflammatory (antifibrotic)
Which cytokine is responsible for the phosphorylation of Smad, causing upregulation of collagen production by fibroblasts?
Which cytokines, overexpressed in systemic sclerosis, are synergistic?
Where does the interstitial fibrosis of the lung in SS have a predilection for?
Lung bases
What are the anti-nuclear antibodies seen most commonly in SS?
anti-topoisomerase I (Scl-70) (diffuse)
anti-centromere ABs (limited)
anti-RNA polymerase (Renal)
What are the gammaglobulins most frequently seen in SS?
IgM rheumatoid factors
What is HLA-B27 associated with?
Spondyloarthropathy, reactive arthritis
Which bacteria is associated with spondyloarthropathy?
Which ethnic group is most associated with HLA-B27?
Native americans (13%)
What other factor besides family history is the biggest risk factor for spondyloarthropathy?
Where does ankylosing spondylitis typically affect?
Axial skeleton
What are conjunctivitis/ uveitis, urethritis, and lower extremity arthritis the hallmarks of?
Reactive arthritis: can't see, can't pee, can't climb a tree
What might asymmetric migrating arthritis in lowerextremities be a presenting sx of?
How does psoriatic spondylitis differ from psoriatic arthritis?
psoriatic spondylitis has HLA-B27 association, PA does not.

PS very similar to AS
What is a Shober test?
Measure change in distance with bending from a 10cm distance when standing straight. Normal is >4cm
What cytokine is targeted in infliximab, etanercept, and adalimumab?
Which two cytokines are most implicated in AS, and are therefore abundant in sacroiliac bx?
TNFalpha - inflammation
TGFb - ossification
What immunologic therapy target is most helpful in treatment of ankylosing spondylitis?
anti-TNFalpha (Infliximab, etanercept, adalimumab)
Which treatments are most helpful in psoriatic arthritis?
Methotrexate (Liver tox)
Etanercept or other TNFa antagonists
Name the site of Ig deposition (endothelium, mesangium or both) for each of the patterns of Lupus GN:

Focal proliferative (segmental)
Diffuse proliferative
Mesangial: mesangium

Focal prolif /Diffuse prolif: both mesangium and endothelium

Membranous: endothelium
Which type of lupus is likelier to present with systemic sx?

Discoid or Malar rash?
Contrast lupus endocarditis with bacterial and rheumatic endocarditis.
Bacterial endocarditis has huge lesions.
Lupus are smaller, but rheumatic are smallest and confined to lines of closure. In lupus, deposits may happen on any surface
What cells from a serosal cavity aspirate are diagnostic for systemc lupus?
LE cells - neutrophils that have eaten DNA and Ig aggregates
Which of the following are the most SENSITIVE and SPECIFIC for lupus?

ANA - sensitive
Anti-smith - specific
Anti-dsDNA - specific
Which arthritis is associated with prominent lymphoid infiltrate?
What is the prominent lymphocytic infiltrate in Sjogren's?
CD4+ T cells - reduced by smoking
What are the prominent antibodies found in Sjogrens?
Anti-SS-A and Anti-SS-B
What is CREST syndrome synonymous with (and what does CREST stand for)?
CREST = limited cutaneous scleroderma
Esophageal dysmotility
What type of collagen is implicated in systemic sclerosis?
Type I (tough stuff)
What therapy is very helpful for mixed CT disease (features of SLE / SS without renal involvement)?
What antibodies are present in mixed CT disease?
Anti-nuclear RNP (U1 RNP) - 100%
What is a malar rash covering nasal folds and elevated CK indicative of?
Dysphagia, breathing problems, and an elevated antisynthetase Jo-1 (histidyl-tRNA synthetase) are indicative of what?
IIM: Idiopathic Inflammatory Myositis
A patient older than 60 with a high sed rate, anemia, and prominant blood vessels at the temples should be evaluated for what?
Temporal arteritis (vision changes, jaw pain)
What test can be ordered to evaluate arteritis?
Which ANCA stains neutrophils in a perinuclear pattern?

(C-ANCA = cytoplasmic)
What enzyme is P-ANCA staining?
What enzyme is C-ANCA staining?