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111 Cards in this Set
- Front
- Back
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Which genetic marker has the highest correlation with developing SLE?
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Complement C1q deficiency - 90% develop SLE
C4 deficiency leads to SLE in 75% C1r/C1s deficiency leads to SLE in 55% |
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What epigenetic phenomenon is associated with SLE?
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DNA hypomethylation
Hydralazine and procainamide interfere with DNA methylation |
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Why is EBV thought to be linked with SLE?
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High number of SLE have EBV infection, and during flares, EBV copies rise
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Why are women thought to develop SLE in greater proportion than men?
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Estradiol/progesterone exposure
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What environmental exposure leads to SLE flares in most patients?
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UV light
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What subtype of antibody is implicated in most SLE, and what is the antigen?
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IgG, directed at nuclear components
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What process is believed to cause SLE patients' antibodies to gain exposure to nuclear components?
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Inefficient apoptosis / phagocytosis deficiency
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What inflammatory marker is released in larger amounts in SLE that enables anti-nuclear activity
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human neutrophil peptide, which circulates with LL-37
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What inflammatory agent is overexpressed in 70% of SLE patients?
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IFNalpha
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What cytokine in SLE stimulates the release of inflammatory IL-6 and TNFalpha?
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IFNalpha
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Name the clinical outcome associated with each antibody:
Anti-SSA/anti-RO Anti-dsDNA 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 |
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Which SLE-associated markers are not associated with a specific clinical presentation?
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Anti-Smith, ANA
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Name the SLE components in MDSOAPBRAIN
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Malar rash
Discoid rash Serositis Oral ulcers Arthritis Photosensitivity Blood abnl (thrombo- lympho-leukocytopenia, hemolytic anemia) Renal (casts / proteinuria) ANAs Immune abnl (Anti-smith, Anti-ds, APA) Neurologic (sz, psychosis) |
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Which ethnicities have more severe SLE phenotypes?
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Hispanics / Af-Amers
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What is the 10-yr prognosis of SLE?
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70% survival at 10 years
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What is the difference between Jaccoud's symmetric polyarthritis of SLE and that of RA?
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SLE is NON-erosive
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What is the likely rheumatologic cause of a Libman-Sacks endocarditis (non-bacterial thrombosed valve)? Name the serologic marker associated.
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SLE - anti-cardiolipin, anti-B2 glycoprotein
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What cardiac abnormalities are SLE likeliest to die of?
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The common ones, unrelated to their SLE:
CAD, premature atherosclerosis |
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What pathogenic marker in SLE is responsible for the serositis presentations? (Pleural effusion, ascites, pericarditis)
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Immune complexes
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What three mechanisms might be responsible for anemia in SLE?
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Aplastic anemia (Parietal cell Ig)
Hemolytic anemia (Anti-phospholipid Ig) Chronic disease anemia (TNFalpha, IL-6) |
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How does presentation of RA differ from OA?
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RA: squishy nodes, in MCP and PIP joints
OA: Hard nodes (Heberden's, Bouchard's), in DIP joints |
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Where are RA nodules likeliest to form?
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Over pressure points (finger joints, elbow)
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Felty's Syndrome of RA (splenomegaly, leukopenia, freq infections) is associated most with which HLA subgroup?
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HLA-DR4 (recognizes Beta-1 chain products)
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Which antibodies might you expect to be positive in a person with Sjogren's syndrome?
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Anti-SS-A (Ro), Anti-SS-B (La)
ANA Rheumatoid Factor |
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What cancers are more likely in Sjogren's patients?
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Lymphomas occur in 5-8% (44X higher than non Sjogren's):
B cell NHL (MALT) |
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Match the synoviocyte with the cell is acts most like:
Type A, Type B Macrophage, fibroblast |
Type A: Mac-like
Type B: Fibroblast-like |
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Describe a rheumatoid pannus.
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Hypertrophied synovium infiltrated with T, B, and lymphocytes and blood vessels. Erodes adjacent cartilage and bone.
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Describe the actions of rheumatoid factor (RF).
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RF is an IgM pentamer or IgG antibody that has Fab portions that bind the Fc portions of other molecules.
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How strong a predictor of clinical presentation is rheumatoid factor?
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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. |
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What are antibodies to cyclic citrullinated peptides (CCP) predictive of in rheumatoid arthritis?
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Earlier stage of disease, severity of extra-articular sx(maybe)
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What serologic factor, when combined with smoking, is associated with 35X increase in risk of developing RA?
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Anti-CCP
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What are T/B cells infiltrating in early RA?
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The synovial membrane on the inner joint capsule. This eventually stimulates angiogenesis, and extends to the articular cartilage, forming a pannus.
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What cytokines are most associated with the effects of RA?
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TNFalpha, IL-1beta, IL-6
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What endogenous immunoglobulin acts as a natural CD80/86 (APC/T cell co-stimulator) antagonist?
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Ig CTLA4
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What endogenous agent inhibits the binding of IL-1beta to IL-1receptor in rheumatoid arthritis?
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IL-1ra
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Why is rituximab indicated for RA?
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Anti-B cell action is helpful in lowering production of IgRF
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Why is tocilizumab indicated for RA?
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Anti-IL-6 antibody
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What is the latest intercellular target of RA therapy?
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JAK-STAT pathway of activated immune cells
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Which joints are implied by Bouchard's and Heberden's nodes?
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Bouchard's = PIP
Heberden's = DIP |
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What is the primary form of collagen in cartilage?
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Type II
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What is the major component of articular cartilage apart from chondrocytes?
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Water (60-80%)
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What are keratin sulfate and chondroitin sulfate components of?
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proteoglycan of articular cartilage (attached to hyaluronic acid)
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What aspect of articular cartilage is made up of N-acetylglucosamine and glucuronic acid?
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Hyaluronic acid
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What aspect of articular cartilage is responsible for it's compressive stiffness, and may be decreased in OA?
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Aggrecan
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What are the changes in proteoglycans and H20 content responsible for OA stiffness and joint permeability?
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Decreased proteoglycans
Increased H20 |
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Describe the changes in levels of matrix metalloproteinases (MMPs)and TIMPs in OA?
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Increased MMPs
Decreased TIMPs favor destruction of collagen, which stimulates chondrocytes to try to repair (they do this badly and create spurs) |
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What do IL-1, TNFalpha, and NO cause in terms of proteinases?
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Stimulate proteinase production and activity. IL-1 suppresses chondrocyte activity
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What factors can block the destructive effects of IL-1 and TNF-alpha?
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IL-1ra (receptor antagonist), TIMP
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What growth factors promote cartilage repair in OA?
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IGF1, TGFbeta
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What directly injected agent can be used to inhibit release of AA, and IL-1 induced PGE2 synthesis by synoviocytes?
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Hyaluronic acid. Injecting stimulates production of endogenous HA.
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At what serum level (normal 2-3mg/dL) is a patient hyperuricemic?
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7mg/dL
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How can you differentiate between a gout tophi and a RA nodule
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Perform arthrocentesis, inspect aspirate under polarized light
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Following an arthrocentesis, what color will the uric acid crystals in a gout patient appear when parallel to the polarizer?
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Yellow
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What does a partial HGPRT deficiency lead to rheumatologically?
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Gout, UA calculi (overproduction of UA)
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What does a complete HGPRT deficiency lead to?
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Lesch-Nyhan syndrome, overproduction of UA (self-mutilation, mental retardation, hyperuricemia, uric acid crystaluria
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What does the disorder PRPP (phosphoribosyl pyrophosphate) synthetase overactivity cause rheumatologically, and how is it inherited?
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gout, deafness, developmental defects from overproduction of UA
X-linked |
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What kidney ion-channel/exchangers are mutated in hyperuricemia patients who have decreased clearance?
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URAT1, UAT
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Which inflammatory mediators are attracted to urate crystals, and what is their effect?
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IgG - increases phagocytosis
ApoE/B - decreases phagocytosis |
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What does TLR2/4 on synovial macrophages / chondrocytes stimulate?
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UA crystal formation
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Which interleukin is particularly implicated in gout?
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IL-1beta
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What is the mechanism of action for Anakinra in gout?
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Anti-IL-1beta
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What is the mechanism of action for febuxostat and allopurinol in gout?
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Inhibit xanthine oxidase, preventing formation of uric acid
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What is the mechanism of action for PEG-uricase in gout?
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enhances breakdown of uric acid
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What is the mechanism of action for colchicine in gout?
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Inhibits PMN adhesion and motility
Inhibits Il-1 / IL-8 |
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What drugs inhibit PGE2 for gout?
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NSAIDS and steroids
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How does Probenecid work for gout?
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Inhibits URAT1, increasing uricosuria
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What is the prototypical collagen-vascular disease?
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Systemic sclerosis
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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 |
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What causes women to develop Raynaud's more frequently than men?
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Estrogen is linked with more a-adrenergic receptors in periphery. These respond to stimuli with vasoconstriction
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What rheumatologic disease can be secondary to use of vibrating tools?
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Raynaud's
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What is TH2 release IL-4, causing release of TGF-b and fibroblast mitogen associated with?
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Fibroblast stimulation: Systemic sclerosis
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What does IL-1 release of platelet-derived growth factor from fibroblasts cause?
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collagen deposition - systemic sclerosis
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What abnormalities are responsible for IPF in SS?
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vascular defects = excess of endothelin causing smooth muscle contraction
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Describe whether each of the following is pro-inflammatory or anti-inflammatory:
TGFb TNFa PDGF IFNg |
anti-inflammatory (profibrotic)
TGFb, PDGF pro-inflammatory (antifibrotic) TNFa, IFNg |
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Which cytokine is responsible for the phosphorylation of Smad, causing upregulation of collagen production by fibroblasts?
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TGFb
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Which cytokines, overexpressed in systemic sclerosis, are synergistic?
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PDGF and TGFb
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Where does the interstitial fibrosis of the lung in SS have a predilection for?
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Lung bases
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What are the anti-nuclear antibodies seen most commonly in SS?
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anti-topoisomerase I (Scl-70) (diffuse)
anti-centromere ABs (limited) anti-RNA polymerase (Renal) |
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What are the gammaglobulins most frequently seen in SS?
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IgM rheumatoid factors
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What is HLA-B27 associated with?
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Spondyloarthropathy, reactive arthritis
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Which bacteria is associated with spondyloarthropathy?
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Klebsiella
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Which ethnic group is most associated with HLA-B27?
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Native americans (13%)
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What other factor besides family history is the biggest risk factor for spondyloarthropathy?
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HLA-B27
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Where does ankylosing spondylitis typically affect?
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Axial skeleton
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What are conjunctivitis/ uveitis, urethritis, and lower extremity arthritis the hallmarks of?
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Reactive arthritis: can't see, can't pee, can't climb a tree
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What might asymmetric migrating arthritis in lowerextremities be a presenting sx of?
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Crohn's/UC
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How does psoriatic spondylitis differ from psoriatic arthritis?
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psoriatic spondylitis has HLA-B27 association, PA does not.
PS very similar to AS |
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What is a Shober test?
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Measure change in distance with bending from a 10cm distance when standing straight. Normal is >4cm
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What cytokine is targeted in infliximab, etanercept, and adalimumab?
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TNFalpha
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Which two cytokines are most implicated in AS, and are therefore abundant in sacroiliac bx?
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TNFalpha - inflammation
TGFb - ossification |
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What immunologic therapy target is most helpful in treatment of ankylosing spondylitis?
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anti-TNFalpha (Infliximab, etanercept, adalimumab)
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Which treatments are most helpful in psoriatic arthritis?
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Methotrexate (Liver tox)
Etanercept or other TNFa antagonists |
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Name the site of Ig deposition (endothelium, mesangium or both) for each of the patterns of Lupus GN:
Mesangial Focal proliferative (segmental) Diffuse proliferative Membranous |
Mesangial: mesangium
Focal prolif /Diffuse prolif: both mesangium and endothelium Membranous: endothelium |
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Which type of lupus is likelier to present with systemic sx?
Discoid or Malar rash? |
Malar
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Contrast lupus endocarditis with bacterial and rheumatic endocarditis.
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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 |
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What cells from a serosal cavity aspirate are diagnostic for systemc lupus?
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LE cells - neutrophils that have eaten DNA and Ig aggregates
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Which of the following are the most SENSITIVE and SPECIFIC for lupus?
ANA Anti-smith Anti-dsDNA |
ANA - sensitive
Anti-smith - specific Anti-dsDNA - specific |
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Which arthritis is associated with prominent lymphoid infiltrate?
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RA
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What is the prominent lymphocytic infiltrate in Sjogren's?
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CD4+ T cells - reduced by smoking
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What are the prominent antibodies found in Sjogrens?
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Anti-SS-A and Anti-SS-B
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What is CREST syndrome synonymous with (and what does CREST stand for)?
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CREST = limited cutaneous scleroderma
Calcinosis Reynaud's Esophageal dysmotility Sclerodactyly Telangiectasia |
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What type of collagen is implicated in systemic sclerosis?
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Type I (tough stuff)
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What therapy is very helpful for mixed CT disease (features of SLE / SS without renal involvement)?
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Steroids
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What antibodies are present in mixed CT disease?
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ANA-70+%
Anti-nuclear RNP (U1 RNP) - 100% |
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What is a malar rash covering nasal folds and elevated CK indicative of?
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Dermatomyositis
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Dysphagia, breathing problems, and an elevated antisynthetase Jo-1 (histidyl-tRNA synthetase) are indicative of what?
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IIM: Idiopathic Inflammatory Myositis
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A patient older than 60 with a high sed rate, anemia, and prominant blood vessels at the temples should be evaluated for what?
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Temporal arteritis (vision changes, jaw pain)
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What test can be ordered to evaluate arteritis?
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ANCA
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Which ANCA stains neutrophils in a perinuclear pattern?
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P-ANCA
(C-ANCA = cytoplasmic) |
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What enzyme is P-ANCA staining?
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MPO
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What enzyme is C-ANCA staining?
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PR3
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