Rheumatologic Disease Flashcards by Andre Lee

what is “the disease of 1000 faces”

systemic lupus erthematosus

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what is the women to men ratio for lupus epidemiology?

9:1

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what heritage is lupus more common in?

hispanic and african heritage

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systemic autoimmune disorder characterized by a number of auto-antibodies - specifically ?

antibodies against nuclear components (ANA)

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what are the ANAs specific to SLE?

anti-ds DNA
anti-smith antigen antibodies

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What does a failure of self-tolerance lead to in autoimmune diseases?

Activation of self-reactive CD4+ T-cells and B-cells that recognize nucleosomal components.

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What type of T-cells and B-cells are found in autoimmune models and patients?

CD4+ cells that recognize nucleosomal components and self-reactive B-cells.

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What does deficient C1q impair, and what does this lead to?

It impairs macrophages’ ability to clear apoptotic bodies, resulting in prolonged presence of nuclear material.

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How does UV light influence autoimmune dermatologic symptoms?

It alters DNA and increases IL-1 production by keratinocytes, worsening symptoms.

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What role do TLRs play in autoimmunity?

They recognize nuclear components, activating APCs and promoting chronic inflammation.

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What primarily causes tissue damage in autoimmune diseases like lupus?

Autoantibodies and immune complex formation.

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How do immune complexes cause damage in autoimmune disease?

By depositing in glomeruli and small blood vessels, leading to inflammation and damage.

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What type of hypersensitivity is immune complex-mediated tissue damage?

Type III hypersensitivity.

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What happens when autoantibodies opsonize blood cells?

They lead to destruction of RBCs, platelets, and leukocytes.

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What type of hypersensitivity is autoantibody-mediated cytotoxicity?

Type II hypersensitivity.

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What vascular pathology may be seen in autoimmune diseases?

Acute necrotizing vasculitis in capillaries, small arteries, and arterioles.

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What characterizes arteritis in autoimmune disease?

Fibrinoid deposits, vessel wall thickening, and luminal narrowing leading to ischemia.

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what does sunlight do to someone with lupus?

sunlight worsens the rash

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what is the type of rash that most people have with lupus called?

malar rash or butterfly rash

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what is discoid lupus?

skin manifestations of lupus with few to no systemic symptoms

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what is a discoid lesion?

skin plaques showing varying degrees of edema, erythema, scaliness, follicular plugging, and skin atrophy surrounded by an elevated erythematous border

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what is seronegative spondyloarthropathies?

Group of disorders characterized by:
- Lack of serum markers (I.e. Rheymatoid Factor, ANA, dsDNA)
- Association with HLA-B27 (most of the diseases in this category)
- Inflammation of synovial joints

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what are the types of seronegative spondyloarthropathies?

ankylosing spondylitis
reactive arthritis
psoriatic arthritis
arthritis associated with IBD

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what is the most common type of seronegative spondyloarthropathies?

ankylosing spondylitis

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what does ankylosing mean?

fusing of a joint - usually through osteophyte formation and calcification of an inflamed synovial joint

what does spondylitis mean?

inflammation of the intervertebral joints

what is the thought to be a major risk factor, or genes located around that locus for ankylosing spondylitis?

HLA-B27

for ankylosing spondylitis, there's chronic inflammation at ?

sites of tendinous or ligamentous insertion sites

ankylosing spondylitis causes insidious onset of what?

low back pain

for ankylosing spondylitis, pain is typically poorly localized to the ?

lower back and gluteal region

ankylosing spondylitis has enthesitis which is what?

inflammatory joint pain that is typically moderate-severe and commonly at site of Achilles tendon insertion

what is the treatment for ankylosing spondylitis?

anti-TNF drugs

what are the two types of reactive arthritis?

post urethritis and enteritis-associated arthritis

what is enteritis-associated arthritis?

arthritis that occurs after a gastrointestinal infections

are reactive arthritis more common in men or women

men

reactive arthritis are strongly associated with ?

HLA B27

what is dactylitis?

significant destruction and deformity of a digit

During inflammation there's activation of ?. When ? is activated by activation of intracellular calcium, then it produces ?. So ? is modified by either the ?.when metabolized by the ?, you'll make mostly ? which is very important for inflammation

phospholipase A2 x2 arachidonic acid x2 5-Lipoxygenase or cyclooxygenase cyclooxygenase prostaglandin-E 2 (PGE2)

what does glucocorticoids block?

the activation of phospholipase A2

NSAIDs block the activity of ?

cyclooxygenase

When NSAIDs block cyclooxygenase what happens?

blocks formation of the various prostaglandins and thromboxane

what happens when thromboxane is blocked?

inhibition of platelet activation -> decreases likelihood of formation of clots

what is COX-1?

a "housekeeping" enzyme that is always present and regulated in a variety of tissues

What is COX-2?

an "induced" enzyme that is mostly produced by immune cells in response to inflammation

only what can irreversibly block thromboxane production by platelets? - thus it is the only NSAID that is used to prevent platelet aggregation

aspirin

most COX-inhibitors block what?

both COX-1 and COX-2

what is the advantage to blocking COX-2 selectively instead of both COX-1 and 2

Selective COX-2 inhibitors are somewhat less likely to cause GI bleeding (less inhibition of gastric mucous production )

Unfortunately, selective COX-2 inhibitors are associated with ?

development of heart attacks and strokes more often than most non-selective medications

what is the only approved selective COX-2 inhibitor?

celecoxib (Celebrex)

Why do NSAIDS (COX-2 inhibitors and many other common NSAIDS) increase the risk of heart attack?

One theory = inhibition of PGI2 formation - PGI2 tends to do one of the housekeeping effects in endothelial cells and they reduced platelet aggregation. So when it is blocked, then there will be increased platelet aggregation in endothelial cells and increased risk of thrombosis

The GI toxicity of oral systemic NSAIDs can be severe in those with a history of bleeding peptic ulcers – can this be avoided?

Patients can take the NSAID with an antacid that reduce the risk of GI damage (proton-pump inhibitor) Patients cant take the NSAID with a medication that activates prostaglandin receptors in the GI tract (misoprostol)

Corticosteroids with strong glucocorticoid effects are in nature

anti-inflammatory

what is the mechanism of action of glucocorticoids?

block of PLA2

Long-term use of glucocorticoid medication can negatively feedback on the ?

anterior pituitary

those on long-term glucocorticoids need to be ? to allow endogenous ACTH to stimulate "regrowth" of the adrenal glands

weaned slowly off their medication

If patients suddenly stop their (long-term, systemic) glucocorticoids they can experience an ? due to inability to produce their own cortisol – dangerous

“adrenal crisis”

what are the two types of immunization?

passive and active

what is passive immunization?

transfer of antibodies from a source outside the patient

what is active immunization?

involves administration of a weakened microbe or portion of a microbe -> production of memory cells

what are toxoids?

Toxoids are inactivated toxins that stimulate antibody production -> neutralization of the toxin's effect

what are subunit vaccines?

A component of the bacterial coat is given to stimulate antibodies against it

what are conjugates?

“conjugate” a weakly immunogenic protein with a strongly immunogenic one

Conjugate vaccines are more effective at eliciting a

CD4+ response -> better memory cells, higher antibody affinities

what are adjuvants?

substances that enhance the immune response to a vaccine

how do mRNA vaccines work?

1. mRNA for a protein that you want to mount an immune response to is sequenced 2. mRNA is placed in a “vehicle” that protects it 3. mRNA is endocytosed or phagocytosed by an immune cell – specifically, an APC 4. mRNA is translated to a protein in the cytosol, using the APC’s cellular machinery (aka ribosomes) 5. The protein is degraded by an immunoproteasome, and expressed by the APC - Multiple types of expression 6. Helper T-cells and B-cells are activated

What are the advantage of mRNA over conventional vaccination?

It’s really, really easy to make mRNA specific for the exact protein that you want to use as the antigen You can make a lot of mRNA really quickly There is pretty much zero chance of the mRNA disrupting the genome of any cell

why aren't all vaccines mRNA?

There are tricky challenges to producing them

Rheumatologic Disease Flashcards

(67 cards)