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Rheumatoid Arthritis Flashcards

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1
Q

Definition of Rheumatoid Arthritis

A

Chronic Inflammatory Disorder primarily involving the joints.
Symmetric, Remitting
Can deform the joint

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2
Q

Pathogenesis of Rheumatoid Arthritis?

A

Etiology unknown, Some HLA assoications

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3
Q

What are the HLA associations with Rheumatoid Arthritis?

A

STAT4 Haplotypes Chromosome 2 (RA and SLE)

TRAF1-C5 on Chromosome 9

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4
Q

Pathophysiology of RA?

A

CD4 T cells activated, stimulate Macrophage with !L-2, IFN-g to make more cytokines.
Macrophage releases TNFa, IL1, IL6
Stimulated CD4s also make B cells release Igs (RF)

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5
Q

What do TNFa, IL1, and IL6 do together?

A

Stimulate chondrocytes, fibroblasts, and osteoclasts to make Metalloproteinases, Catalepsins, and other molecules that erode bone and cart.

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6
Q

IL1 and TNFa do what…

A

Stimulate adhesion molecules

Increase recruitment of PMN cells into a joint

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7
Q

What do PMNS do in a Rheumatoid Arthritis reaction

A

release elastase and proteases that degrade cartilage

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8
Q

What happens to the synovial membrane in Rheumatoid Arthritis?

A

Hyperplasia + Hypertrophy of Synovial lining cells

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9
Q

The growing Synovial membrane triggers what three things to happen?

A

Angiogenesis
CD4 predominant T and B cells infiltrate the membrane
Synovial membrane begins to invade cartilage

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10
Q

What happens to the synovial membrane by late RA?

A

Transformed into inflammatory tissue (Pannus)

The tissue invades and destroys cartilage and bone

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11
Q

Three cell types in a Pannus

A

Type A Synoviocytes (Macrophage Like)
Type B Synoviocytes (Fibroblast like)
Plamsa Cells

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12
Q

Typical Rheumatoid Arthritis patient history

A 
Gradual Onset (weeks-months), Can be pallindromic
Symmetrial, Usually Small Joints
Morning Stiffness for hours, Maybe Malaise+Fatigue
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13
Q

Men or Women – Who gets more Rheumatoid Arthritis?

A

Women

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14
Q

Average Rheumatoid Arthritis age of onset?

A

30-55

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15
Q

Physical findings common in a Rheumatoid Arthritis patient?

A 
Joints are warm, boggy, soft, squishy
Not in DIPS
NEVER, EVER in Lower Back
Characteristic Deformities
Extraarticular Involvement
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16
Q

List Characteristic Deformities of Rheumatoid Arthritis

A

Ulnar Deviation
Swan neck deformities, Boutenaire Deformities
Bayonet Deformities
Heel Valgus
Cervical Damage, atlantoaxial instability
MTP Subluxation

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17
Q

Non-MS systems that may be influenced by Rheumatoid Arthritis?

A

Lung
Cardiac
Hematologic
Ocular

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18
Q

Lung manifestations of Rheumatoid Arthritis?

A 
Pleuresy and Pleuritis
Parenchymal lung disease
Intersitital Fibrosis
Bronchiolitis obliterans w/ organizine pneumonia
Methotrexate pneumonitis
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19
Q

Cardiac manifestations of Rheumatoid Arthritis?

A

Pericarditis and Myocarditis

CV Disease

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20
Q

Hematologic manifestations of Rheumatoid Arthritis?

A

Anemia
Felty’s Syndrome
Large Granular Lymphocyte Syndrome
Lymphoma

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21
Q

What is Felty’s Sndrome?

A

Seropositive Rheumatoid Arthritis, neutropenia, splenomegaly, occasionally leg ulcers

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22
Q

Ocular manifestations of Rheumatoid Arthritis?

A

Sjogren’s Syndrome
Corneal Inflammation/Melt
Episcleritis/Scleritis
Uveitis

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23
Q

Occular problems associated with corticosteroid treatment?

A

Glaucoma and Cataracts

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24
Q

Treatment complications assocaited with hydroxychloroquin treatment?

A

Retinal pigment epithelial toxicity

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25
Special studies to order for an Rheumatoid Arthritis patient?
Acute Phase Reactants RF and CCP antibodies Radiography
26
Rheumatoid Factors are only predictive for...
Patients with inflammatory polyarthritis
27
A patient with a postivie RF and CCP is at a high risk for
Erosions
28
An Anti-CCP test is looking at...
antibodies against the unusual amino acid sequence Citrulline
29
The CCP is very _____ for RA
Specific
30
The presence of both RF and CCP is _____ specific
Very (98%)
31
DDx diseases that should be considered in an RA patient?
``` Inflam. Polyarthritises -- SLE, Scleroderma, Vasculitis Seronegative Spondyloarthropathies Crystal Induced Infectious Polymyalgia Rheumatica Sarcoidosis Cancer ```
32
What is Polymyalgia Rheumatica?
An acute onset of pain in the shoulders and hips Patients are over 50 Very high Sed rate Very responsive to corticosteroids
33
Causes of Infectious Arthritis?
Viral (Parvo B19, Rubella, Hep B) | Gonoccal
34
Two major crystal induced arthritises?
Calcium Pyrophosphate Deposition Disease | Gout
35
List the seronegative spondyloarthropathies
Psoriatic Arthritis Reiter's Syndrome Enteropathic Arthritis (Crohn's, UC, Sprue) Reactive Arth.
36
Function of COX1?
Important to constitutive functions (mucosal lining, platelet fxn)
37
Function of COX2?
Mediation of pain, inflammation
38
Role of NSAIDs in RA management?
Pain and Inflammation management | No modification of disease outcome
39
Four functions of corticosteroids
Cytokine Inhibition Diminished accumulation of inflammatory cells at site Inhibition of Cox 2 synthesis Decrease circulating T cells
40
How do corticosteroids tend to influence skin?
Thinning, purpura, striae (stretch marks)
41
How do corticosteroids tend to negatively influence eyes?
Cataracts, Glaucoma
42
How do corticosteroids tend to negatively influence blood vessels?
Atherosclerosis | Raised BP
43
How do corticosteroids tend to negatively influence GI?
Risk of peptic ulcers increased if taken with NSAIDS
44
How do corticosteroids tend to negatively influence bones?
Osteoporosis | Can cause avascular necrosis in high dose
45
How do corticosteroids tend to negatively influence pediatric patients?
Growth retardation | Steroid Psychosis
46
How do corticosteroids tend to negatively influence CNS
Euphoria, Steroid Psychosis
47
How do corticosteroids tend to negatively influence the endocrine system?
Glucose Intolerance, Diabetes
48
Other potential concerns about corticosteroids?
Weight gain, obesity Myopathy Increased risk of infections
49
Examples of Disease Modifying Antirheumatic Drugs? | DMARDS
``` Antimalarials Sulfasalazine Gold Nucleotide Pathways TNF agonists, IL1 agonists Costim. modulator IL6 Ab JAK inhibitor ```
50
Classically prescribed antimalarial drug for RA?
Hydroxychloroquin
51
Effects of antimalarial use?
Interference of cellular function in compartments in which there is an acid microenvironment (i.e. lysosomes, endosomes, golgi. This alters immune function, enzyme activity, and immune cell fxn.
52
Side effects of antimalarial use?
Generally well tolerated, but watch for renal toxicity
53
Molecular effects of Sulfasalazine?
Inhibits production of various prostanoids such as leukotriene B4, 5-hydroxyeicosatetraenoic acid, thromboxane A2.
54
Result of taking Sulfasalazine?
Results in reduction of circulating lymphocytes, inhibition of B cell activation
55
Side effects of Sulfasalazine?
Monitor for meylosuppressions, photosensitivity, rash
56
Effects of Gold Therapy?
Inhibits acid P-ase, collagenase, PKC, P-lipase C Reduced Ig synthesis Inactivation of Classic and Alternative Complement pathways Inhibition of lymphocyte proliferative response
57
Side effects of Gold therapy?
Monitor for myelosuppression, oral ulcers, rash, proteinuria
58
What drugs can be used to inhibit Purine nucleotide synthesis?
Methotrexate and Axathioprine
59
What drugs can be used to inhibit pyramidine nucleotide synthesis?
Leflunomide (Arava)
60
Why do nucleotide pathway drugs work?
Activiated lymphocytes require de novo synthesis | The combination of MTX and leflunomide can help with this
61
Side effects of Methotrexate?
Monitor for oral ulcers, pneumonitis, hepatic toxicity, myelosuppression
62
Side effects of Azathiprine?
Myelosuppression
63
Side effects of Leflunomide?
Myelosuppression, hepatic toxicity, hair loss, diarrhea, weight loss
64
Name Three common TNF agonists?
Etanercept (Enbrel) Infliximumab (Remicade) Adalimumab (Humira)
65
What is Etanercept (Enbrel)?
A fusion protein of the TNF receptor and the Fc of IgG
66
What is Infliximumab (Remicade)?
Binding region of a mouse antibody to TNF fused to th Tc of human Ig
67
What is Adalimumab (Humira)?
Recombinant fully human IgG antibody to TNF
68
Efficacy of TNF agonists for RA?
Very good
69
Name an IL1 receptor agonist?
Anakinra (Kineret)
70
Downsides of IL1 receptor agonist?
Painful, Daily injection | No shown benefit with etanercept
71
What might you give to biologically support an RA patient who isn't responsive to TNF blockers?
Abatacept, a costimulation modulator | It is a recombinant protein made of the Extracellular domain of CTLA4 and the constant portion of an IgG
72
How might you promote RA heath by drugging B cells?
Give Rituximab (an anti CD20 antibody) with MTX
73
Name the IL6 antibody?
Tocilizumba (Actemra)
74
Example of a Janus Kinase inhibitor
Tofacitinib (Xeljanz)
75
As of 1996, a triple drug combination has been dubbed the most effected treatment for RA. Name those 3 drugs
Methotrexate Sulfasalazine Hydroxychloroquin
76
True or False, Timing of RA therapy is important?
True Rates of remission were higher Fewer erosions

ICM - Infectious Disease (11 decks)

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