RA

Question 1

Arthropathy

Answer 1

Pathology of the joints

Question 2

Inflammatory arthritis

Answer 2

Includes a whole range of disease caused by inflammation. The immune system is at fault here. RA is one of the examples of this

Question 3

Difference between primary and secondary arthritis

Answer 3

Secondary is when it is caused b trauma that may have happened several years ago or caused by genetics

Question 4

Places where primary arthritis affects

Answer 4

Knee, hands, wrist etc More specifically they are PIP, DIP and carpometacarpal.

Question 5

One way to diagnose secondary arthritis

Answer 5

The pain doesn’t happen in places observed with primary arthritis

Question 6

Fundamental differences between RA and OA

Answer 6

OA is usually not bilateral, it is in an isolated joint such as a specific knee or shoulder. For RA these features are observed:

a. Systemic polyarticular involvement: usually 5, more joints than osteo, can be bilateral.
b. Upper and lower extremities are involved
c. PIPs are strongly involved, DIPs are not involved that helps with separating form osteo and rheumatoid
d. Osteo involves backpain, rheumatoid does not. People can have both osteo and rheumatoid so they can present with both of the disease symptoms
e. Predominant morning stiffness, usually last for more than hour, can be for several hours, in untreated patients it can take several hours, goes down with treatment
f. Joints effected are MCPs, PIPs, MTPs and wrists

Question 7

Which one is systemic and which one is local in terms of RA and OA

Answer 7

RA is systemic, OA is local

Question 8

Answer 8

Know where the following features are: Z deformity on the thumb, Swann neck on the left pinky finger, Boutonniere deformity on the ring finger, these are all the signs of untreated rheumatoid arthritis

Question 9

Answer 9

We can see here that the PIPs are swollen, DIPs are not swollen, we can feel the fluid on PIPs on examination and feel the bone on DIPs. Fingernails tell us that the person was a smoker, which is a risk factor of rheumatoid arthritis

Question 10

Pulmonary manifestations of RA

Answer 10

1. Since it is a systemic disease it also affects the lungs, she showed us a CT scan of a person who had very less normal lung tissue because there were honeycomb structures observed which were scarring due to the immune system attacking the lungs. a. There can be pleural disease where the pleural cavity is filled with fluid b. The above describes is interstitial lung disease c. There can also be pulmonary nodules

Question 11

Cardiac manifestations

Answer 11

1. Cardiac manifestation: a. Pericarditis: inflammation of the lining of the heart b. Myocarditis: inflammation of the muscle tissue of the heart c. Pericardial effusion: fluids in the lining of the heart d. Nodules on the valves of the heart e. Early or accelerated cardiac disease or heart diseases – driven by inflammation

Question 12

Skin manifestations

Answer 12

1. Skin manifestations: a. Nodules on the fingers – rheumatoid nodules b. Rheumatoid vasculitis – inflammation of blood vessel at the tip of fingers causing blockade and hypoxia leading to gangerene

Question 13

Eye involvement

Answer 13

1. Eye involvement: a. Dryness in the eye called the secondary Sjogren’s syndrome b. Episcleritis and scleritis which can progress to corneal melt

Question 14

Other manifestations

Answer 14

1. Other manifestations include: a. Felty’s syndrome: splenomegaly, leukopenia and RA b. Leukocytosis, thrombocytosis and anemia

Question 15

First clinical manifestation and the more concerning clinical symptom

Answer 15

1. The very first clnical manifestation of rheumatoid arthirits is the carpal tunnel syndrome due to inflammation in the wrist – an example of entrapment neuropathy. 2. The more concerning symptoms is the inflammation in C1-C2 region of the spine that is gonna press against the brain stem and may lead to paralysis

Question 16

Prevalence and genetic linkage

Answer 16

General population has 1%, monozygotic twins have 20% and dizygotic twins have 5%.

Question 17

Gene

Answer 17

Strongly linked to RA is HLA-DRB1 locus.

Question 18

Environmental factors

Answer 18

a. Silica – miners are more prone b. Smoking c. Periodontal disease which is due to porphyromonas ginigvalis d. Gut microbiome – certain microbes in the gut makes you more prone to have RA

Question 19

Environmental factors

Answer 19

a. Silica – miners are more prone b. Smoking c. Periodontal disease which is due to porphyromonas ginigvalis d. Gut microbiome – certain microbes in the gut makes you more prone to have RA

Question 20

Immune system components involved

Answer 20

a. Th17 cells are at the heart of this b. Antigen presenting B cells are important – because rituximab is effective in treating RA c. Autoantibodies are made which are important to treat to control the symptoms of this disease

Question 21

Mechanism of bone erosion:

Answer 21

Mechanism of bone erosion: a. Synovitis (inflammation in the synovial fluid) has TNF, IL-1 and IL-6. b. These act on the RANK-L c. This activates osteoclast, leading to bone destruction

Question 22

Role of macrophages

Answer 22

They make all the cytokines and recruit neutrophils and mast cells

Question 23

When treating RA why are we only concerned with joint pain and monitoring the progress of joint pain

Answer 23

Joint pain is indicative of other clinical manifestation and it can accuratly predict the progress of RA

Question 24

What are some of the labs that we can order for diagnosis, progress and treatment

Answer 24

For diagnosis: RF and CCP (Anti cyclic citrullinated peptide)

Progress: ESR and CRP

Treatment: CBC with differential and look for creatinine levels, AST and ALT to keep an eye on liver toxicity.

ANA can be done to check for lupus. Sometimes it is positive.

Question 25

What is the realtionship of CRP and RA

Answer 25

IL-6 is released that goes to the liver and leads to CRP activation and release. Increased levels of CRP corresponds with increased joint pain and a worse prognosis

Question 26

RF

Answer 26

Can either be positive or negative, there are alot of false positived due to poor test specificity

Question 27

CCP

Answer 27

To check for antibodies against citrullinated proteins (arginine can be converted to citrulline by PAD in post translational modifications). This test has a higher specificity so its better than the RF test (sensitivity is the same) so there are fewer false positives.

Question 28

How does P. Gingivalis can lead to developing RA

Answer 28

1. P.Gingivalis causes peridontium disease. 2. The bacterium has its own PAD enzyme that citrullinates the host proteins or the bacterial proteins. 3. Our immune system develops antibodies called the ACPAs (anti citrullinated proteins antibodies) to fight off the function 4. People with genetic susceptibility due to HLA-DRB1 gene share epitope with their own citrullinated proteins. ACPAs are made to attack their own proteins. 5. This leads to plasma cells making antibodies that causes RA

Question 29

How does smoking promote RA

Answer 29

Smoking increases PAD enzymes and citrullination in the lung

Question 30

Seropositive vs Seronegative RA

Answer 30

Seronegative = RF and CCP (cyclic citrullinated proteins) negative RA patients Seropositive = one of them is positive 15 to 20% of the people with RA are seronegative

Question 31

What if RF or CCP is positive but they dont have symptoms of RA

Answer 31

You might be catching these patients in the upstream so this might be the pre clinical stage of arthritis. These people are more likely to develop RA since these test check for antibodies that lead to development of RA

Question 32

What is another test to check for RA

Answer 32

Synovial fluid test. Important thing here to check is if there will be a viral or bacterial infection which will rule out RA. 5000 to 50,000 neutrophil count is usually observed

Question 33

Answer 33

Periarticularosteopenia Washing out of the bones at PIP joints due to inflammation

Question 34

Answer 34

Erosion of ulnar styoid

Question 35

Answer 35

Big areas of bone erosions that can be seen only via MRI

Question 36

Answer 36

Psoriatic Arthritis: tips of the fingers and DIPs are severly damaged

Question 37

Comparison of RA and OA

Answer 37

Question 38

DMARDs

Answer 38

Some of the older medication for rheumatoid arthritis. It stands for Disease Modifying Anti-Rheumatic drugs. These are 1. Immunosuppressive drugs 2. Taken orally

Question 39

What is the most common treatment for RA

Answer 39

We dont really know how it works: 1. Inhibits dihydrofolate reducatase, inhibits the synthesis of purines and pyrmaidines for DNA synthesis. 2. Folic acid is given to prevent side effects (in Gen/Neo they said Folate acid increases effectiveness)

Question 40

How is methotrexate given

Answer 40

Oral or via IV. It is used in much smaller doses. Also cant be used in woman who want to get pregnant.

Question 41

What is another medicine given for RA

Answer 41

Lefleunomide 1. Inhibits pyramidine synthesis leading to reduction of lymphocytes. 2. It is a prodrug, liver breaks it down so due to this mechanism it has a longer half life 3. Side effects are diarrhea, cytopenia and liver toxicity

Question 42

What is another drug she mentioned for RA

Answer 42

Hydroxychloroquine (Plaquenil) 1. Inhibits toll like receptors and acidification of lysosomes for antigen processing 2. Taken orally 3. Side effect are rare, retinal toxicity

Question 43

Another drug

Answer 43

Sulfasalazine Side effects: Rash, GI, hepatoxicity, cytopenia Taken orally

Question 44

Last drug she mentioned

Answer 44

Azathiopurine 1. Purine synthesis is inhibited 2. Oral 3. Side effects are: cytopenia, rash, GI upset, pancreatitis

Question 45

What are the biologic medications used in RA

Answer 45

These are the medication that specifically target the components involved in the pathogenesis of RA

Question 46

What is the first example she gave us

Answer 46

Anti TNF 1. Reduces joint inflammation

Question 47

What is another medication used for RA

Answer 47

Tocilizumab 1. Anti-IL-6 2. Reduces inflammation and joint damage 3. IV or subcutaneous administration

Question 48

What are some of the other example she gave us

Answer 48

1. Anakinra - anti IL-1, not effective 2. Abatacept - she said it blocks T cell activation 3. Rituximab - very effective, not known why, administration is IV. 4. Tofacitinib - it is a pill, it is a JAK inhibitor, so reduces development of immune response and inflammation