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Flashcards in RA Deck (48):


Pathology of the joints


Inflammatory arthritis

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


Difference between primary and secondary arthritis

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


Places where primary arthritis affects

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


One way to diagnose secondary arthritis

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


Fundamental differences between RA and OA

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


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

RA is systemic, OA is local


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


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


Pulmonary manifestations of RA

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


Cardiac manifestations

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


Skin manifestations

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


Eye involvement

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


Other manifestations

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


First clinical manifestation and the more concerning clinical symptom

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


Prevalence and genetic linkage

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



Strongly linked to RA is HLA-DRB1 locus.


Environmental factors

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


Environmental factors

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


Immune system components involved

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


Mechanism of bone erosion:

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


Role of macrophages

They make all the cytokines and recruit neutrophils and mast cells


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

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


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

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. 


What is the realtionship of CRP and RA

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



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



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. 


How does P. Gingivalis can lead to developing RA

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


How does smoking promote RA

Smoking increases PAD enzymes and citrullination in the lung


Seropositive vs Seronegative RA

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


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

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


What is another test to check for RA

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



Washing out of the bones at PIP joints due to inflammation


Erosion of ulnar styoid


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


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


Comparison of RA and OA



Some of the older medication for rheumatoid arthritis. It stands for Disease Modifying Anti-Rheumatic drugs. These are

1. Immunosuppressive drugs

2. Taken orally


What is the most common treatment for RA

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)


How is methotrexate given

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


What is another medicine given for RA


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


What is another drug she mentioned for RA

Hydroxychloroquine (Plaquenil)

1. Inhibits toll like receptors and acidification of lysosomes for antigen processing

2. Taken orally

3. Side effect are rare, retinal toxicity


Another drug


Side effects: Rash, GI, hepatoxicity, cytopenia

Taken orally


Last drug she mentioned


1. Purine synthesis is inhibited

2. Oral

3. Side effects are: cytopenia, rash, GI upset, pancreatitis


What are the biologic medications used in RA

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


What is the first example she gave us

Anti TNF

1. Reduces joint inflammation


What is another medication used for RA


1. Anti-IL-6

2. Reduces inflammation and joint damage

3. IV or subcutaneous administration


What are some of the other example she gave us

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