Rheumatoid arthritis is a chronic inflammatory disorder that gradually affects synovial joints,
but can also cause extra-articular disease as well.
Rheumatoid arthritis has been linked to HLA-DR1 and HLA-DR4.
Each time there’s a flare, there’s an increase in synovial and immune cells, and
over time, that results in a thick, swollen synovial membrane with granulation tissue
- called a pannus.
The pannus can damage cartilage and other soft tissues and also erode bone.
Typically, rheumatoid arthritis affects at least three joints, generally ones in the
hands and feet.
The disease tends to be symmetric, progressive, and over time it causes joint deformities
like crooked fingers.
So the typical articular manifestations in rheumatoid arthritis are pain, swelling, and
loss of mobility in the affected joints, but doesn’t usually cause redness or warmth
because the inflammatory process is so gradual.
Usually, there’s morning stiffness that improves after 30 minutes of movement.
The most frequent sites of involvement are the proximal interphalangeal joints and metacarpo-phalangeal
joints of the hand, whereas the distal interphalangeal joints is rarely involved because there’s
very little synovium in that joint.
When these joints are affected, it typically causes reduced grip strength.
In the feet, usually the metatarsophalangeal joints are affected, and it causes a person
to bear more weight on the heels and hyperextend the toes.
Other joints that can be involved are the wrists, elbows, shoulders, knees, and ankles.
Hip involvement usually only happens later in the disease, and that can cause pain in
the groin, thigh, or low back.
One very dangerous spot is the C1-C2 joint, which is only synovial joint in the spine.
When it’s affected it can cause neck pain, and if it’s not managed properly it can
lead to spinal cord compression and tetraplegia.
The system inflammation in rheumatoid arthritis results in cytokines that can cause extra-articular
symptoms.
For example, cytokines can trigger fever, fatigue, and a loss of appetite that can eventually
lead to weight loss.
Rheumatoid arthritis can lead to vasculitis and specifically the formation of atheromatous
plaques, which can lead to myocardial infarction and stroke.
In fact, cardiovascular disease is the primary cause of mortality associated with rheumatoid
arthritis.
In skeletal muscle, cytokines cause muscle breakdown, and in the skin they lead to the
formation of rheumatoid nodules over bony prominences.
Rheumatoid nodules are round collections of macrophages and lymphocytes that have a central
area of necrosis.
In the liver, lots of hepcidin is made and that causes decreased iron absorption in the
intestines, and allows iron to get trapped in the macrophages - leading to lower serum
iron levels.
In the lung, fibroblasts get activated, causing pulmonary fibrosis, and the pleural lining
gets inflamed, leading to pleural effusions.
Laboratory testing typically includes a complete blood count, which might show anemia of chronic
inflammation, thrombocytosis, and a mild leukocytosis.
In addition, an ESR and CRP since they’re markers of systemic inflammation.
It’s also important to test for autoantibodies like rheumatoid factor and anti-cyclic citrullinated
peptide antibodies, both of which are present in most individuals with rheumatoid arthritis.
A minority of individuals may have antinuclear antibodies as well.
Bilateral plain radiographs of the hands, wrists, and feet are also important as a baseline
for monitoring disease progression.
Over time, changes might include decreased bone density around affected joints, soft
tissue swelling, narrowing of the joint space, and bone erosions.
The diagnosis of rheumatoid arthritis can be made if the disease has gone on for at
least 6 weeks, involves at least three joints, there’s a positive rheumatoid factor or
anti-citrullinated peptide antibody, and an elevated CRP or ESR.
In some cases, arthrocentesis may be done to evaluate the synovial fluid, to make sure
there’s no evidence of crystals like in gout or pseudogout or signs of infection.
Now, in 2010 classification criteria were proposed, which establish 10 point scale,
where getting at least 6 points out of 10, supported the diagnosis of rheumatoid arthritis.
The first criterion gives points for either large joint or small joint involvement - whichever
gets the higher point amount.
Looking at large joints, if at least 2 large joints from among the shoulders, elbows, hips,
knees, and ankles are affected - that gives 1 point.
Looking at the small joints, if at least 1 to 3 small joints from among the metacarpophalangeal
joints, proximal interphalangeal joints, second through fifth metatarsophalangeal joints,
thumb interphalangeal joints, and wrists are affected - that gives 2 points.
If 4 to 10 small joints are affected, that gives 3 points; and if more than 10 small
joints are affected, that gives 5 points.
The second criterion gives points based on the autoantibody levels.
If there’s a low positive rheumatoid factor and anti-citrullinated protein antibody, meaning
above normal but below three times the upper limit of normal, than that gives 2 points.
If there’s a high positive rheumatoid factor and anti-citrullinated protein antibody, meaning
more than three times the upper limit of normal, then that gives 3 points.
The third criterion involves the ESR or CRP - if either are elevated that gives 1 point.
And finally, the fourth criterion involves the duration of arthritis, giving 1 point
if it has lasted over 6 weeks.
There’s no cure for rheumatoid arthritis, but medications called disease-modifying antirheumatic
drugs or DMARDs are long-term medications, can minimize symptoms and prevent bone deformity.
Most individuals with rheumatic fever are started on non-biological DMARDs, like methotrexate.
But some individuals like pregnant women can’t take methotrexate, so they should get another
non-biological DMARD like leflunomide, hydroxychloroquine, or sulfasalazine.
And individuals with severe disease get biological DMARDs, also called biologics, all of which
suppress some part of the immune system.
For example, abatacept suppresses T cells, rituximab suppresses B cells.
Some block chemokines, for example, adalimumab, etanercept, and infliximab all inhibit tumor
necrosis factor or TNF, anakinra blocks interleukin 1, and tocilizumab blocks interleukin 6.
Individuals with rheumatoid arthritis should be seen at least every three months to monitor
the response to therapy, and those who don’t respond to initial DMARD therapy should get
a combination of DMARDs, such as methotrexate plus either hydroxychloroquine and sulfasalazine
or a TNF inhibitor.
In addition to long-term medications, short-term medications like NSAIDs or even glucocorticoids
like prednisone can be used to treat an acute flare.
Finally, since individuals with rheumatoid arthritis have an increased cardiovascular
risk, they should take preventive measures like exercise and smoking cessation, as well
as routine use of low doses of aspirin and lipid control with statins.
Alright, as a quick recap… rheumatoid arthritis causes progressive, symmetric destruction
of at least three joints, especially in the hands and feet, over more than 6 weeks.
But the main mortality comes from cardiovascular disease, especially myocardial infarction
and stroke.
Diagnosis is generally based on joint involvement, having an elevated rheumatoid factor and anti-cyclic
citrullinated peptide antibodies, and an elevated ESR and CRP.
In addition, bilateral plain radiographs of the hands, wrists, and feet are generally
obtained during the initial evaluation primarily as a baseline for monitoring disease progression.
The long term management of rheumatoid arthritis is use of non-biological DMARDs.
In addition, severe cases get biological DMARDs.
Treatment of acute flares can be done with NSAIDs, while more severe flares may require
short term use of glucocorticoids like prednisone.
In addition, individuals should take preventive measures for cardiovascular disease like exercise
and smoking cessation, as well as routine use of low doses of aspirin and lipid control
with statins.