Histology of RA

Histology:

The characteristic that is the most common result of rheumatoid arthritis is the erosion/destruction of joints. This result happens due to the increase in number of immune cells in the synovial membrane.
Below are images that illustrate what rheumatoid arthritis looks like at a histological level.

Figure 1:  Rheumatoid Arthritis in the knee joint.

Figure 1: (A) shows the knee joint being exposed in order to show the erosion of the articulate cartilage of the femur. (B) shows the pannus (tissue) growing over and destroying the cartilage. (C) shows the synovium  portraying finger- like projections due to the presence of the inflammatory cells. 



Figure 1: The synovial lining in patients without proliferation of the lining vs. those with proliferation of the lining due to rheumatoid arthritis.

Figure 1: represents the synovial lining comparing between normal lining and the proliferation of the lining due to rheumatoid arthritis. E stands for patients with early rheumatoid arthritis while L stands for long-standing rheumatoid arthritis. In E-02 the "proliferation resulted in less than four layers and a diffuse infiltration of macrophages in the sub lining regions" (Tsubaki). E-07 shows a typical palisading structure of the intimal lining layer in the lining that was proliferated. E-12 shows "proliferation of the synovial lining more than five layers.  It has a typical palisading structure with several non-foreign body type giant cells" (Tsubaki). There are lesions that make the proliferation of the blood vessels visible at the arteriole level. "This is associated with cell infiltrates composed of lymphocytes and plasma cells in the sub lining regions." (Tsubaki)  There are foci resembling lymphoid follicles however, they lack germinal centers. If comparing E-12 with L-01, L-01 does have lymphoid follicles with germinal centers.

 

 

 

 

 

Figure 3: Villous Hypertrophy of the Synovium



Figure 3: shows the increase in the volume of the synovium due to the enlargement of its component cells which causes the synovium to have a fingerlike appearance.




Figure 4: Chronic inflammation

Figure 4: shows chronic inflammation of the synovium which means that the number of cells has increased.

 

 

Figure 5: Synovial Villi eroding cartilage at the joint.

 

Figure 5: Shows how synovial villi can grow and eventually grow over the joint.

 

 

 

 

 

 



Figure 6: Infiltration of chronic inflammatory cells (in the wrist).



Figure 6: Macrophages, lymphocytes, and plasma cells moving into synovial villi from tissue in the wrist.



Figure 7: Increase in the number of synoviocytes.

Figure 7: Shows the increase in the number of the specialized cells in the synovium called synoviocytes. Together with other immune cells, such as macrophages, lymphocytes, neutrophils, mast cells, and platelets create an inflammatory environment that attracts other immune cells, resulting in the erosion of the joint. 

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Figure 8: A rheumatoid arthritis nodule

Figure 8: Shows a rheumatoid arthritis nodule (a symptom of RA) that contains collagen (stained blue towards the bottom) and surrounding it is macrophages or dendritic cells (types of immune cells). 

 



Symptoms of RA

Symptoms:

Symptoms being slowly with minor joint pain and fatigue. Mostly morning stiffness that last for more than an hour is one of the first signs.  The joint can feel warm and tender or even have loss of range of motion due to the deformity of the joint.

Other symptoms include:

 

• chest pain when taking a breathe
• dry eyes and mouth
• itchy burning eyes
• nodules under the skin (shown below)
• numbness, tingling, or burning in the hands and feet
• sleep difficulties



Nodule under skin by the elbow due to rheumatoid arthritis.

Diagnosis of RA

Diagnosis:

There is not a test to determine rheumatoid arthritis but there are two tests that can help diagnose it.

1.  Rheumatoid Factor Test
2. Anti-CCP Antibody Test

The Rheumatoid Factor Test is a blood test that measures the amount of rheumatoid factor antibody in the blood. If the blood that is tested is abnormal there is a high amount of rheumatoid factor present, however, not everyone with higher levels of the rheumatoid factor have rheumatoid arthritis. People with scleroderma, systemic lupus erythematosus, adult still's disease, dermatomyositis, and sarcoidosis can also have higher levels of rheumatoid factor. Besides these diseases  higher levels can also be seen in those with:

•  aids
•  hepatitis
• influenza
•  infectious mononucleosis
•  some kidney diseases
•  bacterial infections
• parasite infections
• leukemia
• myeloma
• lung and liver disease

Even in some cases people who are completely healthy may have higher rheumatoid factors, therefore, relying solely on the rheumatoid factor test will not determine rheumatoid arthritis. The second test to help diagnose rheumatoid arthritis, the anti-CCP antibody test, is a blood test similar to the rheumatoid factor test. Other tests could also include: a synovial fluid analysis, which is done by drawing synovial fluid from a joint through a needle into a syringe, another could be erythrocyte sedimentation rate which is a blood test. This test measures how fast erythrocytes (red blood cells) fall down a tube. Along with these, x-rays and MRIs are also usually done to see if there is any joint deformation. In addition a discussion of a person's medical history with a physical examination  is done to see whether or not there is any swelling, warmth, pain, or tenderness.




 X-ray of the deformities in the small joints of the hand caused by rheumatoid arthritis.

Treatment of RA

Treatment:

There is no cure for rheumatoid arthritis, but there are medications that can help lessen the effect of the disease There are five main different types of medications:

1. analgesic drugs- relieve pain but do not necessarily reduce inflammation
• Example: acetaminophen
2. non-steroidal anti-inflammatory drugs (NSAIDs)-reduce inflammation and relieve pain
• Example: aspirin and ibuprofen
3. corticosteroids-slow joint damage done by inflammation (usually given in low doses)
4. disease-modifying anti-rheumatic drugs (DMARDs)- can be used with NSAIDs to slow joint damage
• Example: Methotrextrate (most common drug used to treat severe rheumatoid arthritis)
5. Biologic DMARDs-reduces the symptoms of moderate to severe rheumatoid arthritis through an injection
• Example: Humira

*Important to note that all of these drugs can have serious side effects

Other treatments include: physical therapy and a proper nutritious diet. In addition if rheumatoid arthritis severely damages joints it may lead to surgery. Either by removing the lining of the joint called, synovectomy or by having a total joint replacement.

What is Rheumatoid Arthritis?

 

 Rheumatoid Arthritis:

A patient with rheumatoid arthritis.

Rheumatoid arthritis is a chronic inflammatory disease that mainly affects the small joints of the body. These small joints consist of the hands and feet. Unlike osteoarthritis which is the "wear and tear" arthritis (meaning the cartilage at the end of bone wears down over time), it affects the linings of the joints. This causes painful swelling that can lead to bone erosion and deformity. Rheumatoid arthritis is considered an autoimmune disorder which means that the immune system attacks the body's own tissues. It is characterized by polyarthritis because there is inflammation of more than one joint. The macrophages, T cells, and B cells penetrate the synovium while the fluid  in the joint is dominated by neutrophils. The synovium is a thin membrane that lines a space in a joint. When the synovium is attacked fluid builds up in the joint causing inflammation and pain. As time goes on much of the cartilage can wear away and the bone erodes which can cause mobility to become limited. Below is a an illustration that portrays the difference between a normal joint vs. a joint effected by rheumatoid arthritis.

 

 

In most patients with rheumatoid arthritis it becomes a big problem because it starts to affect organs such as the heart. It can also affect the skin, eyes, lungs, and blood vessels. The cause of the disease is unknown which is why having the disease is so disturbing. Possible reasons that researchers have suggested are believed to be infection, genes, and hormonal changes. A rheumatologist who monitors the level of the activity of rheumatoid arthritis will encourage patients to stay physically active manage his/her weight, get enough rest, and maintain a healthy diet.