Rheumatoid arthritis - causes, symptoms, diagnosis, treatment, pathology

Summary

This video provides an in-depth explanation of rheumatoid arthritis, a chronic autoimmune disorder that primarily affects the joints. It covers the disease's mechanism, where the immune system mistakenly attacks joint tissues, leading to inflammation, cartilage damage, and bone erosion. The script explores genetic and environmental triggers, the role of immune cells, and how antibodies contribute to joint destruction. It also highlights common symptoms, joint deformities, extra-articular complications, and diagnostic methods. Finally, it outlines treatment options, including disease-modifying drugs, biologics, and anti-inflammatory medications for managing flares.

Takeaways

• 🦠 Rheumatoid arthritis is a chronic, autoimmune inflammatory disorder that mainly affects joints but can also involve other organs like the skin, lungs, and heart.
• 🦴 Healthy joints are protected by articular cartilage and synovial fluid, which help bones glide smoothly and reduce friction.
• 🧬 Rheumatoid arthritis is triggered by a genetic predisposition and environmental factors, leading to an autoimmune response that attacks the body's own tissues.
• 🧪 The immune response involves proteins like citrullinated vimentin and collagen, causing the immune system to target these as foreign antigens.
• 🔬 Activated immune cells produce cytokines that cause inflammation in the joints, leading to the formation of a pannus that damages cartilage and bone.
• 🧫 Antibodies like rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) form immune complexes that contribute to joint inflammation.
• 💉 The condition also causes extra-articular symptoms such as fever, muscle weakness, rheumatoid nodules, and increased risk of heart disease and lung problems.
• 🖐️ Rheumatoid arthritis typically affects multiple joints symmetrically, particularly the small joints in the hands and feet, leading to deformities over time.
• ⚕️ Diagnosis is based on blood tests for antibodies (RF and CCP) and imaging that shows joint damage and bone erosion.
• 💊 Treatment includes disease-modifying antirheumatic drugs (DMARDs) like methotrexate and biologics, along with anti-inflammatory medications for acute flares.

Q & A

What is rheumatoid arthritis?

Rheumatoid arthritis is a chronic, inflammatory autoimmune disorder that primarily affects the joints but can also involve other organs such as the skin and lungs.

How does rheumatoid arthritis affect a healthy joint?

In a healthy joint, two bones are covered with articular cartilage, which acts as a cushion for smooth movement. Rheumatoid arthritis causes inflammation of the synovial membrane, leading to joint damage, cartilage breakdown, and bone erosion.

What is the role of the synovial membrane in joints?

The synovial membrane lines the joint capsule, produces synovial fluid to lubricate the joint, and helps remove debris from the joint space.

What triggers rheumatoid arthritis?

Rheumatoid arthritis is typically triggered by a combination of genetic susceptibility, such as the presence of HLA-DR1 and HLA-DR4 genes, and environmental factors like smoking or bacterial infections, which can cause modifications to proteins in the body.

What is citrullination and how is it related to rheumatoid arthritis?

Citrullination is a process where the amino acid arginine is converted into citrulline in certain proteins. In rheumatoid arthritis, this modification confuses immune cells, leading to an autoimmune response against these proteins.

How does the immune system contribute to joint damage in rheumatoid arthritis?

Immune cells like T-helper cells and antibodies enter the joint, releasing cytokines that recruit inflammatory cells. This leads to the formation of a pannus, which is a thickened synovial membrane that damages cartilage and bone over time.

What is the role of rheumatoid factor (RF) and anti-CCP antibodies in rheumatoid arthritis?

Rheumatoid factor (RF) is an IgM antibody that targets altered IgG antibodies, and anti-CCP antibodies target citrullinated proteins. Both antibodies form immune complexes in the joint, contributing to inflammation and joint damage.

What are some common deformities seen in rheumatoid arthritis?

Common deformities include ulnar deviation of the fingers, boutonniere deformity, and swan neck deformity, which affect the metacarpophalangeal and interphalangeal joints.

How is rheumatoid arthritis diagnosed?

Rheumatoid arthritis is diagnosed using blood tests that detect rheumatoid factor and anti-citrullinated peptide antibodies. Imaging studies like X-rays show joint damage, soft tissue swelling, and bone erosions.

What treatments are available for rheumatoid arthritis?

Long-term treatment includes disease-modifying antirheumatic drugs (DMARDs) like methotrexate, biologics such as abatacept and adalimumab, and medications that block inflammatory cytokines. Acute flares are treated with NSAIDs and short-term glucocorticoids.

Outlines

00:00

🧠 Understanding Rheumatoid Arthritis and Joint Function

This paragraph introduces rheumatoid arthritis as a chronic inflammatory disorder primarily affecting joints but also potentially involving other organ systems like the skin and lungs. It explains the structure of a healthy joint, focusing on the role of articular cartilage in providing a lubricated surface for bones to glide against. The synovial joint, particularly in areas like the knee, is highlighted with an emphasis on the fibrous joint capsule, synovial membrane, and synovial fluid, which help in joint lubrication. Rheumatoid arthritis is described as an autoimmune process triggered by genetic and environmental factors, such as cigarette smoke or bacterial infections, leading to changes in proteins like type II collagen and vimentin.

05:00

🔬 Autoimmune Response and Inflammatory Cascade

This paragraph dives deeper into the autoimmune mechanism of rheumatoid arthritis. It explains how genetic susceptibility (such as having the HLA-DR1 and HLA-DR4 genes) may cause the immune system to mistakenly recognize altered proteins as foreign. It describes the activation of T-helper cells, B-cells, and the production of autoantibodies like rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (CCP). The paragraph further explains the inflammatory cascade, where cytokines like TNF-α, IL-1, and IL-6 drive synovial cell proliferation, leading to the formation of pannus (inflamed, scar tissue in the joints) and the breakdown of cartilage and bone. The role of T-cells in activating osteoclasts to break down bone is also highlighted.

10:07

⚖️ Joint Damage, Deformities, and Extra-Articular Effects

This section discusses the extensive damage caused by rheumatoid arthritis to joints and other organs. Over time, the inflammatory process leads to joint deformities, such as ulnar deviation and boutonniere and swan neck deformities in the fingers. Rheumatoid arthritis also affects large joints, causing swelling, pain, and stiffness, especially during flares. The paragraph further outlines extra-articular manifestations, including systemic symptoms like fever and muscle weakness, as well as organ-specific issues such as rheumatoid nodules, vasculitis, lung fibrosis, pleural effusion, anemia, and the serious condition known as Felty syndrome, which can lead to life-threatening infections.

🩺 Diagnosing and Managing Rheumatoid Arthritis

The final paragraph explains the diagnosis and management of rheumatoid arthritis. Blood tests are crucial for confirming the disease, particularly looking for rheumatoid factor and anti-citrullinated peptide antibodies. Imaging studies like X-rays reveal typical joint damage signs, such as soft tissue swelling and bony erosions. For long-term treatment, disease-modifying antirheumatic drugs (DMARDs), like methotrexate, hydroxychloroquine, and sulfasalazine, are used to suppress inflammation. Biologic drugs, such as abatacept and rituximab, target T-cells and B-cells, while others like adalimumab and infliximab inhibit specific cytokines. Treatment of acute flares involves anti-inflammatory medications and glucocorticoids. The summary recaps that rheumatoid arthritis is an autoimmune systemic disorder with joint destruction and extra-articular involvement.

Keywords

💡Rheumatoid Arthritis

Rheumatoid arthritis is a chronic, autoimmune inflammatory disorder that primarily affects the joints, but can also involve other organ systems like the skin, lungs, and blood vessels. In the video, it is described as a condition where the immune system mistakenly attacks the body's tissues, leading to joint destruction. The explanation also highlights its systemic effects, such as involvement of organs outside the joints.

💡Synovial Joint

A synovial joint is a type of joint in the body where two bones are connected by a fibrous capsule filled with synovial fluid. The fluid lubricates the joint and allows smooth movement between bones. The video explains the anatomy of a healthy synovial joint and contrasts it with what happens during rheumatoid arthritis, where inflammation damages the joint's structure.

💡Cytokines

Cytokines are small proteins released by cells, particularly in the immune system, that mediate and regulate immunity, inflammation, and hematopoiesis. In rheumatoid arthritis, cytokines like tumor necrosis factor (TNF-α), interleukin-1, and interleukin-6 contribute to inflammation and joint destruction, as described in the video.

💡Pannus

A pannus is an abnormal layer of fibrovascular tissue that forms in rheumatoid arthritis as a result of chronic inflammation. It consists of synovial cells, immune cells, and scar tissue, and it gradually damages cartilage and erodes bone. The video explains how the pannus contributes to the joint destruction seen in rheumatoid arthritis.

💡Autoimmune Disease

An autoimmune disease is a condition in which the immune system attacks the body's own tissues. Rheumatoid arthritis is characterized as an autoimmune disease in the video, where the immune system targets synovial joints and other tissues, mistakenly identifying them as harmful.

💡Citrullination

Citrullination is a biochemical process in which the amino acid arginine is converted into citrulline. This process alters proteins like type II collagen and vimentin, which are then targeted by the immune system in individuals with rheumatoid arthritis. The video explains that citrullination can trigger an immune response leading to the development of autoantibodies.

💡T-helper Cells

T-helper cells are a subset of immune cells that play a critical role in activating and directing other immune cells. In rheumatoid arthritis, T-helper cells stimulate B-cells to produce autoantibodies and release cytokines, exacerbating inflammation in the joints, as described in the video.

💡Rheumatoid Factor (RF)

Rheumatoid factor (RF) is an antibody, specifically an IgM antibody, that targets the Fc portion of altered IgG antibodies. It is commonly found in individuals with rheumatoid arthritis and is used as a diagnostic marker. The video explains how RF contributes to the formation of immune complexes that promote joint inflammation.

💡Anti-cyclic Citrullinated Peptide (CCP) Antibodies

Anti-cyclic citrullinated peptide (CCP) antibodies target citrullinated proteins in individuals with rheumatoid arthritis. The presence of these antibodies is a key diagnostic marker for the disease. The video emphasizes their role in forming immune complexes that further exacerbate joint damage.

💡Biologics

Biologics are a class of medications that target specific components of the immune system, such as T-cells or cytokines, to treat autoimmune diseases like rheumatoid arthritis. The video mentions several biologics, such as abatacept, rituximab, and adalimumab, and how they help in managing the disease by suppressing immune activity.

Highlights

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Rheumatoid arthritis is a chronic inflammatory disorder that primarily affects the joints but can involve other organ systems like the skin and lungs.

Healthy joints have two bones covered with articular cartilage, which acts as a cushion for smooth movement.

A synovial joint is lined with a synovial membrane that produces synovial fluid, lubricating the joint and removing debris.

Rheumatoid arthritis is an autoimmune disease, often triggered by genetic and environmental factors, such as cigarette smoke or certain pathogens.

Citrullination, a process where arginine is converted to citrulline, plays a role in rheumatoid arthritis, confusing immune cells into attacking self-proteins.

T-helper cells stimulate B-cells to produce autoantibodies, which attack the joints and trigger chronic inflammation.

The pannus, a thickened synovial membrane formed by immune cells and scar tissue, damages cartilage and erodes bone.

In rheumatoid arthritis, macrophages and T-cells release inflammatory cytokines, worsening joint destruction.

Antibodies like rheumatoid factor and anti-CCP antibodies bind to their targets in the joint, triggering immune complexes and further inflammation.

Chronic inflammation from rheumatoid arthritis affects other organs, causing fever, muscle wasting, vasculitis, and rheumatoid nodules.

Rheumatoid arthritis can lead to joint deformities, such as ulnar deviation, boutonniere deformity, and swan neck deformity.

The disease also causes extra-articular symptoms like anemia, interstitial lung disease, and cardiovascular complications.

Treatment for rheumatoid arthritis includes disease-modifying antirheumatic drugs (DMARDs) like methotrexate and biologics targeting specific immune pathways.

During acute flares, anti-inflammatory medications like NSAIDs and glucocorticoids are used to reduce inflammation and manage symptoms.

Transcripts

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In rheumatoid arthritis, “arthr-“ refers to joints, “-itis” means inflammation,

and “rheumatoid” comes from rheumatism, which more broadly refers to a musculoskeletal

illness.

So, rheumatoid arthritis is a chronic, inflammatory disorder that mostly affects the joints, but

can also involve other organ systems like the skin and lungs as well.

Alright, so a healthy joint typically has two bones covered with articular cartilage

at the ends.

Articular cartilage is a type of connective tissue that acts like a protective cushion

- a lubricated surface for bones to smoothly glide against.

One type of joint, like the knee joint is called a synovial joint.

A synovial joint connects two bones with a fibrous joint capsule that is continuous with

the periosteum or outer layer of both bones.

The fibrous capsule is lined with a synovial membrane that has cells that produce synovial

fluid and remove debris.

The synovial fluid is normally a viscous fluid like the jelly-like part of a chicken egg

and it helps lubricate the joint.

To help serve these synovial cells, the synovial membrane also has blood vessels and lymphatics

running through it.

Together, the synovial membrane and the articular cartilage form the inner lining of the joint

space.

Rheumatoid arthritis is an autoimmune process that is typically triggered by an interaction

between a genetic factor and the environment.

For example, a person with a certain gene for an immune protein like human leukocyte

antigen, or HLA- DR1 and HLA–DR4, might develop rheumatoid arthritis after getting

exposed to something in the environment like cigarette smoke or a specific pathogen like

a bacteria that lives in the intestines.

These environmental factors can cause modification of our own antigens, such as IgG antibodies

or other proteins like type II collagen or vimentin.

Τype II collagen and vimentin can get modified through a process called citrullination.

That’s when the amino acid arginine found in these proteins is converted into another

amino acid, citrulline.

Meanwhile, due to the susceptibility genes HLA- DR1 and HLA–DR4, immune cells sometimes

are not “clever” enough, so they get confused by these changes and they no longer recognize

these proteins as self-antigens.

The antigens get picked up by antigen- presenting cells, and get carried to the lymph nodes

to activate CD4+ T-helper cells.

T-helper cells stimulate the nearby B- cells to start proliferating and differentiate into

plasma cells, which produce specific autoantibodies against these self- antigens.

In rheumatoid arthritis, T- helper cells and antibodies enter the circulation and reach

the joints.

Once there, T- cells secrete cytokines like interferon- γ and interleukin- 17, to recruit

more inflammatory cells like macrophages, into the joint space.

Macrophages will also produce inflammatory cytokines, like tumor necrosis factor, or

TNF- α, interleukin- 1 and interleukin- 6, which together with the T-cell’s cytokines,

stimulate synovial cells to proliferate.

The increase in synovial cells and immune cells creates a pannus, which is a thick,

swollen synovial membrane with granulation or scar tissue, made up of fibroblasts, myofibroblasts

and inflammatory cells.

Over time, the pannus can damage cartilage and other soft tissues and also erode bone.

Activated synovial cells also secrete proteases which break down the proteins in the articular

cartilage.

Without the protective cartilage, the underlying bones are exposed and can directly rub against

one another.

In addition, inflammatory cytokines increase a protein on the surface of T- cells, known

as RANKL or receptor activator of nuclear factor kappa-B ligand.

RANKL allows the T-cells to bind RANK, a protein on the surface of osteoclasts, to get them

to start breaking down bone.

Meanwhile, antibodies also enter the joint space.

One antibody is called rheumatoid factor, or RF, which is an IgM antibody that targets

the constant Fc domain of altered IgG antibodies.

Another antibody is anti-cyclic citrullinated peptide antibody, or CCP, which targets citrullinated

proteins.

When these antibodies bind to their targets, they form immune complexes which accumulate

in the synovial fluid.

There, they activate the complement system, a family of 9 small proteins that work in

an enzymatic cascade to promote joint inflammation and injury.

Finally the chronic inflammation causes angiogenesis, or the formation of new blood vessels around

the joint, which allows even more inflammatory cells to arrive.

As the disease progresses, multiple joints on both sides of the body get inflamed and

gradually destroyed.

But these inflammatory cytokines don’t just stay within the tight joint space.

Instead, they escape through the bloodstream and reach multiple organ systems causing extra-articular

problems, meaning problems beyond the joint space.

For example, interleukin-1 or -6 travel to the brain, where they act as pyrogens, inducing

fever.

In skeletal muscle, they promote protein breakdown and in the skin, as well as in many visceral

organs, they lead to the formation of rheumatoid nodules, which are round- shaped collections

of macrophages and lymphocytes with a central area of necrosis, or tissue death.

Blood vessels can also be affected.

Their walls get inflamed, resulting in various forms of vasculitis and make them prone to

developing atheromatous or fibrofatty plaques.

In response to inflammatory cytokines, the liver also starts producing high amounts of

hepcidin, a protein that decreases serum iron levels by inhibiting its absorption by the

gut and trapping it into macrophages or liver cells.

Meanwhile, within the lung interstitium, fibroblasts get activated and proliferate, causing fibrotic

or scar tissue that makes it harder for the alveolar gas exchange, while also the pleural

cavities surrounding the lungs can get inflamed, filling up with fluid, known as pleural effusion,

and this can sometimes mess with lung expansion.

Rheumatoid arthritis typically involve multiple joints, usually five or more, symmetrically,

meaning the same joint groups on both sides of the body, like both hands for instance.

Commonly affected joints are the small joints like metacarpophalangeal and proximal interphalangeal

joints of the hands, and the metatarsophalangeal joints of the feet.

As the disease worsens, it can start to affect large joints like the shoulders, elbows, knees

and ankles.

During “flares” or sudden worsening of the disease, the affected joints get extremely

swollen, warm, red, and painful.

Over time, they become stiff, especially in the morning or after being inactive for a

prolonged period of time.

People with rheumatoid arthritis may develop specific deformities, usually of the metacarpophalangeal

joints in the hand, such as ulnar deviation of the fingers.

Deformities are also common in the interphalangeal joints, such as the so- called boutonniere

or buttonhole deformity.

This occurs when the extensor tendon in the back of the finger splits and the head of

the proximal phalanges pokes through like a button through a buttonhole, causing flexion

of the proximal interphalangeal joint and hyperextension of distal interphalangeal joint.

Another finger deformity is the swan neck deformity, which is the opposite, so there’s

hyperextension of the proximal interphalangeal joint and flexion of the distal interphalangeal

joint.

Now, in the knee joint, a one-way value can form, with fluid from the swollen knee filling

the semi-membranous bursa.

When that happens, the synovial sac can get so swollen that it bulges posteriorly into

the popliteal fossa, creating a synovial fluid-filled cyst, called a Baker or popliteal cyst.

Now, extra- articular manifestations include non-specific symptoms of inflammation, such

as fever, low appetite, malaise or muscle weakness, and organ- specific, manifistations

include rheumatoid nodules or firm bumps of tissue, and these most commonly in the skin

around pressure points, such as the elbows.

More rarely, in the lungs, the heart, or the sclera of the eye.

There’s also an increased risk of atherosclerosis and therefore, heart attack or stroke.

There’s also anemia, interstitial lung fibrosis and pleural effusions, which can present as

progressive shortness of breath.

One particularly serious condition that’s associated with rheumatoid arthritis is Felty

syndrome which is a triad of rheumatoid arthritis, splenomegaly, and granulocytopenia, and it

can lead to life-threatening infections.

Diagnosis of rheumatoid arthritis usually involves confirmatory blood tests, like looking

for the presence of rheumatoid factor and anti-citrullinated peptide antibody.

Additionally, imaging studies, such as X- ray, usually reveal decreased bone density

around affected joints, soft tissue swelling, narrowing of the joint space, and bony erosions.

The long term management of rheumatoid arthritis is use of disease-modifying antirheumatic

medications like methotrexate, hydroxychloroquine, sulfasalazine, and which can help to suppress

the inflammation.

In addition, there are a variety of medications called biologic response modifiers or biologics.

Some biologics, such as abatacept, work by suppressing the activity of T cells, or others,

such as rituximab suppress B cells.

There are also biologics such as adalimumab, etanercept, and infliximab, that block various

chemokines like tumor necrosis factor.

Anakinra blocks interleukin 1 which is blocked by, and tocilizumab blocks interleukin 6.

Treatment of acute flares can be done with anti- inflammatory medications like NSAIDS

as well as short term use of glucocorticoids.

All right, so as a quick recap, rheumatoid arthritis is a systemic inflammatory disorder

of autoimmune origin that is primarily characterized by progressive, symmetric joint destruction,

especially in the wrists and fingers, but may also affect other joints and many organs,

such as the skin, heart, blood vessels and lungs.

It’s marked by elevated rheumatoid factor and anti- cyclic citrullinated peptide antibodies.