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Osteoarthritis & Rheumatoid Arthritis

Osteoarthritis & Rheumatoid Arthritis

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Overview

Overview

Here, we'll learn about the main forms of arthritis.

Arthritis vs arthropathy

  • Although the strict definition of arthritis suggests an inflammation of the joints, we tend to use the term, clinically, synonymously with "joint disease", regardless of the degree of inflammation.

Non-autoimmune vs Autoimmune arthritides

Denote that we will divide our discussion into:

  • Non-autoimmune-related forms of arthritis
  • Autoimmune-related forms

Osteoarthritis vs Rheumatoid arthritis

In part 1 of these tutorials, we will address:

Additional Non-autoimmune arthritis

In part 2, we will address the following non-autoimmune arthritides:

Additional Autoimmune arthritis

And we will address the following autoimmune arthritides:

Juvenile idopathic arthritis

Osteoarthritis

  • Let's begin with a discuss of osteoarthritis, the most common form of arthritis.

Clinical Features

Joint pain

  • Joint pain, deformities (enlargement and possible twisting), and immobility

Limited morning stiffness

  • There is limited morning stiffness (less than 30 minutes) – which distinguishes it from rheumatoid arthritis

Worsening with activity

  • Symptoms worsen with activity.

pathogenesis

Degenerative

  • Degenerative disorder, due to so-called "wear and tear", with mild inflammation.
    • There is debate about the degree of inflammation in osteoarthritis and its role in the pathogenesis of the disease.

Thinning of articular cartilage

  • The foremost pathological finding is thinning/break-down of articular cartilage.
    • Note that articular cartilage is hyaline cartilage – it is avascular and devoid of lymphatics or nervous system structures.

Knee findings

Healthy Knee Anatomy

  • The knee is a synovial joint: it comprises an articular capsule, articular cartilage, and synovial fluid.
  • Indicate that the knee joint connects the femur and the tibia. Include the fibula for completeness.
  • At the ends of the femur and tibia, draw articular cartilage, which provides a smooth covering to help the bones glide across one another.
  • On the tibia plateau, draw medial and lateral menisci; they comprise fibrocartilage, which acts as a cushion (a shock-absorber).
  • Next, draw the articular capsule, which is continuous with the periosteum of the articulating bones, and show that it comprises a thick, fibrous outer layer, a thin, inner, synovial layer (the synovium or synovial membrane), and indicate that it is filled with synovial fluid.
  • Finally, show ligaments connect the bones – ligaments are bands of fibrous connective tissue that help stabilize the joint and restrict its range of motion.
    • Note that the knee joint ligaments are divided into intracapsular and extracapsular ligaments.

Osteoarthritis

In osteoarthritis, there is:

  • Cartilage degeneration.
    • There is thinning of the articular cartilage, degeneration of the fibrocartilaginous menisci, and resultant joint space narrowing.
    • Articular cartilage thinning is the foremost pathological finding in osteoarthritis (the cartilage swells and then ultimately softens and thins).
  • Bony deformation.
    • Indicate that there is development of bone spurs (osteophytes) at the joint margins and subchondral sclerosis, which is hardening of the bone underneath the cartilaginous surface.
  • Synovial inflammation (synovitis).
    • Damaged cartilage initiates the release of cytokines and other inflammatory mediators that lead to synovial inflammation and further cartilage breakdown.

Predisposing factors

Now, let's address some key predisposing factors for osteoarthritis, which include:

  • Age (roughly half of people over 65 years old have osteoarthritis)
  • Obesity
  • Joint trauma
    • Especially from excessive load bearing – think about obesity and excessive high impact loading as key causes of trauma
  • Female sex
    • Consider that chondrocytes, which are a key component of articular cartilage have estrogen receptors

Labwork

In regards to diagnostic labwork, indicate that:

  • Synovial fluid (obtained via joint fluid aspiration) has less than 2,000 white blood cells (WBCs) per cubic millimeter (remember that the inflammation, if present, is mild).
  • Antibody testing (if no other systemic illness is present) is normal (negative).

Affected Joints

  • We'll indicate those that are jointly affected in rheumatoid arthritis, because a key aspect of our clinical approach to arthritis is differentiating these two disorders.

Asymmetric

  • Draw a human figure – here only draw one-half of a body because osteoarthritis is classically considered to be asymmetrical, although symmetrical disease does commonly occur.
    • This is in comparison to rheumatoid arthritis in which the joints are affected symmetrically.

DIP joints & lower spine

  • As a generality, show that the distal interphalangeal (DIP) joints and lower spine are affected in OA but not RA.
    • Star the finding of DIP joint disease because it helps us distinguish OA from RA, in which the MCP joints are the primary site of disease.
  • Then, show that the proximal interphalangeal (PIP) joints, cervical spine, hips, and knees are affected in both OA and RA.

Finger Deformities

Now, let's look at key finger deformities in OA.

  • Draw a hand and show that OA at the DIP joint is called Heberden's node and at the PIP joint is called Bouchard's node.
    • Note that in a minority of patients, erosive osteoarthritis can lead to more rapid and more pronounced deformation of the joints with twisting and lateral deviation of the distal phalanges.

Rheumatoid Arthritis

Clinical Presentation

Indicate that it typically presents with:

Symmetric joint pain

  • Symmetric joint pain (especially of the hands (MCPs, PIPs, wrists), stiffness, and swelling over at least 6 weeks (remember that OA is classically asymmetric)

Fatigue

  • Prominent fatigue and low-grade fever

Morning stiffness

  • Morning stiffness usually > 60 minutes
    • Remember that morning stiffness in OA was limited to less than 30 minutes.

Pathogenesis

Autoimmune response to citrullinated proteins. Pannus formation.

  • Indicate that its pathophysiology involves an autoimmune response to citrullinated proteins (a loss of self-tolerance to citrulline-containing self-proteins), that leads to joint destruction via synovitis and pannus formation and resultant cartilage and bone break-down, as well as systemic inflammation.

Systemic complications

  • Systemic inflammation produces extra-articular manifestations (disease outside of the joint), which can involve wide-spread organ systems, including cardiac, pulmonary, vascular, neuromuscular, dermatologic, ocular, and hematologic systems.

Knee findings

Cartilage thinning and ankylosis

  • Cartilage thinning and joint space narrowing (like in OA) but also bone fusion (called ankylosis), which is not found in OA.
    • Note that in part 2 of this tutorial, we will address ankylosing spondylitis, which is a disease of prominent joint fusion.
  • Indicate that there is prominent osteopenia and bony erosion, especially at the joint margins; whereas, in OA bone spurs and sclerosis are prominent.

Pannus formation

  • Show prominent synovitis and pannus formation and star this finding, which is the major differentiator of RA vs OA.
    • Indicate that pannus refers to invasive inflammatory synovial tissue – a hyperplastic (thickened, edematous, vascularized) synovial membrane, which comprises inflammatory mediators and neovasculature that invades the joint and destroys bone (via osteoclasts) and cartilage (via synoviocytes (most notably), as well as via other destructive cells such as neutrophils and chondrocytes).

Osteoarthritis vs Rheumatoid Arthritis

  • Most notably, prominent inflammation invades the joint in RA, which does not occur in OA – in OA, there is mild inflammation, at most.
  • In OA, there is prominent formation of bone spurs and sclerosis whereas this these features are negligible in RA.
  • In RA, there is prominent osteopenia and bony erosions, which are negligible in OA.
  • In both conditions, there is prominent joint narrowing via cartilage break-down but in RA, ankylosis – bone fusion – can also occur (which does not occur in OA).

Predisposing factors

Female sex

  • It occurs in women (most commonly in their mid-thirties) roughly 3 times more than men (most commonly in their mid-fifties) (remember that OA tends to occur much later in life).
  • Indicate that the following can upregulate protein arginine deiminases (PADs), which citrullinate proteins:
    • Smoking, which upregulates PAD enzymes in the lungs and confers a ~ 12-fold increase risk of RA.
    • Chronic periodontitis, which changes the oral and gut bacterial microbiome and as a result upregulates PAD enzymes. Remember that citrullinated proteins are thought to be a key trigger for the immune cascade of RA.
  • Indicate that the HLA-DRB1 allele (and the corresponding HLA-DR4 serotype antigen) confers the greatest known genetic risk for developing RA.

Labwork

Inflammatory synovial fluid

  • In regards to labwork, indicate that synovial fluid will have high inflammatory cell counts – greater than 5,000 WBC per cubic millimeter (compare this to OA in which the count is less than 2,000) up to 50,000, with the predominance of being polymorphonuclear cells (PMNs).
    • Note that the synovial fluid does NOT contain crystals and is culture negative (this is important in differentiating it from other inflammatory conditions).

RF vs ACPAs

  • Despite its name, rheumatoid factor (RF) is only 85% specific whereas anti-citrullinated protein antigens (ACPAs) are 95% specific.
    • Note that ACPAs replaced anti-cyclic citrullinated peptide antibodies (anti-CCPs) because ACPA is able to detect non-cyclic citrullinated peptides.

Affected Joints

Symmetric

  • Here, draw both sides of our figure to emphasize that RA affects the joints symmetrically (vs OA which is asymmetric).

Early: Wrists, MCPs, MTPs

  • Start with the most commonly affected joints: those of the hands.
  • Indicate that early on in the disease, the wrists and MCP joints are affected, as well as the PIP joints (which are also affected in OA).
  • And indicate that the metatarsophalangeal joints (MTPs) of the feet are also involved.

Later: Large joints

  • Later in the disease, indicate that the ankles, elbows, and shoulders are involved.
  • As well, show that the cervical spine, hips, and knees are also affected (as they can be in OA).

Hand Deformities

  • Indicate that there can be ulnar deviation of the fingers at the MCPs, which are typically swollen and enlarged, and also swan neck deformities of the fingers (flexion at the DIP joints and hyperextension at the PIP joints secondary to MCP flexion contraction).
  • Other findings include:
    • Fusiform swelling of the PIP joints from PIP synovitis
    • Boutonniere deformity (which is the opposite of swan neck deformity – there is DIP hyperextension and PIP flexion)
    • Hitchhiker thumb (hyperextension of the IP joint with MCP flexion)
    • And piano key ulnar head (with a floating ulnar styloid due to ulnar collateral ligament destruction).

Atlantoaxial (C1-C2) subluxation

  • Indicate that we must be mindful of the potential for atlantoaxial (C1-C2) subluxation, especially when we are intubating RA patients.
    • Atlantoaxial subluxation involves anterior subluxation due to synovial proliferation at the site of the odontoid process articulation with the anterior arch of C1.
    • Ultimately, stretching and rupture of the transverse and alar ligaments can occur and can cause spinal cord compression.
  • Additional cervical spine disease include C1-C2 impaction and stair-stepping at subaxial levels (C2-C3 and/or C3-C4).

Extra-articular (systemic) manifestations

  • Finally, indicate that inflammation produces numerous extra-articular manifestations and that elevated ESR and CRP levels are a nonspecific marker of inflammation seen in RA.

Those manifestations include but are not limited to (by system):

  • General: fatigue, fever, weight loss
  • Cardiac: pericarditis, myocarditis, valvular nodules, coronary vasculitis
  • Dermatologic: palmar erythema, subcutaneous nodules (central fibrinoid necrosis with palisades of elongated histiocytes)
  • Hematologic: Felty's syndrome (RA, splenomegaly, and neutropenia), lymphadenopathy, lymphoma
  • Neuromuscular: peripheral neuropathy, entrapment neuropathies, mononeuritis multiplex
  • Ocular: episcleritis, scleritis, choroid and retinal nodules, sicca symptoms (dry eyes with coexistent Sjogren's syndrome)
  • Pulmonary: pleuritis (pleurisy and pleural effusions), pulmonary nodules, interstitial lung disease, bronchiolitis obliterans
  • Rheumatologic: Sjogren's syndrome
  • Skeletal: osteoporosis
  • Vascular: vasculitis, amyloidosis, atherosclerosis

Board Review

Osteoarthritis

Getting ready for boards? Review these concise, bulleted high yield reviews for your exam.

USMLE & COMLEX-USA

Nurse Practitioner (NP)

Physician Assistant (PA)

Internal Medicine (ABIM)

Board Review: Rheumatoid Arthritis

USMLE & COMLEX-USA

Nurse Practitioner (NP)

Physician Assistant (PA)

Internal Medicine (ABIM)

References

  • Aggarwal, Rohit, Katherine Liao, Raj Nair, Sarah Ringold, and Karen H. Costenbader. "Anti-Citrullinated Peptide Antibody (ACPA) Assays and Their Role in the Diagnosis of Rheumatoid Arthritis." Arthritis and Rheumatism 61, no. 11 (November 15, 2009): 1472–83. https://doi.org/10.1002/art.24827.
  • Choy, Ernest. "Understanding the Dynamics: Pathways Involved in the Pathogenesis of Rheumatoid Arthritis." Rheumatology (Oxford, England) 51 Suppl 5 (July 2012): v3-11. https://doi.org/10.1093/rheumatology/kes113.
  • Efthimiou, Petros. Absolute Rheumatology Review. Springer Nature, 2019.
  • Imboden, John B., David B. Hellmann, and John A. Stone. Current Diagnosis & Treatment in Rheumatology, Fourth Edition. McGraw Hill Professional, 2020.
  • Judkins, Shelley W, and P Joanne Cornbleet. "Synovial Fluid Crystal Analysis," 2018, 6.
  • Kanaan, Sami B., Oyku Sensoy, Zhen Yan, Vijayakrishna K. Gadi, Michael L. Richardson, and J. Lee Nelson. "Immunogenicity of a Rheumatoid Arthritis Protective Sequence When Acquired through Microchimerism." Proceedings of the National Academy of Sciences 116, no. 39 (September 24, 2019): 19600–608. https://doi.org/10.1073/pnas.1904779116.
  • McInnes, Iain B., and Georg Schett. "The Pathogenesis of Rheumatoid Arthritis." Review-article. http://dx.doi.org.proxy.medlib.uits.iu.edu/10.1056/NEJMra1004965. Massachusetts Medical Society, December 7, 2011. World. https://doi.org/10.1056/NEJMra1004965.
  • Queiro, Rubén, Isla Morante, Iván Cabezas, and Belén Acasuso. "HLA-B27 and Psoriatic Disease: A Modern View of an Old Relationship." Rheumatology 55, no. 2 (February 1, 2016): 221–29. https://doi.org/10.1093/rheumatology/kev296.
  • Sophia Fox, Alice J., Asheesh Bedi, and Scott A. Rodeo. "The Basic Science of Articular Cartilage." Sports Health 1, no. 6 (November 2009): 461–68. https://doi.org/10.1177/1941738109350438.
  • West, Sterling. Rheumatology Secrets E-Book. Elsevier Health Sciences, 2014.