Case-2-Rheumatoid Arthritis (Official)

without treatment

What is rheumatoid arthritis (RA)

A chronic inflammatory disease of unknown etiology, characterized by symmetric polyarthritis and is the most common form of chronic inflammatory arthritis

At what age does the incidence of RA increase and decrease

Between 25 and 55 years, and decreases at 75 years onwards

What is a typical symptom of RA related to joint stiffness

Early morning stiffness lasting >1 hour, easing with activity

Which joints are typically first involved in RA

Small joints of the hands and feet

What is the initial pattern of joint involvement in RA

Monoarticular, oligoarticular (≤4 joints), or polyarticular (>5 joints), usually symmetric

What condition can resemble RA with too few affected joints

Undifferentiated inflammatory arthritis

What characteristics suggest undifferentiated arthritis may develop into RA

Higher number of tender/swollen joints, positive serum RF or ACPA, and higher physical disability scores

Which joints are most frequently involved once RA is established

Wrists, MCP, and PIP joints

What joint involvement is more typical of osteoarthritis than RA

DIP joint involvement

What is a hallmark of RA in the tendons

Flexor tendon tenosynovitis

What complications can flexor tendon involvement lead to in RA

Decreased range of motion, reduced grip strength, and "trigger" fingers

Which tendon is most commonly affected by RA leading to tendon rupture

Flexor pollicis longus

What deformity is caused by subluxation of MCP joints with subluxation of proximal phalanx to volar side of the hand in RA?

Ulnar deviation

What is a “swan-neck deformity”

Hyperextension of the PIP joint with flexion of the DIP joint

What is a “boutonnière deformity”

Flexion of the PIP joint with hyperextension of the DIP joint

What is a “Z-line deformity”

Subluxation of the first MCP joint with hyperextension of the first IP joint

What does inflammation of the ulnar styloid and tenosynovitis of the extensor carpi ulnaris cause

"Piano-key movement" of the ulnar styloid

What foot deformity can develop in chronic RA

Pes planovalgus ("flat feet")

Which large joints are often affected in established RA

Knees and shoulders

What percentage of the adult population worldwide is affected by RA

~0.5–1%

What trend has been observed in the incidence and prevalence of RA in recent decades

Incidence has decreased, but prevalence has remained the same because individuals with RA are living longer

How does the prevalence of RA vary globally

It varies by geographic location and among certain ethnic groups

Which North American tribes have reported high prevalence rates of RA

Yakima, Pima, and Chippewa tribes

What prevalence range is reported for RA in some African and Asian populations

0.2–0.4%

How much more common is RA in females than in males

2–3 times more common

What are the RA gender ratios observed in some Latin American and African countries

6–8 females for every 1 male

What theories exist regarding the role of hormones in RA

Theories suggest estrogen may influence immune response, with both stimulatory and inhibitory effects

Which type of tissue is primarily affected by RA

Synovial tissue of diarthrodial joints and underlying cartilage and bone

What is the structure of the synovial membrane in joints?

A thin layer of connective tissue covering articular surfaces, tendon sheaths, and bursae

What are the two cell types in the synovial membrane

Type A (macrophage-derived) and Type B (fibroblast-derived) synoviocytes

What is the primary role of synovial fibroblasts?

To produce structural components like collagen, fibronectin, and laminin

What composes the sublining layer of the synovial membrane?

Blood vessels and a sparse population of mononuclear cells

What are the main components of synovial fluid

Hyaluronan and lubricin

What role does hyaluronan play in the synovial fluid?

It contributes to the fluid’s viscous nature

What are the pathologic hallmarks of RA

Synovial inflammation, proliferation, focal bone erosions, and articular cartilage thinning

What is pannus in RA

A thickened cellular membrane with fibroblast-like synoviocytes and granulation tissue invading cartilage and bone

What cells make up the inflammatory infiltrate in RA

T cells, B cells, plasma cells, dendritic cells, mast cells, and granulocytes

What proportion of the inflammatory infiltrate in RA is made up of T cells?

30–50%

How are lymphocytes organized in RA-affected synovium?

They are usually diffusely organized but may sometimes form lymphoid follicles and germinal centers

What promotes the formation of new blood vessels in the synovial sublining in RA?

Growth factors from synovial fibroblasts and macrophages

What mediates structural damage to mineralized cartilage and subchondral bone in RA?

Osteoclasts

What markers identify osteoclasts?

CD68, tartrate-resistant acid phosphatase, cathepsin K, and calcitonin receptor

Where do osteoclasts form resorption lacunae?

At the pannus-bone interface

Where do bone erosions typically develop in RA?

At radial sites of MCP joints near tendons, ligaments, and synovial insertions

What is periarticular osteopenia in RA

Bone loss with trabecular thinning along the metaphyses of bones near inflamed joints

What imaging technique reveals bone marrow lesions in RA

MRI scans; they appear water-rich with low-fat content and highly vascularized

What is the role of osteoblasts in endosteal bone response in RA

They accumulate and deposit osteoid at bone marrow lesion sites

What is generalized osteoporosis in RA

Thinning of trabecular bone throughout the body

What are the four zones of articular cartilage?

Superficial, middle, deep, and calcified cartilage

How does RA affect articular cartilage?

Loss of proteoglycan, particularly in superficial zones adjacent to synovial fluid

Where does cartilage degradation occur in RA?

In the perichondrocytic zone and areas adjacent to subchondral bone

What factors contribute to the pathogenic mechanisms of synovial inflammation in RA

Genetic, environmental, and immunologic factors

What characterizes the preclinical stage of RA

Breakdown in self-tolerance with presence of autoantibodies like RF and ACPA

What is ACPA in RA directed against

Deaminated peptides from posttranslational modification by PADI4

What proteins do ACPA recognize

Citrulline-containing regions of matrix proteins like filaggrin, keratin, fibrinogen, and vimentin

Which additional autoantigens are targeted by autoantibodies in some RA patients

Type II collagen, human cartilage gp-39, aggrecan, calpastatin, BiP, and glucose-6-phosphate isomerase

How is smoking linked to RA pathogenesis

It may induce protein citrullination in the lung via increased PADI expression, creating neoepitopes that trigger self-reactivity

What receptors recognize microbial products that may influence RA through binding of PAMPs

Toll-like receptors (TLRs)

What types of microbial products do TLR4, TLR2, and TLR3 recognize

Bacterial lipopolysaccharides and heat shock proteins (TLR4), lipoproteins (TLR2), and double-strand RNA viruses (TLR3)

What type of microbial products do TLR9 recognize

Unmethylated CpG DNA from bacteria

TLR2, 3, and 4 are abundantly expressed by _________ in early RA?

Synovial fibroblasts

What is the role of self-reactive T cells in RA

They drive the chronic inflammatory response

How might self-reactive T cells arise in RA

Abnormal central (thymic) selection or lowered peripheral activation threshold

What evidence suggests T-cell antigen stimulation occurs in RA joints

T cells in the synovium show prior antigen exposure and clonal expansion

What changes are seen in peripheral blood T cells in RA patients

Premature aging, loss of telomeric sequences, and decreased thymic output of new T cells

What is the basis for the clinical diagnosis of RA

Signs and symptoms of chronic inflammatory arthritis, with lab and radiographic support

Which organizations revised the RA classification criteria in 2010

American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR)

What score on the 2010 ACR-EULAR criteria is required for definite RA

A score of ≥6

What was the main goal of the revised 2010 ACR-EULAR RA criteria

To improve early diagnosis for early introduction of disease-modifying therapy

How do the new RA criteria differ regarding symptom duration

They no longer require symptoms to be present for >6 weeks

Why was a positive serum ACPA test added in the revised RA criteria

It provides greater specificity for RA diagnosis than a positive RF test

Why are rheumatoid nodules and radiographic joint damage excluded from early RA classification

They are rare in early RA

What is the main purpose of the 2010 ACR-EULAR RA criteria

To classify patients likely to develop chronic disease with persistent synovitis and joint damage

What may inform RA diagnosis in later stages of the disease

Radiographic joint erosions or subcutaneous nodules

What proportion of RA patients test positive for RF and/or ACPA

About three-fourths (seropositive)

What is the term for RA patients who test negative for RF and/or ACPA

Seronegative