Rheumatoid Arthritis Pathophysiology & Pharmacology

Questions and Answers

What primary immune response triggers the inflammation in rheumatoid arthritis?

Recognition of citrullinated self-antigens as foreign (correct)

Misdirection of immune cells towards healthy tissues

Deficiency of pro-inflammatory cytokines

Apoptosis of immune cells

Which demographic group is most commonly diagnosed with rheumatoid arthritis?

Women aged 30 to 70 years (correct)

Individuals under 30 years of age

Men aged 70 years and older

Children and adolescents

What is a characteristic feature of joints affected by rheumatoid arthritis?

Complete regeneration of cartilage

Absence of inflammation

Severe joint deformities and ankylosis (correct)

Enhanced range of motion

Which environmental factor is associated with an increased risk of developing rheumatoid arthritis?

Exposure to cigarette smoke Signup and view all the answers

What happens during a flare of rheumatoid arthritis?

Affected joints become swollen, warm, and painful Signup and view all the answers

What role do antigen-presenting cells (APCs) play in rheumatoid arthritis?

They transport citrullinated antigens to lymph nodes and activate T helper cells Signup and view all the answers

Which of these statements about the pathophysiology of rheumatoid arthritis is true?

Rheumatoid arthritis is an immune-mediated disease causing chronic joint inflammation Signup and view all the answers

Which reason best explains the significance of the HLA-DR variant alleles in rheumatoid arthritis?

They help in the recognition of modified self-antigens Signup and view all the answers

What type of joint involvement is characteristic of rheumatoid arthritis?

Symmetrical polyarthritis involving five or more small joints Signup and view all the answers

Which genetic factor is primarily linked with an increased risk of developing rheumatoid arthritis?

HLA-DR variant alleles Signup and view all the answers

Which modification of self-proteins is recognized as playing a role in the autoimmune response in rheumatoid arthritis?

Citrullination of Type II collagen Signup and view all the answers

What impact do cytokines like TNF, IL-1, and IL-6 have in the context of rheumatoid arthritis?

They promote chronic inflammation and contribute to joint destruction. Signup and view all the answers

Which autoantibodies play a significant role in the inflammation process associated with rheumatoid arthritis?

ACPAs and rheumatoid factor (RF) Signup and view all the answers

What term describes the tumor-like growth in joints caused by the proliferation of synovial cells in rheumatoid arthritis?

Pannus Signup and view all the answers

What is one consequence of rheumatoid arthritis on bone health?

Articular bone loss and systemic osteoporosis Signup and view all the answers

What is the preferred disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis?

Methotrexate Signup and view all the answers

What is the mechanism of action of abatacept in the treatment of rheumatoid arthritis?

Modulates T-cell activation by binding to CD80/CD86 on antigen-presenting cells (APCs) Signup and view all the answers

What is the mechanism of action of rituximab in rheumatoid arthritis?

Depletion of CD20-positive B cells Signup and view all the answers

What is the primary mechanism of action of anti-TNF agents (e.g., infliximab, adalimumab) in rheumatoid arthritis?

Neutralize TNF-alpha by binding to it and preventing its interaction with TNF receptors Signup and view all the answers

Which statement correctly represents the mechanism of action of tofacitinib in the treatment of RA?

Inhibits Janus kinases, disrupting cytokine signaling Signup and view all the answers

Which molecule does tocilizumab specifically target in the treatment of rheumatoid arthritis?

IL-6 receptors Signup and view all the answers

What role do Janus kinases play in immune response signaling?

They are involved in signal transmission from cell surface to nucleus Signup and view all the answers

What is a common effect of rituximab treatment in patients with rheumatoid arthritis?

Reduction of inflammation due to B cell depletion Signup and view all the answers

Which of the following is NOT a target for currently used therapies in rheumatoid arthritis?

Nuclear factor kappa B (NF-kB) Signup and view all the answers

What role do activated T helper cells play in the context of rheumatoid arthritis?

They stimulate B cells to produce antibodies. Signup and view all the answers

Which of the following cytokines is primarily released by activated T cells in the synovium?

Interferon-gamma (IFN-gamma) Signup and view all the answers

What do anti-citrullinated protein antibodies specifically bind to in rheumatoid arthritis?

Citrulline within the joint Signup and view all the answers

What is the effect of the activation of the complement system by immune complexes in rheumatoid arthritis?

It enhances the release of proinflammatory cytokines. Signup and view all the answers

What pathological structure results from the proliferation of synovial cells in rheumatoid arthritis?

Pannus Signup and view all the answers

What is the primary aim of treatment for rheumatoid arthritis?

To inhibit immune cell activation. Signup and view all the answers

What is the consequence of the inflammatory cascade in rheumatoid arthritis?

Cartilage and bone destruction Signup and view all the answers

Which of the following best describes rheumatoid factors?

Nonspecific autoantibodies that bind to IgG Signup and view all the answers

Study Notes

Rheumatoid Arthritis Overview

Rheumatoid Arthritis (RA): A common autoimmune disease marked by chronic joint inflammation due to immune cell activity and pro-inflammatory cytokines.
Typical Symptoms: Includes symmetrical polyarthritis, affecting five or more small joints (hands and feet) and possibly larger joints; often presents with morning stiffness lasting more than 30 minutes.
Flare-ups: Sudden worsening of symptoms including swollen, warm, red, and painful joints.

Pathophysiology

Joint Damage: Inflammation leads to destruction of bone and cartilage, ankylosis (joint fusion), and severe joint deformities.
Genetic Factors: Presence of HLA-DR variant alleles (HLA-DR1 and HLA-DR4) increases disease risk, exacerbated by environmental triggers such as smoking or pathogens.
Citrullination: Modification of self-proteins like Type II collagen converts arginine to citrulline, causing the immune system to mistakenly attack these proteins.

Immune Response Mechanism

Citrullinated Antigens: Recognized as foreign by antigen-presenting cells (APCs), activating T helper cells and leading to B cell proliferation producing autoantibodies (ACPAs) and rheumatoid factor (RF).
Cytokine Release: Activated T-helper cells release Interferon-gamma and IL-17, stimulating macrophages and fibroblasts to release further pro-inflammatory cytokines (TNF, IL-1, IL-6).
Synovial Inflammation: Pannus formation due to synovial cell proliferation leads to the erosion of bone and cartilage, contributing to joint space narrowing and ankylosis.

Consequences of RA

Bone Health: Progression includes articular bone loss and systemic osteoporosis, with inhibited bone repair mechanisms.
Pannus Formation: A "tumor-like growth" that results in cartilage and bone destruction, exacerbating inflammation.

Treatment Strategies

cDMARDs: Conventional Disease-Modifying Anti-Rheumatic Drugs should be initiated immediately to delay disease progression.
Combination Therapy: May involve two cDMARDs or adding biological DMARDs (bDMARD) or Janus kinase inhibitors (JAKi) if monotherapy is ineffective.
NSAIDs or Glucocorticoids: Prescribed for their anti-inflammatory effects as needed.

Key Pharmacological Agents

Methotrexate: Preferred DMARD; acts as a folic acid antagonist, inhibiting cytokine production. Notable side effects include mucosal ulceration and cytopenias, with folic acid as a supplement to alleviate gastrointestinal and hepatic adverse effects.
TNF Biologics: Bind to TNF-α, blocking its interaction with receptors to reduce inflammatory response.
Abatacept: Modulates T-cell activation by binding to CD80/CD86 on APCs, decreasing full T-cell activation.
Rituximab: Monoclonal antibody targeting CD20; depletes B cells contributing to inflammation.
Tocilizumab: Monoclonal antibody inhibiting IL-6 receptors, reducing IL-6 activity.
JAK Inhibitors: Oral drugs disrupting signaling pathways in immune cells, thereby reducing local inflammation.

Exam Questions and Answers

Typical Initial Presentation: Symmetrical polyarthritis involving five or more small joints.
Genetic Factors: Increased risk associated with HLA-DR variant alleles.
Autoimmune Response Modification: Citrullination of Type II collagen triggers immune response.
Cytokine Role: Promote chronic inflammation and contribute to joint destruction.
Autoantibodies: ACPAs and rheumatoid factor (RF) activate inflammation through complement activation.
Tumor-like Growth: Pannus develops due to proliferating synovial cells.
Bone Health Consequences: RA leads to articular bone loss and systemic osteoporosis.

Mechanism of Action of Drugs

Abatacept: Modulates T-cell activation by binding to CD80/CD86 on APCs.
Rituximab: Depletes CD20-positive B cells.
Anti-TNF Agents: Neutralize TNF-alpha, blocking its interaction with receptors.
Tofacitinib: Acts as a JAK inhibitor, disrupting immune signaling pathways.

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Description

This quiz explores the pathophysiology and pharmacology of rheumatoid arthritis (RA). It focuses on understanding the mechanisms of action of antirheumatic drugs, their contraindications, adverse effects, and interactions. Additionally, it covers the radiological changes and bone deformities associated with severe RA.