Rheumatoid Arthritis Flashcards
What is arthritis, and who is more likely to get it?
Arthritis is inflammation of the joints and surrounding tissues, affecting bones, muscles, and joints. It’s an umbrella term for over 100 different conditions. It’s more common in the elderly, women, and individuals with increased weight.
Describe the primary manifestation of rheumatoid arthritis (RA).
The primary manifestation of RA is synovitis, which involves inflammation of the synovial lining of joints, leading to erosion of bone, cartilage, and periarticular structures.
What are the articular clinical features of RA?
Include morning stiffness of ≥30 minutes, pain, swelling, fatigue, weakness, and characteristic joint deformities like boutonniere, swan neck, Z thumb, MCP subluxation, and ulnar deviation.
What are the extra-articular clinical features of RA?
Include nodules (subcutaneous, pulmonary, cardiac), pulmonary complications (interstitial lung disease, pleuritis), ocular manifestations (scleritis, episcleritis), vasculitis, neurological issues, cardiovascular complications, cutaneous manifestations, hematologic abnormalities, malignancies, and renal complications.
How is pyoderma gangrenosum present in patients with RA?
Pyoderma gangrenosum in RA starts as a small pimple, red bump, or blood blister, which rapidly enlarges into a painful ulcer with purple or blue edges. It commonly occurs on the legs and heals after treatment with medications like methotrexate and high-dose oral prednisolone.
What are the differences in joint involvement between rheumatoid arthritis (RA) and osteoarthritis (OA) according to Goldman’s Cecil Medicine?
RA typically shows symmetric joint involvement affecting the wrist, MCP, and PIP joints, with soft tissue swelling. OA, on the other hand, tends to exhibit asymmetric joint involvement affecting the DIP joints and the base of the thumb, with no soft tissue swelling.
What are some of the extra-articular manifestations of rheumatoid arthritis (RA)?
Extra-articular manifestations of RA include nodules (subcutaneous, pulmonary, cardiac), pulmonary complications (interstitial lung disease, pleuritis), ocular manifestations (scleritis, episcleritis), vasculitis, neurological issues, cardiovascular complications, cutaneous manifestations, hematologic abnormalities, malignancies, and renal complications.
How does RA differ from osteoarthritis (OA) in terms of joint involvement
RA typically involves symmetric joint inflammation, affecting the wrist, metacarpophalangeal (MCP), and proximal interphalangeal (PIP) joints with soft tissue swelling. In contrast, OA tends to involve asymmetric joint inflammation, affecting distal interphalangeal (DIP) joints and the base of the thumb, with marginal osteophytes and joint space narrowing.
Explain the prevalence and burden of arthritis in Australia.
In Australia, around 3.7 million people have arthritis, with prevalence increasing with age and being higher in females, individuals with increased waist circumference, and First Nations populations. Arthritis accounts for 13% of the total burden of disease, with significant healthcare expenditure and socioeconomic costs.
What are some of the radiographic features of rheumatoid arthritis (RA) in the wrist?
Typical radiographic features of RA in the wrist include osseous erosion at sites like the triquetrum, pisiform, scaphoid, distal radius, ulnar styloid process, and radiocarpal joint. Diffuse cartilage loss and erosion are also observed.
Describe the clinical presentation and symptoms of atlantoaxial (AA) subluxation in RA.
AA subluxation in RA can lead to symptoms such as pain radiating up to the occiput, slowly progressive spastic quadriparesis, transient medullary dysfunction (altered conscious state, syncope, loss of sphincter control, dysphagia, vertigo), and neurological deficits.
Describe synovium
A thin membrane lining the joint capsule in diarthrodial joints, extending from skeletal tissue and covering the joint cavity.
Describe cell types and their normal function
- Cell Types: It consists of synoviocytes, mainly fibroblast-like synoviocytes (FLS) and macrophages.
- Normal Function: Synoviocytes facilitate joint movement, with FLS producing lubricants like hyaluronan and collagen, while macrophages clean debris and maintain immune balance.
Describe the changes that happen to healthy synovial tissue in RA.
- In RA, synovial tissue undergoes proliferation, infiltration by inflammatory cells (neutrophils, lymphocytes), and neovascularization.
- Proliferation: Synovial lining layer thickens, forming pannus.
- Infiltration: Inflammatory cells invade, leading to inflammation and joint damage.
Describe the cell types present and their functions within the inflamed synovium in RA.
- Cell Types: In RA synovium, various cells are present, including activated fibroblast-like synoviocytes (FLS), inflammatory macrophages, T cells, and B cells.
- Functions: FLS produce pro-inflammatory cytokines and enzymes causing cartilage destruction, while macrophages clean debris and initiate immune responses.
Explain what TNF is what it does in RA
A cytokine produced by various cells in RA synovium, promoting inflammation, leukocyte accumulation, and bone resorption.
Explain IL-1 and what is does in RA.
Pro-inflammatory cytokine inducing chemokine production, metalloproteinase release, and osteoclast differentiation.
Explain what IL-6 is what it does in RA
Stimulates acute phase response, immunoglobulin production, and promotes TH17 cell differentiation, contributing to inflammation and bone resorption.
Explain how JAK-STAT signalling contributes to synovial inflammation.
- JAK-STAT Signalling: Janus Kinase (JAK) and Signal Transducer and Activator of Transcription (STAT) pathways mediate inflammatory responses in RA.
- Contribution: Activated by cytokines like IL-6, JAK-STAT signalling enhances cytokine expression, promotes T cell survival, and induces antibody production, exacerbating synovial inflammation and joint damage.
Explain why animal models are used for pre-clinical studies of RA pathogenesis and treatment.
- Purpose: Animal models, like rodent CIA and hTNF.Tg mice, mimic RA pathogenesis, aiding in understanding disease mechanisms and testing potential therapies.
- Advantages: They allow controlled studies, testing various interventions, and evaluating treatment responses before human trials.
What are two pre-clinical models of RA
- Collagen-Induced Arthritis (CIA)
- hTNF.Tg mice
Describe CIA and how it has helped understand RA and its limitations
- Utility: Mimics synovial inflammation, cartilage, and bone erosion seen in RA.
- Limitations: Dependent on specific mouse strains and collagen antibodies, not perfectly representing human RA.
Describe hTNF.Tg and how it has helped understand RA and its limitations
- Utility: Offers chronic, TNF-driven arthritis model, reflecting RA’s chronic nature and responsiveness to TNF inhibition.
- Limitations: Limited to TNF-driven mechanisms, not reflecting the multifactorial nature of human RA.
Describe how TNF was identified and developed as a therapeutic target for RA treatment
- Identification: TNF, discovered as a factor killing fibrosarcoma cells, was later found elevated in RA synovium, driving inflammation and joint damage.
- Development: Monoclonal antibodies like Infliximab and Adalimumab were developed, targeting TNF and reducing synovial inflammation and bone erosion in RA patients.
Describe the anatomical and molecular structure of bone
Bone comprises trabecular (spongy) and cortical structures. Trabecular bone is found at the ends of long bones and in the vertebrae, while cortical bone forms the outer shell of most bones. Bone contains bone marrow cells, adipocytes, blood vessels, and extracellular components such as osteoid (organic matrix) and mineral salts (hydroxyapatite).
Describe the function of bone
Bones provide mechanical support for movement and protection for internal organs. They also serve as a metabolic store for minerals like calcium and phosphate, regulate hematopoiesis, and produce hormones and cytokines.
Explain the process of bone remodelling
Bone remodeling involves the coordinated action of osteoclasts, which resorb bone, and osteoblasts, which form bone. It is initiated asynchronously throughout the skeleton and is essential for skeletal adaptation and renewal.
Explain how bone remodelling contributes to bone homeostasis
Remodeling removes regions of micro-damage, responds to calcium homeostatic needs by releasing calcium into the bloodstream, and adapts to changes in mechanical needs by redistributing bone. It helps maintain bone density and strength.
Describe osteoclasts and how they resorb bone
Osteoclasts are multinucleated cells derived from hematopoietic precursors. They attach to bone surfaces and resorb bone mineral and collagenous matrix. Osteoclasts create an acidified microenvironment that aids in bone resorption and possess a characteristic “ruffled border” to increase surface area for ion exchange.
Describe osteoblasts and how they form bone
Osteoblasts are specialized stromal cells responsible for bone formation. They produce type I collagen (osteoid) and non-collagenous proteins, which form the organic matrix of bone. Osteoblasts mineralize this matrix, leading to the formation of new bone.
Describe osteocytes and their role in the skeleton
Osteocytes are terminally differentiated osteoblasts embedded within the bone matrix. They act as mechanosensors, detecting changes in mechanical load, and regulating osteoblast and osteoclast activity accordingly. Osteocytes play a crucial role in bone remodeling and adaptation to mechanical stress.