SM_234a: Rheumatoid Arthritis Flashcards
Rheumatoid arthritis is _____
Rheumatoid arthritis is a chronic inflammatory joint disease of autoimmune nature characterized by the development of autoantibodies
(more common in women, occurs earlier in women)
Risk factors for RA include ____, ____, ____, ____, ____, and ____
Risk factors for RA include genetic, epigenetic, female sex, smoking, dust inhalation, and microbiota (periodontal disease, gut microbiome)
Shared epitope is a ______
Shared epitope is a specific amino acid motif commonly encoded by alleles of the HLA-DR loci that confers genetic susceptibility to development of RA
(specific class II HLA antigen loci show strong association with RA, HLA-DRB1*01 and HLDRB1*04 are among strongest risk factors, many loci harbor RA susceptibility variants of variable strength)
Locus involves in RA is _____
Locus involves in RA is HLA DR
Environmental risk factors for RA are ____, ____, and ____
Environmental risk factors for RA are smoking, dust inhalation, and microbiota
- Risk from smoking increases in a graded fashion
- Dust inhalation
- Periodontal disease increases risk of developing RA
- Gut microbiome changes in RA
Healthy synovium has ____ and has a sublining of ____, ____, ____, and ____
Healthy synovium has an intimal lining of macrophage-like and fibroblast-like synoviocytes and sublining of fibroblasts, adipocytes, blood vessels, and immune cells
- Intimal lining is a delicate and leaky and allows free movement of cells and proteins into synovial fluid
Healthy synovium functions to _____ and _____ during homeostasis
Healthy synovium functions to produce lubricants for cartilage and provide nutrients to cartilage during homeostasis
In RA, pathological changes of the synovium include ____, ____, ____, and ____
In RA, pathological changes of the synovium include expansion of intimal lining with activated synoviocytes producing pro-inflammatory cytokines, infiltration of adaptive immiune cells into synovial sublining with hypervascularity, formation of a pannus, and activation of osteoclasts to degrade bone
Pannus is an _____
Pannus is an invasive destructive front of synovial tissue attached to the articular surface
Describe pathological changes in the RA synovium
RA synovium pathological changes
- Intimal lining greatly expands with activated synoviocytes producing pro-inflammatory cytokines
- Infiltration of adaptive immune cells into synovial sublining with hypervascularity
- Pannus: invasive, destructive front of synovial tissue attached to the articular surface
- Activated osteoclasts degrade bone
Pannus is formed by ____, ____, and ____
Pannus is formed by the expansion of activated synoviocytes, infiltration of immune cells, and hypervascularity
Describe the disease coure of RA
RA disease course
- Pre-clinical: citrullination
- Early: synovitis
- Established: joint damage
Pre-clinical RA is characterized by _____
Pre-clinical RA is characterized by citrullination
Early RA is characterized by _____
Early RA is characteirzed by synovitis
Established RA is characterized by _____
Established RA is characterized by joint damage
Describe the disease course and pathogenesis of RA
RA disease course and pathogenesis
- Pre-clinical RA: circulating autoantibodies and pro-inflammatory cytokines are detectable up to 10 years before clinical disease onset
- Citrullination is a key step in RA pathogenesis that leads to immune activation and production of RF and ACPAs
- Synovitis and joint damage are cardinal features of RA driven by pro-inflammatory cytokines IL-1, IL-6, and TNF
Describe the HPI of someone with RA and someone with OA
- RA: usually insidious onset of symmetric polyarthritis (>3 joints) especially in joints of hands and feet, joint swelling, decreased ROM in joints, pain and swelling worse in morning, morning stiffness lasting >1 hour, stiffness after rest (gelling)
- OA: insidious, bony enlargement of joints, morning stiffness lasting < 30=60 minutes, stiffness after rest (gelling)
RA involves joint _____, while OA involves _____ of joints
RA involves joint swelling, while OA involves bony enlargement of joints
Morning stiffness lasts ____ in RA than OA
Morning stiffness lasts longer in RA than OA
Describe joints involved in RA
Joints involved in RA
- Hands: metacarpophalangeal joints (MCPs), proximal interphalangeal joints (PIPs), wrists, elbows, shoulders, hips, knees, ankles, metatarsophalangeal joints (MTPs), and cervical spine
(OA involves the DIPs, does not involve MCPs or ankle, and only involves 1st MTP)
Physical exam findings in early RA include ____ and ____
Physical exam findings in early RA include symmetric joint swelling / tenderness and palpable swelling / synovial boginess
(in OA there is joint enlargement due to bony hypertrophy in osteoarthritis)
Physical exam findings in advanced RA include _____, _____, and _____
Physical exam findings in advanced RA include joint deformity / malalignment, limited ROM, and rheumatoid nodules at pressure points
(MCP joint ulnar deviation and subluxation)
Swan neck deformity in RA is _____
Swan neck deformity in RA is flexion at DIP and hyperextension at PIP
Boutonniere deformity in RA is _____
Boutonniere deformity in RA is flexion at PIP and hyperextension of DIP
_____ and _____ distinguish RA from OA in the hands
Prolonged morning stiffness and sparing of DIP joints distinguish rheumatoid arthritis from OA in the hands
RA patients are at high risk for premature _____
RA patients are at high risk for premature cardiovascular disease
Describe radiographic changes in RA
Radiographic changes in RA
- Soft tissue swelling
- Periarticular osteopenia
- Uniform / symmetric joint space loss
- Marginal erosions
- Symmetric deformities (swan neck, boutonniere, ulnar deviation, subluxation)
Describe late RA changes in the hands
Late RA changes in the hands
- Diffuse joint space narrowing
- MCP subluxation and ulnar deviation
- Demineralization
- Marginal erosions at MCPs
- Carpal joint space narrowing and erosions
____ may occur in RA due to instability resulting from synovitis of the atlantoaxial joint
Atlantoaxial subluxation may occur in RA due to instability resulting from synovitis of the atlantoaxial joint
____, ____, and ____ are characteristic X-ray findings in RA
Soft tissue swelling, periarticular osteopenia, and marginal erosions are characteristic X-ray findings in RA
Laboratory abnormalities in RA include ____, ____, and ____
Laboratory abnormalities in RA include rheumatoid factor (RF), anti-citrullinated peptide antibodies (ACPA), and antinuclear antibody (ANA, in 20-30% of patients)
Describe RF in lab testing of RA
RF in lab testing of RA
- Autoantibodies with specificity for Fc fragment of IgG
- High titers associated with worse prognosis
- Sensitivity 66%, specificity 82%
- Other disease associations
Describe ACPA in lab testing of RA
ACPA in lab testing of RA
- Sensitivity 75%, specificity 95%
- 35% of patients with negative RF will have positive ACPA
- Associated with poor prognosis (erosive disease, extra-articular manifestations)
Inflammatory synovial fluid in RA includes ____, ____, and ____
Inflammatory synovial fluid in RA includes 5-50k WBCs, no crystals, and negative culture
(general signs of inflammation: anemia of chronic disease, thrombocytosis, elevated ESR, elevated CRP)
Positive RF and ACPA blood tests are associated with increased risk of ____ and ____
Positive RF and ACPA blood tests are associated with increased risk of erosive joint disease and development of extra-articular manifestations
Describe goals of treatment for RA
Goal of treatment for RA
- Reduce joint pain and swelling
- Prevent joint damage, minimize disability, and maintain employability
- Begin treatment early: best results when meds started within 3-6 months of synovitis onset
- Treat to target: goal to attain remission or low disease activity
____ and ____ are used for acute symptom control in RA
NSAIDs and corticosteroids are used for acute symptom control in RA
Disease modifying anti-rheumatoid drugs are a diverse group of medications that ____ and ____
Disease modifying anti-rheumatoid drugs are a diverse group of medications that reduce RA symptoms and slow radiographic progression/damage
Methotrexate inhibits _____ to _____
Methotrexate inhibits dihydrofolate reductase to limit DNA synthesis
(most effective)
(inhibits vascular proliferation, inhibits neutrophil activation and adherence, inhibits IL-1 and IL-8 production by mononuclear cells, inhibits TNF production by T cells)
Leflunomide inhibits _____ to _____
Leflunomide inhibits dihydroorotate dehydrogenase to limit DNA synthesis
(also inhibits expression of cell adhesion molecules, teratogen)
Sulfasalazine suppresses _____ and _____ function
Sulfasalazine suppresses lymphocyte and leukocyte function
Hydroxychlorquinone may interfere with ____
Hydroxychlorquinone may interfere with presentation of auto-antigenic peptides
Biologic DMARDs are very effective for RA treatment but have increased risk of _____ compared to non-biologic DMARDs
Biologic DMARDs are very effective for RA treatment but have increased risk of infection compared to non-biologic DMARDs
Describe the general treatment approach for RA
General treatment approach for RA
- Treat to target of remission or low disease activity
- Assess disease activity at 6-12 week intervals initially
- Taper off prednisone as soon as possible
- Maintain DMARD indefinitely once low disease activity attained
____ is the most effective DMARD for RA, and biologic DMARDs are added to non-biologic DMARDs as need to attain ____ and ____
Methotrexate is the most effective DMARD for RA, and biologic DMARDs are added to non-biologic DMARDs as need to attain remission or low disease activity (treat to target)
