234. RA Flashcards
RA (what is it, epidemiology: age, sex, race)
Chronic inflammatory joint disease of autoimmune nature characterized by autoantibody development
F>M, women 40-60y/o. all races (highest in Native Americans)
Risk factors for RA
GENETICS: HLA-DR loci - MHC II HLA antigen loci (HLA-DRB1*01/04 strongest risk alleles)
EPIGENETICS: environmental factors can influence cell activity (HLA methylations can differ)
SEX: W>M, men develop later onset disease, more likely to have positive autoantibodies
SMOKING: increases risk in graded fashion, increases disease activity
DUST INHALATION: occupationals
MICROBIOTA: periodontal disease increases risk of developing RA (mediated by P. gingivalis in mouth)
Pathology of RA
What are the 2 types of synoviocytes, their roles, and how they change in RA
Macrophage-like and Fibroblast-like synoviocytes (MLS/FLS) lubricate and provide nutrients for cartilage on synovial lining
RA: intimal lining expands when activated synoviocytes produce pro-inflammatory cytokines - adaptive immune cells infiltrate + hypervascularity
PANNUS: invasive destructive front of synovial tissue (active osteoclasts) on articular surface
Histology of RA
Hyperplasia of lining layer
Infiltration of immune cells in sublining and hypervascularity
Many MLS (blue) and FLS (brown)
Osteoclasts in synovium invading bone
What is citrullination? How does this lead to RA? Where in disease course does this occur?
C: environmental stressors (smoking) induces PAD - converts Arginine to citrulline in peptides
Citrullinated peptides bind HLA protein on antigen presenting cells
APCs with c-peptides activate T Cells - stimulate B cells to produce auto antibodies (RF, anti-CCP/ACPA)
Occurs in PRECLINICAL RA
What happens in the EARLY RA disease course?
Expansion of autoimmunity
synovitis: influx of inflammatory cells into synovium
Activated synoviocytes secrete proinflammatory cytokines and proteases (IL-1, IL-6, TNFa, MMPs, RANKL)
What happens in ESTABLISHED RA disease course?
Joint damage - cartilage and bone destruction from MMPs from FLS; bone erosion from osteoclasts stimulated by IL-1, IL-6, TNFa, RANKL
Clinical Features of RA
Inflammatory Arthritis Insidious onset of symmetric polyarthritis Joint swelling and decreased ROM Pain/Swelling worse in morning Morning stiffness >1hr Stiffness after rest (Gelling)
Distribution of joint involvement in RA
Hands (MCP, PIPs)
Wrists, Elbow, Shoulder, Hip, Knee Ankle, C-Spine, MTPs
Difference in physical exam between OA and RA
RA: palpable swelling with synovial bogginess (soft/spongy) - not bony
Swan-Neck Deformity: DIP flexed, PIP hyperextended
Buotonniere Deformity: DIP hyperextension, PIP flexion
Common causes of mortality in RA
- CVD - most common - develops atherosclerosis 10 years earlier due to more inflammation and higher prevalence of CVD risk factors (HTN, DM, hyperlipidemia, obesity)
- infection/pneumonia (immune system hyperactive and cant function)
- cancer - lymphomia, leukemia
- amyloidosis/renal disease
Key Radiographic changes in RA
- Soft tissue swelling
- Periarticular Osteopenia (thinning of bone around joint)
- Uniform, symmetric joint space loss and narrowing
- Marginal Erosions
- Symmetric deformities (Swan Neck, Buotonniere, Ulnar Deviation, Subluxation)
Lab Features in RA
RF - specific for Fc fragment of IgG, higher titers = worse prognosis, assoc with aging, chronic infection, Hep C, other chronic inflammatory disease
ACPA/anti-CCP: Assoc with poor prognosis; pts with negative RF can be positive ACPA (highest specificity)
Anemia
Thrombocytosis
high ESR/CRP
Inflammatory synovial fluid, negative cultures
Treatment for RA (Acute Sx Control)
NSAIDs - don’t prevent disease progression
Corticosteroids - more effective, less side effects (HTN, hyperglycemia, osteoporosis)
First Line Treatment for RA
MTX: inhibits dihydrofolate reductase to LIMIT DNA SYNTHESIS - inhibits vascular proliferation, neutrophil activation, IL-1/8 production, TNFa production
