Rheumatoid Arthritis Flashcards
RA basic
Most common chronic inflammatory arthritis, and is characterized by autoantidobidy production, synovial inflmmation, and bony destruction
Genetic and environemtn of RA
Genetic and environmental
Most genetic related to MHC class 2
May have abnormal DNA methylation in MNC and synovial cells
Smoking, viral infections, periodontitis, steessful life events
Patho of RA
INnate immune activated
Neoantigen generation also relevant
Induction of PAD in macrophages, converting arginiine to citruklline…increased citrullination of different matrix proteins creates neoantigens recognized by imimune system
APCs with neoantigens migrate to lymphid and interact with T cells…increases Th1 and Th17 and diminish Th2 and T regs
Th1 activate B cells and rpdocue ACPA and anti-IgG antibodies (RF)
Witihin joints, RA
Activated Th1 cells stimulate macrophages and fibroblast-like synoviocytes to generate proinflam mediators and proteases
B cells produce ACPA(inflammatory process) and RF (immune complexes)
Cytokines and RA
TNFalpha, IL6, IL1
TnF alpha - activating other cytokines and endothelial cell adhesion molecules and suppresses T regs
IL6- pleotropic effect by influencing hematopoiesis and other immune cells…endothelial activation and bone erosions…also induces acute phase protein production (CRP)
IL1 - activates leukocytes, endothelial cells ,and osteoclasts
Net effect of RA
Immune system activation and cytokine production alters function of fibroblast-like synoviocytes within the joint
Increase in population of synoviocytes os tissue proliferation
Synoviocytes release matrix metalloproteases resulting in local destruction
Production of MCSF and RANKL promotr osteoclast
Epidemiology of RA
Females more common
50-75 is peak onset
CM of RA
Polyarticular dz of graudal onset but may have acute presentation
Classic - insidious onset of pain, morning stiffness, and swelling of multiple joints
small joints - MCP, PIP, wrists, MTP
Large - elbows, shoulders, ankles, and knees
Morning lasts ore than 1 hr
May have systemic sx
PE of CM
Pain and swelling of involved joints
Local pressure on joint or passive movement may provoke pain
Boggy feel to a swollen joint bc of synovial hypertrophy
Hematologic
Skin comps
ANemia of chronic d, reactive thrombocytosis, Felty’s syndrome ,diffuse large B cell lymphoma
Reumatoid nodules, pyoderma gangrenosum
Pullm and skeltal RA
Intertstitial lung dz, plueirtis and pleural effusiom lung nodules
Osteoporosis
Cardiac, ocular, AI comps
Pericarditis, ischemic heart dz
Epicleritis, slecereits
Sjorgerns syndrome
Rheumatoid ndoules
Adherent to periosteum or tendons
Typically firm, nontender, and located on forearm or achilles tendon
Deformities
Due to bone erosions
Can lead to vertebral malalignment
Boutonniere and swan neck deformity
Bout - relaation of the PIP joint causing flexion of the PIP joint with hyperextension of DIP
Swan neck causes hyperextension of PIP joint with flexion of the DIP joint
RA diagnosis
May need CBC, ESR, and CRP to confirm inflam arthrtitis
RG and anti-CCP should also be persormed
Joint involvemtn - up to 5 points
Serology - Low ACPA or RF
Acute-phase reactants - CRP or EST
Duration of sx - more than 6 weeks
over 6 is definite RA
Other dx of RA
Arthrocentesis WBC betwen 5 and 50000 and glucose is low
Xray shows joint space narrowing and bny erosions of hands and feet
Methotrexate MOA and adverse effects
Folate antimetabolite interfering with DNA synthesis and producing anti-inflamm effect
Liver, BM, dyspepsia, N/V
Sulfasalazine MOA and SE
Unclear but modulates cytokine mediators of inflamm response
N/V, skin rash and photosensitivity, HA
Hydroxychloroquine MOA and SE
Block stimulation of the B cell receptors through inhibition of TLRs
N/V, skin rash, HA, corneal desposits and retinopathy
Leflunomide MOA and SE
Inhibiyion of pyrimidine synthesis, resultiing in anti-inflamm effects
HTN, N/V
Alopecia
TNF-alpha inhibitor function
Blocks potent proinflammatory and immunoregulatory mediator
TNF alpha inhibitor structures
Monoclonal - adalimummab, golimumab, infliimab
TNF-alpha receptor-Fc fusion protein - Etanercept
Fab’ fragement of TNF-alpha - certolizumab
CD20 function, structure, drug
Loss of CD20 in pre-B cells depletes B cells
Monoclonal AB - rituximab
CD80/86
Blockade of costim of T cells
CTLA4 IgG fusion protein
Abatacept
IL-1
Inhibits production of prostaglangdss and matri metalloproteinase by synovial cells
Receptor antagonist
Anakinra
IL-6 R
Inhibition of cytokine activation of T, B, macro, osteoclasts
Monoclonal Ab - tocilizumab
Janus Kinase
Inference of cytokine and GF singlaing pathways
Small molecular inhibitor
Tofacitinib
Prognosis of RA
Most get flucutations but progression
Joint erosions are detectable within 1st 2 years if no managmenrt
Life span shorten from pensity to develop CV dz (chonic inflamm) and infection (drugs)
