Rheumatoid arthritis Flashcards
Define Rheumatoid arthritis (RA)
systemic inflammatory, autoimmune disorder resulting in synovitis leading to cartilage and bone destruction and joint deformities.
What joints are involved in RA?
mostly peripheral synovial joints in a symmetric pattern(particulatly the small joints of hands and feet), DIP often spared, Cervical spine common (C1-C2), Other synovial joints (cricoarytenoid, ossicles of inner ear, and TMJ)
common symptoms of RA?
morning stiffness, soft tissue swelling around joints, pain, deformities and loss of function
common signs of RA
Joint warmth and swelling, tenderness to palpation with limitation of motion, possible deformities
T or F: Rheumatoid factor (RF) is a common finding in RA
TRUE; seen in 85% of patients
T or F: ESR and C-reactive protein are often normal in RA
FALSE: they are elevated
T or F: Citrullinated proteins can be found in many sites of inflammation in RA
TRUE
T or F: Anti-cyclic citrullinated peptide (Anti-CCP) antibodies are not commonly found in RA
FALSE: they are present in 70% of cases and are highly specific for RA
How do peptides contain citrulline?
Enzyme peptidyl arginine deiminase (PAD) modifies an arginine residue
What does the synovial fluid analysis look like in RA?
inflammatory (>2000 WBC/uL) with predominant neutrophils, complement and glucose levels usually low
What are some common radiographic findings in RA? (4 things)
1) soft tissue swelling, 2) Juxta-articular osteopenia, 3) Symmetric loss of joint space, 4) Erosions in marginal distributions
Extra-articular manifestations of RA
Fatigue, malaise, anorexia, weight loss, low-grade fever, Rheumatoid nodules on extensor surfaces and tendon sheaths and internal organs (ie lungs)
What organs can be involved in RA
Numerous organ systems in ~20% of pts, including eyes (scleritis), lungs (fibrosis or nodules), peripheral nerves (neuropathy), vasculitis, or granulomatous infiltration
What is the ratio of RA in females compared to males?
~2.5:1
Are there any genetic factors involved in RA?
YES! Concordance rate of monozygotic twins is ~30% and HLA-DR4 in present in 50% or more of cases
T or F: RA is primarily a synovial-based with secondary affects on articular cartilage and junta-articular bone
TRUE
Early events in the synovial tissue in RA are characterized by what?
microvascular injury and edema
what cell changes occur in RA synovial tissue early on
synovial lining cell hyperplasia and infiltration of the sunlining region with CD4+ Tcells, B cells, plasma cells, monocytes/macrophages, and fibroblasts.
T or F: Neutrophils are distinctly rare in early events of RA
TRUE
What events can help lead to chronic phase of RA
genetic susceptibility (shared epitope), T and B cell function, and activation of MACs and fibroblasts
What is the chronic stage distinguished by?
neutrophilic infiltration of synovial fluid
T or F: Rheumatoid factor (RF) is produced locally by plasma cells and binds IgG in synovial fluid
TRUE
What can help cause the neutrophil chemotaxis?
IL-8 and RF activation of complement
How do MACs contribute to cartilage and bone damage?
IL-1, TNF-alpha, IL-6, etc. release stimulates production of MMPs
What inflammatory agents may induce catabolic function of chondrocytes and osteoclasts?
prostaglandin E2, and IL-1. leads to juxta articular osteopenia and loss of cartilage
How do neutrophils fuck the shit?
ROS, proinflammatory eicosanoids, and shear numbers overwhelming proteinase inhibitors
how do TNFalpha, IL-1, and IL-17 induce bone reabsorption?
induce osteocyte expression of RANKL, which binds RANK receptor on osteoclast precursors, thus activating reabsorption.
what does osteoprotegerin (OPG) do?
competitively binds RANKL and modulates its activity
T or F: bony reabsorption in RA is due to RANKL:OPG ratio
TRUE
What are some treatment options to prevent bone resorption?
anti-TNF therapies and monoclonal antibody against RANKL (denosumab)
What drugs are given early on in RA to relieve symptoms and prevent further tissue destruction
NSAIDs AND disease-modifying anti-rheumatic drugs (DMARDs)
What drugs are DMARDs and what do they do?
hydroxycloroquine, sulfasalazine, leflunomide, and methotrexate. Primarily inhibit MACs and lymphocytes
What do newer therapeutic agents target for RA?
IL-1, TNF-alpha, IL-6, T-cells inactivation, deplete B-cells, and JAK inhibitors
What is the significance QKRAA sequence in the HLA-DRB1 class II MHC?
hypervariable portion of DRB1 that surrounds antigen-binding groove and may interact with side chains of bound antigen and with T cell receptor. It determines susceptibility and severity of disease. Enhance binding of citrullinated proteins and is sen with anti-CCP antibodies
T or F: Pannus can be seen in RA
TRUE. It?s the spongey material that forms in joint from infiltrating cells and hyperplasia of synovial cells
