Rheumatology: Rheumatoid Arthritis Flashcards
RA is a systemic, inflammatory, autoimmune disorder of unknown etiology that results in predominantly _____, symmetric, inflammatory synovitis leading to cartilage and bone destruction and deformities.
peripheral
Which joints does RA typically manifest in?
small joints of the hands and feet EXCEPT the DIPs, C1-C2, crycoartenoid, ossicles of the ear, and TMJ
What are the symptoms of RA?
morning stiffness, soft tissue swelling around joints, pain, deformities, loss of function
What are the signs of RA?
joint warmth and swelling, tenderness to palpation, deformities
What are the serologic findings in RA?
RF present ESR or CRP elevated anemia, hypergammaglobinemia CCP Abs inflammatory (>2000 WBC/microL), mostly neutrophils Low complement and glucose
Name a known risk factor for RA.
smoking
What radiographic findings are seen in RA?
swelling
juxta-articular osteopenia
symmetric loss of joint space
erosions in marginal distribution
What are rheumatoid nodules and how often are they seen?
nodules of extensor surfaces, tendon sheaths, or lungs; 20-25% of those that are RF positive
RA has other end-organ involvement. Where?
eyes (scleritis), lungs (pulm. fibrosis or nodules), pericardium, peripheral nerves (neuropathy)
What is the fem:male ratio of RA?
2.5:1
What allele is associated with RA?
HLA-DR4
RA begins with inflammation in the _____, with later destruction of the articular cartilage, bone, and periarticular structures.
synovium
In the early stages of RA, the synovial fluid is mostly composed of ____ cells.
mononuclear
What is pannus?
an organized mass of granulation tissue consisting of macs, T cells, B cells, and fibroblasts
Which gene is probably the most important for RA?
DRB1 (QKRAA)
What is the QKRAA sequence?
it surrounds the antigen binding groove and interacts with side chains of the bound antigen and the T cell receptor; determines both susceptibility to and severity of disease
Name 3 genes other than DRB1/QKRAA that are associated with RA.
PTPN22, STAT4, and TRAF1-C5
RA begins with inflammation in the synovium, with later destruction of the _____, ____, and ______.
articular cartilage, bone, and periarticular structures
What is the arthritogenic peptide hypothesis?
some sort of RA-associate MHC II molecule binds to and presents an arthritogenic peptide
What is an organized mass of granulation tissue consisting of macs, T cells, B cells, and fibroblasts called?
a pannus
What is the “selection of the T cell repertoire” hypothesis?
RA-associated class II molecules are involved in a selection of a particular set of T cells
What is the “class II peptide as an antigen itself” hypothesis?
sequence homology btw the shared epitope in the 3rd hypervariable region of the RA-associated MHC II causing cross-reaction
How do macs play a role in RA?
they secret pro-inflammatory cytokines (IL-1, TNFalpha, an IL-6) and proteolytic enzymes
Where does RF and anti-CCP come from?
B cells
_____ are immunoglobulins that recognize epitopes present within the Fc portion of IgG.
RF
Most RF are what kind of Ig?
IgM
Immune complexes of RF and IgG lead to _____ via the _____ pathway.
complement activation; classical
What are the treatments for RA?
- anti-inflammatory/analgesic drugs (NSAIDs, aspirin, prednisone)
- DMARDs (hydrochloroquine, sulfasalazine, leflunomide, methotrexate); cytokines, B cell inhibitors (rituximab)
- PT
- surgery (joint replacement)
RF are immunoglobulins that recognize epitopes present within the _____.
Fc portion of IgG
