Rheumatoid Arthritis Flashcards
what is a normal immune response?
acute and chronic response
resolution
what are the potential problems associated with the immune response?
-bystander damage
-non resolution
-self-recognition and attack
what is autoimmunity?
loss of immunological tolerance to self
what is tolerance?
controlled unresponsiveness to self (despite the capacity to do so)
how common are autoimmune diseases?
5% of population, 1 in 20
what are the various meachanisms that result in autoimmunity?
-dysfunction in tolerance
-presentation of self antigens
-molecular mimicry
-loss of regulatory mechanisms
how many hits generally do we need to develop autoimmunity?
2 hit hypothesis
what are the effects of endocrine cells autoimmunity?
diabetes, hyperthyroidism, Addisons disease and premature ovarian failure
what is. the effect of autoimmunity on the liver?
autoimmune hepatitis, primary biliary cirrhosis
what is the effect of autoimmunity on the bowel?
pernicious anaemia, inflammatory bowel disease
what is the effect of autoimmunity on the kidneys?
nephritis, glomerulonephritis
what is the effect of autoimmunity on the joints?
rheumatoid arthritis
what is the effect of autoimmunity on the skin?
vitiligo, pemphigus, psoriasis
what is the effect of autoimmunity on the eyes?
scleritis, karatitus, uveitis
what is the effect of autoimmunity on the nervous system?
MS
what is rheumatoid arthritis?
most common inflammatory arthritis, widespread joint pain, stiffness and swelling leading to joint destruction
how prevelant is RA?
0.8% of UK
who has a higher risk of developing RA?
females, 2-3x greater than males
what are the symptoms of RA?
joint pain
stiffness
joint swelling
fatigue
systemic
weight loss
fevers
extra articularfeatures
what does RA affect?
synovial tissue, lining of joints
-can also affects extra articular manifestations
what is the systemic autoimmunity phase before arthritis?
-onset is unclear
-autoantibodies
-increased cytokines and chemokine
-altered cholesterol metabolism
what is rheumatoid factor (RF)?
antibody directed against Fc or IgG
what is anti-CCP antibodies/ACPA?
CCP- cyclic citrullinated peptide
ACPA - anti citrullinated protein antibodies
citrulline replaces arginine (post translational modifications)
why does joint inflammation start?
-unclear (maybe permeably or citrullinated. peptides)
-activated monocytes/macrophages, neutrophils, osteoclasts
-release cytokines and chemokine which lead to damage
how is RA treated?
-NSAIDs
-corticosteroids
-DMARDs
conventional synthetic DMARDs (csDMARDs0
biologics (biological DMARDs/ bDMARDs0
small molecule inhibitors (tsDMARDs)
-combinations are better than single drug
what are NSAIDs?
non steroidal anti-inflammatory drugs
what are DMARDs?
disease modifying anti-rheumatic drugs
what are some of the commonly used DMARDs for RA?
-methotrexate
-sulphasalazine
-leflunomide
-gold
-hydroxychloroquine
-cyclosporin
-azathioprine
-penicillamine
(non specific immune suppressing drugs)
what are biological agents?
drugs such as monoclonal antibodies, receptors or peptides, which have been developed rationally by targeting processes important in disease pathogenesis eg cytokines, T cells and B cells
how id TNF- a pivotal in RA?
-ability to block cytokine signalling via its receptor
-TNF seen as ‘conductor’ of pathology in RA
what are the remaining uncertainties of biosimilars?
-longterm efficacy and safety
-immunogenecity
-interchangeability
-many are made by non traditional pharmaceutical companies eg Samsung
what are some examples of biological agents?
infliximab
adalimumab
what are some examples of DMARDs?
methotrexate
leflunomide
sulfasalazine
what is an example of a corticosteroid?
prednisolone
what would a radiograph of RA show?
joint space narrowing
cartilage loss
osteopenia
what are subcutaneous rheumatoid nodules?
systemic symptom
fibroid necrosis of subcutaneous tissue
which joints of the hands are generally spared by RA?
distal interphalangeal joints
what would analysis of synovial fluid form a RA affected joint show?
high protein levels
>50% increased neutrophils
what is rheumatoid factor?
an autoantibody found in 80% of RA cases
what does the swan neck deformity affect?
proximal interphalangeal (PIP) joint hyperextension and the distal interphalangeal (DIP) joint flexion
what is sulfasalazine?
combination of sulfapyridine and 5-aminosalicyclic acid used for RA treatment (csDMARD
what is an antibody more specific to RA than rheumatoid factor?
anti-cyclic citrullinated peptide
what is pannus?
synovial tissue proliferation which leads to cartilage destruction and joint ankylosis
what kind of Ig is a classic lab finding in RA?
IgG
