Introduction to Rheumatology Flashcards
what is a tendon?
cords of strong fibrous collagen tissue attaching muscle to bone
what is a ligament?
flexible fibrous connective tissue which connect two bones
components of a synovial joint
synovium
synovial fluid
articular cartilage
two major divisions of arthritis are?
osteoarthritis (degenerative) inflammatory arthritis (main type is rheumatoid arthritis)
what is inflammation?
physiological response to deal with injury or infection
inflammation manifests clinically as?
rubor (redness) dolor (pain) calor (heat) tumor (swelling) loss of function
list physiological, cellular and molecular changes of inflammation
increased blood flow
migration of WBC
activation/differentiation of leucocytes
cytokine production e.g. TNFalpha, IL1, IL6, IL17
two main types of crystal arthritis
gout
pseudogout
immune mediated joint inflammation
rheumatoid arthritis
Seronegative spondyloarthropathies
Connective tissue diseases
infective causes of joint arthritis
septic arthritis
tuberculosis
what is gout?
syndrome caused by deposition of urate (uric acid) crystals -> inflammation
risk factor for gout
High uric acid levels (hyperuricaemia)
causes of hyperuricaemia
genetic tendency increased intake of purine rich food reduced excretion (kidney failure)
what is pseudogout?
syndrome caused by deposition of calcium pyrophosphate dihydrate (CPPD) crystal deposition crystals -> inflammation
risk factors for pseudogout
background osteoarthritis
elderly patients
intercurrent infection
acute gout can lead to?
gouty arthritis
tophi (aggregated deposits of MSU in tissue)
gouty arthritis commonly affects which joint?
metatarsophalangeal joint of the big toe (‘1st MTP joint’)
overview of gouty arthritis
Abrupt onset
Extremely painful
Joint red, warm, swollen and tender
Resolves spontaneously over 3-10 days
gout finding on x-ray
juxta-articular ‘rat bite’ erosions at the MTPJ of the great toe
investigations for suspected crystal arthritis (gout)
joint aspiration - synovial fluid analysis
management for an acute attack of gout
colcihine
NSAIDs
steroids
management for chronic gout
allopurinol
synovial fluid samples are analysed for
pathogens + crystals
rapid Gram stain > culture > antibiotic sensitivity assay
polarising light microscopy
gout vs pseudogout examination findings
gout: urate crystals, needle shape, negative birefrigence
pseudogout: calcium pyrophosphate dihydrate crystals, brick shaped, positive birefrigence
what is rheumatoid arthritis?
chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis
(inflammation of the synovial membrane) of synovial (diarthrodial) joints
synovium becomes a pannus in rheumatoid arthritis due to?
Neovascularisation Lymphangiogenesis inflammatory cells: activated B and T cells plasma cells mast cells activated macrophages
pathogenesis of rheumatoid arthritis
Dominant detrimental role of TNFα (GO BACK TO SLIDES)
how is TNFα inhibition achieved?
parenteral administration (most commonly sub-cutaneous injection) of antibodies or fusion proteins
key features of rheumatoid arthritis
chronic arthritis (polyarthritis, early morning stiffness, joint erosions on radiographs) extra articular disease can occur e.g. rheumatoid nodules autoantibody against IgG may be in blood
pattern of joint involvement of rheumatoid arthritis
symmetrical
affects multiple joints (polyarthritis)
particularly hands and feet
commonest affected joints in rheumatoid arthritis
Metacarpophalangeal joints (MCP), proximal interphalangeal joints (PIP), wrists , knees, ankles, metatarsophalangeal joints (MTP)
primary site of synovial inflammation in rheumatoid arthritis is?
synovium
synovial inflammation in rheumatoid arthritis includes?
proximal inter-phalangeal joint synovitis
extensor tenosynovitis
olecranon bursitis
common extra-articular features of rheumatoid arthritis
fever
weight loss
subcutaneous nodules
uncommon extra-articular features of rheumatoid arthritis
vasculitis
Ocular inflammation e.g. episcleritis
Neuropathies
Amyloidosis
Lung disease – nodules, fibrosis, pleuritis
Felty’s syndrome – triad of splenomegaly, leukopenia and rheumatoid arthritis
what are subcutaneous nodules in rheumatoid arthritis?
central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
subcutaneous nodules in rheumatoid arthritis occurs in what percentage of patients?
approximately 30%
subcutaneous nodules in rheumatoid arthritis are associated with?
severe disease
extra-articular manifestations
rheumatoid factor
list the two antibodies found in the blood of patients with rheumatoid arthritis
rheumatoid factor (recognize the Fc portion of IgG as target antigen, typically IgM antibodies) antibodies to citrullinated protein antigens
Patients with RA test with rheumatoid factor present at __% at disease onset and further __% over first 2 years of diagnosis.
70
10-15
treatment goal for RA
prevent joint damage
RA treatment requires?
Early recognition of symptoms, referral and diagnosis
Prompt initiation of treatment: joint destruction = inflammation x time
Aggressive treatment to suppress inflammation
1st line drug treatment for RA
methotrexate in combination with hydroxychloroquine or sulfasalazine
2nd line drug treatment for RA
Biological therapies offer potent and targeted treatment strategies
New therapies include Janus Kinase inhibitors : Tofacitinib & Baricitinib
what are DMARDs?
Disease-modifying anti-rheumatic drugs
avoid long term use of what in the treatment of RA and for what reason?
glucocorticoid therapy (prednisolone)
side effects
what are biological therapies?
proteins (usually antibodies) that specifically target a protein such as an inflammatory cytokine
examples of biological therapies mechanisms for rheumatoid arthritis
inhibition of TNFalpha
B cell depletion
modulation of T cell co-stimulation
inhibition of IL6 signalling
name the biological therapies that treat RA via inhibition of TNFalpha
antibodies (infliximab, and others) fusion proteins (etanercept)
name the biological therapies that treat RA via B cell depletion
Rituximab – antibody against the B cell antigen, CD20
name the biological therapies that treat RA via modulation of T cell co-stimulation
Abatacept - fusion protein - extracellular domain of human cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) linked to modified Fc (hinge, CH2, and CH3 domains) of human immunoglobulin G1
name the biological therapies that treat RA via inhibition of IL6 signalling
Tocilizumab (RoActemra) – antibody against interleukin-6 receptor.
Sarilumab (Kevzara) – antibody against interleukin-6 receptor.
difference between joints in RA and osteoarthritis on x-ray
osteo no spaces but still some space for RA
what is ankylosing spondylitis?
type of arthritis in the spine, causing inflammation and gradual fusing of the vertebrae
common demographic of ankylosing spondylitis
20-30 years
male
ankylosing spondylitis is associated with what genetic marker on the MHC?
HLA B27
clinical presentation of ankylosing spondylitis
lower back pain + stiffness (early morning, improves w/ exercise) reduced spinal movement peripheral arthritis plantar fascitis, achilles tendonitis fatigue
investigations for ankylosing spondylitis
bloods
imaging: x-ray, MRI
positive results in bloods for ankylosing spondylitis?
Normocytic anaemia
Raised CRP, ESR
HLA-B27
positive results in imaging for ankylosing spondylitis?
Squaring Vertebral bodies, Romanus lesion
Erosion, sclerosis, narrowing SIJ
Bamboo Spine
Bone marrow oedema
management of ankylosing spondylitis
physiotherapy
exercise regime
NSAIDs
peripheral joint disease - DMARDs
are rheumatoid factors present in ankylosing arthritis?
no
‘seronegative’
what is psoriasis?
autoimmune disease affecting the skin (scaly red plaques on extensor surfaces eg elbows and knees)
psoriatic arthritis classically clinically presents as?
asymmetrical arthritis affecting IPJs
psoriatic arthritis can also manifest as?
Symmetrical involvement of small joints (rheumatoid pattern)
Spinal and sacroiliac joint inflammation
Oligoarthritis of large joints
Arthritis mutilans
investigations for psoriatic arthritis?
X-rays of affected joints – pencil in cup abnormality
MRI – sacroiliitis and enthesitis
Bloods – no antibodies as seronegative
management for psoriatic arthritis?
DMARDs – methotrexate
avoid what drug in the treatment of psoriatic arthritis? why?
oral steroids
risk of pustular psoriasis due to skin lesions
list other connective tissue diseases
Systemic Sclerosis
Myositis
Sjogrens syndrome
Mixed connective tissue disease
what is Reiter syndrome?
describes the triad of arthritis, urethritis and conjunctivitis in a patient following a bacterial infection
reactive arthritis
Sterile inflammation in joints following infection especially urogenital (e.g. Chlamydia trachomatis) and gastrointestinal (e.g. Salmonella, Shigella, Campylobacter infections) infections
Important extra-articular manifestations of reactive arthritis include?
Enthesitis (tendon inflammation)
Skin inflammation
Eye inflammation
Reactive arthritis may be first manifestation of what infections?
HIV
hepatitis C
reactive arthritis commonly presents in what demographic?
young adults with genetic predisposition (e.g. HLA-B27) and environmental trigger (e.g. Salmonella infection)
management of reactive arthritis
usually self-limiting – can be managed with NSAIDS or DMARDs if required
epidemiology of SLE
F:M ratio 9:1
Presentation 15 - 40 yrs
Increased prevalence in African and Asian ancestry populations
Prevalence varies 4-280/100,000
clinical tests for SLE
Antinuclear antibodies:
^ sensitivity for SLE but not specific, -ve test rules out SLE, but a + ve test does not mean SLE.
Anti-double stranded DNA antibodies
what is lupus?
multi-system autoimmune disease
