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Year 1 - BRS > 5.7 - Introduction to Rheumatology Part 2 > Flashcards

5.7 - Introduction to Rheumatology Part 2 Flashcards

1
Q

What is the structural classification of joints?

A
  • fibrous joints
  • cartilaginous joints
  • synovial joints
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2
Q

What is the functional classification of joints?

A
  • synarthroses
  • amphiarthroses
  • diarthroses
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3
Q

Define and give examples of fibrous joints.

A
  • no space between the bones
  • e.g. sutures in skull, syndesmosis (sheet of connective tissue) in tibia and fibula joint (ankle)
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4
Q

Define and give examples of cartilaginous joints.

A
  • joints in which the bones are connected by cartilage
  • e.g. joints between spinal vertebrae
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5
Q

Define and give examples of synovial joints.

A
  • have a space between the adjoining bones (synovial cavity)
  • this space is filled with synovial fluid
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6
Q

What are synarthroses and which joint structures do they belong to?

A
  • generally allow no movement
  • fibrous and cartilaginous joints can be this type
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7
Q

What are amphiarthroses and which joint structures do they belong to?

A
  • allow very limited movement
  • fibrous and cartilaginous joints can be this type
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8
Q

What are diarthroses and which joint structures do they belong to?

A
  • allow for free movement of the joint
  • synovial joints are the type
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9
Q

What are the components of a synovial joint?

A
  • bone
  • articular cartilage
  • joint cavity containing synovial fluid
  • articular cartilage
  • bone
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10
Q

What is a synovium made up of?

A
  • 1-3 cell deep lining containing macrophage-like phagocytic cells (type A synoviocyte) and fibroblast-like cells that produce hyaluronic acid (type B synoviocyte)
  • type I collagen
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11
Q

What is synovial fluid made up of?

A

Hyaluronic acid-rich viscous fluid

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12
Q

What is articular cartilage made up of?

A
  • ECM: type II collagen, water, proteoglycans (mainly aggrecan)
  • chondrocytes - specialised cells
  • avascular - no blood supply, so it heals poorly after injury
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13
Q

Describe aggrecan.

A
  • a proteoglycan that possesses many chondroitin sulfate and keratin sulfate chains
  • characterised by its ability to interact with hyaluronan (HA) to form large proteoglycan aggregates
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14
Q

What is rheumatoid arthritis?

A
  • chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis
  • primary site of pathology is in the synovium
  • synovitis - inflammation of synovial membrane
  • synovium found at synovial (diarthrodial) joints, tenosynovium surrounding tendons and bursa
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15
Q

What are the key features of rheumatoid arthritis?

A
  • chronic arthritis
  • polyarthritis
  • early morning stiffness in and around joints
  • may lead to joint damage and destruction - ‘joint erosions’ on radiographs
  • extra-articular disease can occur
  • auto-antibodies may be detected in blood (against IgG) - rheumatoid factor
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16
Q

What is the pattern of joint involvement in rheumatoid arthritis?

A
  • symmetrical
  • affects multiple joints (polyarthritis)
  • affects small and large joints, but particularly hands, wrists and feet
  • commonest affected joints: metacarpophalangeal joints (MCP), proximal interphalangeal joints (PIP), wrists, knees, ankles, metatarsophalangeal joints (MTP)
  • tends to spare DIP joints in contrast to osteoarthritis
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17
Q

What are the common extra-articular features of rheumatoid arthritis?

A
  • fever
  • weight loss
  • subcutaneous nodules
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18
Q

What are the uncommon extra-articular features of rheumatoid arthritis?

A
  • lung disease - nodules, fibrosis, pleuritis
  • ocular inflammation - episcleritis
  • vasculitis - blood vessel
  • neuropathies - nerve damage = motor weakness/loss of sensation
  • Felty’s syndrome - triad of splenomegaly, leukopenia and rheumatoid arthritis
  • amyloidosis - chronic untreated inflammation
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19
Q

What are subcutaneous nodules?

A
  • found just distal to elbow and on fingers
  • characterised by central area of fibrinoid necrosis surrounded by histiocytes (macrophages) and peripheral layer of connective tissue
  • occur in 30% of patients
  • associated with severe disease, extra-articular manifestations, rheumatoid factor
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20
Q

What is the pathogenesis of rheumatoid arthritis?

A
  • synovial membrane is abnormal
  • synovium becomes a proliferated mass of tissue (pannus) due to:
  • neovascularisation - formation of new blood vessels
  • lymphangiogenesis - formation of new lymph vessels
  • inflammatory cells - activated B and T, plasma, mast, activated macrophages
  • recruitment, activation and effector functions of these cells is controlled by a cytokine network
  • there is an excess of pro-inflammatory vs anti-inflammatory cytokines
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21
Q

What is the dominant pro-inflammatory cytokine and what effects does it have?

A
  • TNF-alpha in the rheumatoid synovium
  • has pleotropic actions (affects multiple processes)
  • activates osteoclasts –> bone resorption to bone erosion
  • affects synoviocytes –> joint inflammation and swelling
  • activates chondrocytes –> cartilage degradation –> joint space narrowing
  • angiogenesis, leukocyte accumulation, endothelial cell activation, chemokine release, proinflammatory cytokine release, hepcidin induction, PGE2 production
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22
Q

How is TNF-alpha treated?

A

TNF-alpha inhibition has been successful using parenteral administration (subcutaneous injection usually) of antibodies / fusion proteins

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23
Q

What are blood test results like for rheumatoid arthritis (RA), osteoarthritis (OA) and septic arthritis (SA)?

A
  • Hb - decreased/normal, normal, normal
  • MCV - normal, normal, normal
  • white cell count - normal, normal, increased (leukocytosis)
  • platelet count - normal/increased, normal, normal/increased
  • ESR - increased, normal, normal/increased
  • CRP - increased, normal, increased
24
Q

What is rheumatoid factor?

A
  • antibody found in the blood of RA patients
  • antibodies that recognise the Fc portion of IgG as their target antigen
  • typically IgM antibodies e.g. IgM anti-IgG antibody
  • positive in 70% at disease onset and further 10-15% become positive over first 2 years of diagnosis
25
Q

What are antibodies to citrullinated protein antigens (ACPA)?

A
  • antibody found in the blood of RA patients
  • highly specific for RA
  • sometimes called anti-cyclic citrullinated peptide antibodies (anti-CCP antibody)
  • citrullination of peptides is mediated by peptidyl arginine deaminases (PADs) which convert arginine to citrulline
26
Q

How can X-rays be used to image RA?

A
  • soft tissue swelling
  • peri-articular osteopenia - darkening of bone
  • bony erosions
  • erosions only occur in established disease - the aim of modern therapy is to treat early before erosions (permanent damage) has ocurred
  • information from X-rays is limited to bony structures
27
Q

How is ultrasound (US) used to image RA?

A
  • much better test for detecting synovitis - detects:
  • synovial hypertrophy (thickening)
  • increased blood flow (seen as doppler signal)
  • may detect smaller erosions not seen on plain X-ray
  • US (usually of hands and wrists) can be performed alongside clinical assessment in a dedicated early arthritis clinic
28
Q

Why is MRI not used much to image RA?

A

Can also be used but is expensive and time-consuming

29
Q

Describe the principles of management of RA.

A
  • treatment goal - prevent joint damage (irreversible)
  • requires:
  • early recognition of symptoms, referral and diagnosis
  • prompt initiation of treatment: joint destruction = inflammation x time
  • aggressive pharmacological treatment to suppress inflammation
  • MDT input where needed e.g. physiotherapy, occupational therapy, surgery
30
Q

What are pharmacological treatment options for RA?

A
  1. glucocorticoid therapy (steroids) - useful acutely but avoid long-term use due to side-effects
  2. NSAIDs (non-steroidal anti-inflammatory drugs e.g. ibuprofen) - symptoms relief but increasingly less important
  3. DMARDs (disease-modifying anti-rheumatic drugs) - drugs that control the disease process (usually immunosuppressive)
31
Q

What is the first line treatment regime for RA?

A
  • IM or short course of oral steroids
  • start combination DMARD therapy - usually methotrexate + hydroxychloroquine and/or sulfasalazine
32
Q

What is the second line treatment regime for RA?

A
  • biological therapies offer potent and targeted treatment strategies
  • new therapies include Janus Kinase inhibitors - Tofacitinib & Baricitinib
33
Q

How does steroids/glucocorticoid therapy work?

A
  • glucocorticoids bind the glucocorticoid receptor (GR)
  • GR resides in cytoplasm
  • on binding to glucocorticoids, steroid-GR complex translocates to nucleus and binds DNA response elements, affecting transcription
34
Q

What are methods of steroid administration?

A
  • oral prednisolone
  • intramuscular (IM) methyl prednisolone
  • intravenous (IV)
  • intra-articular (IA)
35
Q

What are the side effects of steroids?

A
  • Cushing’s syndrome
  • mood disturbance - mania, depression, anxiety
  • cataracts
  • sleep apnoea (weight gain)
  • increased BP, CVD risk
  • T2DM
  • weight gain, central obesity
  • osteoporosis
  • skin thinning
  • myopathy
  • increased infection risk
36
Q

What is the mechanism for methotrexate?

A
  • inhibits dihydrofolate reductase (‘folate antagonist’)
  • side effects: nausea, hair loss, fall in white cell count, abnormal liver function, pneumonitis, infection risk
37
Q

How do biological therapies work?

A
  • biological therapies are proteins (usually antibodies) that specifically target a protein such as an inflammatory cytokine
  1. inhibition of TNF-alpha
  2. B cell depletion
  3. modulation of T-cell co-stimulation
  4. inhibition of IL-6 signalling
38
Q

What is seronegative arthritis?

A
  • rheumatoid factors not present
  • psoriatic arthritis
  • reactive arthritis
  • ankylosing spondylitis
  • IBD-associated
  • subacute/chronic
  • mono/oligo large joint
  • may involve spine
  • asymmetrical
39
Q

What is psoriatic arthritis?

A
  • psoriasis is an autoimmune disease affecting the skin
  • scaly red plaques on extensor surfaces (e.g. elbows and knees)
  • 10% of psoriasis patients also have joint inflammation
  • unlike RA, rheumatoid factors are not present (seronegative)
40
Q

How does psoriatic arthritis present clinically?

A
  • varied clinical presentations
  • classically asymmetrical arthritis affecting IPJs

Can also manifest as:

  • symmetrical involvement of small joints (rheumatoid pattern)
  • oligoarthritis of large joints
  • arthritis mutilans
  • spinal and sacroiliac joint inflammation
41
Q

How do we investigate psoriatic arthritis and what would we see?

A
  • X-rays of affected joints - pencil in cup abnormality
  • MRI - sacroiliitis and enthesitis (inflammation of where a tendon/ligament attaches to bone)
  • bloods - no antibodies as it is seronegative
42
Q

How do we manage psoriatic arthritis?

A
  • DMARDs - methotrexate
  • avoid oral steroids - risk of pustular psoriasis due to skin lesions
43
Q

What is reactive arthritis?

A
  • sterile inflammation in joints following infection elsewhere in the body
  • common infections - urogenital (e.g. Chlamydia trachomatis), GI (e.g. Salmonella, Shigella, Campylobacter infections)
44
Q

What are the important extra-articular manifestations of reactive arthritis?

A
  • enthesitis (tendon inflammation)
  • skin inflammation
  • eye inflammation
  • may be the first manifestation of HIV or hepatitis C infection
45
Q

Who does reactive arthritis affect commonly?

A
  • young adults with genetic predisposition (e.g. HLA-B27) and environmental trigger (e.g. Salmonella infection)
  • symptoms follow 1-4 weeks after infection and this infection may be mild
46
Q

What are the differences between reactive arthritis and septic arthritis?

A
  • reactive arthritis not the same as infection in joints (septic arthritis) where there is active infection in joint, but with reactive arthritis it is sterile = infection has cleared
  • synovial fluid culture: +ve for SA, sterile for RA
  • antibiotic therapy: yes for SA, no for RA
  • joint lavage: yes (for large joints) for SA, no for RA
47
Q

What is the pathophysiology of ankylosing spondylitis?

A
  • characterised by enthesitis - inflammation of entheses (sites where tendon and ligaments join to bone)
  • large genetic component
  • many genetic variants associated with the disease (polygenic)
  • HLA-B27 is the strongest genetic risk factor
  • HLA-B27 is positive in 90% of AS, 10% in general population
  • used as a diagnostic biomarker but HLA-B27 +ve alone does not equal AS
  • cytokines play an important role in pathogenesis - TNF-alpha, IL-17, IL-23
  • aberrant peptide processing pathways (aminopeptidases) in the endoplasmic reticulum
48
Q

What is the natural history of untreated AS?

A

Spinal enthesitis –> bridging syndesmophytes (new bone growth between adjacent vertebra) –> spinal fusion

49
Q

What can MRIs detect in ankylosing spondylitis?

A

MRI can detect spinal inflammation before X-rays changes develop

50
Q

How is ankylosing spondylitis managed?

A
  1. physiotherapy and a life-long regular exercise programme
  2. pharmacological:
  • 1st line - NSAIDs e.g. ibuprofen, naproxen, diclofenac
  • mechanism: NSAIDs inhibit cyclooxygenase 1&2
  • risks: peptic ulcer, renal, asthma exacerbation, increased atherothrombosis risk
  • selective COX2 inhibitors reduce GI ulcer risk
  • 2nd line: biological therapies
  • therapeutic monoclonal antibodies targeting specific molecules
  • use if inadequate disease control after trying 2 NSAIDs
  • anti-TNF-alpha
  • anti-IL17
51
Q

What is lupus?

A

A multi-system autoimmune disease

52
Q

What body parts does systemic lupus erythematous usually affect?

A
  • multi-site inflammation - can affect almost any organ
  • often joints, skin, kidneys, haematology, lungs, CNS
  • said to be a great mimic - can present as seeming like a lot of other diseases
  • malar / butterfly rash common
53
Q

What is systemic lupus erythematous associated with?

A

Antibodies to self antigens (autoantibodies) directed against components of the cell nucleus (nucleic acids and proteins)

54
Q

What are clinical tests for systemic lupus erythematous?

A
  • antinuclear antibodies (ANA) - high sensitivity for SLE but not specific - a negative test rules out SLE but a positive test does not mean SLE
  • anti-double stranded DNA antibodies (anti-dsDNA Abs) - high specificity for SLE in the context of the appropriate clinical signs
55
Q

Who does systemic lupus erythematous affect more?

A
  • F:M ratio 9:1
  • presentation 15-40 years
  • increased prevalence in African and Asian ancestry populations
  • prevalence varies 4-280 per 100k

Year 1 - BRS (73 decks)

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