INTRODUCTION TO RHEUMATOLOGY Flashcards
What is rheumatology?
Specialty dealing with diseases of the musculoskeletal system including joints, tendons, ligaments, muscles and bones
What is the synovium and what makes it up?
1-3 cell deep lining containing phagocytic cells and fibroblast=like cells that make hyaluronic acid
Type 1 collagen
What is synovial fluid?
Hyaluronic acid-rich viscous fluid contained in the synovial joint cavity
What is articular cartilage made of?
Type II collagen
Proteoglycan (aggrecan)
What are the 2 divisions of arthritis?
Osteoarthritis (degenerative arthritis) Inflammatory arthritis (RA is main type)
What are the clinical signs of inflammation?
Rubor Dolor Calor Tumor Loss of function
What are the physiological/cellular and molecular changes in inflammation
Increased blood flow
Migration of leukocytes into the tissues
Activation/differentiation of leukocytes
Cytokine production (TNF-alpha, IL1…)
What are the 3 causes of inflammatory arthritis?
Name examples for each
Crystal arthritis:
- Gout
- Pseudogout
Immune-mediated (autoimmune):
- Rheumatoid arthritis
- Seronegative spondyloarthropathies e.g. ankylosing
spondylitis
- Connective tissue diseases e.g. SLE, psoriatic arthritis
Infection:
- Septic arthritis
- Tuberculosis
What is gout and what are its risk factors?
Syndrome caused by deposition of monosodium urate (MSU)(uric acid) crystals in joint causing inflammation
Hyperuricaemia increases risk of gout:
- Genetic tendency
- Increased intake of purine rich foods
- Reduced excretion
What is pseudogout and what are its risk factors?
Syndrome caused by deposition of calcium pyrophosphate dihydrate (CPPD) crystals causing inflammation
Risk factors:
- Background osteoarthritis
- Elderly patients
- Intercurrent infection
How does gouty arthritis present?
Commonly monoarthritic 1st MTP joint (big toe) - podagra
Tophi - crystals in subcutaneous locations
Sudden onset
Extremely painful
Red, warm, swollen and tender
Resolves spontaneously over 3-10 days
What does an xray of a patient with gout typically show?
Juxta-articular rat bite erosions at the MTP joint of big toes if chronic
Usually in acute gout - looks normal
How can you investigate a patient suspected with gout?
Joint aspiration for synovial fluid analysis of crystals
How is gout managed?
Acute attack - colchicine, NSAIDs, steroids
Chronic - allopurinol
What does a synovial fluid examination involve?
Rapid Gram stain followed by culture and antibiotic sensitivity assays
Polarising light microscopy to detect crystals
What do the crystals in a patient with gout/pseudogout look like under polarising light microscopy?
Gout - Needle shaped with negative birefringence
Pseudogout - Brick shaped with positive birefringence
What is the most common autoimmune inflammatory joint disease?
Rheumatoid arthritis
What is rheumatoid arthritis?
Chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis of synovial joints
What is synovitis?
Inflammation of synovial membrane
What is the pathogenesis of rheumatoid arthritis?
Idiopathic
Neovascularisation
Lymphangiogenesis
Inflammatory cells - T/B, plasma, mast cells and macrophages
All causing synovium to become a proliferated mass of tissue (pannus)
Recruitment, activation of these cells controlled by cytokine network (cytokine imbalance of excess pro-inflammatory vs anti-inflammatory) - TNF-alpha has a major role and can be targeted in therapy via antibodies/fusion proteins
What cell is the main producer of TNF alpha
Activated macrophages in rheumatoid synovium
How does rheumatoid arthritis present?
Chronic polyarthritis (> 6 weeks) Swollen small joints of hand and wrist common Symmetrical Early morning stiffness in and around joints Joint erosions on radiographs
Extra-articular features (rheumatoid nodules…)
Rheumatoid factor may be detected in blood
Which joints are most commonly affected in rheumatoid arthritis?
MCP joints PIP joints MTP joints Wrists Knees Ankles
What is the primary site of pathology in RA and what can this cause?
Synovium
Synovitis of synovial joints Extensor tenosynovitis (tenosynovium surrounding tendons) Olecranon bursitis (bursa)
List the extra-articular features that might be seen in a patient with RA
Fever
Weight loss
Rheumatoid nodules
Uncommon:
- Vasculitis
- Ocular inflammation
- Neuropathies
- Amyloidosis
- Lung disease
- Felty’s syndrome
What are rheumatoid nodules?
Subcutaneous nodules with central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
Occurs in ~ 30% patients and associated with severe disease and rheumatoid factor
What are the 2 autoantibodies that are found in RA patients?
Rheumatoid factor
Antibodies to citrullinated protein antigens (ACPA)
What is rheumatoid factor?
Typically IgM antibodies that bind to Fc portion of IgG as their target antigen (IgM anti-IgG antibody)
Positive in 70% at disease onset and further 10-15% over the first 2 years
What are antibodies to citrullinated protein antigens (ACPA)?
AKA anti-cyclic citrullinated peptide antibody (anti-CCP antibody)
What is the citrullination of peptides mediated by?
Peptidyl arginine deaminases (PADs)
Describe the management of a patient with RA
Aggressive treatment as early as possible to prevent joint damage
Drugs:
- DMARDs
- Glucocorticoids (prednisolone) but avoid long-term use
1st line: methotrexate with hydroxychloroquine/sulfasalazine
2nd line: Biological therapies e.g. Janus Kinase inhibitors (Tofacitinib, Baricitinib)
Multidisciplinary too e.g. physiotherapy, occupational therapy, hydrotherapy, sugery
What are DMARDs?
Disease modifying anti-rheumatic drugs
Drugs which control the disease process
What are the different ways biological therapies work for RA?
- Anti-TNF alpha (Infliximab - antibody, fusion proteins)
- B cell depletion (Rituximab - antibody against CD20)
- T cell co-stimulation modulation (Abatacept)
- Inhibition of IL-6 signalling (Tocilizumab, Sarilumab)
What is ankylosing spondylitis?
Form of seronegative spondyloarthropathy so no positive autoantibodies. Causes chronic sacroillitis (inflammation of sacroiliac joints) and results in ankylosis (spinal fusion)
What antigen/gene is ankylosing spondylitis associated with?
HLA B27 on leukocytes
What is the common demographic of ankylosing spondylitis?
20-30 year old men
How does ankylosing spondylitis present clinically?
Lower back pain and stiffness (early morning and improves with exercise)
Reduced spinal movements
Poor posture (hyperextended neck, no lumbar lordosis, flexed hip and knees)
Peripheral arthritis
Plantar fasciitis, achilles tendonitis
Fatigue
What investigations can you do for ankylosing spondylitis and what would the results be?
Bloods:
- Normocytic anaemia
- Raised CRP, ESR
- HLA B27 +ve
- no rheumatoid factor
Imaging:
- X-ray
- MRI (squaring vertebral bodies, romanus lesion, erosion, sclerosis, narrowing SIJ, bamboo spine, bone marrow oedema)
What is the management for ankylosing spondylitis?
Physiotherapy
Exercise regimes
NSAIDs
DMARDs for peripheral joints disease
What is psoriatic arthritis?
Joint inflammation associated with 10% of psoriasis patients. Seronegative
How does psoriatic arthritis present?
Classically asymmetrical arthritis affected IPJs
But can also: Symmetrical involvement of small joints (rheumatoid pattern) Spinal and sacroiliac joint inflammation Oligoarthritis of large joints Arthritis mutilans
These are the 5 types of psoriatic arthritis
What investigations can be done for psoriatic arthritis and what can be seen?
Bloods:
- Seronegative
Imaging:
- X-ray (pencil in cup abnormality)
- MRI (sacroiliitis and enthesitis)
What is the management for psoriatic arthritis?
DMARDs - methotrexate
Avoid oral steroids as risk of pustular psoriasis
What is reactive arthritis?
Sterile inflammation in joints following infection elsewhere especially urogenital and GI
May be first manifestation of HIV or hepatitis C infection
How does reactive arthritis present?
Joint inflammation Extra-articular manifestations: - Enthesitis - Skin inflammation - Eye inflammation
Symptoms usually 1-4 weeks after infection
How is reactive arthritis managed?
Symptoms are usually self limiting
Can be managed with NSAIDs or DMARDs if needed
What is the common demographic of reactive arthritis?
Young adults with genetic predisposition (e.g. HLA B27) and environmental trigger (infection)
What is SLE and its pathology?
System Lupus Erythmatous
Multi system autoimmune inflammation which can affect almost any organ and joints. Autoantibodies against cell nucleus components (nucleic acids and proteins)
What clinical tests for autoantibodies in SLE be done diagnostically?
Antinuclear antibodies (ANA);
- High sensitivity for SLE but not specific
- -ve rules out SLE but +ve doesn’t mean SLE
Anti-double stranded DNA antibodies (anti-dsDNA Abs):
- High specificity for SLE but in context of appropriate clinical signs
What is the epidemiology of SLE?
F:M 9:1
15-40 years old
Increased prevalence in african and asian populations
