intro to rheumatology Flashcards
what is rheumatology?
Rheumatology =
The medical specialty dealing with diseases of the musculoskeletal system including:
Joints = where 2 bone meets
Tendons = cords of strong fibrous collagen tissue attaching muscle to bone
Ligaments = flexible fibrous connective tissue which connect two bones
Muscles
Bones
what are the components of a synovial joint?
articular cartilage -
Type II collagen
Proteoglycan (aggrecan)
joint cavity
synovial membrane (synovium) - 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
synovial fluid -
Hyaluronic acid-rich viscous fluid
what is arthritis and its types?
Arthritis = disease of the joints
There are many different types of arthritis, but there are 2 major divisions:
Osteoarthritis
(Degenerative arthritis)
Inflammatory arthritis (main type is rheumatoid arthritis)
what is inflammation?
Inflammation = a physiological response to deal with injury or infection
However, excessive/inappropriate inflammatory reactions can damage the host tissues
Manifests clinically as:
- RED (rubor)
- PAIN (dolor)
- HOT (calor)
- SWELLING (tumor)
- LOSS OF FUNCTION
Physiological, cellular and molecular changes:
-Increased blood flow
-Migration of white blood cells (leucocytes) into the tissues
-Activation/differentiation of leucocytes
-Cytokine production
E.g. TNF-alpha, IL1, IL6, IL17
what are some condition that involve joint inflammation?
1)Crystal arthritis:
Gout – uric acid
Pseudogout – calcium pyrophospahate
2) Immune-mediated (“autoimmune”) E.g. Rheumatoid arthritis Seronegative spondyloarthropathies Connective tissue diseases
3) Infection
Septic arthritis
Tuberculosis
what is crystal arthritis and its types?
Gout:
a syndrome caused by deposition of urate (uric acid) crystals -> inflammation
High uric acid levels (hyperuricaemia) = risk factor for gout
Causes of hyperuricaemia:
Genetic tendency
Increased intake of purine rich foods (beer)
Reduced excretion (kidney failure)
Pseudogout:
a syndrome caused by deposition of calcium pyrophosphate dihydrate (CPPD) crystal deposition crystals -> inflammation
Risk factors: background osteoarthritis, elderly patients, intercurrent infection
what is gout?
Acute gout is a good example of arthritis
A disease in which tissue deposition of monosodium urate (MSU) crystals occurs as a result of hyperuricaemia and leads to one or more of the following:
Gouty arthritis
Tophi (aggregated deposits of MSU in tissue)
Gouty arthritis commonly affects the metatarsophalangeal joint of the big toe (‘1st MTP joint’)
symptoms: podagra Abrupt onset Extremely painful Joint red, warm, swollen and tender Resolves spontaneously over 3-10 days monoarthritis rat bite erosions seen on x ray
what are the investigations and management of gout?
Investigations:
Joint aspiration – synovial fluid analysis (usually don’t have to coz it Is so characteristic)
Management:
Acute attack – colcihcine, NSAIDs, Steroids
Chronic – allopurinol
what role does synovial fluid examination play in gout?
Synovial fluid samples are routinely examined for pathogens and crystals:
Rapid Gram stain followed by culture and antibiotic sensitivity assays
Polarising light microscopy to detect crystals which can be seen in arthritis due to gout or pseudogut
gout:
urate crystals
needle shaped
negative birefringence
pseudo gout:
calcium pyrophosphate dehydrate (CPPD) crystals
rhomboid shaped
positive birefringence
what is immune mediated inflammatory joint disease?
Most common form is rheumatoid arthritis (RA)
RA = chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis
(inflammation of the synovial membrane) of synovial (diarthrodial) joints
what is the pathogenesis of rheumatoid arthritis?
Synovial membrane is abnormal in rheumatoid arthritis:
The synovium becomes a proliferated mass of tissue (pannus) due to:
Neovascularisation Lymphangiogenesis inflammatory cells: activated B and T cells plasma cells mast cells 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 (‘cytokine imbalance’)
Sterile – not associated with infection
what is a key cytokine involved in rheumatoid arthritis?
Dominant detrimental role of TNFα in rheumatoid arthritis validated by the therapeutic success of TNFα inhibition in this condition
TNFα inhibition is achieved through parenteral administration (most commonly sub-cutaneous injection) of antibodies or fusion proteins
what are the key features of rheumatoid arthritis?
Chronic arthritis:
Polyarthritis - swelling of the small joints of the hand and wrists is common
Symmetrical
Early morning stiffness in and around joints
May lead to joint damage and destruction - ‘joint erosions’ on radiographs
Extra-articular disease can occur:
Rheumatoid nodules – under skin on ulnar border of elbow
Others rare e.g. vasculitis, episcleritis
Rheumatoid ‘factor’ may be detected in blood:
Autoantibody against IgG - should really call this rheumatoid ‘antibody’ not ‘factor’
what is the pattern of joint involvement in rheumatoid arthritis?
Symmetrical
Affects multiple joints (polyarthritis)
Affects small and large joints, but particularly hands and feet
Commonest affected joints: Metacarpophalangeal joints (MCP) Proximal interphalangeal joints (PIP) Wrists Knees Ankles Metatarsophalangeal joints (MTP)
what is the primary site of pathology in rheumatoid arthritis?
the synovium, which includes:
synovial joints
tenosynovium surrounding tendons
bursa
what are the extra-articular features of rheumatoid arthritis?
Common:
Fever, weight loss
Subcutaneous nodules
Uncommon:
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?
Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
Occur in ~30% of patients
Associated with:
Severe disease
Extra-articular manifestations
Rheumatoid factor
what is rheumatoid factor?
Rheumatoid factor:
Antibodies that recognize the Fc portion of IgG as their target antigen
typically IgM antibodies i.e. IgM anti-IgG antibody !
(IgM, the autoantibody is pentameric)
(IgG, the one we all have is a single antibody)
Positive in 70% at disease onset and further 10-15% become positive over the first 2 years of diagnosis
what are anti-CCP antibodies?
Antibodies to citrullinated protein antigens (ACPA):
Antibodies to citrullinated peptides are highly specific for rheumatoid arthritis
Anti-cyclic citrullinated peptide antibody ‘anti-CCP antibody’
Citrullination of peptides is mediated by enzymes termed:
Peptidyl arginine deiminases (PADs)
how is rheumatoid arthritis treated?
Treatment goal: prevent joint damage
Requires:
Early recognition of symptoms, referral and diagnosis
Prompt initiation of treatment: joint destruction = inflammation x time
Aggressive treatment to suppress inflammation
Drug treatment:
Disease-modifying anti-rheumatic drugs (‘DMARDs’) = drugs that control the disease process
1st line treatment:
methotrexate in combination with hydroxychloroquine or sulfasalazine
2nd line:
Biological therapies offer potent and targeted treatment strategies
New therapies include Janus Kinase inhibitors : Tofacitinib & Baricitinib
Important roles for glucocorticoid therapy (prednisolone) but avoid long-term use because of side-effects.
Multidisciplinary approach also important e.g. physiotherapy, occupational therapy, hydrotherapy, surgery
what are the biological therapies used in rheumatoid arthritis?
Biological therapies are proteins (usually antibodies) that specifically target a protein such as an inflammatory cytokine
- Inhibition of tumour necrosis factor-alpha (‘anti-TNF’)
antibodies (infliximab, and others)
fusion proteins (etanercept) - B cell depletion
Rituximab – antibody against the B cell antigen, CD20 - 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 - Inhibition of interleukin-6 signalling
Tocilizumab (RoActemra) – antibody against interleukin-6 receptor.
Sarilumab (Kevzara) – antibody against interleukin-6 receptor.
what is ankylosing spondylitis?
Seronegative spondyloarthropathy – no positive autoantibodies
Chronic sacroillitis – inflammation of sacroiliac joints
Results in spinal fusion – ankylosis
Common demographic: 20-30yrs, M
Associated with HLA B27
what is the clinical presentation of ankylosing spondylitis?
Lower back pain + stiffness
Early morning
Improves with exercise
Reduced spinal movements
Peripheral arthritis
Plantar Fasciitis, Achilles Tendonitis
Fatigue
Back pain >3 months, <45 years is suggestive of possible Ank Spond
what investigations are done for ankylosing spondylitis?
Bloods:
Normocytic anaemia
Raised CRP, ESR
HLA-B27
Imaging: X-Ray MRI Squaring Vertebral bodies, Romanus lesion Erosion, sclerosis, narrowing SIJ Bamboo Spine Bone Marrow Oedema
what is the management of ankylosing spondylitis?
Management: Physiotherapy Exercise regimes NSAIDs Peripheral joint disease - DMARDs
what is psoriatic arthritis?
Psoriasis is an autoimmune disease affecting the skin (scaly red plaques on extensor surfaces eg elbows and knees)
~10% of psoriasis patients also have joint inflammation
Unlike RA, rheumatoid factors are not present (“seronegative”)
Varied clinical presentations:
-Classically asymmetrical arthritis affecting IPJs
But also can manifest as:
- Symmetrical involvement of small joints (rheumatoid pattern)
- Spinal and sacroiliac joint inflammation
- Oligoarthritis of large joints
- Arthritis mutilans
what are the investigations for psoriatic arthritis?
X-rays of affected joints – pencil in cup abnormality
MRI – sacroiliitis and enthesitis
Bloods – no antibodies as seronegative
how is psoriatic arthritis managed?
DMARDs – methotrexate
Avoid oral steroids – risk of pustular psoriasis due to skin lesions
what is 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 include:
Enthesitis (tendon inflammation)
Skin inflammation
Eye inflammation
Reactive arthritis may be first manifestation of HIV or hepatitis C infection
Commonly 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
Condition is usually self-limiting – can be managed with NSAIDS or DMARDs if required
Reactive arthritis is distinct from infection in joints (septic arthritis)
what is systemic lupus erythematous?
Lupus = a multi-system autoimmune disease
Multi-site inflammation: can affect any almost any organ.
Often joints, skin, kidneys, haematology. Also: lungs, CNS involvement
Associated with antibodies to self antigens (‘autoantibodies’)
Autoantibodies are directed against components of the cell nucleus (nucleic acids and proteins)
Autoantibodies can be useful diagnostically. Clinical tests include:
- 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.
Epidemiology: F:M ratio 9:1 Presentation 15 - 40 yrs Increased prevalence in African and Asian ancestry populations Prevalence varies 4-280/100,000
may come with a malar or ‘butterfly’ rash
what are some other connective tissue diseases?
Systemic Sclerosis
Myositis
Sjogrens syndrome
Mixed connective tissue disease
