Rheumatoid Arthritis Flashcards
What is Rheumatology? Which parts of the MSK system does it include?
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?
2 bones meet
Joint cavity lined by the synovium containing the synovial fluid
Articular cartilage on either side
What is the synovium? What is it made of?
Synovium = connective tissue that lines the inside of the joint capsule
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
What is the synovial fluid made up of?
Hyaluronic acid-rich viscous fluid
What is the articular cartilage made up of?
Type II collagen
Proteoglycan (aggrecan)
What is the main joint disease?
Arthritis = disease of the joints
What are the 2 types of arthritis?
Osteoarthritis = degenerative arthritis
Inflammatory arthritis = main type is called rheumatoid arthritis, but also includes reactive arthritis, psoriatic arthritis, ankylosing spondylitis and more
What is inflammation?
What happens if there is too much inflammation?
Inflammation = a physiological response to deal with injury or infection
Excessive/inappropriate inflammatory reactions = damage to the host tissues
How does excessive inflammation manifest as clinically?
- RED (rubor)
- PAIN (dolor)
- HOT (calor)
- SWELLING (tumor)
- LOSS OF FUNCTION
What are the physiological changes at the site of inflammation?
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
Specific cytokines e.g. TNF-a, IL1, IL6, IL17 = important for targetting medications (biologics) at these as treatment options
What are the 3 main types of inflammatory arthritis that cause joint inflammation?
- Crystal arthritis
- Gout
- Pseudogout - Immune-mediated (“autoimmune”)
- Rheumatoid arthritis
- Seronegative spondyloarthropathies
- Connective tissue diseases - Infection
- Septic arthritis
- Tuberculosis (TB)
What are the 2 types of crystal arthritis?
Gout = tissue deposition of monosodium urate (MSU) crystals occurs as a result of hyperuricaemia –> inflammation
Pseudogout = deposition of calcium pyrophosphate dihydrate (CPPD) crystal deposition crystals –> inflammation
What are risk factors / causes for gout?
High uric acid levels (hyperuricaemia) = risk factor for gout
Causes of hyperuricaemia:
Genetic tendency
Increased intake of purine rich foods
Reduced excretion (kidney failure)
What are some risk factors for pseudogout?
Background osteoarthritis
Elderly patients
Intercurrent infection
What is acute gout? How does acute gout present clinically?
Acute gout - inflammatory arthritis due to deposition of MSU crystals leading to fouty arthritis and/or tophi (aggregated deposits of MSU in tissue)
Presents clinically as: Abrupt onset Extremely painful 10/10 Joint looks red, warm, swollen, and tender Resolves spontaneously over 3-10 days
Which joint is most affected in gouty arthritis?
1st MTP (metatarsophalangeal) joint i.e. the big toe
What is seen on an x-ray (radiograph) image of gout?
Black parts on the bones called ‘rat bite’ erosions
How can gout and pseudogout be investigated?
Joint aspiration - for synovial fluid analysis and to rule out septic arthritis
Not always possible - depends on size and site of the joint
How can gout be managed?
Acute = colcihine (anti-inflammatory drug), NSAIDs, steroids
Chronic = alopeuranol (works to reduce uric acid formation in the body)
How is synovial fluid examined from the joint aspiration?
Some of the sample is rapid Gram stain followed by culture and antibiotic sensitivity assays to check for septic arthritis
Some of the sample is analysed under polarising light microscopy to detect crystals which can be seen in arthritis due to gout or pseudogut
- Gout = needle shaped crystals; negative birefringence
- Pseudogout - brick shaped cyrstals, positive birefringence
What are some other immune mediated inflammatory joint diseases?
RA - rheumatoid arthritis
Lupus / SLE
What is rheumatoid arthritis (RA)?
Chronic autoimmune disease characterised by pain, stiffness and symmetrical synovitis (inflammation of the synovial membrane) of synovial (diarthrodial) joints
What is the pathogenesic of RA?
Synovial membrane is abnormal - so synovium becomes proliferated mass of tissue due to: Neovascularisation Lymphangiogenesis inflammatory cells: - Activated B and T cells - Plasma cells - Mast cells - Activated macrophages
Recruitment and activation of these cells is controlled by the cytokine network - excess of pro-inflammatory VS lack anti-inflammatory cytokines = ‘cytokine imbalance’
Leads to inflammation
What is the main / dominant cytokine in RA?
TNF-alpha = most dominant cytokine in RA
Shown this is dominant due to biologic medications that inhibit TNFa
Which have been proven to be very effective
= TNFa is a strong pro-inflammatory esp. in RA as it recruits other cytokines / interleukins
How does TNFa cause painful symptoms in RA?
When TNFa is recruited - it causes:
proinflammatory cytokine release, chemokine release, hepcidin induction, endothelial activation, leukocyte accumulation, angiogenes, chondrocyte activation, oesteoclast activation etc.
Leading to:
Synovitis –> joint inflammation and selling –> bone erosion –> joint space narrowing
What are the key features of RA seen clinically?
Chronic arthritis:
- Polyarthritis - swelling of the smeall joins fo the hands 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 - appear on the skin
- Others rare e.g. vasculitis, episcleritis (eyes)
Rheumatoid factor (RF) may be detected in blood - RF = autoantibody against IgG
What is a key investigation for RA?
Blood test = elevated CRP, high levels of RF
USS - look for swelling
X-ray - look for bone erosions
Whta is the pattern of joint involvement for RA?
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)
Where is the primary site of inflammation in RA?
Where else in RA can there be inflammation?
RA = synovial inflammation
so:
Primarily = synovium is inflammed e.g. in the proximal interphalageal joints (ITPJs)
But inflammation can also spread to:
Tenosynovium = surrounding tendons
Bursa (lubricated fluid-filled thin sac located between bone and surrounding soft tissue)
What are the common and uncommon extra-articular features of RA?
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 subcutaenous nodules? How do the subcutaneous nodules appear in RA?
Central area of fibrinoid necrosis surrounded by histiocytes and peripheral layer of connective tissue
Occur in 30% of patients but generally associated with severe disease, extra-auricular manifestations, and rheumatoid factor
What is a key investigation for RA?
2 types of antibodies are found in the blood of RA patients:
- Rheumatoid factor =
Immunoglobulin M (IgM) autoantibodies against the Fc fragment of immunoglobulin G (IgG) are called rheumatoid factors (RFs) i.e. IgM anti-IgG antibody
Positive in 70% of patient at disease onset, and further 10-15% over the first 2 years of diagnosis - Anti-cyclic citrullinated peptide antibody ‘anti-CCP antibody’ = antibodies against citrulinated peptides - highly specific for rheumatoid arthritis
What are citrulinated peptides mediated by?
An enzyme called peptidyl arginine deiminase (PAD) = works by converting arginine to citrulline
How is RA managed clinically? What is the treatment goal and what does this require?
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
Patient is then given drug treatment(s)
What are the drug treatments given for RA?
DMARDS = disease-modifying anti-rheumatic drugs = drugs that control the disease process
Glucocorticoid therapy e.g. prednisolone is avoided long term, so DMARDS are given instead as they can be used long term
1st line treatment = Methotrexate in combination with hydroxychloroquine or sulfasalazine
2nd line treatment = biologics e.g. new therapies include Janus Kinase inhibitors: Tofacitinib & Baricitinib
Multidisciplinary approach also important e.g. physiotherapy, occupational therapy, hydrotherapy, surgery
What are the different available / emerging biological therapies and when are they used?
Usually given to those with severe RA
Biological therapies offer potent and targeted treatment strategies
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 x-ray findings may be found in RA?
Affects MCPJs in hands (knuckles)
May see bony erosions if RA has progressed enough
Ulnar rotation / tilt of fingers
Some osteoporosis at the joints
What are the differences in the x-rays of RA VS OA?
RA = affects MCP joints more (knuckles), also loss of joint space but mainly knuckles, also see some osteoporosis of the joints and bony erosions (black areas on the bone)
OA = distal joints = almost no joint space
What other conditions can cause inflammatory arthritis other than rheumatoid causes?
Seronegative =
Reactive arthritis
Ankylosing spondylitis (AS)
Psoriatic arthritis
Seropositive =
SLE
What are the features of ankylosing spondilitis (AS)?
Seronegative = no positive autoantibodies
Anklylosis = spinal fusion
Characterised by chronic sacroillitis – inflammation of sacroiliac joints
Commonly found in males between 20-30 years
Associated with HLA B27
What is the clinical presentation of AS?
Lower back pain + stiffness
- Early morning
- Improves with exercise
Reduced spinal movements
Peripheral arthritis
Inflammation of other connective tissue e.g. plantar fasciitis, achilles tendonitis
Fatigue
Back pain >3 months, <45 years is suggestive of possible AS
What investigations are ordered for suspected AS?
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 for AS?
Phsyiotherapy = improvement with exercise
Pain medications = usually NSAIDS as they also reduce the inflammation
Exercise regimes
Peripheral joint disease = prescribe DMARDs
What is psoriatic arthritis and what are its features?
Psoriasis = autoimmune skin disease
Psoriasis presents clinically as scaly red plaques on extensor surfaces e.g. elbows and knees)
But 10% of these patients also have joint inflammation
Also seronegative - no positive autoantibodies
What is the clinical presentation of Psoriatic athritis?
Varied clinical presentations - classicially asymmetrical arthritis affecting the IPJs (interphalangeal joints)
But can also manifest as:
- Symmetrical involvement of small joints (rheumatoid pattern)
- Spinal and sacroiliac joint inflammation
- Oligoarthritis of large joints
- Arthritis mutilans
What are the investigations conducted for psoriatic arthritis?
Blood test = analyse to make sure it is not rheumatoid arthritis (RA) - check for autoantibodies; psoriatic arthritis = seronegative
X-ray of affected joints = pencil in cup abnormality
MRI of affected joints = sacrolitis and enthesitis
What are the management options for psoriatic arthritis?
Avoid oral steroids as skin psoriasis becomes worse with these
But long-term = DMARDs e.g. methotrexate
What is reactive arthritis? What are its features?
Sterile inflammation in joints following infection especially urogental (e.g. Chlamydia trachomatis) and/or GI gastrointestinal (e.g. Salmonella, Shigella, Campylobacter) infections
What are some extra-auricular manifestations of reactive arthritis?
Enthesitis (tendon inflammation)
Skin inflammation
Eye inflammation
What demographic does reactive arthritis affect? How may it present clinically?
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 VS septic arthritis?
Reactive arthritis is distinct from infection in joints (septic arthritis)
As reactive arthritis is STERILE and septic arthritis is NOT
What is SLE (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)
What clinical investigations are suitable for suspected SLE in patients?
Blood test for autoantibodies -
- 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.
What demographic is SLE found in?
F:M ratio 9:1
Presentation 15 - 40 yrs
Increased prevalence in African and Asian ancestry populations
Prevalence varies 4-280/100,000
What are some other connective tissue diseases?
Systemic Sclerosis
Myositis
Sjogrens syndrome
Mixed connective tissue disease
