Week 2 Flashcards
RA - aetiology, and how is it mediated?
- Can affect both sexes, but women are 3 times as commonly affected
- Can affect any age group
- Cause is unknown
- Potential triggers could include infections, stress and cigarette smoking
- HLA-DR4 mediated
Main structure affected in RA is the synovium. Name some synovium-lined joints
- C1/C2 joint in the spine
- Hands
- Wrists
- Elbows
- Shoulders
- TMJs
- Knees
- Hips
- Ankles
Importantly, which joints are spared in RA?
DIP joints are not affected by RA due to low amounts of synovial fluid.
This is an important diagnostic distinction from other forms of arthritis.
Tendon sheaths can also become inflamed (appears as something similar to a large ganglion cyst)
Generally speaking, what is the difference between RA and OA regarding pathological mechanism?
RA - inflammation/swelling of synovial membrane
OA - loss of/thinning of cartilage, leading to bone-on-bone abrasion and “creaking”
What does “pannus” mean? When is it present?
Pannus is the term for spongy inflammation felt at a joint in RA. Release of inflammatory cytokines by e.g. macrophages, dendritic cells, B and T cells etc. cause damage to the joint, and this must be treated relatively quickly in order to prevent permanent damage.
Osteoclasts are also present, and ‘eat up’ bone.
Pannus is seen in RA but not seen in OA
What pro-inflammatory cytokines are released by macrophages in RA?
Name some medications that target each of these.
What medications can be used to target B cells producing antibody and to blockade T cell co-stimulation?
- TNF-alpha
- infliximab, etanercept, adalimumab, certolizumab, golimumab
- IL-1
- anakinra
- IL-6
- tocilizumab
Rituximab can be used to target B cells, and abatacept can be used to prevent T cell co-stimulation
What is the name of the new classification system for RA, and what categories does it contain?
ACR/EULAR classification criteria for RA (2010)
- Joint distribution
- Serology
- Symptom duration
- Acute phase reactants
Greater than or equal to 6 score = RA
What investigations could be performed if RA is suspected?
History and clinical examination - forms the bulk of the diagnosis
- Pain?
- Stiffness? (early in the morning? Lasting longer than 30 mins?)
- Swelling?
- Symmetrical? DIP joints spared?
Blood tests - anaemia due to chronic disease? Raised plateletes?
Inflammatory markers present? (CRP, ESR/plasma viscosity)
Screen for autoantibodies - may be present, but absence does not mean disease isn’t present
Imaging - changes can only be seen after damage has occurred
What quick physical test can be performed if RA is suspected?
Squeeze test of hands/feet - areas will be very sensitive in patients with RA
What are some of the clinical presentations that could be seen with RA?
- PIPs, MCPs, wrist inflammation
- Monoarthritis, progressing to polyarthritis
- Tenosynovitis, inflammation in the fluid surrounding tendon sheaths
- Trigger finger
- Carpal tunnel syndrome, compression of nerve
- Polymyalgia rheumatica, pain/weakness/stiffness in shoulders
- Palindromic rheumatism
- Systemic symptoms
- Poor grip strength
What auto-antibodies can be tested for in RA?
Rheumatoid factor (rheumatoid IgM) - somewhat old-fashioned
- sensitivity 50-80%
- specificity 70-80% - not confirmatory!
Cyclic citrullinated peptide antibodies (anti-CCP antibodies)
- sensitivity 60-70%
- Specificity 90-99% - almost certain!
- can be present for several years prior to symptoms
- co-related with disease activity
- also associated with a previous or current smoking history
- patients will remain anti-CCP-positive despite treatment
In terms of imaging, what is the gold standard for RA patients?
MRI - bone marrow oedema on MRI is associated with inflammatory joint disease and be a forerunner of erosion
Also allows assessment of tendon intergrity, can be used to monitor disease activity and allows for earlier detection of erosions.
Cost is prohibitive
What system is used to assess disease activity in RA patients?
DAS28 scoring - 28 separate areas on the body
- Objective, patient’s response to treatment can be measured
- Score cut offs
- >5.1 = active disease
- 3.2 - 5.1 = moderate disease
- 2.6 - 3.2 = low disease activity
- <2.6 = disease is in remission
RA - management
- Aim for early recognition and diagnosis to prevent permanent changes
- Involve care with a rheumatologist and a multi-disciplinary team
- Early use of DMARDs in all patients (disease-modifiying anti-rheumatic drugs)
- Use of NSAIDs and steroids only as adjuncts
- patients may be started on a combo therapy of DMARD and steroid, and gradually weaned off the latter - important not to suddenly stop treatment!
- Patient education
DMARDs - examples and order of treatment
-
Methotrexate (1st line) start at 15mg a week with rapid escalation. Max dose is 25mg a week (systemic toxicity can develop), then add in the following order…
- Sulfasalazine
- Hydroxychloroquine - doesn’t prevent erosions!
- Leflunomide
- Gold injections, penicillamine, azathioprine - hardly ever used now
What important side effect should patients be aware of with use of methotrexate?
Methotrexate use has a risk of pneumonitis, so if patients experience SoB/dry cough etc. they need to notify their GP immediately and look at alternative medications
Methotrexate is also teratogenic, so advise effective contraception
Provide some examples of biologics.
What important side effect should be kept in mind?
- anti-TNF-alpha agents - Infliximab, Etanercept, Adalimumab, Certolizumab, Golimumab
- T cell receptor blockers - Abatacept
- B cell depletor - Rituximab
- IL-6 blocker - Tocilizumab
Use of these leaves the patient at increased risk of infection. If the patient has a latent TB infection present in the lungs as granulomas, these could break down and lead to a development of active infection.
Biologics are expensive! What are the guidelines for use of biologics in the UK?
What is always co-prescribed?
Failure to respond to 2 DMARDs including methotrexate and DAS28 greater than 5.1 on two occasions 4 weeks apart.
Methotrexate is also always co-prescribed when giving biologics
What is the primary target of treatment in RA?
Remission
This is defined as the absence of signs and symptoms of significant inflammatory arthropathy.
What are some of the complications of untreated RA?
- Joint damage and deformities - swan necking of the fingers
- Boutonniere deformity of the thumb (loss of space between thumb and palm)
- Subluxation and loss of fat pad at the soles of the feet, feels like walking on pebbles/marbles
- Atlanto-axial subluxation - odontoid process is eroded away leading to spinal cord compression
Osteoarthritis - general description of pathophysiology
Progressive degenerative condition affecting the joints due to a gradual thinning of the cartilage, loss of joint space and the formation of bony spurs (osteophytes)
What is cartilage mostly made up of? How is this affected in osteoarthritis?
Cartliage is mostly made up of Type II collagen, and the matrix is formed by the chondrocytes which are embedded within it.
In disease…
- loss of matrix
- release of inflammatory cytokines by the chondrocytes - IL-1, TNF alpha, metalloproteinases, prostaglandins
- fibrillation of the cartilage surface and attempted repair with osteophyte formation
Osteoarthritis - symptoms
- gradual onset, taking months to years
- mechanical pain i.e. worse on activity and at the end of the day, relieved by rest
- Crepitus - grinding/creaking of the joints
- Stiffness for less than 30 minutes
- Bony swellings and joint deformities
- can result in effusions and soft tissue swelling
Osteoarthritis - commonly affected areas
- Neck
- Lower back
- Hips
- Base of thumbs
- Ends of fingers - DIPs, PIPs and 1st CMC joints, not red, hot or “spongy” as in RA
- Knees
- Base of big toe
What are bony enlargements called when they are…
- seen at DIPs
seen at PIPs?
- DIPs - Heberden’s nodes
- PIPs - Bouchard’s nodes
What is the pathogenesis of gout? What part of this pathway does Allopurinol/Febuxostat affect?
From our diet we get purines, which are broken down into hypoxanthine, then into xanthine, and finally into plasma urate which is excreted by the kidneys
Purine formation is also caused by any breakdown of cells in our body e.g. crash diets, chemotherapy, trauma etc.
Allopurinol is a xanthine oxidase-inhibitor and prevents the conversion of hypoxanthine to xanthine, thus reducing blood uric acid levels.
