R arthiritis Flashcards
what is Inflammatory arthritis
symptoms
Group of diseases characterised by inflammation of the joints and often other tissues. Include (but are not limited to):
RA, psoriatic arthritis, ankylosing spondylitis, juvenile idiopathic arthritis.
Symptoms: typically characterised by joint pain (and joint swelling) and joint stiffness in the morning and also after inactivity, lasting more than 30 min.
Synovial inflammation i.e. synovitis is a predominant feature
Note: non-joint structures can also be affected (e.g. skin, eyes, lungs, heart).
Patients also often have:
Normochromic and normocytic anaemia: reduced numbers of normal-sized erythrocytes (red blood cells) with normal haemoglobin content which is associated with chronic disease.
Raised inflammatory markers: erythrocyte sedimentation rate (ESR) and also C reactive protein (CRP).
what is rheumatoid arthritis (RA
RA is a chronic, disabling autoimmune disorder affecting 1% of UK population (0.5%-3% worldwide): 15% have severe disease.
Characterised by synovitis (synovial inflammation) of small and large joints, destruction of cartilage and bone.
Chronic symmetrical polyarthritis (unknown cause).
Pre-menopause, affects roughly 3x as many women as men (1:1 after menopause).
Can present at any age, but peak prevalence is seen between 40-60 years of age.
Gradual onset of symptoms most common; people usually present with joint pain and swelling:
Symptoms vary in severity and may ‘come and go’: periods of increased disease activity, i.e. flares, may alternate with periods of remission (i.e. when swelling and pain fade/disappear).
causes of RA
We understand what causes inflammation in RA, but what exactly causes RA itself is unknown.
Proposed mechanism is:
Generalised, non-specific inflammatory response, localised tissue damage and release of neo-autoantigens leading to T cell activation (initiating event).
B cells activated and produce autoantibodies (e.g. rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP)) which form immune complexes, bind to complement, stimulating neutrophils to produce pro-inflammatory cytokines (e.g. IL-1, TNF-alpha) and chemokines.
Chronic inflammation seen in RA is maintained by e.g. rheumatoid factor and by continuous stimulation of macrophages which release pro-inflammatory cytokines and chemokines.
RA is a multifactorial disease: both genetic (accounts for ~60%!) and environmental factors play an important role.
RA: pathology
RA is characterised by chronic synovitis (inflammation of synovial lining of joints, tendon sheaths or bursae): this is due to migration and retention of inflammatory cells at the site of inflammation.
In response to proinflammatory mediators, leukocytes and vascular cells are activated; T cells and other immune cells eventually extravasate from blood vessels into the synovium (the ‘inflammation zone’), where they are retained. New blood vessels formed.
Synovial hyperplasia, tissue grows out over cartilage surface, and forms a pannus.
Pannus destroys articular cartilage and subchondral bone, producing bony erosions.
Subcutaneous rheumatoid nodules may form
RA: clinical features
Insidious (gradual) onset of pain.
Early-morning stiffness (lasting more than 30 minutes).
Swelling in small joints of hands and feet (symmetrical).
Joint capsules are weakened leading to instability, subluxation (partial dislocation) and deformity.
Multiple joints may become involved:
Wrists, elbows, shoulders, cervical spine, knees, ankles, feet.
Joint effusions (increased fluid in tissue surrounding the joint) and muscle wasting.
RA: other manifestations
Non-articular features (tendons, ligaments, fascia):
Bursitis (inflammation/swelling of bursa).
Tenosynovitis (inflammation of the lining
of the tendon sheath around a tendon).
Extra-articular features (beyond joints):
Fever.
Fatigue.
Anaemia.
Nodules (present in <30% of cases).
Muscle wasting.
Sjögren’s syndrome (dry eyes and mouth due to destruction of epithelial exocrine glands; can also affect joints – autoimmune disease).
Carpal tunnel syndrome (median nerve compression: wrist).
People with RA have an increased risk of CVD (atherosclerosis), infection (commonly pulmonary) and osteoporosis.
RA: initial investigations
suspected
refer to specialist opinion - (rheumatologist)
investigations
info and support after diagnosis
management
Refer urgently (even if normal acute-phase response, negative anti-CCP antibodies or rheumatoid factor, RF) if:
Small joints of hands or feet are affected.
> one joint is affected.
Been a delay of > 3 months between onset of symptoms and seeking medical advice.
Investigations for diagnosis of RA:
Offer blood test for RF in adults with suspected RA: have synovitis on clinical examination.
Consider anti-cyclic citrullinated peptide (CCP) antibody measurement in adults with suspected RA, if negative for RF.
X-ray the hands and feet (early in disease course) in adults with suspected RA and persistent synovitis: look for reduced joint space, erosion, deformities.
RA: investigationsfollowing diagnosis
If anti-CCP antibodies present, or bone erosions are seen on X-ray emphasise the importance for individual to monitor their condition, and seek quick access to specialist care, if:
Disease worsens.
They have a flare (review slide 4).
what is treat-treat strategy
Disease activity scores (DAS): a measure used to assess response to treatment in RA: value is based on clinical assessment (e.g. number of swollen joints) and inflammation biomarkers (e.g. ESR, CRP). DAS28, remission: score of <2.6; low disease activity: score of ≤3.2.
Treat active RA in adults (or those at risk of developing RA) with the aim of achieving a target of remission, or low disease activity if remission is not achieved.
what is Disease activity Score 28 (DAS28)
Mathematical formula calculates score based on:
Number of swollen joints (out of the 28),
Number of tender joints (out of the 28),
C reactive protein (CRP) and/or erythrocyte sedimentation rate (ESR) test results
Patient health assessment questionnaire
Generally, a DAS28 score of:
DAS28 > 5.1 indicates high disease activity
DAS28 of 3.2 to 5.1 indicates moderate disease activity
DAS28 of 2.6 to <3.2 indicates low disease activity
DAS28 < 2.6 indicates disease remission
RA: non-pharmacologicalmanagement
Adults with RA should have access to:
Specialist physiotherapy:
Improve general fitness, encourage regular exercise.
Learn exercises to enhance joint flexibility, muscle strength.
Learn about short-term pain relief methods: transcutaneous electrical nerve stimulators (TENS) and wax baths.
Specialist Occupational therapy, if:
Have issues with everyday activities or hand function.
Hand exercise programmes (delivered by practitioner), if:
Not on a drug regimen.
Have been on stable RA drug regimen for >3 months.
Podiatrist, if have foot problems (discuss e.g. insoles).
Psychological interventions, i.e. stress management.
Pharmacological options
Pharmacological treatments available for RA, which include:
Analgesics: non-steroidal anti-inflammatory drugs (NSAIDs).
Glucocorticoids (corticosteroids): e.g. prednisolone.
Disease-modifying anti-rheumatic drugs (DMARDs):
‘Traditional’ conventional synthetic DMARDs (cDMARDs): methotrexate, sulfasalazine, leflunomide, gold salts, antimalarials (hydroxychloroquine), D-penicillamine, etc.
Biological DMARDs (bDMARDs): sarilumab, adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab, abatacept, etc.
Targeted synthetic DMARDs (tsDMARDs): tofacitinib (first Janus Kinase [JAK] inhibitor, ‘jakinibs’, approved for treatment of RA), fostamatinib, baricitinib, apremilast, etc.
RA: initial treatment
Adult with newly diagnosed RA
First line - cDMARD monotherapy: (oral) methotrexate, leflunomide or sulfasalazine (within 3 months of persistent symptom presentation (Consider hydroxychloroquine as 1st line as an alternative to these cDMARDs for mild or palindromic disease*)
Not effective, even after dose escalation
STEP up stratergy
Offer additional cDMARD (combination): (oral) methotrexate, leflunomide, sulfasalazine or hydroxychloroquine if target treatment not achieved
(Consider short-term bridging treatment with glucocorticoids (oral, intramuscular or intra-articular) when starting a new cDMARD.)
-> Step-down strategy: adults who have maintained treatment target for 1 year+ without glucocorticoids, consider cautiously reducing drug doses, or stopping drugs
Inadequate response to cDMARDs
Combine sarilumab (bDMARD) with methotrexate to treat active RA in adults if: (a) disease is severe (DAS28 >5.1), (b) company provides sarilumab with discount.
->
Consider sarilumab as monotherapy for people who cannot take methotrexate (contraindicated or intolerance)
or
DMARD naive - Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept (bDMARDs)
all in combination with methotrexate to treat active RA in adults if: (a) disease is severe (DAS28 >5.1), (b) disease not responded to intensive therapy with combination of cDMARDs, (c) companies provide.
->
Adalimumab, etanercept, certolizumab pegol or tocilizumab as monotherapy for people who cannot take methotrexate (contraindicated or intolerance)
Continue treatment only if there is a moderate response at 6 months after starting therapy.
MODERATE TO SEVERE RA:
Tofacitinib (tsDMARD) with methotrexate (or as monotherapy if methotrexate issues as above); same for baricitinib (tsDMARD).
If inadequate response or intolerance to bDMARDs, and
rituximab is suitable, then combine with methotrexate…
NSAIDs/COX-2 inhibitors
example
use
Relieve pain and stiffness (i.e. used only for symptom control); they do not slow RA disease progression (i.e. are not DMARDs).
NSAIDs should be used at the lowest dose and for the shortest time possible (e.g. ibuprofen 200-400mg tbs).
Gastric protection is recommended: proton pump inhibitors e.g. lansoprazole.
Pain relief is rapid (full effect obtained within 1 week) but anti-inflammatory effect of NSAID(s) may take up to 3 weeks.
Individual response to different NSAIDs varies considerably despite their similarity:
60% of patients will respond to any NSAID.
Those that do not respond to one NSAID will respond to another.
Slow-release preparation at night can help morning symptoms (stiffness).
corticosteroids
use
caution
Bridging treatment: glucocorticoids are used for a short period of time when a person is starting a new DMARD:
Intention is to improve symptoms while waiting for the new DMARD to take effect (as it can take 2-3 months).
Managing flares:
Offer short-term treatment in adults with recent or established disease to rapidly decrease inflammation.
Long-term use of glucocorticoids:
Only for those with established RA when long-term complications have been discussed, and when all other treatment options have been offered.
Concerns over long-term safety: infections, diabetes, osteoporosis, gastrointestinal and cardiovascular events.
