Rheumatoid Arthritis (DONE)` Flashcards
How does a normal joint work?
The ends of your bones are covered with cartilage, allowing them to move against each other almost without friction.
The joint is surrounded by the synovium, which produces synovial fluid that nourishes the cartilage and lubricates the joint.
The synovium has a tough outer layer called the capsule that holds your joint in place.
Tendons anchor the muscles to the bones.
How does a joint affected by rheumatoid arthritis work?
Causes inflammation in the synovium
Joint pain due to nerve endings irritated by inflammatory markers and the capsule stretched by the swelling in the joint
Joint damage is caused every time the joint is inflamed, and the joint can be worn away after repeated flare ups
Joints affected by rheumatoid arthritis
Shoulders Wrists Knuckles and middle joints of fingers Knees Ankles Middle joints of toes Balls of feet
Epidemiology
Affects 0.5-1% of world population Affects 1% of UK population More common in women Can occur at any age, peak at 65-74 years Reduces life expectancy
Aetiology
Exact cause is not known
Autoimmune disease
It may run in some families (HLA-DRV1 gene) but genetic factors alone do not cause it
More common in people who smoke, eat a lot of red meat or drink a lot of coffee
Less common in people who have a high vitamin C intake or drink alcohol in moderation
Symptoms
Joint pain and swelling Stiffness Tiredness, depression, irritability Anaemia Flu-like symptoms, such as feeling generally ill, feeling hot and sweating
Joint involvement
Pain worse in the morning Inflammation, swelling and tenderness Usually symmetrical Most common in hands, wrists and feet Can progress to muscle wasting, joint deformity and joint erosion Measure joint involvement with DAS-28
Joint deformity
Ulnar deviation of fingers
Z deformity of thumb
Swan neck
Boutonniere deformity
Systemic involvement
Non-specific: tiredness, depression, fever
Dermatological: nodules, palmar erythema
Circulatory: Raynaud’s syndrome, vasculitis, anaemia, CV disease
Ophthalmic: decreased production of tears. dry eyes, red eyes
Neurological: trapped nerves, peripheral neuropathy
Pulmonary: lung nodules, pleurisy, pulmonary fibrosis
Diagnosis
There is no single test for rheumatoid arthritis
Physical exam: look at joints for signs of swelling or tenderness
Symptoms and past health
Blood tests, x-rays, and other tests to find out if another problem is causing the joint pain
Aims of treatment
Relieve pain and inflammation
Prevent joint destruction or deformity
Preserve or improve function
Maintain patient’s normal lifestyle
Treatment of RA
Treatment continues throughout life
Includes medicine, exercise and lifestyle changes
Getting treatment early may control the condition or keep it from getting worse
Many of the medicines involved have side effects, so it is important to have regular check ups
Drugs
NSAIDs Disease modifying anti-rheumatic drugs (DMARDs) Biologic therapies Glucocorticoids Analgesics
How do NSAIDs work?
Inhibit the activity of COX-1 and COX-2, stopping the synthesis of prostaglandins and thromboxanes
Prostaglandins are messenger molecules that promote inflammation
Not effective in reducing joint damage
Often taken in combination
Short term use
Non-selective vs selective NSAIDs
Non-selective: ibuprofen, naproxen
COX-2 selective: celecoxib, etoricoxib
NSAIDs side effects
GI irritation in 60%, ulcers in 14-31%
Use lowest dose possible, take with food, use protective agents, selective COX-2 inhibitor in limited patients
Use with caution in patients with renal impairment or asthma
All thought to increase risk of vascular events such as MI and stroke
DMARDs
Can often slow or stop the progression of RA
Reduction of pain, swelling and stiffness
Slow acting
Slows down the disease and its effects on joints
Because DMARDs target the immune system, they can also weaken the immune system’s ability to fight infections
Examples of DMARDs
Methotrexate Sulfasalazine Leflunomide Gold compounds Penicillamine Hydroxychloroquine Methotrexate and sulfasalazine is a common combination
Methotrexate
Most effective DMARD
Inhibits activation of T lymphocytes
Onset of action in 4-6 weeks
Dose: 7.5-25mg once weekly
Side effects of methotrexate
Nausea, diarrhoea Oral ulceration Mild alopecia Pneumonitis (cough, SOB) Bone marrow suppression Hepatic fibrosis, cirrhosis Teratogenic Oliogspermia Some side effects reduced by taking folic acid
Biologics
A medicinal product made by or derived from a biological source e.g. an animal cell or microorganism
Often protein and/or antibody based
Examples of biologics
TNF inhibitors- adalimumab, certolizumab pegol, etanercept, golimumab and infliximab
Interleukin inhibitors- anakinra, tocilizumab
T-cell activation inihbitors- abatacept
B-cell depletion- rituximab
TNF and IL6
TNF-a and IL6 are key mediators of cell migration and inflammation in RA
IL-6, in particular, acts directly on neutrophils through membrane bound IL-6R
Activated neutrophils contribute to inflammation and joint destruction by secreting proteolytic enzymes
Use of biologics
Use in accordance with guidelines
Assess patients carefully before starting, rule out TN
Patient education, especially regarding side effects- immunosuppression
Stop during active infection or before surgery
Supply via home healthcare providers
Glucocorticoids
Strong anti-inflammatory drugs that can also block other immune responses
Suppress cytokines
Achieve rapid improvement
Severe long term side effects: osteoporosis, diabetes, suppression of adrenal secretions
Short term use only- until a DMARD becomes effective or during a flare
Drug treatment schedule
Start two DMARD regime once diagnosed, using titration regimens
Use anti-inflammatories, paracetamol, corticosteroids until effective
Review after 6 months, increase dose or switch as clinical condition determines
