Rheumatoid arthritis Flashcards
In what age range does RA most commonly develop?
25-50 years old
What is the difference in prevalence of RA in men and women?
RA is more common in women- the ratio of cases of men to women in 2-3:1
- around 1.5 men and 3.6 women developing RA per 10,000 people per year in the UK
What percentage of the UK population have RA?
1%
What are the causes of rheumatoid arthritis?
Is though to be multi-factorial, but causes aren’t exactly known:
- Genetic predisposition- 70% of patients express the human leukocyte antigen, HLA-DR4
- Other genes are also though to be involved including STAT4, TRAF1/C5 and PTPN22, MHC allele HLA-DRB1
- Environmental factors- occupational exposure e.g. oil or silicas, tobacco smoke, air pollution
- Smoking
- Autoimmunity, including antibodies such as anti-citrullinated peptide antibodies (ACPAs) and rheumatoid factors (RFs), is associated with RA
- Hormones- more common in women
- Infection- multiple viruses have been suggested to link to RA but haven’t been proven e.g. Epstein-Barr virus, streptococcus and parvovirus
What type of condition is rheumatoid arthritis?
A systemic autoimmune disease
What are the stages of rheumatoid arthritis?
- INITIATOR PHASE:
The initiating event is unknown and reason for joint specific localisation is unknown.
It could be due to injury, infection, exposure to toxic substances - The antigen-presenting cells and citrillination of proteins are now seen as non-self.
- INFLAMMATION PHASE:
Self-antigens are presented which causes an immune reaction; clonal expansion of t and b-cells = proliferate
There is insufficient control by T-regulatory cells, so t and b-cells are activated in the joint (we don’t want them to be activated here) = tissue damage. B-cells produce autoantibodies e.g. Rheumatoid factor (RF) and anti-citrullinated peptides- which can activate the complement system and also can bind to activated macrophages in the synovium= prolong inflammation indefinitely. T-cell can activate monocytes, macrophages and fibroblasts = production of cytokines e.g. TNF alpha, IL-6, IL-1= these induce MMP production= MMPs degrade cartilage. (ALL CONNECT TO DESTRUCTION PHASE BELOW??) - SELF-PERPETUATING PHASE:
The inflammatory damage in the synovial means that self-antigens previously ‘unseen’ by the immune system become exposed. This causes an immune response against cartilage and there is an infiltration of immune cells. This doesn’t go back to resolution - DESTRUCTION PHASE:
Cytokines such as TNF, IL-6 activate the synovial fibroblasts and osteoclasts (resorb/degrade bone). This leads to the bone and cartilage being destroyed. Also, the RANK ligand can promote osteoclasts to resorb the bone.
What are examples of the co-morbidities associated with RA, that can be caused due to circulating inflammatory mediators e.g. cytokines?
- TNF-𝛼 : Insulin resistance in muscle, free fatty acid, atherosclerosis of blood vessels that can leas to MI or stroke, low mineral bone density= fractures
- IL-6: Blood vessel, fat as above. + impacts on the acute-phase response in the liver and low stress tolerance in the brain= depression
What are the symptoms of RA?
Symptoms usually have an insidious onset (gradual):
- Pain, swelling, redness and stiffness most commonly of the small synovial joints of the hands, wrists, and feet
- Pain and stiffness is usually worse after rest/sleeping. Morning stiffness should last longer than 30 minutes- or could be a sign of osteoarthritis
- May also present with fever, malaise, weakness, weight loss, poor appetite
- May have RA nodules- subcutaneous lumps around the joints
- May also affect other areas of the body e.g. the eyes or chest
Discuss the general progress of RA symptoms over time?
- Often starts with the insidious onset of a fever, malaise or weakness and pain in the joints
- This then leads to inflammation in the synovial joints usually in the hands, wrists and feet. This presents as pain, tenderness, swelling, stiffness, redness or warmth
- Overtime, can cause progressive articular deterioration (loss of function):
Inflammation
Destruction of bone and cartilage
Deformity in joint
Limited motion/pain on motion
can also cause weight loss, Low mental health, fatigue at this stage.
Can then go on to affect other organs e.g. lungs (pulmonary fibrosis), Heart (cardiovascular disease), Eyes, skin and bone - In 20% of patients, they develop rheumatoid nodules- firm lumps that appear subcutaneously under the skin. often where the joints under the most trauma. The incidence of patients developing these is decreasing nowadays due to the development of RA treatments.
- Usually patients will have exacerbations and flare ups and then periods of remission. overtime, chronic progression and deterioration is likely.
What is the clinical course of RA?
Usually patients will have exacerbations and flare ups and then periods of remission
What are the possible co-morbidities of RA?
- Increased cardiovascular risk
- Increased infection risk
- Respiratory problems
- Osteoporosis
- Malignancy- cancers such as lung and lymphomas
- Depression
How is rheumatoid arthritis diagnosed?
NO ONE TEST PROVIDES A RA DIAGNOSIS
BLOOD TESTS-
Inflammatory markers:
- Erythrocyte sedimentation rate (ESR)- Alerts us on the degree of inflammation within the joints. The higher the rate, the more inflammation is present
- C-reactive protein (CRP)- A protein that is produced in the liver as part of the innate immune response.
(NOTE- both of these 2 can be increased due to other inflammation/surgery)
Immunological parameters:
- Rheumatoid factor (RF)- an autoantibody that is found in 70% of RA patients. But it is not specific enough for RA or essential for diagnosis
- Anti-nuclear antibody (ANA)- Autoantibody in 40% of RA patients
- Anti-cyclic citrullinated peptide (Anti-ccp)- Autoantibody against cytrilline
HAEMATOLOGY
RADIOLOGY: Looks at the damage and inflammation within the joints ( this is not always visable on x-rays)
EXAMINATION:
- LIMITED MOTION TEST- the patient finds it hard to form a tight fist
- METACARPOPHALANGEAL (hand) OR METATARSOPHALANGEAL (feet) SQUEEZE: Squeeze the knuckle joints. If the patient has RA, it would feel gel-like at the joints and would be very painful- undue pain.
What is the difference between the metocarpophalangeal squeeze and the metatarsophalangeal squeeze?
Metocarpophalangeal = squeezing the hands metatarsophalangeal = squeezing the feet
What are the inflammatory markers associated with RA?
- Erythrocyte sedimentation rate (ESR)- Alerts us on the degree of inflammation within the joints. The higher the rate, the more inflammation is present
- C-reactive protein (CRP)- A protein that is produced in the liver as part of the innate immune response.
(NOTE- both of these 2 can be increased due to other inflammation/surgery)
What are the immunological markers associated with RA?
- Rheumatoid factor (RF)- an autoantibody that is found in 70% of RA patients. But it is not specific enough for RA or essential for diagnosis
- Anti-nuclear antibody (ANA)- Autoantibody in 40% of RA patients
- Anti-cyclic citrullinated peptide (Anti-ccp)- Autoantibody against cytrilline
What does it mean if a RA patient is sero-positive?
if their blood tests are positive for autoantibodies- Rheumatoid factor and/or Anti-CCP
What guidelines are used in the management of rheumatoid arthritis?
NICE 2018- Rheumatoid arthritis in adults: management
+
EULAR- European league against rheumatism (2019)
When does a patient need to be referred from primary care to secondary care when presenting to a GP with RA symptoms?
If suspected synovitis (inflammation of synovial membrane)
Should be urgent if:
- Is affecting the small joints in the hand or feet
- if more than one joint is affected
- If the patient has waited more than 3 months before seeking medical attention
(even with a normal acute-phase response, negative anti-cyclic citrullinated peptide [CCP] antibodies or rheumatoid factor)
What is the diagnostic process should a patient have synovitis (swelling of the joints) on a clinical examination?
Do a blood test:
- look for rheumatoid factor
- If is negative for RF, test for anti-ccp antibodies
- x-ray the hands and feet
- health assessment questionnaire (HAQ)- looks at the patients functional ability, disability, pain, drug side effects and toxicity, costs etc
