Rheumatoid arthritis Flashcards
What are some of the symptoms a patient may initially experience before joint inflammation occurs?
Fever
Malaise
Weakness
Arthralgia
Which joints are most commonly affected by RA?
Joints of the hand, feet, knee and hip
How many people in the UK are affected by RA?
600,000 people and prevalence is said to be roughly 0.5-1%
At what age do people tend to develop RA?
Between 25-50 years
Define Rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease.
What is the key characterisation of RA?
Proliferative synovitis and inflammatory arthritis with erosions
What is the ratio of women to men that have RA?
2-3:1
Due to possible effect of the female hormones (oestrogen) as in addition use of the contraceptive pill shows higher proportion of RA sufferers.
Explain the role of genetics in RA predisposition?
It is believed that RA is multifactorial meaning that there is not one singular cause but is a combination of genetics, environmental and immunological factors but having said that there is a genetic predisposition.
What are some of the genes involved in RA?
70% of RA sufferers have HLA-DR4 present
STAT-4
TRAF1/C5
PTPN22
Describe some of the environmental factors that perhaps link to RA?
Tobacco smoke
Air pollution
Mineral oil
Silica
Infectious agents
Describe some of the immunological factors involved in the pathogenesis of RA?
RF
Anti-citrullinated cyclic peptide
Immune dysregulation
Antibody responses to modified peptides
Increased production of cytokines and chemokines
What is the concordance rate of twins with RA?
15-20% (15% in monozygotic twins)
Which allele is associated with an increased risk of RA?
MHC allele HLA-DRB1 increased risk of 4-12 times
What are some of the potential infections said to be associated with the onset of RA?
Mycobacterium
Mycoplasma
Streptococcus
Epstein Barr virus
Parvovirus
All suggested, nothing confirmed
What are the role of B cells in RA pathophysiology?
Produce auto-antibodies which cause complement activation
Bind to activated macrophages which they perpetuate inflammation
What are the roles of auto-antibodies in RA pathophysiology ?
Rheumatoid factor is directed against Fc factor fragment of IgG
Anti-citrullinated peptides are directed against antigens in the joint
What are the roles of T cells in RA pathophysiology?
They activate monocytes or macrophages and synovial fibroblasts by producing TNF-alpha, IL-1B or IL-6 which results in the production of MMPs which lead to the degradation of cartilage
Joint destruction might be caused by CD4 (+) T cell cytokines.
What is the function of the RANK ligand?
Promotes osteoclasts
Briefly outline the pathogenesis of RA.
There is normally an initiator event such as injury, infection and illness however then there is persistent inflammation where APCs are recruited and there is citrullination of proteins and it is perceived as a non-self immune response. Tis leads to a clonal expansion of B and T cells uncontrolled by T regulatory.
There is now inflammatory damage in the synovium, self antigens that were previously unseen now become exposed and the immune system attacks the cartilage, there is an infiltration of immune cells.
Fibroblasts and osteoclasts become activated by pro-inflammatory cytokines TNF and IL-6 resulting in the destruction of the bone.
State the co-morbidities of RA associated with systemic pro-inflammatory cytokines.
Iron redistribution in the liver
Free fatty acid deposition
Insulin resistance in the muscle
Lone bone mineral density - osteoporosis
Low stress tolerance, depression
Atherogenesis, MI, stroke
Which cytokines are associated with iron redistribution in the liver?
IL-6
Which cytokines are associated with free fatty acid deposition?
TNF-a and IL-6
Which cytokines are associated with insulin resistance in the muscle?
TNF-a and IL-1
Which cytokines are associated with low mineral bone density?
TNF-a, IL-6, IL-1
Which cytokines are associated with low stress tolerance and depression?
TNF-a, IL-6, IL-1
Which cytokines are associated with cardiac related complications MI, stroke etc?
Complement immune activation
IL-6 and TNF-a
When should an urgent referral be made from primary care with suspected synovitis?
Small joints of the hands or feet are affected
More than one joint is affected
There has been a delay of 3 months or longer between onset of symptoms and seeking medical advice
These symptoms should still be referred even if the patient is negative Rheumatoid Factor or Negative anti-cyclic citrullinated peptide [CCP] antibodies
Aside from the referral criteria which other symptoms would you expect from somebody with suspected Rheumatoid Arthritis?
Symmetrical in inflammation
Pain, tenderness, swelling, stiffness of the joint
Stiffness of the joint lasts from approximately 30 minutes after getting up in the morning
Joint redness and warmth
Symptoms tend to be in the small synovial lined joints of the hands, wrist or feet
The pain is becoming more persistent but were insidious in first presentation
What is important to consider about the symptoms regarding the duration of the inflammation of the joints?
Rheumatoid arthritis is a chronic, auto-immune condition therefore if somebody has waited for symptoms to resolve before getting them investigated, may present with symptoms indicating more severe joint deterioration (2 hours of morning joint stiffness).
Aside from symptoms directly relating to the joint inflammation, what other more generalised symptoms may a patient experience?
Weight loss
Fatigue
Changes in mental health
If Rheumatoid arthritis is left untreated what will eventually happen to the joint?
Results in progressive articular deterioration which means there will be a loss of function of the joint / bone / cartilage
Symptomatic presentation is deformity, limited motion and pain on motion and the fusion / dislocation of joints
What is also a characteristic appearance of Rheumatoid arthritis?
20% of patients who suffer with Rheumatoid arthritis will also have RA nodules. RA nodules are firm, noticeable lumps that form underneath the skin of some rheumatoid arthritis patients. They generally form on or near the base of the arthritic joints.
What symptoms could make a clear distinction between Osteoarthritis and Rheumatoid Arthritis?
Rheumatoid arthritis is an systemic auto-immune disease whereas Osteoarthritis can be seen as ‘wear and tear’ of the joint. Therefore the systemic symptoms associated with RA such as weight loss, fatigue and fever would not be associated with osteoarthritis.
What is some of the extra-articular manifestations that can occur with Rheumatoid Arthritis?
It can affect:
Lungs - patients are at risk of pulmonary fibrosis, interstitial lung disease
Heart - cardiovascular disease, increased risk of myocardial infarction, congestive cardiac failure, stroke
Eyes - Sjögren’s syndrome (very dry eyes)
Skin
Bone - increased risk of osteoporosis
How does the presentation of symptoms relate to the progression of the disease?
A patient with Rheumatoid Arthritis would experience fluctuations in their symptoms, known as flares and periods of apparent remission.
As the disease progresses the flares become more frequent and more severe, with each flare not recovering as well as the last
Describe what happens during chronic intermittence during the disease progression.
Chronic intermittence are periods of disease improvement.
What is responsible for a 1/3 of deaths in patients with RA?
Cardiovascular related illnesses
Outline how Rheumatoid arthritis links to Cardiovascular disease regarding the pathophysiology.
RA has widespread systemic inflammation so this can lead to vascularitis (inflammation of the blood vessels) resulting in changes to the vessel function.
RA also impacts cholesterol and blood clotting.
What is responsible for a 10% of deaths in patients with RA?
Respiratory disease and complications
Aside from the five previously mentioned which other more generalised extra-articular manifestations are there associate with RA?
Increased infection risk
Increased risk of depression
Increased risk of malignancies
Which malignancies are shown to be of an increased risk and which are shown to be associated with a decreased risk of RA?
Those with RA have be shown to have an increased risk of lung and lymphoma
But are shown to have a decreased risk of breast and bowel cancer
When is important to consider regarding extra-articular manifestations and drug therapy for RA?
-Use of DMARDs and biological therapies are good for reversing or at least halting disease progression, they themselves come with the potential of adverse events many of which can play into the extra-articular risks. For example biologics can increase risk of non-melanoma skin cancer
- Therefore there is a strong balance between controlling the disease, the co-morbidities associated with the disease and the risk of adverse effects
-Patient outcomes are compromised when treatment is delayed, progression of the disease, increased risk of extra-articular manifestations
-Supply of appropriate treatments can alter the duration of the disease
According to NICE what investigations should you to make for diagnosis if a patient has presented with symptoms that align with that of Rheumatoid Arthritis.
Found to have synovitis on clinical examination
Taking a blood test for:
Rheumatoid factor
Anti-cyclic citrullinated peptide (If RF negative)
X-ray the hands and feet in adults with suspected RA and persistent synovitis.
What is Rf and what is the significance of it?
Rf which stands for Rheumatoid Factor, is an auto-antibody found in around 70% of patients with RA.
It is a poor prognostic factors and usually indicates severe disease.
What is a limitation of using Rf?
Other inflammatory conditions will increase the Rf value and hence is not diagnostic as a singular marker.