Auto immune lecture 7-21 Flashcards
what is meant by articular inflammatory Auto immune disease
is an auto immune disease
for RA, SpA and other
what is meant by Degenerative
A person will have both degenerative and inflammatory disease where they cross each other
- Degenerative is more known as a wear and tear type of disease. Abnormal weight bearing can cause degenerative disease and affect large joints.
what is non articular generalise Auto immune disease
- Non articular is non-joint which can be classified as generalised and local
affects all over the body
what is meant by non-articular local
- Non articular is non-joint which can be classified as generalised and local
what is the prognosis of RA
- 1% of population
- F:M 3:1
- Bimodal
- Younger onset 30 – 50’s more aggressive form that it can cause more problems. See this now in this age range due to more testing being available.
- Older onset >60 years (different presentation)
- Often symmetrical Involvement- if one joint is affected then usually the other joint is affected on the other side.
- Small (hands & feet) joint always + large joints
- Historical Features
- EMS > 30 min, pain with activity (to a point). “Gel phenomenon”- their joints feels glued
- Soft tissue swelling around the joints
what is meant by serology
- Serology is the antibodies that is forming in the body. Can have seronegative antibodies and still have arthritis but wouldn’t be classified as RA
what is meant by acute phase reactants
- Acute phase reactants which are indicators of inflammation. As you have a raised cute phase you will get extra points
- If you get a score of 6 or above you have RA and would have to start treatment to get the patient into remission
what is the ACR/EULAR classifiaction system of RA
if you get over 6 point then likely diagnosis of RA from joint distribution serology symptom duration acute phase reactants
- If you get a score of 6 or above you have RA and would have to start treatment to get the patient into remission
- If they have a high score on presentation there is a risk that they will have tissue damage leading to joint damage so need to stop it as quickly as possible
- Small joints are weighted higher than large joints.
how does RA progress
- Rheumatoid arthritis usually has a slow, insidious onset over weeks to months-general pattern
- About 15-20% of individuals have a more rapid onset that develops over days to weeks
- About 8-15% have acute onset of symptoms that develop over days. Subclinical markers. Only when the switch is on then you get these symptoms and this is when they get joint damage.
what are RA non joint features
- Nodules- growth of abnormal tissue doesn’t harm you but looks nasty. They grow again and can get scar tissue. Can cause the joints to stop functioning. This is why surgeons don’t remove them . Can add steroid to help them to shrink.
- Sicca- dry eye syndrome. May need to be co-prescribed lubricating eye drops
- Eyes
- Vasculitis- where the blood vessel gets inflamed and there will be a plaque inside of them leading to a clot.
- There is 10x of cardiovascular risk because the walls of their tissue is inflamed so there is a risk of heart attack.
- Others (uncommon)
what are some of the causes of RA
- Genetic and environmental- leukocyte antigen plays a role in determining the severity of the disease.
- Complex and poorly understood
- HLA determines severity and involves different gene systems
- Trigger could be injury/virus/infection
what can occur to people if RA is not treated
§ Disability- joint destruction can leave you impaired
§ Damage
§ Deformity
§ Death
how can joint erosion occur in RA?
- Erosion of the interphalangeal which can happen in 2-3 years if there is no treatment.
- A hole has been developed and will be very painful as they will be swollen
what are some of the treatments of RA?
- NSAIDS . don’t use aspirin as it causes GI problems. Use naproxen because it has anti-platelet activity so it lowers cardiovascular disease. They also need to be on PPIs
- Steroids- don’t want to overuse them
- Conventional synthetic disease modifying antirheumatic drugs (csDMARDs) such as methotrexate, hydroxyquinone. Co -prescribe PPIs as it protects the stomach.
- Targeted synthetic disease modifying antirheumatic drugs (tsDMARDs) such as gene kinase inhibitors
- Biologic disease modifying antirheumatic drugs (bDMARDs)
what are some of the surgical procedures for RA
- arthroplasty
- Reconstruction/fusion
- high risk procedure
- questionable outcomes
- removal of inflamed synovium
Really hard to do surgery to replace the joints as they are small and they don’t really function as well. Poor outcome. Although it removes the pain the functional outcome is not good.
what are some other inflammatory RA
- Uncommon
- Significant impact
- Arthritis (only in some)
- Examples include
- Systemic lupus erythematosus
- Scleroderma (hardening of skin)
- Myositis (inflammation of muscles)
- Vasculitis (inflammation of blood vessel walls)
what is lupus
- Systemic lupus erythematosus is an autoimmune disease of the body’s connective tissues.
- There is an accumulation of immunoglobulin that join together and are very big which can get stuck anywhere where there’s blood perfusion and can clot. This can cause an inflammatory episode and damage the surrounding tissue.
- SLE affects tissues throughout the body. Five times as many women as men get SLE.
- Most people develop the disease between the ages of 15 and 40, although it can show at any age.
describe the anatomy of how lupus is formed
- SLE causes tissue inflammation and blood vessel problems pretty much anywhere in the body.
- Note the granular appearance of the cortex of these lupus affected kidneys – it’s across the entire surface of both kidneys suggesting a chronic condition. The kidney is scarred due to all the inflammation on the surface and that’s because the kidneys have a big volume of blood that goes through it.
- In some cases, the kidney may need to be replaced because it is damaged by the lupus.
describe the inflammation of SLE seen in lupus
- The inflammation of SLE can be seen in the lining, covering, and muscles of the heart. The heart can be affected even if you are not feeling any heart symptoms. The most common problem is bumps and swelling of the endocardium,
- SLE also causes inflammation and breakdown in the skin. Rashes can appear anywhere, but the most common spot is across the cheeks and nose.
- People with SLE are very sensitive to sunlight. Being in the sun for even a short time can cause a painful rash. Some people with SLE can even get a rash from fluorescent lights.
- Rashes caused by SLE are red, itchy, and painful. The most typical SLE rash is called the butterfly rash, which appears on the face – particularly the cheeks and across the nose. SLE can also causes hair loss. The hair usually grows back once the disease is under control.
how does lupus affects the joints
• Almost everyone with SLE has joint pain or inflammation. Any joint can be affected, but the most common spots are the hands, wrists, and knees. Usually the same joints on both sides of the body are affected. The pain can come and go, or it can be long lasting. The soft tissues around the joints are often swollen, but there is usually no excess fluid in the joint. Many SLE patients describe muscle pain and weakness, and the muscle tissue can swell.
what else can lupus affect
- Lupus can also affect the nervous system causing headaches, seizures, and organic brain syndrome.
- It can cause anemia due to blood loss or from the kidney disease (it does not directly affect the red blood cells).
- Pregnancy: the chances of miscarriage, premature birth, and death of the baby in the uterus are high.
what is Spondyloarthropathies (SpA)
- Consist of a group of related disorders that include Reiter’s syndrome, ankylosing spondylitis, psoriatic arthritis, and arthritis in association with inflammatory bowel disease
- Occurs more age at diagnosis in the third decade and a peak commonly among young men, with a mean incidence between ages 25 and 34
- The prevalence appears to be about 1%
- The male-to-female ratio approaches 4 to 1 among adult Caucasians
- Genetic factors play an important role in the susceptibility to each disease
what is the cause of SpA
- The cause is unclear, but there is strong evidence that the initial event involved interaction between genetic factors and environment factors, particularly bacterial infections
- Reiter’s syndrome may follow a wide range of GI infections
- Bowel inflammation has been implicated in the pathogenesis of endemic Reiter’s syndrome, psoriatic arthritis, and ankylosing spondylitis
what common things does SpA share with RA
- The spondyloarthropathies share certain common features, including the absence of serum rheumatoid factor, an oligoarthritis commonly involving large joints in the lower extremities, frequent involvement of the axial skeleton, familial clustering, and linkage to HLA-B27
- These disorders are characterised by inflammation at sites of attachment of ligament, tendon, fascia, or joint capsule to bone (enthesopathy)
Sacroiliitis a type of SpA
- Sacroiliitis is an inflammation of the sacroiliac joint (hip area)
- Picture on the bottom right shows an individual with – sacroiliitis and Ankylosing Spondylitis. The arrows point to the inflamed and narrowed SI joints. They are white due to bony sclerosis around the joints. The joints fuse together and all the ligaments can become inflamed that connect the joints together to make it stable.
Ankylosing Spondylitis
- Chronic disease that primarily affects the spine and may lead to stiffness of the back. The joints and ligaments that normally permit the back to move become inflamed. The joints and bones may grow (fuse) together.
- The effects are inflammation and chronic pain and stiffness in the lower back that usually starts where the lower spine is joined to the pelvis or hip.
- Diagnosis is made through: (a) medical history including symptoms, (b) X-rays, and possibly (c) blood tests for HLA-B27 gene
what is the treatment option for Ankylosing Spondylitis
• Treatment options:
– With early diagnosis and treatment, pain and stiffness can be controlled and may reduce fusing. In women, AS is usually mild and hard to diagnose.
– Exercise
– Medications: NSAIDs (phenylbutazone-rarely used because causes a lot of blood problems also pyrazoline also aspirin), sulfasalazine (dMARD)
– Posture management
– Self-help aids
– Surgery- to straighten the back
what is Reiter’s Syndrome
- Arthritis that produces pain, swelling, redness and heat in the joints. It can affect the spine and commonly involves the joints of the spine and sacroiliac joints. It can also affect many other parts of the body such as arms and legs. Main characteristic features are inflammation of the joints, urinary tract, eyes, and ulceration of skin and mouth.
- The symptoms are fever, weight loss, skin rash, inflammation, sores, and pain.
- They will be seronegative you wouldn’t find any antibodies. Will look like they have RA, but don’t fit the criteria because they’re seronegative and don’t fit the criteria because they are young
how does Reiters syndrome progress
- Reiter’s often begins following inflammation of the intestinal or urinary tract. It sets off a disease process involving the joints, eyes slightly inflamed , urinary tract, and skin. Many people have periodic attacks that last from three to six months. Some people have repeated attacks, which are usually followed by symptom-free periods.
- Diagnosis is made through a physical exam, skin lesions, and a test for the HLA-B27 gene
what part of the body does Reiters syndrome affect
• For different parts of the body, different treatments are used:
– Medications: NSAIDs, antibiotics, topical skin medications
– Eye drops
– Joint protection
what is Psoriatic Arthritis
• Causes pain and swelling in some joints and scaly skin patches on some areas of the body.
• The symptoms are:
– About 95% of those with psoriatic arthritis have swelling in joints outside the spine, and more than 80% of people with psoriatic arthritis have nail lesions. The course of psoriatic arthritis varies, with most doing reasonably well. Will be a seronegative so they don’t have antibodies testing for rheumatoid factor. Slower development of process
– Silver or grey scaly spots on the scalp, elbows, knees and/or lower end of the spine.
– Pitting of fingernails/toenails
– Pain and swelling in one or more joints
– Swelling of fingers/toes that gives them a “sausage” appearance.
how do you diagnose Psoriatic Arthritis
• Diagnosis may involve X-rays, blood tests, and joint fluid tests. • Treatment options: – Skin care – Light treatment (UVB or PUVA) – Corrective cosmetics – Medications: glucocorticoids, NSAIDs, DMARDs – Exercise – Rest – Heat and cold – Splints – Surgery (rarely)
what is meant by inflammatory bowel disease
• IBD consists of two separate diseases that cause inflammation of the bowel and can cause arthritis or inflammation in joints:
– Crohn’s Disease involves inflammation of the colon or small intestines.
– Ulcerative Colitis is characterized by ulcers and inflammation of the lining of the colon.
• The amount of the bowel disease usually influences the severity of arthritis symptoms. Other areas of the body affected by inflammatory bowel disease include ankles, knees, bowel, liver, digestive tract, skin, eyes, spine, and hips.
• Treatment options:
– Diet
– Exercise
– Medication: Corticosteroids, Immunosuppressants, NSAIDs, Sulfasalazine or Alimta which dampens the immune system.
– Surgery
Functional Presentation and disability of the Spondylarthropathies
- When the axial skeleton is involved, the initial symptom is morning stiffness and lower back pain
- As the disease worsens, there is progressive diminution of motion of the spine
- Eventually, the sacroiliac joints, lumbar, thoracic, and cervical spine become fused
- At this stage, the spine is no longer painful, but the person has lost all ability to flex or rotate the spine and generally develops a hunched-over posture with fused flexion of the cervical spine and flexion contracture of the hips to compensate for the loss of the lordosis curvature in the lumbar spine
Degenerative articular rheumatic disease (Osteoarthritis)
- Most common rheumatic disease and is characterized by progressive loss of cartilage and reactive changes at the margins of the joint and in the subchondral bone.
- The disease usually begins in one’s 40s
- Prevalence increases with age and the disease becomes almost universal in individuals aged 65 and older
- Primarily affects weight-bearing joints such as the knees, hips, and lumbrosacral spine
what causes Osteoarthritis)
- Cause is unclear
- Considered to be a “wear and tear” arthritis
- Obesity is frequently associated with it
- Genetic factors play a role in the development that is sex-influenced and dominant in females, resulting in an incidence 10 times greater than in men
- The final outcome is full-thickness loss of cartilage down to bone so can get bine touching bine so the connective tissue has eroded.
what is the prevalence of OA
§ F > M
§ Increases with age
§ Begins often in youth
§ Creates cause of medical disability because joints becomes painful
how does OA progress
- In early disease, pain occurs only after joint use and is relieved by rest
- As the disease progresses, pain occurs with minimal motion or even at rest. This is because the joint specie decreases so the cartilage protection decreases. Bone touching bone.
- Nocturnal pain is commonly associated with severe disease. Scarring occurs also which are boney outgrowth so pressure increases as the bine is eroded, the bone tries to regrow. But it cant regrow in places of high pressure, so it regrows in places of lower pressures which tends to be at the end of the joint. Start to get these bony outcrops start to appear. Looks like nodules called habitant nodes.
- Start to see them growing these little lumps on the end of the bones
what are the functional limitations of Degenerative Joint Disease-OA
- Limited use of the involved joint
- Walking and transfer activities may be impaired
- Generally, ADLs will not be significantly impaired
Treatment and Prognosis of Degenerative Joint Disease OA
- Meds- can use NSAIDs but it isn’t an inflammatory it is a degenerative disease. The problem with treating osteoarthritis with non-steroidal drugs is that they are analgesics too and they have a risk associated with them
- Early PT/exercises
- Heat/cold therapy
- Joint protection
- Surgery because joints are larger they are better patients for surgery. So joint replacement can be effective
- Osteoarthritis is a slowly progressive disease
- The eventual outcome is complete destruction of the joint, and ultimately surgical intervention is required
give an example of Common Localized Non-Articular Disorders
- common localised non articulate disorders
Non joint related disorders which are located in just one single area - Good example is bursitis or tendinitis which is only limited to one part of the body. Not multiple joints its not systemic
- Not inside the joints its outside the joints.
- Associated joint structures that are resources that are located near to the joints that can be inflamed but they are not part of the joint themselves.
what is Generalised Non-articular Disorders
Fibromyalgia syndrome
• A chronic musculoskeletal syndrome characterized by diffuse pain in the absence of synovitis or myositis (muscle inflammation). There is no detectable disorder in the joints to the surrounding structures
what is the prevalence of Fibromyalgia syndrome FMS
- 10-12% general population (2% adults)
* Strong female preponderance
what are the presentations of FMS
- Normal physical examination
- No significant abnormalities on joint examination
- Characteristic finding is tenderness upon palpation of discrete anatomical locations termed tender points. Antibody negative normal renal function everything will appear to be okay.
- These are tender points where if you press them the patient will tend to complain about those points.
what are the Associated Complaints of FMS
- diffuse aching/stiffness, worse in am (may mimic RA)
- fatigue/exhaustion/sleep disturbance
- sensation of swelling of hands/feet (examination normal)
- paresthesias (normal EMGs)
- tension headaches / migraines
- symptoms of irritable bowel syndrome
- anxiety/depression
- weight gain (++)
FMS- working model
• Working model:
– A disorder of pain processing
– Central nervous system “sensitisation” – they perceive non painful stimuli as painful
– Makes usually non-painful stimuli feel painful
Local non articular disease- they will be located in one particular area. They wouldn’t be attached to joints
The typical example if IDDM, but Hashimoto thyroiditis is also a good example of an organ specific (localised) not articular autoimmune disease. This is when the thyroid will self-destruct by making antibodies to those tissues that should be producing thyroxine.
Another example is type 1 diabetes as the tissues will destroy that particular area.
what is Hashimoto’s thyroiditis
- characterized by the destruction of thyroid cells by various cell- and antibody-mediated immune processes. Will become hypothyroid
- Presence of typically anti-TPO (anti-thyroid peroxidase) and anti-Tg (anti-thyroglobulin) antibodies suggests Hashimoto thyroiditis however, 10-15% of patients with Hashimoto thyroiditis may be antibody negative
what is the treatment for Hashimoto’s thyroiditis
- Just like any other hypothyroid state
- The treatment of choice for Hashimoto thyroiditis is thyroid hormone replacement
- The drug of choice is individually tailored and titrated levothyroxine sodium administered orally, usually for life.
what is the Classification and epidemiology of rheumatoid arthritis
- Childhood and current low socioeconomic status are associated with increased risk of RA.
- Hormonal and reproductive factors contribute to the female predominance in RA; parity, breastfeeding, and exogenous hormones.
how does nutrition increase the risk of RA?
- Conflicting results with some showing:
- Protective link between olive oil/fish
- Higher risk between red meat and protein
- However neither proven in large cohort studies
- Low Vit D and C and possibly copper and selenium may have a role. No studies because no money to fud the research.
how may medication influence RA
- Statins have modest anti-inflammatory activity. Patients should be on a cardiovascular risk protection anyway.
- Studies show RA risk possibly reduced by up to 40% in those taking statins
- Ongoing research in progress to assess the anti-inflammatory effects
how can Infectious agents may be a trigger to RA
- These are potential associations, although epidemiological confirmation has not been possible
- Epstein-Barr virus
- Human Parvovirus B19
how can socioeconomic status influence RA
- The data is varied
- Most recent data suggests lower education level and occupational class favours RA
- A study in Sweden suggests that those without a university degree have a 40% higher risk of RA. Lifestyle of smoking triggers RA and poorer diets in people with lower socioeconomic status.
how can Reproductive and endocrine factors influence RA
- Pregnancy seems to affect the onset of RA because hormone is messed up.
- One study showed that the risk of RA during pregnancy is reduced, but increases in the 12 months after delivery
- Some hormonal factors are in play, possibly androgen although yet unknown
how can birth weight influence RA
- Higher birth weight has been shown to link to RA
- Babies > 4.5kg have double the risk of developing RA
- Probably a hypothalamic-pituitary axis dysfunction- hormones may have had an effect on the switching of those genes.
what are the preclinical features of RA
- Autoantibodies precede disease
- Can be 5-10 years before symptoms
- Levels rise as symptoms emerge
- Rheumatoid factor (RF)
- Anti-cyclic citrullinated peptide antibodies (Anti-CCP)
- Not everyone is seropositive
describe the development of autoimmunity
- Preclinical stage you have the antibodies at a low level
- All of a sudden you get this inflammation as it increases with the antibody production
- You get this auto-anti autoimmune which has been triggered by something which then get these antibodies produced and then you get these symptoms which is recognised by the patient and then the joints are affected.
- Yellow part can stretch out between 5-20 years
Natural history of the disease
- There is a genetic risk and an environmental exposure
- Get a switching of that genetic kind of mix to be auto immune.
- Can get pre-clinical autoimmune that you can measure but there are no signs
- Get clinical presentation then will get diagnosed when they’ve got auto immunity. There are all of the factors as well as all of the symptoms
Antibody changes
- You have these protein antibodies increase and as a result this increases IgG response.
- Building up this pool of anti-CCP and they affect the body. They will charge the immune system
- They fix complements and they activate Fc receptors and can act like antigen presenting cells where there is an amplified effect in the immune response
- Can tell how strong the RA is and will be an indicator how they will do in the tests and most likely they will do poorly and will need to start aggressive treatment.
Predicting onset and possible prevention of antibodies
- Currently being investigated
- Aim is to ID the high risk RA autoantibodies and address the preclinical phase before it transitions
- ? Role for statins
- ? (Anti) Anti-CCP
• In the preclinical phase of RA, what three markers of the disease become apparent and why is this important as a prognostic indicator?
- RF and anti-CCP antibodies and the acute reactant phase (CRP)
- If you had a patient who was seropositive for all of the things so high ESR, high anti- CCP and high factor positive (RF) then you would get an idea that the prognostic value is very high. Important because it is important to start treating the patient early and very aggressively to get their disease under control because they are at a risk of deteriorating because of the indicators.
what are the clinical features of RA
- Inflammatory polyarthritis many joints affected) is central
- Particularly the small joints of hands and feet. People who have arthritis in larger joints tend to be more degenerative like osteoarthritis
- 80% of RA patients have RF and Anti-CCP Abs. if you measure their ESR and their CEPR it will always be more raised
- Inflammatory markers are raised
- Joint erosion and destruction can occur and can affect every day things. It is irreversible.
- Joints become swollen and tender (synovitis)- where the joint capsule becomes swollen and tender. Both presentations together
describe the difference between a healthy joint and an inflamed joint
- On the left hand side of the diagram there are healthy joints.
- On the right hand side of the diagram the joints have been affected by rheumatoid.
- There are lots of mediator cells in the capsule and they are always bad because they will be acting as antigen presenting cells and they will be doing things such as fixing complements, turbocharging local immune reaction.
- This will ultimately get a cytokine production which will act as a proteinase solution and will destroy the protein structures surrounding it.
- The structures that are primarily attacked are the bine and the synovial membrane which will become scarred and thickened so it doesn’t work as well. The bone will go with it and it wouldn’t be able to be repaired and will lead to permanent joint damage
- In early disease you will see fingers and knuckles being swollen so the mCPs and the PIPs are swollen
- Difficult to see this presentation
what are the two types of progressive diseases
- If you don’t treat the disease can develop swan neck deformity and boutonnière deformity
- boutonnière deformity is where you start to get this kind of fixed flexion of the joints and the finger starts looking like this. will happen to all of the fingers in the hand.
- Swan neck deformity is where the joints are fixed up in this way
- Can have a severe impact on a person’s daily life. Affects quality of life
wht is ulnar drift
The joints starts to rotate and kind of collapse in on itself. Cant straighten your hands out
describe the patterns of onset
• Gradual
– Most common, small joints, EMS prominent, symmetrical
• Slow, monoarticular
– Less common, larger joints spreading to smaller over weeks
• Abrupt, acute polyarthritis
– Widespread affecting small and large joints leading to incapacity
describe the patterns of progression
- Lots of inter patient variability. Typically it is a gradual onset. Can have on and off
- Brief/self-limited
- Palindronic
- Prolonged and progressive
- All of the above can range from mild to severe
describe the Assessing disease activity
HAQ-DI score (Health Assessment Questionnaire Disability Index)
- Count the number of joints in specific places and then look at how many of these joints are tender and hoe many of the joints are swollen
- Then look at the acute phase reactants so you can do and ESR and then do a global health assessment asking ho active their RA has been and that will equate to a number between 0-100 and then put all the numbers into the DAS-28 formula.
- What’s good about the das 28 is not only can it categorise disease activity in a single measurement but it can also tell you how effective that’s changed over time. If you do a das score when you initially see the patient and then after a period of time the das score will have improved. It is really helpful to give those threshold for treatment.
- You have to have a das score of 5.1 to be classified as having an active disease and you can say that you can give drugs that are either very toxic or very expensive. People with higher disease activity because they are more likely to receive a benefit than those who have a low active disease.
- Can also use das score to continue therapy. If you started a new drug and then after a period of time you take another das score and it comes out worse you will be able to say that that particular drug hasn’t worked so you can change it to something different
- You can also measure the impact of the disease on patients quality of life by using the HAQ-DI score. Ask them a range of questions.
- 0 = no disability
- 3 = unable to carry out tasks
Change of 0.22 is significant
describe the prognosis
- HAQ score at baseline is a predictor of outcome- if they score really poorly when first diagnosed then it is unlikely that they are going to make massive improvement from that. Can make significant improvements but the score will still be bad.
- Radiographic changes at baseline are a poor indicator
- Acute phase reactants predict damage- anti-CCP, RF can predict the amount of damage that the patient is in
- Early treatment, tight control is the key
what is meany by nodules
Fibrous growth caused by pooling of RF immune complexes- they don’t cause any medical problems jus not very nice to look at. Because they are not medically life threatening surgeons wouldn’t remove them.
- The only way in which a nodule can cause a problem is that if they form at a joint or a bend because it will cause restriction in the movement of that joint.
- Problem is that they often grow back again in the same place. You have removed the nodule but you have also developed scar tissue from the surgery. If the nodule grows underneath the scar tissue can make the situation worse.
- Can inject nodules with a steroid to make them shrink a little bit and if the patients drug therapy is good nodules can also decrease in size
how does RA affect pulmonary involvement
- Occurs frequently – often missed
- Pulmonary nodules
- Interstitial lung disease (ILD) happens in about 7%of RA patients, but they have a 3x increase in risk of death.
- Methotrexate is an anchor drug in RA as it always used unless there is a problem with either side effects or the tolerance. Methotrexate can cause pulmonary fibrosis. Have a higher rate of interstitial lung disease and then you have also got a drug that can predispose someone to put more fibrosis.
- Before you start methotrexate you should check the lungs by doing an x-ray to make sure they are okay and don’t have any sign of nodules of our lung disease before you start the patient of methotrexate
how does RA affect Cardiac disease
- RA may lead to generalised vascular disease
- Pericarditits is often seen
- Cardiovascular disease is common and risk of cardiac death is high. Need to do a QRISK. Make sure their blood pressure is okay
- Important to treat risk i.e. antiplatelet/statin/anti-hypertensive
- DMARD therapy significantly lowers risk
how does RA affect ocular involvement
- Episcleritis – sudden onset of redness and pain
- Sicca syndrome also common- dry eyes and the patient will often ask for a lubricant eye drop for their eyes
what are the genetic links to RA
- Many chronic inflammatory diseases have been shown to occur preferentially in individuals carrying certain variants of genes in the MHC (major histocompatibility complex). Part of the human leukocyte antigen and more precisely the MHC complex of human chromosome-6. If you express this gene then more likely to be susceptible of having certain types of inflammatory diseases.
The contribution of genetic factors to RA
• Twin and family studies show a contribution of genetic factors to RA
• HLA-DRB1 is the most likely genetic link- twins c
• HLA-DRB1 is modified by smoking and other environmental factors
what are the indicators of RA
- RH and anti-CPP antibodies are indicators to see how well the patient is going to do as their disease progresses
what is meant by rheumatoid factor
- Autoantibodies recognise antigens on IgG
- Leads to compliment fixation (ie turbocharges the formation of immune complexes)
- Detected in 50-80% of RA patients depending on stage of disease
- High titre is more specific (>40IU/mL)
- RF predicts disease, high titre = more severe RA, rapid progression, worse outcome
what is meant by Anti-citrullinated peptide antibodies (ACPAs)
- RA patients have epitopes that come from citrulline, recognised by autoantibodies
- Anti-cyclic citrullinated peptide antibody test is the way we check for these antibodies (Anti-CCP antibodies)
- Highly specific (>95% for RA)
