Arthritis: A Deeper Dive
Arthritis: A Deeper Dive, provides an overview of the disease, with scientific and medical expressions explained in simple terms.
What is arthritis?Arthritis isn’t a single disease, it’s actually an umbrella term for the various causes of joint pain or joint disease. As a result there are over 100 specific types of arthritis, and they affect people of all ages, sexes and races. The symptoms can include swelling, pain, stiffness and decreased range of motion. The symptoms may not be continuous, and they may get worse over time. Some types of arthritis can result in permanent damage to the joints.
What causes arthritis?Arthritis (from the Greek word for joint) is a chronic multifactorial disease. The term ‘multifactorial disease’ simply means a disease that is caused by multiple factors. Arthritis is thought to be caused by a combination of genetic components and environmental factors, each of which alone would not cause the condition. This means that it’s a bit of a lottery, some people have a few of the genetic components but never suffer from arthritis. Others are exposed to exactly the right environmental factors to trigger the disease, yet never get it. While some people with the same genetic or environmental circumstances will suffer.
A brief history of arthritisArthritis has been around for as long as creatures and people have had bones.
- In 2012 a research team at Bristol University reported arthritis-like conditions in the skeletons of a 150-million-year-old Pliosaurus, a 90-million-year-old Iguanodon.
- Neanderthal skeletons from as far back as 250,000 to 35,000 years ago show evidence of what could be osteoarthritis.
- The remains of Native Americans dating back to 4500 BC have been shown to exhibit signs of rheumatoid arthritis.
- A papyrus scroll dating from 1550 BC describes gout, a type of arthritis, as a disorder and recommends treating as Imhotep advised, which suggests that the ancient Egyptians recognised arthritis 1000 years earlier than that.
- In 1528, Charles I of Spain developed gouty arthritis, and by 1556 it had became so bad that he gave up the throne to his son.
- 1591: Guillaume de Baillou identified a condition characterised by swelling, stiffness, and pain, as rheumatism. The timing of this is significant, as it coincides with the discovery of the Americas and an infection, which caused inflammation in the joints, being carried back to Europe. This infection, coupled with tobacco smoking, which was introduced to the Europeans by the Native Americans, might have given rise to increased cases of arthritis (smoking is a known risk factor of rheumatoid arthritis).
- 1715: William Musgrave wrote the De Arthritide Symptomatica, the earliest text to describe in detail the symptoms of rheumatoid arthritis.
- In 1818, Jean-Louis-Marc Alibert first identified a relationship between psoriasis and arthritis.
- 1859: Dr Garrod named rheumatoid arthritis as distinct from osteoarthritis.
- In 1860, the term “psoriasis arthritiqe” was first used.
- In 1886, John Kent Spender coined the term osteoarthritis.
- In 1904, SpondyloArthritis was named by Fraenkel after formative discoveries by the neurologists Vladimir Bechterew and Pierre Marie, and pathologist Eugen Fraenkel. This in turn has lead to the more specific classification of axial spondyloarthritis and peripheral spondyloarthritis.
Different types of arthritisThe two most common types of arthritis are osteoarthritis and rheumatoid arthritis and they are very different in cause, in effect, and in treatment.
OsteoarthritisIn osteoarthritis the cartilage that protects the ends of the bone as it bends and rotates at the joint, breaks down. This causes the bones to rub together, causing pain and swelling. As the body tries to heal itself, bony growths can develop, which can create a ‘rough surface’, which makes the pain and swelling worse. As osteoarthritis is caused by wear and tear on the joints:
- It usually begins much later in life.
- Onset is slow, often taking years to develop.
- The affected joints ache and feel tender, but there is little to no swelling.
- Symptoms are not symmetrical, so if the wear-and-tear has been more pronounced on one side, then the arthritis will affect only the joints on on that side. The problem is that the body is likely to compensate for the pain, causing wear-and-tear on the joints on the other side of the body, so symptoms often spread.
- Stiffness in the morning usually lasts less than an hour, but may return at the end of the day or after physical activity.
- The patient will not experience general bodily symptoms, like being overly fatigued or feeling unwell.
The causesApart from general wear and tear, the exact cause is unknown, but some contributory factors are thought to be:
- Age - the older the person the more time their joints have had to wear down.
- Genetics - osteoarthritis can run in families, although no studies have been able to identify a gene that might be responsible.
- Obesity - the extra strain put on joints by excess weight, can cause them to wear more quickly.
- Injury - often put down to overuse after an accident or operation.
- Contributing conditions - osteoarthritis can occur in joints that are damaged by another condition, like gout.
TreatmentsThere is no cure for arthritis as damage to the cartilage is irreparable. The condition can get worse, or it can remain the same for years without progressing. The main treatments include:
- Maintaining a healthy weight and continuing to exercise.
- Maintaining joint mobility and flexibility.
- Medication for pain relief.
- Supportive therapies to make everyday activities easier.
- Analgesics - Pain relievers that include acetaminophen, opioids (narcotics) and tramadol. These are available over-the-counter or by prescription.
- Non-steroidal anti-inflammatory drugs like aspirin, ibuprofen, naproxen, and celecoxib.
- Corticosteroids - powerful anti-inflammatory injections directly into the affected joint, available at most GP practices.
- Hyaluronic acid - available by injection at most GP practices. Hyaluronic acid occurs naturally in the synovial fluid, which lubricates the bone, and this fluid is broken down in joints affected by arthritis.
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Rheumatoid arthritisRheumatoid arthritis is an autoimmune disease. Autoimmune disorders happen when the immune system malfunctions and begins to attack the body’s own tissues and organs. This sounds simple, but the reality is that somewhere in the incredibly complex interactions that happen within the immune system, one element is misbehaving. In very simple terms, the immune system works when cells react to one another. The way cells react is called a signalling cascade:
- Cells have minute receptors on their surface
- These specific receptors join to specific cells
- When they join it causes a change in the cell itself
- This creates cytokines, proteins or other cells
- Those new cytokines, proteins or cells travel off to join with other cell receptors
- New cytokines, proteins or cells bind with unfriendly cells and neutralise them
In rheumatoid arthritis, the cells being attacked are in the synovial tissue.
Synovial tissues include the synovial membrane, which is situated between bones in a joint, and holds the synovial fluid, which provides lubricant for the joint itself. As the synovial tissue is attacked, the body attempts to heal itself, increasing blood flow to the area and causing inflammation. The inflammation causes pain as the ligaments attaching the bone to the muscle, stretch. When the flare-up subsides the ligaments are still stretched, which means the joint isn’t held in place as tightly as it should be. This means that the bone can settle in an unusual position, leading to further discomfort and/or deformity. The immune system is body-wide, which is why rheumatoid arthritis usually occurs in multiple joints.
The characteristics of rheumatoid arthritis
- It can begin at any time in life.
- It commonly starts in the hands and feet, then progresses to the wrists, knees, elbows and/or shoulders.
- Once it takes hold it can spread rapidly, usually in a few weeks or months.
- Joints become painful, swollen, stiff and warm, as blood flow increases.
- It causes joint damage in 80% to 85% of patients, with most of the damage occurring in the first 2 years.
- The effects are symmetrical, for instance both knees and both hands.
- Stiffness in the morning usually lasts longer than an hour.
- The patient will often feel fatigued and ill as a result of their condition, and may lose weight.
- Before the onset of the more extreme symptoms, the patient may get coldness in their hands and feet, along with numbness and tingling.
The causesIt’s not yet known what triggers the signalling cascade in the immune system, leading to rheumatoid arthritis. What is known is that it’s more common in women than in men, it usually develops between the ages of 40 and 60, and there is some evidence that there’s a genetic predisposition to the disease. There is also some evidence that cigarette smoking, infection, or trauma may trigger the disease. In this instance, trauma refers to a physical accident that impacts on a joint.
The treatmentsEvery person with rheumatoid arthritis is different and will react differently to treatment. Therefore, the medications below will often be used together in different combinations, and more than one combination might be tried before a successful medication regime is found.
DMARDs (Disease Modifying Anti-Rheumatic Drugs)Treatment often starts with DMARDs, which are usually in tablet form. These ease symptoms and slow the progression of the disease. DMARDs block the effects of the chemicals released when the immune system attacks the joints, which could otherwise cause further damage to the bones, ligaments and cartilage.
Common DMARD medicationsMethotrexate - common side effects include nausea, loss of appetite, sore mouth, diarrhoea, headaches, hair loss. Methotrexate is an immunosuppressant and is the go-to DMARD treatment as people usually don’t experience bad side effects, and it’s often taken alongside another DMARD. Immunosuppressants suppress the immune system in general, and as it's the immune system that attacks the joints, it is hoped that suppressing it will help to stop the symptoms. It can have a negative effect on blood counts and liver function, routine blood tests are vital. Additionally, methotrexate can affect the lungs, so regular chest x-rays and breathing tests should be scheduled. Leflunomide - common side effects include diarrhoea (20% of patients), nausea, stomach pain, indigestion, rash, hair loss. Leflunomide is an immunosuppressant that blocks the reproduction of cells that causes the painful swelling in joints. It can also have a negative effect on the liver and blood counts, so regular blood tests are a must. It can also cause lung problems, so respiratory tests should be scheduled. Hydroxychloroquine - common side effects include headache, nausea, loss of appetite and weight loss, changes in mood, skin rash, and hair loss. It isn’t known how hydroxychloroquine works, but it’s believed that it disrupts the signalling cascade in the immune system that leads to the painful swelling and negative effects of rheumatoid arthritis. Hydroxychloroquine can cause damage to the retina, and if the patient experiences any problems with their vision they are advised to seek medical attention immediately. It is also poisonous and often fatal if taken in high doses, especially in children, so extra care is required. It is well worth investing in a pill sorter to avoid accidental overdose. Sulfasalazine - common side effects include stomach pain, headache, heartburn, nausea, loss of appetite. Sulfasalazine is a combination of salicylate (the main ingredient in aspirin) and a sulfa antibiotic. It works to decrease the pain and swelling of rheumatoid arthritis. This medication may cause serious side-effects, one of which is called Stevens-Johnson Syndrome and it's important that if the patient experiences any unusual rashes or blistering anywhere on the skin or mouth, they seek medical attention as soon as possible. Other side effects that require immediate attention are seizures, fever, signs of liver problems and chest pain.
Biological treatmentsThese treatments are often taken alongside a DMARD and are normally only taken if DMARDs alone aren't working. These medications are given by injection, usually 1 or 2 times a week and they work to disrupt the immunological signalling cascade that causes the reaction that leads to rheumatoid arthritis. Each one targets a different cell or receptor or cytokine, or protein and aims to neutralise it. Etanercept - common side effects include itching, pain, headache, dizziness and ENT (ear, nose and throat) problems. Etanercept is a TNF-⍺ inhibitor. TNF-⍺ (tumor necrosis factor - alpha) is a protein that’s part of the signalling cascade that causes inflammation. Etanercept is a protein made from two TNF receptors, coupled with a section of monoclonal antibody. This new cell binds to TNF-⍺ and stops it from working.
Receptors are the parts of a cell that reach out and bind to other cells, and monoclonal antibodies are cells in the immune system that want to bind to targeted cells.
This means that a specific type of monoclonal antibody that can harm TNF-⍺, is given arms that will bind to TNF-⍺, when usually it wouldn’t harm TNF-⍺ because TNF-⍺ is a natural part of the immune system.
When it’s working properly, TNF-⍺ is an important part of the immune system, so taking a TNF-⍺ inhibitor will limit the immune system as a whole. This can lead to higher instances of infection. In very bad cases, etanercept may cause cancer, multiple sclerosis, myelitis (inflammation in the spinal cord that causes nerve damage) and optic neuritis. New cases or worsening of congestive heart failure may also occur. Infliximab - common side effects include coughing, rash, sinus infection, sore throat, stomach pain. Infliximab is another TNF-⍺ inhibitor. The main difference between infliximab and etanercept is that while etanercept is more likely to bind to the active TNF-⍺ cells, infliximab binds to both inactive and active TNF-⍺ cells. The side effects and reported complications that go with taking Infliximab are generally in line with those experienced with etanercept, except infliximab has a higher risk of fungal lung infections and reactivation of tuberculosis.
With all treatments for rheumatoid arthritis it is vital that regular checks are carried out on heart, lung, and liver health.
Adalimumab - common side effects include back pain, headache, or itching, bruising, bleeding, pain at the site of injection. Adalimumab is another TNF-⍺ inhibitor. Both adalimumab and infliximab can destroy the cells that create TNF-⍺, whereas etanercept binds to them but doesn’t destroy them. Adalimumab comes with increased risk of infection, certain cancers including lymphoma or leukaemia. Certolizumab pegol - common side effects include increased risk of infection (including possible reactivation of tuberculosis), sore throat and/or fever, coughing, diarrhea. Certolizumab pegol is another TNF-⍺ inhibitor that is built in a slightly different way. Etanercept, Infliximab and Adalimumab are relatively large components, while certolizumab pegol is smaller and more lightweight. As it’s smaller, it would usually be destroyed by the body before it could do any good. To make it last longer, it undergoes a process called PEGylation, which is when the chemical PEGOL is added to the protein that neutralises TNF-α. The resulting molecule lasts much longer in the body, so it only needs to be injected every 2 weeks. With certolizumab pegol it’s important to be wary of coming into contact with chicken pox or shingles, and it can also cause skin cancer. Rituximab - side effects include fever, wheeziness, rash and drop in blood pressure. Rituximab is a B-cell depleting, anti-CD20 antibody. This means that it removes B-cells or B-lymphocytes. B-cells are white blood cells that can mature and trigger inflammation. Rituximab works by targeting and blocking the CD20, which would prompt the B-cells to mature, which would prompt TNF-α cells to be made. Abatacept - side effects include dizziness, headaches, nausea, sore throat, cough, unexpected weight loss. Further up the chain still, abatacept is a T-cell signaling inhibitor. This means that it disrupts the T-cells that would cause the response in B-cells that would cause more TNFα cells to be made. As you can see, each one of these medications selects a specific part of the chain to disrupt. Tocilizumab - side effects include cough, sore throat, headaches, diziness, mouth ulcers, conjunctivitis, high blood pressure, weight gain, skin rashes, stomach irritation. The newest treatment that affects the chain one link further up, is tocilizumab, an anti-interleukin-6 receptor antibody. This means that it stops Interleukin-6 (IL-6) from binding with the receptor IL-6R, which stops the signals that would summon the inflammatory reactions in the T-cells and B-cells targeted by rituximab and abatacept.
A helpful metaphorMetaphors help to clarify things, and as immunobiology is one of the most complex areas of biology to talk about, help is usually necessary. I therefore invite you to think of a stampede. Imagine a herd of 2000 wildebeest on an African plain. These wildebeest represent the cells in the immune system. In a healthy immune system the wildebeest stampede is triggered by real threats, like lions. However, when a patient has an autoimmune disease, 200 of the wildebeest can’t tell the difference between a lion and a zebra. It only takes a few wildebeest to start running, and very quickly the rest of the herd starts to run too. DMARD treatments aim to prevent the stampede by tying two out of four legs on every wildebeest. This stops them from stampeding, but it makes their movement slow in general. It also means that the real threats, like lions, can just wander up and attack wherever they like. On the other hand, biologics go through the herd, tying the legs of the wildebeest that run away from zebra. This supposedly keeps the rest of the herd mobile, but tying the legs of these few can affect the rest of the herd in unpredictable ways. Both of these options can stop the immuno-stampede, which is good when it comes to psoriatic arthritis, but it’s not so good when one considers the lions. Everyone’s inner-wildebeest herd is triggered by different things, and finding the right solution is often a case of trial and error.
The comorbiditiesA comorbidity is a separate medical problem that is directly caused by an original disease or condition. The most common comorbidities are depression and anxiety, and as these can have a serious impact on quality of life, and can lead to loss of interest in maintaining treatment regimes, it is very important that they are treated. Rheumatoid arthritis can also cause:
- Twice the risk of heart attack.
- 40% higher risk of atrial fibrillation.
- 30% higher risk of stroke.
- Interstitial lung disease, a leading cause of death amongst those with rheumatoid arthritis.
- Twice the risk of developing osteoporosis.
- Cancers, including leukaemia, lung cancer, lymphoma and multiple myeloma.
Diagnosing rheumatoid arthritisRheumatoid arthritis can be difficult to diagnose, especially as quite a few conditions cause swelling and joint stiffness. However, early diagnosis is important, so a GP should be seen as soon as possible after the symptoms begin.
- The GP will carry-out a physical examination.
- If they suspect rheumatoid arthritis they will refer their patient to a rheumatologist.
- Blood tests may be arranged, which might help, but they’re not necessarily conclusive. They will test for: - Erythrocyte sedimentation rate (ESR) - C-reactive protein (CRP) - Full blood count
- Scans, including X-rays, MRI and Ultrasound, may be organised to test for joint damage and inflammation.
How does arthritis affect life?Arthritis is a degenerative disease that has an effect on almost every aspect of life. For those with osteoarthritis the effects are often minimal until later in life. In the early stages, symptoms can be managed with over-the-counter medications and holistic therapies like exercise and muscle strengthening routines. Rheumatoid arthritis is a different story. The decline can be slow, but it can also be rapid and will often lead to disfigurement and a need for constant care. Rheumatoid arthritis can affect people of any age, but it is most likely to affect those aged between 40 and 60. This means that quality of life at an otherwise active time can be seriously impaired.
Caring for someone with arthritisThe key way to help someone with arthritis is to stay positive and be sensitive to their mental health and wellbeing. Pain isn’t fun, and the reality that the condition will only get worse can be difficult to face. It’s important to adhere to medication and treatment regimens, and to keep-up with regular physical activity. If your loved one has been diagnosed with rheumatoid arthritis it is vitally important to stay informed about the various side effects associated with the complex medications prescribed, and aware of any abnormalities in behaviour and health. It is also important to take care of yourself. Caring for someone is rewarding, but it can also be incredibly challenging and stressful. Making sure you don’t neglect yourself can make a big difference to your own long-term health. . If you are caring for someone with arthritis, HomeTouch can help. Simply search by postcode and browse the profiles of self-employed carers near you. All of the carers on our site have gone through a thorough 42-point vetting process, and only 5% are accepted. You choose the carer you want to work with, and we provide support with contracts, payments, and holiday and sickness cover.
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