Chapter I Rheumatoid arthritis

Chapter I Rheumatoid arthritis

1. Overview
Rheumatoid arthritis, sometimes referred to as rheumatoid disease, is a chronic, progressive and disabling autoimmune disease that causes inflammation and pain in the joints, the tissue around the joints, and other organs in the human body. Rheumatoid arthritis usually affects the joints in the hands and feet first, but any joint may become affected. Patients with rheumatoid arthritis commonly have stiff joints and feel generally unwell and tired.

Rheumatoid arthritis is an autoimmune disease. Our immune system is a complex organization of cells and antibodies designed to seek out and destroy organisms and substances which harm us, such as infections. When our immune system starts attacking our own bodies, mistaking body tissues for foreign invaders, we have an autoimmune disease. Individuals with an autoimmune disease have antibodies in their blood which target their own body tissues, resulting in inflammation. The immune system of a patient with rheumatoid arthritis attacks the lining of the joints, causing them to swell. As opposed to the wear-and-tear damage which occurs with osteoarthritis, rheumatoid arthritis affects the lining of the joints, resulting in painful swelling that can lead to bone erosion and joint deformity. Eventually the affected joints may become permanently damaged. Rheumatoid arthritis is referred to as a systemic illness. Systemic means it affects the entire body; in the case of rheumatoid arthritis, multiple organs in the body
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can be affected. The patient may also have fevers and experience fatigue. Rheumatoid arthritis may also produce diffuse (spreading) inflammation in the lungs, the membrane around the lungs (pleura), pericardium (a double-walled sac that contains the heart and the roots of the great blood vessels) and the tough white outer coat over the eyeball (sclera); it can produce nodular lesions, most commonly in subcutaneous tissue under the skin. Rheumatoid arthritis is much more common that MS (multiple sclerosis) or leukemia. However, awareness of the diseases effects and severity are more restricted to patients, their caregivers and their relatives because it is not well publicized. Rheumatoid arthritis symptoms generally come and go. On some occasions symptoms may be mild, while on others they may be severe and extremely painful. A patient has aflare up when symptoms are bad. It is impossible to know when a flare up may come. Rheumatoid arthritis can be a very painful condition, leading to considerable loss of functioning and mobility. Diagnosis is made chiefly as a result of identifying signs and symptoms, as well as rheumatoid factor blood tests and X-rays. Diagnosis and the long-term management of the disease is generally carried out by a rheumatologist; a specialist in rheumatology. Rheumatoid arthritis affects all ages, races, and social and ethnic groups. It is most likely to strike people 35-50 years of age, but it can occur in children, teenagers, and elderly people. (A similar disease affecting young people is known as juvenile rheumatoid arthritis). Worldwide, about 1% of people are believed to have rheumatoid arthritis, but the rate varies among different groups of people. For example, rheumatoid arthritis affects about 5%-6% of some Native American groups, while the rate is very low in some Caribbean peoples of African descent. The rate is about 2%-3% in people who have a close relative with rheumatoid arthritis, such as a parent, brother or sister, or child. As many as half of those with rheumatoid arthritis are no longer able to work 10-20 years after their condition is diagnosed. Although the disease has no cure, early diagnosis and prompt subsequent treatment of symptoms may slow the progression down, as well as making the patient more comfortable.

2. History

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The first known traces of arthritis date back at least as far as 4500 BC. A text dated 123 AD first describes symptoms very similar to rheumatoid arthritis. It was noted in skeletal remains of Native Americans found in Tennessee. In the Old World the disease is vanishingly rare before the 1600s and on this basis investigators believe it spread across the Atlantic during the Age of Exploration. In 1859 the disease acquired its current name. An anomaly has been noticed from investigation of Precolumbian bones. The bones from the Tennessee site show no signs of tuberculosis even though it was prevalent at the time throughout the Americas. Jim Mobley, at Pfizer, has discovered a historical pattern of epidemics of tuberculosis followed by a surge in the number of rheumatoid arthritis cases a few generations later. Mobley attributes the spikes in arthritis to selective pressure caused by tuberculosis. A hypervigilant immune system is protective against tuberculosis at the cost of an increased risk of autoimmune disease. The art of Peter Paul Rubens may possibly depict the effects of rheumatoid arthritis. In his later paintings, his rendered hands show, in the opinion of some physicians, increasing deformity consistent with the symptoms of the disease. Rheumatoid arthritis appears to some to have been depicted in 16th century paintings. However, it is generally recognised in art historical circles that the painting of hands in the sixteenth and seventeenth century followed certain stylised conventions, most clearly seen in the Mannerist movement. It was conventional, for instance to show the upheld right hand of Christ in what now appears a deformed posture. These conventions are easily misinterpreted as portrayals of disease. They are much too widespread for this to be plausible. The first recognized description of rheumatoid arthritis was in 1800 by the French physician Dr Augustin Jacob Landr-Beauvais (17721840) who was based in the famed Salptrire Hospital in Paris. The name "rheumatoid arthritis" itself was coined in 1859 by British rheumatologist Dr Alfred Baring Garrod. Notable cases

Dorothy Hodgkin, Nobel prize winning scientist, developed severe deforming rheumatoid arthritis at age 28. In spite of this she continued her career and developed X-ray crystallography, which underpins much of the information known about rheumatoid arthritis. She also discovered the structure of insulin and enabled the discovery of the genetic code. Auguste Renoir, impressionist painter, whose later 'softer' style might have reflected in some way his severe disability. Christiaan Barnard, the first surgeon to perform a human-to-human heart transplant had to retire owing to the condition. He also wrote a book on living with arthritis.

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James Coburn claimed to have healed the condition using pills containing a sulfur-containing compound on his return to acting. Erik Lindbergh, aviator and member of the X-Prize administration. Erik has been a spokesman for the arthritis drug Enbrel, as a result of his success with the treatment. Bob Mortimer British comedian and actor. Kathleen Turner and Aida Turturro have worked to raise public awareness of the condition Billy Bowden, international cricket umpire who had to retire from active play because of rheumatoid arhtirits. Melvin Franklin, bass singer of the Temptations. He treated RA with cortisone shots so he could perform. Jamie Farr, American actor, famous for his role as Max Klinger on the 1970s television series M*A*S*H. Sandy Koufax, An American Hall-of-Fame baseball pitcher who played from 1955 to 1966 for the Los Angeles Dodgers. Jeffrey Gottfurcht An American who is attempting to be the first person with RA to climb to the top of Mt. Everest March 2011.

3.

Signs and symptoms

A symptom is something the patient feels and reports, while a sign is something other people, such as the doctor detect. For example, pain may be a symptom while a rash may be a sign. The symptoms of rheumatoid arthritis come and go, depending on the degree of tissue inflammation. When body tissues are inflamed, the disease is active. When tissue inflammation subsides, the disease is inactive (in remission). Remissions can occur spontaneously or with treatment and can last weeks, months, or years. During remissions, symptoms of the disease disappear, and people generally feel well. When the disease becomes active again (relapse), symptoms return. The return of disease activity and symptoms is called a flare. The course of rheumatoid arthritis varies among affected individuals, and periods of flares and remissions are typical. When the disease is active, symptoms can include fatigue, loss of energy, lack of appetite, low-grade fever, muscle and joint aches, and stiffness. Muscle and joint stiffness are usually most notable in the morning and after periods of inactivity. Arthritis is common during disease flares. Also during flares, joints frequently become red, swollen, painful, and tender. This occurs because the lining tissue of the joint (synovium) becomes inflamed, resulting in the production of excessive joint fluid (synovial fluid). The synovium also thickens with inflammation (synovitis).
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In rheumatoid arthritis, multiple joints are usually inflamed in a symmetrical pattern (both sides of the body affected). The small joints of both the hands and wrists are often involved. Simple tasks of daily living, such as turning door knobs and opening jars, can become difficult during flares. The small joints of the feet are also commonly involved. Occasionally, only one joint is inflamed. When only one joint is involved, the arthritis can mimic the joint inflammation caused by other forms of arthritis, such as gout or joint infection. Chronic inflammation can cause damage to body tissues, including cartilage and bone. This leads to a loss of cartilage and erosion and weakness of the bones as well as the muscles, resulting in joint deformity, destruction, and loss of function. Rarely, rheumatoid arthritis can even affect the joint that is responsible for the tightening of our vocal cords to change the tone of our voice, the cricoarytenoid joint. When this joint is inflamed, it can cause hoarseness of the voice. The most commonly affected joints are: The proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints of the hands (middle and base joints of the finger)

The wrists, especially the ulnar-styloid articulation The shoulders Elbows Knees Ankles Metatarsophalangeal (MTP) joints (in the toes)

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Note: The distal interphalangeal (DIP) joints are not usually affected (top joint of the finger) The spine is never affected, except the atlanto-axial articulation in late disease.

Morning stiffness - morning stiffness is a hallmark symptom of rheumatoid arthritis, especially if it lasts more than an hour. Experts say that the duration of morning stiffness is usually a good indication of the inflammatory activity of the disease. Although patients with other forms of arthritis may have early morning joint stiffness, they tend not to last for more than an hour. There may be stiffness after long periods of inactivity, which tends to last longer than in cases of degenerative arthritis. Joint pain and swelling - the lining of the affected joint becomes inflamed - the skin over the joint becomes warm, red and swollen. The area is painful and tender to the touch.

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Anemia - according to The National Health Service (NHS), UK, approximately 80% of patients with rheumatoid arthritis are anemic - there is a low number of red blood cells; the blood is unable to carry enough oxygen. Loss of appetite/Weight loss - a significant number of patients may experience loss of appetite, and subsequent weight loss. The patient may have red and puffy hands. The following non-specific systemic flu-like symptoms may be felt weeks to months before other symptoms appear:

Fatigue (tiredness) Malaise Depression

Fever - usually low grade (37 - 38C; 99 - 100F). Experts say that a higher fever often indicates an infectious cause (another illness). Flare-ups The symptoms of rheumatoid arthritis tend to be intermittent (sporadic); they come and go. Sometimes the patient will have a flare-up - the symptoms will be more intense and severe. Although flare-ups can occur at any time, they tend to be more painful in the morning, when the patient wakes up. As the day progresses symptoms will start to ease. Rheumatoid arthritis is a systemic illness (one that affects the entire body) Multiple organs in the body can be affected, including: Inflammation in the lungs - this usually causes no symptoms. If the patient develops shortness of breath medications may be prescribed to reduce inflammation in the lungs.

Inflammation of the membrane around the lungs (pleura)

Inflammation of the pericardium - a double-walled sac that contains the heart and the roots of the great blood vessels.

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Inflammation of the tough white outer coat over the eyeball (sclera) affects about 5% of patients. Symptoms may include red, painful and possibly dry eyes.

Nodular lesions - about 1 in every 4 rheumatoid arthritis patients develops lumps under the skin - rheumatoid nodules. They tend to occur on the skin over the elbows and forearms. They may be painful, but not usually.

Inflammation of the tear glands Inflammation of the salivary glands

Inflammation of the cricoarytenoid joint - this is a joint in the larynx (voice box). When it is inflamed it can cause hoarseness.

4. Cause
The smooth lining of the membranes (thin layer of cells) that surround our joints is called the synovium. A flexible joint is lined by a synovial membrane. The synovium produces a clear substance - synovial fluid - which lubricates and nourishes the cartilage and bones inside the joint capsule. When the immune system attacks the synovium, rheumatoid arthritis may occur. Antibodies attack the synovium, leaving it sore and inflamed - the synovium becomes thicker and may eventually invade and destroy cartilage (the stretchy connective tissue between bones) and bone inside the joint. The joint is held together by tendons (tissue that connects bone to muscle) and ligaments (tissue that connects bone and cartilage). These tendons and ligaments weaken and stretch, and the joint eventually loses its shape and configuration. The joint may eventually be completely destroyed. Nobody really knows what starts off this process. Even though infectious agents such as viruses, bacteria, and fungi have long been suspected, none has been proven as the cause. The cause of rheumatoid arthritis is a very active area of worldwide research. It is believed that the tendency to develop rheumatoid arthritis may be genetically inherited. It is also suspected that certain infections or factors in the environment might trigger the activation of the immune system in susceptible individuals. Environmental factors also seem to play some role in causing rheumatoid arthritis. For example, scientists have reported that smoking tobacco increases the risk of developing rheumatoid arthritis.

5. Diagnosis
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In its early stages rheumatoid arthritis may be difficult to diagnose. Its signs and symptoms - especially stiffness and inflammation - are similar to several other conditions. A GP (general practitioner, primary care physician) will carry out a physical examination. The doctor will carefully check the joints to see if there is any swelling (e.g. pain on squeeze test on the knuckles), as well as determining how easily they move. The patient will be asked about symptoms.

The doctor may also order the following tests: Blood tests Erythrocyte sedimentation rate (ESR or sed rate) - this blood test detects and monitors inflammation in the body by measuring the rate at which red blood cells in a test tube separate from blood serum over a set period, becoming sediment in the bottom of the test tube. A high sedimentation rate is linked to more inflammation. In other words, if the red blood cells sink faster to the bottom of the test tube, it could mean that the patient has an inflammatory condition, such as rheumatoid arthritis.

C-reactive protein (CRP) - CRP is produced by the liver. A higher CRP level is linked to the presence of inflammation in the body.

Anemia - a significant proportion of patients with rheumatoid arthritis also have anemia; when not enough oxygen is carried in the blood, because of a lack of red blood cells. If the patient is found to have anemia it does not necessarily mean they have rheumatoid arthritis.

Rheumatoid factor - this blood test determines whether rheumatoid factor (an antibody) is present in the patients blood. The majority of rheumatoid arthritis patients have this abnormal antibody in their bloodstream. During the early stages of the disease it is sometimes difficult to detect rheumatoid factor. As this antibody

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is present in a small proportion of people without rheumatoid arthritis, this test cannot confirm the disease definitively. Imaging scans and X-rays - an X-ray of the patients joints can help the doctor determine what type of arthritis is present. Several X-rays can help track the progression of rheumatoid arthritis in the joints over time.

MRI (magnetic resonance imaging) scans - can help the doctor determine more specifically what damage has been done to a joint. A MRI machine uses a magnetic field and radio waves to create detailed images of the body.

Signs of destruction and inflammation on ultrasonography and magnetic resonance imaging in the second metacarpophalangeal joint in established rheumatoid arthritis. Thin arrows indicate an erosive change; thick arrows indicate synovitis. Ultrasonography (left side of image) in the (a) longitudinal and (b) the
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transverse planes shows both signs of destruction and inflammation. Axial T1weighted magnetic resonance images were obtained (c) before and (d) after contrast administration, also demonstrating synovitis. Additionally, a coronal T1-weighted magnetic resonance image (e) before contrast administration visualizes the same bone erosion as shown in panels c and d. The American College of Rheumatology has developed a system for classifying rheumatoid arthritis that is primarily based upon the X-ray appearance of the joints. This system helps medical professionals classify the severity of rheumatoid arthritis. Stage I

no damage seen on X-rays, although there may be signs of bone thinning

Stage II

on X-ray, evidence of bone thinning around a joint with or without slight bone damage slight cartilage damage possible joint mobility may be limited; no joint deformities observed atrophy of adjacent muscle abnormalities of soft tissue around joint possible

Stage III

on X-ray, evidence of cartilage and bone damage and bone thinning around the joint joint deformity without permanent stiffening or fixation of the joint extensive muscle atrophy abnormalities of soft tissue around joint possible

Stage IV

on X-ray, evidence of cartilage and bone damage and osteoporosis around joint

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joint deformity with permanent fixation of the joint (referred to as ankylosis) extensive muscle atrophy abnormalities of soft tissue around joint possible

Rheumatologists also classify the functional status of people with rheumatoid arthritis as follows:

Class I: completely able to perform usual activities of daily living Class II: able to perform usual self-care and work activities but limited in activities outside of work (such as playing sports, household chores) Class III: able to perform usual self-care activities but limited in work and other activities Class IV: limited in ability to perform usual self-care, work, and other activities Distinguishing rheumatoid arthritis from other medical conditions

Several other medical conditions can resemble RA, and usually need to be distinguished from it at the time of diagnosis:

Crystal induced arthritis (gout, and pseudogout) - usually involves particular joints and can be distinguished with aspiration of joint fluid if in doubt Osteoarthritis - distinguished with X-rays of the affected joints and blood tests Systemic lupus erythematosus (SLE) - distinguished by specific clinical symptoms and blood tests (antibodies against double-stranded DNA) One of the several types of psoriatic arthritis resembles RA - nail changes and skin symptoms distinguish between them Lyme disease causes erosive arthritis and may closely resemble RA - it may be distinguished by blood test in endemic areas Reactive arthritis (previously Reiter's disease) - asymmetrically involves heel, sacroiliac joints, and large joints of the leg. It is usually associated with urethritis, conjunctivitis, iritis, painless buccal ulcers, and keratoderma blennorrhagica. Ankylosing spondylitis - this involves the spine and is usually diagnosed in males, although a RA-like symmetrical small-joint polyarthritis may occur in the context of this condition.

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Hepatitis C - RA-like symmetrical small-joint polyarthritis may occur in the context of this condition. Hepatitis C may also induce Rheumatoid Factor autoantibodies Rarer causes that usually behave differently but may cause joint pains:

Sarcoidosis, amyloidosis, and Whipple's disease can also resemble RA. Hemochromatosis may cause hand joint arthritis. Acute rheumatic fever can be differentiated from RA by a migratory pattern of joint involvement and evidence of antecedent streptococcal infection. Bacterial arthritis (such as streptococcus) is usually asymmetric, while RA usually involves both sides of the body symmetrically. Gonococcal arthritis (another bacterial arthritis) is also initially migratory and can involve tendons around the wrists and ankles.

6. Pathophisiology
The key pieces of evidence relating to pathogenesis are: 1. A genetic link with HLA-DR4 and related allotypes of MHC Class II and the T cellassociated protein PTPN22. 2. A link with cigarette smoking that appears to be causal 3. A dramatic response in many cases to blockade of the cytokine TNF (alpha). 4. A similar dramatic response in many cases to depletion of B lymphocytes, but no comparable response to depletion of T lymphocytes. 5. A more or less random pattern of whether and when predisposed individuals are affected. 6. The presence of autoantibodies to IgGFc, known as rheumatoid factors (RF), and antibodies to citrullinated peptides (ACPA). These data suggest that the disease involves abnormal B cell - T cell interaction, with presentation of antigens by B cells to T cells via HLA-DR eliciting T cell help and consequent production of RF and ACPA. Inflammation is then driven either by B cell or T cell products stimulating release of TNF and other cytokines. The process may be facilitated by an effect of smoking on citrullination but the stochastic (random) epidemiology suggests that the rate limiting step in genesis of disease in
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predisposed individuals may be an inherent stochastic process within the immune response such as immunoglobulin or T cell receptor gene recombination and mutation. (See entry under autoimmunity for general mechanisms). If TNF release is stimulated by B cell products in the form of RF or ACPA containing immune complexes, through activation of immunoglobulin Fc receptors, then RA can be seen as a form of Type III hypersensitivity. If TNF release is stimulated by T cell products such as interleukin-17 it might be considered closer to type IV hypersensitivity although this terminology may be getting somewhat dated and unhelpful. The debate on the relative roles of immune complexes and T cell products in inflammation in RA has continued for 30 years. There is little doubt that both B and T cells are essential to the disease. However, there is good evidence for neither cell being necessary at the site of inflammation. This tends to favour immune complexes (based on antibody synthesised elsewhere) as the initiators, even if not the sole perpetuators of inflammation. Moreover, work by Thurlings and others in Paul-Peter Tak's group and also by Arthur Kavanagh's group suggest that if any immune cells are relevant locally they are the plasma cells, which derive from B cells and produce in bulk the antibodies selected at the B cell stage Although TNF appears to be the dominant, other cytokines (chemical mediators) are likely to be involved in inflammation in RA. Blockade of TNF does not benefit all patients or all tissues (lung disease and nodules may get worse). Blockade of IL-1, IL-15 and IL-6 also have beneficial effects and IL-17 may be important. Constitutional symptoms such as fever, malaise, loss of appetite and weight loss are also caused by cytokines released in to the blood stream. As with most autoimmune diseases, it is important to distinguish between the cause(s) that trigger the process, and those that may permit it to persist and progress.

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Possible infectious triggers It has long been suspected that certain infections could be triggers for this disease. The "mistaken identity" theory suggests that an infection triggers an immune response, leaving behind antibodies that should be specific to that organism. The antibodies are not sufficiently specific, though, and set off an immune attack against part of the host. Because the normal host molecule "looks like" a molecule on the offending organism that triggered the initial immune reaction - this phenomenon is called molecular mimicry. Some infectious organisms suspected of triggering rheumatoid arthritis include Mycoplasma, Erysipelothrix, parvovirus B19 and rubella, but these associations have never been supported in epidemiological studies. Nor has convincing evidence been presented for other types of triggers such as food allergies. Epidemiological studies have confirmed a potential association between RA and two herpesvirus infections: Epstein-Barr virus (EBV) and Human Herpes Virus 6 (HHV-6). Individuals with RA are more likely to exhibit an abnormal immune response to the Epstein-Barr virus. The allele HLA-DRB1*0404 is associated with low frequencies of T cells specific for the EBV glycoprotein 110 and predisposes one to develop RA. Psychological factors There is no evidence that physical and emotional effects or stress could be a trigger for the disease. The many negative findings suggest that either the trigger varies, or that it might in fact be a chance event inherent with the immune response, as suggested by Edwards et al. Continued abnormal immune response The factors that allow an abnormal immune response, once initiated, to become permanent and chronic, are becoming more clearly understood. The genetic association with HLA-DR4, as well as the newly discovered associations with the gene PTPN22 and with two additional genes , all implicate altered thresholds in regulation of the adaptive immune response. It has also become clear from recent studies that these genetic factors may interact with the most clearly defined environmental risk factor for rheumatoid arthritis, namely cigarette smoking .Other environmental factors also appear to modulate the risk of acquiring RA, and hormonal factors in the individual may explain some features of the disease, such as the higher occurrence in women, the not-infrequent onset after child-birth, and the (slight) modulation of disease risk by hormonal medications. Exactly how altered regulatory thresholds allow the triggering of a specific autoimmune response remains uncertain. However, one possibility is that negative feedback mechanisms that normally maintain tolerance of self are overtaken by aberrant positive feedback
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mechanisms for certain antigens such as IgG Fc (bound by RF) and citrullinated fibrinogen (bound by ACPA) (see entry on autoimmunity). Once the abnormal immune response has become established (which may take several years before any symptoms occur), plasma cells derived from B lymphocytes produce rheumatoid factors and ACPA of the IgG and IgM classes in large quantities. These are not deposited in the way that they are in systemic lupus. Rather, they appear to activate macrophages through Fc receptor and perhaps complement binding. This can contribute to inflammation of the synovium, in terms of edema, vasodilation and infiltration by activated T-cells (mainly CD4 in nodular aggregates and CD8 in diffuse infiltrates). Synovial macrophages and dendritic cells further function as antigen presenting cells by expressing MHC class II molecules, leading to an established local immune reaction in the tissue. The disease progresses in concert with formation of granulation tissue at the edges of the synovial lining (pannus) with extensive angiogenesis and production of enzymes that cause tissue damage. Modern pharmacological treatments of RA target these mediators. Once the inflammatory reaction is established, the synovium thickens, the cartilage and the underlying bone begin to disintegrate and evidence of joint destruction accrues.

7. Treatement
There is no known cure for rheumatoid arthritis. To date, the goal of treatment in rheumatoid arthritis is to reduce joint inflammation and pain, maximize joint function, and prevent joint destruction and deformity. Early medical intervention has been shown to be important in improving outcomes. Aggressive management can improve function, stop damage to joints as monitored on X-rays, and prevent work disability. Optimal treatment for the disease involves a combination of medications, rest, joint-strengthening exercises, joint protection, and patient (and family) education. Treatment is customized according to many factors such as disease activity, types of joints involved, general health, age, and patient occupation. Treatment of rheumatoid arthritis is a team effort involving at its core:

The patient The specialist (rheumatologist) The nurse practitioner

Other members of the rheumatology team include the:

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Chiropodist GP (general practitioner) Occupational therapist Orthopaedic surgeon Orthotist Pharmacist Physical therapist (UK: physiotherapist) Podiatrist Primary care nurse

Although not automatically part of every rheumatology team, patients may also benefit from counseling services. Medications Two classes of medications are used in treating rheumatoid arthritis: fastacting "first-line drugs" and slow-acting "second-line drugs" (also referred to as disease-modifying antirheumatic drugs or DMARDs). The first-line drugs, such as aspirin and cortisone (corticosteroids), are used to reduce pain and inflammation. The slow-acting second-line drugs, such as gold, methotrexate, and hydroxychloroquine (Plaquenil), promote disease remission and prevent progressive joint destruction, but they are not anti-inflammatory agents. The degree of destructiveness of rheumatoid arthritis varies among affected individuals. Those with uncommon, less destructive forms of the disease or disease that has quieted after years of activity ("burned out" rheumatoid arthritis) can be managed with rest and pain and anti-inflammatory medications alone. In general, however, function is improved and disability and joint destruction are minimized when the condition is treated earlier with second-line drugs (disease-modifying antirheumatic drugs), even within months of the diagnosis. Most people require more aggressive second-line drugs, such as methotrexate, in addition to anti-inflammatory agents. Sometimes these second-line drugs are used in combination. In some cases with severe joint deformity, surgery may be necessary.

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"First-line" medications Acetylsalicylate (aspirin), naproxen (Naprosyn), ibuprofen (Advil, Medipren, Motrin), and etodolac (Lodine) are examples of nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs are medications that can reduce tissue inflammation, pain, and swelling. NSAIDs are not cortisone. Aspirin, in doses higher than those used in treating headaches and fever, is an effective anti-inflammatory medication for rheumatoid arthritis. Aspirin has been used for joint problems since the ancient Egyptian era. The newer NSAIDs are just as effective as aspirin in reducing inflammation and pain and require fewer dosages per day. Patients' responses to different NSAID medications vary. Therefore, it is not unusual for a doctor to try several NSAID drugs in order to identify the most effective agent with the fewest side effects. The most common side effects of aspirin and other NSAIDs include stomach upset, abdominal pain, ulcers, and even gastrointestinal bleeding. In order to reduce gastrointestinal side effects, NSAIDs are usually taken with food. Additional medications are frequently recommended to protect the stomach from the ulcer effects of NSAIDs. These medications include antacids, sucralfate (Carafate), protonpump inhibitors (Prevacid and others), and misoprostol (Cytotec). Newer NSAIDs include selective Cox-2 inhibitors, such as celecoxib (Celebrex), which offer antiinflammatory effects with less risk of stomach irritation and bleeding risk. Corticosteroid medications can be given orally or injected directly into tissues and joints. They are more potent than NSAIDs in reducing inflammation and in restoring joint mobility and function. Corticosteroids are useful for short periods during severe flares of disease activity or when the disease is not responding to NSAIDs. However, corticosteroids can have serious side effects, especially when given in high doses for long periods of time. These side effects include weight gain, facial puffiness, thinning of the skin and bone, easy bruising, cataracts, risk of infection, muscle wasting, and destruction of large joints, such as the hips. Corticosteroids also carry some increased risk of contracting infections. These side effects can be partially avoided by gradually tapering the doses of corticosteroids as the individual achieves improvement in symptoms. Abruptly discontinuing
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corticosteroids can lead to flares of the disease or other symptoms of corticosteroid withdrawal and is discouraged. Thinning of the bones due to osteoporosis may be prevented by calcium and vitamin D supplements. For further information on corticosteroids, please read the article on prednisone "Second-line" or "slow-acting" drugs (Disease-modifying anti-rheumatic drugs or DMARDs) While "first-line" medications (NSAIDs and corticosteroids) can relieve joint inflammation and pain, they do not necessarily prevent joint destruction or deformity. Rheumatoid arthritis requires medications other than NSAIDs and corticosteroids to stop progressive damage to cartilage, bone, and adjacent soft tissues. The medications needed for ideal management of the disease are also referred to as disease-modifying antirheumatic drugs or DMARDs. They come in a variety of forms and are listed below. These "second-line" or "slow-acting" medicines may take weeks to months to become effective. They are used for long periods of time, even years, at varying doses. If maximally effective, DMARDs can promote remission, thereby retarding the progression of joint destruction and deformity. Sometimes a number of DMARD second-line medications are used together as combination therapy. As with the first-line medications, the doctor may need to try different second-line medications before treatment is optimal. Recent research suggests that patients who respond to a DMARD with control of the rheumatoid disease may actually decrease the known risk (small but real) of lymphoma (cancer of lymph nodes) that exists from simply having rheumatoid arthritis. The various available DMARDs are reviewed next. Hydroxychloroquine (Plaquenil) is related to quinine and is also used in the treatment of malaria. It is used over long periods for the treatment of rheumatoid arthritis. Possible side effects include upset stomach, skin rashes, muscle weakness, and vision changes. Even though vision changes are rare, people taking Plaquenil should be monitored by an eye doctor (ophthalmologist). Sulfasalazine (Azulfidine) is an oral medication traditionally used in the treatment of mild to moderately severe inflammatory bowel diseases, such as ulcerative colitis and Crohn's colitis. Azulfidine is used to treat rheumatoid arthritis in combination with anti-inflammatory medications. Azulfidine is generally well tolerated. Common side effects include rash and upset stomach. Because Azulfidine is made up of sulfa and salicylate compounds, it should be avoided by people with known sulfa allergies. Methotrexate has gained popularity among doctors as an initial second-line drug because of both its effectiveness and relatively infrequent side effects. It also has an advantage in dose flexibility (dosages can be adjusted according to needs). Methotrexate is an immune-suppression drug. It can affect the bone marrow and the
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liver, even rarely causing cirrhosis. All people taking methotrexate require regular blood tests to monitor blood counts and liver function. Gold salts have been used to treat rheumatoid arthritis throughout most of the past century. Gold thioglucose (Solganal) and gold thiomalate (Myochrysine) are given by injection, initially on a weekly basis, for months to years. Oral gold, auranofin (Ridaura), was introduced in the 1980s. Side effects of gold (oral and injectable) include skin rash, mouth sores, kidney damage with leakage of protein in the urine, and bone marrow damage with anemia and low white cell count. Those receiving gold treatment are regularly monitored with blood and urine tests. Oral gold can cause diarrhea. These gold drugs have lost favor because of the availability of more effective treatments, and many companies no longer manufacture them. D-penicillamine (Depen, Cuprimine) can be helpful in selected cases of progressive forms of rheumatoid arthritis. Side effects are similar to those of gold. They include fever, chills, mouth sores, a metallic taste in the mouth, skin rash, kidney and bone marrow damage, stomach upset, and easy bruising. People taking this medication require routine blood and urine tests. D-penicillamine can rarely cause symptoms of other autoimmune diseases and is no longer commonly used for the treatment of rheumatoid arthritis. Immunosuppressive medicines are powerful medications that suppress the body's immune system. A number of immunosuppressive drugs are used to treat rheumatoid arthritis. They include methotrexate (Rheumatrex, Trexall) as described above, azathioprine (Imuran), cyclophosphamide (Cytoxan), chlorambucil (Leukeran), and cyclosporine (Sandimmune). Because of potentially serious side effects, immunosuppressive medicines (other than methotrexate) are generally reserved for those who have very aggressive disease or those with serious complications of rheumatoid inflammation, such as blood vessel inflammation (vasculitis). The exception is methotrexate, which is not frequently associated with serious side effects and can be carefully monitored with blood testing. Methotrexate has become a preferred second-line medication as a result. Immunosuppressive medications can depress bone-marrow function and cause anemia, a low white cell count, and low platelet counts. A low white count can increase the risk of infections, while a low platelet count can increase the risk of bleeding. Methotrexate rarely can lead to liver cirrhosis and allergic reactions in the lung. Cyclosporine can cause kidney damage and high blood pressure. Because of potentially serious side effects, immunosuppressive medications are used in low doses, usually in combination with anti-inflammatory agents.

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Newer treatments Newer "second-line" drugs for the treatment of rheumatoid arthritis include leflunomide (Arava) and the "biologic" medications etanercept (Enbrel), infliximab (Remicade), anakinra (Kineret), adalimumab (Humira), rituximab (Rituxan), abatacept (Orencia), golimumab (Simponi), certolizumab pegol (Cimzia), and tocilizumab (Actemra). Each of these medications can increase the risk for infections, and the development of any infections should be reported to the health-care professional when taking these newer second-line drugs. Leflunomide (Arava) is available to relieve the symptoms and halt the progression of the disease. It seems to work by blocking the action of an important enzyme that has a role in immune activation. Arava can cause liver disease, diarrhea, hair loss, and/or rash in some people. It should not be taken just before or during pregnancy because of possible birth defects and is generally avoided in women who might become pregnant. Newer medications that represent a novel approach to the treatment of rheumatoid arthritis are products of modern biotechnology. These are referred to as the biologic medications or biological response modifiers. In comparison with traditional DMARDs, the biologic medications have a much more rapid onset of action and can have powerful effects on stopping progressive joint damage. In general, their methods of action are also more directed, defined, and targeted. Etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol are biologic medications that intercept a messenger protein in the joints (tumor necrosis factor or TNF) that promotes inflammation of the joints in rheumatoid arthritis. These TNF-blockers intercept TNF before it can act on its natural receptor to "switch on" the process of inflammation. This effectively blocks the TNF inflammation messenger from recruiting the cells of inflammation. Symptoms can be significantly, and often rapidly, improved in those using these drugs. Etanercept must be injected subcutaneously once or twice a week. Infliximab is given by infusion directly into a vein (intravenously). Adalimumab is injected subcutaneously either every other week or weekly. Golimumab is injected subcutaneously on a monthly basis. Certolizumab pegol is injected subcutaneously every two to four weeks. Each of these medications is being evaluated by doctors in practice to determine what role they may have in treating patients in various stages of rheumatoid arthritis. Research has shown that biological response modifiers also prevent the progressive joint destruction of rheumatoid arthritis. They are currently recommended for use after other second-line medications have not been effective. The biological response modifiers (TNFinhibitors) are expensive treatments. They are also frequently used in combination with methotrexate and other DMARDs. Furthermore, it should be noted that the TNFblocking biologics all are more effective when combined with methotrexate. These medications should be avoided by persons with significant congestive heart failure or
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demyelinating diseases (such as multiple sclerosis) because they can worsen these conditions. Anakinra is another biologic treatment that is used to treat moderate to severe rheumatoid arthritis. Anakinra works by binding to a cell messenger protein (IL-1, a proinflammatory cytokine). Anakinra is injected under the skin daily. Anakinra can be used alone or with other DMARDs. The response rate of anakinra does not seem to be as high as with other biologic medications. Rituximab (rituxan) is an antibody that was first used to treat lymphoma, a cancer of the lymph nodes. Rituxan can be effective in treating autoimmune diseases like rheumatoid arthritis because it depletes B-cells, which are important cells of inflammation and in the production of abnormal antibodies that are common in these conditions. Rituxan is now available to treat moderate to severely active rheumatoid arthritis in patients who have failed treatment with the TNF-blocking biologics. Preliminary studies have shown that Rituxan was also found to be beneficial in treating severe rheumatoid arthritis complicated by blood vessel inflammation (vasculitis) and cryoglobulinemia. Rituximab (Rituxan) is an intravenous infusion given in two doses, two weeks apart, approximately every six months. Abatacept (Orencia) is a biologic medication that blocks T-cell activation. Orencia is now available to treat adult patients who have failed treatment with a traditional DMARD or TNF-blocking biologic medication. Abatacept (Orencia) is an intravenous infusion given monthly. Tocilizumab (Actemra) has recently been approved for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more tumor necrosis factor (TNF) antagonist therapies. Tocilizumab (Actemra) is the first approved biologic medication that blocks interleukin-6 (IL-6), which is a chemical messenger of the inflammation of rheumatoid arthritis. Tocilizumab (Actemra) is an intravenous infusion given monthly. While biologic medications are often combined with traditional DMARDs in the treatment of rheumatoid arthritis, they are generally not used with other biologic medications because of the unacceptable risk for serious infections. The Prosorba column therapy involves pumping blood drawn from a vein in the arm into an apheresis machine, or cell separator. This machine separates the liquid part of the blood (the plasma) from the blood cells. The Prosorba column is a plastic cylinder about the size of a coffee mug that contains a sand-like substance coated with a special material called Protein A. Protein A is unique in that it binds unwanted antibodies from the blood that promote the arthritis. The Prosorba column works to counter the effect of these harmful antibodies. The Prosorba column is indicated to reduce the signs and symptoms of moderate to severe rheumatoid
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arthritis in adult patients with long-standing disease who have failed or are intolerant to disease-modifying antirheumatic drugs (DMARDs). The exact role of this treatment is being evaluated by doctors, and it is not commonly used currently. Other treatments There is no special diet for rheumatoid arthritis. One hundred years ago, it was touted that "night-shade" foods, such as tomatoes, would aggravate rheumatoid arthritis. This is no longer accepted as true. Fish oil may have anti-inflammatory beneficial effects, but so far this has only been shown in laboratory experiments studying inflammatory cells. Likewise, the benefits of cartilage preparations remain unproven. Symptomatic pain relief can often be achieved with oral acetaminophen (Tylenol) or over-the-counter topical preparations, which are rubbed into the skin. Antibiotics, in particular the tetracycline drug minocycline (Minocin), have been tried for rheumatoid arthritis recently in clinical trials. Early results have demonstrated mild to moderate improvement in the symptoms of arthritis. Minocycline has been shown to impede important mediator enzymes of tissue destruction, called metalloproteinases, in the laboratory as well as in humans. The areas of the body other than the joints that are affected by rheumatoid inflammation are treated individually. Sjogren's syndrome (described above, see symptoms) can be helped by artificial tears and humidifying rooms of the home or office. Medicated eyedrops, cortisporine ophthalmic drops (Restasis), are also available to help the dry eyes in those affected. Regular eye checkups and early antibiotic treatment for infection of the eyes are important. Inflammation of the tendons (tendinitis), bursae (bursitis), and rheumatoid nodules can be injected with cortisone. Inflammation of the lining of the heart and/or lungs may require high doses of oral cortisone. Proper, regular exercise is important in maintaining joint mobility and in strengthening the muscles around the joints. Swimming is particularly helpful because it allows exercise with minimal stress on the joints. Physical and occupational therapists are trained to provide specific exercise instructions and can offer splinting supports. For example, wrist and finger splints can be helpful in reducing inflammation and maintaining joint alignment. Devices such as canes, toilet seat raisers, and jar grippers can assist in the activities of daily living. Heat and cold applications are modalities that can ease symptoms before and after exercise. Surgery may be recommended to restore joint mobility or repair damaged joints. Doctors who specialize in joint surgery are orthopedic surgeons. The types of joint surgery range from arthroscopy to partial and complete replacement of the joint. Arthroscopy is a surgical technique whereby a doctor inserts a tube-like instrument into the joint to see and repair abnormal tissues.
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Total joint replacement is a surgical procedure whereby a destroyed joint is replaced with artificial materials. For example, the small joints of the hand can be replaced with plastic material. Large joints, such as the hips or knees, are replaced with metals. Finally, minimizing emotional stress can help improve the overall health in people with rheumatoid arthritis. Support and extracurricular groups provide those with rheumatoid arthritis time to discuss their problems with others and learn more about their illness. Future treatments Scientists throughout the world are studying many promising areas of new treatment approaches for rheumatoid arthritis. These areas include treatments that block the action of the special inflammation factors, such as tumor necrosis factor (TNFalpha) and interleukin-1 (IL-1), as described above. Many other drugs are being developed that act against certain critical white blood cells involved in rheumatoid inflammation. Also, new NSAIDs with mechanisms of action that are different from current drugs are on the horizon. Better methods of more accurately defining which patients are more likely to develop more aggressive disease are becoming available. Recent antibody research has found that the presence of citrulline antibodies in the blood (see above, in diagnosis) has been associated with a greater tendency toward more destructive forms of rheumatoid arthritis. Studies involving various types of the connective tissue collagen are in progress and show encouraging signs of reducing rheumatoid disease activity. Finally, genetic research and engineering is likely to bring forth many new avenues for earlier diagnosis and accurate treatment in the near future. Gene profiling, also known as gene array analysis, is being identified as a helpful method of defining which people will respond to which medications. Studies are under way that are using gene array analysis to determine which patients will be at more risk for more aggressive disease. This is all occurring because of improvements in technology. We are at the threshold of tremendous improvements in the way rheumatoid arthritis is managed. Lifestyle When a flare-up occurs the patient should rest as much as possible. Exerting very swollen and painful joints frequently results in worsening symptoms. Generally, when flare ups are not present, the patient should exercise regularly; this will help their general health and mobility. If rheumatoid arthritis has caused muscles around the joints to become weak, exercise will help strengthen
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them. Exercises that do not strain the joints are best, such as swimming. A qualified physical therapist can teach the patient exercises that improve mobility.

Applying heat or cold - tense and painful muscles may benefit from the application of heat. A 15 minute hot bath or shower may help. Some people find that using a hot pack or an electric heating pad (set at lowest setting) helps. Pain may be dulled with cold treatment. The numbing effect of cold may also decrease muscle spasms. Patients with poor circulation or numbness should not use cold treatments. Examples of cold treatment include cold packs, soaking the affected joint in cold water, and ice massage. Some people benefit from placing the affected joints in warm water for a few minutes, followed by cool water for one minute; repeating the cycle for about 30 minutes, ending with a warm water soak.

Relaxation - finding ways of alleviating mental stress may help control pain. Examples include hypnosis, guided imagery, deep breathing and muscle relaxation.

Complementary therapies - these are commonly used by people with rheumatoid arthritis. Few studies have been carried out on how effective they are. Examples include:
o o o o o

Acupuncture Chiropractic Electrotherapy Hydrotherapy Massage

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Nutritional supplements - for example, fish oil, glucosamine sulphate and chondriotin.
o o

Osteopathy

8. Right price of the prescription

Prescription medication is an expense that many families cannot afford. If there are some persons that dont have an insurance plan that will cover their prescriptions and are a low-income family, then they are not alone. Fortunately, there are some programs available to assist them with their medications, but finding them can be a struggle. Here are a few options that could help this people afford their medicines: First of all, patients should communicate with their doctor on some aspects: if they are without prescription coverage their doctor can truly be their greatest alley and can help them in a variety of ways. If their doctor starts them on a new prescription drug, there are a series of questions they can ask to make sure they get the best deal. Patients should begin by asking their doctor if he has any free samples they can have, to try the medication. Explain their insurance situation and see if their doctor will offer them the medication for free. If their doctor does not have any samples for them to take home, they should ask him if he could call the drug representative from that company to send some samples to them. These drug representatives stop in regularly to restock their supply and are happy to get more clients under their belt. This can be a win-win situation for all the parties involved. If samples are unavailable, they should ask their doctor if they can have a "trial prescription," so that they can buy fewer of the tablets at first. This can be a good way to find out if a medication will work for them and also to see if they can tolerate any nasty side effects. If the drug does not work for them, they will not have invested in a month's supply that they will be unable to use. There are also specific questions that patients can ask about the medications they are taking. For example, to ask their doctor if there is a generic equivalent to the medication they are taking because they are exploring less expensive alternatives. If there are no generic equivalents to this medication, they can also ask about over-the-counter (OTC) medications. Sometimes, there are OTC medications patients can take that will achieve the same results as the actual prescription drug. Another question patients can ask is if they could buy a double dosage of the medication, in pill form, and split the tablets in half for their regular dosage. There are many prescriptions that can be purchased and then can easily be halved. This can result in a fifty-percent savings on patients medication.

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Their doctor may also know about specific aid from the drug manufacturer. Many prescription companies have programs to give medication to patients who have no way to pay for their prescription drugs. Programs vary from manufacturer to manufacturer, but all require the doctor to submit the application for the patients. Patients should explore this route with their doctor and see what the company requirements are and if this type of aid is available for them. Finally, patients should check in yearly with their doctor to see if cheaper versions of their medications have becomeavailable. Another alternative to get cheaper treatment is to try to buy the medications online: online stores can offer a lot of savings for their customers, particularly Canadian pharmacies where drug prices are much cheaper (savings of up to half on many prescriptions). Patients must make sure that they research the company well to ensure that the company is not a fake. Examples of things to look for are a toll free number, real operators who answer their phone, a physical company address, and a secure website to do their shopping. They will also want to make sure the pharmacy is approved by the organization that governs the state/country where the pharmacy is located. State assistance, can be a real help somtimes: make sure to investigate what patients state offers in assisting with the cost of his/her prescription drugs. These programs are typically available to the elderly, disabled, and low-income families. People can obtain information about these programs through their state's website or by calling the office of their state senator or representative. Patients having cost problems with their medication, and should not be afraid or ashamed to ask their doctor, the drug company, or their pharmacy about assistance programs. There are great savings in asking and exploring for cheaper alternatives.

9. Prognosis
It isn't possible to predict exactly how rheumatoid arthritis will progress for each patient. The inflammation in rheumatoid arthritis damages the cartilage and sometimes the bone itself. It may also damage any ligaments within the joints. Inflammation causes the tough capsules that surround joints to stretch. When the swelling goes down the capsule remains stretched and can no longer hold the joint in its proper position. As a result the joint becomes unstable and this can lead to deformities of the joints. Some damage is done every time the joints are inflamed and once joints are damaged they don't heal properly. This is why most treatment aims to prevent joint damage by minimizing inflammation as early as possible in the disease.
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Inflammation can sometimes affect the blood vessels, the lungs and, rarely, the membrane around the heart. People with rheumatoid arthritis are also more at risk of heart attack and strokes. This seems to be caused by the inflammation and the risk is probably reduced by controlling the disease. Most people follow a pattern of flare-ups with periods of months or even years when there is little inflammation. There's likely to be some damage in a number of joints. People whose disease follows this pattern are likely to have some problems with their joints and may have to change their activities a little, but overall probably won't notice too great an impact on their lives. Some people, maybe as many as 1 in 5, always have very mild rheumatoid arthritis that causes few problems. People in this group will usually have only minor damage to a small number of joints. A few people, no more than 1 in 20, will have rheumatoid arthritis that becomes progressively worse, often quite quickly. These individuals are likely to have severe damage to many of their joints, and are also more likely to have inflammation in other parts of the body besides their joints. The course of the disease varies greatly. Around 20%-30% will have subcutaneous nodules (known as rheumatoid nodules); this is associated with a poor prognosis. Disability

Daily living activities are impaired in most individuals. After 5 years of disease, approximately 33% of sufferers will not be working. After 10 years, approximately half will have substantial functional disability. Prognostic factors

Poor prognostic factors include persistent synovitis, early erosive disease, extra-articular findings (including subcutaneous rheumatoid nodules), positive serum RF findings, positive serum anti-CCP autoantibodies, carriership of HLA-DR4 "Shared Epitope" alleles, family history of RA, poor functional status, socioeconomic factors, elevated acute phase response (erythrocyte sedimentation rate [ESR], Creactive protein [CRP]), and increased clinical severity. Mortality Estimates of the life-shortening effect of RA vary; most sources cite a lifespan reduction of 5 to 10 years. According to the UK's National Rheumatoid Arthritis Society, "Young age at onset, long disease duration, the concurrent presence of
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other health problems (called co-morbidity), and characteristics of severe RA such as poor functional ability or overall health status, a lot of joint damage on x-rays, the need for hospitalisation or involvement of organs other than the joints have been shown to associate with higher mortality". Positive responses to treatment may indicate a better prognosis. A 2005 study by the Mayo Clinic noted that RA sufferers suffer a doubled risk of heart disease, independent of other risk factors such as diabetes, alcohol abuse, and elevated cholesterol, blood pressure and body mass index. The mechanism by which RA causes this increased risk remains unknown; the presence of chronic inflammation has been proposed as a contributing factor.

10. Prevalence of arthritis

Disability-adjusted life year for rheumatoid arthritis per 100,000 inhabitants in 2004. no data 100-110
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less than 40 40-50 110-120 120-130

50-60 60-70 70-80 130-140 more than 140

80-90

90-100

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The incidence of RA is in the region of 3 cases per 10,000 population per annum. Onset is uncommon under the age of 15 and from then on the incidence rises with age until the age of 80. The prevalence rate is 1%, with women affected three to five times as often as men. It is 4 times more common in smokers than nonsmokers. A study in 2010 found that those who drank modest amounts of alcohol regularly were four times less likely to get rheumatoid arthritis than those who never drank. Some Native American groups have higher prevalence rates (5-6%) and people from the Caribbean region have lower prevalence rates. First-degree relatives prevalence rate is 2-3% and disease genetic concordance in monozygotic twins is approximately 15-20%. It is strongly associated with the inherited tissue type Major histocompatibility complex (MHC) antigen HLA-DR4 (most specifically DR0401 and 0404) hence family history is an important risk factor. Rheumatoid arthritis affects women three times more often than men, and it can first develop at any age. The risk of first developing the disease (the disease incidence) appears to be greatest for women between 40 and 50 years of age, and for men somewhat later. RA is a chronic disease, and although rarely, a spontaneous remission may occur, the natural course is almost invariably one of persistent symptoms, waxing and waning in intensity, and a progressive deterioration of joint structures leading to deformations and disability.

11. Travel tips for people with Rheumatoid arthritis

Some people with arthritis develop a reluctance to try new things or experience activities that their physical limitations might make more of a challenge. For example, people with arthritis often become reluctant to travel. With forethought and careful planning, people with arthritis can travel too. If traveling with arthritis is a concern, it is wise to take short trips at first and have someone along who could be of assistance if necessary. As short trips are accomplished and enjoyed successfully, longer trips can be planned with confidence. The short trips allow them to experience traveling and at the same time learn what difficulties occur that can be either avoided or planned for. Make their needs known If a travel agent is utilized when planning more extensive trips, patients should be specific about their restrictions and requirements. Do not assume that all will be well and all will be understood. They must make their needs known. Ask the travel agent questions that will solve their concerns. Ask about:
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walking distance the amount of stairs location of elevators hand rails in tubs and near the toilet elevated toilet seats wheelchair accessibility availability of room service at destination

The travel agent has the information and ability to put persons in a setting that will address their needs. Plan Ahead Planning ahead is the key to successful travelling. Whatever they need at home they will likely need as they travel. It is important to make sure that patients pack enough medications to last the entire trip. It is wise to get extra prescriptions from the doctor also, in case they are gone longer than expected. Since luggage can be lost, it is not wise to pack all the medications in his/her luggage. Keep some medications in another handbag. When packing, patient should pack light, but bring all the important items that make their arthritis more manageable. Along with their medications,they should bring their doctor's name and phone number in case they unexpectedly need him or his advice. Remember to bring any assistive devices / arthritis aids that thet use daily, such as: raised toilet seat long handled brushes or reachers special pillows heating pads

Sunscreen, a hat, and comfortable clothing also are important items. Patients should use lightweight luggage with wheels and/or shoulder straps to make it easier to transport. When possible ask porters to carry luggage or use luggage carts if available. Pace theirselves The most important tip for enjoying a vacation is to begin the trip well rested and allow time at their destination for rest. Prioritize activities and do not overdo by trying to do too much in one day. It is a good idea to alternate active and restful
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periods. However, even though pacing theirselves is important, remember to also try new things. Allow theirselves the chance to try things they may think they can no longer do. They may surprise theirselves. Achieving new things or accomplishing what they thought they couldn't do boosts confidence enormously. More Travel Tips
Tips for air travel: Reserve seats ahead and make requests for any special

needs; allow extra time to get to and through the airport; request airport wheelchair if patient has difficulty walking; curbside check-in saves on luggage carrying and long lines; check all luggage through to final destination.
Tips for car travel: Keep medications, snacks, maps, emergency kit, and first

aid kit in the car. Consider having a cellular phone in case of emergency. For a most comfortable ride, bring along pillows, push seat back to afford as much leg room as possible, and stop to stretch every couple of hours or as needed.
Tips for train travel: Once again, make reservations early and request

special assistance. Request wheelchair if needed. Inquire if restrooms, bedrooms, and aisles are easily accessible. Inquire if train personnel will be able to offer assistance.
Tips for bus travel: Ask if assistance is available; schedule trips when fewer

people are traveling such as mid-week; avoid too many transfers to other buses; bring pillow or snacks along for a more comfortable trip.
Tips for cruise ship travel: Ask for a cabin near the elevator and a table in

the dining area near the entrance; choose cruise with fewer stops to minimize getting on and off the ship; inquire if ship is wheelchair accessible; take motion sickness medication prescribed by doctor.

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12. What patients need to know when traveling with medications

When away from home for a period of time or when traveling, it's important to manage medications appropriately. These tips will help patients avoid problems with medication when traveling. Determine what medications they will need to take with them when traveling. Decide if they have enough pills to last through their trip or if they need refills before they go. It's best to get all of their refills before they travel. If it's too early to get a refill before they leave but they will need more medication while they are gone, patients should ask their doctor and pharmacist if they will refill early as a one-time special consideration because they are traveling. Be aware that large, national pharmacy chains allow patients to refill wherever they are nationwide because their computers are linked. Before a patient travels, it's important to know how many pills he/she has, how many he/she will need, if he/she can refill early, or if he/she can refill while away. Keep their medications with them in a large tote bag or in carry-on luggage. It's very important that patients keep their medications with them when traveling. They should not pack medications in luggage which will be checked-in and don't stick their medications in another person's suitcase. The reason is obvious -loss prevention. Besides minimizing the risk of losing their medications by keeping those with them, it's easier to access their medications if they should need them. Patients should also pack extra medication in case of delays. It's best to have an additional week of medication on-hand. Make sure all prescription medications have the name of the drug, the name of the doctor, and patients name on the label. In times of heightened security, patients may need to prove that the name on their prescription bottles matches their identification: -

Medications must be labeled so they are identifiable. Medications in daily dosage containers are allowed through the checkpoint once they been screened. Medication and related supplies are normally X-rayed. Transport Security Administration allows patients the option of requesting a visual inspection of their medication and supplies which they must arrange before the screening process begins.

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If patients need to pack syringes, they should carry a copy of the prescription for the syringes and other information proving medical necessity. Some travelers fear that they won't be able to get through security with needles or syringes. By carrying information which proves the syringes were prescribed for a medical reason and information which shows it was prescribed for them and by whom, they should avoid any problems. Be aware of optimal storage requirements for the medications they will be taking on their trip. All medications are labeled with an optimal range of temperatures for storage. If the patient is traveling to an area which is hot, humid, or sunny, he/she musnt keep medications in direct sunlight or near the bathroom where humidity is higher. Storing in the glove compartment of their car where heat builds up is also a bad idea. They should try to keep medications in a cool, dry, dark environment when possible. Some medications require refrigeration when stored. For example Enbrel must be refrigerated and kept cool at 36 to 46 F. Enbrel must not be frozen. The manufacturer of Enbrel recommends carrying it in a small, insulated cooler bag with an ice pack for short periods of time. When traveling for more than a few hours, Enbrel should be wrapped in bubble wrap and placed in a travel cooler, then packed with ice. Put a thermometer in the cooler and check it every few hours, adding ice as necessary to maintain the optimal temperature. Some hotels may have a small refrigerator available on request when you reach your destination. If any of patients medications cause him/her to be sensitive to the sun, they should be prepared. Many medications cause photosensitivity or sun-sensitivity. Patient should know if any of the medications he/she takes has that as a possible side effect. If any of their medications can cause sun sensitivity, talk to their doctor and pharmacist about how to best prepare. Find out the best skin protection factor for them, and buy sun screen with the appropriate SPF. Consider clothing which will cover patient and protect exposed skin from the sun. A wide-brim hat, extra towels, or pillows may help protect their skin. Discuss with their doctor how to adjust medication for different time zones. Patients usual medication schedule may have to be altered if he/she will be traveling through different time zones. Discuss their travel plans with their doctor and get advice on when to change the time they take their pills, especially on the day of travel. It's important that patient doesnt skip doses nor takes too much medication. Doctor can help patient to make necessary but temporary changes to his/her medication schedule based on whether he/she will be losing or gaining time as he/she travels.
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Anticipate any written prescriptions the patient will need to have on hand while traveling. It may be a good idea to have a standby prescription in hand for certain drugs which the patient may possibly need when traveling. A prescription for an antibiotic, a cough medication, or a Medrol dose pack may come in handy if someone gets sick or have a flare of arthritis symptoms while traveling. It may be easier than trying to find a doctor in an unfamiliar city. Be sure the patient carries all pertinent information related to his/her medical care. Patients should carry a list of all of their current medications and a list of contact information for their primary care physician and rheumatologist. Have their doctor provide this on their letterhead if possible. Carry the name, location, and phone number of their local pharmacy. If questions arise about their medications, they will be glad to have the contact information close by.

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13. References
1. Majithia V, Geraci SA (2007). "Rheumatoid arthritis: diagnosis and

management". Am. J. Med.

2. Turesson C, O'Fallon WM, Crowson CS, Gabriel SE, Matteson EL (2003).

"Extra-articular disease manifestations in rheumatoid arthritis: incidence trends and risk factors over 46 years" 3. Wolfe F, Mitchell DM, Sibley JT, et al (April 1994). "The mortality of rheumatoid arthritis". 4. Avia-Zubieta JA, Choi HK, Sadatsafavi M et al (Dec 2008). "Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies". 5. Gupta A and Fomberstein B (August 2009). "Evaluating cardiovascular risk in rheumatoid arthritis". Journal of Musculoskeletal Medicine 26 6. Westwood OM, Nelson PN, Hay FC (April 2006). "Rheumatoid factors: what's new?"Rheumatology (Oxford) http://rheumatology.oxfordjournals.org/cgi/content/full/45/4/379. 7. Nishimura K, Sugiyama D, Kogata Y, et al (June 2007). "Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody and rheumatoid factor for rheumatoid arthritis" (PDF) http://acr.confex.com/acr/2008/webprogram/Paper2009.html. 8. "National Rheumatoid Arthritis Society (NRAS)". http://www.rheumatoid.org.uk/. NRAS - National Rheumatoid Arthritis Society 9. "Within Our Reach: Finding a Cure for Rheumatoid Arthritis". American College of Rheumatology Research and Education Foundation. http://www.withinourreach.info. 10. Rheumatoid arthritis at the Open Directory Project 11. "Rheumatoid Arthritis". Arthritis Foundation. http://www.arthritis.org/conditions/DiseaseCenter/RA/default.asp. 12. "Rheumatoid Arthritis". Arthritis Research Campaign. http://www.arc.org.uk/arthinfo/patpubs/6033/6033.asp. 13. Charles Weber. "History of rheumatoid arthritis". http://charles_w.tripod.com/arthritis2.html. 14. "Rheumatoid Arthritis Details". NIH Senior Health. http://nihseniorhealth.gov/rheumatoidarthritis/toc.html.
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Chapter I Rheumatoid arthritis 15. "National Institute of Arthritis and Musculoskeletal and Skin Diseases".

National Institute of Arthritis and Musculoskeletal and Skin Diseases. http://www.niams.nih.gov/. 16. "Arthritis Related Statistics". Centers for Disease Control and Prevention (CDC). http://www.cdc.gov/arthritis/data_statistics/arthritis_related_stats.htm. 17. "Rheumatoid Arthritis". MedlinePlus. http://www.nlm.nih.gov/medlineplus/rheumatoidarthritis.html.

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