Rheumatoid Arthritis Essentials:
RA is one of the most delibitating autoimmune disease in the over 100 different types of rheumatic diseases in the arthritis family-group of musculoskeletal diseases. Rheumatoid arthritis is one of the most misrepresented and misquoted rheumatic disease.There are basically,mild,moderate,severe and,RA that charachterizes stiffness as the main feature. Each type affects patients in different forms and effects. That also applies to therapy. One medication will be efficacious for one and do nothing for another patient.
Educate yourself ! Get control of your disease ! Avoid "hear- say" advice. Distinguish truth from fiction. Avoid advice about Aunt Martha's arthritis and how Cousin Jane coped with her condition.
RA affects 1% of the population in the U.S.A.,this low prevelance means that many physicians and health care workers are unfamiliar with the different types and effects of rheumatoid arthritis that exists. RA is a systemic disease meaning that if your left side of the body e.g., hand/knee is affected then it is more then likely that your right hand/knee will be also affected. Disease symptoms can occur suddenly or develop gradually. Full symptoms may not occur at onset. Remission is rare but when it occurs it is usually,more associated with the milder form of disease. There are periods when the disease is less active and episodes of "flare ups" where disease activity is more pronounced.
There are many articles written about rheumatoid arthritis but be aware of the accuracy of information provided. Search engines use"keywords" Most popular sites is often the incorrect avenue to pursue. Since their are over 100 different "arthritis" or rheumatic disease groups in the family tree.
Advice is cheap and abundant but the wrong advice can be costly. Do not always believe what you hear! There are many family physicians experienced in the management and treatment of rheumatoid arthritis but there are many who are not and this relates more to medications with some side effects. There are nurses with advanced training in the management of rheumatic diseases but there are many who have had little or no experience and training with the different types of rheumatic diseases.
There are pain syndromes like fibromyalgia (FM)-chronic fatigue syndrome (CFS). Most people do not associate gout with arthritis or realize tuberculosis is associated with infectious arthritis. Lupus has many different types and some forms of the disease can be life-threatening while some types can last for a short period and quickly go into remission, with no lasting effect,some people don't even have to take medications. Others think the only arthritis is degenerative osteoarthritis. "Live long enough and most people will have some form of arthritis."
The typical case of rheumatoid arthritis begins insidiously, with the slow development of signs and symptoms over weeks to months. Often the patient first notices stiffness in one or more joints, usually accompanied by pain on movement and by tenderness in the joint. The number of joints involved is highly variable, but almost always the process is eventually polyarticular, involving five or more joints. Rheumatoid arthritis is an additive polyarthritis, with the sequential addition of involved joints, in contrast to the migratory or evanescent arthritis of systemic lupus erythematosus or the episodic arthritis of gout. Occasionally, patients experience an explosive polyarticular onset occurring over 24 to 48 hours.
The joints involved most often are the proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints of the hands, the wrists (particularly at the ulnar-styloid articulation), shoulders, elbows, knees, ankles, and metatarsophalangeal (MTP) joints. The distal interphalangeal (DIP) joints are generally spared. The spine except the atlanto-axial articulation in late disease is never affected.
Morning stiffness, persisting more than one hour but often lasting several hours, may be a feature of any inflammatory arthritis but is especially characteristic of rheumatoid arthritis. Its duration is a useful gauge of the inflammatory activity of the disease. Similar stiffness can occur after long periods of sitting or inactivity (gel phenomenon). In contrast, patients with degenerative arthritis complain of stiffness lasting but a few minutes.
Nonspecific systemic symptoms primarily fatigue, malaise, and depression, may commonly precede other symptoms of the disease by weeks to months. Patients complain of severe fatigue 4 to 6 hours after wakening. Fever occasionally occurs and is almost always low grade (37° to 38°C; 99° to 100°F). A higher fever suggests another illness, and infectious causes must be considered.
It is typical of patients with rheumatoid arthritis that their symptoms wax and wane often making diagnosis and treatment decisions difficult. Atypical presentations include intermittent joint inflammation that can be confused with gout or pseudogout, proximal muscle pain and tenderness mimicking polymyalgia rheumatica or diffuse musculoskeletal pain seen in fibromyalgia
Symmetric joint swelling, although not invariable, is characteristic of rheumatoid arthritis. Careful palpation of the joints can help to distinguish the swelling of joint inflammation from the bony enlargement seen in osteoarthritis. Fusiform swelling of the PIP joints of the hands is a common early finding. MCP, wrists, elbows, knees, ankles and MTP are other joints commonly affected where swelling is easily detected. In contrast to gout or septic arthritis, redness of affected joints is not a prominent feature of rheumatoid arthritis. Pain on passive motion is the most sensitive test for joint inflammation. Occasionally inflamed joints will feel warm to the touch. Inflammation, structural deformity, or both may limit the range of motion of the joint. To institute proper therapy, it is important to determine which of these processes is the major factor limiting joint function.
Permanent deformity is an unwanted result of the inflammatory process. Persistent tenosynovitis and synovitis leads to the formation of synovial cysts and to displaced or ruptured tendons. Extensor tendon rupture at the dorsum of the hand is a common and disabling problem.
Although the joints are almost always the principal focus of the rheumatoid arthritis, other organ systems may also be involved. Extra-articular manifestations of rheumatoid arthritis occur most often in seropositive patients with more severe joint disease. Interestingly, extra-articular manifestations can occur in later stages of the disease when there is little active synovitis ("burnt-out" disease). In contrast to the predilection of rheumatoid arthritis for women, extra-articular manifestations of the disease are more common in men.
Rheumatoid Nodules: The subcutaneous nodule is the most characteristic extra-articular lesion of the disease. Nodules occur in 20 to 30% of cases, almost exclusively in seropositive patients. They are located most commonly on the extensor surfaces of the arms and elbows but are also prone to develop at pressure points on the feet and knees. Rarely, nodules may arise in visceral organs, such as the lungs, the heart, or the sclera of the eye.
Cardiopulmonary Disease: There are several pulmonary manifestations of rheumatoid arthritis, including pleurisy with or without effusion, intrapulmonary nodules, rheumatoid pneumoconiosis (Caplan's syndrome), diffuse interstitial fibrosis, and rarely, bronchiolitis obliterans pneumothorax. On pulmonary function testing, there commonly is a restrictive ventilatory defect with reduced lung volumes and a decreased diffusing capacity for carbon monoxide. Although mostly asymptomatic, of greatest concern is distinguishing these manifestations from infection and tumor. Pericarditis is the most common cardiac manifestation.
Ocular Disease: Keratoconjunctivitis of Sjogren's syndrome is the most common ocular manifestation of rheumatoid arthritis. Sicca (dry eyes) is a common complaint. Episcleritis occurs occasionally and is manifested by mild pain and intense redness of the affected eye. Scleritis and corneal ulcerations are rare but more serious problems.
Neurologic Disease; The most common neurologic manifestation of rheumatoid arthritis is a mild, primarily sensory peripheral neuropathy, usually more marked in the lower extremities. Entrapment neuropathies (e.g., carpal tunnel syndrome and tarsal tunnel syndrome) sometimes occur in patients with rheumatoid arthritis because of compression of a peripheral nerve by inflamed edematous tissue. Cervical myelopathy secondary to atlantoaxial subluxation is an uncommon but particularly worrisome complication potentially causing permanent, even fatal neurologic damage.
Felty's Syndrome: Felty's syndrome is nowadays a rare complication of rheumatoid arthritis and is characterized by splenomegaly, and leukopenia Epredominantly granulocytopenia. Recurrent bacterial infections and chronic refractory leg ulcers are the major complications.
Rheumatoid Vasculitis; The most common clinical manifestations of vasculitis are small digital infarcts along the nailbeds. The abrupt onset of an ischemic mononeuropathy (mononeuritis multiplex) or progressive scleritis is typical of rheumatoid vasculitis. The syndrome ordinarily emerges after years of seropositive, persistently active rheumatoid arthritis; however, vasculitis may occur when joints are inactive.
Sjogren's Syndrome: Approximately 10 to 15% of patients with rheumatoid arthritis, mostly women develop Sjogren's syndrome, a chronic inflammatory disorder characterized by lymphocytic infiltration of lacrimal and salivary glands. This leads to impaired secretion of saliva and tears and results in the sicca complex: dry mouth (xerostomia) and dry eyes (keratoconjunctivitis sicca).
Patients with Sjogren's syndrome have a variable expression of disease in other exocrine glands. This is manifested clinically as dry skin, decreased perspiration, dry vaginal membranes, or a nonproductive cough. Commonly, there is also a polyclonal lymphoproliferative reaction characterized by lymphadenopathy and splenomegaly. This can mimic and rarely transform into a malignant lymphoma.
Clinical Course: The course of rheumatoid arthritis cannot be predicted in a given patient. Several patterns of activity have been described: I)a spontaneous remission particularly in the seronegative patient within the first 6 months of symptoms (less than 10%) recurrent explosive attacks followed by periods of quiescence most commonly in the early phases. II)the usual pattern of persistent and progressive disease activity that waxes and wanes in intensity.
Disability is higher among patients with rheumatoid arthritis with 60% being unable to work 10 years after the onset of their disease. Recent studies have demonstrated an increased mortality in rheumatoid patients. Median life expectancy was shortened an average of 7 years for men and 3 years for women compared to control populations. In more than 5000 patients with rheumatoid arthritis from four centers, the mortality rate was two times greater than in the control population. Patients at higher risk for shortened survival are those with systemic extra-articular involvement, low functional capacity, low socioeconomic status, low education, and prednisone use.
Disease modifying drugs (DMARDs)are designed to stop progression of the constant erosive damage caused by rheumatoid arthritis. Anti-inflammatory drugs (NSAIDs) help to ease the symptoms of the disease but do not stop the on-going damage to bone and tissue. Corticosteriods are a type of steriodal drug that is used in RA therapy to serve as a "bridge" before the effects of the DMARDs come into play. Steriods have serious side effects such as osteoporosis for long term use. The physician will use the lowest dose possible and yet maintain effectiveness.
Not all drugs will work equally all for all patients therefore the physician and patient must be aware when a drug is not working and another drug or doseage must be altered/changed. Each drug has an estimated time-period for efficacy. Undesired side effects may result of medications used in therapy.
The progress in Research and Development in drugs and knowledge of the disease is progressing at a speed unforseen in the past.
Biotechnology has created medications that has helped rheumatoid arthritis patients who previously could not be helped. Cost factor and provincial health plans are the chief drawbacks from having these new medications available to all patients in need.
Major Warning Signs:
Scientist currently do not know what causes rheumatoid arthritis nor do they have a cure
Factors related to RA:
Some researchers have suggested a virus triggers the disease but there is no
scientific evidence to suggest the validity of this view. It is currently thought
that genetrics may be a contributing factor in the presence of RA in a patient.
Mild RA Moderate RA Severe RA RA characterized by stiffness
30 to 35% of RA 35 to 40% of patients 10 to 20% of patients 25 to 20% of patients have
patients have this have this type of disease. have this type. marked stiffness rather then
form of disease. More joints are involved Severe means severe. swelling. The stiffness is
It usually presents along with more day-to-day Extra-articular marked. Mobility is usually
a short,mild course. difficulties and the features may be affected. Patients will have
Non-erosive erosions. course may be life-long. presented-deformity. difficulty raising their arms
present. More pain then mild. Symptoms are pronounced. above their heads.
Erosive erosions.
Health Care Professionals and Workers Involved in RA Therapy:
Inflammation in RA is a very complex process. Scientists believe it starts when one of the class of cells that guards the body against foreign invaders( in ordinary inflammation these are usually viruses or bacteria )comes into contact with something that triggers the alarm. One form the alarm takes is a whole battery of chemical messengers,called cytokines,that are released into the joint.
These recruit other cells,the white blood cells that attack and kill other cells and bacteria. One form this killing takes is the release into the immediate area of very "corrosive"" chemicals. Joint tissue,an innocent bystander,is damaged. Furthermore,cytokines stimulate the lining of the joint to grow and produce other chemicals that break down cartilage.
Cytokines are released into the blood stream,and cause fever and fatigue. Because the body is so finely balanced,there are also cytokines released that tend to damp down the inflammation. Unfortunately,in the RA joint these "good" cytokines tend to become overwhelmed by the "bad" or pro-inflammatory cyctokines.
One of the key cytokines that promotes inflammation is a substance called TNF-alpha. Produced by both the "guard" cells (macrophages) and the joint lining tissues,it is released into the surrounding tissues,joint fluid,and blood. It stimulates other while blood cells to expand the inflammatory reaction. To do this it must attach itself to the other cells a a specific binding site-like a key in a lock.
Etanercept (Enbrel) and Infliximab (Remicade) have been designed to interfere with this stimulatory action of TNF-alpha. Etanercept does this very cleverly;it's a molecule that looks exactly like the keyhole. As long as there is enough of it in circulation (it has to be self-injected twice weekly under the skin ),it will prevent enough keys from finding the lock they were intended for,and the inflammation will be damped down. It absobs excessive TNF
Infliximab has a similar effect,but it consists of an antibody ( a protein specifically designed to attach to another protein ) against TNF-alpha. Once the key has a antibody stuck to it,it no longer fits the lock. Infliximab too has to be given by needle-in this case into a vien-once every two months. Infliximab is called a monoclonal antibody,meaning it's a protein made with a mouse part,and a human protein is added to make it less allergic or immunogenic. Methotrexate is added because it decreases the mouse part reaction. Chimeric definition means,it's made of two animals,one is mouse and one is human. It "kills" excessive TNF-alpha (Tumour Necrosis Factor).
Leflunomide (Arava) is different. It doesn't block TNF-alpha,but it interferes with the normal functioning-one of the key cells ( the lymphocyte) affected by TNF-alpha,and thus interferes with the development of joint inflammation.
People with rheumatoid arthritis tend to have excess TNF-alpha. There is a family of Interleukins,involved in the disease process,too. IL-1,Il-2,IL-'s etc, Anakinra or Kineret inhibits IL-1 alpha. Scientists are working on a pill form of TNF inhibitors. Not everyone,will benefit from biological therapy,and some patients will not react favourably to conventional disease modifying medication.
Rheumatoid arthritis may be better classified into four different types: spontaneous remitting disease,remitting,remitting progressive,and progressive.
Spontaneous remission means that without treatment or just with NSAIDs,the symptoms of the disease disappear. They may return later,and you may need to start taking NSAIDs again,but for a while you have complete relief or almost. In rare cases,about 5 to 10 % of people with RA,the symptoms never return.
Remitting disease means that the person has a series of flare-ups with a return to normal in between. This can be difficult to deal with,because it is not known when a remission is going to occur and when the symptoms will return. DMARDs may be needed to prevent joint damage during the flare-ups.
People suffering from remitting progressive disease experience flare-ups but never quite return to normal in between. There is a good chance that the joints with this type of disease will be damaged without DMARD therapy.
The person with progressive disease never experiences remission or flare-ups,just a gradual increase in the pain,swelling,and joint damage over time. Usually the progression is slow,but in some cases one can become disabled rather quickly.
New ACR guidelines recommended DMARD therapy to all RA patients upon diagnosis.
Factors that correlate with prognosis: More favorable factors; Onset at a younger age,absence of rheumatoid nodules (small bumps over pressure points),absence of,or few,manifestations outside of joints,absence of rheumatoid factor in the blood and perhaps male gender.
Possible less favourable prognosis : Rapid onset at a younger age,high levels of rheumatoid factor,early in the disease,early involvement of large joints,female,presence of rheumatoid nodules,early appearance of erosions in the joints,vasculitis (blood disorder-veins become inflamed ),manifestations outside of the joints,and scleritis. It was once thought that the marker HLA-DR4 in the blood was a indicator of severe disease,but some recent research suggests it may not be related to severe disease. It remains debateable.
Two decades ago,the typical RA patient was kept on NSAID therapy until they showed evidence of joint damage or increased disease activity. During the last 10 to 15 years,however,rheumatologists have become more aggressive about starting DMARDs much earlier in the course of the disease. The principle agents used are hydroxychloroquine (HCQ),sulfasalazine (SSZ),and methotrexate (MTX). Gold salts while still available,are not often utilized,especially in their oral form. D-penicillamine has fallen out of favor,predominantly because of its side effects. Other medications, such as cyclosporine,are generally reserved for combination therapy or refractory disease.
During the last 5 years,our therapeutic options increased significantly. The introduction of leflunomide (Arava).a pyrimidine synthesis inhibitor (suppresses cells that are rapidly dividing),has provided an alternative for patients who cannot tolerate methotrexate or provide another option. Etanercept (Enbrel),a fusion protein that interrupts the inflammatory cascade by binding to tumour necrosis factor (TNF)-alpha,can be used in early disease or when conventional therapy do not work (limited by cost factor and insurance coverage). Another TNF-alpha inhibitor, Infliximab (Remicade),would probably work very well in early disease,but currently its use is limited to refractory (people who do not respond to conventional therapy) cases,in which it is given in combination with traditional medications such as MTX (high cost).
Recently (2003)another TNF-alpha inhibitor Formerly known as DE27,(Adalimumab)now called Humira has been approved by the F.D.A. for RA therapy. In the U.S.,the manufacturer,Abott Laboratory has introduced a promotional aspect to senior citizens on medicare whereby the drug is offered,free of charge. The manufacturer estimates it will cost them 30 million per annum.
Kineret is a Il-1ra (interleukin family)inhibitor introduced in early 2002. It can be used with MTX,but currently, combination with other TNF inhibitor is not recommended because of recent poor clinical trials results. Researchers believe the serious side effects may be dose related and scientists are working on the problem. Kineret is another option in the rheumatologist's arsenal to fight RA.
Both Remicade and Enbrel improve function,and there is good evidence they slow radiographic progression of RA(Arava also,but Arava ,a DMARD,might be more suitable for patients that cannot tolerate MTX). This would argue for both Etanercept and Infliximab use early in the disease,especially in patients who seem likely to have a aggressive or a destructive course.
Traditional disease-modifying agents can also slow radioraphic progression,however,and they are much less expensive then the newer agents. Consequenty,governments (provincial health plans have different guidelines in different provinces in Canada) and third-party payers impose restrictions on the use of the new biologic drugs. They may stipulate that patients must first be unresposive to as many as three traditional agents before they will pay for treatment with a TNF-alpha inhibitor. Often,important health care decisions are made by individuals (government bureaucrats) who are least knowledgeable about the subject.
These restrictions are being relaxed somewhat,slowly,as evidence of the new agents, efficacy and safety accumulates. Enbrel recently released a 5 year safety data,but drugs like methotrexate (what to expect-side effects-safety)-has a long track record.
For physicians whose choice of initial therapy is limited to traditional agents,the first question is whether to start with a single agent or combination therapy. Possible combinations include HCQ with SSZ or MTX,SSZ with MTX,or all three together. The choice of initial therapy can be a difficult one. They do not want to administer more medication than is necessary,yet we want to be aggressive enough to improve function and prevent the development of radiographic destruction,therby ultimately minimzing functional impairement and keeping down the long-term cost of care.
At present the most common strategy is to start with methotrexate alone. However,to minimize the risk of hepatoxicity, the patient must agree not to consume alcohol (or to do so only very modestly). If a patient is not tolerant to MTX,Arava can be tried.
Most rheumatologists choose not to start treatment with HCQ monotheraphy (single),except perhaps in patients with mild disease. Physicians are beginnining to use,more and more,use of HCQ in combination with MTX or SSZ,then in the past. Another alternative would be to start with SSZ alone,but the approach is less common (increasing) in North America than in Europe.
In the past a typical RA patient's MTX doseage (7.5 mg orally once a week) would have been titrated up slowly over six months or even a year. Now rheumatologists tend to move much faster,starting with up to 10 mg per week and taking dose to as 20-25 mg a week within the first two to three months. In 1998 a clinical trial was conducted with subcutaneous MTX injection with a equivalent dose of 25 mg and they found it more efficacious on patients,along with less accompaning side effects.
Faster dose escalation requires more frequent follow-ups. Some physicians will try another approach. But they all look for abnormalities on liver function tests,mouth sores or ulcerations,significant fatigue,nausea,or discomfort during the first 24 hours after taking the drug. Patients are asked to return two weeks (more or less)after first taking the drug,at which point the dose may be increased to 12.5 mg. Then they usually,return within four weeks. If they have had not a good response,the dose might be increased to 15 mg-17.5 mg. Four weeks after that,if patients still have not responded well enough,the dose may be increased to 20 to 25mg. But at that point,more than likely, subcutaneous injection of MTX will be introduced.
Clinical trials suggest that about 50 % of patients respond to methotrexate monotheraphy. Unfortunately,the average degree of improvement tends to be about 25 %. For example,the number of tender or swollen joints may decrease from 20 to 16,but there are always exceptions to the rule.
A few years ago,monotherapy was usually continued for six months to a year,and patients who had not responded might be switched to another drug. Today,if patients do not respond sufficiently to a adequate dose of medication, another DMARDs-HCQ,SSZ,or (if possible) Enbrel,Remicade,or Arava.
Arava is the least-cost wise of the new drugs,but is less efficacious of the other two-Enbrel and Remicade. Arava can stay in the body for up to 2 years after discontinuation of the drug A loading dose of 300 mg is given,100 mg for the first three day,at the start,and given in 10 or 20 mg ,tablet form,thereafter.
The physician might consider switching to one of the newer agents,but if the patient has shown some improvement and has not been troubled by side effects,most rheumatologists will add rather then switch.
HCQ can be added at a doseage of 400 mg once a day or 200 mg twice a day. SSZ is usually added at a doseage of 500 mg once or twice a day,escalating to a total dose of 1 gm twice a day. The escalation schedule traditionally recommended is for the patient to take one tablet a day for the first week,one tablet twice a day for the second week,one in the morning and two in the evening during the third week,one in the morning and two in the evening during the third week,and two tablets twice a day during the fourth week and thereafter.
For patients on combination therapy,physicians generally follow the same schedule for toxicity monitoring as with methotrexate, They obtain a complete blood count and liver function test and look for myelosuppression. The other medications do not need to be monitored as frequently as methotrexate,but since the patient is in the office anyway,all the monitoring can be done at the same time.
If combination therapy does not produce substantial impprovement within three months,the physician has a good clinical basis to move to biologic (anticytokine) therapy,and hope there should be little difficulty in convincing a third party payer of the necessity of using these agents.
If a patient responds well to DMARD treatment,the physician should eventually think about reducing doseage or withdrawing the agents one by one. The goal is to provide just enough therapy to keep the disease under control,which drug is kept for maintenance purposes will depend on the rheumatologist and the patient.
Patients must undestand that current treatments can provide significant improvement,but complete relief is unlikely. Patients need to learn the importance of avoiding trauma or stress in involved joints and of physical and occupational therapy to improve structures around the joints to decrease pain and improve function Education about the disease and medication is also vital Patients need to know the potential complications and toxicities of the drugs they are taking. They must be aware that some DMARDs take time to display their benefits,and be aware of a drug ,once efficacious,has become less effective. The bridge is usually low-dose glucocorticoid therapy (e.g.,up to 7.5 mg of predisone/daily).
Many RA patients are at risk of gastrointestinal complications from standard non-steriod drugs (NSAIDs). These patients tend to be older,have existing diseases such as diabetes,kidney,liver etc., and take glucocortoids and they may or may not have a history of coronary artery disease. The cyclooxygenase (Cox-2) inhibitors ,since they appear to have a lower risk of gastrointestinal toxicity. The improved safety of these drugs shoud not be assumed to imply improved efficacy. No NSAID alone can alter the course of RA,they do not change radiographic progression or slow joint destruction For that reason,they should be used as adjuncts,never as monotheraphy. If a patient has heart problems,selection of NSAID may be important and that also applies to others, existing disease present,must be fully recognized and adjustments made in therapy.
With chronic treatment with aspirin or an regular NSAID (in some existing disease conditions,it may be necessary to use a standard NSAID like Naproxen),and add a gastroprotective agent (e.g.,misoprostol cytotec or a proton pump inhibitor).
Many RA patients have this so called "secondary OA" or mechanical problem. We as patients will in all probability will not be able to escape that part of pain. In other words,is pain caused by mechanical,or inflammatory forces. If it a mechanical problem we have to attack the problem in different other ways; exercise,heat,cold,anagesics etc.
*All my sites.--I have written many articles over the years.*Disregard any reference to "Vioxx" which was taken off the market by the FDA a few years ago. The NSAID had proven to have negative adverse heart problems to many patients--rise in blood pressure. Every RA patient's prognosis,medication,effects and form may be different. Don't waste your time,money or health on "cures". See a rheumatologist to treat your disease.Build Date: 7/10/02.