Rheumatoid arthritis
Rheumatoid arthritis (
RA) is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium (synovitis) secondary to hyperplasia of synovial cells, excess synovial fluid, and the development of pannus in the synovium. The pathology of the disease process often leads to the destruction of articular cartilage and ankylosis of the joints. Rheumatoid arthritis can also produce diffuse inflammation in the lungs, pericardium, pleura, and sclera, and also nodular lesions, most common in subcutaneous tissue under the skin. Although the cause of rheumatoid arthritis is unknown, autoimmunity plays a pivotal role in both its chronicity and progression, and RA is considered as a systemic autoimmune disease.
About 1% of the world's population is afflicted by rheumatoid arthritis, women three times more often than men. Onset is most frequent between the ages of 40 and 50, but people of any age can be affected. It can be a disabling and painful condition, which can lead to substantial loss of functioning and mobility if not adequately treated. It is a clinical diagnosis made on the basis of symptoms, physical exam, radiographs(X-rays) and labs; although the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) publish diagnostic guidelines. Diagnosis and long-term management are typically performed by a rheumatologist, an expert in auto-immune diseases.
Various treatments are available. Non-pharmacological treatment includes physical therapy, orthoses, occupational therapy and nutritional therapy but do not stop progression of joint destruction. Analgesia (painkillers) and anti-inflammatory drugs, including steroids, are used to suppress the symptoms, while disease-modifying antirheumatic drugs (DMARDs) are required to inhibit or halt the underlying immune process and prevent long-term damage. In recent times, the newer group of biologics has increased treatment options.
Signs and symptoms
While rheumatoid arthritis primarily affects joints, problems involving other organs of the body are known to occur. Extra-articular ("outside the joints") manifestations other than anemia (which is very common) are clinically evident in about 15-25% of individuals with rheumatoid arthritis.
It can be difficult to determine whether disease manifestations are directly caused by the rheumatoid process itself, or from side effects of the medications commonly used to treat it - for example, lung fibrosis from methotrexate or osteoporosis from corticosteroids.
JOINT
A diagram showing how rheumatoid arthritis affects a joint
The arthritis of joints known as synovitis is inflammation of the synovial membrane that lines joints and tendon sheaths. Joints become swollen, tender and warm, and stiffness limits their movement. With time RA nearly always affects multiple joints (it is a polyarthritis), most commonly small joints of the hands, feet and cervical spine, but larger joints like the shoulder and knee can also be involved. Synovitis can lead to tethering of tissue with loss of movement and erosion of the joint surface causing deformity and loss of function.
Rheumatoid arthritis typically manifests with signs of inflammation, with the affected joints being swollen, warm, painful and stiff, particularly early in the morning on waking or following prolonged inactivity. Increased stiffness early in the morning is often a prominent feature of the disease and typically lasts for more than an hour. Gentle movements may relieve symptoms in early stages of the disease. These signs help distinguish rheumatoid from non-inflammatory problems of the joints, often referred to as osteoarthritis or "wear-and-tear" arthritis. In arthritis of non-inflammatory causes, signs of inflammation and early morning stiffness are less prominent with stiffness typically less than 1 hour, and movements induce pain caused by mechanical arthritis.
In RA, the joints are often affected in a fairly symmetrical fashion, although this is not specific, and the initial presentation may be asymmetrical.
As the pathology progresses the inflammatory activity leads to tendon tethering and erosion and destruction of the joint surface, which impairs range of movement and leads to deformity. The fingers may suffer from almost any deformity depending on which joints are most involved. Medical students are taught to learn names for specific deformities, such as ulnar deviation, boutonniere deformity, swan neck deformity and "Z-thumb," but these are of no more significance to diagnosis or disability than other variants. "Z-thumb" or "Z-deformity" may occur in rheumatoid arthritis. It consists of hyperextension of the interphalangeal joint, and fixed flexion and subluxation of the metacarpophalangeal joint and gives a "Z" appearance to the thumb; however, this finding is also typical of osteoarthritis of the thumb as well.
Skin
The
rheumatoid nodule, which is often subcutaneous, is the cutaneous feature most characteristic of rheumatoid arthritis. The initial pathologic process in nodule formation is unknown but may be essentially the same as the synovitis, since similar structural features occur in both. The nodule has a central area of fibrinoid necrosis that may be fissured and which corresponds to the fibrin-rich necrotic material found in and around an affected synovial space. Surrounding the necrosis is a layer of palisading macrophages and fibroblasts, corresponding to the intimal layer in synovium and a cuff of connective tissue containing clusters of lymphocytes and plasma cells, corresponding to the subintimal zone in synovitis. The typical rheumatoid nodule may be a few millimetres to a few centimetres in diameter and is usually found over bony prominences, such as the olecranon, the calcaneal tuberosity, the metacarpophalangeal joint, or other areas that sustain repeated mechanical stress. Nodules are associated with a positive RF (rheumatoid factor) titer and severe erosive arthritis. Rarely, these can occur in internal organs or at diverse sites on the body.
Several forms of
vasculitis occur in rheumatoid arthritis. A benign form occurs as microinfarcts around the nailfolds. More severe forms include livedo reticularis, which is a network (reticulum) of erythematous to purplish discoloration of the skin caused by the presence of an obliterative cutaneous capillaropathy.
Other, rather rare, skin associated symptoms include:
- pyoderma gangrenosum, a necrotizing, ulcerative, noninfectious neutrophilic dermatosis.
- Sweet's syndrome, a neutrophilic dermatosis usually associated with myeloproliferative disorders
- drug reactions
- erythema nodosum
- lobular panniculitis
- atrophy of digital skin
- palmar erythema
- diffuse thinning (rice paper skin), and skin fragility (often worsened by corticosteroid use).
Lungs
Fibrosis of the lungs is a recognised response to rheumatoid disease. It is also a rare but well recognised consequence of therapy (for example with methotrexate and leflunomide). Caplan's syndrome describes lung nodules in individuals with rheumatoid arthritis and additional exposure to coal dust. Pleural effusions are also associated with rheumatoid arthritis.
Kidneys
Renal amyloidosis can occur as a consequence of chronic inflammation.
Rheumatoid arthritis may affect the kidney glomerulus directly through a vasculopathy or a mesangial infiltrate but this is less well documented. Treatment with Penicillamine and gold salts are recognized causes of membranous nephropathy.
Heart and blood vessels
People with rheumatoid arthritis are more prone to atherosclerosis, and risk of myocardial infarction (heart attack) and stroke is markedly increased.
Other possible complications that may arise include: pericarditis, endocarditis, left ventricular failure, valvulitis and fibrosis.
Many people with rheumatoid arthritis do not experience the same chest pain that others feel when they have angina or myocardial infarction. To reduce cardiovascular risk, it is crucial to maintain optimal control of the inflammation caused by rheumatoid arthritis (which may be involved in causing the cardiovascular risk), and to use exercise and medications appropriately to reduce other cardiovascular risk factors such as blood lipids and blood pressure. Doctors who treat rheumatoid arthritis patients should be sensitive to cardiovascular risk when prescribing anti-inflammatory medications, and may want to consider prescribing routine use of low doses of aspirin if the gastrointestinal effects are tolerable.
Cause
Rheumatoid arthritis is a form of autoimmunity, the causes of which are still incompletely known. It is a systemic (whole body) disorder principally affecting synovial tissues.
Diagnosis Imaging
X-ray of the hand in rheumatoid arthritis.
Signs of destruction and inflammation on ultrasonography and magnetic resonance imaging in the second metacarpophalangeal joint in established rheumatoid arthritis.
X-rays of the hands and feet are generally performed in people with a polyarthritis. In rheumatoid arthritis, there may be no changes in the early stages of the disease, or the x-ray may demonstrate juxta-articular osteopenia, soft tissue swelling and loss of joint space. As the disease advances, there may be bony erosions and subluxation. X-rays of other joints may be taken if symptoms of pain or swelling occur in those joints.
Other medical imaging techniques such as magnetic resonance imaging and ultrasound are also used in rheumatoid arthritis.
There have been technical advances in ultrasonography. High-frequency transducers (10 MHz or higher) have improved the spatial resolution of ultrasound images; these images can depict 20% more erosions than conventional radiography. Also, color Doppler and power Doppler ultrasound, which show vascular signals of active synovitis depending on the degree of inflammation, are useful in assessing synovial inflammation. This is important, since in the early stages of rheumatoid arthritis, the synovium is primarily affected, and synovitis seems to be the best predictive marker of future joint damage.
Blood tests
When RA is clinically suspected, immunological studies are required, such as testing for the presence of rheumatoid factor (RF, a non-specificantibody).
A negative RF does not rule out RA; rather, the arthritis is called
seronegative. This is the case in about 15% of patients.
During the first year of illness, rheumatoid factor is more likely to be negative with some individuals converting to seropositive status over time. RF is also seen in other illnesses, for example Sjögren's syndrome, Hepatitis C, chronic infections and in approximately 10% of the healthy population, therefore the test is not very specific.
Because of this low specificity, new serological tests have been developed, which test for the presence of the anti-citrullinated protein antibodies (ACPAs) or anti-CCP. Like RF, these tests are positive in only a proportion (67%) of all RA cases, but are rarely positive if RA is not present, giving it a specificity of around 95%.
As with RF, there is evidence for ACPAs being present in many cases even before onset of clinical disease.
The most common tests for ACPAs are the anti-CCP (cyclic citrullinated peptide) test and the Anti-MCV assay (antibodies against mutated citrullinated Vimentin). Recently a serological point-of-care test (POCT) for the early detection of RA has been developed. This assay combines the detection of rheumatoid factor and anti-MCV for diagnosis of rheumatoid arthritis and shows a sensitivity of 72% and specificity of 99.7%.
Also, several other blood tests are usually done to allow for other causes of arthritis, such as lupus erythematosus. The erythrocyte sedimentation rate (ESR), C-reactive protein, full blood count, renal function, liver enzymes and other immunological tests (e.g., antinuclear antibody/ANA) are all performed at this stage. Elevated ferritin levels can reveal hemochromatosis, a mimic RA, or be a sign of Still's disease, a seronegative, usually juvenile, variant of rheumatoid.
Criteria
In 2010 the
2010 ACR / EULAR Rheumatoid Arthritis Classification Criteria were introduced.
These new classification criteria overruled the "old" ACR criteria of 1987 and are adapted for early RA diagnosis. The "new" classification criteria, jointly published by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) establish a point value between 0 and 10. Every patient with a point total of 6 or higher is unequivocally classified as an RA patient, provided he has synovitis in at least one joint and given that there is no other diagnosis better explaining the synovitis. Four areas are covered in the diagnosis:
- joint involvement – depending on the type and number of joints: up to 5 points
- serological parameters – including the rheumatoid factors as well as ACPA – "ACPA" stands for "anti-citrullinated protein antibody": up to 3 points depending on titre level
- acute phase reactants: 1 point for elevated erythrocyte sedimentation rate, ESR, or elevated CRP value (c-reactive protein)
- duration of arthritis: 1 point for symptoms lasting six weeks or longer
The new criteria accommodate to the growing understanding of rheumatoid arthritis and the improvements in diagnosing RA and disease treatment. In the "new" criteria serology and autoimmune diagnostics carries major weight, as ACPA detection is appropriate to diagnose the disease in an early state, before joints destructions occur. Destruction of the joints viewed in radiological images was a significant point of the ACR criteria from 1987.
This criterion no longer is regarded to be relevant, as this is just the type of damage that treatment is meant to avoid.
The criteria are not intended for the diagnosis for routine clinical care; they were primarily intended to categorize research (
classification criteria). In clinical practice, the following criteria apply
- two or more swollen joints
- morning stiffness lasting more than one hour for at least six weeks
- the detection of rheumatoid factors or autoantibodies against ACPA such as autoantibodies to mutated citrullinated vimentin can confirm the suspicion of rheumatoid arthritis. A negative autoantibody result does not exclude a diagnosis of RA.
Differential diagnosis
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.
- Hepatitis C - RA-like symmetrical small-joint polyarthritis may occur in the context of this condition. Hepatitis C may also induce Rheumatoid Factor auto-antibodies
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.
Pathophysiology
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 cell-associated 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 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.
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
[26] , 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 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 begins to disintegrate and evidence of joint destruction accrues.
Treatment
There is no known cure for rheumatoid arthritis, but many different types of treatment can alleviate symptoms and/or modify the disease process. Recommendations of the American College of Rheumatology (ACR), published in 2008, followed a trend in supporting earlier, more aggressive treatment of RA, and reflected heightened expectations of treatment effectiveness, including remission or substantial alleviation of symptoms for a rising percentage of patients.
The goal of treatment is twofold: alleviating the current symptoms, and preventing the future destruction of the joints with the resulting handicap if the disease is left unchecked. These two goals may not always coincide: while pain relievers may achieve the first goal, they do not have any impact on the long-term consequences. For these reasons, the ACR recommends that RA should generally be treated with at least one specific anti-rheumatic medication, also named DMARD (see below), to which other medications may be added depending on how long a person has had RA, how active the disease is, and prognostic factors (such as X-ray evidence of bone erosion; elevation of blood factors such as Rheumatoid factor, anti-cyclic citrullinated peptide, C-reactive protein, and erythrocyte sedimentation rate; age and gender; physical functioning; and smoking, for example)
Cortisone therapy has offered relief in the past, but its long-term effects have been deemed undesirable.
However, cortisone injections can be valuable adjuncts to a long-term treatment plan, and using low dosages of daily cortisone (e.g., prednisone or prednisolone, 5-7.5 mg daily) can also have an important benefit if added to a proper specific anti-rheumatic treatment.
Pharmacological treatment of RA can be divided into disease-modifying antirheumatic drugs (DMARDs), anti-inflammatory agents and analgesics.
Treatment also includes rest and physical activity.
Disease modifying anti-rheumatic drugs (DMARDs)
Main article: Disease-modifying antirheumatic drug
The term Disease modifying anti-rheumatic drug (DMARD) originally meant a drug that affects biological measures such as ESR and haemoglobin and autoantibody levels, but is now usually used to mean a drug that reduces the rate of damage to bone and cartilage. DMARDs have been found both to produce durable symptomatic remissions and to delay or halt progression. This is important as such damage is usually irreversible. Anti-inflammatories and analgesics improve pain and stiffness but do not prevent joint damage or slow the disease progression.
There is an increasing recognition among rheumatologists that permanent damage to the joints occurs at a very early stage in the disease. In the past it was common to start with just an anti-inflammatory drug, and assess progression clinically and using X-rays. If there was evidence that joint damage was starting to occur then a more potent DMARD would be prescribed. Ultrasound and MRI are more sensitive methods of imaging the joints and have demonstrated that joint damage occurs much earlier and in more sufferers than was previously thought. People with normal X-rays will often have erosions detectable by ultrasound that X ray could not demonstrate. The aim now is to treat before damage occurs.
There may be other reasons why starting DMARDs early is beneficial as well as prevention of structural joint damage. From the earliest stages of the disease, the joints are infiltrated by cells of the immune system that signal to one another in ways that may involve a variety of positive feedback loops (it has long been observed that a single corticosteroid injection may abort synovitis in a particular joint for long periods). Interrupting this process as early as possible with an effective DMARD (such as methotrexate) appears to improve the outcome from the RA for years afterwards. Delaying therapy for as little as a few months after the onset of symptoms can result in worse outcomes in the long term. There is therefore considerable interest in establishing the most effective therapy with early arthritis, when they are most responsive to therapy and have the most to gain.
Disease modifying anti-rheumatic drugs have been used in the treatment of rheumatic arthritis for a long time now. Over 90% of rheumatologists now use combination therapy of multiple disease modifying drugs for rheumatoid arthritis as it has become apparent that using combination of these drugs does not increase their relative toxicity profiles.
Common combinations of DMARDs include methotrexate - hydroxychloroquine, methotrexate - Sulphasalazine, Sulphasalazine - hydroxychloroquine, and methotrexate - hydroxychloroquine - Sulphasalazine.
In order to be effective, disease modifying anti-rheumatic drugs must be administered before the deformities appear or the erosive disease occurs. Usually, Rheumatologists do not wait for the fulfillment of the criteria for classification of RA as published by the American College of Rheumatology (ACR) and start treatment with this type of drugs if the pain and synovitis persist and the function is compromised.
Traditional small molecular mass drugs
Chemically synthesised DMARDs:
- azathioprine
- ciclosporin (cyclosporine A)
- D-penicillamine
- gold salts
- hydroxychloroquine
- leflunomide
- methotrexate (MTX)
- minocycline
- sulfasalazine (SSZ)
Cytotoxic drugs:
The most important and most common adverse events relate to liver and bone marrow toxicity (MTX, SSZ, leflunomide, azathioprine, gold compounds, D-penicillamine), renal toxicity (cyclosporine A, parenteral gold salts, D-penicillamine), pneumonitis (MTX), allergic skin reactions (gold compounds, SSZ), autoimmunity (D-penicillamine, SSZ, minocycline) and infections (azathioprine, cyclosporine A).
Hydroxychloroquine may cause ocular toxicity, although this is rare, and because hydroxychloroquine does not affect the bone marrow or liver it is often considered to be the DMARD with the least toxicity. Unfortunately hydroxychloroquine is not very potent, and is usually insufficient to control symptoms on its own.
Methotrexate is considered by many rheumatologists to be the most important and useful DMARD, largely because of lower drop-out rates for reasons of toxicity. Nevertheless, methotrexate is often considered as a very 'toxic' drug. This reputation is not entirely justified, and at times can result in people being denied the most effective treatment for their arthritis. Although methotrexate does have the potential to suppress bone marrow or cause hepatitis, these effects can be monitored using regular blood tests, and the drug withdrawn at an early stage if the tests are abnormal before any serious harm is done (typically the blood tests return to normal after stopping the drug). In clinical trials, where one of a range of different DMARDs were used, people who were prescribed methotrexate stayed on their medication the longest (the others stopped because of either side-effects or failure of the drug to control the arthritis). Methotrexate is often preferred by rheumatologists because if it does not control arthritis on its own then it works well in combination with many other drugs, especially the biological agents. Other DMARDs may not be as effective or as safe in combination with biological agents.
Although it appears to be a highly efficient drug in the treatment of rheumatoid arthritis, sulphasalazine may cause side effects that can range in severity from mild to serious. Mild side effects that may arise from treatment with sulphasalazine include nausea and skin rash. Generally, nausea that appears as a result of treatment with this DMARD occurs in the first days of treatment and then it tends to diminish to disappearance. To avoid nausea, specialists recommend starting with low doses and then gradually increasing them until the usual dosage is achieved. Skin rash has been reported in nearly 5% of the patients and it may present pruritus. Rare side effects include Stevens-Johnson syndrome and reduced fertility due to reversible oligospermia. Severe side effects that can appear from therapy with sulphasalazine, though rare, are aplastic anemia and neutropenia which may result in the death of the patient. The latter is estimated to have occurred in approximately 2% of the patients but death and further complications were avoided by removing the drug from the patient's therapy. Also, according to WHO, there have been approximately 700 of patients in whom this medicine caused blood dyscrasis. Leukopenia has also been reported in therapies with sulphasalazine, but in very rare cases.
Anti-malarials such as chloroquine and hydroxychloroquine have been used to treat rheumatoid arthritis. It has been pointed out, through clinical studies, that chloroquine has a higher toxicity compared to hydroxychloroquine. Although hydroxyxhloroquine appears to be more efficient in treating rheumatoid arthritis than placebo, it is also inferior to sulphasalazine, especially in what concerns preventing the joint damage that is caused by the disease. As most drugs, anti-malarials may also produce side effects. Mild side effects from hydroxychloroquine include nausea and skin rash. More serious, bone marrow suppression may occur, though rare. Also, aplastic anemia and agranulocytosis can develop as a result of anti-malarial therapy and may potentially cause the death of the patient. A much more worrisome side effect from treatment with anti-malarials is the damage that these drugs seem to be causing to the cornea and retina. Recent studies have however shown that if the dosage of hydroxychloroquine given to the patients does not exceed 6.5 mg/kg, the risks of developing ocular complications are minimal.
Gold compounds are also options in treating this type of disease. Specialists agree that injectable gold is much more effective in the treatment of rheumatoid arthritis than auranofin. Yet, this type of drug has been shown to be more efficient than placebo and even though its level of toxicity is quite low, auranofin seems to be causing more side effects than any other type of DMARD. Auranofin is therefore not considered efficient in the treatment of rheumatoid arthritis because of its poor results and because it is intolerable for most patients. Sodium aurothiomalate (Myocrisin) on the other hand is another type of gold compound that is injected and which appears to be as efficient as sulphasalazine, d-penicillamine and methotrexate. Given that there is not enough proof that gold compounds are indeed efficient in preventing the progression of erosions and the high toxicity of these drugs, they are usually not included in the treatment plan for rheumatoid arthritis.
Hydrotherapy : soothing away the aches and pains of arthritis
Exercise can put excess strain on your joints and muscles, especially when they already are stiff because of arthritis. Performing exercises in water allows joints and muscles to be worked gently and safely because it does not cause excess strain. Strength and flexibility are increased while pain and stiffness are decreased.
