Many Faces Of Arthritis Biology Essay

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Rheumatoid arthritis is a chronic inflammation of flexible joints which may affect tissues and organs. This disorder of the joints is one of the most common types of systemic inflammatory arthritis. To date, the root cause of rheumatoid arthritis is unknown, but the disorder is generally considered a systematic autoimmune disease which results when the immune system mistakenly attacks the host's own tissues and joints. Rheumatoid arthritis is named such since it is one of the pathological conditions that characterize rheumatism, a general term used to refer to a wide range of conditions affecting the joints, tendons, bones and nerves. There is no effective cure yet for rheumatoid arthritis, but it can be effectively managed with the help of new drugs, joint protection techniques, exercises and self-management techniques. Based on the official report of the World Health Organization (WHO), approximately one percent of adults around the world aged fifteen years and above have rheumatoid arthritis. [1] 

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<a>Prevalence and Statistics</a>

There are around fifty million people in the United States alone who have been diagnosed arthritis by their doctors. In the United States of America, nearly twenty-four percent of the adult population report having doctor diagnosed arthritis. [2] Between the year of 2007 and 2009, fifty percent of people older than sixty-five, had an arthritis diagnosis. The case of juveniles is even worse with around 294,000 children under the age of eighteen having some form of arthritis. The ratio is horribly high and is around one in every 250 children in the United States. The most common form of arthritis prevalent is osteoarthritis. However, there are other rheumatic conditions such as gout, fibromyalgia and rheumatoid arthritis which are quite common. In the year 2005, nearly twenty-seven million adults had osteoarthritis. The figure for rheumatoid arthritis in 2007 among adults was around 1.7 million. [3] 

There were approximately three million gout patients in 2005. [4] The doctor diagnosed arthritis is often reported more by overweight subjects than normal weight ones. This is an established fact wherein around sixteen percent of normal weight adults report doctor diagnosed arthritis. [5] On the contrary, roughly thirty percent of obese people report doctor diagnosed arthritis which establishes the likelihood of obese people developing arthritis to be much higher than normal people. [6] An interesting figure is that about sixty-five percent of adults among those diagnosed with arthritis are overweight or obese. [7] The prevalence of rheumatic arthritis in the Western world is between 0.3 and one percent and a reasonable overall prevalence for definite rheumatoid arthritis is of 0.8 percent adults. [8] 

<a>Signs and Symptoms of Rheumatoid Arthritis</a>

Rheumatoid arthritis starts with the swelling of synovial cells. Synovia are relatively acellular areas with very vulnerable intimal lining that surrounds the joints. Other signs are accumulation of synovial fluid and development of lesion in the synovium, leading to damages in articular cartilage and fusion of joints. Rheumatoid arthritis affects the joints found between the fingers and the hands and those between the toes and the feet, with the aggressive front of synovium attacking the local articular structures. White blood cells such as CD4+ T-cells, macrophages and B-cells, sometimes form lymphoid aggregates with germinal centers.

Hyperplasia of the intimal lining ensues as macrophage-like and fibroblast-like synoviocytes grow. Serine proteases, metalloproteinases, aggrecanases and other degradative enzymes weaken the extracellular matrix and soon damage the articular structures. As the disease progresses, it normally spreads to other joint areas such as ankles, knees, hips, elbows, and shoulders. The symptoms are typically felt in the same joints on both the left and right sides of the body. Tissues of major organs such as heart, lungs, and eyes may be affected. There is also a risk of nodular lesions, especially in subcutaneous tissues. The symptoms may fade and intensify again from time to time, and flares may come and go simultaneously with periods of relative remission when the inflammation and pain subside or disappear. In worse cases, rheumatoid arthritis can lead to deformed and dislocated joints.

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<a>Classification</a>

In 1987, the American Rheumatism Association (ARA) identified seven critical criteria for classifying rheumatoid arthritis. [9] They are as follows:

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Morning joint stiffness lasting for at least an hour prior to maximal improvement

Swelling of soft tissues of three or more joint areas

Inflammation of the proximal interphalangeal, metacarpophalangeal, or wrist joints

Symmetric joint inflammation

Rheumatoid nodules

Development of rheumatoid factor

Radiographic erosions and/or periarticular osteopenia in the joints of hand and/or wrists.

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The first four conditions must have been persisting for at least six months. To get diagnosed with rheumatoid arthritis, the ARA requires the presence of at least four of the seven above-mentioned conditions. Additional qualifications (classic, definite, or probable) or specific exclusions were not necessary. These criteria were improved in 2010 based on a series of clinical tests with the purpose of classifying newly presenting patients for clinical trials. [10] Under the revised score-based diagnostic system, patients with an erosive disease typical of rheumatoid arthritis with conditions that are compatible with the prior fulfillment of the latest criteria are still considered to be having rheumatoid arthritis. Those with longstanding disease, including cases of an inactive one which meet the 2010 criteria based on retrospective data available, should still be classified as having rheumatoid arthritis. The 2010 classification system is based on a scale ranging from one to ten, with six set as the minimum score needed to be classified as having a rheumatoid arthritis. Differential diagnoses differ from patient to patient depending on conditions, which may include gout, systemic lupus erythematosus or psoriatic arthritis. Patients who scored less than six can be reassessed and previous scores can be aggregated to arrive at diagnosis.

<a>Risk Factors</a>

Gender, genes, age and smoking are known to be risk factors of rheumatoid arthritis. Some experts think that genes could have an indirect role in triggering this immune disorder since they can make living things more susceptible to environmental health risks that may be causing rheumatoid arthritis. Women and older people are generally more susceptible to rheumatoid arthritis.

<b>Gender and Age</b>

Women are more prone to rheumatoid arthritis than are men. People from the forty to sixty-year bracket have a higher risk of developing the disease. [11] Women are also at greater risk of suffering fracture than men when age is taken into account. The risk of bone fracture does not surface in male rheumatoid arthritis patients until they get old, whereas their women counterparts suffer from higher risk even those under the age of fifty years. [12] 

<b>Genes</b>

Family history is deemed a possible risk factor of rheumatoid arthritis based on the theory that predisposition to rheumatoid arthritis is genetic. However, there has been no conclusive study that identifies specific genes associated with the disease, although there have been convincing pieces of evidence that warrant further studies. In 1987, Peter Gregersen and colleagues found a string of five amino acids that seems to be unique to rheumatoid arthritis patients. The team proposed that these string within the major histocompatibility complex (MHC) may be playing a big role in developing susceptibility to the disease. The team called this string a "shared epitope." [13] 

Gregersen, whose research continues up to the present as the director of the Feinstein Institute's Robert S. Boas Center for Genomics and Human Genetics, and other members of the North American Rheumatoid Arthritis Consortium (NARAC) are responsible for building a massive genetic database containing profiles of more than 1,000 people with rheumatoid arthritis as well as their family members. Gregersen's team also accessed the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) database. The two databases gave researchers more than 3,000 genetic speciments for their studies. In 2007, Gregersen's team announced the discovery of the variants of STAT4 and TRAF1-C5 genes which seem to be contributing to higher risk of rheumatoid arthritis. [14] Prior to this, Gregersen had found strong evidence that the PTPN2 gene is associated with twofold risk of developing rheumatoid arthritis and other autoimmune disorders. This was followed by the discovery of PADI4, which is believed to be a major risk factor in Asian population, although less of a risk factor among people of European descent. People with two copies of STAT4 are twice as likely to develop lupus and have sixty percent increased risk to incur rheumatoid arthritis as compared with people who do not have a copy of the genetic variant. TRAF1-C5 are two genes found lying close to each other on chromosome nine. It is still unknown which of these genes is a risk factor. Research findings suggest that having this variant at chromosome nine results in a thirty-five percent increased risk of getting rheumatoid arthritis.

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The 1987 discovery from Dr. Gregersen got a major boost in 2011 with the release of the collaborative research studies from other research partners. The research group validated and advanced Gregersen's 1987 study. The collaborating teams used fine-mapping strategy to examine genetic samples derived from 20,000 people. Genetic variants in the MHC of people with rheumatoid arthritis were compared with versions of genes found in patients who do not have this joint disease. The study identified positions in two amino acids from the so-called "shared epitope" and discovered two more amino acids that may be risk factors as well. These amino acids are found in key immune system proteins called HLA, specifically at the base of peptide-binding groove which has the capability to detect and bind foreign bodies. [15] The findings are expected to pave the way for the discovery of rheumatoid arthritis' autoantigen or the material that causes the immune system to attack the tissues and joints.

<b>Smoking</b>

Smoking is also associated with increased risk of developing rheumatoid arthritis. One-third of cases involving the common forms of this joint disorder can be attributed to smoking. The risk is higher among smokers who have genetic predisposition to develop the disease, estimated at fifty percent. [16] 

The correlation between smoking and higher risk of rheumatoid arthritis is not as pronounced as the effect of smoking on lung cancer susceptibility. Rather, the risk of rheumatoid arthritis due to smoking increases in a way similar to that of heart diseases caused by smoking. Rheumatoid arthritis is more likely to develop in people who smoke longer and more frequently. It has been proposed that smoking triggers the immune system to attack healthy tissues and joints by causing proteins to change. The pace of development and reaction may differ depending on genetic factors. A study [17] by Saedis Saevarsdottir showed that smoking can also affect the efficacy of rheumatoid arthritis treatments. Smokers with rheumatoid arthritis are less likely to respond to methotrexate (MTX) and tumor necrosis factor (TNF) inhibitors as compared with patients who are non-smokers. The ten-year study proved that those who have never smoked in the past have good response rate to these medications. Saevarsdottir and co-researchers at Karolinska University Hospital and Karolinska Institute in Stockholm examined the records of approximately 1,400 patients entering the epidemiological investigation of rheumatoid arthritis (EIRA) in 1996 and 2006. The age of the patients ranged from eighteen to seventy years. They entered the population-controlled study ten months from the onset of symptoms. The results showed that after three months of MTX treatment, current smokers showed less improvements compared with those who never smoked. The smoking group had a twenty-seven percent response rate, while the nonsmoking group had thirty-six percent. In the TNF inhibitor study, twenty-nine percent of smokers had good response rate, compared with forty-three percent among non-smokers. Past smoking history showed no correlation to MTX or TNF inhibitor response rate. Around fourteen percent of smokers were able to respond well to medications after three months, compared with thirty-four percent of patients who never smoked. The researchers underscored the need for further studies to determine if smoking cessation prior to initiating treatment would improve response rate.

<a>Distinguishing Characteristics of Rheumatoid Arthritis</a>

<b>Hands and Fingers</b>

The joints connecting the fingers to hands or the toes to feet are usually affected first. There are several types of deformities associated with rheumatoid arthritis such as Z-thumb (deformed metacarpophalangeal joint marked by "squared" appearance), swan neck deformity (the joint nearest to the fingertip turns toward the palm), ulnar deviation and boutonniere deformity. These conditions are not specific to the rheumatoid type of arthritis. They may also manifest in cases of osteoarthritis. Rheumatoid arthritis can still be distinguished from non-inflammatory joint disorders such as osteoarthritis in which signs of swelling and morning stiffness are less remarkable and stiffness only lasts for an hour. At the onset of rheumatoid arthritis, pain may be asymmetrical, but the condition usually turns symmetrical soon. The rheumatoid nodule, also known as cutaneous, is the most common defining characteristic of rheumatoid arthritis. Pathologists call this inflammatory reaction "necrotizing granuloma." Rheumatologists do not know yet how the pathological process starts, but it may be basically the same as that of synovitis since both have similar structural symptoms. Various forms of vasculitis can be experienced by people with rheumatoid arthritis. Benign microinfarcts may develop around the nailfolds. In worse cases, patients may experience livedo reticularis, a purplish discoloration of the skin due to damaged capillaries.

<b>Rarities</b>

The following rare skin symptoms are associated with rheumatoid arthritis:

Palmar erythema, a reddening of the palm as a result of pathological and physiological factors.

Atrophy of digital (finger) skin, a condition characterized by thinning of digital skin.

Erythema nodosum, an inflammatory disease characterized by red bumps under the skin.

Sweet's syndrome, an acute case of neutrophilic dermatosis marked by erythematous plaques, lesions, fever and sometimes blisters with an annular or arciform pattern.

Pyoderma gangrenosum, a type of non-infectious dermatosis causing tissues to be necrotic, leading to deep ulcers.

Lobular panniculitis, an inflammation of subcutaneous adipose tissue characterized by tender skin nodules.

<a>Techniques and Research</a>

Detecting rheumatoid arthritis is mainly based on physical symptoms, radiographic indication of joint damage and patient history. Rheumatoid arthritis is difficult to detect at early stage, and most treatments available today only offer temporary relief. Some of the conditions that resemble the early signs of rheumatoid arthritis include crystal induced arthritis, osteoarthritis, systemic lupus erythematosus, psoriatic arthritis, Lyme disease, reactive arthritis, ankylosing spondylitis and hepatitis C. Laboratory tests and radiographic imaging are normally used to distinguish rheumatoid arthritis from such conditions. Initial diagnosis can be quite challenging and it may take nine months starting from the onset period for the disease to be effectively diagnosed. The discovery of an effective cure for rheumatoid arthritis depends on clear understanding of the root causes of the disease. Research studies aimed at understanding the pathology of the disease have made significant progress over the past decades, thanks to advances in biotechnology and genetic engineering.

<b>Physical Diagnosis</b>

Due to the difficulty of diagnosing rheumatoid arthritis at its early stage, the American College of Rheumatology and the European League against Rheumatism collaborated to revise the recommended screening protocol for classifying rheumatoid arthritis. Modern drugs for managing rheumatoid arthritis such as the disease-modifying anti-rheumatic drug methotrexate (MTX) and recent biologic agents have greatly improved the quality of life of patients. This is partly due to early administration of therapeutic intervention which not only improves response rate but also mitigates joint damage and disability. The collaborative initiative aims to allow drug researchers to enroll patients during the early stage of the disease by setting a standardized and more comprehensive assessment procedure for detecting early rheumatoid arthritis. Rheumatoid arthritis cannot be diagnosed with a single test. Several physical symptoms and laboratory results have to be taken into consideration. The 2010 classification system assigns the following scores when weighing the signs of rheumatoid arthritis for clinical trial purposes. This screening procedure is aimed at patients with at least one swollen joint and synovitis that cannot be explained better by another disease:

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One point when two to ten large joints are involved

Two points when one to three small joints are involved regardless of the presence of a large swollen joint

Three points when four to ten points are involved, regardless of the presence of a large swollen joint

Four points when more than ten joints are affected

Two points for the presence of low-positive rheumatoid factor or low-positive anti-citrullinated protein antibody or ACPA [18] 

Three points for elevated, positive rheumatoid factor or high-positive ACPA

One point for high erythrocyte sedimentation rate or C-reactive protein value

One point for cases lasting for six weeks or longer.

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The new diagnostic criteria agree with the latest understanding of disease and treatment techniques. Unlike the 1987 criteria, the 2010 system does not put emphasis on the destruction of joints since this condition is what early detection is meant to prevent. In medical practice, however, the 1987 criteria are still widely applied and require the presence of at least four of the specified conditions in a certain period of time.

<b>Laboratory Tests</b>

To confirm if certain physical symptoms are indicative of rheumatoid arthritis, laboratory tests may be required. Rheumatoid factor (RF) is a highly recognized indicator of rheumatoid arthritis. This can be measured via latex fixation/immunoturbidimetry which determines the levels of different immunoglobulin isotopes: IgM RF, IgA RF, and IgG RF. The normal sensitivity of RF for rheumatoid arthritis ranges from sixty to ninety percent. As the disease progresses, seropositivity likewise increases. Specificity is quite relatively low (between seventy and eighty percent), and those who suffer from other forms of rheumatism have high RF level. Clinical findings show that the elevation of either IgG RF or IgA RF, or both, in people who have also IgM RF and joint disease is a significant indicator of rheumatoid arthritis. These combinations are rare in other cases of rheumatic diseases in which there is a presence of IgM RF. IgA and IgG RF are, however, not highly sensitive and their use in RA diagnosis is quite limited.

Anti CCP-sensitivity is more specific than RF when diagnosing rheumatoid arthritis. As compared with RF marker, anti-CCP is considered equally sensitive and more specific. Combining the two markers results into greater sensitivity than either marker alone. Based on a study involving more than 550 patients with suspected rheumatoid arthritis, anti-CCP was present in thirty of eighty-seven subjects who had no elevated level of three RF isotypes (IgM, IgA, and IgG by enzyme linked immunosorbent assays or ELISA). [19] 

<b>Prognosis</b>

It is possible for RF and anti-CCP to be detected years prior to the manifestation of symptoms. A study involving blood donors estimated the sensitivity of anti-CCP level in the prognosis of rheumatoid arthritis between twenty-nine and thirty-seven percent, with a specificity of about ninety-eight percent.12 With the passage of time, the level of sensitivity increases. Anti-CCP testing may also be useful in the future diagnosis of rheumatoid arthritis in patients suffering from undifferentiated arthritis. Rheumatic or rheumatoid arthritis may progress or remain stable. Some patients eventually suffer from progressive joint damage, others have self-limiting condition. Predicting the course of progression would be a big help in the proper prescription of disease-modifying anti-rheumatic drugs and prevention of misdiagnosis. Elevated level of RF suggests higher risk of progressive joint damage. Very high titers can be an indication of severe joint conditions. Rheumatoid nodules, Felty's syndrome, peripheral neuropathy, vasculitis, skin ulcers, and IgA and IgG RF positivity in early stage of rheumatoid arthritis may be signs of a more severe disease and higher risk of radiographic progression. Anti-CCP testing can predict the course of progression in a ten-year period following the onset of the disease. Research findings showed that baseline anti-CCP (sixty-seven percent) and RF (sixty-nine percent) had similar sensitivity for prediction of radiographic progression at five years, but anti-CCP markers had significantly higher specificity at fifty-six percent compared with twenty-four percent for RF. [20] 

Patients who are positive in anti-CCP but negative in RF may still be susceptible to rheumatoid arthritis, although the risk is lower in patients with positive RF and negative anti- CCP test results. People who have negative results on both markers have minimal risk of developing rheumatoid arthritis, but negative test results on both assays do not rule out existing rheumatoid arthritis. People with elevated RF and chronic HCV or other polyarticular arthritis-induced infections are likely to be diagnosed with rheumatoid arthritis if the anti-CCP test result is positive. Abnormal levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) may indicate progression of rheumatoid arthritis, although these conditions can also be caused by other diseases. The level of disease activity is relatively low when ESR and CRP are in normal amounts. When CRP and ESR findings are discordant, CRP seems to be a more reliable indicator of disease activity. One study showed that high level of CRP may be a predictor of long-term progression of rheumatoid arthritis. [21] 

<b>Gut Microbe as a Prognostic Marker</b>

The Mayo Illinois Alliance for Technology-Based Healthcare reported that gut bacteria could have a role in rheumatic arthritis when they exceed the normal count. Mayo conducted a study involving genetically engineered mice with predisposition to rheumatic arthritis. The findings showed that the immune response of mice to gut bacteria seemed to mimic the gender risk trends found in humans as female mice were prone to develop rheumatic arthritis. Through genomic sequencing technologies, the Alliance rendered solid evidence on the potential role of gut microbe as a prognostic biomarker for rheumatic arthritis. [22] The research is the first to offer strong evidence that bacterial infection may have a role in the development of rheumatoid arthritis.

<a>Modern Research Findings</a>

Genetic engineering has played a key role in recent discoveries of possible ways to cure rheumatoid arthritis. Biologics have become the preferred treatment for rheumatoid arthritis, but several of these medications lose effectiveness over time and are more expensive than standard medications such as disease-modifying anti-rheumatic drugs. Introduced in the 1990s, biologic treatments mimic the natural antibodies to control inflammation. These medications are usually prescribed when cheaper drugs do not work or as substitute for drugs with side-effects. Response rate also varies from patient to patient.

<b>PS-372424</b>

Recent work on possible rheumatoid arthritis treatments focuses on controlling inflammation at immune system level. A recent study involved the PS-372424 compound demonstrated a potential capacity to prevent white blood cells from finding their way to the joints. By preventing these cells from reaching the joints, bone damage can be prevented or mitigated. The study involved mice which were genetically engineered to possess a human-like immune system. The compound was able to prevent activated T-cells from damaging the joints. Only the T-cells implicated in the disease were affected. The compound binds to receptor CXCR3 which only the activated T-cells possess, thus causing no harm on other white blood cells. The mechanism has the advantage of being more specific and perhaps safer since it does not compromise the entire immune system. The compound opens the possibility of completely preventing the onset of inflammation that leads to rheumatoid arthritis. [23] 

<b>MMP-9</b>

An enzyme called MMP-9 that belongs to a class of protein, has also been the subject of a study with the aim of developing treatment for autoimmune diseases. The enzyme performs critical roles such as facilitating wound repair, but it triggers autoimmune problems when it is synthesized excessively. The research team used a vaccine to induce the immune system of mice to synthesize antibodies that can target the enzyme. The technique works in the same way as injecting a vaccine with dead virus to trick the immune system into killing live virus. In this experiment, the mice received an artificial metal zinc-histidine complex. Blood samples derived from the laboratory mice had antibodies with structural and functional similarities with MMP inhibitors. Dubbed as metallobodies, these antibodies can bind tightly to MMP-2 and MMP-9 of both mice and humans. The novel technique has the potential to treat autoimmune diseases such as rheumatoid arthritis and regional enteritis or Crohn's disease. [24] 

<b>Anti-Interleukin (IL)-6 Receptor Antibody</b>

Another study, led by Austrian researchers, showed that anti-interleukin (IL)-6 receptor antibody can remarkably slow down the progression of joint damage even if the rheumatoid arthritis has been active. [25] After a year of treatment, rheumatoid arthritis patients taking methotrexate and placebo got an average score of around 21.7 on the clinical disease activity index, whereas patients who took tocilizumab (Actemra) in addition to methotrexate got a mean score of 20.2. The remarkable difference between the two was evident in the progress of the disease as shown in radiographic findings - with a mean change of 1.2 points for the first group and 0.4 points among tocilizumab patients. Recent data revealed that tumor necrosis factor inhibitors can slow down or prevent radiographic progression, even in people who have been symptomatic or those who chronically develop high level of acute phase reactants. To determine if the same is true with IL-6 inhibition, the researchers drew data from a randomized trial involving 531 patients grouped into two: those who received methotrexate plus placebo and those who received methotrexate and tocilizumab. Those who were randomized to get placebo demonstrated significant association between worsening of radiographic scores and disease activity indices at the first year, whereas those receiving tocilizumab showed low correlation between X-ray progression and any disease variables including swollen joint counts, C-reactive protein levels, and the simplified disease activity index. Erosion scores differ significantly between the two groups throughout the duration of the study, with the placebo group reporting a change of 0.65 points while the second group had 0.25 points. Corresponding changes on the narrowing of joint space were 0.53 and 0.14 points, respectively. The data indicates that tocilizumab interferes with the progression of radiographic progression of rheumatoid arthritis irrespective of disease activity.

<b>Anti-TNF Agents</b>

Clinical tests confirm the efficacy of anti-TNF agents in terms of slowing down the progress of rheumatoid arthritis. The biologic agent is assumed to work by suppressing osteoclasts in joint lesions. More cytokines regulating matrix degradation may be involved as suggested by results of several animal studies. [26] 

Recently, researchers discovered osteoclast-mediated bone resorption that is controlled by the receptor activator of nuclear factor kB ligand (RANKL), which is found in a wide range of cell types, such as T cells and synoviocytes, that play a role in the development of rheumatoid arthritis. Findings suggest that these cells have a role in osteoclast maturation and activation in the presence of cytokines such as TNF-a and M-CSF. Those with rheumatoid arthritis have high level of soluble decoy receptors to RANKL, but their number normalizes following intake of TNF inhibitors.

<b>Side-Effects</b>

When the prescribed dosage is followed, anti-tumor necrosis factor (anti-TNF) drugs would not expose patients to higher risk of infection, according to a study published on the Annals of the Rheumatic Diseases. [27] When doses exceed the recommended level, however, anti-TNF agents would double the risk of developing infections. These findings were drawn from the analysis of data from eighteen trials involving 8,800 patients with rheumatoid arthritis, with an average follow-up period of about one year. Those who were treated with anti-TNF agents with the right dosage did not experience higher risks of death and other severe adverse conditions such as infections, non-melanoma skin cancers, lymphoma or non-cutaneous cancers. Those who took the drug two or three times more than the recommended dose were more likely to get serious infection, although their risk level fell as the trial progressed.

<a>Analysis</a>

Just as with other autoimmune disorders, the pathological mechanism of rheumatoid arthritis is still unclear. Genetic engineers have made promising discoveries that give clues as to how the disease can be stopped from progressing, but more is yet to be learned in terms of specific factors that cause the immune system to attack healthy synovial membranes. Advanced gene mapping and sequencing technologies allow researchers to gain better understanding of the pathology of autoimmune disorders such as rheumatoid arthritis. So far, these advances have led to the discoveries of genes that could be a causative factor. Other experiments have resulted into biologics that alter the way immune system behaves at the onset of rheumatoid arthritis. In recent years, heath care professionals specifically addressing rheumatoid arthritis have renewed their efforts to manage the disease by emphasizing early diagnosis, thus optimizing the efficacy of anti-rheumatic drugs and biologics. Clinical studies pointed out throughout this writing provide invaluable help in diagnosing and distinguishing rheumatoid arthritis, which shares many common physical symptoms with other types of inflammatory and autoimmune disorders. Laboratory tests focus on the detection of rheumatoid factor and anti-citrullinated protein antibody to rule out or diagnose the disorder at the earliest stage possible so as to increase the chance of rheumatoid arthritis remission through medications.

Moreover, rheumatoid arthritis is only one kind of inflammatory arthritis. [28] An inflammatory arthritis is an autoimmune disease wherein a person's own immune system attacks the synovial membrane, inflaming it and making it overproduce synovial fluid, which is the natural joint lubricant. This type of arthritis also damages and wears the articular cartilage. [29] The chronic rheumatoid arthritis develops in joints on both sides of the body such as the limbs and their parts. Rheumatoid arthritis is often distinguished from other types of arthritis by this bilateral occurrence involving many joints. Additionally, rheumatoid arthritis may also affect not only the joints but as well as organs outside of the joints, including the skin, the eyes, the lungs, the kidneys, the heart, the nerves, or even the blood. [30]