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Rheumatoid Arthritis:
Rheumatoid Arthritis (RA) is a systemic rheumatic disease characterized by arthritis of many joints,usually in a systemic pattern (involving the right and left sides of the body roughly equally). Typically,RA causes pain, stiffness, warmth, redness and swelling of the joints.
Over time,the affected joints may become misshapen,misaligned and damaged, but not all patients have erosive (joint-damaging) disease. Synovial tissue surrounding the smooth,shiny cartilage -that lines the joint becomes inflamed and filled with cells called lymphocytes, macrophages,polymorphs,and fibroblasts. This thick,inflamed synovial membrane  is called the pannus.
The cells within the pannus becomes activated and release enzymes and chemicals that both permanently damage the cartilage and the bone and also attract more cells into the inflamed tissue.
In RA,this inflammatory process is like a one way highway,the inflammation can continue indefinitely causing more and more damage,possibly leading to joint deformity destruction, and may erode the surrounding ligaments and bones as it spreads.
The joint lining,can normally be seen with the aid of a microscope but in RA patients it becomes thick and squishy like bread -dough, resulting in pain and inflammation.The rheumatoligist are trained so they can feel it. This distinct manifestation does not occur in osteoarthritis.
This inflammatory process is part of the body's immune system.The immune system is a natural defense against invaders such as bacteria,viruses,and even cancer. The cells of the immune system recognize and respond to invaders by making antibodies to combat invaders or by attacking invaders directly.
 Although the immune system is normally activated by a foreign agent,it can be activated to attack normal cells. In RA,for unknow reasons,the immune system becomes activated and causes marked inflammation in the synovial membrane. Many of the drugs used to fight RA have anti-bacterial and/or anti-immune system activity.
The damage to the joints caused by RA is thought to be caused by the interaction of many inflammatory cells and chemicals. Cytokines,like tumour necrosis factor (TNF),are secreated by synovial fibroblasts and other cells resulting in pain and inflammation. TNF may also be responsible for influencing other inflammatory compounds including the interleukins,collagenase,and prostaglandins.
The most disabling form of arthritis,RA generally affects more than one joint at a time,the elbows,shoulders,hips,knees and neck. Ordinarily,it affects both hands or both feet (sole of the feet-toes may be involved). It can result in loose,deformed joints,loss of mobility,and diminished strength.
It is common to have 30 minutes to an hour or more of morning stiffness. Affected joints feel warm to the touch. On days when the disease is more active,one may experience more fatigue,loss of appetite,low-grade fever, sweats,and difficulty sleeping.
Inflammation in the membranes surrounding internal organs,such as the heart, lungs or eyes may become involved in the more severe type of disease. The course of the disease varies betwen patients. Mild disease is common,in which patients have pain and stiffness,but no joint damage occurs and the course of the disease is short. For other patients, damage occurs early,requiring aggressive medical,surgical treatment and the disease persists for a long time (life-long).  
Patients  may notice worsening and improvement  for no apparant reason. Over time,the synovium membrane (the thin layer of cells lining the joint) become inflamed,enzymes are released---The synovium becomes thick and invasive, and the enzymes eat away at cartilage, bone,tendons and ligaments near the joint causing havoc for many patients with the moderate-severe type of disease.
The most important goals in treating RA are maintaining function,reducing pain and preventing future joint damage. If these are successfully achieved,quality of life will be improved. The treatment themselves involving drug therapy  may cause their own problems therefore appropiate considerations of risks and benefits and proper monitoring of therapy are critical steps for all patients.

Toxicity of drugs used in RA therapy  may range from mild to serious and from reversible to irreversible. The definition of rare toxicities are those which occur in <1% of patients using the agent,uncommon in 1-10%,and common in >10%.  Toxicities of drugs used in RA that require monitoring include gastrointestinal (GI) bleeding, hypertension, hyperglycemia,mascular damage, renal damage, hepatotoxicity, and myelosuppression.
Reduction in the incedence,severity,and unfavorable outcomes of these toxicities can be attempted by:
1) pre-treatment assessment to identify patients with risk factors of toxicity.
2) careful patient and physician education about safe doseage and the signs and symptoms of toxicity.
3) appropiate monitoring with physician follow-up and periodic laboratory studies.
Since multiple physicians may be following a patient with RA,an explicit plan should be made among the physicians and the patient to assign responsibility for monitoring at the beginning of treatment. This plan should also detail who will make adjustments in the anti-rheumatic medications.

The toxicities of NSAIDs include dyspepsia (common),gastric or ulceration (uncommon) renal insufficiency (rare),confusion,depression,rash,headache (rare),and hepatic toxicities (rare). NSAIDs may also reversibly inhibit platelet function and prolong bleeding time.
Patients with prior aspirin hypersensitivity are also at risk for developing bronchial spasms (rare),when taking NSAIDs. There appears to be few differences in the frequency of serious toxicities among  the different NSAIDs.
All NSAIDs can cause renal complications,including reversible renal insufficiency,papillary necrosis,nephrotic syndrome,intestitial nephritis,and renal failure. High-risk groups for renal toxicity include the elderly,particularly those receiving diuretics and patients with pre-existing renal disease,congestive heart failure,cirrhosis or altherosclerotic heart disease or any altered physiologic state in which renal blood flow is being maintained by compensatory vasodilatation (dilation of blood vessels).
To prevent renal toxicities in patients at risk NSAIDs should be started in modest doses and then carefully increased. Patients should be instructed  to report signs of fluid retension evidenced by weight gain or edema development if they become ill and dehydrated or if they are to begin treatment with diuretics or angiotensin-converting enzyme (ACE) inhibitors.
NSAIDs may cause elevation of liver enzyme levels but severe hepatotoxicity is rare. There is no evidence that abnormal findings on liver function tests in the absence of clinical symptoms change the outcome or are associated with serious hepatotoxicity.
The value of routine liver finction test monitoring for most patients receiving NSAIDs is uncertain. Liver function should be monitored in patients who are treated with diclofenac or in those who have intrinsic liver disease or in whom it is suspected.
Prevention of toxicity may be enchanced by pre-treatment assessment of individual risk factors for toxicity and by careful patient and physician education about safe use of the drug.
Patients and their physicians must be alert to the signs and symptoms of toxicity that should prompt discontinuation of the drug and physician reassessment. Some drug toxicity may be discovered by appropiate laboratory monitoring before serious problems become clinically apparent. The effects of  toxicity can result in  serious consequences,especially in a setting,where it is undetected.
The 3 major drug categories for the treatment of  RA are the NSAIDs, DMARDs and glucocoriticoids. Most NSAIDs have common GI and renal toxicity that may be averted by careful  patient selection and administeration of the drug.
The individual DMARDs have specific toxicities for which monitoring protocols have been developed. The serious side effects of systemic glucocorticoids  are largely related to dose and duration of treatment.   Build Date  2001-S.F.K.

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