Rheumatoid Incidence

NSAIDs are used as the first-line treatment of rheumatoid arthritis, osteoarthritis, systemic lupus erythematosis and other inflammatory diseases, and are thus amongst the most widely used dtugs in the developed world. This widespread use inevitably entailed a considerable associated morbidity, in particular a high incidence of gastric toxicity. In the USA alone, perforations, ulcers and bleeds lead to the hospitalisation of 100,000 patients per year, and about 15% of these die while under intensive care. 

Gridley, G. et al., Incidence of cancer among patients with rheumatoid arthritis, J. Natl. Cancer Inst., 85, 307, 1993. 

Stolt P. et al., Quantification of the influence of cigarette smoking on rheumatoid arthritis results from a population based case-control study, using incident cases, Am. Rheum. Dis., 62, 835, 2003. 

The first-line agents in the treatment of rheumatoid arthritis are non-steroidal anti-inflammatory drugs such as diclofenac. Diclofenac and indometacin, another NSAID, tend to have similar activity hov/ever, indometacin has a higher incidence of side-effects and therefore diclofenac is more appropriate for initial treatment. Sodium aurothiomalate is classified as a disease-modifying antirheumatic drug and is used as a second-line treatment in rheumatoid arthritis, but has been superseded by methotrexate, administered v/eekly. Paracetamol is often indicated in the management of osteoarthritis. Local intra-articular injections of dexamethasone may be administered for the relief of soft-tissue inflammatory conditions. 

The sahcylates are useful in the treatment of minor musculoskeletal disorders such as bursitis, synovitis, tendinitis, myositis, and myalgia. They may also be used to relieve fever and headache. They can be used in the treatment of inflammatory disease, such as acute rheumatic fever, rheumatoid arthritis, osteoarthritis, and certain rheumatoid variants, such as ankylosing spondylitis, Reiter s syndrome, and psoriatic arthritis. However, other NS AIDS are usually favored for the treatment of these chronic conditions because of their lower incidence of GI side effects. Aspirin is used in the treatment and prophylaxis of myocardial infarction and ischemic stroke. 

Methotrexate is one of the few anticancer drugs that can be safely administered intrathecally for the treatment of meningeal metastases. Its routine use as prophylactic intrathecal chemotherapy in acute lymphoblastic leukemia has greatly reduced the incidence of recurrences in the CNS and has contributed to the cure rate in this disease. Daily oral doses of methotrexate are used for severe cases of the nonneoplastic skin disease psoriasis (see Chapter 41), and methotrexate has been used as an immunosuppressive agent in severe rheumatoid arthritis. 

It has become apparent that reduction in the dose of the constituents of oral contraceptives has markedly reduced mild and severe adverse effects, providing a relatively safe and convenient method of contraception for many young women. Treatment with oral contraceptives has also been shown to be associated with many benefits unrelated to contraception. These include a reduced risk of ovarian cysts, ovarian and endometrial cancer, and benign breast disease. There is a lower incidence of ectopic pregnancy. Iron deficiency and rheumatoid arthritis are less common, and premenstrual symptoms, dysmenorrhea, endometriosis, acne, and hirsutism may be ameliorated with their use. 

Other potential adverse responses include malignancy (e.g., lymphoma), liver disease, heart failure, lupuslike disease, irritation around the injection site, and demyelinating disorders that mimic multiple sclerosis.34,70 88 The incidence of these adverse effects, however, seems to be fairly low. For the most part, these drugs provide an acceptable risk-to-benefit ratio for most people with rheumatoid arthritis. Patients should, however, be screened carefully for any risk factors before beginning drug therapy, and should likewise be monitored periodically for any potential adverse reactions to these drugs. 

Correct answer = C. Among the NSAIDs, aspirin is among the worst for causing gastric irritation. Aspirin is an effective analgesic and is used to reduce muscle pain. It also has antipyretic actions so that it can be used to treat fever. Because of its anti-inflammatory properties, aspirin is used to treat pain related to the inflammatory process, for example, in the treatment of rheumatoid arthritis. Low doses of aspirin also decrease the incidence of transient ischemic attacks. 

Rheumatoid arthritis is a chronic, recurrent systemic inflammatory disorder that primarily affects the joints. The incidence is typically between 1% and 3% of the UK population with a female preponderance of 3 1. Age of onset is typically between the ages of 20 and 40 years. The small joints of the hands and feet are usually affected first and presentation is usually symmetrical. Deformities may arise and the condition may progress to larger joints. In the most severe of cases, extra-articular tissues may be affected, including the lungs, muscle tissues and blood vessels. Additional complications may include Sjdgren s syndrome and Felty s syndrome. 

Posterior subcapsular cataracts (PSCs) can occur with all routes of administration (Figure 12-2), including systemic, topical, cutaneous, nasal aerosols, and inhalation corticosteroids. In a study of 44 rheumatoid arthritis patients treated with various steroids, including prednisone and dexamethasone, 17 (39%) developed bilateral PSCs. Dosage and duration of therapy appeared to be correlated with the incidence of cataract development. Patients who received prednisone therapy for 1 to 4 years showed an 11% incidence if the dose range was less than 10 mg/day a 30% incidence if the dose was... 

Additional evidence became available when several investigators observed an increased incidence of PSCs in children receiving systemic steroid therapy for rheumatoid arthritis, systemic lupus erythematosus, and the nephrotic syndrome. Although steroid-related PSCs do not usually occur in adults within the first year of therapy, regardless of dose, children can manifest lens changes at lower doses and within shorter periods. 

There is indirect evidence of sex differences in immunology. Women have a higher incidence of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. The influence of sex hormones on the immune system may provide insight into these immunological disorders. For example, estrogen stimulates both humoral and cell-mediated immunity, whereas testosterone has the opposite effect (126). Therefore, it is not surprising that there is sex-dependent variability in response to immunosuppressive agents. 

Intake of dietary sources of n-3 fatty acids is associated with reduced incidence and severity of inflammatory disorders, cardiovascular diseases, and some cancers in humans (12, 98-103). Populations consuming fish that are rich in n-3 fatty acids are known to have a low incidence of atherosclerotic disorders (104). Dietary fish oil, which is high in EPA and DHA, also was shown to reduce myocardial ischemic damage (105) and ventricular fibrillation (106). The antitumorigenic effect of n-3 fatty acids was demonstrated in breast cancer (107), colon cancer (108-110), and pancreatic neoplasm (111). In addition to their beneficial influence on cardiovascular disorders and cancers, n-3 fatty acids are also known to decrease the severity and minimize symptoms of inflammatory diseases, including rheumatoid arthritis (15) and inflammatory bowel disease (16), and may be of benefit in correcting psychological disorders (17). 

Incidence of second cancers in patients treated for primary cancer can be as high as 15 times the normal rate. The use of immunosuppression in, e.g. rheumatoid arthritis and organ transplants, also increases the incidence of cancers. 

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