Rheumatoid Clinical symptoms

It has been estimated that 1-2 per cent of the US population suffer from autoimmune conditions, including rheumatoid arthritis, MS and some forms of diabetes. In many instances, an autoimmune response results from the inappropriate activation of a specific subset of B- and/or T-lymphocytes. The most common immunotherapeutic approach to potentially treat such diseases is to induce depletion of the individual s T- and B-cell populations. This could be achieved by administration of an antibody raised against a surface antigen present on such cells. Initial trials, for example, have shown that injection of an (unconjugated) anti-CD4 antibody (cell surface glycoprotein present on many T-lymphocytes) over 7 days significantly reduced the clinical symptoms of rheumatoid arthritis for several months. 

The tetracycline antibiotic minocycline (Minocin) is modestly effective in the treatment of rheumatoid arthritis and is generally well tolerated. Radiographic evidence of its efficacy as a DMARD is lacking, although clinical symptoms do abate. It can be useful in the treatment of early, mild disease. A more detailed description of the pharmacology and chnical uses of minocycline is found in Chapter 47. 

The drug is effective against all four types of malaria with the exception of chloroquine-resistant P. falciparum Chloroquine destroys the blood stages of the infection and therefore ameliorates the clinical symptoms seen in P. malariae, P. vivax, P. ovale, and sensitive P. falciparum forms of malaria. The disease will return in P. vivax and P. ovale malaria, however, unless the liver stages are sequentially treated with primaquine after the administration of chloroquine. Chloroquine also can be used prophylactically in areas where resistance does not exist. In addition to its use as an antimalarial, chloroquine has been used in the treatment of rheumatoid arthritis and lupus erythematosus (see Chapter 36), extraintestinal amebiasis, and photoallergic reactions. 

Even the best therapy currently available does not completely eliminate all signs and symptoms of rheumatoid arthritis for most patients. Clinicians struggle with determining how much treatment is enough. Also, some patients show evidence of disease progression despite apparent control of clinical symptoms. How can these patients be identified and the treatment course changed before progression occurs ... 

Recently, a case of MCTD in a male patient occupationally exposed to PVC and other toxic agents was presented. Clinical symptoms consisted of typical signs of systemic LE, rheumatoid arthritis, and lupoid hepatitis. MCTD diagnosis was confirmed serologically by the presence of u i-ribonucleoprotein-autoantibo-dies. Prednisone, 60 mg daily, produced remission (Panaszek et al. 1993). Studnicka et al. (1995) presented a 58-year-old patient exposed to thermoplastic dusts, mainly PVC, for 10 years. He developed pneumoconiosis and secondary SSc. 

A 40-year-old female was treated with leflxmomide for 10 years because of rheumatoid arthritis and presented with clinical symptoms suggestive of pulmonary tuberculosis, which was confirmed by sputum smear examination. She started on antitubercular treatment but there was no improvement of cough symptoms. The cough improved markedly after discontinuation of leflxmomide therapy [71 ]. 

This point of view overlooks the fact that every well and normal individual is potentially an ill individual, and the roots of disease may be present in his make-up years before there is any overt disease. A dozen young men used as normal controls may each have metabolic peculiarities that point toward a different metabolic derangement gout, multiple sclerosis, diabetes, anemia, atherosclerosis, hypertension, nephrosis, hypothyroidism, rheumatoid arthritis, rheumatic heart disease, liver cirrhosis, and myasthenia gravis, for example, and yet at the time of their use as controls these young men may show no symptoms of the disease which is to appear later in life. It seems far from safe to assume that because an individual on clinical examination seems well, all of his blood values, for example, are normal and meaningless so far as disease susceptibilities are concerned. 

The safety and efficacy of Remicade when given in conjunction with methotrexate (MTX) were assessed in a multicenter, randomized, double-blind, placebo-controlled study of 428 patients with active rheumatoid arthritis despite treatment with MTX. All patients were to have received MTX for >6 months and be on a stable dose >12.5mg/week for 4 weeks prior to study. All Remicade and placebo groups continued their stable dose of MTX and folic acid. In addition to MTX, patients received placebo or Remicade by intravenous infusion at weeks 0, 2, and 6 followed by additional infusions every 4 or 8 weeks thereafter. The primary end point was the proportion of patients at week 30 who attained an improvement in signs and symptoms as measured by the American College of Rheumatology criteria (ACR 20). An ACR 20 response is defined as at least a 20% improvement in both tender and swollen joint counts and in 3 of 5 clinical criteria. At week 30, 43/86 (50%) of patients treated every 8 weeks with 3 mg/kg of Remicade plus MTX attained an ACR 20 compared with 18/88 (20%) of patients treated with placebo plus MTX ip < 0.001). 

Abatacept can be used as monotherapy or in combination with other DMARDs in patients with moderate to severe rheumatoid arthritis who have had an inadequate response to other DMARDs. It reduces the clinical signs and symptoms of rheumatoid arthritis, including slowing of radiographic progression. It is also being tested in early rheumatoid arthritis. 

Infliximab is used to reduce signs, symptoms and progression of rheumatoid arthritis. It is indicated for patients with moderate to severe active rheumatoid arthritis, where infliximab reduces infiltration of inflammatory cells into the inflamed areas of joints. Infliximab is also indicated in moderate to severely active Crohn s disease. It is used to reduce signs and symptoms and to maintain clinical remission. The number of draining enterocutaneous and rectovaginal fistulas is reduced by infliximab. It helps to maintain fistula closure in patients with fistulizing Crohn s disease. 

Meloxicam is an enolcarboxamide related to piroxicam that has been shown to preferentially inhibit COX-2 over COX-1, particularly at its lowest therapeutic dose of 7.5 mg/d. It is not as selective as the other coxibs. The drug is popular in Europe and many other countries for most rheumatic diseases and has recently been approved for treatment of osteoarthritis in the USA. Its efficacy in this condition and rheumatoid arthritis is comparable to that of other NSAIDs. It is associated with fewer clinical gastrointestinal symptoms and complications than piroxicam, diclofenac, and naproxen. Similarly, while meloxicam is known to inhibit synthesis of thromboxane A2, it appears that even at supratherapeutic doses its blockade of thromboxane A2 does not reach levels that result... 

Inflammation is associated with various diseases such as rheumatoid arthritis, cancer, myocarditis, arteriosclerosis, bowel diseases, multiple sclerosis, asthma, and many others. While several inflammatory markers are commonly expressed during any inflammatory disorder, some are symptom specific. Therefore, the gene array data will be particularly helpful in indicating the appropriate disease model for subsequent preclinical and clinical tests. Only functional, active extracts with potentially safe and novel modes of actions may then be subjected to labor-intensive large-scale extraction, fractionation, characterization, and isolation of novel bioactive components. We believe that the strategy as described schematically in Figure 4.1 will allow efficient use of plant extracts and other natural resources toward identification of novel drug leads for human health care. 

Complex scales, often made up of arbitrary combinations of symptoms and clinical signs, are also problematic. A review of 196 trials in rheumatoid arthritis identified more than 70 different outcome scales (Gotzsche 1989). A review of 2000 trials in schizophrenia... 

Women suffer far more frequently than men. Clinically, there is arthralgia of varying intensity and symptoms of chronic proliferative inflammation of the synovial fluid in the diseased joints. Systemic manifestations can be recognized on the basis of haematological, neurological, pulmonary, renal, cardiovascular and hepatic symptoms. Laboratory parameters show marked inflammatory criteria (s. tab. 38.2) as well as a rise in y-globulins and immunoglobulins M and G. The rheumatoid factor is often detectable, (s. p. 118) Alkaline phosphatase may be elevated. (lOO)... 

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