Autoimmune disorders rheumatoid arthritis

Photophoresis is a variant of PUVA treatment (Edelson et al., 1987 Horio, 2000). Leukocytes from patients with cutaneous T-cell lymphoma or autoimmune disorders (rheumatoid arthritis and systemic sclerosis) are exposed to UVA radiation in the presence of a psoralen and given back to the patients. It is believed that PUVA changes some surface markers of T-cells and thus triggers the immune system. Thus, this treatment can be regarded as a beneficial application of a photoallergic reaction. 

TNF is a pleiotropic cytokine exerting a wide range of cellular responses, that affect biological processes such as lipid metabolism, coagulation, and insulin resistance and the function of endothelial cells. As a major proinflammatory cytokine TNF is also involved in progression of diseases like cancer, Alzheimer, Diabetes type II, cardiovascular, pulmonary or neurological disorders, and many autoimmune diseases. Blocking the action of TNF clearly reduces its inflammatory potential on various autoimmune disorders like Crohn s disease, rheumatoid arthritis (RA), and psoriasis. 

The definition of an overlap syndrome dictates that the criteria for diagnosis of both disorders (in the present context, of PM/DM and of some other connective tissue disorder), are fulfilled. It is not unexpected that those syndromes which overlap with PM/DM are also either known autoimmune conditions or ones in which an autoimmune basis is strongly suspected. The association of these disorders with PM/DM syndromes may not materially alter the basic histopathological featmes expected in PM/DM but some differences may be identifiable. The disorders most frequently associated with an overlap syndrome are rheumatoid arthritis, systemic lupus erythematosis, scleroderma, and mixed connective tissue disease. 

Chronic autoimmune disorders or infections, such as human immunodeficiency virus (HIV) infection or rheumatoid arthritis (anemia of chronic disease)... 

Besides anemia associated with cancer and CKD, anemia of chronic disease can result from inflammatory processes and occurs commonly in autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus. In treating these types of anemia of chronic disease, the most important principle is treating the underlying disease. These patients also may have iron deficiency and should be treated in the manner already discussed. Erythropoietin therapy such as epoetin-alfa therapy at a dose of 150 units/kg three times a week also may be used in these patients. 

If you look in the medical literature, you will often see the term placebo defined as a non-specific treatment. What does it mean to say that a treatment is not specific It could mean that the treatment is effective for many different disorders, rather than for only one particular condition. In this sense, placebos are indeed non-specific. Besides depression, placebos have been shown to affect anxiety, pain, ulcers, irritable bowel syndrome, Parkinson s disease, angina, autoimmune diseases, Alzheimer s disease, rheumatoid arthritis, asthma, gastric function, sexual dysfunction and skin conditions. We know this from the thousands of studies in which placebos have been used as control conditions, against which the effects of medication have been evaluated, and from studies that were specifically designed to assess the placebo effect. 

In addihon to treahng tumors, and because depleting B cells in humans with rituximab has been found to be safe, Rituxan is now in clinical trials and has shown efficacy for a number of autoimmune disorders. These include rheumatoid arthritis, idiopathic thrombocytopenia purpura (ITP, a platelet-depletion disorder), and lupus. It is expected that depleting B cells with rituximab will be approved in a nononcology indication within several years. 

Autoimmune disorders Development or exacerbation of autoimmune disorders, including myositis, hepatitis, idiopathic thrombocytopenic purpura, psoriasis, rheumatoid arthritis, interstitial nephritis, thyroiditis, and systemic lupus erythematosus have been reported in patients receiving alpha interferon. 

Cyclosporine appears to have promise in the treatment of autoimmune diseases. It has a beneficial effect on the course of rheumatoid arthritis, uveitis, insulin-dependent diabetes, systemic lupus erythematosus, and psoriatic arthropathies in some patients. Toxicity is more of a problem in these conditions than during use in transplantation, since higher doses of cyclosporine are often required to suppress autoimmune disorders. 

Azathioprine also has applications in certain disorders with autoimmune components, most commonly rheumatoid arthritis. It is as effective as cyclophosphamide in the treatment of Wegener s granulomatosis. It has largely been replaced by cyclosporine in immunosuppressive therapy. Relative to other cytotoxic agents, the better oral absorption of azathioprine is the reason for its more widespread clinical use. 

Because of these immunosuppressant activities, hydroxychloroquine is used to treat some autoimmune disorders, eg, rheumatoid arthritis and systemic lupus erythematosus. It has also been used to both treat and prevent graft-versus-host disease after allogeneic stem cell transplantation. 

The effectiveness of immunosuppressive drugs in autoimmune disorders varies widely. Nonetheless, with immunosuppressive therapy, remissions can be obtained in many instances of autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, type 1 diabetes, Hashimoto s thyroiditis, and temporal arteritis. Improvement is also often seen in patients with systemic lupus erythematosus, acute glomerulonephritis, acquired factor VIII inhibitors (antibodies), rheumatoid arthritis, inflammatory myopathy, scleroderma, and certain other autoimmune states. 

Until the role of echinacea in immune modulation is better defined, this agent should be avoided in patients with immune deficiency disorders (eg, AIDS, cancer), autoimmune disorders (eg, multiple sclerosis, rheumatoid arthritis), and patients with tuberculosis. While there are no reported drug interactions for echinacea, some preparations have a high alcohol content and should not be used with medications known to cause a disulfiram-like reaction. In theory, echinacea should also be avoided in persons taking immunosuppressant medications (eg, organ transplant recipients). 

Autoimmune responses seem to be the underlying basis for a number of diseases, including rheumatoid arthritis, diabetes mellitus, myasthenia gravis, systemic lupus erythematosus, scleroderma, polymyositis/der-matomyositis, and several other disorders.25,27,44 As indicated previously, it is not exactly clear what factors cause autoimmune responses, as well as why certain individuals are more prone to autoimmune-related diseases. Nonetheless, drugs that suppress the immune system can limit damage to various other tissues, and these drugs may produce dramatic improvements in patients with diseases that are caused by an autoimmune response. 

Clinical Use. Cyclophosphamide (Cytoxan, Neosar) is an anticancer alkylating agent that is commonly used in a variety of neoplastic disorders (see Chapter 36). This drug may also be helpful in suppressing the immune response in certain autoimmune diseases, such as multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis.12 43 High doses of cyclophosphamide are also used to prevent tissue rejection in patients receiving bone marrow transplants and other organ transplants. 

Therapists also deal with the rehabilitation of musculoskeletal disorders that are caused by an autoimmune response. Many of these diseases attack connective tissues, and autoimmune diseases such as rheumatoid arthritis, dermatomyositis, and systemic lupus erythematosus are often the primary reason that patients undergo rehabilitation. Patients with a compromised immune system may develop musculoskeletal problems related to their immunodeficient state. Hence, immunomodulating drugs are frequently used in many patients receiving physical therapy and occupational therapy. 

One controlled, double-blind trial plus anecdotal evidence attest to the efficacy of chlorambucil in rheumatoid arthritis. Chlorambucil has also been used in Behef s disease, systemic lupus erythematosus, vasculitis, and other autoimmune disorders. 

Increased levels of ROS due to oxidative stress have been consistently found in cardiovascular diseases as atherosclerosis or hypertension [18]. There is certain evidence that the free radicals involved in Parkinson s disease are mainly due to the production of increased levels of free radicals during oxidative metabolism of dopamine [19]. Oxidative stress, manifested by protein oxidation and lipid peroxidation (LP), among other alterations, is a characteristic of Alzheimer s disease [20] and in the pathogenesis of diabetes related complications. Treatment with antioxidants seemed to be a promising therapeutic option for these diseases [21], The inflammatory nature of rheumatoid arthritis implies that a state of oxidative stress may also exist in this disease [22,23]. Also, free radicals have a certain role in Huntington s disease [24,25], age related degeneration [26], and some autoimmune disorders [27],... 

Chronic inflammation is often associated with diabetes mellitus and autoimmune disorders such as rheumatoid arthritis and organ failure. Hyper-insulinemia increases WBC and elastase [103, 104], Excess heavy chains can result due to uncoupling of Bik from the cell matrix during chronic inflammation. PAR-triggered cells appear to be a primary cause of gene expression polymorphism and likely precede detectable abnormalities within damaged cells. 

Leucovorin or folinic acid, a mixture of the 6R- and 6S,-diastereomers of 5-formyltetrahydrofolic acid, is an important clinical agent which may be used as a remedy for megaloblastic anemia and as an antidote for inadvertent overdosages of antifolates in patients with cancer, parasitic diseases, or autoimmune disorders such as psoriasis and rheumatoid arthritis. In view of these applications it is surprising that few significant improvements in the manufacture of leucovorin have occurred... 

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