Systemic lupus erythematosus, and

Kovacic, P.J., J.D., Systemic lupus erythematosus and other autoimmune diseases from endogenous and exogenous agents unifying theme of oxidative stress, Mini Rev. Med Chem., 3, 568, 2003. 

Other studies describe similar beneficial effects for PUFA-enriched diets to treat Crohn s disease, other inflammatory bowel diseases such as ulcerative colitis, as well as psoriasis, asthma, systemic lupus erythematosus, and multiple sclerosis [57], Thus, immunomodulation by PUFAs appears to be a promising intervention for the treatment of many autoimmune and inflammatory diseases. 

A recent report by the National Institutes of Health estimated that at 14 to 22 million people in the United States are affected by an autoimmune disease.1 As a group, these diseases represent a leading cause of death among women under age 65, with systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes being the major sources of this impact on mortality.2 The autoimmune thyroid diseases, type 1 diabetes and rheumatoid arthritis are the most common of the autoimmune diseases (Table 25.1).3-5 Most autoimmune diseases disproportionately affect women. In the thyroid diseases, primary biliary cirrhosis, scleroderma, systemic lupus erythematosus, and Sjogren s syndrome, more than 85% of patients are female, but it is not known why the female predominance is so high in these specific diseases. 

For some autoimmune diseases, little is known about environmental factors involved in the initiation or progression of the disease. For other diseases, however, considerable research has been conducted on one or more types of exposures. Most epidemiologic studies of environmental influences have focused on multiple sclerosis, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, and small vessel vasculitis, but experimental studies using murine models of these diseases is limited (Table 25.1). 

Frostegard, J. et al., Lipid peroxidation is enhanced in patients with systemic lupus erythematosus and is associated with arterial and renal disease manifestations, Arthritis Rheum., 52, 192, 2005. 

Mohan, A.K. et al., Drug-induced systemic lupus erythematosus and TNF-alpha blockers, Lancet 360,646, 2002. 

Richardson, B. et al., Evidence for impaired T cell methylation in systemic lupus erythematosus and rheumatoid arthritis, Arthritis Rheum., 33,1665, 1990. 

Lp(a), Systemic Lupus Erythematosus, and Anti-phospholipid Syndromes. 103... 

Of the DMARDs, methotrexate (Rheumatrex) is the most widely prescribed. It is indicated for the treatment of rheumatoid arthritis and psoriasis it is also used for psoriatic arthritis, systemic lupus erythematosus, and... 

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. 

Agranulocytosis and neutropenia maybe noted in those with collagen vascular disease, including scleroderma and systemic lupus erythematosus, and impaired renal function. 

Azathioprine is approved for use in rheumatoid arthritis and is used at a dosage of 2 mg/kg/d. Controlled trials show efficacy in psoriatic arthritis, reactive arthritis, polymyositis, systemic lupus erythematosus, and Behget s disease. 

Although antimalarials improve symptoms, there is no evidence that these compounds alter bony damage in rheumatoid arthritis at their usual dosages (up to 6.4 mg/kg/d for hydroxychloroquine or 200 mg/d for chloroquine). It usually takes 3-6 months to obtain a response. Antimalarials are often used in the treatment of the skin manifestations, serositis, and joint pains of systemic lupus erythematosus, and they have been used in Sjogren s syndrome. 

MMF is effective for the treatment of renal disease due to systemic lupus erythematosus and may be useful in vasculitis and Wegener s granulomatosis. Although MMF is occasionally used at a dosage of 2 g/d to treat rheumatoid arthritis, there are no well-controlled data regarding its efficacy in this disease. 

The authors commented that fever associated with glucocorticoids occurs frequently, whereas leukopenia is rare. Fever and leukopenia are important signs of an exacerbation of systemic lupus erythematosus, and it would be difficult to distinguish between an exacerbation of the disease and an adverse effect of glucocorticoids. 

Among the adverse effects of pulse glucocorticoid therapy, joint manifestations are rare. A woman with systemic lupus erythematosus and nephritis developed transient bilateral knee effusions during pulse therapy with high doses of glucocorticoids (279). 

Zonana-Nacach A, Barr SG, Magder LS, Petri M. Damage in systemic lupus erythematosus and its association with corticosteroids. Arthritis Rheum 2000 43(8) 1801-8. 

Rhabdomyolysis occurred when atorvastatin was combined with ciclosporin for 2 months in a woman with systemic lupus erythematosus and a renal transplant (27). 

Bizzaro, N., Tonutti, E., Villalta, D., Tampoia, M., and R. Tozzoli, 2005, Prevalence and clinical correlation of anti-phospholipid-binding protein antibodies in anticardiolipin-negative patients with systemic lupus erythematosus and women with unexplained recurrent miscarriages. Arch Pathol Lab Med.l29(l) 61-8. 

Nojima, J., Kuratsune, H., Suehisa, E., Futsukaichi, Y., Yamanishi, H., Machii, T., Iwatani, Y., and Y. Kanakura, 2001, Association between the prevalence of antibodies to beta(2)-glycoprotein I, prothrombin, protein C, protein S, and annexin V in patients with systemic lupus erythematosus and thrombotic and thrombocytopenic complications. Clin Chem. 47(6) 1008-15. 

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. 

---