Lupus factors

Immunological abnormalities were reported in 23 adults in Woburn, Massachusetts, who were exposed to contaminated well water and who were family members of children with leukemia (Byers et al. 1988). These immunological abnormalities, tested for 5 years after well closure, included persistent lymphocytosis, increased numbers of T-lymphocytes, and depressed helper suppressor T-cell ratio. Auto-antibodies, particularly anti-nuclear antibodies, were detected in 11 of 23 adults tested. This study is limited by the possible bias in identifying risk factors for immunological abnormalities in a small, nonpopulation-based group identified by leukemia types. Other limitations of this study are described in Section 2.2.2.8. A study of 356 residents of Tucson, Arizona, who were exposed to trichloroethylene (6-500 ppb) and other chemicals in well water drawn from the Santa Cmz aquifer found increased frequencies of 10 systemic lupus erythematosus symptoms, 5 (arthritis, Raynaud s phenomenon, malar rash, skin lesions related to sun exposure, seizure or convulsions) of which were statistically significant (Kilbum and Warshaw 1992). 

Activated partial thromboplastin time aPTT is performed by adding calcium phospholipids and kaolin to citrated blood and measures the time required for a fibrin clot to form. In this manner, aPTT measures the activity of intrinsic and common pathways. Prolongation of aPTT may be due to a deficiency or inhibitor for factors II, V, VIII, IX, X, XI, and XII. It also may be due to heparin, direct thrombin inhibitors, vitamin K deficiency, liver disease, or lupus anticoagulant. 

Non-infectious causes of meningitis include malignancy, medications, autoimmune disease (such as lupus), and trauma.8,9 The most common pathogens causing bacterial meningitis, by age group and other risk factors, are found in Table 67-1. 

Whereas (32 glycoprotein 1 ((J2-GPI) is the target of anticardiolipin antibodies, prothrombin is the antigen for most lupus anticoagulants. Both these antibodies are risk factors for both venous and arterial thrombosis. In addition, complications such as thrombocytopenia and recurrent miscarriages are manifestations of the so-called antiphospholipid syndrome (97). 

Cooper, G.S. et al., Occupational risk factors for the development of systemic lupus erythematosus, J. Rheumatol., 31, 1928, 2004. 

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). 

Cooper, G.S. and Parks, C.G., Occupational and Environmental Exposures as Risk Factors for Systemic Lupus Erythematosus, Cu.r. Rheum. Reports, 6, 367, 2004. 

Morita, C., Horiuchi, T., Tsukamoto, H., et al. (2001) Association of tumor necrosis factor receptor type II polymorphism 196R with systemic lupus erythematosus in the Japanese molecular and functional analysis. Arthritis and Rheumatism. 44, 2819-2827. 

Twenty-five patients with systemic lupus erythematosis had high IgD antinuclear factor, and mean higher serum IgD concentrations were found in two groups of Vietnamese populations who live in an area endemic for malaria. 

Adalimumab is a recombinant, fully human antitumor necrosis factor monoclonal antibody approved in the US and Europe for the treatment of adult patients with moderate to severe, active rheumatoid arthritis. It has to be injected subcutaneously. The most common side effects of adalimumab are injection site reactions. Adalimumab increases the risk of rare serious infections. Rare side effects include worsening or initiation of congestive heart failure, a lupus-like syndrome, a promotion of lymphoma, medically significant cytopenias, and worsening or initiation of a multiple sclerosis like neurological disease. 

Prescribing perspective is to recognize that the previously acceptable counts, on treatment, between (500-650) X (f are hazardous since microvas-cular occlusion, including stroke, remain risks. The concurrent role of aspirin continues to be defined. Thus, while this has a sound theoretical benefit and is recommended to decrease platelet-endothelial cell interaction, occasional gastrointestinal tract bleeding may be found. Furthermore, associated hypercoagulability may be found and determinations of proteins C and S, mutations of factor V and II or elevated homocysteine, as well as the presence of anti-cardiolipin syndrome or lupus anticoagulant should not be overlooked. 

Long-term drug use leads to increased antinuclear antibody titers in more than 80% of patients more than 30% of patients receiving long-term procainamide therapy develop a clinical lupus erythematosus-like syndrome. The symptoms may disappear within a few days of cessation of procainamide therapy, although the tests for antinuclear factor and lupus erythematosus cells may remain positive for several months. 

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. 

Striking clinical results have been reported in inflammatory and auto-immune diseases, although in a somewhat limited number of cases . A low molecular mass chromosome-breaking agent was identified in the serum of patients with systemic lupus erythematosus. The chromosome aberrations in cultures of normal lymphocytes in the presence of this factor were reduced to normal values by the addition of BESOD to the culture medium... 

What are the predisposing factors identified in human patients that are important in the immune-media ted adverse effect lupus erythematosus caused by the drug hydralazine ... 

The predisposing factors for susceptibility to hydralazine-induced lupus identified in humans are (a) dose, (b) duration of therapy, (c) the ace ty la tor phenotype, (d) HLA (tissue) type, and (e) gender. 

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