Multiple organ dysfunction syndrome.

Multiple organ dysfunction syndrome, including acute respiratory distress syndrome (ARDS) and renal failure, is described, its clinical features outlined, its origins in tissue oxidative stress following severe infections, surgical trauma, ionizing radiation, high-dosage drugs and chemicals, severe hemorrhage, etc., are defined, and its prevention and treatment prescribed.

Antimalarial drugs in systemic lupus erythematosus: use in pregnancy.

The 4-aminoquinoline radical containing antimalarial drugs are also used in the management of various connective tissue diseases including systemic lupus erythematosus (SLE) and rheumatoid arthritis. These agents are particularly useful for the management of inflammatory polyarthritis and skin disease. By raising the pH in intracellular compartments, these drugs interfere with normal phagocytic function which consequently enables them to interfere with antigen processing. Other actions include inhibition of platelet aggregation, this is advantageous in patients with phospholipid antibodies (aPL) which are known to predispose patients to recurrent arterial and venous clinical thrombotic events. Hydroxychloroquine has also been demonstrated to reduce serum lipid levels including cholesterol, triglycerides and low density lipoproteins. As it is now known that patients with SLE are at risk for accelerated artherogenesis and premature heart disease, this action may be an added benefit for these patients. The use of the 4-aminoquinoline radical containing antimalarial drugs during pregnancy is controversial. It is known that these agents can cross the placenta and are deposited in fetal pigmented tissues. These findings have led to the recommendation that these agents should be discontinued in pregnancy for patients with connective tissue diseases even though they have long been recommended for malarial prophylaxis in pregnant women travelling to malarial infested areas. Flares of SLE disease have been documented when these agents are discontinued and as flares of SLE disease activity are known to be detrimental to pregnancy outcome in patients with SLE, it is our opinion that these drugs should not be discontinued during pregnancy in a patient with lupus, particularly when the known terminal elimination half life is 1 to 2 months.

Sjögren's syndrome: a women's health problem.

Like many other systemic connective tissue diseases, Sjögren's syndrome (SS) occurs more frequently in women, with a female to male ratio of 9:1. Unlike other diseases, such as systemic lupus erythematosus, this syndrome occurs more frequently in menopausal and postmenopausal women, although there is now evidence to suggest some patients may have autoimmune diathesis years before they develop sicca complaints. Several clinical features of SS have particular relevance for the female patient. An abnormal pregnancy, as occurs in the neonatal lupus syndrome, may be the initial manifestation of an autoimmune diathesis. Dyspareunia and chronic fatigue are important complaints that are not taken seriously. This paper will address the clinical manifestations of SS, with particular emphasis on those features that demonstrate that SS is a women's health problem.

Sjögren's syndrome: History, clinical and pathological features.

The history, ocular and oral clinical features, and histopathology of Sjögren's syndrome are described. Primary Sjögren's syndrome is defined when only the ocular and oral components are present, while the secondary form refers to the association with a connective tissue disorder, especially rheumatoid arthritis, or other illness such as AIDS, hepatitis C infection, or biliary cirrhosis. Sjögren's syndrome is a common, but often overlooked disorder. Patients with severe disease run a forty-times risk of developing lymphoma usually of the B cell type.

Lupus-related mitral valve disease: embolic coronary occlusion as a unique cause of myocardial infarction.

Early diagnosis and greatly improved treatment have markedly altered the clinical evolution of systemic lupus erythematosus; the pattern of cardiac involvement in lupus has also changed. To illustrate this, a young woman who died from severe mitral valve disease, including a coronary embolus from verrucous endocarditis, is presented. Mitral valve involvement in lupus is no longer limited to the small benign lesions described by Libman and Sacks.

Placental pathology in systemic lupus erythematosus and phospholipid antibody syndrome.

Fetal loss is increased in women who meet the Arthritis and Rheumatism Association criteria for systemic lupus erythematosus (SLE) and in women who have phospholipid antibody syndrome (APS). There are multiple causes for this fetal loss, and in patients with SLE, disease activity appears to be an important contributing factor. In APS patients, it appears that some individuals will experience recurrent fetal loss and will continuously fail to complete pregnancy naturally. Placental examination has helped to elucidate some of the pathology that may be contribute to this fetal loss and our studies have shown that the same pathology is repeated in subsequent pregnancies. Placental examination in SLE or APS patients with recurrent fetal loss is vital if we are going to be able to determine appropriate therapy to prevent fetal loss.

Antimalarial drugs in pregnancy--the North American experience.

The use of the 4-aminoquinoline antimalarials in pregnancy is controversial. The current practice of discontinuing these medications because of pregnancy makes little sense as the half-life of these medications is so long. Patients with SLE have increased fetal wastage and one of the factors known to contribute to this fetal wastage is disease activity. It is also known that discontinuing the 4-aminoquinoline antimalarial drugs can precipitate flares of disease in lupus patients. Mothers and their potential offspring are therefore at risk for flares of disease and pregnancy failure if these medications are discontinued because of pregnancy. This review addresses the North American experience of the use of antimalarial drugs in pregnant lupus patients. Unlike most centers in North America, we continue our patients on these medications throughout pregnancy and to date have documented 16 lupus patients who have taken these drugs throughout pregnancy. Our most recent study documents nine pregnancies in eight women. All of these pregnancies resulted in live births (five pre-term deliveries and four full-term deliveries). There were no congenital abnormalities in these infants and follow-up to date has revealed no evidence of ocular or oral deficits in any of these children. One patient experienced a flare of disease when her antimalarial therapy was temporarily discontinued.

Chemical-induced inflammation and inflammatory diseases.

It is now known that human exposure to certain chemicals e.g. benzene, halocarbons, ketones, nitrosamines, etc. can result in adverse health effects that are often not easily recognised as manifestations of chemical toxicity. These are inflammatory states, such as hepatitis, nephritis, scleroderma, and lupus, due to production of reactive oxygen species (ROS) through activation of cytochrome P4502E1 by the chemical, or by metabolism of the chemical to reactive intermediates and neoantigens which initiate immunotoxic effects. Intracellular glutathione (GSH), vitamins C, E and A protect against this ROS toxicity and inflammation; fasting and consumption of alcohol exacerbate it. Chronic inflammatory states may subsequently develop, including rheumatoid disease, atherosclerosis, diabetes, infertility and birth defects, multiple system organ failure (MSOF), Alzheimer's disease, and cancer.

Hepatic disease, the gastrointestinal tract, and rheumatic disease.

In previous years, this review concentrated on the relationship between pathology in the gastrointestinal tract and rheumatologic complaints associated with this pathology. This year, we have emphasized the relationship between hepatic disorders and rheumatologic complaints, although a resumé of recent literature pertaining to the gastrointestinal tract and its rheumatologic consequences is also presented. We believe it is necessary to divert our primary focus of attention because of recent developments in identifying the extrahepatic effects of hepatitis C infection and the current interest in abnormalities of drug metabolism in various rheumatic and autoimmune disorders. These recent developments bring us full circle in incriminating not only bacterial and dietary antigens in the pathogenesis of the spondyloarthropathies but also viruses and exogenous chemicals as potential etiologic agents in genetically predisposed hosts, resulting in the development of a variety of diseases, including glomerulonephritis, vasculitis, Sjögren's syndrome, and systemic lupus erythematosus.

Antimalarial drugs, pregnancy and lactation.

Disease activity has been demonstrated to be one of the major factors contributing to fetal loss in SLE patients, and discontinuation of antimalarial therapy can precipitate a flare of disease. It is therefore important to determine whether it is safe to continue antimalarial therapy throughout pregnancy. We have previously stated that we consider lupus patients and their fetuses to be at risk for disaster if antimalarial therapy is discontinued during pregnancy, and it has been our experience that lupus patients can produce normal offspring even if they are taking daily chloroquine or hydroxychloroquine. Several other reports now support our findings that it is probably safe to continue antimalarial therapy during pregnancy, although there are no large studies published. Data on the secretion of hydroxychloroquine in the breast milk of patients on steady-state hydroxychloroquine therapy are minimal, and further studies are required to determine whether these women can safely nurse their infants while taking hydroxychloroquine daily.

Gastrointestinal disorders and rheumatic diseases.

Although we continue to learn more about the persistence of bacterial antigens in patients with HLA-B27, the significance of this persistence in the pathogenesis of the spondyloarthropathies remains unclear. The role of dietary antigen exposure and the ability of true food allergy to produce rheumatic complaints is even less definite, although most authors now agree that dietary manipulation using allergen-free or allergen-restricted diets may benefit a small number of patients with rheumatic disease complaints. Dietary manipulation substituting omega-3 for omega-6 fatty acids, however, is frequently beneficial to rheumatoid patients. Is this the way of the future? It is certain that dietary manipulation is less toxic than the standard therapies. It is also certain that we cannot guarantee that any standard therapy will work, except perhaps for prednisone administration. We really have nothing to lose by pursuing this therapeutic approach, and I am surprised that although we have become very diet conscious, dietary manipulation as therapy for patients with rheumatic diseases continues to be underinvestigated, particularly in systemic lupus erythematosus and Sjögren's syndrome.

The thrombotic diathesis associated with the presence of phospholipid antibodies may be due to low levels of free protein S.

PURPOSE: To determine if abnormalities in the protein C/protein S anticoagulant system exist in patients with phospholipid antibodies who had the primary clinical complaint of fetal wastage. PATIENTS AND METHODS: Eleven patients with fetal wastage and phospholipid antibodies were selected for study. Some patients also gave a history of previous thrombotic events related to oral contraceptives and/or pregnancy, but patients were not selected because of a history of clinical thrombosis. The levels of protein C (chromogenic assay), protein S (both free and bound) (Laurell rocket), and C4b-binding protein (Laurell rocket) were measured, and assays for the presence of antibodies against protein S or protein C were performed. RESULTS: Seven of the 11 patients were found to have low levels of free protein S. Total protein S and protein C levels were within the normal range in all patients. Antibodies to protein C and protein S were not found in any patient. These findings suggest that free protein S levels may be abnormally low in some patients with phospholipid antibodies. CONCLUSION: Free protein S levels are abnormally low in some patients with phospholipid antibodies, and this abnormality may be a factor contributing to the thrombotic diathesis associated with phospholipid antibodies.

Gastrointestinal disorders in rheumatic diseases.

Abnormal exposure to bacterial or dietary antigen across a diseased bowel wall may result in extraintestinal clinical complaints. Persistence of this antigen for years at these extraintestinal sites does occur, resulting in chronic and sometimes autoreactive disease. Treating the bowel disease can "cure" the extraintestinal complaints, but identifying the etiology of the original bowel disorder remains a problem, especially with the inflammatory bowel diseases. In 1992, nonsteroidal anti-inflammatory drugs remain essential in the treatment of various rheumatologic complaints. Although these drugs do work, they also produce gastrointestinal disease that may be far more extensive than was formerly appreciated. This risk is obviously a problem, and those who demand a change in our therapeutic approach to arthritis probably have the right idea.

The prevalence of antiphospholipid antibodies in women with recurrent spontaneous abortion, women with successful pregnancies, and women who have never been pregnant.

Antibodies to negatively charged phospholipids are associated with a predisposition to both arterial and venous thrombosis, recurrent fetal wastage, and thrombocytopenia. These associations have been reported in patients who do not fulfill criteria for connective tissue diseases. In this study, we determined the prevalence of antiphospholipid antibodies in 81 women who had had recurrent spontaneous abortion (3 or more fetal losses), in 88 women whose pregnancies were successful, and in 64 women who had never been pregnant. Antiphospholipid antibodies were found in 16% of women with recurrent spontaneous abortion, and at a statistically greater prevalence than in women who had successful pregnancies (7%) as well as those who had never been pregnant (3%). A false-positive VDRL and IgG anticardiolipin antibodies were more specific for fetal wastage than was either the lupus anticoagulant or IgM anticardiolipin antibodies.