Ann Parke

Anti-inflammatory and immunosuppressive drugs and reproduction

Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given.

Catastrophic antiphospholipid syndrome: clues to the pathogenesis from a series of 80 patients.

The antiphospholipid syndrome (APS), originally defined as the combination of venous or arterial thrombotic events, recurrent fetal loss, and, frequently, a moderate thrombocytopenia in association with antiphospholipid antibodies (aPL), was subsequently greatly expanded to include diverse conditions, for example, heart valve lesions, adrenal insufficiency, and pulmonary syndromes such as acute respiratory distress syndrome (ARDS), “capillaritis,” and pulmonary alveolar hemorrhage, among others (16, 17). It was then realized that several “microangiopathic syndromes” also existed, as opposed to large vessel occlusive disease. Single organs, such as the kidneys, heart, skin, and brain, have been affected by this “thrombotic microangiopathy” in the context of the “classic” or “simple” APS. The temporal occurrence of thrombotic events in patients with this classic APS usually extends over months or years. In 1992, the existence of a new “subset” was described in which multiple vascular occlusive events, usually affecting small vessels supplying organs and presenting over a short period of time, were the outstanding features. This subset was termed the “catastrophic” APS. Although large vessel occlusions were also present, their prevalence did not in any way approach that in patients with the classic APS. The occlusions occurred over days to several weeks, and more than 50% of patients usually succumbed despite seemingly adequate therapy, including anticoagulation, steroids, etc. (6). In 1998, a comprehensive review article with the clinical and laboratory description of 50 such patients was published (8). In the present paper we describe the clinical and serologic features of the largest series of patients with catastrophic APS hitherto reported, including 30 new cases from interested physicians in many different countries, as well as a comprehensive literature review of 50 additional recently published case reports with this syndrome. This new series, comprising a total of 80 patients, enables us to analyze further and clarify not only the clinical importance of this syndrome, but also its pathogenesis. 0025-7974/01/8006-0355/0 MEDICINE® 80: 355-77, 2001 Vol. 80, No. 6 Copyright

Pregnancy and reproduction in autoimmune rheumatic diseases

Despite evidence for the important role of oestrogens in the aetiology and pathophysiology of chronic immune/inflammatory diseases, the previous view of an unequivocal beneficial effect of oestrogens on RA compared with a detrimental effect on SLE has to be reconsidered. Likewise, the long-held belief that RA remits in the majority of pregnant patients has been challenged, and shows that only half of the patients experience significant improvement when objective disease activity measurements are applied. Pregnancies in patients with SLE are mostly successful when well planned and monitored interdisciplinarily, whereas a small proportion of women with APS still have adverse pregnancy outcomes in spite of the standard treatment. New prospective studies indicate better outcomes for pregnancies in women with rare diseases such as SSc and vasculitis. Fertility problems are not uncommon in patients with rheumatic disease and need to be considered in both genders. Necessary therapy, shortly before or during the pregnancy, demands taking into account the health of both mother and fetus. Long-term effects of drugs on offspring exposed in utero or during lactation is a new area under study as well as late effects of maternal rheumatic disease on children.

Pulmonary Manifestations of Primary Sjögren's Syndrome

Sjögrens syndrome (SS) is a systemic disease with a predilection for the exocrine glands. It also is considered to be an autoimmune epitheliitis, and, as the respiratory system is lined throughout with epithelial cells, it should not be surprising that patients who have SS may develop pulmonary disease. This article describes these manifestations.

The Role of IVIG in the Management of Patients with Antiphospholipid Antibodies and Recurrent Pregnancy Losses

Intravenous immune gamma-globulin appears to have a role in the management of some autoimmune-mediated diseases. The exact mechanisms whereby IVIG is beneficial to patients with these diseases are not understood. The antiphospholipid-antibody syndrome is a recently recognized syndrome in which antibodies to negatively charged phospholipids are associated with a thrombotic diathesis, fetal wastage, and thrombocytopenia. The association between these antibodies and the clinical complaints is unknown. Recent evidence has suggested that a cofactor, a serum protein or glycoprotein (of approx 50 kDa) is essential for so-called antiphospholipid antibodies to bind to phospholipids. It may be that variations in this cofactor and its binding are some of the factors that determine whether high levels of antiphospholipid antibodies result in pathological consequences. Patients with antiphospholipid antibodies who have experienced previous fetal losses will continue to experience fetal wastage without some form of therapeutic intervention. The optimum therapy for these patients is yet to be determined, but recent isolated anecdotal reports suggest that IVIG may be of some benefit. IVIG appears to be less toxic to the mother than prednisone. The true benefit of IVIG, however, can be determined only by randomized, well controlled trials. Adequate numbers of patients could only be obtained by multicenter studies, and these should be designed to compare anticoagulation alone with anticoagulation and IVIG. Justifying a placebo group is difficult, as it is known that greater than 90% of pregnancies in women with aPL who have previously experienced fetal wastage fail to produce a live infant. It is only by doing such studies that the true role of IVIG in the management of pregnant patients with aPL can be determined.

New Treatment Guidelines for Sjögren's Disease

Sjögrens disease is associated with a high burden of illness, diminished quality of life, and increased health care costs. The Sjögrens Syndrome Foundation developed the first US clinical practice guidelines for management of the oral, ocular, and rheumatologic or systemic manifestations. Guideline recommendations were reviewed by a consensus expert panel using a modified Delphi process. This initiative should improve the quality and consistency of care for Sjögrens disease in the United States, guide insurance reimbursement, and define areas for future study. Guidelines will be periodically reviewed and revised as new information becomes available.

Treatment Guidelines for Rheumatologic Manifestations of Sjögren's Syndrome: Use of Biologic Agents, Management of Fatigue, and Inflammatory Musculoskeletal Pain

The Sjögrens Syndrome Foundation clinical practice guidelines (CPGs) are designed to improve quality and consistency of care in Sjögrens syndrome by offering recommendations for management.

Neuroendocrine Manifestations of Phospholipid Antibody Disease Identified by Long-Term Follow-Up Study of Patients with Phospholipid Antibodies

Abstract:  Recurrent clinical thrombotic episodes and/or recurrent fetal wastage are the clinical features of phospholipid antibody (aPL) syndrome, which is characterized by a bland thrombosis, but is not inflammatory, as is found in other connective tissue diseases such as systemic lupus erythematosus (SLE). Previous reports have suggested that some patients with primary aPL syndrome may progress to develop other autoimmune diseases, including inflammatory diseases such as SLE. The aim of this study was to determine the long‐term outcome of women with aPL antibodies, with regard to progression of their underlying autoimmune disease. To that end, a retrospective study was made of women with aPL and primary aPL syndromes who had been followed at our institution for a minimum of 3 years. Charts were reviewed, patients interviewed, and laboratory tests were performed to determine whether the clinical nature of the disease and/or its autoantibody profile had changed. Thirty patients were enrolled into the study (29 with aPL syndrome, 1 with consistent aPL and no syndrome). Follow‐up ranged from 3 to 22 years. Results were as follows: The autoimmune clinical features were unchanged in 27 patients, but 3 patients developed inflammatory disease, presenting with nasal chondritis (2), cutaneous vasculitis (3), and mucosal ulcer (1). In each case, these changes occurred during pregnancy or the immediate postpartum period. One patient fulfilled criteria for SLE as seen by a change in her autoantibody profile. Another incidental finding was that three other patients were diagnosed with papillary thyroid cancer, two being diagnosed during the follow‐up period. In conclusion: (1) Inflammatory disease may develop in some patients with aPL and appears to be set off by pregnancy, a known trigger for clinical thrombotic events in aPL patients. (2) Thyroid cancer may be associated with aPL, and this association warrants further study with larger number of patients.

The use of antirheumatic disease drugs during pregnancy.

Many connective tissue diseases occur more frequently in women, the female:male ratio for systemic lupus erythematosus is 9:1 and for rheumatoid arthritis is 3:1. These diseases frequently afflict young women, many of whom wish to become mothers. While some diseases (for example, rheumatoid arthritis) generally improve during pregnancy, other immune-mediated diseases may be exacerbated by pregnancy, putting both the mother and fetus at risk and making control of maternal disease a top priority. This review examines the current literature pertaining to the use of antirheumatic drugs during pregnancy, including aspirin and nonsteroidal anti-inflammatory drugs, corticosteroids, anticoagulants, the 4-aminoquinoline antimalarial drugs, immunomodulating drugs, antimetabolite drugs and other agents including sulfasazine and anticytokine therapy.

102 – Pregnancy—Success or Failure: The Influence of Autoimmune Diseases

Autoimmune disease is known to be associated with infertility; increased fetal wastage; and significant fetal and neonatal pathology, which may be a consequence of transplacental passage of maternal immunoglobulin. This chapter discusses in detail how maternal autoimmune disease can prevent or disrupt pregnancy. Autoimmune disease can also produce transient or permanent pathology in offspring, which is sometimes influenced by as-yet-unknown fetal and maternal factors. Pregnancy may exacerbate or ameliorate maternal clinical autoimmune disease, but its benefits are typically temporary with the disease flaring in the postpartum period. Reports suggest to consider that pregnancy might even contribute to the pathogenesis of autoimmune disease. Studies suggest that microchimerism may play a role in the pathogenesis of systemic sclerosis, autoimmune thyroid disease, and even multiple sclerosis.