Pregnancy in rheumatic disease patients.

T his report provides an overview of pregnancy in rheumatic diseases with an emphasis on systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), including recent information on pregnancy outcome, neonatal outcome, and potential complications in rheumatic disease patients as well as a general approach to patients with rheumatic disease when they are contemplating pregnancy. Planning is important in these patients, as with any chronic disease patient hoping to become pregnant. Of note, most of the medications discussed, as with rheumatology medications in general, are not Food and Drug Administration approved for the indications that we will be addressing. First, let us review some relevant points about pregnancy that sometimes make it confusing or challenging to take care of patients during this period. Pregnancy affects the maternal immune system to permit fetal survival: cell-mediated immunity is depressed, immunoglobulin secretion increases, and pregnancyspecific proteins suppress lymphocyte function. The TH2 cytokine profile is dominant and important in sustaining pregnancy, which may have different implications for different autoimmune diseases. There are a number of ways in which one can view the impact of our diseases on pregnancy and vice versa. First, pregnancy-induced changes in immune function may affect the connective tissue disease (CTD) itself, for example, increased risk of flare in lupus pregnancy or pregnancy-induced remission in rheumatoid arthritis (RA) patients. Conversely, autoimmune dysfunction that characterizes particular CTDs can affect maternal or fetal outcome, particularly presence of antiphospholipid antibodies, which may lead to increased risk of miscarriage, fetal loss, and preeclampsia. Transplacental passage of pathogenic autoantibodies can directly affect the fetus, notably antiYRo/SS-A and La/SS-B, which may lead to neonatal lupus erythematosus. Finally, severe maternal illness or preexisting damage from autoimmune disease can have a significant effect on both maternal and fetal or neonatal outcomes. Pregnancy induces many physiologic changes in the mother in addition to the immune system changes. If one is unfamiliar with these changes, it can be difficult to understand what is happening with our patients during this period. There is a significant increase in intravascular volume that may stress patients who have renal disease or cardiac disease. The glomerular filtration rate increases by about 50% in a normal pregnancy, so a patient with preexisting proteinuria almost certainly will see some increase in proteinuria over the course of pregnancy. Pregnancy induces a prothrombotic state based on changes in both procoagulant and fibrinolytic systems and leads to contributing mechanical factors such as venous stasis, compression by the gravid uterus, or bed rest when necessary. There is an increase in gastroesophageal reflux, frequent gum swelling and bleeding, and potentially significant reversible bone loss due to pregnancy and lactation, especially worrisome for patients who may have preexisting steroid-induced osteoporosis. These normal pregnancy changes can exacerbate CTD-related symptoms for our patients. Normal or pathologic changes including pregnancy-induced hypertension can also mimic activity of CTD, making it challenging to differentiate between pregnancy and disease flare. For example, facial flushing or pigmentation can easily be confused with malar rash. Palmar erythema in pregnant patients can look like cutaneous vasculitis. Anemia and low platelets due to hemodilution, common during the course of pregnancy, may mimic hematologic manifestations of CTD. The erythrocyte sedimentation rate increases because of elevation in fibrinogen, and so is no longer useful as a marker of disease activity. The white blood cell count generally increases as well, which may be confusing in conditions where we expect the white blood cell count to elevate with disease activity, such as vasculitis. Diffuse arthralgias and even bland effusions are common: any woman who has gone through pregnancy will attest to a variety of musculoskeletal symptoms that can be confusing, especially to a woman in her first pregnancy. The hypertension, proteinuria, renal insufficiency, and edema associated with preeclampsia can mimic a variety of disease exacerbations including lupus nephritis, scleroderma renal crisis, or vasculitis flare. HELLP (hemolysis, elevated liver enzymes, low platelets count) syndrome, a preeclampsia variant characterized by low platelets with increased liver function tests, hemolysis, and abdominal pain, can also mimic SLE or a vasculitis exacerbation. Finally, eclampsia, which includes seizures and rarely stroke, may be confused with central nervous system lupus or vasculitis. This is one of the biggest challenges of following rheumatic disease patients through pregnancy: being able to make the distinctionVif possibleVbetween pregnancy and autoimmune disease manifestations.