Systemic Lupus Erythematosus and Pregnancy

Author: Ritu Khurana, MD, Assistant Professor of Medicine, Temple University Hospital
Coauthor(s): Robert E Wolf, MD, PhD, Professor Emeritus, Department of Medicine, Louisiana State University Health Sciences Center at Shreveport; Chief, Rheumatology Section, Medical Service, Overton Brooks Veterans Administration Medical Center of Shreveport

Introduction

Background

Systemic lupus erythematosus (SLE) is one of the most common autoimmune disorders that affect women during their childbearing years. Typical clinical symptoms of SLE include fatigue, fever, arthralgias, arthritis, a photosensitive rash, serositis, Raynaud phenomenon, glomerulonephritis, vasculitis, and hematologic abnormalities. Flares of SLE are uncommon during pregnancy and are often easily treated. The most common symptoms of these flares include arthritis, rashes, and fatigue.
SLE increases the risk of spontaneous abortion, intrauterine fetal death, preeclampsia, intrauterine growth retardation, and preterm birth. Prognoses for both mother and child are best when SLE is quiescent for at least 6 months before the pregnancy and when the mother's underlying renal function is stable and normal or near normal.
The mother's health and fetal development should be monitored frequently during pregnancy. In addition, an obstetrician with experience in high-risk care should conduct the follow-up of pregnant women with SLE.

Pathophysiology

The pathophysiology of disease activity during pregnancy remains unknown.
Increased SLE disease activity is expected during pregnancy because of increased levels of estrogen, prolactin, and T–helper cell 2 cytokines. The incidence of exacerbations during pregnancy and the postpartum period, especially in women in remission at the beginning of pregnancy, has been progressively diminishing in the last 30 years. Possible causes for flare-ups during the postpartum period include decreased levels of anti-inflammatory steroid, elevated levels of prolactin (ie, proinflammatory hormone), and changes in the neuroendocrine axis.

Frequency

United States

The prevalence of SLE is 14.6-50.8 cases per 100,000 general population.

The frequency of exacerbation or persistently active disease varies with disease activity at conception. Rates range from 7-33% in women who have been in remission for at least 6 months to 61-67% in women who have active disease at the time of conception.

In the United States, the overall average incidence of SLE between 1950 and 1990 was estimated to be 1.8-7.6 cases per 100,000 person-years.

International

Incidences in 4 European cohorts from Iceland, England, and Sweden were similar to those observed in the United States. Rates in these cohorts were 3.3-4.8 cases per 100,000 person-years.

Mortality/Morbidity

Over the past 50 years, the survival rate in patients with SLE has improved dramatically. In 1955, the 5-year survival rate was only 50%, whereas, in the 1990s, the 10-year survival rate approached or exceeded 90%, and the 20-year survival rate approached 70%. Factors contributing to this improvement include early diagnosis, increased potency of pharmaceutical agents, and improved treatments (eg, dialysis, kidney transplantation).
Nonetheless, despite improved survival rates, mortality rates among patients with SLE remain 3-5 times greater than those in the general population.

As with studies of incidence and prevalence, research about factors predictive of mortality in patients with SLE has focused on the patient's sex, race or ethnicity, socioeconomic status, or age at disease onset.

In one prospective study, hypertension during pregnancy, preterm delivery, unplanned cesarean delivery, postpartum hemorrhage, and maternal venous thromboembolism were more common in women with SLE than in women without SLE. In addition, fetal growth restriction and neonatal deaths were most often seen in association with SLE.

Race

Evidence suggests that SLE is more common in African American groups than in white populations. In general, prognoses are worse in African American or Hispanic patients with SLE than in white patients.
In North America and Europe, prognoses are worse in patients with SLE who are of Asian, Indian, African Caribbean, or Hispanic race than in white patients.
When the prevalence of SLE is stratified by race, the prevalence among African Caribbean individuals was approximately 5 times the rate observed in people of white descent.
In the United States, the prevalence of SLE in female African Americans ranges from 17.9-283 cases per 100,000.
A West Indian study of female patients with SLE reported a prevalence of 83.8 cases per 100,000.

Sex

The incidence of lupus is dramatically higher in women than in men. The race- and sex-specific incidence rates of definite SLE per 100,000 persons were 0.4 (95% CI, 0.2-0.7) in white males, 3.5 (95% CI, 2.9-4.2) in white females, 0.7 (95% CI, 0-2) in African American males, and 9.2 (95% CI, 6.8-12.5) in African American females.

Age

SLE in pregnancy affects female adolescents and women of reproductive age.

The incidence peaks between ages 15 and 45 years, ie, the childbearing years, when the female-to-male ratio is about 12:1.
In patients with SLE that begins during childhood or later, the female-to-male ratio is approximately 2:1.

Clinical

History

History taking is targeted at identifying disease activity, complications related to pregnancy, and adverse effects of various medications.

General considerations
- Currently, more than 50% of all pregnancies in women with lupus have a normal outcome.
- About 25% of women with lupus deliver healthy babies prematurely.
- Fetal loss due to spontaneous abortion occurs in less than 20% of cases.
Symptoms due to pregnancy
- Nausea, vomiting, and morning sickness can occur during the first trimester.
- The aforementioned symptoms may prevent absorption of medications.
Symptoms suggestive of lupus disease activity
- Constitutional symptoms may be present.
- Most patients with lupus report fatigue during pregnancy.
- The likelihood of developing renal disease during pregnancy is not increased if the patient was in remission at the time of conception.
Differentiation of signs and symptoms of normal pregnancy from those of exacerbations of lupus
- Differentiate malar rash from chloasma.
- Differentiate proteinuria secondary to preeclampsia from proteinuria due to lupus nephritis.
- Differentiate thrombocytopenia in pregnancy (ie, hemolysis, elevated liver enzyme levels, and low platelet counts [HELLP] syndrome) from thrombocytopenia of lupus exacerbation (ie, thrombocytopenic purpura [TTP] or idiopathic TTP [ITP]).
- Pedal edema and fluid accumulation in joints, especially the knees, can occur in the late stages of pregnancy and should be differentiated from the arthritis of systemic lupus erythematosus (SLE).

Physical

Flares
- In general, pregnancy does not cause flares.
- Flares that do develop often occur during the first or second trimester or during the first few months after delivery.
- Most flares are mild and easily treated with small doses of corticosteroids.
Renal disease
- Patients with organ damage at the time of pregnancy may have difficulty because pregnancy adds to the burden on malfunctioning organs. This phenomenon is particularly important in patients with renal disease.
- Pregnancy in women with lupus nephritis is associated with an increased risk of fetal loss (up to 75%) and with worsening of the renal and extrarenal manifestations, as shown in most studies. Although the incidence is not high, severe renal exacerbations are possible. Thus, women with lupus nephritis should be encouraged to delay pregnancy until the disease can be rendered inactive for at least 6 months.
- Although the risk of adverse effects on the fetus are minimized if conception and pregnancy occur in the absence of glucocorticoids or other immunosuppressive drugs, continuing glucocorticoids at the lowest effective dose and/or cautious use of azathioprine may be preferred in some patients.
Other comorbidities
- Patients with preexisting hypertension, proteinuria, and azotemia are at an increased risk.
- Pregnancy outcomes in women with SLE who receive renal transplants are remarkably similar to those of other transplant recipients.¹
Preeclampsia
- Preeclampsia is a frequent complication of pregnancy in SLE, occurring in approximately 13% of patients.
- Preeclampsia is often difficult to distinguish from lupus nephritis. Laboratory testing is occasionally useful in distinguishing preeclampsia from nephritis.
- Preeclampsia is most likely in patients with antiphospholipid antibodies, diabetes mellitus, or a previous episode of preeclampsia.
- Pre-existing thrombocytopenia may also be a risk factor.
Thrombosis
- Pregnancy, and especially the postpartum period, represents an additional thrombotic risk in patients with SLE who have antiphospholipid antibodies.
- Patients who are already taking warfarin because of a past venous or arterial thrombotic event should be switched to therapeutic doses of heparin (either unfractionated or low molecular weight heparin) as soon as the pregnancy is recognized.
- Patients who have had only fetal losses or other pregnancy morbidity due to antiphospholipid antibody syndrome are treated with prophylactic doses of heparin and low-dose aspirin (81 mg) during subsequent pregnancies.
- Currently, no accepted prophylaxis is available for women with SLE who have antiphospholipid antibodies and no past morbidity, although many consider the use of low-dose aspirin (81 mg), with or without hydroxychloroquine.
Other causes of morbidity
- In addition to the obvious morbidity from SLE flares and their treatment, other morbidity is also increased in a pregnancy associated with SLE.
- Rates of urinary tract infections, diabetes mellitus, hypertension, preterm premature rupture of membranes, and preeclampsia are all increased in SLE.
Risk assessment: Risk assessment in terms of checking for antiphospholipid antibodies (for a risk of fetal loss) and for anti-Ro and anti-La antibodies (for a risk of neonatal lupus) should be performed before pregnancy.
Neonatal lupus
- Neonatal lupus manifests as congenital heart block or as lupus rash. It is rare in SLE pregnancies, occurring in 3.5% of cases in one series. Neonatal lupus is highly associated with maternal anti-Ro (usually also with anti-La) antibodies, although the rash may occur with anti-RNP antibodies.
- Because not all pregnancies in the setting of anti-Ro/La antibodies are associated with congenital heart block, prophylactic treatment is not appropriate. Instead, fetal 4-chamber cardiac echocardiography performed at 16-28 weeks' gestation is recommended.
- If heart block of any degree is found, dexamethasone 4 mg/day is given to the mother because it crosses the placenta.
- Third-degree heart block is rarely reversible.
- In rare cases, neonatal lupus manifests as hepatic or hematologic involvement.
- Most babies with congenital heart block can be delivered at term; if severe hydrops is present, early cesarean delivery is necessary.
- Pacing is occasionally required in the neonate. Rare children with congenital heart block develop a connective tissue disease in adolescence.
Fetal loss
- Rates of pregnancy loss are substantially increased in patients with SLE compared with control groups.
- Fetal loss is possible in any trimester.
- First-trimester losses are associated with antiphospholipid antibodies and with markers of lupus activity (eg, low complement concentrations and increased anti–double-stranded DNA [anti-dsDNA] antibodies) and renal disease.
- Late losses are associated with antiphospholipid antibodies.
- Hypercoagulable states other than antiphospholipid antibody syndrome are also associated with increased fetal loss.
- Women with SLE with fetal losses who are negative for antiphospholipid antibodies (including lupus anticoagulant, anticardiolipin, and anti-beta2 glycoprotein 1) should be screened for genetic causes of hypercoagulability, such as factor V Leiden, prothrombin mutation, and hyperhomocysteinemia.
Breastfeeding
- Breastfeeding is feasible for most women with SLE. However, some medications may enter breast milk. Therefore, immunosuppressive agents are contraindicated, and long-acting NSAIDs are inadvisable. Short-acting NSAIDs, antimalarials, low-dose prednisone (<15-20 mg/d), warfarin, and heparin seem to be safe.
- Women with anti-Ro/SSA and anti-La/SSB antibodies may have detectable amounts of these antibodies in breast milk, but no evidence suggests that neonatal lupus results from breastfeeding.
Fertility: SLE is not associated with infertility unless the woman has been treated with cyclophosphamide, which leads to premature ovarian failure.

Differential Diagnoses

Glomerulonephritis, Diffuse Proliferative
Preeclampsia (Toxemia of Pregnancy)
Systemic Lupus Erythematosus

Workup

Laboratory Studies

At the first visit after or when pregnancy is confirmed, the following assessments are recommended:
- Physical examination, including blood pressure evaluation
- Renal function tests, including determination of the glomerular filtration rate, urinalysis, and tests of the urine protein–to–urine creatinine ratio
- CBC count
- Test for anti-Ro/SSA and anti-La/SSB antibodies
- Lupus anticoagulant and anticardiolipin antibody studies
- Anti-dsDNA test
- Complement (CH50 or C3 and C4) tests
During the first 2 trimesters, a monthly platelet count or CBC count is recommended.
The following evaluations are recommended at the end of each trimester of pregnancy:
- Determination of the glomerular filtration rate and measurement of the urine protein–to–urine creatinine ratio
- Anticardiolipin antibody measurement
- Complement (CH50 or C3 and C4) test
- Anti-dsDNA antibody study

Imaging Studies

Women who have antibodies to Ro/SSA and/or La/SSB are at increased risk of pregnancies complicated by fetal heart block and may benefit from serial fetal echocardiographic monitoring.
The goal is to detect fetal heart block at an early stage, when therapeutic interventions may prevent its progression.

Other Tests

Fetal monitoring: Women with systemic lupus erythematosus (SLE) are at increased risk for intrauterine growth restriction and preterm birth. Therefore, menstrual dating should be confirmed with ultrasonography at the first prenatal visit to accurately estimate the gestational age.

Treatment

Medical Care

Preconception counseling is recommended.
Counsel patients about the teratogenicity and adverse effects of the medications used to treat systemic lupus erythematosus (SLE) before therapy is initiated.
Patients may need to be reminded about the importance of using contraception while they are taking methotrexate, leflunomide, cyclophosphamide, and mycophenolate.
Educate patients that, because of prolonged half-lives, some medications may need to be discontinued several months before the planned conception. In addition, measures may need to be undertaken to enhance elimination of some medications as soon as pregnancy is detected.
In the absence of any historical features of antiphospholipid syndrome (recurrent pregnancy loss, venous or arterial thromboembolism), patients with lupus anticoagulant and/or high levels of anticardiolipin antibodies should receive low-dose aspirin. Some suggest the use of low-dose heparin and aspirin for such patients, even in the absence of previous pregnancy complications.
Women with lupus and the antiphospholipid antibody syndrome require more frequent monitoring than those with SLE alone.
In 2007, the European League Against Rheumatism (EULAR) released new recommendations for the treatment of SLE.

Surgical Care

Patients with SLE may have increased rates of emergency or cesarean delivery secondary to flares of renal disease or preeclampsia.

Consultations

A rheumatologist, an obstetrician experienced with high-risk care, and a nephrologist (if renal disease present or if it develops later) should work as a team to care for a pregnant patient with lupus.

Diet

A low-salt diet is recommended in pregnancy to prevent weight increase and hypertension.
An exercise program may help prevent bone loss and depression.
Calcium and vitamin D supplementation may be advised to prevent osteoporosis.

Activity

Strenuous activity is best avoided when patients have flare-ups.

Medication

None of the medications used in the treatment of systemic lupus erythematosus (SLE) is absolutely safe during pregnancy. Hence, whether to use medications should be decided after careful assessment of the risks and benefits in consultation with the patient. During the first trimester, most of the drugs listed should be avoided.

Nonsteroidal anti-inflammatory drugs
(NSAIDs)

These agents have analgesic, antipyretic, and anti-inflammatory activity. Their mechanism of action is not known, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may also exist. These may include inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions.

Ibuprofen (Motrin, Advil)

DOC for patients with mild to moderate pain. NSAIDs are used for their analgesic, anti-inflammatory, and antipyretic activities. NSAIDs should be stopped at the beginning of menstrual cycle when conception is planned; NSAIDs interfered with blastocyst implantation in animal studies. Possible maternal effects include prolonged gestation and labor, increased peripartum blood loss, and increased anemia. Potential adverse effects to the fetus include premature closure of ductus arteriosus, leading to pulmonary hypertension, impaired renal function with oligohydramnios, and increased cutaneous and intracranial bleeding. Short-acting NSAIDs (eg, ibuprofen, indomethacin, diclofenac) are preferred over long-acting agents.

Adult

400 mg PO q4-6h, 600 mg q6h, or 800 mg q8h while symptoms persist; start at low end of dosing range and titrate prn; not to exceed 3.2 g/d

Pediatric

20-70 mg/kg/d PO divided tid/qid; start at low end of dosing range and titrate prn; not to exceed 2.4 g/d

Coadministration with aspirin increases risk of serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; closely monitor prothrombin time (PT) (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may increase when administered concurrently

Documented hypersensitivity; peptic ulcer disease; recent GI bleeding or perforation; renal insufficiency; high risk of bleeding

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Category D in third trimester of pregnancy; caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy

Indomethacin (Indocin)

Rapidly absorbed; metabolism occurs in liver by demethylation, deacetylation, and glucuronide conjugation. Inhibits prostaglandin synthesis.

Adult

25-50 mg PO bid/tid; 75 mg SR PO bid; not to exceed 200 mg/d

Pediatric

1-2 mg/kg/d PO divided bid/qid; not to exceed 4 mg/kg/d or 150-200 mg/d

Coadministration with aspirin increases risk of serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may increase when administered concurrently

Documented hypersensitivity; GI bleeding or renal insufficiency

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Category D in third trimester of pregnancy; acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in pre-existing renal disease or compromised renal perfusion; reversible leukopenia may occur; discontinue if persistent leukopenia, granulocytopenia, or thrombocytopenia is present

Disease modifying agents

These agents modify immune responses to diverse stimuli.

Hydroxychloroquine (Plaquenil)

Inhibits chemotaxis of eosinophils and locomotion of neutrophils. Impairs complement-dependent antigen-antibody reactions. Hydroxychloroquine sulfate at 200 mg equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate.

Adult

200-400 mg/d PO in divided doses

Pediatric

Not established

Serum levels increase with cimetidine; magnesium trisilicate may decrease absorption

Documented hypersensitivity; psoriasis; retinal and visual-field changes attributable to 4-aminoquinolones

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in hepatic disease, G-6-PD deficiency, psoriasis, and porphyria; perform periodic (eg, 6 mo) ophthalmologic examinations; test periodically for muscle weakness

Immunosuppressive drugs

These agents may suppress mechanisms responsible for autoimmune reactions.

Azathioprine (Imuran)

Purine analog that antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. In SLE, decreases levels of circulating B and T lymphocytes, immunoglobulin synthesis, and cytokine production. May be needed for patients with history of severe nephritis after cyclophosphamide or mycophenolate treatment. Can also be used as steroid-sparing agent.

Adult

1 mg/kg/d PO for 6-8 wk; increase 0.5 mg/kg q4wk until response or dosage 2.5 mg/kg/d

Pediatric

Not established

Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine

Documented hypersensitivity to azathioprine or any component of the formulation

Pregnancy

D - Unsafe in pregnancy

Precautions

Increases risk of neoplasia; caution in liver disease and renal impairment; hematologic toxicities may occur; check TPMT level before therapy and monitor liver, renal, and hematologic function; pancreatitis or neonatal immunosuppression in rare cases

Mycophenolate mofetil (CellCept, Myfortic)

Prodrug enzymatically broken down into active metabolite MPA. Mycophenolic acid inhibits purine synthesis and decreases lymphocyte production and adhesion.

Adult

2-3 g/d PO in divided doses

Pediatric

Not established

Combination with acyclovir or ganciclovir may increase levels of both because of competition for renal tubular excretion; aluminum and/or magnesium present in some antacids, and cholestyramine-containing products may decrease absorption, reducing levels (do not administer together); probenecid may increase levels; salicylates and azathioprine may increase toxicity; may decrease area under the concentration-time curve (AUC) for levonorgestrel; may decrease immune response to live-virus vaccine; may increase free-fraction levels of theophylline when used in combination

Documented hypersensitivity

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Increases risk for infection (monitor blood count); patients with severe renal impairment (CrCl <25 mL/min) may have increased adverse effects due to increased free MPA; caution in active peptic ulcer disease; incidence of malignancies and lymphoma consistent with those of other immunosuppressants (0.9%); constipation, nausea, diarrhea, urinary tract infection, and nasopharyngitis are common; interstitial lung disorders, colitis, pancreatitis, intestinal perforation, GI hemorrhage, gastric ulcers, duodenal ulcers, and ileus may occur (rare); do not chew, crush, or cut Myfortic tab

Cyclophosphamide (Cytoxan)

Should not be used in pregnancy. Long-term treatment for lupus cerebritis and/or nephritis should be followed by yearly urine cytology to screen for bladder cancer.

Adult

500-750 mg/m² IV qmo

Pediatric

Not established

Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; toxicity may increase with chloramphenicol; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia; coadministration with succinylcholine may increase neuromuscular blockade by inhibiting cholinesterase activity

Documented hypersensitivity; severely depressed bone marrow function

Pregnancy

X - Contraindicated in pregnancy

Precautions

Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; young male patients should be counseled about sperm banking; women should be made aware of infertility risk

Cyclosporine A (Neoral, Sandimmune)

Cyclic peptide of 11 amino acids and natural product of fungi. Acts on T-cell replication and activity. Specific modulator of T-cell function. Depresses cell-mediated immune responses by inhibiting function of T helper cells. Preferential and reversible inhibition of T lymphocytes in G0 or G1 phase of cell cycle suggested.

Binds to cyclophilin (intracellular protein), which, in turn, prevents formation of interleukin (IL)–2 and subsequent recruitment of activated T cells. Mechanism of action involves inhibition of cytotoxic T cells, decreasing production of IL-2.

Bioavailability about 30%, but interindividual variability is considerable. Specifically inhibits T-lymphocyte function with minimal activity against B cells. Maximum suppression of T-lymphocyte proliferation requires drug to be present during first 24 h of antigenic exposure.

Suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease) for various organs.

Adult

2.5-5 mg/kg/d PO in divided doses

Pediatric

Administer as in adults

Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin; mutual inhibition with methylprednisolone that increases plasma levels of both

Documented hypersensitivity; uncontrolled hypertension or malignancies; risk of preterm delivery and/or low birth weight; do not administer concomitantly with PUVA or UVB irradiation in psoriasis (may increase risk of cancer)

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Evaluate renal and liver functions often by measuring BUN, serum creatinine, serum bilirubin, and liver enzyme levels; may increase risk of infection and lymphoma; reserve IV use for only patients who cannot take PO; not teratogenic in animals or humans, but isolated case of renal damage reported in fetal rat

Corticosteroids

These agents have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli.

These drugs are used to treat the fetus in mothers with positive anti-SSA antibodies.

Dexamethasone (Decadron)

Has many pharmacologic benefits but clinically significant adverse effects. Stabilizes cell and lysosomal membranes, increases surfactant synthesis, increases serum vitamin A concentration, inhibits prostaglandin and proinflammatory cytokines (eg, tumor necrosis factor [TNF]–alpha, IL-6, IL-2, and interferon [IFN]–gamma). Inhibition of chemotactic factors and factors that increase capillary permeability inhibits recruitment of inflammatory cells into affected areas. Suppresses lymphocyte proliferation by direct cytolysis and inhibits mitosis. Breaks down granulocyte aggregates and improves pulmonary microcirculation.

Adverse effects include hyperglycemia, hypertension, weight loss, GI bleeding or perforation synthesis, cerebral palsy, adrenal suppression, and death. Most adverse effects of corticosteroids are dose or duration dependent.

Readily absorbed from GI tract and metabolized in liver. Inactive metabolites excreted through kidneys. Lacks salt-retaining property of hydrocortisone.

Can be switched from IV to PO regimen in 1:1 ratio. Given to pregnant mother if fetal heart block detected in patients with anti-SSA antibodies. Crosses placenta.

Adult

4 mg IV divided q6-12h

Pediatric

Not established

Effects decrease with coadministration of barbiturates, phenytoin, and rifampin; dexamethasone decreases effect of salicylates and vaccines for immunization

Documented hypersensitivity; viral, fungal, or tubercular skin infections

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Increases risk of several complications, including severe infections; monitor adrenal insufficiency when tapering drug; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications of glucocorticoid use

Prednisone (Deltasone, Orasone, Sterapred)

May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. If steroid treatment desired for mother, prednisone, cortisone, or hydrocortisone should be chosen, as low concentration of active steroid reaches fetus.

Adult

5-60 mg/d PO qd; administer lowest effective dose

Pediatric

0.05-2 mg/kg/d PO divided tid/qid

Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics; may alter levels of warfarin

Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, fungal or tubercular skin infections; GI disease

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use; high doses may result in growth retardation and cleft palate in fetus; if used during pregnancy, newborn must be monitored for adrenal suppression and infection

Methylprednisolone (Medrol, Solu-Medrol)

Decreases inflammation by suppressing migration of polymorphonuclear (PMN) leukocytes and reversing increased capillary permeability. Metabolized by placenta; thus, lowered concentrations reach fetus. Therefore, this is the preferred corticosteroid treatment.

Adult

5-20 mg/d PO qd; 1 g/d for 3 d IV in life-threatening disease (renal disease secondary to lupus nephritis or cerebritis); administer lowest effective dose

Pediatric

Not established

Further Inpatient Care

Patients may require admission for management of the complications of labor and delivery.

Further Outpatient Care

All patients should be screened for postpartum depression.
Patients must be monitored closely after delivery because some are likely to have flare-ups during the postpartum period.

Inpatient & Outpatient Medications

Patients can breastfeed if they are not taking azathioprine, methotrexate, cyclophosphamide, or mycophenolate.
Hydroxychloroquine is also secreted in breast milk; therefore, this drug should be used with caution. Hydroxychloroquine may displace bilirubin, resulting in kernicterus.
Prednisone can be used safely during breastfeeding because small amounts (5% of the glucocorticoid dose) are secreted in breast milk. At doses of prednisone higher than 20 mg once or twice daily, breast milk should be pumped and discarded 4 hours after the dose to minimize drug exposure to the infant.
NSAIDs can be used with caution in newborns without jaundice because NSAIDs can displace bilirubin and predispose the fetus to kernicterus.

Transfer

Transfer to intensive care unit may be required for emergency intervention or monitoring during flares.

Deterrence/Prevention

Patients should avoid pregnancy when lupus is active, especially in the presence of renal disease.
Patients should use contraception while they are taking immunosuppressive disease-modifying drugs.

Complications

Complications due to flare of the disease during pregnancy or the adverse effects of drugs on the fetus are possible.

Prognosis

The long-term effect of pregnancy in patients with systemic lupus erythematosus (SLE) is unknown.
Data from retrospective studies suggest no clinically significant adverse or positive effect of pregnancy on the course of SLE.

Patient Education

Patients should be aware of the potential teratogenic effects of the drugs they are taking.
Preconception counseling must be stressed.
Use of contraception must be stressed frequently while patients are taking teratogenic medications.
When treatment is recommended during pregnancy, patients must be informed of the potential adverse effects of the drugs on the fetus.

Miscellaneous

Medicolegal Pitfalls

Failure to inform patients of the teratogenic effects of certain immunosuppressive drugs
Failure to inform patients about the potential adverse maternal and fetal effects of the drugs recommended during pregnancy
Failure to diagnose pregnancy before teratogenic disease-modifying agents are started
Failure to inform patients to not breastfeed while they are taking certain drugs (eg, azathioprine, mycophenolate, cyclophosphamide)

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