Williams Manual of Pregnancy Complications, 23 ed.

CHAPTER 55. Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a disease of unknown etiology in which tissues and cells are damaged by autoantibodies and immune complexes directed at one or more components of cell nuclei. Its prevalence in childbearing-aged women is about 1 in 500. The 10- and 20-year survival rates are 75 and 50 percent, respectively, with infection, lupus flares, end-organ failure, and cardiovascular disease accounting for most deaths.

EFFECTS OF LUPUS ON PREGNANCY

A number of factors determine the effects of lupus on pregnancy outcome. These include the disease state at the beginning of pregnancy, age and parity, coexistence of other medical or obstetrical disorders, and antiphospholipid antibodies. Lupus improves in a third of women during pregnancy, a third remain unchanged, and a third worsen. Major morbidity during pregnancy, with estimates of a 1 in 20 chance of a life-threatening event, has been reported (see Table 55-1). Generally, these are due to renal impairment, myocarditis, or serositis, but complications associated with preeclampsia and antiphospholipid antibody syndrome are worrisome.

TABLE 55-1. Maternal and Perinatal Effects of Systemic Lupus Erythematosus

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In general, pregnancy outcome is better in following cases:

1. Lupus activity has been quiescent for at least 6 months.

2. There is no active renal involvement manifest by proteinuria or renal dysfunction.

3. Superimposed preeclampsia does not develop.

4. There is no evidence of antiphospholipid antibody activity.

EFFECTS OF LUPUS ON THE FETUS

Neonatal lupus is an unusual syndrome characterized by skin lesions—lupus dermatitis—and a variable degree of hematological and systemic derangements, and occasionally congenital heart block. Cutaneous lupus, thrombocytopenia, and autoimmune hemolysis are transient and clear within a few months. The recurrence risk for neonatal cutaneous lupus is 25 percent.

Anti-SS-A (Ro) and anti-SS-B (La) antibodies (see Table 55-2) may lead to diffuse fetal myocarditis and fibrosis in the region between the atrioventricular node and bundle of His causing congenital heart block. However, in infants of women with antibodies to the SS-A and SS-B antigens, the incidence of arrhythmia is only 3 percent. Of those affected, the cardiac lesion is permanent and a pacemaker is generally necessary. The recurrence risk for congenital heart block is 10 to 15 percent.

TABLE 55-2. Some Autoantibodies Produced in Patients with Systemic Lupus Erythematosus

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CLINICAL PRESENTATION

Lupus is notoriously variable in its presentation, course, and outcome. Clinical manifestations may be confined initially to one organ system, with other systems becoming involved as the disease progresses; or the disease may manifest initially with multisystem involvement. Common findings are listed in Table 55-3.

TABLE 55-3. Clinical Manifestations of Systemic Lupus Erythematosus

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DIAGNOSIS

The recently revised criteria of the American Rheumatism Association (1997) for diagnosis of systemic lupus are shown in Table 55-4. If any four or more of these 11 criteria are present, serially or simultaneously, the diagnosis of lupus is made. Identification of antinuclear antibodies (ANA) is the best screening test; however, a positive test is not specific for lupus. For example, low titers are found in some normal individuals, other autoimmune diseases, acute viral infections, and chronic inflammatory processes; several drugs can also cause a positive ANA. Almost all patients with lupus have a positive ANA test. Antibodies to double-stranded DNA (dsDNA) and to Sm (Smith) antigens are relatively specific for lupus, whereas other antibodies shown in Table 55-2 are not.

TABLE 55-4. The 1997 Revised Criteria of American Rheumatism Association for Systemic Lupus Erythematosusa

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Drug-Induced Lupus

Numerous drugs have been reported to induce a lupus-like syndrome. This syndrome usually regresses when the medication is discontinued and is rarely associated with glomerulonephritis. Drugs associated with this syndrome include procainamide, quinidine, hydralazine, α-methyldopa, phenytoin, and phenobarbital.

Lupus versus Preeclampsia–Eclampsia

Preeclampsia is common in women with lupus and superimposed preeclampsia is encountered even more often in those with lupus nephropathy. It may be difficult, if not impossible, to differentiate lupus nephropathy from severe preeclampsia. Central nervous system involvement with lupus may culminate in convulsions similar to those of eclampsia. Thrombocytopenia, with or without hemolysis, may further confuse the diagnosis.

MANAGEMENT

Current management consists primarily of monitoring the clinical conditions of both mother and fetus. Frequent hematological evaluation and assessment of renal and hepatic functions are suggested to detect changes in disease activity during pregnancy and the puerperium.

Monitoring of lupus activity and the identification of pending lupus flares by a variety of laboratory techniques has been recommended by some clinicians. However, the sedimentation rate is uninterpretable because of pregnancy-induced hyperfibrinogenemia. Although falling or low levels of complement components C3, C4, and CH50 are more likely to be associated with active disease, higher levels provide no assurance against disease activation.

There is no doubt that fetal growth restriction and perinatal mortality and morbidity are increased significantly in pregnancies complicated by lupus (See Table 55-1). The American College of Obstetricians and Gynecologists: Antepartum fetal surveillance. Practice Bulletin No. 9, October 1999, Reaffirmed 2007 recommends weekly antepartum fetal surveillance (see Chapter 12) beginning at 32 to 34 weeks. Prognosis is worsened with a lupus flare, significant proteinuria, renal impairment, and with associated hypertension and/or the development of preeclampsia. Unless hypertension develops, or there is evidence for fetal compromise or growth restriction, pregnancy is allowed to progress to term. Delivery decisions are made using obstetrical criteria.

Pharmacologic Treatment

There is no cure for lupus and complete remissions are rare. Arthralgia and serositis may be managed with nonsteroidal anti-inflammatory drugs, including aspirin. Because of the risk of premature closure of the fetal ductus arteriosus, therapeutic doses probably should not be used after 24 weeks. Low-dose aspirin, however, can be used safely throughout gestation in the management of the antiphospholipid antibody syndrome (see Chapter 54).

Life-threatening and severely disabling manifestations are managed with corticosteroids such as prednisone, 1 to 2 mg/kg per day. After the disease is controlled, this is tapered to a daily dose of 10 to 15 mg given each morning. For severe lupus flares, pulse therapy has been recommended which consists of methylprednisolone, 1000 mg per 24 hours for 3 days, with return to maintenance doses if possible. Corticosteroid therapy can result in the development of gestational or even insulin-dependent diabetes. Peripartum corticosteroids in “stress doses” (e.g., hydrocortisone 100 mg intravenously every 8 hours) are given to women who are taking these drugs or who recently have done so.

Immunosuppressive agents such as azathioprine are avoided during pregnancy unless life-threatening complications develop. Cyclophosphamide, a cytotoxic agent, has been reported to be teratogenic. Antimalarials help control skin disease and some clinicians recommend their continuation if in use prior to pregnancy.

Contraception

In general, women with lupus and associated chronic vascular or renal disease should limit family size because of the morbidity associated with the disease, as well as, increased adverse perinatal outcome. Therefore, tubal sterilization may be advantageous and it is performed with greatest safety postpartum or any other time when the disease is quiescent. Oral contraceptives must be used with caution because vascular disease is a relatively common component of lupus. Progestin-only injections and implants provide effective contraception with no known effects on lupus flares. Use of intrauterine devices is controversial due to the possibility of increased infection rates.


For further reading in Williams Obstetrics, 23rd ed.,

see Chapter 54, “Connective Tissue Disorders.”