Lupus vs. Preeclampsia

Case Study


Michael D. Lockshin, MD

Attending Rheumatologist, Hospital for Special Surgery
Professor of Medicine, Weill Cornell Medical College
Director, Barbara Volcker Center for Women and Rheumatic Disease

Doruk Erkan, MD

Associate Attending Rheumatologist, Hospital for Special Surgery
Associate Professor of Medicine, Weill Cornell Medical College
Associate Physician-Scientist, Barbara Volcker Center for Women and Rheumatic Disease

  1. Case Presentation
  2. Physical Examination
  3. Initial Laboratory Investigation
  4. Preeclampsia versus Systemic Lupus Erythematosus
  5. Further Lab Tests 1
  6. Further Lab Tests 2
  7. Postpartum laboratory tests
  8. Renal Biopsy: Diffuse Proliferative Glomerulonephritis
  9. Diagnosis
  10. Discussion Points
  11. Preeclampsia vs. Systemic Lupus Erythematosus-Discussion

 

Case Presentation

A 30 year old, previously healthy, 31-week pregnant [G3A1P1] black woman was admitted for further work-up of a two-week history of worsening lower extremity swelling, increasing blood pressure, and rapidly rising proteinuria. Her pregnancy was uneventful until 2 weeks before admission when proteinuria was detected. She denied any other complaints and review of systems was negative for shortness of breath (SOB), fever, rash, arthralgia, alopecia, oral ulcers, Raynaud's phenomenon or miscarriage. Past medical history was significant for surgery for recurrent sinusitis during childhood. She smoked 4 cigarettes/day, which she quit at the beginning of pregnancy. She was taking multivitamins and FeSO4 325-mg PO BID; family history was negative for hematologic and rheumatologic disease. Two weeks before presentation urine dipstick showed 3(+) protein and 1(+) blood. She had 4 grams of protein in the 24-hour urine collection 4 days before admission.

Physical Examination

On physical examination the patient had blood pressure ranging between 130-140/70-95 mmHg. Other significant findings were periorbital edema, nasal perforation (which she attributed to her sinus surgery during the childhood) and 3(+) pitting edema of lower extremities. All joints had full range of motion without active synovitis.

The initial laboratory investigation demonstrated a leukocyte count of 5.9 K/ul (normal 3.4-11.2 K/ul) with a normal differential, hemoglobin 9.4 mg/dl (normal 12-16 mg/dl) and platelet count of 293,000/mm3 (normal 150-450x103/mm3). Serum electrolytes, liver function tests, blood urea nitrogen, creatinine levels, and coagulation studies were within normal limits. Urinalysis revealed 0-2 red blood cells, 0-2 white blood cells, 3(+) proteinuria, and 10.56 grams of protein in 24-hour urine collection but no cellular casts.

Preeclampsia versus Systemic Lupus Erythematosus

The patient was admitted to the hospital with the initial diagnosis of preeclampsia (PEC). The triad of hypertension, edema, and proteinuria is the hallmark of preeclampsia in late pregnancy. However, the magnitude of proteinuria was disproportionate for blood pressure elevation. This led us to consider possible diagnosis of systemic lupus erythematosus (SLE) and an anti-nuclear antibody (ANA) test was ordered, which was positive (1.71) in homogeneous pattern.

Further Laboratory Tests #1

After admission the test results described above were obtained. At this point, the diagnostic possibilities included PEC, SLE, and primary glomerulopathies. The presence of positive ANA and low complement levels were suggestive but not diagnostic of SLE. The patient was started on prednisone 20 mg TID for the presumed diagnosis of SLE.

Further Laboratory Tests #2

Other significant laboratory findings are shown above. The negative double-stranded anti-DNA antibodies (ds-DNA) was contrary to the diagnosis of SLE whereas the high titer anti-Ro antibody favored the diagnosis. However, anti-Ro antibody is not diagnostic of SLE as this antibody can be seen in healthy women. Over the next week she was started on furosemide due to increased edema and weight gain of 30 lbs. Nine days after admission, blood pressure was difficult to control and she was started on methyldopa 250 mg PO BID increasing to 500 mg over the next 3 days. Two weeks after admission (34 weeks of pregnancy) blood pressure was 180/120 mmHg despite addition of labetolol 100 mg PO BID. She had an induced delivery for worsening maternal hypertension.

Postpartum laboratory tests

One month after the delivery patient was seen in the rheumatology clinic. She was asymptomatic at that time, prednisone had been tapered, and she remained only on labetolol 100 mg PO BID. Laboratory findings obtained at that visit are shown above. Due to persistent hypertension and proteinuria, a renal biopsy was done. The baby was found to have anti-Ro antibody but no congenital heart block, neonatal lupus or other medical problems.

Renal Biopsy: Diffuse Proliferative Glomerulonephritis

The renal biopsy was consistent with diffuse proliferative glomerulonephritis. This slide demonstrates (on higher magnification) hypercellular glomeruli with endocapillary proliferative process, scattered neutrophils, and pyknotic nuclear debris indicating focal necrosis (Arrow: active cellular crescents).

Left arrow: Glomeruli displaying active cellular crescents (about one-third of the glomeruli) Right arrow: Fibrinoid necrosis.

Renal Biopsy: Diffuse Proliferative Glomerulonephritis

This slide demonstrates a necrotic glomerulus.

Diagnosis

The patient was diagnosed with SLE and lupus nephritis. She was started on pulse corticosteroids and intravenous monthly cyclophosphamide.

Discussion Points

This case illustrates several clinical discussion points: differential diagnosis of proteinuria in a pregnant woman, lupus nephritis as the initial and only manifestation of SLE during pregnancy, and the significance of autoantibodies during pregnancy.

Preeclampsia vs. Systemic Lupus Erythematosus-Discussion

1. How do you differentiate PEC from SLE flare during pregnancy? Proteinuria during pregnancy requires a very careful evaluation whether a patient has SLE or not. Preeclampsia (PEC) is the major concern in non-lupus population. Patients are usually normal during early pregnancy but hypertension, edema, and proteinuria appear suddenly during the third trimester. In the SLE population however, the differential diagnosis is worsening or new onset lupus nephritis, preeclampsia or both. As the above slide demonstrates (1), it may be impossible to differentiate between SLE nephritis and PEC during pregnancy. Rapid worsening of proteinuria over several days, clinical signs of active SLE, and the appearance of erythrocyte casts favor the diagnosis of lupus glomerulonephritis. Specific indicators of SLE activity, such as anti-DNA antibody, usually do not change during pregnancy. Thus a rising titer of anti-DNA antibody indicates a possible flare in a pregnant woman just as it does in a nonpregnant woman. Normal serum complement levels favor PEC. Erythrocyte sedimentation rate is increased in normal pregnancy and in PEC and thus is an unreliable measure of lupus worsening during pregnancy. Thrombocytopenia, hypertension, and hyperuricemia occur in both SLE and PEC and often are not helpful. The distinction between pregnancy-induced and SLE-induced complications is critical because prednisone given in the absence of lupus flare can induce PEC.

2. How commonly does SLE present during pregnancy? The initial presentation of SLE with or without nephritis during pregnancy is rare. Our experience is limited to several cases, in which patients presenting with nephrotic range proteinuria or anuric renal failure were biopsied and subsequently diagnosed with SLE.

3. What is the significance of a positive ANA in healthy pregnant woman? When ANA is discovered in a pregnant woman, especially in the setting of worsening proteinuria, it is a diagnostic challenge for the physician. In the healthy population the prevalence of ANA is 1-5%. In a pregnant healthy woman, the literature indicates that the incidence of positive ANA ranges between 0.68-10.7% (2) and healthy pregnant women may demonstrate a higher prevalence rate of serum ANA compared with healthy nonpregnant women. A prospective study showed that the incidence of ANA in pregnant women (10.7%) is significantly higher than in nonpregnant women (2%), and they reach their highest level at the end of pregnancy (2,3). In our experience, transient ANA positivity can occur during pregnancy and can disappear following delivery.

4. What is the significance of positive anti-Ro during pregnancy? The anti-Ro/SS-A antibody is present in the serum of >10% of patients with connective tissue disorders (4), and mostly occur in patients with primary Sjogren's syndrome and SLE. Neonatal lupus and/or congenital heart block are almost invariably associated with maternal anti-Ro antibody (5). The prevalence of anti-Ro in the population of normal women of reproductive age is 1% and many individuals have no obvious illness (6). Mavridis et al. demonstrated that 0.35% of healthy women have laboratory evidence of anti-Ro antibody (7). Besides anti-Ro, anti-La/SS-B antibody is also associated with neonatal lupus, congenital heart block, or transient skin rash.

5. Diagnostic challenge: Systemic lupus erythematosus versus preeclampsia Our patient presented with increasing proteinuria, hypertension, edema, and weakly positive ANA. There was no history of SLE or any systemic symptoms suggestive of SLE. Our initial diagnosis of PEC was based on the fact that: she had classical findings of PEC; SLE presentation is rare during the pregnancy; and a weakly positive ANA can be seen during the pregnancy. Given the significant proteinuria but disproportionately elevated blood pressure, the patient was started on prednisone for presumed diagnosis of SLE. Although this was supported by high titer anti-Ro antibody, still we were not sure about the definite diagnosis. Postpartum persistent proteinuria led us to obtain a renal biopsy, which was diagnostic.

References:

  1. Lockshin MD, Sammaritano LR, Schwartzman S. Lupus pregnancy. In Lahita RG (editor): Systemic lupus erythematosus. 1999;507-536

  2. Farnam J, Lavastida MT, Grant JA, Reddi RC, Daniels JC. Antinuclear antibodies in the serum of normal pregnant women: a prospective study. J Allergy Clin Immunol 1984;73(5 Pt 1):596-599

  3. Piura B, Tauber E, Dror Y, Sarov B, Buskila D, Slor H, Shoenfeld Y. Antinuclear autoantibodies in healthy nonpregnant and pregnant women and their offspring. Am J Reprod Immunol 1991;26(1):28-31

  4. Bouffard P, Laniel MA, Boire G. Anti-Ro (SSA) antibodies: clinical significance and biological relevance. J Rheumatol 1996;23(11):1838-1841

  5. Zimmermann C, Smolen JS, Graninger W, Petera P, Fabini G, Hassfeld W, Hofler E, Steiner G Fine specificity of anti-Ro(SSA) autoantibodies and clinical manifestations in patients with systemic lupus erythematosus. J Rheumatol 1996;23(11):1897-1903

  6. Harley JB, Scofield RH, Reichlin M. Anti-Ro in Sjogren's syndrome and systemic lupus erythematosus. Rheum Dis Clin North Am 1992;18(2):337-358

  7. Mavridis AK, Ming LX, Hatzipetrou P, Lentzaris G, Papanikolaou NG, Tzioufas AG, Moutsopoulos HM. Prevalence of non-organ-specific autoantibodies in pregnant and non-pregnant healthy women. Lupus 1992;1(3):141-144

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