Is pregnancy a risk factor for Systemic Lupus Erythematosus (SLE)?

From the Guidelines

Pregnancy is indeed a risk factor for lupus flares, and women with systemic lupus erythematosus (SLE) may experience disease exacerbations during pregnancy, with approximately 40-60% of lupus patients experiencing flares during this time, as supported by the most recent evidence from 2020 1.

Key Considerations

• The hormonal changes during pregnancy, particularly the increase in estrogen levels, can trigger immune system dysregulation in susceptible individuals, potentially activating or worsening lupus symptoms.
• For women with lupus who are pregnant or planning pregnancy, careful medical management is essential, including continuing hydroxychloroquine (200-400mg daily) throughout pregnancy as it helps prevent flares and improves pregnancy outcomes, as recommended by the 2020 American College of Rheumatology guideline 1.
• Corticosteroids like prednisone may be used at the lowest effective dose to manage flares, and certain immunosuppressants like azathioprine (up to 2mg/kg/day) can be continued if necessary.
• Regular monitoring with more frequent prenatal visits (typically every 2-4 weeks), blood tests to check disease activity, and specialized ultrasounds to monitor fetal growth are crucial components of care for pregnant women with lupus.

Management Recommendations

• Hydroxychloroquine should be continued during pregnancy if possible, and started if not already taking it, due to its beneficial effects on disease activity and pregnancy outcomes, as supported by the 2020 American College of Rheumatology guideline 1.
• Low-dose aspirin (81 or 100 mg daily) may be considered for women with SLE or antiphospholipid syndrome (APS) to prevent or delay the onset of gestational hypertensive disease.
• Active disease affects maternal and pregnancy outcome, and monitoring SLE disease activity with clinical history, examination, and laboratory tests at least once per trimester is recommended as good practice.

Important Considerations for Medication Use

• Mycophenolate mofetil, cyclophosphamide, and methotrexate must be discontinued due to their teratogenic effects.
• Belimumab should not be used during pregnancy unless the benefit outweighs the risk to the fetus, as supported by the 2017 EULAR recommendations 1.
• Cyclophosphamide should not be administered during the first trimester of pregnancy due to the risk of fetal loss, and should be reserved only for the management of severe, life-threatening or refractory SLE manifestations during the second or third trimester, as supported by the 2017 EULAR recommendations 1.

From the Research

Risk Factors for Lupus During Pregnancy

• Pregnancy can be a risk factor for lupus flares, with studies showing that flare-ups occur in 85.3% of cases, particularly when there is renal involvement 2.
• The relationship between lupus and pregnancy is problematic, with maternal and fetal outcomes being worse than in the general population, and the management of flare-ups being difficult during this period 2.
• Risk factors for lupus flares during pregnancy include anti-DNA, hypocomplementemia, previous thrombosis, triple antiphospholipid (aPL) antibody positivity, active lupus nephritis, and discontinuation of medications such as hydroxychloroquine and azathioprine 3.

Protective Factors for Lupus During Pregnancy

• Achieving remission before pregnancy and antimalarial use at baseline and during pregnancy are protective factors against lupus flares 4.
• Managing SLE disease activity prior to pregnancy is critical to minimize flare risks, and identifying significant risk and protective factors associated with flares can facilitate better clinical management strategies for pregnant women with SLE 4.

Clinical Management of Lupus During Pregnancy

• The management of lupus nephritis has dramatically changed with the introduction of cyclophosphamide, and its prognosis has greatly improved 5.
• Mycophenolate mofetil has emerged as the first-line treatment of lupus nephritis due to its better safety profile compared with cyclophosphamide 6.
• Therapeutic monitoring of the serum mycophenolic acid level to enhance the efficacy of mycophenolate mofetil in lupus nephritis is being explored 6.