What are the symptoms and treatment options for a woman of childbearing age with systemic lupus erythematosus (SLE)?

Systemic Lupus Erythematosus: Symptoms and Management in Women of Childbearing Age

Clinical Manifestations

Systemic lupus erythematosus presents with a constellation of constitutional, mucocutaneous, musculoskeletal, renal, hematologic, and neuropsychiatric symptoms that vary widely between patients. 1, 2

Constitutional and Mucocutaneous Symptoms

• Fever occurs during disease flares and must be distinguished from infection 1
• Fatigue is among the earliest and most common complaints 2
• Lupus-specific skin lesions include acute cutaneous lupus (malar rash), subacute cutaneous lupus, chronic cutaneous lupus (discoid lesions), and intermittent cutaneous lupus 1
• Mouth ulcers and alopecia are frequent early manifestations 2

Musculoskeletal Manifestations

• Arthritis and joint pain are among the most common presenting symptoms 1, 2
• Myalgia frequently accompanies joint symptoms 2
• Serositis (pleuritis, pericarditis) may occur and correlates with disease activity 3, 1

Renal Manifestations

• Lupus nephritis develops in approximately 40% of patients and presents with proteinuria, hematuria, or impaired renal function 1, 4
• Hypertension is common, especially with renal involvement 1
• Renal disease relapses occur in up to 45% of patients 1
• Approximately 10% of patients with lupus nephritis progress to end-stage renal disease within 10 years 4

Hematologic Manifestations

• Anemia may indicate organ involvement and disease progression 1
• Thrombocytopenia can indicate renal disease and worse prognosis 1
• Leukopenia and lymphopenia increase infection risk 1

Neuropsychiatric Manifestations

• Headache, mood disorders, seizures, and cognitive impairment are the most common neuropsychiatric syndromes 1
• Psychosis and seizures correlate with worse outcomes 3

Cardiovascular Manifestations

• Increased risk of atherosclerosis and cardiovascular disease is a major concern 1
• Pericarditis and other cardiac manifestations may occur 1

Laboratory Findings

• Low complement levels (C3, C4) often correlate with disease activity 1
• Antiphospholipid antibodies indicate increased risk for thrombosis and pregnancy complications 1
• Anti-dsDNA antibodies correlate with disease activity and renal involvement 3
• C-reactive protein is typically not elevated unless infection or serositis is present 1

Treatment Approach for Women of Childbearing Age

Baseline Therapy for All Patients

Hydroxychloroquine is the backbone of SLE therapy and should be prescribed to all patients at ≤5 mg/kg real body weight, as it reduces disease activity, prevents flares, and improves survival. 5, 4

• Hydroxychloroquine has been associated with significant reduction in mortality and is standard of care 4
• This medication is safe during pregnancy and should be continued 3

Management of Mild-to-Moderate Disease

For patients with constitutional symptoms, arthritis, rash, or mild serositis without major organ involvement:

• Oral prednisone 0.5-1 mg/kg/day with tapering over 2-4 weeks 5
• Add immunosuppressive agents (azathioprine, mycophenolate mofetil, or methotrexate) when patients cannot reduce steroids below acceptable doses for chronic use 3
• Target maintenance dose <7.5 mg/day prednisone with goal of eventual withdrawal, as chronic glucocorticoid use correlates with infections, osteonecrosis, irreversible damage, and increased mortality 5

Management of Severe/Organ-Threatening Disease

For active lupus nephritis, neuropsychiatric manifestations, severe cytopenias, cardiopulmonary involvement, or vasculitis:

• Pulse intravenous methylprednisolone provides immediate therapeutic effect and allows lower starting doses of oral glucocorticoids 5
• Glucocorticoids combined with immunosuppressive agents are effective against progression to end-stage renal disease 3
• For proliferative lupus nephritis: mycophenolate mofetil has demonstrated at least similar efficacy compared with pulse cyclophosphamide with a more favorable toxicity profile 3, 4
• Failure to respond by 6 months should prompt discussions for intensification of therapy 3

Pregnancy Considerations

Pregnancy planning and management require special attention in women with SLE, as pregnancy may increase disease activity and carries risks for both mother and fetus. 3

Maternal Risks

• Pregnancy may increase lupus disease activity, though flares are usually mild 3
• Patients with lupus nephritis and antiphospholipid antibodies are at higher risk for pre-eclampsia and require closer monitoring 3, 1

Fetal Risks

• Increased risk of miscarriage, stillbirth, premature delivery, intrauterine growth restriction, and fetal congenital heart block (2-4.5%), especially with maternal history of lupus nephritis, antiphospholipid antibodies, anti-Ro, and/or anti-La antibodies 3

Safe Medications During Pregnancy

• Prednisolone, azathioprine, hydroxychloroquine, and low-dose aspirin may be used in lupus pregnancies 3
• Mycophenolate mofetil, cyclophosphamide, and methotrexate must be avoided during pregnancy 3

Contraception

• Combined hormonal contraceptives (oral pill, vaginal ring, transdermal patch) are safe in SLE patients with inactive or stable active disease and negative antiphospholipid antibodies 3
• Combined hormones should be discouraged in women with positive antiphospholipid antibodies (with or without definite APS) 3
• Intrauterine devices (copper or levonorgestrel-containing) can be offered to all patients unless there is a gynecological contraindication 3
• Progestin-only methods (pill, subcutaneous depot injections) are suitable for women with antiphospholipid antibodies, though thrombosis risk should be weighed 3

Fertility Preservation

• GnRH analogues should be considered for prevention of premature ovarian failure in patients requiring cyclophosphamide, administered 2 days before or concomitantly with the alkylating agent 3
• In non-life-threatening disease, less gonadotoxic regimens should be considered over alkylating agents 3

Antiphospholipid Syndrome Management

• Low-dose aspirin may be considered for primary prevention of thrombosis and pregnancy loss in patients with antiphospholipid antibodies 3
• For first venous thrombosis: oral anticoagulation targeting INR 2.0-3.0 3
• For arterial or recurrent thrombosis: high-intensity anticoagulation (target INR 3.0-4.0) 3
• In pregnant patients with antiphospholipid syndrome: combined unfractionated or low-molecular-weight heparin and aspirin reduce pregnancy loss and thrombosis 3

Adjunct Therapy and Lifestyle Modifications

• Photo-protection for patients with skin manifestations 3
• Smoking cessation, weight control, and exercise improve patient outcomes 3
• Low-dose aspirin, calcium/vitamin D, bisphosphonates, statins, and antihypertensives (including ACE inhibitors) should be considered based on individual risk factors 3, 5

Monitoring Strategy

At each visit, assess the following to detect flares and guide treatment:

• Validated activity indices 5
• Anti-dsDNA, C3, C4 levels 5
• Complete blood count 5
• Serum creatinine, proteinuria, and urine sediment 5
• Screen for infections 5

Cancer Screening

All SLE patients should follow cancer screening guidelines recommended for the general population, with particular attention to cervical cancer screening. 6

• SLE significantly increases risk of non-Hodgkin lymphoma (3-5 fold), lung cancer, cervical cancer, and hepatobiliary cancers 6
• Cervical dysplasia and cervical cancer show increased prevalence (up to 16% abnormal cervicovaginal cytology), particularly with cyclophosphamide therapy 6

Common Pitfalls to Avoid

• Do not delay hydroxychloroquine initiation—it is the foundation of therapy for all patients 5, 4
• Do not use combined hormonal contraceptives in women with positive antiphospholipid antibodies due to increased thrombosis risk 3
• Do not continue mycophenolate mofetil, cyclophosphamide, or methotrexate during pregnancy—switch to safe alternatives before conception 3
• Do not maintain chronic high-dose glucocorticoids—aggressively add steroid-sparing immunosuppressive agents to taper below 7.5 mg/day 5
• Do not assume C-reactive protein elevation indicates lupus activity—it typically suggests infection or serositis 1