What are the common symptoms and treatment options for a woman of childbearing age with lupus?

Lupus Symptoms and Management in Women of Childbearing Age

Systemic lupus erythematosus (SLE) predominantly affects women of childbearing age and presents with a constellation of constitutional, mucocutaneous, musculoskeletal, and organ-specific manifestations that require early recognition and comprehensive management. 1, 2

Common Clinical Manifestations

Constitutional and Mucocutaneous Symptoms

• Fatigue is among the earliest and most common complaints 3, 4
• Fever may occur during disease flares and must be distinguished from infection 2
• Lupus-specific skin lesions include acute cutaneous lupus (malar/butterfly rash), subacute cutaneous lupus, chronic cutaneous lupus (including discoid lesions), and intermittent cutaneous lupus 2, 5
• Photosensitivity with worsening of skin manifestations after ultraviolet light exposure 5, 4
• Mouth ulcers and alopecia are frequent early manifestations 3

Musculoskeletal Manifestations

• Joint pain and arthritis are among the most common presenting symptoms 1, 2, 3
• Myalgia (muscle pain) frequently accompanies joint symptoms 3
• Serositis (inflammation of serous membranes) including pericarditis may occur 2

Renal Manifestations

• Kidney involvement presents with proteinuria, hematuria, or impaired renal function 2
• Lupus nephritis occurs in 20-60% of SLE patients over their lifetime and is associated with higher mortality 1
• Renal disease relapses are common, occurring in up to 45% of patients 2
• Hypertension is particularly common with renal involvement 2

Cardiovascular Manifestations

• Increased risk of atherosclerosis and cardiovascular disease is a major concern 2
• Pericarditis and other cardiac manifestations may develop 2

Neuropsychiatric Manifestations

• Headache, mood disorders, seizures, and cognitive impairment are the most common neuropsychiatric syndromes 2
• Psychosis and acute confusional states may occur in severe cases 1

Hematologic Abnormalities

• Anemia may indicate organ involvement and disease progression 2
• Thrombocytopenia can signal renal disease and worse prognosis 2
• Leukopenia and lymphopenia increase infection risk 2

Laboratory Findings

• Low complement levels (C3/C4) often correlate with disease activity 2
• Anti-dsDNA antibodies and other autoantibodies provide diagnostic and prognostic information 1
• Antiphospholipid antibodies indicate increased risk for thrombosis and pregnancy complications 2
• C-reactive protein is typically not elevated unless infection or serositis is present 2

Treatment Approach for Women of Childbearing Age

General Management Principles

Hydroxychloroquine should be used in all lupus patients unless contraindicated, as it reduces disease activity, prevents flares, and improves long-term outcomes. 1

• Glucocorticoids are effective for controlling disease activity but should be tapered to the lowest effective dose (ideally ≤7.5 mg/day prednisone equivalent) to minimize toxicity 1
• For patients unable to reduce steroids to acceptable chronic doses, add immunosuppressive agents such as azathioprine, mycophenolate mofetil, or methotrexate 1

Lifestyle Modifications and Adjunct Therapy

• Photo-protection is beneficial for patients with skin manifestations 1
• Smoking cessation, weight control, and regular exercise should be strongly encouraged 1
• Low-dose aspirin should be considered for cardiovascular protection and in patients with antiphospholipid antibodies 1
• Calcium/vitamin D supplementation and bisphosphonates for osteoporosis prevention, particularly in patients on chronic glucocorticoids 1

Contraception Considerations

Combined hormonal contraceptives (oral pills, vaginal ring, transdermal patch) are safe in women with inactive or stable SLE who are negative for antiphospholipid antibodies, but should be avoided in those with positive antiphospholipid antibodies due to thrombosis risk. 1

• Intrauterine devices (IUD) can be offered to all patients unless gynecological contraindications exist 1
• Copper IUD is safe for any patient 1
• Levonorgestrel-containing IUD should only be used if hormonal benefits outweigh thrombosis risk 1
• Progestin-only contraceptives (pill, depot injections) are suitable for women with antiphospholipid antibodies, though thrombosis risk must be considered 1

Pregnancy Planning and Management

Pregnancy should be planned only when lupus has been inactive for at least 6 months, with acceptable medications, and proteinuria <50 mg/mmol with preferably GFR >50 ml/min. 1

Safe Medications During Pregnancy

• Hydroxychloroquine should be continued throughout pregnancy 1
• Prednisone and other non-fluorinated glucocorticoids are acceptable 1
• Azathioprine is safe during pregnancy 1
• Tacrolimus and cyclosporine (calcineurin inhibitors) are considered safe 1
• Low-dose aspirin should be started before 16 weeks of gestation to reduce pre-eclampsia risk 1

Medications to Avoid During Pregnancy

• Mycophenolate mofetil must be discontinued at least 3 months before conception 1
• Cyclophosphamide must be avoided 1
• Methotrexate is contraindicated 1
• Biological agents should be stopped at least 4 months before conception, depending on the specific agent 1

Pregnancy Monitoring

• Patients should be assessed every 4 weeks by a specialist physician and obstetrician 1
• Symptoms may worsen during pregnancy, particularly in patients with lupus nephritis and antiphospholipid antibodies 2
• Increased risk of miscarriage, stillbirth, premature delivery, intrauterine growth restriction, and fetal congenital heart block (associated with anti-Ro/anti-La antibodies) 1

Fertility Preservation

For women requiring cyclophosphamide therapy, gonadotropin-releasing hormone analogues (GnRH-a) should be administered prior to or concomitantly with cyclophosphamide to protect against premature ovarian failure. 1

• GnRH-a have demonstrated efficacy with a relative risk reduction of 0.12 for premature ovarian failure 1
• Ovarian reserve assessment may be considered at a younger age than in the general population if multiple risk factors for impaired fertility exist 1

Lupus Nephritis-Specific Treatment

For proliferative lupus nephritis, glucocorticoids combined with immunosuppressive agents (cyclophosphamide or mycophenolate mofetil) are effective against progression to end-stage renal disease. 1

• Mycophenolate mofetil has demonstrated similar efficacy to cyclophosphamide with a more favorable toxicity profile in short- and medium-term trials 1
• Failure to respond by 6 months should prompt consideration for treatment intensification 1
• Monitoring should occur every 2-4 weeks for the first 2-4 months after diagnosis or flare, then every 3-6 months lifelong 1

Antiphospholipid Syndrome Management

In SLE patients with antiphospholipid antibodies, low-dose aspirin should be considered for primary prevention of thrombosis and pregnancy loss. 1

• For non-pregnant patients with thrombosis, long-term anticoagulation with warfarin (target INR 2.0-3.0 for venous thrombosis, INR 3.0-4.0 for arterial or recurrent thrombosis) is effective for secondary prevention 1
• In pregnant patients with antiphospholipid syndrome, combined low-molecular-weight heparin and aspirin reduce pregnancy loss and thrombosis 1

Common Pitfalls and Caveats

• Do not delay renal biopsy when proteinuria ≥0.5 g/24 hours with glomerular hematuria or cellular casts is present, as clinical and laboratory tests cannot accurately predict histological findings 1
• Distinguish lupus flares from infection, as fever can occur in both scenarios and infection is a major cause of morbidity 2, 6
• Screen for cancer according to general population guidelines, as SLE patients have increased risk of certain malignancies (non-Hodgkin lymphoma, lung cancer, cervical cancer) but undergo screening less frequently than recommended 7
• Monitor for cardiovascular disease and osteoporosis, as these comorbidities significantly impact long-term outcomes 1, 3
• Ensure close post-partum surveillance for renal flares, as risk remains elevated 1