What is the standard treatment protocol for Systemic Lupus Erythematosus (SLE)?

Standard Treatment Protocol for Systemic Lupus Erythematosus (SLE)

Overarching Treatment Principles

All patients with SLE should receive hydroxychloroquine (or chloroquine where HCQ is unavailable) as the backbone of therapy, except those who refuse or have absolute contraindications. 1, 2 This is the single most important foundational principle, as hydroxychloroquine reduces disease activity, morbidity, and mortality. 3

Core Treatment Goals

• The therapeutic goal is to achieve and maintain remission or low disease activity as soon as diagnosis is made and for as long as possible. 1
• Glucocorticoids, when clinically needed, should be prescribed at the lowest possible dose (≤7.5 mg prednisone equivalent) and for the shortest period of time. 1
• Treatment must include photo-protection, osteoporosis prevention, cardiovascular risk management, metabolic syndrome prevention, infection prevention, psychological support, and pregnancy counseling. 1

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Organ-Specific Treatment Protocols

Musculoskeletal Manifestations

Start with standard of care (SOC) alone: hydroxychloroquine plus low-dose glucocorticoids (prednisone ≤7.5 mg) if clinically indicated. 1

• If SOC fails, add methotrexate, leflunomide, belimumab, or abatacept. 1
• Cost and availability favor methotrexate as the first add-on agent. 1
• NSAIDs are first-line for pain and stiffness in musculoskeletal manifestations. 4

Mucocutaneous Manifestations

Use SOC (hydroxychloroquine ± low-dose glucocorticoids) as initial therapy. 1

• For patients failing SOC, add methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, cyclophosphamide, or belimumab. 1
• Cost and availability favor methotrexate and azathioprine. 1

Lupus Nephritis

Induction Therapy

Use high-dose glucocorticoids (prednisone 1-2 mg/kg/day, maximum 60 mg/day) plus either mycophenolate mofetil OR cyclophosphamide. 1

• Both mycophenolate mofetil and cyclophosphamide show significant benefits compared to glucocorticoids alone. 1
• Low-dose cyclophosphamide is favored over high-dose due to better safety profile with comparable efficacy. 1
• Cost and availability may favor cyclophosphamide, but consider gonadal toxicity risk (ovarian reserve reduction and sperm abnormalities). 1
• Mycophenolate mofetil may require dosing increases due to differential pharmacokinetic effects in lupus nephritis. 1

Maintenance Therapy

Use azathioprine OR mycophenolate mofetil over cyclophosphamide for maintenance. 1

• Both azathioprine and mycophenolate mofetil have better safety profiles than cyclophosphamide with comparable efficacy. 1
• Cost and availability favor azathioprine. 1

Cardiac Manifestations

Lupus Pericarditis

Use SOC plus colchicine, which significantly decreases pericarditis recurrence rate. 5

• Add low to moderate dose glucocorticoids for 4 weeks with slow tapering. 5

Lupus Myocarditis

Initiate high-dose glucocorticoids: intravenous methylprednisolone 1000 mg/day initially, followed by high-dose oral prednisone at 1-2 mg/kg/day for 1-2 weeks. 5

• Add immunosuppressive therapy with mycophenolate mofetil, cyclophosphamide, or azathioprine. 5
• Consider intravenous immunoglobulin in refractory cases. 5

Pulmonary Manifestations

Diffuse Alveolar Hemorrhage (DAH)

Treat with intravenous glucocorticoids plus cyclophosphamide AND/OR intravenous immunoglobulin AND/OR therapeutic plasma exchange AND/OR rituximab. 1

• This is a life-threatening situation requiring intense and early aggressive approach without prioritizing one intervention over another. 1
• Cost and availability favor glucocorticoids plus cyclophosphamide. 1

Neuropsychiatric Manifestations

For severe, acute neuropsychiatric manifestations, use glucocorticoids plus cyclophosphamide. 1

• This applies to seizures, psychosis, myelitis, peripheral neuropathy, brain stem disease, and optic neuritis. 1
• Glucocorticoids plus rituximab is an alternative, but evidence certainty is better for cyclophosphamide, and rituximab was only evaluated in refractory patients. 1
• Cost and availability favor cyclophosphamide. 1

Hematological Manifestations

Severe Hemolytic Anemia (Hemoglobin ≤8 g/dL)

Use high-dose glucocorticoids as first-line therapy. 1

• Add rituximab for life-threatening hemolytic anemia and/or for those in whom high-dose glucocorticoid treatment fails. 1
• Cost and availability may prompt use of immunosuppressants instead of rituximab, though no data support this. 1

Severe Thrombocytopenia (Platelet Count ≤30 x10⁹/L)

Use high-dose glucocorticoids as first-line therapy. 1

• In life-threatening situations, add rituximab or intravenous immunoglobulin for their beneficial effect on platelet count. 1
• Rituximab increases infection risk (moderate harm), while intravenous immunoglobulin has small harms (infusion reactions). 1
• Cost and availability considerations favor glucocorticoids alone when possible. 1

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Comorbidity Prevention and Monitoring

Infection Prevention

Screen all patients for HIV, HCV, HBV based on risk factors, particularly before immunosuppressive drugs including high-dose glucocorticoids. 1

• Screen for tuberculosis according to local guidelines, especially before immunosuppressive drugs. 1
• Administer inactivated vaccines (especially influenza and pneumococcus) following CDC guidelines for immunosuppressed patients, preferably when SLE is inactive. 1
• At follow-up visits, assess for severe neutropenia (<500 cells/mm³), severe lymphopenia (<500 cells/mm³), and low IgG (<500 mg/dL). 1

Osteoporosis Prevention

Assess all patients for adequate calcium and vitamin D intake, regular exercise, and smoking habits. 1

• Screen and follow for osteoporosis according to existing guidelines for postmenopausal women and patients on steroids. 1

Cancer Screening

Follow cancer screening guidelines for the general population, including cervical smear tests. 1

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Common Pitfalls to Avoid

• Never accept breakthrough symptoms without treatment modification. Guidelines emphasize a treat-to-target approach with the goal of remission or low disease activity. 6
• Prolonged use of high-dose glucocorticoids (>7.5 mg/day prednisone equivalent) increases risk of irreversible organ damage. 4
• Always assess medication adherence, especially to hydroxychloroquine. Non-adherence is associated with higher flare rates and increased pain. 4
• Inadequate disease activity monitoring makes it impossible to objectively assess treatment response and justify continuation. 6
• Consider comorbidities before starting medium/high-dose glucocorticoid treatment: diabetes, glucose intolerance, cardiovascular disease, peptic ulcer disease, and recurrent infections. 5