What is the recommended treatment approach for managing lupus?

Management of Systemic Lupus Erythematosus (SLE)

Hydroxychloroquine (HCQ) is recommended as the foundation of treatment for all patients with SLE, regardless of disease severity or organ involvement, at a dose not exceeding 5 mg/kg real body weight. 1

General Treatment Approach

First-Line Therapy

• Hydroxychloroquine (HCQ):
  • Indicated for all SLE patients 1, 2
  • Dosing: Maximum 5 mg/kg real body weight 1
  • Benefits: Reduces disease activity, prevents flares, reduces organ damage, improves survival 3, 4
  • Monitoring: Baseline ophthalmological screening, then after 5 years, and yearly thereafter 1
  • Caution: Risk of retinal toxicity increases with duration of treatment, dose, chronic kidney disease, and pre-existing retinal disease 1

Disease Without Major Organ Involvement

• HCQ + Glucocorticoids (GCs):
  • For mild-moderate disease activity 1
  • GCs should be minimized to <7.5 mg/day prednisone equivalent and, when possible, withdrawn 1
  • NSAIDs may be used judiciously for short periods in patients at low risk for complications 1

For Patients Unable to Reduce GCs or with Inadequate Response

• Add immunomodulatory agents:
  • Methotrexate (preferred for skin/joint manifestations) 1
  • Azathioprine 1
  • Mycophenolate mofetil 1

For Persistent Disease Activity Despite Standard Therapy

• Add belimumab for patients with inadequate response to standard therapy with residual disease activity not allowing tapering of glucocorticoids 1, 3

For Refractory or Organ-Threatening Disease

• Rituximab may be considered in organ-threatening disease refractory to standard immunosuppressive agents 1
• Cyclophosphamide for severe organ-threatening or life-threatening SLE or as "rescue" therapy 1

Organ-Specific Management

Lupus Nephritis (LN)

• Early recognition and diagnostic renal biopsy are essential 1
• Treatment based on ISN/RPS classification:
  • For Class III-IV LN: Mycophenolate mofetil or low-dose IV cyclophosphamide with glucocorticoids 1
  • For Class V LN with nephrotic-range proteinuria: Mycophenolate mofetil with oral glucocorticoids 1
  • Maintenance therapy: Mycophenolate mofetil or azathioprine for at least 3 years 1
  • Treatment goal: Complete renal response (proteinuria <0.5 g/24h with normal/near-normal renal function) 1

Skin Disease

• First-line: Topical agents (GCs, calcineurin inhibitors), antimalarials (HCQ, quinacrine), and/or systemic GCs 1
• For non-responsive cases: Add methotrexate, retinoids, dapsone, or mycophenolate 1

Neuropsychiatric Disease

• Inflammatory manifestations (optic neuritis, acute confusional state, neuropathy, psychosis, myelitis): Immunosuppressive therapy 1
• Atherothrombotic/aPL-related manifestations: Antiplatelet/anticoagulants 1

Hematological Disease

• Acute thrombocytopenia: High-dose GCs (including IV methylprednisolone) and/or IVIG 1
• Maintenance: Mycophenolate, azathioprine, or cyclosporine 1
• Refractory cases: Rituximab or cyclophosphamide 1

Special Considerations

Pregnancy

• Safe medications: Prednisolone, azathioprine, hydroxychloroquine, low-dose aspirin 1
• Avoid: Mycophenolate mofetil, cyclophosphamide, methotrexate 1
• Monitoring: Closer monitoring for patients with lupus nephritis and antiphospholipid antibodies due to increased risk of pre-eclampsia 1

Antiphospholipid Syndrome

• Primary prevention: Low-dose aspirin for SLE patients with antiphospholipid antibodies 1
• Secondary prevention: Long-term anticoagulation for patients with APS-associated thrombosis 1
• Pregnancy: Combined unfractionated or LMW heparin and aspirin 1

Co-morbidity Management

• Cardiovascular risk: Assess and manage traditional risk factors (hypertension, dyslipidemia, diabetes) 1
• Bone health: Consider calcium/vitamin D supplementation and bisphosphonates 1
• Infection risk: Vigilant monitoring, especially with immunosuppressive therapy 1

Treatment Goals and Monitoring

• Primary goal: Achieve remission or low disease activity in all organ systems 1
• Low disease activity definition: SLEDAI ≤3 on antimalarials, or SLEDAI ≤4, PGA≤1 with GC ≤7.5 mg of prednisone and well-tolerated immunosuppressants 1
• Monitoring tools: Clinical manifestations, laboratory tests (CBC, renal function, urinalysis), immunological tests (C3/C4, anti-dsDNA), and validated activity indices 1

Common Pitfalls and Caveats

• HCQ adherence: Poor adherence is common; drug blood levels can assess compliance 1
• GC dependence: Minimize GC exposure to prevent damage; use steroid-sparing agents early 1
• Delayed diagnosis of organ involvement: Regular monitoring for early detection of kidney, neurological, or hematological involvement is crucial
• Retinal toxicity with HCQ: Regular ophthalmological screening is essential, especially after 5 years of use 1
• Infection risk: Balance immunosuppression with infection prevention strategies 1

The evidence strongly supports that early intervention with HCQ and appropriate immunosuppressive therapy based on disease severity and organ involvement can significantly improve morbidity, mortality, and quality of life in SLE patients.