## First-Line Agent for Mild-to-Moderate SLE **Key Point:** Hydroxychloroquine is the foundational drug for all SLE patients, regardless of disease severity, and is particularly effective for articular and cutaneous manifestations. ### Mechanism of Action - Accumulates in lysosomes and inhibits toll-like receptor (TLR) signaling - Reduces antigen presentation and T-cell activation - Anti-inflammatory and immunomodulatory effects ### Efficacy in SLE - **Articular disease:** Effective for arthralgia and non-erosive polyarthritis - **Cutaneous disease:** Gold standard for malar rash, discoid lesions, and photosensitivity - **Systemic effects:** Reduces disease flares, improves survival, and decreases thrombotic risk - **Renal protection:** May slow progression of lupus nephritis when used as adjunct ### Dosing & Safety - Standard dose: 200–400 mg daily (max 5 mg/kg/day) - Well-tolerated with long-term use - Baseline ophthalmology exam required; annual screening for retinopathy (rare at current dosing) **High-Yield:** Hydroxychloroquine is started in ALL SLE patients at diagnosis and continued indefinitely. It is NOT reserved for mild disease — it is the backbone of SLE therapy. ### Why Other Agents Are Not First-Line Here - **Methotrexate, mycophenolate, azathioprine:** Reserved for moderate-to-severe disease, renal involvement, or inadequate response to hydroxychloroquine + NSAIDs/corticosteroids - **Corticosteroids:** Used adjunctively for flares but not as monotherapy for stable mild disease **Clinical Pearl:** The combination of hydroxychloroquine + NSAIDs (or low-dose prednisolone) is the standard induction regimen for non-severe SLE. [cite:Harrison 21e Ch 297]
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