A 35-year-old woman with SLE on hydroxychloroquine develops worsening proteinuria of 3.8 g/day. Renal biopsy shows mesangial hypercellularity, subendothelial deposits, and wire-loop lesions with full-house immunofluorescence (IgG, IgM, IgA, C3, C1q). The ISN/RPS class and MOST appropriate first-line induction therapy are:
- A Class IV; mycophenolate mofetil 2-3 g/day or cyclophosphamide ✓
- B Class III; mycophenolate mofetil 2-3 g/day
- C Class V; tacrolimus monotherapy
- D Class II; increase hydroxychloroquine dose
Correct answer: A. Class IV; mycophenolate mofetil 2-3 g/day or cyclophosphamide
Explanation
Wire-loop lesions are characteristic of ISN/RPS Class IV (diffuse proliferative) lupus nephritis, the most severe form, with subendothelial immune deposits and full-house pattern on IF. First-line induction therapy per ACR/EULAR 2019 guidelines is either mycophenolate mofetil (2-3 g/day, preferred in Black/Hispanic patients) or low-dose cyclophosphamide (Euro-lupus protocol: 6x500 mg IV), combined with high-dose corticosteroids and continued hydroxychloroquine. Tacrolimus is used in Class V (membranous). Class III shows focal (< 50% glomeruli) involvement.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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