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<p>Patients with features of multiple systemic vasculitides are rare but do exist and can be diagnostically challenging. In particular, it can be difficult to distinguish granulomatosis with polyangiitis (GPA) with eosinophilia, proteinase 3 (PR3)-ANCA–positive eosinophilic granulomatosis with polyangiitis (EGPA), and overlap of GPA and EGPA in clinical practice. Nevertheless, in severe cases, rapid therapeutic decisions are required. We report such a life-threatening case of PR3-ANCA–positive vasculitis with eosinophilia, refractory to conventional therapy, that achieved remission with simultaneous biologic therapy using mepolizumab (MPZ) and rituximab (RTX) and provide a case-based review of the efficacy and safety of this dual biologic therapy. An 18-year-old man presented with cough, hemoptysis, leg purpura, and marked eosinophilia (4575/μL). Chest CT revealed alveolar hemorrhage (DAH). Proteinase 3 (PR3)–anti-neutrophil cytoplasmic antibody (ANCA) was positive, and skin biopsy showed leukocytoclastic vasculitis with eosinophil infiltration, consistent with EGPA. He was refractory to methylprednisolone (mPSL) pulse therapy and intravenous cyclophosphamide (IVCY), and DAH worsened, requiring non-invasive ventilation. Plasma exchange, MPZ (300&#xa0;mg), and RTX (375&#xa0;mg/m<sup>2</sup> weekly × 4) were administered. DAH resolved rapidly after MPZ administration. Eosinophils dropped to 0/μL, but PR3-ANCA remained positive, and thereafter, nephritis developed. At 3&#xa0;months after disease onset, renal biopsy showed pauci-immune crescentic glomerulonephritis with little eosinophil infiltration. Additional mPSL pulses induced remission, which was maintained with MPZ and RTX. PR3-ANCA turned negative, and proteinuria resolved within 12&#xa0;months. Glucocorticoids (GCs) were discontinued after 2.5&#xa0;years, with a Vascular Damage Index (VDI) of 0. No serious infections or adverse events occurred. Although the development of glomerulonephritis after normalization of eosinophil count and DAH remission suggested possible EGPA–GPA overlap, the absence of granulomatous features and the potential phenotypic shift under anti–IL-5 therapy supported a final diagnosis of PR3-ANCA–positive EGPA. In life-threatening situations, the priority should be to initiate agents effective across both entities rather than to delay treatment until classification is certain. Our review suggests that simultaneous biologic therapy with MPZ and RTX can be effective with minimal adverse events and should be considered without hesitation in such critical cases.</p>

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Glucocorticoid-free remission with simultaneous mepolizumab and rituximab in life-threatening PR3-ANCA-positive eosinophilic granulomatosis with polyangiitis: a case report and literature review

  • 期刊论文

  • 发表日期：

    2025年12月2日

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  • Takashi Yamane,
  • Ayaka Inoue,
  • Chihiro Ichikawa

摘要

Patients with features of multiple systemic vasculitides are rare but do exist and can be diagnostically challenging. In particular, it can be difficult to distinguish granulomatosis with polyangiitis (GPA) with eosinophilia, proteinase 3 (PR3)-ANCA–positive eosinophilic granulomatosis with polyangiitis (EGPA), and overlap of GPA and EGPA in clinical practice. Nevertheless, in severe cases, rapid therapeutic decisions are required. We report such a life-threatening case of PR3-ANCA–positive vasculitis with eosinophilia, refractory to conventional therapy, that achieved remission with simultaneous biologic therapy using mepolizumab (MPZ) and rituximab (RTX) and provide a case-based review of the efficacy and safety of this dual biologic therapy. An 18-year-old man presented with cough, hemoptysis, leg purpura, and marked eosinophilia (4575/μL). Chest CT revealed alveolar hemorrhage (DAH). Proteinase 3 (PR3)–anti-neutrophil cytoplasmic antibody (ANCA) was positive, and skin biopsy showed leukocytoclastic vasculitis with eosinophil infiltration, consistent with EGPA. He was refractory to methylprednisolone (mPSL) pulse therapy and intravenous cyclophosphamide (IVCY), and DAH worsened, requiring non-invasive ventilation. Plasma exchange, MPZ (300 mg), and RTX (375 mg/m2 weekly × 4) were administered. DAH resolved rapidly after MPZ administration. Eosinophils dropped to 0/μL, but PR3-ANCA remained positive, and thereafter, nephritis developed. At 3 months after disease onset, renal biopsy showed pauci-immune crescentic glomerulonephritis with little eosinophil infiltration. Additional mPSL pulses induced remission, which was maintained with MPZ and RTX. PR3-ANCA turned negative, and proteinuria resolved within 12 months. Glucocorticoids (GCs) were discontinued after 2.5 years, with a Vascular Damage Index (VDI) of 0. No serious infections or adverse events occurred. Although the development of glomerulonephritis after normalization of eosinophil count and DAH remission suggested possible EGPA–GPA overlap, the absence of granulomatous features and the potential phenotypic shift under anti–IL-5 therapy supported a final diagnosis of PR3-ANCA–positive EGPA. In life-threatening situations, the priority should be to initiate agents effective across both entities rather than to delay treatment until classification is certain. Our review suggests that simultaneous biologic therapy with MPZ and RTX can be effective with minimal adverse events and should be considered without hesitation in such critical cases.