D2.386 - Intravenous Immunoglobulin–Associated Severe Prolonged Neutropenia: A Rare but Life-Threatening Complication in Primary Immunodeficiency

Introduction

Intravenous immunoglobulin (IVIG) is a cornerstone therapy for inborn errors of immunity (IEI) and is generally well tolerated. IVIG-associated neutropenia has been reported but is usually transient and mild. Severe, persistent neutropenia with life-threatening infection is rare. We describe a patient with Common Variable Immunodeficiency (CVID) who developed severe neutropenia after IVIG therapy.

Case Presentation

A 27-year-old woman was diagnosed with CVID based on recurrent respiratory infections, agammaglobulinemia, and absent vaccine responses. She was started on IVIG (30 g every 21 days). Five days after the second infusion, she developed profound neutropenia (absolute neutrophil count [ANC]: 0/µL). Viral serologies and autoimmune markers were negative. Despite filgrastim, neutropenia persisted.

Eight days after the third IVIG infusion, she presented with fever, hypotension, cough, and oropharyngeal fungal plaques. ANC was 20/µL. Thoracic computed tomography showed findings consistent with invasive fungal infection, confirmed as Aspergillus spp.

Bone marrow biopsy excluded myelodysplastic syndrome and malignancy but demonstrated reactive T-lymphocyte expansion, increased cellular immune activation, hemophagocytosis, and suppressed hematopoiesis. Hemophagocytic lymphohistiocytosis criteria were not fulfilled. Findings were suggestive of with IVIG-induced immune-mediated marrow suppression.

Methylprednisolone (1 mg/kg/day) led to rapid neutrophil recovery (ANC 5,930/µL). IVIG was discontinued and switched to subcutaneous immunoglobulin (SCIG) with short-term corticosteroid prophylaxis. After SCIG initiation, neutrophil counts stabilized (ANC 1,550–1,810/µL). The temporal relationship between immunoglobulin therapy and ANC are shown in Figure 1.

Conclusion

Although IVIG-induced neutropenia is usually transient, severe G-CSF–refractory cases may occur, especially in immune dysregulation. Proposed mechanisms include complement-mediated margination, immune-mediated clearance, and apoptosis. Persistent neutropenia after IVIG should raise suspicion for immune-mediated marrow suppression. Corticosteroids and transition to SCIG may be effective management strategies.