Microbiology · Year 2 · from Microbiology

Case 2: Invasive Aspergillosis in Neutropenic Patient

Presentation

A 55-year-old man undergoing induction chemotherapy for acute myeloid leukemia has been neutropenic (ANC <100 cells/μL) for 18 days. He has been on broad-spectrum antibiotics for persistent fever without a clear source. He now develops pleuritic chest pain, cough, and hemoptysis. CT chest shows a 3 cm nodule in the right upper lobe surrounded by ground-glass attenuation (halo sign). Serum galactomannan index is elevated at 2.4 (positive >0.5). Bronchoscopy with bronchoalveolar lavage is performed; galactomannan of BAL fluid is markedly elevated.

Clinical Image

CT scan of the chest demonstrating a pulmonary nodule with surrounding ground-glass opacity (halo sign), representing hemorrhage around the invasive fungal focus - characteristic of invasive aspergillosis in neutropenic patients.

Image Source: Lecture image - invasive aspergillosis imaging

Questions

  1. What is the most likely diagnosis, and what features support this diagnosis?
  1. Explain the pathophysiology of the halo sign and hemoptysis.
  1. What is the appropriate treatment, and what determines prognosis?
  1. What preventive strategies exist for high-risk patients?

Answers

  1. Diagnosis and supporting features: This is invasive pulmonary aspergillosis (IPA), most likely caused by Aspergillus fumigatus. Supporting features include:
  • Prolonged neutropenia (>10 days) - the major risk factor
  • Fever unresponsive to broad-spectrum antibiotics
  • Characteristic imaging: Pulmonary nodule with halo sign
  • Elevated serum galactomannan: A cell wall component detected as a biomarker
  • Hemoptysis: Suggests angioinvasion

The combination of host risk factors, clinical presentation, imaging, and biomarker positivity establishes the diagnosis with high probability.

  1. Pathophysiology of halo sign and hemoptysis: Aspergillus demonstrates angioinvasive behavior in neutropenic patients - the fungal hyphae invade blood vessel walls. This causes:
  • Thrombosis of invaded vessels
  • Hemorrhage around the infected focus (produces the halo sign = ground-glass surrounding nodule)
  • Tissue infarction from vascular occlusion
  • Hemoptysis from erosion into airways
  • Later, as neutropenia resolves, the air-crescent sign appears as necrotic tissue separates
  1. Treatment and prognosis:
  • First-line therapy: Voriconazole (IV then oral) - superior to amphotericin B
  • Alternative: Isavuconazole (similar efficacy, fewer drug interactions, better tolerated)
  • Salvage therapy: Liposomal amphotericin B
  • Combination therapy: Sometimes used for refractory cases

Prognosis depends on:

  • Immune reconstitution - most critical factor; mortality drops significantly when neutropenia resolves
  • Early diagnosis and treatment
  • Extent of infection
  • Underlying disease status

Overall mortality ranges from 30-80% depending on these factors.

  1. Prevention strategies:
  • Antifungal prophylaxis: Posaconazole for high-risk patients (prolonged neutropenia, HSCT with GVHD)
  • HEPA-filtered rooms to reduce airborne spore exposure
  • Galactomannan monitoring: Twice-weekly testing enables early preemptive therapy
  • Avoid high-risk exposures: Construction sites, gardening, areas with decaying vegetation
  • Prompt empiric therapy for suspected fungal infection in high-risk neutropenic patients

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