What is the best course of treatment for a patient with eosinophilia, a positive galactomannan (GM) test, and bowel wall thickening, suggestive of invasive aspergillosis?

Management of Eosinophilia with Positive Galactomannan and Bowel Wall Thickening

Initiate voriconazole immediately as first-line systemic antifungal therapy, perform urgent surgical debridement of necrotic bowel tissue, and reduce immunosuppression if feasible—this triad represents the cornerstone of management for gastrointestinal invasive aspergillosis. 1

Immediate Antifungal Therapy

Voriconazole is the standard of care for invasive aspergillosis regardless of anatomic location, demonstrating superior survival compared to amphotericin B (71% vs 58% at 12 weeks) in the pivotal randomized trial. 1, 2

Dosing Regimen

• Loading dose: 6 mg/kg IV every 12 hours for the first 24 hours 1, 2
• Maintenance dose: 4 mg/kg IV every 12 hours for a minimum of 7 days 1, 2
• Transition to oral: 200 mg twice daily once clinically stable 1, 2

Alternative First-Line Option

• Liposomal amphotericin B (L-AMB) at 3 mg/kg/day IV is an alternative for patients who cannot tolerate voriconazole or have contraindications 2

Urgent Surgical Management

Urgent surgical exploration with resection of necrotic bowel is mandatory in gastrointestinal invasive aspergillosis presenting with bowel wall thickening and necrosis. 1 The combination of surgical debridement and antifungal therapy improves survival significantly. 1

Surgical Considerations

• Assess the extent of bowel necrosis and perforation risk 3
• Evaluate for potential complications including fatal hemorrhage, perforation, obstruction, and infarction 3
• Weigh the patient's coagulopathy status and surgical morbidity before proceeding 3

Immunosuppression Reduction

Reduce or discontinue immunosuppressive medications when medically feasible, as this is the third essential pillar of treatment alongside antifungals and surgery. 1 The ultimate response to antifungal therapy is largely related to host factors, including resolution of neutropenia, return of neutrophil function, and lessening immunosuppression. 3

Diagnostic Confirmation and Monitoring

Galactomannan Interpretation

• Positive serum galactomannan has 80-100% sensitivity and 90-100% specificity in neutropenic patients, with a positive predictive value of 88% when both PCR and galactomannan are positive 1
• The negative predictive value is >90% for excluding invasive aspergillosis 1

Serial Monitoring Protocol

• Perform serial galactomannan testing every 3-4 days initially, then twice weekly 1
• A progressive decrease in galactomannan optical density index during the first 2 weeks predicts satisfactory response 1
• Regular CT scans should be performed to assess lesion resolution 1
• Progressive increase in Aspergillus antigen levels over time signifies a poor prognosis 2

Treatment Duration

Continue antifungal therapy for a minimum of 6-12 weeks, throughout the period of immunosuppression, and until lesions have resolved. 2, 4 Duration should be determined by resolution of clinical and radiological findings, not solely by normalization of antigenemia. 3

Salvage Therapy Options

If initial voriconazole therapy fails or is not tolerated, consider: 1, 2

• Liposomal amphotericin B formulations
• Echinocandins (caspofungin or micafungin)
• Itraconazole as alternative azole

Note that caspofungin is FDA-approved only for invasive aspergillosis in patients who are refractory to or intolerant of other therapies, not as initial therapy. 5

Critical Pitfalls to Avoid

Corticosteroid Use

Avoid corticosteroids where possible—their role in this context is deleterious. 3 There may be a tendency to use corticosteroids in patients with eosinophilia, but this should be resisted in the setting of invasive aspergillosis.

Differential Diagnosis Considerations

• Recognize that other angioinvasive filamentous fungi (Zygomycetes, Fusarium species, Scedosporium species) may cause similar clinical presentations 3
• If the etiological organism is not definitively known, initiate an amphotericin B formulation to cover possible zygomycosis, as voriconazole lacks activity against Zygomycetes 3

False Positives and Negatives

• Galactomannan can yield false-negative results in patients receiving antimold prophylaxis 6
• False-positive galactomannan results can occur, particularly in children 3
• Culture and direct smear results may be falsely negative in patients already receiving systemic antifungal therapy 3

Prognostic Factors

Poor prognostic indicators include: 1

• Hematologic malignancy
• Recent chemotherapy
• Recent bone marrow transplant
• Neutropenia at diagnosis
• Renal or hepatic failure