A 55-year-old man comes to the emergency department due to 4 days of worsening fever, cough, and chest pain. The cough is productive of yellow sputum and occasionally streaked with blood. The patient underwent allogeneic hematopoietic stem cell transplantation 6 weeks ago due to aplastic anemia. His recovery was complicated by acute graft-versus-host disease, which is improving with high-dose corticosteroids and modification of immunosuppressive therapy. He has also had prolonged neutropenia and is receiving infection prophylaxis with valganciclovir, fluconazole, trimethoprim-sulfamethoxazole, and levofloxacin. The patient has no other medical problems and does not use tobacco, alcohol, or illicit drugs. Temperature is 38.6 C (101.5 F), blood pressure is 115/70 mm Hg, pulse is 105/min, and respirations are 22/min. Pulse oximetry is 91% on ambient air. Physical examination is notable for left lung crackles. Laboratory testing shows a leukocyte count of 1,500/mm³ with 10% neutrophils. Chest x-ray reveals an infiltrate in the left upper lobe, and subsequent CT scan of the chest shows a cavitary nodule with surrounding ground-glass opacities in the left upper lobe. Which of the following is the most likely cause of this patient's current lung condition?

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Explanation: 11ec2b69_c16b_7c12_8f63_ab96c66390c6_MD0005_00 Aspergillus spores are frequently inhaled due to their ubiquity in the environment. Healthy individuals easily clear the organism and rarely develop disease, but those with severe immunosuppression (eg, prolonged neutropenia, chronic corticosteroid use) are at risk for life-threatening infection. Pulmonary aspergillosis is the most common manifestation and is characterized by the classic triad of cough, pleuritic chest pain, and hemoptysis. Chest imaging typically reveals nodules with surrounding ground-glass opacities ("halo sign") or cavitations with air-fluid levels ("air crescent sign"). The diagnosis is usually confirmed by serum fungal biomarkers (galactomannan and beta-D-glucan assay) and sputum sampling for fungal staining and culture. Bronchoscopy with bronchoalveolar lavage and/or biopsy may be required if these diagnostic tests are inconclusive. Treatment with intravenous voriconazole and a reduction of immunosuppressive medications is the standard of care, but 1-year mortality is >80%. Fluconazole is sometimes administered for Candida prophylaxis, but this antifungal agent has no activity against Aspergillus. (Choice B) Cytomegalovirus (CMV) pneumonia usually causes fever, cough, dyspnea, and diffuse ground-glass opacities (not a nodular infiltrate). This patient is on CMV prophylaxis with valganciclovir, making this infection unlikely. (Choice C) Legionella can cause cough, chest pain, hemoptysis, and a nodular pulmonary infiltrate (although a lobar or an interstitial infiltrate is more common). However, patients usually have high fever and gastrointestinal symptoms (eg, nausea, vomiting, diarrhea) prior to the onset of pulmonary symptoms. In addition, this patient is on levofloxacin, which is an effective treatment for Legionella. (Choice D) Pneumocystis pneumonia is a common infection in patients with recent stem cell transplantation and usually manifests with diffuse interstitial pulmonary infiltrates and fulminant respiratory failure. This patient is receiving prophylaxis for Pneumocystis with trimethoprim-sulfamethoxazole. (Choice E) Streptococcus pneumoniae is the most common bacterial cause of pneumonia but is usually associated with a lobar (not a nodular) pulmonary infiltrate and is less likely to occur in the setting of prophylactic levofloxacin. Educational objective: Invasive aspergillosis is a common cause of pulmonary disease in patients with severe immunocompromise, particularly those with prolonged neutropenia or on chronic corticosteroids. Manifestations usually include cough, pleuritic chest pain, and hemoptysis. Suspicion should be raised when a CT scan of the chest shows nodular disease with surrounding ground-glass opacities or cavitations with air-fluid levels. References: Invasive zygomycosis in patients with graft-versus-host disease after allogeneic stem cell transplantation. (http://www.ncbi.nlm.nih.gov/pubmed/20002357)

A 55-Year-Old Man Comes to the Emergency Department Due to 4