A 37-year-old man comes to the office after coughing up a small amount of bright red blood. He has had 3 days of fever, pleuritic chest pain, and cough productive of thick brown sputum. He started oral antibiotics for these symptoms 2 days ago but has seen no improvement. The patient received allogenic stem cell transplantation for acute myeloid leukemia 6 weeks ago, which was complicated by acute graft-versus-host disease and prolonged neutropenia. Temperature is 39 C (102.2 F), blood pressure is 102/66 mm Hg, and pulse is 112/min. Pulmonary examination shows right sided crackles. Laboratory results are as follows:
| Hematocrit | 28% |
| Platelets | 140,000/mm3 |
| Leukocytes | 1500/mm3 |
Chest x-ray reveals a dense right upper lobe infiltrate, which has grown in size when compared to the x-ray from 2 days ago. CT scan of the chest reveals several nodular lesions with surrounding ground-glass opacities in the right upper lobe. Sputum Gram stain shows inflammatory cells but no organisms. Which of the following is the most likely diagnosis?
Invasive aspergillosis | Chronic pulmonary aspergillosis* | |
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*Simple aspergilloma (fungus ball in preexisting lung cavity) is a form of chronic pulmonary aspergillosis but is usually quiescent with occasional hemoptysis. | ||
Aspergillus is a ubiquitous fungus that most people encounter daily. Conidia are inhaled into the lung and convert to potentially pathogenic hyphae. Infection is rare in immunocompetent patients as macrophages, neutrophils, and T cells rapidly neutralize and clear the organism. However, patients with severe immunocompromise (eg, prolonged neutropenia, post-transplant) are far more likely to develop invasive disease.
Invasive pulmonary aspergillosis is characterized by the classic triad of fever, pleuritic chest pain, and hemoptysis. CT scan of the chest usually reveals nodules with surrounding ground-glass opacities ("halo sign"). Diagnostic testing includes serum biomarkers for cell wall components (eg, galactomannan assay) and sputum stain/culture. However, sensitivity is low; and bronchoscopy with bronchoalveolar lavage (BAL) and biopsy are required if noninvasive testing (eg, sputum stain/culture) is inconclusive, as in this patient. Among lower respiratory cultures, BAL has the highest positive predictive value in patients who have hematologic malignancies or are hematologic transplant recipients. Patients are treated with 1-2 weeks of intravenous voriconazole plus an echinocandin (eg, caspofungin) and then transitioned to prolonged therapy with oral voriconazole alone. The mortality rate is >50%.
This patient's pancytopenia is likely due to his recent stem cell transplant combined with immunosuppressive therapy.
(Choice A) Cytomegalovirus is a common opportunistic infection that may cause pneumonitis marked by dyspnea, nonproductive cough, low-grade fever, and (usually) patchy or diffuse ground-glass opacities on CT scan. This patient with hemoptysis, chest pain, productive cough, and nodules with a "halo sign" is more likely to have aspergillosis.
(Choice C) Candida rarely causes active infection in the lung. Invasive Candida more commonly causes eye, skin, muscle, vascular, or central nervous system disease.
(Choice D) Pneumocystis pneumonia is a common opportunistic infection characterized by dyspnea, nonproductive cough, fever, and (usually) bilateral, diffuse, interstitial infiltrates on chest imaging. Hemoptysis, productive cough, and a "halo sign" on CT scan make this diagnosis less likely.
(Choice E) Reactivation of pulmonary tuberculosis commonly occurs in patients with immunosuppression and may manifest with fever, hemoptysis, dyspnea, and upper lobe pulmonary disease; however, thick sputum and nodules with surrounding ground glass opacities are more characteristic of aspergillosis.
Educational objective:
Invasive aspergillosis primarily affects immunocompromised patients and typically causes the triad of fever, pleuritic chest pain, and hemoptysis. CT scan often reveals pulmonary nodules with surrounding ground-glass opacities ("halo sign"). Treatment usually requires a combination of voriconazole and an echinocandin (eg, caspofungin).