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Journal of Clinical Oncology, Vol 26, No 13 (May 1), 2008: pp. 2214-2215 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.15.2777
Invasive Pulmonary Aspergillosis Associated With Marijuana Use in a Man With Colorectal CancerDepartment of Medicine, University of Toronto, Toronto, Canada
Department of Microbiology, The Hospital of Sick Children, University of Toronto, Toronto, Canada
Department of Medicine, University Health Network, University of Toronto, Toronto, Canada
Department of Pathology, University Health Network, University of Toronto, Toronto, Canada
Department of Medicine, University Health Network, University of Toronto, Toronto, Canada In November 2006, a 65-year-old man presented for routine oncology follow-up with a 1-month history of cough, exertional dyspnea, and fever. Two years earlier, he had been diagnosed with colorectal cancer and treated with resection and adjuvant chemotherapy (fluorouracil and folinic acid). Nine months before his current visit, he was diagnosed with metastatic disease in his lungs and pelvis and had completed eight cycles of combination chemotherapy (capecitabine, irinotecan, and bevacizumab every 3 weeks), resulting in a significant reduction in tumor burden. At the clinic visit, his scheduled ninth cycle of chemotherapy was postponed, and he was prescribed a 7-day course of empiric moxifloxacin for presumed bacterial pneumonia. Despite this, he experienced progressive fatigue, increasing dyspnea, and small-volume hemoptysis, and presented to the emergency department. He had no other medical history of note. He was born in Canada and had no known exposure to tuberculosis. He took no regular medications. Although he had never smoked cigarettes, he had started smoking marijuana for the palliation of chemotherapy-induced nausea 6 weeks before presentation. Physical examination, including pulse oximetry and chest auscultation, was normal. The WBC (7.9 x 109/L) and neutrophil (5.2 x 109/L) counts were also normal, and no significant neutropenia had been documented during the course of the patient's chemotherapy. Cultures of blood and sputum for bacteria, mycobacteria, and fungi were negative. A computed tomography scan of the chest revealed a new 4.3-cm cavitary lesion (Fig 1, arrow) in the left lower lobe with surrounding ground-glass opacities. A computed tomography–guided fine-needle aspirate of the cavity was performed; microscopic examination demonstrated necrosis, inflammation, and masses of hyaline fungal hyphae with dichotomous branching and septations, compatible with Aspergillus species (Fig 2A). Fragments of plant matter, likely inhaled cannabis, were also present in the sample (Fig 2B). There were no malignant cells. Although no organisms were detected by conventional microbiologic techniques, polymerase chain reaction–based nucleic acid amplification and sequencing confirmed the presence of Aspergillus fumigatus in the aspirate. A 3-month course of voriconazole, the current standard therapy,1 was administered for a diagnosis of invasive pulmonary aspergillosis. Six months after completing antifungal therapy, the patient has had total symptomatic and radiographic resolution of his infection.
Aspergillus is a ubiquitous filamentous fungus (mold) found worldwide in water, soil, and in particular, decaying vegetation. Invasive aspergillosis (IA) is a significant cause of morbidity and mortality in immunocompromised hosts. As in the patient we describe, infection is most often due to A fumigatus, and most frequently occurs in the lungs. Prolonged (> 3 weeks) and profound neutropenia is the most important predisposing condition for IA: patients with hematologic malignancies and hematopoietic stem-cell transplant recipients are at particularly high risk.2 IA is less common among patients with solid tumors, but often occurs in the absence of neutropenia in this setting.3 Other risk factors for IA include corticosteroid or anti–tumor necrosis factor therapy, solid organ transplantation, advanced HIV/AIDS, primary immunodeficiencies, chronic lung disease, and critical illness.2 Inhalation of marijuana via smoking may also lead to invasive pulmonary aspergillosis, through both the contamination of the marijuana with fungal spores and the deleterious effects of marijuana smoke on alveolar macrophage function.4-6 Although detailed epidemiologic data are scarce, marijuana is used by patients with cancer and other chronic diseases for the palliation of symptoms including nausea, pain, and cachexia.7 When surveyed, 30% of US oncologists supported the legalization of medicinal marijuana, though only a minority of these would prescribe it with any frequency.8 In Canada, medicinal marijuana that is both tested for fungi and irradiated to eliminate pathogens may be obtained legally. However, difficulties in distribution and availability mean that many patients, including the patient we report, obtain their supply from sources lacking these safeguards. Although this patient with cancer was not neutropenic, a detailed history revealing marijuana use suggested invasive aspergillosis as the cause of his cavitary lung disease; this diagnosis was ultimately confirmed by invasive sampling. Given that many potential users of medicinal marijuana may be immunosuppressed, it is important to recognize this risk of infection and to counsel patients appropriately. Consensus guidelines specifically recommend avoidance of the use of marijuana in hematopoietic stem-cell transplant recipients.9 Furthermore, invasive aspergillosis should be considered in the differential diagnosis of respiratory illnesses occurring in the context of marijuana use, regardless of the patient's immune status. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES
1. Herbrecht R, Denning DW, Patterson TF, et al: Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 347:408-415, 2002 2. Barnes PD, Marr KA: Aspergillosis: Spectrum of disease, diagnosis, and treatment. Infect Dis Clin North Am 20:545-561, 2006[CrossRef][Medline] 3. Ohmagari N, Raad II, Hachem R, et al: Invasive aspergillosis in patients with solid tumors. Cancer 101:2300-2302, 2004[Medline] 4. Kagen SL: Aspergillus: An inhalable contaminant of marihuana. N Engl J Med 304:483-484, 1981[Medline] 5. Verweij PE, Kerremans JJ, Voss A, et al: Fungal contamination of tobacco and marijuana. JAMA 284:2875, 2000 6. Shay AH, Choi R, Whittaker K, et al: Impairment of antimicrobial activity and nitric oxide production in alveolar macrophages from smokers of marijuana and cocaine. J Infect Dis 187:700-704, 2003[CrossRef][Medline] 7. Hall W, Christie M, Currow D: Cannabinoids and cancer: Causation, remediation, and palliation. Lancet Oncol 6:35-42, 2005[Medline] 8. Schwartz RH, Voth EA, Sheridan MJ: Marijuana to prevent nausea and vomiting in cancer patients: A survey of clinical oncologists. South Med J 90:167-172, 1997[Medline] 9. Sullivan KM, Dykewicz CA, Longworth DL, et al: Preventing opportunistic infections after hematopoietic stem cell transplantation: The Centers for Disease Control and Prevention, Infectious Diseases Society of America, and American Society for Blood and Marrow Transplantation Practice Guidelines and beyond. Hematology Am Soc Hematol Educ Program 392-421, 2001
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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