Aspergillosis Clinical Presentation
- Author: Eloise M Harman, MD; Chief Editor: Ryland P Byrd, Jr, MD more...
The four most common manifestations of Aspergillus lung disease (ie, allergic bronchopulmonary aspergillosis [ABPA], aspergilloma, chronic necrotizing pulmonary aspergillosis [CNPA], and invasive aspergillosis) have quite different clinical manifestations.
Allergic bronchopulmonary aspergillosis
ABPA is a syndrome occurring in asthmatic persons and patients with cystic fibrosis (CF) that results from a hypersensitivity reaction to Aspergillus colonization of the tracheobronchial tree. This syndrome may cause fever and pulmonary infiltrates that are unresponsive to antibacterial therapy.
Patients often have a cough and produce mucous plugs, which may form bronchial casts. They may have hemoptysis. People with asthma who have ABPA may have poorly controlled disease and difficulty tapering off oral corticosteroids. ABPA may occur in conjunction with allergic fungal sinusitis, with symptoms including chronic sinusitis with purulent sinus drainage.
Aspergilloma may manifest as an asymptomatic radiographic abnormality in a patient with preexisting cavitary lung disease due to sarcoidosis, tuberculosis, or other necrotizing pulmonary processes. In patients with HIV disease, aspergilloma may occur in cystic areas resulting from prior Pneumocystis jiroveci pneumonia. Of patients with aspergilloma, 40-60% experience hemoptysis, which may be massive and life threatening. Less commonly, aspergilloma may cause cough and fever.
Chronic necrotizing pulmonary aspergillosis
CNPA manifests as a subacute pneumonia unresponsive to antibiotic therapy, which progresses and cavitates over weeks or months. Patients with CNPA have underlying disease, such as steroid-dependent chronic obstructive pulmonary disease (COPD) or alcoholism, with symptoms that may include fever, cough, night sweats, and weight loss. Usually, patients have received prolonged courses of antibiotic therapy and sometimes empiric antituberculous therapy without response prior to diagnosis via biopsy or culture.
Invasive aspergillosis typically manifests as fever, cough, dyspnea, pleuritic chest pain, and sometimes hemoptysis in patients with prolonged neutropenia or immunosuppression.
Aspergillus infection after organ transplantation most often occurs in bone marrow recipients. However, invasive aspergillosis may be observed in patients who have received lung, heart, and other solid organ transplants. Of these solid organ transplants, lung transplant recipients are at significant risk. In bone marrow transplant recipients, invasive aspergillosis has a bimodal distribution, occurring early with prolonged neutropenia before engraftment and later in the context of high-dose corticosteroid therapy for graft versus host disease.
In patients with leukemia and lymphoma, aspergillosis may occur after chemotherapy-induced bone marrow suppression, with resultant prolonged neutropenia, manifesting with persistent fever and pulmonary infiltrates despite broad-spectrum antibiotic therapy. Radiographic and CT scan images may reveal characteristic patterns, including nodules, cavitary infiltrates, and focal infiltrates.
Invasive aspergillosis is being increasingly observed in patients with COPD on long-term corticosteroid therapy.[2, 3]
Physical findings in patients with aspergillosis are nonspecific.
In ABPA, the patient may have fever. Wheezing may be noted upon auscultation of the chest. The patient may produce mucous plugs upon coughing.
In patients with aspergilloma, signs of the underlying lung disease may be noted, including clubbing in patients with CF. Hemoptysis is frequently present.
In CNPA and invasive aspergillosis, the patient is febrile and may have evidence of lung consolidation. Patients may have hemoptysis. Patients with invasive aspergillosis may be tachypneic and have rapidly progressive worsening hypoxemia.
ABPA is found in people with asthma and/or CF who are allergic to Aspergillus. The thick mucus found in the airways of these patients may make clearing inhaled Aspergillus spores difficult. Additionally, evidence of genetic susceptibility has been reported. Patients who have certain HLA alleles, particularly HLA-DR2, have increased susceptibility to ABPA, whereas HLA-DQ2 appears to be protective.
Risk factors involved in the development of CNPA include underlying pulmonary disease (including COPD, interstitial lung disease, and previous thoracic surgery) and altered immune status due to chronic corticosteroid therapy, alcoholism, collagen-vascular disease, or chronic granulomatous disease.
Aspergilloma typically develops in the context of preexisting cavitary disease. Aspergillomas may develop in patients with invasive aspergillosis or chronic necrotizing Aspergillus pneumonia.
Invasive aspergillosis occurs almost exclusively in patients who are immunocompromised. Neutropenia and corticosteroid therapy are major risk factors. In addition to patients who have undergone transplantation, patients profoundly neutropenic after receiving chemotherapy for hematologic malignancies or lymphoma, children with chronic granulomatous disease, and patients with late-stage HIV disease also are at risk.
Specific risk factors for invasive aspergillosis after bone marrow transplantation include prolonged neutropenia, graft versus host disease, high-dose corticosteroid therapy, disruption of normal mucosal barriers, mismatched or unrelated donor transplants, and the presence of central venous catheters.
Invasive Aspergillus infection in patients without malignancy or prior chemotherapy (who probably are nevertheless not immunocompetent) is most commonly seen in those with critical illness and COPD who are taking long-term corticosteroid therapy.
Brooks M. FDA Clears IV Formulation of Antifungal Posaconazole. Medscape Medical News. Available at http://www.medscape.com/viewarticle/822125. Accessed: March 25, 2014.
Samarakoon P, Soubani AO. Invasive pulmonary aspergillosis in patients with COPD: a report of five cases and systematic review of the literature. Chron Respir Dis. 2008. 5(1):19-27. [Medline].
Ader F, Bienvenu AL, Rammaert B, Nseir S. Management of invasive aspergillosis in patients with COPD: rational use of voriconazole. Int J Chron Obstruct Pulmon Dis. 2009. 4(2):279-87. [Medline]. [Full Text].
Maertens J, Verhaegen J, Lagrou K, Van Eldere J, Boogaerts M. Screening for circulating galactomannan as a noninvasive diagnostic tool for invasive aspergillosis in prolonged neutropenic patients and stem cell transplantation recipients: a prospective validation. Blood. 2001 Mar 15. 97(6):1604-10. [Medline].
Pfeiffer CD, Fine JP, Safdar N. Diagnosis of invasive aspergillosis using a galactomannan assay: a meta-analysis. Clin Infect Dis. 2006 May 15. 42(10):1417-27. [Medline].
Kuhlman JE, Fishman EK, Siegelman SS. Invasive pulmonary aspergillosis in acute leukemia: characteristic findings on CT, the CT halo sign, and the role of CT in early diagnosis. Radiology. 1985 Dec. 157(3):611-4. [Medline].
Salez F, Brichet A, Desurmont S, Grosbois JM, Wallaert B, Tonnel AB. Effects of itraconazole therapy in allergic bronchopulmonary aspergillosis. Chest. 1999 Dec. 116(6):1665-8. [Medline].
Stevens DA, Schwartz HJ, Lee JY, Moskovitz BL, Jerome DC, Catanzaro A, et al. A randomized trial of itraconazole in allergic bronchopulmonary aspergillosis. N Engl J Med. 2000 Mar 16. 342(11):756-62. [Medline].
Wark PA, Gibson PG, Wilson AJ. Azoles for allergic bronchopulmonary aspergillosis associated with asthma. Cochrane Database Syst Rev. 2003. (3):CD001108. [Medline].
Wark PA, Hensley MJ, Saltos N, Boyle MJ, Toneguzzi RC, Epid GD, et al. Anti-inflammatory effect of itraconazole in stable allergic bronchopulmonary aspergillosis: a randomized controlled trial. J Allergy Clin Immunol. 2003 May. 111(5):952-7. [Medline].
Giron JM, Poey CG, Fajadet PP, Balagner GB, Assoun JA, Richardi GR, et al. Inoperable pulmonary aspergilloma: percutaneous CT-guided injection with glycerin and amphotericin B paste in 15 cases. Radiology. 1993 Sep. 188(3):825-7. [Medline].
Mal H, Rullon I, Mellot F, Brugiere O, Sleiman C, Menu Y, et al. Immediate and long-term results of bronchial artery embolization for life-threatening hemoptysis. Chest. 1999 Apr. 115(4):996-1001. [Medline].
Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002 Aug 8. 347(6):408-15. [Medline].
Maertens J, Raad I, Petrikkos G, Boogaerts M, Selleslag D, Petersen FB, et al. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis. 2004 Dec 1. 39(11):1563-71. [Medline].
Addrizzo-Harris DJ, Harkin TJ, McGuinness G, Naidich DP, Rom WN. Pulmonary aspergilloma and AIDS. A comparison of HIV-infected and HIV-negative individuals. Chest. 1997 Mar. 111(3):612-8. [Medline].
Virnig C, Bush RK. Allergic bronchopulmonary aspergillosis: a US perspective. Curr Opin Pulm Med. 2007 Jan. 13(1):67-71. [Medline].
Meersseman W, Vandecasteele SJ, Wilmer A, Verbeken E, Peetermans WE, Van Wijngaerden E. Invasive aspergillosis in critically ill patients without malignancy. Am J Respir Crit Care Med. 2004 Sep 15. 170(6):621-5. [Medline].
Smith NL, Denning DW. Underlying conditions in chronic pulmonary aspergillosis including simple aspergilloma. Eur Respir J. 2011 Apr. 37(4):865-72. [Medline].
Stevens DA, Moss RB, Kurup VP, Knutsen AP, Greenberger P, Judson MA, et al. Allergic bronchopulmonary aspergillosis in cystic fibrosis--state of the art: Cystic Fibrosis Foundation Consensus Conference. Clin Infect Dis. 2003 Oct 1. 37 Suppl 3:S225-64. [Medline].
Chai LY, Kullberg BJ, Johnson EM, Teerenstra S, Khin LW, Vonk AG, et al. Early Serum Galactomannan Trend as a Predictor of Outcome in Invasive Aspergillosis. J Clin Microbiol. 2012 May 2. [Medline].
Becker MJ, Lugtenburg EJ, Cornelissen JJ, Van Der Schee C, Hoogsteden HC, De Marie S. Galactomannan detection in computerized tomography-based broncho-alveolar lavage fluid and serum in haematological patients at risk for invasive pulmonary aspergillosis. Br J Haematol. 2003 May. 121(3):448-57. [Medline].
Guo YL, Chen YQ, Wang K, Qin SM, Wu C, Kong JL. Accuracy of BAL galactomannan in diagnosing invasive aspergillosis: a bivariate metaanalysis and systematic review. Chest. 2010 Oct. 138(4):817-24. [Medline].
Luong ML, Clancy CJ, Vadnerkar A, et al. Comparison of an Aspergillus real-time polymerase chain reaction assay with galactomannan testing of bronchoalvelolar lavage fluid for the diagnosis of invasive pulmonary aspergillosis in lung transplant recipients. Clin Infect Dis. 2011 May. 52(10):1218-26. [Medline].
Agarwal R. Allergic bronchopulmonary aspergillosis. Chest. 2009 Mar. 135(3):805-26. [Medline].
Gruson D, Hilbert G, Valentino R, Vargas F, Chene G, Bebear C, et al. Utility of fiberoptic bronchoscopy in neutropenic patients admitted to the intensive care unit with pulmonary infiltrates. Crit Care Med. 2000 Jul. 28(7):2224-30. [Medline].
Patterson R, Greenberger PA, Radin RC, Roberts M. Allergic bronchopulmonary aspergillosis: staging as an aid to management. Ann Intern Med. 1982 Mar. 96(3):286-91. [Medline].
van der Ent CK, Hoekstra H, Rijkers GT. Successful treatment of allergic bronchopulmonary aspergillosis with recombinant anti-IgE antibody. Thorax. 2007 Mar. 62(3):276-7. [Medline].
Krishnan-Natesan S, Chandrasekar PH. Current and future therapeutic options in the management of invasive aspergillosis. Drugs. 2008. 68(3):265-82. [Medline].
Magill SS, Chiller TM, Warnock DW. Evolving strategies in the management of aspergillosis. Expert Opin Pharmacother. 2008 Feb. 9(2):193-209. [Medline].
Kontoyiannis DP, Hachem R, Lewis RE, Rivero GA, Torres HA, Thornby J, et al. Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies. Cancer. 2003 Jul 15. 98(2):292-9. [Medline].
Brooks M. FDA Okays Antifungal Delayed-Release Tablets. Available at http://www.medscape.com/viewarticle/815030. Accessed: December 3, 2013.
National Institutes of Health. Isavuconazole (BAL8557) for primary treatment of invasive Aspergillosis.NLM identfier: NCT00412893. ClinicalTrials.gov. Available at http://clinicaltrials.gov/ct2/show/NCT00412893. Accessed: April 2, 2015.
Pidhorecky I, Urschel J, Anderson T. Resection of invasive pulmonary aspergillosis in immunocompromised patients. Ann Surg Oncol. 2000 May. 7(4):312-7. [Medline].
Schubert MS, Goetz DW. Evaluation and treatment of allergic fungal sinusitis. I. Demographics and diagnosis. J Allergy Clin Immunol. 1998 Sep. 102(3):387-94. [Medline].
Boyle BM, McCann SR. The use of itraconazole as prophylaxis against invasive fungal infection in blood and marrow transplant recipients. Transpl Infect Dis. 2000 Jun. 2(2):72-9. [Medline].
Cordonnier C, Maury S, Pautas C, Bastie JN, Chehata S, Castaigne S, et al. Secondary antifungal prophylaxis with voriconazole to adhere to scheduled treatment in leukemic patients and stem cell transplant recipients. Bone Marrow Transplant. 2004 May. 33(9):943-8. [Medline].
Kontoyiannis DP, Lionakis MS, Lewis RE, Chamilos G, Healy M, Perego C. Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. J Infect Dis. 2005 Apr 15. 191(8):1350-60. [Medline].
Wirk B, Wingard JR. Current approaches in antifungal prophylaxis in high risk hematologic malignancy and hematopoietic stem cell transplant patients. Mycopathologia. 2009 Dec. 168(6):299-311. [Medline].
Mohammad RA, Klein KC. Inhaled amphotericin B for prophylaxis against invasive Aspergillus infections. Ann Pharmacother. 2006 Dec. 40(12):2148-54. [Medline].
Avery RK. Aspergillosis in hematopoietic stem cell transplant recipients: risk factors, prophylaxis, and treatment. Curr Infect Dis Rep. 2009 May. 11(3):223-8. [Medline].
Denning DW, Park S, Lass-Florl C, et al. High-frequency triazole resistance found In nonculturable Aspergillus fumigatus from lungs of patients with chronic fungal disease. Clin Infect Dis. 2011 May. 52(9):1123-9. [Medline]. [Full Text].
Bartlett JG. Aspergillosis update. Medicine (Baltimore). 2000 Jul. 79(4):281-2. [Medline].
Caillot D, Casasnovas O, Bernard A, Couaillier JF, Durand C, Cuisenier B, et al. Improved management of invasive pulmonary aspergillosis in neutropenic patients using early thoracic computed tomographic scan and surgery. J Clin Oncol. 1997 Jan. 15(1):139-47. [Medline].
Clancy CJ, Nguyen MH. Invasive sinus aspergillosis in apparently immunocompetent hosts. J Infect. 1998 Nov. 37(3):229-40. [Medline].
Cockrill BA, Hales CA. Allergic bronchopulmonary aspergillosis. Annu Rev Med. 1999. 50:303-16. [Medline].
Collin BA, Ramphal R. Pneumonia in the compromised host including cancer patients and transplant patients. Infect Dis Clin North Am. 1998 Sep. 12(3):781-805, xi. [Medline].
Denning DW. Invasive aspergillosis. Clin Infect Dis. 1998 Apr. 26(4):781-803; quiz 804-5. [Medline].
Graybill JR. Itraconazole: managing mycotic complications in immunocompromised patients. Semin Oncol. 1998 Jun. 25(3 Suppl 7):58-63. [Medline].
Jean-Baptiste E. Clinical assessment and management of massive hemoptysis. Crit Care Med. 2000 May. 28(5):1642-7. [Medline].
Klastersky J. Antifungal therapy in patients with fever and neutropenia--more rational and less empirical?. N Engl J Med. 2004 Sep 30. 351(14):1445-7. [Medline].
Klein NC, Cunha BA. New antifungal drugs for pulmonary mycoses. Chest. 1996 Aug. 110(2):525-32. [Medline].
Marr KA, Boeckh M, Carter RA, Kim HW, Corey L. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis. 2004 Sep 15. 39(6):797-802. [Medline].
Massachusetts General Hospital. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 24-2001. A 46-year-old woman with chronic sinsusitis, pulmonary nodules, and hemoptysis. N Engl J Med. 2001 Aug 9. 345(6):443-9. [Medline].
Mehrad B, Paciocco G, Martinez FJ, Ojo TC, Iannettoni MD, Lynch JP 3rd. Spectrum of Aspergillus infection in lung transplant recipients: case series and review of the literature. Chest. 2001 Jan. 119(1):169-75. [Medline].
Mylonakis E, Barlam TF, Flanigan T, Rich JD. Pulmonary aspergillosis and invasive disease in AIDS: review of 342 cases. Chest. 1998 Jul. 114(1):251-62. [Medline].
Nagappan V, Deresinski S. Reviews of anti-infective agents: posaconazole: a broad-spectrum triazole antifungal agent. Clin Infect Dis. 2007 Dec 15. 45(12):1610-7. [Medline].
Nepomuceno IB, Esrig S, Moss RB. Allergic bronchopulmonary aspergillosis in cystic fibrosis: role of atopy and response to itraconazole. Chest. 1999 Feb. 115(2):364-70. [Medline].
Novey HS. Epidemiology of allergic bronchopulmonary aspergillosis. Immunol All Clin North Am. 1998. 18:641-53.
Paterson DL, Singh N. Invasive aspergillosis in transplant recipients. Medicine (Baltimore). 1999 Mar. 78(2):123-38. [Medline].
Patterson TF, Kirkpatrick WR, White M, Hiemenz JW, Wingard JR, Dupont B, et al. Invasive aspergillosis. Disease spectrum, treatment practices, and outcomes. I3 Aspergillus Study Group. Medicine (Baltimore). 2000 Jul. 79(4):250-60. [Medline].
Sambatakou H, Dupont B, Lode H, Denning DW. Voriconazole treatment for subacute invasive and chronic pulmonary aspergillosis. Am J Med. 2006 Jun. 119(6):527.e17-24. [Medline].
Saraceno JL, Phelps DT, Ferro TJ, Futerfas R, Schwartz DB. Chronic necrotizing pulmonary aspergillosis: approach to management. Chest. 1997 Aug. 112(2):541-8. [Medline].
Serody JS, Shea TC. Prevention of infections in bone marrow transplant recipients. Infect Dis Clin North Am. 1997 Jun. 11(2):459-77. [Medline].
Singh N, Limaye AP, Forrest G, Safdar N, Munoz P, Pursell K, et al. Combination of voriconazole and caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients: a prospective, multicenter, observational study. Transplantation. 2006 Feb 15. 81(3):320-6. [Medline].
Smith J, Safdar N, Knasinski V, Simmons W, Bhavnani SM, Ambrose PG, et al. Voriconazole therapeutic drug monitoring. Antimicrob Agents Chemother. 2006 Apr. 50(4):1570-2. [Medline].
Stevens DA, Kan VL, Judson MA, Morrison VA, Dummer S, Denning DW, et al. Practice guidelines for diseases caused by Aspergillus. Infectious Diseases Society of America. Clin Infect Dis. 2000 Apr. 30(4):696-709. [Medline].
Tillie-Leblond I, Tonnel AB. Allergic bronchopulmonary aspergillosis. Allergy. 2005 Aug. 60(8):1004-13. [Medline].
Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007 Jan 25. 356(4):335-47. [Medline].
Viscoli C, Machetti M, Cappellano P, Bucci B, Bruzzi P, Van Lint MT, et al. False-positive galactomannan platelia Aspergillus test results for patients receiving piperacillin-tazobactam. Clin Infect Dis. 2004 Mar 15. 38(6):913-6. [Medline].
[Guideline] Walsh TJ, Anaissie EJ, Denning DW, Herbrecht R, Kontoyiannis DP, Marr KA, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008 Feb 1. 46(3):327-60. [Medline].
Walsh TJ, Hiemenz JW, Anaissie E. Recent progress and current problems in treatment of invasive fungal infections in neutropenic patients. Infect Dis Clin North Am. 1996 Jun. 10(2):365-400. [Medline].
Walsh TJ, Teppler H, Donowitz GR, Maertens JA, Baden LR, Dmoszynska A, et al. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med. 2004 Sep 30. 351(14):1391-402. [Medline].
Ward S, Heyneman L, Lee MJ, Leung AN, Hansell DM, Muller NL. Accuracy of CT in the diagnosis of allergic bronchopulmonary aspergillosis in asthmatic patients. AJR Am J Roentgenol. 1999 Oct. 173(4):937-42. [Medline].
Yao Z, Liao W. Fungal respiratory disease. Curr Opin Pulm Med. 2006 May. 12(3):222-7. [Medline].
Zmeili OS, Soubani AO. Pulmonary aspergillosis: a clinical update. QJM. 2007 Jun. 100(6):317-34. [Medline].