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aspergillosis

Etiology: 1) infection with Aspergillus & other fungi a) Aspergillus fumigatus b) Neosartorya udagawae (Aspergillus udagawae) 2) major risk factors - neutropenia - graft vs host disease - CMV infection - hematopoietic stem cell tranplantation - solid organ transplantation - systemic glucocorticoids (> 1 mg/kg/day) or inhaled glucocorticoids - hematologic malignancy 3) minor risk factors - glucorticoids for COPD - cirrhosis - burns - solid organ malignancy - immunosuppressants - HIV1 infection with CD4 count < 50/uL - gram negative bacterial pneumonia 4) other risk factors a) antibiotics b) irradiation c) debilitating disease d) severe influenza with admission to the ICU predicts risk for invasive pulmonary aspergillosis [9] e) bone marrow transplantation Epidemiology: - aquisition through inhalation of airborne spores - Aspergillus is common flora in patients with COPD Pathology: - allergic bronchopulmonary aspergillosis - aspergilloma (fungus ball) - chronic necrotizing pulmonary aspergillosis - invasive pulmonary aspergillosis - multiorgan dysfunction Clinical manifestations: 1) pulmonary aspergillosis a) may manifest as - asymptomatic colonization, - allergic bronchopulmonary aspergillosis - aspergilloma - invasive pulmonary aspergillosis - necrotizing pulmonary aspergillosis [2] b) tracheobronchitis may precede widespread pulmonary disease c) fever, dyspnea, cough, purulent sputum d) hemoptysis is usually minor, but may be catastrophic e) pleuritic chest pain, pleural rub 2) rhinosinusitis in immunocompromised hosts 3) disseminated aspergillosis a) fever b) skin eruptions; hemorrhagic skin lesions c) arthralgias d) infection of ears, eyes, sinuses e) coma (late manifestation) 4) focal neurologic defects [2] Laboratory: 1) microscopy demonstrating hyphae & culture of Aspergillus a) sputum culture & microscopy (multiple) b) bronchial brushings culture & microscopy c) tissue biopsy culture & microscopy d) septate hyphae with acute angle branching [2] 2) invasive aspergillosis a) histopathology, cytology, & culture examination b) galactomannan Ag useful in diagnosis & follow-up - galactomannan Ag in serum/plasma - galactomannan Ag in bronchoalveolar lavage c) Aspergillus DNA in tissue from bronchoalveolar lavage [2] - blood Aspergillus DNA testing unreliable [7] 3) blood cultures rarely positive [2] 4) eosinophilia Special laboratory: - bronchoscopy with bronchoalveolar lavage* [8] * diagnostic procedure of choice [2] Radiology: 1) chest X-ray: - may be normal early - infiltration, infarction, nodules, cavitation (late) - crescentic radiolucency surrounding a circular shadow (pulmonary aspergilloma) 2) computed tomography (CT): a) nodular infiltrates often with a halo around them [2] - halo sign strongly suggestive of aspergillosis - target lesion with surrounding ground glass attenuation (hemorrhage) b) fungus ball is uncommon in invasive aspergillosis 3) noncontrast CT for follow-up [7] Differential diagnosis: 1) Fusarium 2) Pseudallescheria Management: 1) also see allergic bronchopulmonary aspergillosis 2) invasive aspergillosis a) voriconizole* is the drug of choice for patients with invasive pulmonary aspergillosis, including immunosuppressed patients [2,3,5] - therapeutic drug monitoring recommended for voriconazole [8] b) posaconazole*, isavuconazole* FDA-approved May 2013 c) liposomal amphotericin B may be an alternative to voriconizole, posaconazole or isavuconazole in some patients [2] d) amphotericin B, itraconazole, posaconazole, or echinocandin for patients refractory to or intolerant of voriconazole [2] e) combinations antifungal treatment not recommended as primary treatment option [8] f) bone marrow transplant patients - protected environment to reduce mold exposure [7] - amphotericin not effective - surgical resection of lesion - granulocyte colony-stimulating factor (G-CSF) - mortality > 75% g) solid organ transplant patients - amphotericin B - itraconazole - response rate > 50% h) AIDS: ultimately refractory to therapy g) central nervous system involvement - generally fatal - high dose itraconazole > 800 mg/day may be helpful 3) prevention: posaconazole [7] - acute myelogenous leukemia or myelodysplastic syndrome during induction chemotherapy [8] * preferred agents for first-line treatment of pulmonary invasive aspergillosis [8]

Related

Aspergillus

Specific

allergic bronchopulmonary aspergillosis; allergic bronchopulmonary mycosis (ABPA)

General

mycosis; fungal infection

References

  1. DeGowin & DeGowin's Diagnostic Examination, 6th edition, RL DeGowin (ed), McGraw Hill, NY 1994, pg 867-68
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  3. Journal Watch 22(7):55, 2002 Denning DW et al Efficacy and safety of voriconazole in the treatment of acute invasive aspergillosis. Clin Infect Dis 34:563, 2002 PMID: 11807679
  4. Infectious disease, Veterans Administration, Los Angeles
  5. Walsh TJ, Anaissie EJ, Denning DW 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 PMID: 18177225 (corresponding National Guideline Clearinghouse entry withdrawn Dec 2013)
  6. Karthaus M, Buchheidt D. Invasive aspergillosis: new insights into disease, diagnostic and treatment. Curr Pharm Des. 2013;19(20):3569-94. Review. PMID: 23278538
  7. Patterson TF, Thompson GR 3rd, Denning DW et al Executive Summary: Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Aug 15;63(4):433-42. PMID: 27481947 - Patterson TF, Thompson GR 3rd, Denning DW et al Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Aug 15;63(4):e1-e60. PMID: 27365388
  8. Ullmann AJ, Aguado JM, Arikan-Akdagli S et al Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline. Clin Microbiol Infect. 2018 Mar 12 PMID: 29544767
  9. Schauwvlieghe A, Rijnders B, Philips N et al Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study, Lancet Respir Med, July 31, 2018 PMID: 30076119 https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(18)30274-1/fulltext
  10. Cadena J, Thompson GR 3rd, Patterson TF. Invasive Aspergillosis: Current Strategies for Diagnosis and Management. Infect Dis Clin North Am. 2016 Mar;30(1):125-42. Review. PMID: 26897064