Blastomycosis and Phaeohyphomycosis

  • María Guadalupe Frías-De-León
  • Erick Martínez-Herrera
  • María del Rocío Reyes-Montes
  • Gustavo Acosta-Altamirano


The incidence of the mycoses affecting the central nervous system has increased in recent years. These mycoses occur in both immunocompetent and immunosuppressed individuals and are caused by primary fungi (yeasts and filamentous fungi). Among these fungi, Blastomyces spp. and phaeoid fungi stand out, which are characterized by reaching the CNS through hematogenous dissemination or neurotropism. The mortality of patients with CNS infection caused by these fungi is high, because it is difficult to make a specific diagnosis opportunely. The initial treatment of these mycoses is amphotericin B, although many patients may require lifetime treatment with some azole antifungal to avoid relapses. Therefore, these infections require an opportune and precise diagnosis, as well as careful treatment strategies to ensure the proper management of patients. This chapter presents a review of the epidemiology, pathogenesis, clinical characteristics, diagnosis, and treatment of CNS infections caused by Blastomyces spp. and phaeoid fungi.


Blastomycosis Phaeohyphomycosis Blastomyces spp. Phaeoid fungi SNC Meningitis Brain abscess Amphotericin B Azole antifungals 



Acquired immune deficiency syndrome


Central nervous system


Cerebrospinal fluid


Gomori methenamine silver




Human immunodeficiency virus


Periodic acid-Schiff


Polymerase chain reaction




United States of America


  1. Al Abdely HM, Alkhunaizi AM, Al Tawfiq JA, Hassounah M, Rinaldi MG, Sutton DA. Successful therapy of cerebral phaeohyphomycosis due to Ramichloridium mackenziei with the new triazole posaconazole. Med Mycol. 2005;43(1):91–5.CrossRefGoogle Scholar
  2. Babady NE, Buckwalter SP, Hall L, Le Febre KM, Binnicker MJ, Wengenack NL. Detection of Blastomyces dermatitidis and Histoplasma capsulatum from culture isolates and clinical specimens by use of real-time PCR. J Clin Microbiol. 2011;49:3204–8.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Bariola JR, Perry P, Pappas PG, Proia L, Shealey W, Wright PW, et al. Blastomycosis of the central nervous system: a multicenter review of diagnosis and treatment in the modern era. Clin Infect Dis. 2010;50:797–804.PubMedPubMedCentralCrossRefGoogle Scholar
  4. Baumgardner DJ, Temte JL, Gutowski E, Agger WA, Bailey H, Burmester JK, et al. The differential diagnosis of pulmonary blastomycosis using case vignettes: a Wisconsin Network for Health Research (WiNHR) study. WMJ. 2011;110(2):68–73.PubMedPubMedCentralGoogle Scholar
  5. Ben-Ami R, Lewis RE, Raad II, Kontoyiannis DP. Phaeohyphomycosis in a tertiary care cancer center. CID. 2009;48:1033–41.CrossRefGoogle Scholar
  6. Bentley RT, Reese MJ, Heng HG, Long Lin T, Shimonohara N, Fauber A. Ependymal and periventricular magnetic resonance imaging changes in four dogs with central nervous system blastomycosis. Vet Radiol Ultrasound. 2013;54(5):489–96.PubMedCrossRefGoogle Scholar
  7. Bradsher RW. Clinical features of blastomycosis. Semin Respir Infect. 1997;12(3):229–34.PubMedGoogle Scholar
  8. Bradsher RW, Bariola JR. Blastomycosis. In: Kauffman CA, Pappas PG, Sobel JD, et al., editors. Essentials of clinical mycology. 2nd ed. New York: Springer; 2011. p. 337–48.CrossRefGoogle Scholar
  9. Bradsher RW, Chapman SW, Pappas PG. Blastomycosis. Infect Dis Clin North Am. 2003;17(1):21–40.PubMedCrossRefGoogle Scholar
  10. Brandt ME, Warnock DW. Epidemiology, clinical manifestations, and therapy of infections caused by dematiaceous fungi. J Chemother. 2003;15(Suppl 2):36–47.PubMedCrossRefGoogle Scholar
  11. Brick KE, Agger WA. Successful treatment of brainstem blastomycosis with fluconazole. Clin Med Res. 2011;10(2):72–4.PubMedCrossRefGoogle Scholar
  12. Brick KE, Drolet BA, Lyon VB, Galbraith SS. Cutaneous and disseminated blastomycosis: a pediatric case series. Pediatr Dermatol. 2013;30:23–8.PubMedCrossRefGoogle Scholar
  13. Brown EM, McTaggart LR, Zhang SX, Low DE, Stevens DA, Richardson SE. Phylogenetic analysis reveals a cryptic species Blastomyces gilchristii, sp. nov. within the human pathogenic fungus Blastomyces dermatitidis. PLoS One. 2013;8(3):e59237.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Bush JW, Wuerz T, Embil JM, Del Bigio MR, McDonald PJ, Krawitz S. Outcomes of persons with blastomycosis involving the central nervous system. Diagn Microbiol Infect Dis. 2013;76:175–81.PubMedCrossRefGoogle Scholar
  15. Cano MV, Ponce-de-Leon GF, Tippen S, Lindsley MD, Warwick M, Hajjeh RA. Blastomycosis in Missouri: epidemiology and risk factors for endemic disease. Epidemiol Infect. 2003;131:907–14.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Carlos WG, Rose AS, Wheat LJ, Norris S, Sarosi GA, Knox KS, et al. Blastomycosis in Indiana: digging up more cases. Chest. 2010;138:1377–82.PubMedCrossRefGoogle Scholar
  17. Carman WF, Frean JA, Crewe-Brown HH, Culligan GA, Young CN. Blastomycosis in Africa. A review of known cases diagnosed between 1951 and 1987. Mycopathologia. 1989;107(1):25–32.PubMedCrossRefGoogle Scholar
  18. Castillo CG, Kauffman CA, Miceli MH. Blastomycosis. Infect Dis Clin North Am. 2016;30(1):247–64.CrossRefGoogle Scholar
  19. Centers for Disease Control & Prevention. Blastomycosis. Atlanta, GA: CDC. Accessed 13 July 2018.
  20. Chakrabarti A, Kaur H, Rudramurthy M, Appannanavar SB, Patel A, Mukherjee KK, et al. Brain abscess due to Cladophialophora bantiana: a review of 124 cases. Med Mycol. 2016;54:111–9.PubMedCrossRefGoogle Scholar
  21. Chander B, Deb P, Sarkar C, Garg A, Mehta VS, Sharma MC. Cerebral blastomycosis: a case report. Indian J Pathol Microbiol. 2007;50(4):821–4.PubMedGoogle Scholar
  22. Chapman SW, Lin AC, Hendricks KA, Nolan RL, Currier MM, Morris KR, et al. Endemic blastomycosis in Mississippi: epidemiological and clinical studies. Semin Respir Infect. 1997;12:219–28.PubMedGoogle Scholar
  23. Chapman SW, Dismukes WE, Proia LA, Bradsher RW, Pappas PG, Threlkeld MG, et al. Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America. Clin Infect Dis. 2008;46:1801–12.CrossRefGoogle Scholar
  24. Cooper K, Lalloo UG, Naran HK. Cerebral blastomycosis. A report of 2 cases. S Afr Med J. 1988;74(10):521–4.PubMedGoogle Scholar
  25. Cottle LE, Gkrania-Klotsas E, Williams HJ, Brindle HE, Carmichael AJ, Fry G, et al. A multinational outbreak of histoplasmosis following a biology field trip in the Ugandan rainforest. J Travel Med. 2013;20(2):83–7.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Crampton TL, Light RB, Berg GM, Meyers MP, Schroeder GC, Hershfield ES, et al. Epidemiology and clinical spectrum of blastomycosis diagnosed at Manitoba hospitals. Clin Infect Dis. 2002;34:1310–6.PubMedCrossRefGoogle Scholar
  27. Davis JA, Costello DJ, Venna N. Laboratory investigation of fungal infections of the central nervous system. Neurol India. 2007;55:233–40.PubMedCrossRefGoogle Scholar
  28. De Groote MA, Bjerke R, Smith H, Rhodes LV III. Expanding epidemiology of blastomycosis: clinical features and investigation of 2 cases in Colorado. Clin Infect Dis. 2000;30:582–4.PubMedCrossRefGoogle Scholar
  29. Dixon DM, Merz WG, Elliott HL, Macleay S. Experimental central nervous system phaeohyphomycosis following intranasal inoculation of Xylohypha bantiana in cortisone-treated mice. Mycopathologia. 1987;100:145–53.PubMedCrossRefGoogle Scholar
  30. Dworkin MS, Duckro AN, Proia L, Semel JD, Huhn G. The epidemiology of blastomycosis in Illinois and factors associated with death. Clin Infect Dis. 2005;41:e107–11.CrossRefGoogle Scholar
  31. Emmens RK, Richardson D, Thomas W, Hunter S, Hennigar RA, Wingard JR, et al. Necrotizing cerebritis in an allogeneic bone marrow transplant recipient due to Cladophialophora bantiana. J Clin Microbiol. 1996;30:1330–2.Google Scholar
  32. Fica A, Diaz MC, Luppi M, Olivares R, Saez L, Baboor M, Vasquez P. Unsuccessful treatment with voriconazole of a brain abscess due to Cladophialophora bantiana. Scand J Infect Dis. 2003;35(11–12):892–3.PubMedCrossRefGoogle Scholar
  33. Gilchrist TC. Protozoan dermatitidis. J Cutan Gen Dis. 1894;12:496.Google Scholar
  34. Gómez LV, Cardona-Castro N. Feohifomicosis, una infección fúngica oportunista emergente. Rev CES Med. 2016;30(1):66–77.CrossRefGoogle Scholar
  35. Gottfredsson M, Perfect JR. Fungal meningitis. Semin Neurol. 2000;20(3):307–22.PubMedCrossRefGoogle Scholar
  36. Hamilton AJ, Gomez BL. Melanins in fungal pathogens. J Med Microbiol. 2002;51:189–91.PubMedCrossRefGoogle Scholar
  37. Jacobson ES. Pathogenic roles for fungal melanins. Clin Microbiol Rev. 2000;13:708–17.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Klein BS, Vergeront JM, DiSalvo AF, Kaufman L, Davis JP. Two outbreaks of blastomycosis along rivers in Wisconsin: isolation of Blastomyces dermatitidis from riverbank soil and evidence of its transmission along waterways. Am Rev Respir Dis. 1987;136:1333–8.PubMedCrossRefGoogle Scholar
  39. Koneti A, Linke MJ, Brummer E, Stevens DA. Evasion of innate immune responses: evidence for mannose binding lectin inhibition of tumor necrosis factor alpha production by macrophages in response to Blastomyces dermatitidis. Infect Immun. 2008;76:994–1002.PubMedCrossRefGoogle Scholar
  40. Levin TP, Baty DE, Fekete T, Truant AL, Suh B. Cladophialophora bantiana brain abscess in a solid-organ transplant recipient: case report and review of the literature. J Clin Microbiol. 2004;42(9):4374–8.PubMedPubMedCentralCrossRefGoogle Scholar
  41. Litchevski V, Goldschmidt A, Nass D, Rahav G, Cohen ZR. Cerebral phaeohyphomycosis in an immunocompetent patient: a case report and literature summary. Clin Neurol Neurosurg. 2014;124:179–81.PubMedCrossRefGoogle Scholar
  42. Litvinjenko S, Lunny D. Blastomycosis hospitalizations in northwestern Ontario: 2006–2015. Can Commun Dis Rep. 2017;43(10):200–5.PubMedPubMedCentralCrossRefGoogle Scholar
  43. Lyons RW, Andriole VT. Fungal infections of the CNS. Neurol Clin. 1986;4(1):159–70.PubMedCrossRefGoogle Scholar
  44. Lyons MK, Blair JE, Leslie KO. Successful treatment with voriconazole of fungal cerebral abscess due to Cladophialophora bantiana. Clin Neurol Neurosurg. 2005;107(6):53–4.CrossRefGoogle Scholar
  45. Matsumoto T, Ajello L, Matsuda T, Szaniszlo PJ, Walsh TJ. Developments in hyalohyphomycosis and phaeohyphomycosis. J Med Vet Mycol. 1994;32(Suppl 1):329–49.PubMedCrossRefGoogle Scholar
  46. Mukhopadhyay S, Gal AA. Granulomatous lung disease: an approach to the differential diagnosis. Arch Pathol Lab Med. 2010;134:667–90.PubMedGoogle Scholar
  47. Ochiai H, Kawano H, Minato S, Yoneyama T, Shimao Y. Cerebral phaeohyphomycosis: case report. Neuropathology. 2012;32(2):202–6.PubMedCrossRefGoogle Scholar
  48. Pappas PG, Bradsher RW, Kauffman CA, Cloud GA, Thomas CJ, Campbell GD Jr, et al. Treatment of blastomycosis with higher doses of fluconazole. The National Institute of Allergy and Infectious Diseases Mycoses Study Group. Clin Infect Dis. 1997;25:200–5.PubMedCrossRefGoogle Scholar
  49. Patel AJ, Gattuso P, Reddy VB. Diagnosis of blastomycosis in surgical pathology and cytopathology: correlation with microbiologic culture. Am J Surg Pathol. 2010;34:256–61.PubMedCrossRefGoogle Scholar
  50. Pearson GJ, Chin TW, Fong IW. Case report: treatment of blastomycosis with fluconazole. Am J Med Sci. 1992;303(5):313–5.PubMedCrossRefGoogle Scholar
  51. Pfaff BL, Agger WA, Volk TJ. Blastomycosis diagnosed in a nonhyperendemic area. WMJ. 2014;113(1):11–8.PubMedGoogle Scholar
  52. Randhawa HS, Chowdhary A, Kathuria S, Roy P, Misra DS, Jain S, et al. Blastomycosis in India: report of an imported case and current status. Med Mycol. 2013;51:185–92.PubMedCrossRefGoogle Scholar
  53. Revankar SG. Phaeohyphomycosis. Infect Dis Clin North Am. 2006;20(3):609–20.PubMedCrossRefGoogle Scholar
  54. Revankar SG, Sutton DA. Melanized fungi in human disease. Clin Microbiol Rev. 2010;23(4):884–928.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Revankar SG, Sutton DA, Rinaldi MG. Primary central nervous system phaeohyphomycosis: a review of 101 cases. CID. 2004;38:206–16.CrossRefGoogle Scholar
  56. Richer SM, Smedema ML, Durkin MM, Brandhorst TT, Hage CA, Connolly PA, et al. Development of a highly sensitive and specific blastomycosis antibody enzyme immunoassay using Blastomyces dermatitidis surface protein BAD-1. Clin Vaccine Immunol. 2014;21:143–6.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Rinaldi MG. Phaeohyphomycosis. Dermatol Clin. 1996;14(1):147–53.PubMedCrossRefGoogle Scholar
  58. Roos KL, Bryan JP, Maggio WW, Jane JA, Scheld WM. Intracranial blastomycoma. Medicine (Baltimore). 1987;66(3):224–35.CrossRefGoogle Scholar
  59. Roy M, Benedict K, Deak E, Kirby MA, McNiel JT, Sickler CJ, et al. A large community outbreak of blastomycosis in Wisconsin with geographic and ethnic clustering. Clin Infect Dis. 2013;57:655–62.PubMedPubMedCentralCrossRefGoogle Scholar
  60. Saccente M, Woods GL. Clinical and laboratory update on blastomycosis. Clin Microbiol Rev. 2010;23:267–81.CrossRefGoogle Scholar
  61. Scully EP, Baden LR, Katz JT. Fungal brain infections. Curr Opin Neurol. 2008;21:347–52.PubMedPubMedCentralCrossRefGoogle Scholar
  62. Smith JA, Riddell J, Kauffman CA. Cutaneous manifestations of endemic mycoses. Curr Infect Dis Rep. 2013;15:440–9.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Sundaram C, Umabala P, Laxmi V, Purohit AK, Prasad VSSV, Panigrahi M, et al. Pathology of fungal infections of the central nervous system: 17 years’ experience from Southern India. Histopathology. 2006;49(4):396–405.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Vasquez JE, Mehta JB, Agrawal R, Sarubbi FA. Blastomycosis in northeast Tennessee. Chest. 1998;114:436–43.PubMedCrossRefGoogle Scholar
  65. Ward BA, Parent AD, Raila F. Indications for the surgical management of central nervous system blastomycosis. Surg Neurol. 1995;43(4):379–88.PubMedCrossRefGoogle Scholar
  66. Wüthrich M, Gern B, Hung CY, Ersland K, Rocco N, Pick-Jacobs J, et al. Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice. J Clin Invest. 2011;121:554–68.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • María Guadalupe Frías-De-León
    • 1
  • Erick Martínez-Herrera
    • 1
  • María del Rocío Reyes-Montes
    • 2
  • Gustavo Acosta-Altamirano
    • 1
  1. 1.Research UnitHospital Regional de Alta Especialidad de IxtapalucaIxtapalucaMexico
  2. 2.Microbiology and Parasitology Department, School of MedicineUniversidad Nacional Autónoma de MéxicoMexico CityMexico

Personalised recommendations