Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Paracoccidioidomycosis Treatment & Management

  • Author: Duane R Hospenthal, MD, PhD, FACP, FIDSA, FASTMH; Chief Editor: Mark R Wallace, MD, FACP, FIDSA  more...
 
Updated: Mar 23, 2015
 

Approach Considerations

Systemic antifungal medications are the mainstay of medical management in paracoccidioidomycosis. Supportive measures and hospitalization may be warranted for patients with severe disease. If present, anemia and nutritional deficiencies should be treated.

Pregnancy

Paracoccidioidomycosis is uncommon in women of childbearing age. In one case of paracoccidioidomycosis in pregnancy, P brasiliensis was found in the placenta, but the child was not infected.

Amphotericin B is the only antifungal medication in pregnancy category B that is effective against P brasiliensis. All of the other medications that are currently used are category C or D.

Patients with HIV/AIDS

Patients with AIDS acquire a form of paracoccidioidomycosis that resembles the subacute juvenile type. Widespread disease quickly develops, and the meninges are more commonly involved in patients with AIDS than in patients who do not have AIDS.

Paracoccidioidomycosis is an AIDS-associated opportunistic infection. However, the incidence is lower than that expected by comparison to other endemic fungal infections. The use of trimethoprim-sulfamethoxazole (TMP-SMZ) for Pneumocystis jiroveci pneumonia prophylaxis and azoles (eg, fluconazole, itraconazole, ketoconazole) for oropharyngeal candidiasis prophylaxis in HIV-infected patients may aid in the reduction in disseminated paracoccidioidomycosis.

AIDS is seen primarily in urban areas, whereas paracoccidioidomycosis is found mainly in rural areas, possibly contributing to the fact that the rate of paracoccidioidomycosis occurrence is lower than expected.

The paracoccidioidin skin test is frequently negative in infected patients with AIDS.

Supportive care

Supportive care among patients with paracoccidioidomycosis includes the following:

  • Treatment of anemia
  • Improvement of diet
  • Ensuring patient rest
  • Advising the patient to stop smoking and consuming alcohol

Surgery

Occasionally, specific surgical treatments are warranted for life- or organ-threatening disease, such as neurosurgical procedures to relieve granuloma-induced spinal cord compression or hydrocephalus. Reconstructive surgery is sometimes needed to alleviate fibrotic sequelae.

Deterrence/prevention

No vaccine against Paracoccidioides has been developed, although several peptide vaccines have been studied. No known control measures prevent paracoccidioidomycosis.

Next

Antifungal Treatment

Triazoles (itraconazole, voriconazole, posaconazole)

Itraconazole is considered the drug of choice for paracoccidioidomycosis, with a reported effectiveness of 95%. The course of therapy is typically 200 mg/day for 6 months. Itraconazole is considered superior to ketoconazole because of shorter treatment course, lower toxicity profile, and lower relapse rate (3-5%). Fluconazole is not typically used, because of its lower response rates and more frequent relapse.

Voriconazole, a newer azole agent, has in vitro activity against the yeast cells of P brasiliensis and has been shown in open-label trials to be an effective agent.[27] Another newer azole, posaconazole, has been used with reported success in this disease.

Imidazoles (ketoconazole)

Ketoconazole is also an effective agent for paracoccidioidomycosis, with a cure rate of 85-90% and an associated relapse rate of less than 10%. A dose of 200-400 mg/day in adults or 5 mg/kg/day in children for 6-18 months is required. Ketoconazole is associated with significant toxicities, including hepatic dysfunction and sex hormone alterations, as well as with many drug-drug interactions.

Sulfonamides (sulfadiazine, trimethoprim-sulfamethoxazole)

The maximum dose of sulfadiazine is 4 g/day in adults and 60-100 mg/kg/day in divided doses in children. Once clinical and mycologic response is evident, this dose can be cut in half. For long-acting compounds, the dosing is 0.5 g/day, following an initial dose of 1 g/day for 2-3 weeks. Patients should be treated for 3-5 years. This results in a 70% cure rate, but there is also a 30% relapse rate.

Trimethoprim-sulfamethoxazole (TMP-SMX) is typically dosed as one double-strength tablet (160 mg trimethoprim, 800 mg sulfamethoxazole) twice daily (8-10 mg/kg/day [based on trimethoprim] for children). Compared to itraconazole in a recent study, TMP-SMX treatment was associated with a 51% cure rate (versus 86% for itraconazole) with a median treatment time of 23 months (versus 12 months for itraconazole).[28]

Amphotericin B

Reserve this drug for severe cases of paracoccidioidomycosis that are refractory to other forms of therapy. Cumulative doses range from 1-2 g based on clinical response. The drug is not curative; therefore, maintenance therapy with a sulfonamide or an azole is subsequently required. Only the intravenous formulation of this drug is effective, but its use is limited because of associated toxicities. The associated rate of improvement and relapse rate are similar to those of sulfonamide.

Previous
Next

Consultations

Consult an infectious disease specialist for difficult diagnoses, especially in nonendemic areas, and for patients who require long-term treatment with potentially toxic medications (eg, amphotericin B).

Consider the following consultations as well, depending on organ involvement and severity of disease:

  • Pulmonologist
  • Internal medicine specialist
  • Dermatologist
  • Surgeon
Previous
Next

Long-Term Monitoring

During and after treatment for paracoccidioidomycosis with antifungal medications, patients must be regularly evaluated to ensure an adequate response to therapy and monitor for relapse.

Complement fixation tests can be used to track the response to therapy; antibody levels decrease with improvement. Complement fixation also can be used to detect relapse because antibody levels increase again. The new antibody tests directed against P brasiliensis antigenic glycoproteins may prove useful in monitoring disease activity and response to therapy.

Absence of symptoms for 2 years after antifungal therapy is considered by some to indicate a cure. Others believe that mycologically negative results in 3 specimens after the cessation of therapy indicate a cure.

Previous
 
 
Contributor Information and Disclosures
Author

Duane R Hospenthal, MD, PhD, FACP, FIDSA, FASTMH Adjunct Professor of Medicine, Department of Medicine, University of Texas Health Science Center at San Antonio

Duane R Hospenthal, MD, PhD, FACP, FIDSA, FASTMH is a member of the following medical societies: Alpha Omega Alpha, American Medical Association, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, International Society for Infectious Diseases, International Society of Travel Medicine, Medical Mycological Society of the Americas, Armed Forces Infectious Diseases Society, International Society for Human and Animal Mycology, American College of Physicians, American Society for Microbiology, Society for Healthcare Epidemiology of America

Disclosure: Nothing to disclose.

Coauthor(s)

Kendall M Egan, MD, FAAD Dermatologist, Veteran's Affairs Medical Center; Dermatologist, Spruce Health, Dermatologist, DermOne

Kendall M Egan, MD, FAAD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists

Disclosure: Nothing to disclose.

Chief Editor

Mark R Wallace, MD, FACP, FIDSA Clinical Professor of Medicine, Florida State University College of Medicine; Clinical Professor of Medicine, University of Central Florida College of Medicine

Mark R Wallace, MD, FACP, FIDSA is a member of the following medical societies: American College of Physicians, American Medical Association, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, Florida Infectious Diseases Society

Disclosure: Nothing to disclose.

Acknowledgements

Asgar A Boxwalla, MD Staff Physician, Department of Internal Medicine, Division of Infectious Diseases, St John Detroit Riverview Hospital

Disclosure: Nothing to disclose.

David F Butler, MD Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Pranatharthi Haran Chandrasekar, MBBS, MD Professor, Department of Internal Medicine, Director of Infectious Disease Fellowship, Harper Hospital, Wayne State University School of Medicine

Pranatharthi Haran Chandrasekar, MBBS, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Julie E Dixon, MD, FAAD Private Practice, Ironwood Dermatology, Tucson, Arizona

Julie E Dixon, MD, FAAD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and American Medical Association

Disclosure: Nothing to disclose.

Dirk M Elston, MD Director, Ackerman Academy of Dermatopathology, New York

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Franklin Flowers, MD Chief, Division of Dermatology, Professor, Department of Medicine and Otolaryngology, Affiliate Associate Professor of Pediatrics and Pathology, University of Florida College of Medicine

Franklin Flowers, MD, is a member of the following medical societies: American College of Mohs Micrographic Surgery and Cutaneous Oncology

Disclosure: Nothing to disclose.

Ronald A Greenfield, MD Professor, Department of Internal Medicine, University of Oklahoma College of Medicine

Ronald A Greenfield, MD is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Society for Microbiology, Central Society for Clinical Research, Infectious Diseases Society of America, Medical Mycology Society of the Americas, Phi Beta Kappa, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology

Disclosure: Pfizer Honoraria Speaking and teaching; Gilead Honoraria Speaking and teaching; Ortho McNeil Honoraria Speaking and teaching; Abbott Honoraria Speaking and teaching; Astellas Honoraria Speaking and teaching; Cubist Honoraria Speaking and teaching; Forest Pharmaceuticals Speaking and teaching

Norman Levine, MD Private Practice, Tucson, AZ

Norman Levine is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Jeffrey J Miller, MD Associate Professor of Dermatology, Pennsylvania State University College of Medicine; Staff Dermatologist, Pennsylvania State Milton S Hershey Medical Center

Jeffrey J Miller, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, Association of Professors of Dermatology, North American Hair Research Society, and Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Christina M Schofield, MD Instructor of Medicine, Uniformed Services University of the Health Sciences; Consulting Staff, Department of Infectious Disease, Wilford Hall Medical Center, Lackland Air Force Base

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Acknowledgments

The views expressed in this manuscript are those of the authors and do not reflect the official policy of the Department of the Navy, Department of the Army, Department of Defense, or the U.S. Government.

References
  1. Marques-da-Silva SH, Rodrigues AM, de Hoog GS, Silveira-Gomes F, Camargo ZP. Occurrence of Paracoccidioides lutzii in the Amazon region: description of two cases. Am J Trop Med Hyg. 2012 Oct. 87(4):710-4. [Medline]. [Full Text].

  2. Lupi O, Tyring SK, McGinnis MR. Tropical dermatology: fungal tropical diseases. J Am Acad Dermatol. 2005 Dec. 53(6):931-51, quiz 952-4. [Medline].

  3. Brazão-Silva MT, Andrade MF, Franco T, Ribeiro RI, Silva Wdos S, Faria G, et al. Paracoccidioidomycosis: a series of 66 patients with oral lesions from an endemic area. Mycoses. 2011 Jul. 54(4):e189-95. [Medline].

  4. Bagagli E, Sano A, Coelho KI, Alquati S, Miyaji M, de Camargo ZP, et al. Isolation of Paracoccidioides brasiliensis from armadillos (Dasypus noveminctus) captured in an endemic area of paracoccidioidomycosis. Am J Trop Med Hyg. 1998 Apr. 58(4):505-12. [Medline].

  5. de Farias MR, Condas LA, Ribeiro MG, Bosco Sde M, Muro MD, Werner J, et al. Paracoccidioidomycosis in a dog: case report of generalized lymphadenomegaly. Mycopathologia. 2011 Aug. 172(2):147-52. [Medline].

  6. Trejo-Chávez A, Ramírez-Romero R, Ancer-Rodríguez J, Nevárez-Garza AM, Rodríguez-Tovar LE. Disseminated paracoccidioidomycosis in a Southern two-toed sloth (Choloepus didactylus). J Comp Pathol. 2011 Feb-Apr. 144(2-3):231-4. [Medline].

  7. Benard G, Kavakama J, Mendes-Giannini MJ, Kono A, Duarte AJ, Shikanai-Yasuda MA. Contribution to the natural history of paracoccidioidomycosis: identification of the primary pulmonary infection in the severe acute form of the disease--a case report. Clin Infect Dis. 2005 Jan 1. 40(1):e1-4. [Medline].

  8. Bellissimo-Rodrigues F, Bollela VR, Da Fonseca BA, Martinez R. Endemic paracoccidioidomycosis: relationship between clinical presentation and patients' demographic features. Med Mycol. 2013 Apr. 51(3):313-8. [Medline].

  9. Paniago AM, de Freitas AC, Aguiar ES, Aguiar JI, da Cunha RV, Castro AR, et al. Paracoccidioidomycosis in patients with human immunodeficiency virus: review of 12 cases observed in an endemic region in Brazil. J Infect. 2005 Oct. 51(3):248-52. [Medline].

  10. Corti M, Villafañe MF, Negroni R, Palmieri O. Disseminated paracoccidioidomycosis with peripleuritis in an AIDS patient. Rev Inst Med Trop Sao Paulo. 2004 Jan-Feb. 46(1):47-50. [Medline].

  11. Azenha MR, Caliento R, Brentegani LG, de Lacerda SA. A retrospective study of oral manifestations in patients with paracoccidioidomycosis. Braz Dent J. 2012. 23(6):753-7. [Medline].

  12. Mayr A, Kirchmair M, Rainer J, Rossi R, Kreczy A, Tintelnot K, et al. Chronic paracoccidioidomycosis in a female patient in Austria. Eur J Clin Microbiol Infect Dis. 2004 Dec. 23(12):916-9. [Medline].

  13. Blotta MH, Mamoni RL, Oliveira SJ, Nouér SA, Papaiordanou PM, Goveia A, et al. Endemic regions of paracoccidioidomycosis in Brazil: a clinical and epidemiologic study of 584 cases in the southeast region. Am J Trop Med Hyg. 1999 Sep. 61(3):390-4. [Medline].

  14. Maluf ML, Pereira SR, Takahachi G, Svidzinski TI. [Prevalence of paracoccidioidomycosis infection determined by sorologic test in donors' blood in the Northwest of Paraná, Brazil]. Rev Soc Bras Med Trop. 2003 Jan-Feb. 36(1):11-6. [Medline].

  15. Cabral-Marques O, Schimke LF, Pereira PV, Falcai A, de Oliveira JB, Hackett MJ, et al. Expanding the clinical and genetic spectrum of human CD40L deficiency: the occurrence of paracoccidioidomycosis and other unusual infections in Brazilian patients. J Clin Immunol. 2012 Apr. 32(2):212-20. [Medline].

  16. Nogueira LM, Santos M, Ferreira LC, Talhari C, Rodrigues RR, Talhari S. AIDS-associated paracoccidioidomycosis in a patient with a CD4+ T-cell count of 4 cells/mm³. An Bras Dermatol. 2011 Jul-Aug. 86(4 Suppl 1):S129-32. [Medline].

  17. Desjardins CA, Champion MD, Holder JW, Muszewska A, Goldberg J, Bailão AM, et al. Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis. PLoS Genet. 2011 Oct. 7(10):e1002345. [Medline]. [Full Text].

  18. Shankar J, Restrepo A, Clemons KV, Stevens DA. Hormones and the resistance of women to paracoccidioidomycosis. Clin Microbiol Rev. 2011 Apr. 24(2):296-313. [Medline]. [Full Text].

  19. Coutinho ZF, Silva Dd, Lazera M, Petri V, Oliveira RM, Sabroza PC, et al. Paracoccidioidomycosis mortality in Brazil (1980-1995). Cad Saude Publica. 2002 Sep-Oct. 18(5):1441-54. [Medline].

  20. Pereira RM, Tresoldi AT, da Silva MT, Bucaretchi F. Fatal disseminated paracoccidioidomycosis in a two-year-old child. Rev Inst Med Trop Sao Paulo. 2004 Jan-Feb. 46(1):37-9. [Medline].

  21. de Almeida SM, Queiroz-Telles F, Teive HA, Ribeiro CE, Werneck LC. Central nervous system paracoccidioidomycosis: clinical features and laboratorial findings. J Infect. 2004 Feb. 48(2):193-8. [Medline].

  22. Moreto TC, Marques ME, de Oliveira ML, Moris DV, de Carvalho LR, Mendes RP. Accuracy of routine diagnostic tests used in paracoccidioidomycosis patients at a university hospital. Trans R Soc Trop Med Hyg. 2011 Aug. 105(8):473-8. [Medline].

  23. Hahn RC, Rodrigues AM, Fontes CJ, Nery AF, Tadano T, Queiroz Lde P Jr. Fatal fungemia due to Paracoccidioides lutzii. Am J Trop Med Hyg. 2014 Aug. 91(2):394-8. [Medline].

  24. Kalmar EM, Alencar FE, Alves FP, et al. Paracoccidioidomycosis: an epidemiologic survey in a pediatric population from the Brazilian Amazon using skin tests. Am J Trop Med Hyg. 2004 Jul. 71(1):82-6. [Medline].

  25. Freitas RM, Prado R, Prado FL, Paula IB, Figueiredo MT, Ferreira CS, et al. Pulmonary paracoccidioidomycosis: radiology and clinical-epidemiological evaluation. Rev Soc Bras Med Trop. 2010 Nov-Dec. 43(6):651-6. [Medline].

  26. Reis F, Collier PP, Souza TF, Lopes GP, Bronzatto E, Silva Junior NA, et al. Neuroparacoccidioidomycosis (NPCM): magnetic resonance imaging (MRI) findings. Mycopathologia. 2013 Feb. 175(1-2):181-6. [Medline].

  27. Queiroz-Telles F, Goldani LZ, Schlamm HT, Goodrich JM, Espinel-Ingroff A, Shikanai-Yasuda MA. An open-label comparative pilot study of oral voriconazole and itraconazole for long-term treatment of paracoccidioidomycosis. Clin Infect Dis. 2007 Dec 1. 45(11):1462-9. [Medline].

  28. Borges SR, Silva GM, Chambela Mda C, Oliveira Rde V, Costa RL, Wanke B, et al. Itraconazole vs. trimethoprim-sulfamethoxazole: A comparative cohort study of 200 patients with paracoccidioidomycosis. Med Mycol. 2014 Apr. 52(3):303-10. [Medline].

  29. Travassos LR, Taborda CP, Colombo AL. Treatment options for paracoccidioidomycosis and new strategies investigated. Expert Rev Anti Infect Ther. 2008 Apr. 6(2):251-62. [Medline].

  30. Ollague JM, de Zurita AM, Calero G. Paracoccidioidomycosis (South American blastomycosis) successfully treated with terbinafine: first case report. Br J Dermatol. 2000 Jul. 143(1):188-91. [Medline].

 
Previous
Next
 
Approximate distribution of paracoccidioidomycosis in North, Central, and South America, based on case reports.
Granulomatous lesion involving the nose in patient with paracoccidioidomycosis; note the resemblance to cutaneous leishmaniasis.
Potassium hydroxide (KOH) preparation from pus; note the multiple budding and variation in cell size with Paracoccidioides.
Crusted plaques over the central part of the face in a man with paracoccidioidomycosis. Courtesy of Rolando Vasquez, MD, Professor of Dermatology, Guatemala.
Ulcerated nodule on the tongue in a man with paracoccidioidomycosis. Courtesy of Heidi Logemann, Professor of Mycology, Universidad de San Carlos, Guatemala.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.