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Semin Respir Crit Care Med 2011; 32(6): 735-744
DOI: 10.1055/s-0031-1295721
© Thieme Medical Publishers

Pulmonary Histoplasmosis

David S. McKinsey1 , 2 , Joel P. McKinsey1 , 2
  • 1Infectious Disease Associates of Kansas City, Kansas City, Missouri
  • 2University of Kansas Medical Center, Kansas City, Kansas
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Publication History

Publication Date:
13 December 2011 (online)

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ABSTRACT

Pulmonary histoplasmosis is an important cause of morbidity in the United States. Several outbreaks of acute pulmonary histoplasmosis have been linked to potentially preventable environmental exposures. Progressive disseminated histoplasmosis, which is seen frequently in the growing population of immunocompromised hosts, often presents with prominent pulmonary manifestations and is more commonly encountered in hospitalized patients than acute, subacute, or chronic pulmonary histoplasmosis. A battery of diagnostic studies including serology, antigen, cytology/histopathology, and culture should be obtained in suspected cases of histoplasmosis. The yield of antigenuria detection is highest when the multiple body fluids are tested; the level of antigenuria correlates with severity of disease. Amphotericin B is the treatment of choice for severe pulmonary or disseminated histoplasmosis, and itraconazole is effective for mild to moderately severe infection. Posaconazole exhibits promise as a salvage agent. Antifungal prophylaxis is not routinely recommended for at-risk populations. Measures to minimize environmental contamination may reduce the risk of epidemic-type acute pulmonary histoplasmosis related to high-risk exposures.

KEYWORDS

Histoplasmosis - epidemics - pulmonary - disseminated - antigen

REFERENCES

  • 1 Darling S T. A protozoan general infection producing pseudotubercles in the lungs and fatal necroses in the liver, spleen, and lymph nodes.  JAMA. 1906;  46 1283-1285
    Google Scholar
  • 2 Dodd K, Tompkins E. A case of histoplasmosis of Darling in an infant.  Am J Trop Med Hyg. 1934;  14 127-137
    Google Scholar
  • 3 DeMonbreun W A. The cultivation and cultural characteristics of Darling’s Histoplasma capsulatum .  Am J Trop Med Hyg. 1934;  14 93-125
    Google Scholar
  • 4 Christie A, Peterson J C. Pulmonary calcification and sensitivity to histoplasmin, tuberculin and haplosporangin.  J Am Med Assoc. 1946;  131 658-660
    Google Scholar
  • 5 Palmer C E. Geographic differences in sensitivity to histoplasmin among student nurses.  Public Health Rep. 1946;  61 475-487
    Google Scholar
  • 6 McKinsey D S, Smith D L, Driks M R, O’Connor M C. Histoplasmosis in Missouri: historical review and current clinical concepts.  Mo Med. 1994;  91 (1) 27-32
    Google Scholar
  • 7 Furcolow M L, Grayston J T. Occurrence of histoplasmosis in epidemics; etiologic studies.  Am Rev Tuberc. 1953;  68 (3) 307-320
    Google Scholar
  • 8 Huhn G D, Austin C, Carr M et al.. Two outbreaks of occupationally acquired histoplasmosis: more than workers at risk.  Environ Health Perspect. 2005;  113 (5) 585-589
    Google Scholar
  • 9 Luby J P, Southern Jr P M, Haley C E, Vahle K L, Munford R S, Haley R W. Recurrent exposure to Histoplasma capsulatum in modern air-conditioned buildings.  Clin Infect Dis. 2005;  41 (2) 170-176
    Google Scholar
  • 10 Lemhart S, Shafer M, Singal M, Hajjeh R. Histoplasmosis: Protecting Workers at Risk. Bethesda, MD: U.S. Department of Health and Human Services; 1997. DHHS (NIOSH) publication no. 97–146
    Google Scholar
  • 11 Kauffman C A. Histoplasmosis: a clinical and laboratory update.  Clin Microbiol Rev. 2007;  20 (1) 115-132
    Google Scholar
  • 12 Connolly P A, Durkin M M, Lemonte A M, Hackett E J, Wheat L J. Detection of histoplasma antigen by a quantitative enzyme immunoassay.  Clin Vaccine Immunol. 2007;  14 (12) 1587-1591
    Google Scholar
  • 13 Wheat L J, Freifield A G, Kleiman M B Infectious Diseases Society of America et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America.  Clin Infect Dis. 2007;  45 (7) 807-825
    Google Scholar
  • 14 Limper A H, Knox K S, Sarosi G A American Thoracic Society Fungal Working Group et al. An official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients.  Am J Respir Crit Care Med. 2011;  183 (1) 96-128
    Google Scholar
  • 15 Ajello L. Distribution of Histoplasma capsulatum in the United States. In: Ajello L, Chick W, Furculow M F, eds. Histoplasmosis. Springfield, IL: Charles C. Thomas; 1971: 103-122
    Google Scholar
  • 16 Chamany S, Mirza S A, Fleming J W et al.. A large histoplasmosis outbreak among high school students in Indiana, 2001.  Pediatr Infect Dis J. 2004;  23 (10) 909-914
    Google Scholar
  • 17 Furcolow M L, Tosh F E, Larsh H W, Lynch Jr H J, Shaw G. The emerging pattern of urban histoplasmosis. Studies on an epidemic in Mexico. Missouri.  N Engl J Med. 1961;  264 1226-1230
    Google Scholar
  • 18 Mirsky S. Shakespeare to blame for introduction of European starlings to US. Scientific American. June 2008. http://www.scientificamerican.com/article.com/article.cfm?id=call-of-the-reviled Accessed June 30, 2011
    Google Scholar
  • 19 Assi M A, Sandid M S, Baddour L M, Roberts G D, Walker R C. Systemic histoplasmosis: a 15-year retrospective institutional review of 111 patients.  Medicine (Baltimore). 2007;  86 (3) 162-169
    Google Scholar
  • 20 Wynne J W, Olsen G N. Acute histoplasmosis presenting as the adult respiratory distress syndrome.  Chest. 1974;  66 (2) 158-161
    Google Scholar
  • 21 Hage C A, Ribes J A, Wengenack N L et al.. A multicenter evaluation of tests for diagnosis of histoplasmosis.  Clin Infect Dis. 2011;  53 (5) 448-454
    Google Scholar
  • 22 McKinsey D, Waxman M, Idstrom M. Differentiation of disseminated histoplasmosis from Pneumocystis pneumonia in AIDS.  Infect Med. 1993;  10 30-38
    Google Scholar
  • 23 Conces Jr D J, Stockberger S M, Tarver R D, Wheat L J. Disseminated histoplasmosis in AIDS: findings on chest radiographs.  AJR Am J Roentgenol. 1993;  160 (1) 15-19
    Google Scholar
  • 24 Goodwin R A, Nickell J A, Des Prez R M. Mediastinal fibrosis complicating healed primary histoplasmosis and tuberculosis.  Medicine (Baltimore). 1972;  51 (3) 227-246
    Google Scholar
  • 25 Goodwin Jr R A, Snell Jr J D. The enlarging histoplasmoma. Concept of a tumor-like phenomenon encompassing the tuberculoma and coccidioidoma.  Am Rev Respir Dis. 1969;  100 (1) 1-12
    Google Scholar
  • 26 McKinsey D S. Histoplasmosis in AIDS: advances in management.  AIDS Patient Care STDS. 1998;  12 (10) 775-781
    Google Scholar
  • 27 Wheat L J, Connolly-Stringfield P A, Baker R L et al.. Disseminated histoplasmosis in the acquired immune deficiency syndrome: clinical findings, diagnosis and treatment, and review of the literature.  Medicine (Baltimore). 1990;  69 (6) 361-374
    Google Scholar
  • 28 Vail G M, Young R S, Wheat L J, Filo R S, Cornetta K, Goldman M. Incidence of histoplasmosis following allogeneic bone marrow transplant or solid organ transplant in a hyperendemic area.  Transpl Infect Dis. 2002;  4 (3) 148-151
    Google Scholar
  • 29 Freifeld A G, Iwen P C, Lesiak B L, Gilroy R K, Stevens R B, Kalil A C. Histoplasmosis in solid organ transplant recipients at a large midwestern university transplant center.  Transpl Infect Dis. 2005;  7 (3-4) 109-115
    Google Scholar
  • 30 Wallis R S, Broder M, Wong J, Lee A, Hoq L. Reactivation of latent granulomatous infections by infliximab.  Clin Infect Dis. 2005;  41 (Suppl 3) S194-S198
    Google Scholar
  • 31 Allendoerfer R, Deepe Jr G S. Blockade of endogenous TNF-alpha exacerbates primary and secondary pulmonary histoplasmosis by differential mechanisms.  J Immunol. 1998;  160 (12) 6072-6082
    Google Scholar
  • 32 Lee J H, Slifman N R, Gershon S K et al.. Life-threatening histoplasmosis complicating immunotherapy with tumor necrosis factor alpha antagonists infliximab and etanercept.  Arthritis Rheum. 2002;  46 (10) 2565-2570
    Google Scholar
  • 33 McKinsey D S, Spiegel R A, Hutwagner L et al.. Prospective study of histoplasmosis in patients infected with human immunodeficiency virus: incidence, risk factors, and pathophysiology.  Clin Infect Dis. 1997;  24 (6) 1195-1203
    Google Scholar
  • 34 Jones J L, Hanson D L, Dworkin M S et al.. Surveillance for AIDS-defining opportunistic illnesses, 1992-1997.  MMWR CDC Surveill Summ. 1999;  48 (2, SS-2) 1-22
    Google Scholar
  • 35 Anderson A M, Mehta A K, Wang Y F, Jing Qian , Easley K, Nguyen M L. HIV-associated histoplasmosis in a nonendemic area of the United States during the HAART era: role of migration from endemic areas and lack of antiretroviral therapy.  J Int Assoc Physicians AIDS Care (Chic). 2010;  9 (5) 296-300
    Google Scholar
  • 36 Cuellar-Rodriguez J, Avery R K, Lard M et al.. Histoplasmosis in solid organ transplant recipients: 10 years of experience at a large transplant center in an endemic area.  Clin Infect Dis. 2009;  49 (5) 710-716
    Google Scholar
  • 37 Hage C A, Bowyer S, Tarvin S E, Helper D, Kleiman M B, Joseph Wheat L. Recognition, diagnosis, and treatment of histoplasmosis complicating tumor necrosis factor blocker therapy.  Clin Infect Dis. 2010;  50 (1) 85-92
    Google Scholar
  • 38 US Food and Drug Administration .Information for healthcare professionals: Cimzia (certolizumab pegol), Enbrel (etanercept), Humira (adalimumab), and Remicade (infliximab). September 4, 2008. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124185.htm Accessed June 28, 2011
    Google Scholar
  • 39 McKinsey D S, McKinsey J P, Brune P R. Diagnosis and management of histoplasmosis.  Curr Fungal Infect Rep. 2008;  2 94-102
    Google Scholar
  • 40 Davies S F. Serodiagnosis of histoplasmosis.  Semin Respir Infect. 1986;  1 (1) 9-15
    Google Scholar
  • 41 Wheat L J. Nonculture diagnostic methods for invasive fungal infections.  Curr Infect Dis Rep. 2007;  9 (6) 465-471
    Google Scholar
  • 42 Swartzentruber S, Rhodes L, Kurkjian K et al.. Diagnosis of acute pulmonary histoplasmosis by antigen detection.  Clin Infect Dis. 2009;  49 (12) 1878-1882
    Google Scholar
  • 43 Wheat L J, Kohler R B, Tewari R P. Diagnosis of disseminated histoplasmosis by detection of Histoplasma capsulatum antigen in serum and urine specimens.  N Engl J Med. 1986;  314 (2) 83-88
    Google Scholar
  • 44 Wheat J, Wheat H, Connolly P et al.. Cross-reactivity in Histoplasma capsulatum variety capsulatum antigen assays of urine samples from patients with endemic mycoses.  Clin Infect Dis. 1997;  24 (6) 1169-1171
    Google Scholar
  • 45 McKinsey D S, McKinsey J P, Northcutt N, Sarria J C. Interlaboratory discrepancy of antigenuria results in 2 patients with AIDS and histoplasmosis.  Diagn Microbiol Infect Dis. 2009;  63 (1) 111-114
    Google Scholar
  • 46 Hage C A, Davis T E, Fuller D et al.. Diagnosis of histoplasmosis by antigen detection in BAL fluid.  Chest. 2010;  137 (3) 623-628
    Google Scholar
  • 47 Tang Y W, Li H, Durkin M M et al.. Urine polymerase chain reaction is not as sensitive as urine antigen for the diagnosis of disseminated histoplasmosis.  Diagn Microbiol Infect Dis. 2006;  54 (4) 283-287
    Google Scholar
  • 48 Kohler S, Wheat L J, Connolly P et al.. Comparison of the echinocandin caspofungin with amphotericin B for treatment of histoplasmosis following pulmonary challenge in a murine model.  Antimicrob Agents Chemother. 2000;  44 (7) 1850-1854
    Google Scholar
  • 49 McKinsey D S, Kauffman C A, Pappas P G The National Institute of Allergy and Infectious Diseases Mycoses Study Group et al. Fluconazole therapy for histoplasmosis.  Clin Infect Dis. 1996;  23 (5) 996-1001
    Google Scholar
  • 50 Wheat J, MaWhinney S, Hafner R National Institute of Allergy and Infectious Diseases Acquired Immunodeficiency Syndrome Clinical Trials Group and Mycoses Study Group et al. Treatment of histoplasmosis with fluconazole in patients with acquired immunodeficiency syndrome.  Am J Med. 1997;  103 (3) 223-232
    Google Scholar
  • 51 Parker J D, Sarosi G A, Doto I L, Bailey R E, Tosh F E. Treatment of chronic pulmonary histoplasmosis.  N Engl J Med. 1970;  283 (5) 225-229
    Google Scholar
  • 52 Wheat L J, Connolly P, Smedema M et al.. Activity of newer triazoles against Histoplasma capsulatum from patients with AIDS who failed fluconazole.  J Antimicrob Chemother. 2006;  57 (6) 1235-1239
    Google Scholar
  • 53 Connolly P, Wheat L J, Schnizlein-Bick C et al.. Comparison of a new triazole, posaconazole, with itraconazole and amphotericin B for treatment of histoplasmosis following pulmonary challenge in immunocompromised mice.  Antimicrob Agents Chemother. 2000;  44 (10) 2604-2608
    Google Scholar
  • 54 Restrepo A, Tobón A, Clark B et al.. Salvage treatment of histoplasmosis with posaconazole.  J Infect. 2007;  54 (4) 319-327
    Google Scholar
  • 55 Freifeld A, Proia L, Andes D et al.. Voriconazole use for endemic fungal infections.  Antimicrob Agents Chemother. 2009;  53 (4) 1648-1651
    Google Scholar
  • 56 McKinsey D S, Wheat L J, Cloud G A National Institute of Allergy and Infectious Diseases Mycoses Study Group et al. Itraconazole prophylaxis for fungal infections in patients with advanced human immunodeficiency virus infection: randomized, placebo-controlled, double-blind study.  Clin Infect Dis. 1999;  28 (5) 1049-1056
    Google Scholar
  • 57 Kaplan J E, Benson C, Holmes K H, Brooks J T, Pau A, Masur H. Centers for Disease Control and Prevention (CDC); National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America . Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.  MMWR Recomm Rep. 2009;  58 (RR-4) 1-207
    Google Scholar
  • 58 Hajjeh R A, Pappas P G, Henderson H National Institute of Allergy and Infectious Diseases Mycoses Study Group et al. Multicenter case-control study of risk factors for histoplasmosis in human immunodeficiency virus-infected persons.  Clin Infect Dis. 2001;  32 (8) 1215-1220
    Google Scholar

David S. McKinseyM.D. 

6400 Prospect, Ste. 392

Kansas City, MO 64132

Email: david.mckinsey@hcamidwest.com

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