Semin Respir Crit Care Med 2004; 25(2): 129-144
DOI: 10.1055/s-2004-824898
Copyright © 2004 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Pulmonary Histoplasmosis Syndromes: Recognition, Diagnosis, and Management

L. Joseph Wheat1 , Dewey Conces2 , Stephen D. Allen3 , Deborah Blue-Hnidy3 , James Loyd4
  • 1Private Practice, Indianapolis, Indiana
  • 2Department of Radiology, Indiana University School of Medicine, Indianapolis, Indiana
  • 3Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana
  • 4Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
Further Information

Publication History

Publication Date:
19 April 2004 (online)

Pulmonary manifestations are the hallmark of histoplasmosis. Clinical syndromes range from asymptomatic infection to diffuse alveolar disease causing respiratory difficulty and even death. Serologic tests for antibodies and antigen detection are especially helpful in the diagnosis of histoplasmosis but are frequently overlooked. Detection of Histoplasma capsulatum antigen in bronchoalveolar lavage fluid may be particularly helpful in patients with acute pulmonary histoplasmosis or disseminated disease with pulmonary involvement. Topics of special importance for pulmonary disease specialists include the approach to the exclusion of histoplasmosis in the evaluation of patients with suspected sarcoidosis, differentiation of pulmonary histoplasmosis and malignancy in those with lung masses or mediastinal lymphadenopathy, and recognition and management of chronic pulmonary and mediastinal manifestations of histoplasmosis. Although histoplasmosis is mild and self-limited in most healthy individuals, antifungal therapy is indicated in those with acute diffuse pulmonary infection, chronic pulmonary histoplasmosis, progressive disseminated disease, and perhaps mediastinal adenitis accompanied by obstructive symptoms. Antifungal therapy to prevent reactivation of histoplasmosis during immunosuppressive therapy, or transition of mediastinal adenitis to fibrosing mediastinitis, although controversial, is not recommended. Several new drugs active against H. capsulatum offer alternatives in patients failing or intolerant of current therapies.

REFERENCES

  • 1 Goodwin R A, Loyd J E, des Prez R M. Histoplasmosis in normal hosts.  Medicine (Baltimore). 1981;  60 231-266
  • 2 Ost D, Fein A M, Feinsilver S H. The solitary pulmonary nodule.  N Engl J Med. 2003;  348 2535-2542
  • 3 Gaebler J W, Kleiman M B, Cohen M et al.. Differentiation of lymphoma from histoplasmosis in children with mediastinal masses.  J Pediatr. 1984;  104 706-709
  • 4 Reynolds R JI, Penn R L, Grafton W D, George R B. Tissue morphology of Histoplasma capsulatum in acute histoplasmosis.  Am Rev Respir Dis. 1984;  130 317-320
  • 5 Rubin H, Furcolow M L, Yates J L, Brasher C A. The course and prognosis of histoplasmosis.  Am J Med. 1959;  27 278-288
  • 6 Sollod N. Acute fulminating disseminated histoplasmosis.  J S Carol Med Assoc. 1971;  67 231-234
  • 7 Sathapatayavongs B, Batteiger B E, Wheat L J, Slama T G, Wass J L. Clinical and laboratory features of disseminated histoplasmosis during two large urban outbreaks.  Medicine (Baltimore). 1983;  62 263-270
  • 8 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;  69 361-374
  • 9 Wheat L. Histoplasmosis in the acquired immunodeficiency syndrome.  Curr Top Med Mycol. 1996;  7 7-18
  • 10 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 15-19
  • 11 Wheat L J, Stein L, Corya B C et al.. Pericarditis as a manifestation of histoplasmosis during two large urban outbreaks.  Medicine (Baltimore). 1983;  62 110-119
  • 12 Picardi J L, Kauffman C A, Schwarz J, Holmes J C, Phair J P, Fowler N O. Pericarditis caused by Histoplasma capsulatum .  Am J Cardiol. 1976;  37 82-88
  • 13 Goodwin R A, Nickell J A, des Prez R M. Mediastinal fibrosis complicating healed primary histoplasmosis and tuberculosis.  Medicine (Baltimore). 1972;  51 227-246
  • 14 Davis A, Pierson D, Loyd J E. Mediastinal fibrosis.  Semin Respir Infect. 2001;  16 119-130
  • 15 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 1-12
  • 16 Peebles R S, Carpenter C T, Dupont W D, Loyd J E. Mediastinal fibrosis is associated with human leukocyte antigen-A2.  Chest. 2000;  117 482-485
  • 17 Weinstein J B, Aronberg D J, Sagel S S. CT of fibrosing mediastinitis: findings and their utility.  AJR Am J Roentgenol. 1983;  141 247-251
  • 18 Goodwin Jr R A, Owens F T, Snell J D et al.. Chronic pulmonary histoplasmosis.  Medicine (Baltimore). 1976;  55 413-452
  • 19 Wheat L J, Wass J, Norton J, Kohler R B, French M LV. Cavitary histoplasmosis occurring during two large urban outbreaks: analysis of clinical, epidemiologic, roentgenographic, and laboratory features.  Medicine (Baltimore). 1984;  63 201-209
  • 20 Garrett Jr H E, Roper C L. Surgical intervention in histoplasmosis.  Ann Thorac Surg. 1986;  42 711-722
  • 21 Arrigoni M G, Bernatz P E, Donoghue F E. Broncholithiasis.  J Thorac Cardiovasc Surg. 1971;  62 231-237
  • 22 Vix V A. Radiographic manifestations of broncholithiasis.  Radiology. 1978;  128 295-299
  • 23 Conces Jr D J, Tarver R D, Vix V A. Broncholithiasis: CT features in 15 patients.  AJR Am J Roentgenol. 1991;  157 249-253
  • 24 Wheat L J, French M LV, Wass J L. Sarcoidlike manifestations of histoplasmosis.  Arch Intern Med. 1989;  149 2421-2426
  • 25 Gulati M, Saint S, Tierney L. Impatient inpatient care.  N Engl J Med. 2001;  342 37-40
  • 25a 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 83-88
  • 25b Williams B, Fojtasek M, Connolly-Stringfield P, Wheat J. Diagnosis of histoplasmosis by antigen detection during an outbreak in Indianapolis, Ind.  Arch Pathol Lab Med. 1994;  118 1205-1208
  • 25c Durkin M M, Connolly P A, Wheat L J. Comparison of radioimmunoassay and enzyme-linked immunoassay methods for detection of Histoplasma capsulatum var. capsulatum antigen.  J Clin Microbiol. 1997;  35 2252-2255
  • 26 Wheat L J. Laboratory diagnosis of histoplasmosis: a review.  Semin Respir Infect. 2001;  16 131-140
  • 27 Wheat L J, Kauffman C A. Histoplasmosis.  Infect Dis Clin North Am. 2003;  17 1-19
  • 28 Mashburn J D, Dawson D F, Young J M. Pulmonary calcifications and histoplasmosis.  Am Rev Respir Dis. 1961;  84 208-216
  • 28a Buxton J A, Dawar M, Wheat L J et al.. Outbreak of histoplasmosis in a school party that visited a cave in Belize: role of antigen testing in diagnosis.  J Travel Med. 2002;  9 48-50
  • 29 Wheat L J, Connolly-Stringfield P A, Williams B et al.. Diagnosis of histoplasmosis in patients with the acquired immunodeficiency syndrome by detection of Histoplasma capsulatum polysaccharide antigen in bronchoalveolar lavage fluid.  Am Rev Respir Dis. 1992;  145 1421-1424
  • 30 Davies S F. Serodiagnosis of histoplasmosis.  Semin Respir Infect. 1986;  1 9-15
  • 31 Loyd J E, Tillman B F, Atkinson J B, des Prez  RM. Mediastinal fibrosis complicating histoplasmosis.  Medicine (Baltimore). 1988;  67 295-310
  • 32 Wheat J, Sarosi G, McKinsey D et al.. Practice guidelines for the management of patients with histoplasmosis.  Clin Infect Dis. 2000;  30 688-695
  • 33 Mocherla S, Wheat L J. Treatment of histoplasmosis.  Semin Respir Infect. 2001;  16 141-148
  • 34 Wheat L J, Slama T G, Eitzen H E, Kohler R B, French M LV, Bieseckler J L. A large urban outbreak of histoplasmosis: clinical features.  Ann Intern Med. 1981;  94 331-337
  • 35 Wheat L J, Smith E J, Sathapatayavongs B et al.. Histoplasmosis in renal allograft recipients: two large urban outbreaks.  Arch Intern Med. 1983;  143 703-707
  • 36 Wood K L, Hage C A, Knox K S et al.. Histoplasmosis after treatment with anti-TNF-(alpha) therapy.  Am J Respir Crit Care Med. 2003;  167 1279-1282
  • 37 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;  4 148-151
  • 38 Hughes W T. Hematogenous histoplasmosis in the immunocompromised child.  J Pediatr. 1984;  105 569-575
  • 39 Wheat L J, Slama T G, Norton J A et al.. Risk factors for disseminated or fatal histoplasmosis.  Ann Intern Med. 1982;  96 159-163
  • 40 Wynne J W, Olsen G N. Acute histoplasmosis presenting as the adult respiratory distress syndrome.  Chest. 1974;  66 158-161
  • 41 Johnson P C, Wheat L J, Cloud G A et al.. Safety and efficacy of liposomal amphotericin B compared with conventional amphotericin B for induction therapy of histoplasmosis in patients with AIDS.  Ann Intern Med. 2002;  137 105-109
  • 42 Chapman S W, Bradsher Jr R W, Campbell Jr G D, Pappas P G, Kauffman C A. Practice guidelines for the management of patients with blastomycosis.  Clin Infect Dis. 2000;  30 679-683
  • 43 Taylor G D, Fanning E A, Ferguson J P, Jewell L D, Sekhon A S. Disseminated histoplasmosis in a nonendemic area.  Can Med Assoc J. 1985;  133 763-765
  • 44 Greenwood M F, Holland P. Tracheal obstruction secondary to Histoplasma mediastinal granuloma.  Chest. 1972;  62 642-645
  • 45 Savides T J, Gress F G, Wheat L J, Ikenberry S, Hawes R H. Dysphagia due to mediastinal granulomas: Diagnosis with endoscopic ultrasonography.  Gastroenterology. 1995;  109 366-373
  • 46 Jenkins D W, Fisk D E, Byrd R B. Mediastinal histoplasmosis with esophageal abscess.  Gastroenterology. 1976;  70 109-111
  • 47 Dines D E, Payne W S, Bernatz P E, Pairolero P C. Mediastinal granuloma and fibrosing mediastinitis.  Chest. 1979;  75 320-324
  • 48 Doyle T P, Loyd J E, Robbins I M. Percutaneous pulmonary artery and vein stenting: a novel treatment for mediastinal fibrosis.  Am J Respir Crit Care Med. 2001;  164 657-660
  • 49 Recto M R, Bousamra M, Yeh Jr T. Late superior vena cava perforation and aortic laceration after stenting to treat superior vena cava syndrome secondary to fibrosing mediastinitis.  J Invasive Cardiol. 2002;  14 624-629
  • 50 Mathisen D J, Grillo H C. Clinical manifestations of mediastinal fibrosis and histoplasmosis.  Ann Thorac Surg. 1992;  54 1053-1058
  • 51 Furcolow M L. Comparison of treated and untreated severe histoplasmosis.  JAMA. 1963;  183 121-127
  • 52 Putnam L R, Sutliff W D, Larkin J C et al.. Histoplasmosis cooperative study: chronic pulmonary histoplasmosis treated with amphotericin B alone and with amphotericin B and triple sulfonamide.  Am Rev Respir Dis. 1968;  97 96-102
  • 53 Connolly P, Wheat J, Schnizlein-Bick C et al.. Comparison of a new triazole antifungal agent, Schering 56592, with itraconazole and amphotericin B for treatment of histoplasmosis in immunocompetent mice.  Antimicrob Agents Chemother. 1999;  43 322-328
  • 54 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 1850-1854
  • 55 Goldberg J, Connolly P, Schnizlein-Bick C et al.. Comparison of nikkomycin Z with amphotericin B and itraconazole for treatment of histoplasmosis in a murine model.  Antimicrob Agents Chemother. 2000;  44 1624-1629
  • 56 Li R K, Ciblak M A, Nordoff N, Pasarell L, Warnock D W, McGinnis M R. In vitro activities of voriconazole, itraconazole, and amphotericin B against Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum. .  Antimicrob Agents Chemother. 2000;  44 1734-1736
  • 57 Hott J S, Horn E, Sonntag V K, Coons S W, Shetter A. Intramedullary histoplasmosis spinal cord abscess in a nonendemic region: case report and review of the literature.  J Spinal Disord Tech. 2003;  16 212-215

L. Joseph WheatM.D. 

MiraVista Diagnostics, 4444 Decatur Blvd., Ste. 300, Indianapolis, IN 46241

Email: jwheat@miravistalabs.com

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