• Fungal infection caused by Histoplasma capsulatum[1]
  • Endemic to the Ohio, Missouri, and Mississippi River valleys in the United States[2]
  • Exposure from disruption of soil containing organisms leads to aerosolization[3]
  • Activities associated with high-level exposure include spelunking, excavation, and demolition of old buildings
Histoplasmosis after return from Pennsylvania, United States


  • Infection occurs via inhalation[4]
  • In immunocompetent patients:
    • Phagocytes and epithelial cells eventually organize and form granulomas that go on to fibrose and calcify
  • In immunocompromised patients:
    • The infection is not contained and can disseminate

Clinical Features

Disease manifestation depends on intensity of exposure, immune status, and underlying lung architecture

Acute Pulmonary Histoplasmosis

  • 90% asymptomatic, and usually self-limited
  • Symptoms 1-4 weeks after exposure and consist of flu-like illness[5]
    • Fever/chills
    • Headache
    • Malaise
    • Myalgias
    • Abdominal pain
    • Arthralgias
    • Dyspnea
    • Cough, hemoptysis
  • Hilar/mediastinal lymphadenopathy on CXR

Chronic Pulmonary Histoplasmosis

  • Mostly older patients or smokers with underlying structural lung disease[6]
  • Symptoms:
    • Cough
    • Weight loss
    • Low-grade fever
    • Malaise
    • Night sweats
    • Sometimes hemoptysis, sputum production, dyspnea
  • CXR may show:
    • Upper lobe infiltrates
    • Fibrosis, scarring
    • Cavitations

Progressive Disseminated Histoplasmosis

  • Seen in immunocompromised patients
  • SIRS
  • Acute form:
    • Diffuse interstitial or reticulonodular lung infiltrates
    • Respiratory failure
    • Coagulopathy
    • Multiorgan failure
  • Subacute form depends on focal organ system affected:
    • Fever
    • Weight loss
    • Hepatosplenomegaly
    • Meningitis, brain lesions
    • Mucosal or GI ulcerations
    • Adrenal insufficiency
    • Pericarditis
  • Chronic form: constitutional sx


  • Enlarged lymph nodes that may undergo necrosis
  • This leads to granulomatous mediastinitis
  • Can lead to:
    • Superior vena cava syndrome
    • Obstruction of pulmonary vessels
    • Airway obstruction
    • Recurrent pneumonia
    • Hemoptysis
    • Respiratory failure

Differential Diagnosis

Causes of Pneumonia







  • CXR
    • Normal in 40-70% of cases
    • Pneumonitis with hilar adenopathy
    • Focal pulmonary infiltrates with light exposure
    • Diffuse infiltrates with heavy exposure
  • CBC - mild anemia in chronic disease
  • Liver panel - alkaline phosphatase elevated in disseminated and chronic disease
  • LDH - elevated in AIDS patients with disseminated disease
  • Definitive diagnosis by:
    • Sputum cultures
    • Blood cultures
    • Antibody testing
    • Serum/urine antigen testing
  • Further imaging if concerned for specific organ involvement in disseminated disease (Head CT, Abdominal CT or Lumbar puncture)


Acute Pulmonary Histoplasmosis

  • Do not treat if asymptomatic
    • Not progressive, resolves without treatment, only rarely reactivates

Progressive Disseminated Histoplasmosis

  • Pulmonary cases: Itraconazole x 6-12 weeks[7]
  • Severe disease: Amphotericin B x 1 week then Itraconazole x 1 year[8]
  • Surgical intervention may be necessary in some cases

Chronic Pulmonary Histoplasmosis


  • Discharge asymptomatic cases
  • Discharge mildly symptomatic immunocompetent patients with primary care follow up
  • Admit severe symptoms or symptomatic immunocompromised patients

See Also

External Links


  1. Lowell JR. Diagnosis of histoplasmosis. Ann Intern Med. Feb 1983;98(2):260
  2. Outbreak of histoplasmosis among travelers returning from El Salvador--Pennsylvania and Virginia, 2008. MMWR Morb Mortal Wkly Rep. Dec 19 2008;57(50):1349-53
  3. Hage, Chadi A., and L. Joseph Wheat. "Chapter 199. Histoplasmosis." Harrison's Principles of Internal Medicine, 18e. Eds. Dan L. Longo, et al. New York, NY: McGraw-Hill, 2012. n. pag. AccessMedicine. Web. 4 Dec. 2014
  4. “Histoplasmosis.” CDC. (2014, Sept. 25) Web 4 Dec. 2014. http://www.cdc.gov/fungal/diseases/histoplasmosis
  5. http://www.ncbi.nlm.nih.gov/pubmed/24528944
  6. http://www.ncbi.nlm.nih.gov/pubmed/23664715
  7. Wheat LJ, Freifeld AG, Kleiman MB, 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;45:807-825
  8. Hospenthal DR, Becker SJ. Update on Therapy for Histoplasmosis. Infect Med. April 13 2009;26:121-124