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Source: Carver PL. Invasive Fungal Infections. In: DiPiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 8th edition. Accessed June 23, 2012.

  • Systemic fungal infection

  • Inhalation of dust-borne Histoplasma capsulatum
  • Acute histoplasmosis may occur in epidemics when soil disturbed.

  • Aerosolized H. capsulatum inhaled and settles in lungs
  • Tissue granulomas form over 2–4 months.
  • Foci become encapsulated and calcified over several years.
  • Low-inoculum exposure results in benign disease course.
  • Higher-inoculum exposure results in acute, self-limited illness
    • Fever
    • Chills
    • Headache
    • Myalgia
    • Nonproductive cough
  • Chronic pulmonary histoplasmosis
    • Progressive disease over period of years
      • Cavitation
      • Bronchopleural fistulas
      • Involvement of both lungs
      • Pulmonary insufficiency
      • Death
  • Immunocompromised hosts
    • Progressive, disseminated histoplasmosis
  • Acute disseminated histoplasmosis
    • Infants and young children: fatal in 1–2 months if untreated.
    • Adults: untreated patients ill for 10–20 years, with long asymptomatic periods.

  • Localized along Ohio and Mississippi River valleys in United States.
  • Found in nitrogen-enriched soils, particularly those contaminated by avian or bat guano.

  • Immunosuppression (e.g., AIDS)

  • Immunocompromised hosts
    • Adults with AIDS present with acute form of disseminated disease that resembles syndrome seen in infants and children.

Signs and Symptoms

  • Chronic pulmonary histoplasmosis
    • Chronic pulmonary symptoms
    • Apical lung lesions
  • Acute disseminated histoplasmosis
    • Infants and young children
      • Unrelenting fever
      • Anemia
      • Leukopenia or thrombocytopenia
      • Enlargement of liver, spleen, and visceral lymph nodes
      • Gastrointestinal (GI) symptoms: nausea, vomiting, diarrhea
    • Adults
      • Long asymptomatic periods interrupted by
        • Weight loss
        • Weakness
        • Fatigue

Means of Confirmation and Diagnosis

  • Serologic testing
    • Complement fixation
    • Immunodiffusion
    • Latex antigen agglutination antibody tests

Laboratory Tests

  • Culture
    • Identification of mycelial isolates from clinical cultures can be made by conversion of mycelium to yeast form (requires 3–6 weeks) or by more rapid (2 hours) and 100%-sensitive DNA probe that recognizes ribosomal DNA.


  • Chest radiograph

Diagnostic Procedures

  • Bone marrow biopsy and culture best method to establish diagnosis in AIDS patients with progressive disseminated histoplasmosis.

Differential Diagnosis

  • Resolution of clinical abnormalities
  • Prevention of relapse
  • Eradication of infection
    • Chronic suppression for immunosuppressed patients

  • Asymptomatic or mildly ill patients and patients with sarcoid-like disease generally do not benefit from antifungal therapy.
  • Therapy may be helpful in symptomatic patients whose conditions have not improved during first month of infection.

  • Recommended therapy for treatment of histoplasmosis summarized in Table 1.
  • Patients with mild, self-limited disease, chronic disseminated disease, or chronic pulmonary histoplasmosis with no underlying immunosuppression can usually be treated with oral itraconazole or IV amphotericin B.
  • AIDS patients
    • Intensive 12-week primary (induction and consolidation therapy) antifungal therapy followed by lifelong suppressive (maintenance) therapy with itraconazole.

Table 1. Clinical Manifestations and Therapy of Histoplasmosis

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