Histoplasmosis

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. http://accesspharmacy.com/content.aspx?aid=8005562. 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.

Imaging

• Chest radiograph

Diagnostic Procedures

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

Differential Diagnosis

• Influenza
• Atypical pneumonia
• Tuberculosis
• Lymphoma
• Other fungal infection

• 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.