Histoplasmosis

Aka: Histoplasmosis, Histoplasma capsulatum

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II. Pathophysiology

  1. Etiology: Histoplasma capsulatum
  2. Transmission: Inhalation
  3. Sources (infection often with heavy cleaning of source)
    1. Soil contaminated with bird and bat droppings (fungus may persist for years)
    2. Old houses (especially attics)
    3. Farms (especially barns and chicken coops)
  4. Infection course
    1. Initial phase (controlled by Macrophages)
      1. Fungus spores inhaled into lung alveoli
      2. Travel to Lymph Nodes at hilum and mediastinum
      3. Spreads from lung, lymph to liver, Spleen, marrow
    2. Second phase (controlled by cellular Immunity)
      1. Occurs 10-14 days after spore inhalation
      2. Infected sites necrose, caseate, and fibrose
      3. Calcified Granulomas form within a few years
      4. Disseminated infection if cellular Immunity defect
  5. Risks for disseminated infection
    1. Infants and young children
    2. Intense exposure to airborne spores
    3. Immunocompromised patients
      1. HIV with CD4 <200
      2. Lymphoma
      3. Immunosuppressant medication (e.g. Corticosteroid)

III. Epidemiology

  1. Consider in Immunocompromised patients
    1. Undifferentiated fever
    2. Pneumonia
    3. Mucocutaneous disease
  2. United States
    1. Incidence: 500,000 new cases per year
    2. Prevalence: Up to 80% of young adults in endemic regions have antibodies from prior exposure
    3. Endemic Areas (Ohio and Mississippi river valleys)
      1. Southeast
      2. Mid-Atlantic
      3. Central States
    4. Endemic in some cities
      1. Indianapolis
      2. Kansas City
      3. Houston

IV. Symptoms and Signs: Acute Pulmonary Histoplasmosis

  1. Symptoms
    1. Most cases (95%) are asymptomatic or mild
    2. Fever
    3. Non-productive Cough
    4. Substernal Chest Pain
    5. Dyspnea
    6. Headache
    7. Malaise
    8. Diaphoresis
    9. Weight loss
  2. Signs
    1. Hepatomegaly
    2. Splenomegaly
    3. Adenopathy
    4. Erythema Nodosum
    5. Erythema Multiforme

V. Symptoms and Signs: Chronic Pulmonary Histoplasmosis

  1. Exaggerated immune response to fungal Antigens
  2. Typical patient is middle aged white male with COPD
  3. Symptoms (Similar to Tuberculosis)
    1. Productive cough
    2. Fever
    3. Night Sweats

VI. Symptoms and Signs: Disseminated Histoplasmosis

  1. Most patients (80%) are Immunocompromised (e.g. HIV, Chemotherapy)
  2. Associated with severe or fatal lung infections that may spread to mediastinum or more widely
  3. Symptoms
    1. Fever (most common)
    2. Headache
    3. Weight loss
    4. Cough (<50% of cases)
    5. Abdominal cramps, Diarrhea, Melena (rare)
  4. Signs
    1. Hepatomegaly
    2. Splenomegaly
    3. Lymphadenopathy
    4. Jaundice
    5. Ulcerative lesions in nose, mouth, Larynx (25%)

VII. Imaging: General

  1. Necrotizing Granulomata
  2. Chest XRay (see below)
  3. PET Scan is diagnostic

VIII. Imaging: Chest XRay

  1. Acute Pulmonary Histoplasmosis
    1. Usually normal
    2. Hilar Adenopathy
    3. Pneumonitis involving lower lung fields
  2. Chronic Pulmonary Histoplasmosis
    1. Calcified fibronodular apical infiltrates
    2. Underlying Emphysematous changes
    3. No adenopathy
  3. Disseminated Histoplasmosis
    1. Discrete Pulmonary Nodules or miliary pattern
    2. Adenopathy rarely occurs

IX. Labs: Diagnosis

  1. Sputum Culture (Gold standard for definitive diagnosis)
    1. Requires 2-6 weeks of growth
    2. Test Sensitivity for disseminated Histoplasmosis: 85%
    3. Sensitivity chronic pulmonary Histoplasmosis: 85%
    4. Not sensitive for limited acute pulmonary disease
  2. Serologic Titers (positive if > 1:32)
    1. Sensitivity acute or chronic pulmonary disease: >98%
    2. Moderate sensitivity in disseminated disease: 71%
    3. False Negatives
      1. False Negatives in Immunocompromised
      2. False Negatives in first 6 weeks of infection
    4. False Positives
      1. Histoplasmosis Infection within last 5 years
      2. Other fungus cross reactivity
        1. Blastomyces
        2. Aspergillus
  3. Fungal staining of Bone Marrow or tissue histopathology
    1. Bone Marrow in disseminated disease: 75% sensitivity
    2. Difficult to differentiate from other organisms
      1. Candida glabrata
      2. Pneumocystis carinii
  4. Histoplasma Antigen testing (Urine and serum Antigens)
    1. High Test Sensitivity in disseminated disease (92%)
    2. Low sensitivity in acute and chronic pulmonary Histoplasmosis
    3. Useful for monitoring treatment outcomes
  5. Skin Test
    1. Useless in diagnosing acute disease
    2. High False Positive Rate in endemic areas
    3. High False Negative Rate in disseminated and chronic

X. Labs: Disseminated Histoplasmosis

  1. Liver Function Test abnormalities
  2. Complete Blood Count: Pancytopenia
    1. Anemia
    2. Leukopenia

XI. Complications: Acute pulmonary Histoplasmosis

  1. Mediastinal Granuloma (Chest Pain, Hemoptysis)
  2. Pericarditis (Chest Pain, fever) - delayed response
  3. Arthritis (symmetric and Polyarticular)

XII. Course

  1. Chronic pulmonary Histoplasmosis
    1. 33% stabilize or improve spontaneously

XIII. Management

  1. Acute Pulmonary Histoplasmosis
    1. Severe disease
      1. First 2 weeks
        1. Amphotericin B 0.7 mg/kg/day
        2. Prednisone 20 mg qd
      2. Next 12 weeks
        1. Itraconazole dosed as in mild to moderate disease
    2. Mild to moderate disease
      1. Itraconazole 200 mg qd to bid for 12 weeks
  2. Chronic Pulmonary Fibrosis
    1. Severe disease
      1. Start: Amphotericin B 0.7 mg/kg/day
      2. Next: Itraconazole as below for 12-24 months
    2. Moderate disease
      1. Itraconazole 200 mg PO qd to bid for 12-24 months
  3. Disseminated Histoplasmosis
    1. Severe disease
      1. Start: Amphotericin B 0.7 to 1.0 mg/kg/day
      2. Next: Itraconazole as below for 6-18 months
        1. Stop when urine and serum Antigen <4 units
    2. Moderate disease
      1. Itraconazole 200 mg PO qd to bid for 6-18 months
      2. Continue Itraconazole for life if HIV positive

XIV. References

  1. Kurowski (2002) Am Fam Physician 66(12):2247-52 [PubMed]
  2. Wheat (2000) Clin Infect Dis 30:688-95 [PubMed]
  3. Mocherla (2001) Semin Respir Infect 16(2):141-8 [PubMed]

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