Histoplasmosis

Etiology: Histoplasma capsulatum
Transmission: Inhalation
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)
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
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)

Consider in Immunocompromised patients
1. Undifferentiated fever
2. Pneumonia
3. Mucocutaneous disease
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

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

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

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
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
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
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
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