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Histoplasmosis
Aka: Histoplasmosis, Histoplasma capsulatum
- See Also
- Fungal Lung Infection
- Pathophysiology
- Etiology: Histoplasma capsulatum
- Transmission: Inhalation
- Sources (infection often with heavy cleaning of source)
- Soil contaminated with bird and bat droppings
- Old houses (especially attics)
- Farms (especially barns and chicken coops)
- Infection course
- Initial phase (controlled by Macrophages)
- Fungus spores inhaled into lung alveoli
- Travel to Lymph Nodes at hilum and mediastinum
- Spreads from lung, lymph to liver, Spleen, marrow
- Second phase (controlled by cellular Immunity)
- Occurs 10-14 days after spore inhalation
- Infected sites necrose, caseate, and fibrose
- Calcified Granulomas form within a few years
- Disseminated infection if cellular Immunity defect
- Risks for disseminated infection
- Infants and young children
- Intense exposure to airborne spores
- Immunocompromised patients
- HIV with CD4 <200
- Lymphoma
- Immunosuppressant medication (e.g. Corticosteroid)
- Epidemiology
- Consider in Immunocompromised patients
- Undifferentiated fever
- Pneumonia
- Mucocutaneous disease
- United States
- Incidence: 500,000 new cases per year
- Endemic Areas (Ohio and Mississippi river valleys)
- Southeast
- Mid-Atlantic
- Central States
- Endemic in some cities
- Indianapolis
- Kansas City
- Houston
- Symptoms and Signs: Acute Pulmonary Histoplasmosis
- Symptoms
- Most cases are asymptomatic or mild
- Fever
- Non-productive Cough
- Dyspnea
- Headache
- Malaise
- Diaphoresis
- Weight loss
- Signs
- Hepatomegaly
- Splenomegaly
- Adenopathy
- Erythema Nodosum
- Erythema Multiforme
- Symptoms and Signs: Chronic Pulmonary Histoplasmosis
- Exaggerated immune response to fungal Antigens
- Typical patient is middle aged white male with COPD
- Symptoms (Similar to Tuberculosis)
- Productive cough
- Fever
- Night Sweats
- Symptoms and Signs: Disseminated Histoplasmosis
- Most patients (80%) are Immunocompromised
- Symptoms
- Fever (most common)
- Headache
- Weight loss
- Cough (<50% of cases)
- Abdominal cramps, Diarrhea, Melena (rare)
- Signs
- Hepatomegaly
- Splenomegaly
- Lymphadenopathy
- Jaundice
- Ulcerative lesions in nose, mouth, Larynx (25%)
- Imaging: General
- Necrotizing Granulomata
- Chest XRay (see below)
- PET Scan is diagnostic
- Imaging: Chest XRay
- Acute Pulmonary Histoplasmosis
- Usually normal
- Hilar Adenopathy
- Pneumonitis involving lower lung fields
- Chronic Pulmonary Histoplasmosis
- Calcified fibronodular apical infiltrates
- Underlying Emphysematous changes
- No adenopathy
- Disseminated Histoplasmosis
- Discrete Pulmonary Nodules or miliary pattern
- Adenopathy rarely occurs
- Labs: Diagnosis
- Sputum Culture (Gold standard for definitive diagnosis)
- Requires 2-6 weeks of growth
- Test Sensitivity for disseminated Histoplasmosis: 85%
- Sensitivity chronic pulmonary Histoplasmosis: 85%
- Not sensitive for limited acute pulmonary disease
- Serologic Titers (positive if > 1:32)
- Sensitivity acute or chronic pulmonary disease: >98%
- Moderate sensitivity in disseminated disease: 71%
- False Negatives
- False Negatives in Immunocompromised
- False Negatives in first 6 weeks of infection
- False Positives
- Histoplasmosis Infection within last 5 years
- Other fungus cross reactivity
- Blastomyces
- Aspergillus
- Fungal staining of Bone Marrow or tissue histopathology
- Bone Marrow in disseminated disease: 75% sensitivity
- Difficult to differentiate from other organisms
- Candida glabrata
- Pneumocystis carinii
- Histoplasma Antigen testing (Urine and serum Antigens)
- High Test Sensitivity in disseminated disease (92%)
- Low sensitivity in acute and chronic pulmonary Histoplasmosis
- Useful for monitoring treatment outcomes
- Skin Test
- Useless in diagnosing acute disease
- High False Positive Rate in endemic areas
- High False Negative Rate in disseminated and chronic
- Labs: Disseminated Histoplasmosis
- Liver Function Test abnormalities
- Complete Blood Count: Pancytopenia
- Anemia
- Leukopenia
- Complications: Acute pulmonary Histoplasmosis
- Mediastinal Granuloma (Chest Pain, Hemoptysis)
- Pericarditis (Chest Pain, fever) - delayed response
- Arthritis (symmetric and Polyarticular)
- Course
- Chronic pulmonary Histoplasmosis
- 33% stabilize or improve spontaneously
- Management
- Acute Pulmonary Histoplasmosis
- Severe disease
- First 2 weeks
- Amphotericin B 0.7 mg/kg/day
- Prednisone 20 mg qd
- Next 12 weeks
- Itraconazole dosed as in mild to moderate disease
- Mild to moderate disease
- Itraconazole 200 mg qd to bid for 12 weeks
- Chronic Pulmonary Fibrosis
- Severe disease
- Start: Amphotericin B 0.7 mg/kg/day
- Next: Itraconazole as below for 12-24 months
- Moderate disease
- Itraconazole 200 mg PO qd to bid for 12-24 months
- Disseminated Histoplasmosis
- Severe disease
- Start: Amphotericin B 0.7 to 1.0 mg/kg/day
- Next: Itraconazole as below for 6-18 months
- Stop when urine and serum Antigen <4 units
- Moderate disease
- Itraconazole 200 mg PO qd to bid for 6-18 months
- Continue Itraconazole for life if HIV positive
- References
- Kurowski (2002) Am Fam Physician 66(12):2247-52 [PubMed]
- Wheat (2000) Clin Infect Dis 30:688-95 [PubMed]
- Mocherla (2001) Semin Respir Infect 16(2):141-8 [PubMed]