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A. Organismnavigator

  1. Histoplasma capsulatum - dimorphic fungus
  2. Growth inside macrophages initially in lymph nodes
  3. Spread with frequent involvement of upper lung zones (similar to TB)
  4. In USA, found primarily in Southeastern areas and Ohio River Valley
  5. ~500,000 new cases occur each year, most asymptomatic
  6. Found in soil, especially in areas contaminated with bird or bat droppings
  7. Not transmissible with person to person contact
  8. Symptoms begin 10-14 days after exposure
  9. Intact cellular immunity required to fight infection

B. Presentation [2] navigator

  1. Aysmptomatic Infection
    1. Determined with serological screening
    2. Solitary pulmonary nodule on chest radiography (CXR) may be seen
  2. Acute Pulmonary Histoplasmosis
    1. Cough, sputum production prominent
    2. Pain, dyspnea, fever
    3. Hemoptysis is less common
    4. Abnormalities on chest radiograph (CXR) usually not observed
    5. Hilar and mediastinal adenopathy may be seen
    6. More severe infections may show small diffuse pulmonary nodules
    7. Sequelae: mediastinal granuloma, pericarditis, arthritis may occur
  3. Chronic Pulmonary Histoplasmosis
    1. Associated with preexisting abnormal lung function or anatomy
    2. Productive cough common
    3. Fevers, malaise, night sweats
    4. Weight loss over time
    5. Symptoms similar to TB
    6. CXR usually with emphysematous lung, apical bullae, thickened cavity walls
    7. Lymphadenopathy usually absent
  4. May cause Cavitary (TB-like) Lesions with Granulomas
    1. Pulmonary lesions, often necrotizing
    2. Broncholithiasis (healed, encapsulated, calcified lymph nodes) [4]
    3. Granulomatous hepatitis
    4. Bone marrow infection with cytopenias
    5. Caseating and non-caseating granulomas may be seen
  5. Diffuse gastrointestinal involvement may be seen with malabsorption, weight loss [5]
  6. Disseminated Histoplasmosis
    1. May be especially virulent in patients with suppressed cellular immunity
    2. Patients with HIV and AIDS most susceptible (CD4 <200/µL)
    3. ~20% of cases occur in patients with intact immune system
    4. High risk of mortality in patients with HIV/AIDS
    5. Bone marrow involvement can lead to pancytopenia
    6. Ulceration on the palate is commonly seen
    7. Liver often involved
    8. CXR with small, diffuse, nodular opacities

C. Differential Diagnosis [1,2] navigator

  1. Other fungal infections
  2. Tuberculosis (TB)
  3. Sarcoidosis - usually with bilateral hilar adenopathy, uveitis, lupus pernio, hypercalcemia
  4. Vasculitis or other autoimmune disease
  5. Lymphoma

D. Diagnosis [1]navigator

  1. Variety of methods are available
  2. Serology
    1. Best overall test for acute and other forms of disase
    2. False negative results can occur mainly in immunocompromised persons
    3. Antibody titers remain elevated for up to 5 years after treatment
  3. Antigen test: urine and serum
    1. 92% sensitive for disseminated disease
    2. Rapid and useful in monitoring therapy
    3. Poor sensitivity (~20%) for acute and chronic pulmonary forms
  4. Fungal culture
    1. ~85% sensitivity for chronic and disseminated disease
    2. Poor sensitivity (15%) for acute and self-limited disease
    3. Requires 2-4 weeks for culture to grow
  5. Fungal stain is rarely used (poor sensitivity and specificity)

E. Treatment navigator

  1. Induction Therapy [3]
    1. Amphotericin B deoxycholate (ABD) is preferred agent in severe disease including disseminated disease (particularly in AIDS patients)
    2. Liposomal ABD 3mg/kg/d more effective, better tolerated than standard ABD for histoplasmosis in AIDS [6]
    3. Itraconazole (Sporanox®) 200mg bid-tid for moderate disease may be used for induction
    4. Itraconazole 200mg qd-bid effective except in chronic cavitary disease
  2. Recurrent Disease
    1. Consider liposomal ABD 3mg/kg/d x 2-4 weeks
    2. Itraconazole 200mg po bid-tid with good results
    3. Mild cases even in AIDS patients may be treated with itraconazole throughout disease [7]
    4. Patients with AIDS should remain on lifelong therapy if CD4 counts remain low
  3. Other Agents
    1. Fluconazole (Diflucan®) 800mg po qd may be effective in about 50% of patients
    2. Fluconazole is preferred for central nervous system involvement
    3. Lung resection is advocated in very difficult cases
  4. Glucocorticoids
    1. May initially reduce symptoms but can promote dissemination
    2. Should be used in pericardial disease and considered with arthritis
    3. When used in conjunction with antifungal agents, dissemination does not occur

References navigator

  1. Kurowski R and Ostapchuk M. 2002. Am Fam Phys. 66(12):2247 abstract
  2. Gulati M, Saint S, Tierney LM Jr. 2000. NEJM. 342(1):37 (Case Discussion) abstract
  3. Wheat J, MaWhinney S, Hafner R, et al. 1997. Am J Med. 103(3):223 abstract
  4. Daly JS and Mark EJ. 2002. NEJM. 346(19):1475 (Case Record) abstract
  5. Goulet CJ, Moseley RH, Tonnerre C, et al. 2005. NEJM. 352(5):489 (Case Discussion) abstract
  6. Johnson PC, Wheat LJ, Cloud GA, et al. 2002. Ann Intern Med. 137(2):105 abstract
  7. Wheat J, Hafner R, Korzun AH, et al. 1995. Am J Med. 98(4):336 abstract