histoplasmosis (Ohio Valley fever)

Etiology

• infection caused by Histoplasma capsulatum
• largely a disease associated with immunosuppression
  • HIV1 infection/AIDS
  • hematologic malignancy

Epidemiology

• most common endemic mycosis in U.S.
• most likely fungal infection in traveler returning from Central America or South America
• endemic to Mississipi River Valley, Ohio River Valley, Mexico, Central America & South America
• found in soil contaminated with bird or bat droppings
• infection is acquired by inhalation of the mold form of the fungus
• 4 cases found in Montana 2012-2013; case in northen Georgia
• 19 cases of pulmonary histoplasmosis associated with a family gathering that included a bonfire that burned bamboo from a grove that had been a red-winged blackbird roost
• probably underdiagnosed
  • 1/3 of cases receive antibacterial agents before diagnosis
  • only 36% undergo fungal-specific tests

Pathology

• disseminated disease commonly involves the lungs, liver, spleen, lymph nodes, bone marrow, & central nervous system
• necrotizing granulomatous pneumonitis
• rarely causes cavitary lung lesions
• eye may be involved

Clinical manifestations

• most patients asymptomatic
  • symptom onset 1-3 weeks after exposure
  • spontaneous recovery in 3 weeks common
• constitutional symptoms
  • malaise, weight loss, headache, fever
  • generally indolent course
• pulmonary: flu-like syndrome
  • non-productive cough, dyspnea, rales
  • broncholithiasis
  • pulmonary nodules (histoplasmomas)
  • reticulonodular infiltrates
• mediastinitis
  • granulomatous mediastinitis
  • fibrosing mediastinitis
• acute & chronic disseminated disease
• gastrointestinal
  • abdominal cramps
  • diarrhea
  • melena
  • obstruction
  • bowel perforation
• meningitis
• ulcers on tongue & lips, case with tongue pain
• pharyngitis
  • case with associated tonsillar mass
• lymphadenopathy, hilar adenopathy
• splenomegaly
• hepatomegaly

Laboratory

• complete blood count
  • anemia, thrombocyotopenina, leukopenia
• liver function tests
  • elevated serum transaminases
  • elevated serum alkaline phosphatase
• peripheral blood smear may show small yeast forms within neutrophils
• Histoplasma antigen in tissue/body fluid
  • Histoplasma capsulatum Ag in urine (first line)
    • sensitivity & specificity > 85% in acute & disseminated infection but < 50% in chronic infection
  • Histoplasma capsulatum Ag in serum
  • Histoplasma capsulatum Ab in CSF
• culture of organisms from:
  • blood
  • sputum
  • mouth
  • bone marrow
  • urine
  • cerebrospinal fluid (CSF)
• increasing complement fixation titer
• serum ferritin may be > 10,000 ug/L
• serum lactate dehydrogenase generally high
• Histoplasma capsulatum DNA
• positive skin testing

Radiology

• chest X-ray
  • pneumonitis
    • scattered nodular opacities or diffuse reticular pattern
  • pulmonary infiltrates, hilar adenopathy
  • single round opacity in lower low indistinguishable from blastomycocosis
  • calcified lesions in later phases of disease
• chest CT
  • diffuse reticulonodular infiltrates

Differential diagnosis

• blastomycosis
  • hilar adenopathy & history of exposure to bat or bird dropping distinguish histoplasmosis
  • yeast forms of blastomycosis have a distinct appearance with broad-based budding
• coccidioidomycosis
  • chest imaging: focal opacity, thin walled, apical cavities
• paracoccidioidomycosis
  • asymptomatic primary pulmonary infection, acute disseminated infection <10%
• Listeria monocytogenes*
• tuberculosis
• sarcoidosis: pancytopenia not common
• malignancy
• methotrexate toxicity: no lymphadenopathy

* both histoplasmosis & listeriosis associated with immunodeficiency due to TNF-alpha inhibitors

* Listeria monocytogenes more likely to cause diarrhea

Management

• mild forms may not require antifungal therapy (even with pulmonary infiltrates & hilar adenopathy)
  • most patients recover spontaneosly within 3 weeks
• itraconazole
  • 200 mg TID for 3 days, then
    • 200 mg PO BID for 6-12 weeks (mild-moderate infection)
    • 200 mg PO QD for lifelong suppression (98% effective)
• liposomal amphotericin B followed by itraconazole for severe infection
  • disseminated infection, immunocompromised, mechanical ventilation
  • conventional amphotericin B 0.5-0.6 mg/kg/day for several weeks is alternative
• fluconazole is less effective than itraconazole
  • up to 800 mg/day is required for 74% suppression

More general terms

• mycosis; fungal infection

Additional terms

• Histoplasma capsulatum
• histoplasmin (Histolyn-CYL)