Episode #27 – Millet Seeds of Destruction

Clinical forms of histoplasmosis

• *Majority of infections will be asymptomatic or mild and nonprogressive in healthy hosts*
• Acute symptomatic pulmonary histoplasmosis
  • • Typical incubation is between 7-21 days (commonly ~2 wks)
    • Influenza-like illness with fever, cough, chest pain, headache, malaise, fatigue
      • • **Might be indistinguishable from community acquired pneumonia or viral upper respiratory syndrome
    • Focal patchy or nodular infiltrates on chest imaging.  A clue may be mediastinal or hilar lymphadenopathy on imaging
    • Rheumatologic manifestations may accompany acute pulmonary infection: arthralgias, erythema nodosum or multiforme
      • • Rosenthal J, Brandt KD, Wheat LJ, Slama TG. Rheumatologic manifestations of histoplasmosis in the recent Indianapolis epidemic. Arthritis Rheum. 1983;26(9):1065-1070. doi:10.1002/art.1780260902
    • Pericarditis may also occur rarely. Organisms rarely found in tissue or pericardial fluid, so thought to not be direct invasion but rather granulomatous inflammatory response (in mediastinal lymph nodes adjacent to pericardium)
      • • Wheat LJ, Stein L, Corya BC, et al. Pericarditis as a manifestation of histoplasmosis during two large urban outbreaks. Medicine (Baltimore). 1983;62(2):110-119. doi:10.1097/00005792-198303000-00004
    • Severity is thought to correlate with higher spore exposure
    • Complications or sequelae:
      • • Acute re-infection can occur if re-exposed to large inoculum
        • Persistent mediastinal granuloma may occur with massive enlargement of mediastinal lymph nodes from exuberant granulomatous inflammation.  Nodes can impinge on major local airways, pulmonary vessels, or esophagus leading to post-obstructive pneumonia, bronchiectasis, or SVC syndrome.  
        • Fibrosing mediastinitis: after abnormal host inflammatory response, can develop calcification and fibrosis.  Might not be able to identify prior acute episode of histoplasmosis.  No effective treatment with steroids or antifungals
        • Histoplasmoma: mass lesion that resembles fibroma
• Chronic pulmonary histoplasmosis
  • • Can be due to initial / primary infection or reactivation later
    • Symptoms >6 weeks duration (low grade fever, cough, dyspnea, weight loss) and evidence of progressive pulmonary infiltrates or cavities
    • Symptoms may resemble pulmonary TB or lung cancer with fevers, weight loss, hemoptysis 
    • Also often characterized by fibrotic apical infiltrates with or without cavitation.  Areas can enlarge and may results in formation of bronchopleural fistulae in rare cases
    • Often described in men over the age of 50 with chronic lung disease

• Progressive disseminated histoplasmosis
  • • More common in immunocompromised hosts such as those with advanced HIV/AIDS, solid organ or hematopoietic stem cell transplant recipients, TNF-alpha blockade, elderly, or cellular immunodeficiency
    • Fevers, respiratory symptoms, weight loss → spread through reticuloendothelial system can lead to lymphadenopathy, hepatosplenomegaly, bone marrow infiltration
    • Possible presentations:
      • • Adrenal insufficiency
        • Oral ulcers that may be painful and with heaped up borders resembling cancer
        • GI: colonic mass lesions, colitis with ulcerations
        • Cutaneous dissemination: typically nodules, papules, plaques, or ulcers
        • Ocular: uveitis or panophthlamitis
        • CNS involvement
        • Endocarditis
    • Labs can demonstrate pancytopenia, transaminitis, elevated alk phos
    • Presentation can often be rapidly progressive, but there are some patients who might have subacute or chronic wasting type illness
    • High case fatality rate
    • Need high index of suspicion and often misdiagnosed as disseminated TB