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Fungal Infections

Justin Smith



  • Endemic to Ohio and Mississippi river valley

  • Pulmonary infiltrate with hilar or mediastinal LAD, pulmonary nodule/cavitary lesion, pulmonary syndrome with erythema nodosum

  • DDx: TB, malignancy, sarcoidosis (if considering sarcoidosis, rule out histoplasmosis as sarcoidosis treatment can induce disseminated histoplasmosis)


  • Antigen (requires attending approval): For acute pulmonary histoplasmosis, 65% urine sensitivity, 69% serum sensitivity, and 83% sensitivity when co-tested. Thus, both serum and urine Ag are usually sent together

    • Lower rates of positivity when disease is localized, versus diffuse throughout the lungs or disseminated.
    • There are relatively high rates of cross-reactivity, where histoplasma antigen will be positive with blastomycosis; therefore, do not order blasto Ag if ordering histo Ag in MOST cases
  • Serology: Consider Histoplasma Ab if evaluating for pulmonary disease

  • Culture: most useful in chronic infections, sensitivity is low in acute/localized and may take >6 weeks to grow.

  • Bronchoscopy: If clinical suspicion is high and work up negative, consider interventional pulmonology consult for consideration of bronchoscopy


  • Outpatient/Mild disease:

    • Tx not required if symptoms \<4 weeks, initiate if symptomatic beyond 4 weeks
    • Itraconazole: 200mg TID x3 days loading, then BID (adjusted by levels which are drawn 2 weeks post-start) for 6-12 weeks minimum
    • Can use oral formulation or capsules (capsules require high acidity, give with food consumption or OJ or coke; do not use capsules if patient is on H2 blockers/PPI)
    • Voriconazole, Posaconazole: used if not tolerating itraconazole or as salvage therapy
  • Inpatient/Moderate to Severe Disease:

    • Amphotericin: 1-2 weeks induction, followed by PO itraconazole for 12 weeks (total)

    • Methylprednisolone: help to prevent ARDS with significant lung involvement

Additional Information

  • Complications: Pericarditis, arthritis/arthralgias with erythema nodosum, chronic cavitary lesions, fibrosing mediastinitis, broncholithiasis

  • Disseminated Histoplasmosis:

    • Typically found in immunocompromised populations
    • Clinical presentations: FUO, weight loss, disseminated LAD, cutaneous manifestations, bone marrow suppression/pancytopenia, liver enzymes elevation, various solid organ involvement on imaging (liver, spleen, adrenals, nodes)
    • Management
      • Mild: itraconazole
      • Moderate to Severe: amphotericin induction followed by itraconazole
      • CNS involvement: amphotericin for 4-6 weeks as induction



  • Endemic to Mississippi/Ohio river valley, southern and midwestern US, great lakes

  • Pulmonary syndrome: cough, fever, hemoptysis, chest pain, dyspnea

    • Can result in both an acute or chronic pneumonia, as well as ARDS
  • Cutaneous: raised verrucous lesion, varying in color, with irregular borders

  • MSK: osteolytic lesion, draining sinus, soft tissue swelling

  • Multi-system: up to 20-40% of cases, most typically lung/skin involvement.


  • Culture: typically takes 1-4 weeks

  • Ag: urine >serum. ~90% sensitive, but only 80% specific because of cross-reactivity

  • Serology: available, but not very useful because of high degree of cross-reactivity


  • Mild: PO itraconazole for 6-12 months with loading, check level at 2 weeks

  • Moderate to Severe: induction with Amphotericin, followed by 6-12 months of PO itraconazole



  • Oropharyngeal: white plaques in mouth, change in taste, erythema without plaques

    • Usually seen in infants, older adults, immunocompromised host (HIV or chemotherapy), inhaled steroid users
  • Esophageal: odynophagia, especially retrosternal pain (AIDS defining illness)

  • Vulvovaginitis: itching, burning, vaginal discharge, vulvar erythema, vulvar edema, dyspareunia, dysuria

  • Balanitis: painful white plaques with burning and itching on the glans penis

  • Mastitis: erythema, tenderness in breast feeding woman.


  • Depends on specifics, but typically nystatin or fluconazole EXCEPT C. glabrata (proof of fluconazole susceptibility needed) and C. krusei (intrinsically resistant to fluconazole)

  • Cx generally not indicated unless complicated pt with extensive tx history for Candida

Additional Information

  • Disseminated disease
    • Presentation: Primarily immunocompromised populations (hematologic malignancies, solid organ transplant recipients, receiving chemotherapy, TPN, steroid use, broad spectrum antibiotics) and ICU settings (especially, burn, trauma, and neonatal)
    • Diagnosis: Candida in a bacterial blood culture (NEVER contaminant)
    • Start micafungin 100mg IV and consult ID for candidemia or if concerned for disseminated disease

Last update: 2022-06-21 22:35:37