Fungal Infections

Fungal Infections – Justin Smith

Histoplasmosis

Background

  • Endemic to Ohio and Mississippi river valley
  • Most commonly presents as pulmonary disease but can be disseminated (see below)
  • Pulmonary infiltrate with hilar or mediastinal LAD, hilar or mediastinal LAD alone, pulmonary nodule/cavitary lesion, pulmonary syndrome with erythema nodosum
  • Differential: tuberculosis, malignancy, sarcoidosis (if considering sarcoidosis, rule out histoplasmosis as sarcoidosis treatment can induce disseminated histoplasmosis)

 

Evaluation

  • 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.
  •  
  • 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

 

Management

  • 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 (HIV, solid organ transplant recipient, TNF-alpha treatment). Rare in immunocompetent adults
  • 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)
  • Diagnosis:
    • Antigen: urine, serum, BAL, CSF (urine & serum Ag 97-100& sensitivity/specificity in AIDS patients)
    • Serology: less likely to be positive in immunocompromised host
  • Management
    • Mild: itraconazole
    • Moderate to Severe: amphotericin induction followed by itraconazole
    • CNS involvement: amphotericin for 4-6 weeks as induction

 

Blastomycosis

Background

  • 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.

 

Evaluation

  • 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

 

Management

  • Mild pulmonary: PO itraconazole for 6-12 months with loading as described above, level at 2 weeks, and with same caveats re: capsules
  • Moderate to Severe: induction with Amphotericin, followed by 6-12 months of PO itraconazole

 

 

Candida

Background

  • 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.

 

Management

  • Depends on specifics, but typically nystatin or fluconazole EXCEPT C. glabrata (proof of fluconazole susceptibility needed) and C. krusei (intrinsically R 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). Consider if Candida growth from 2 sites (ie sputum and urine)
    • Start micafungin 100mg IV and consult ID for candidemia or if concerned for disseminated disease