Dimorphic Endemic Fungi Quiz

Dimorphic Endemic Fungi

• Coccidioidomycosis ("Valley Fever"):

  • Etiology: Mold in soil, yeast in the body.
  • Epidemiology: Southwest US (AZ, NV), Mexico, Central America, South America.
  • Transmission: Inhalation of airborne spores, rare from solid organ transplant.
  • Course: Subclinical and spontaneous resolution in 50% of patients. Lifelong immunity prevents recurrence.
  • Risk factors: Exposure to endemic region, dusty outdoor activities, HIV, DM, elderly, Black/Filipino patients, pregnancy.
  • Symptoms: General (fever, fatigue, headache, night sweats, weight loss, arthralgias), chest (productive cough, dyspnea, hemoptysis, pleuritic chest pain), rash (erythema nodosum, erythema multiforme). Typical presentation: Arizona man working in construction.
  • Testing: IgM and IgG titers, moderate leukocytosis and eosinophilia, variable imaging.
  • Treatment: Uncomplicated cases resolve spontaneously. Itraconazole 200 mg PO BID x 6 months. Progressive cases: Amphotericin B IV until titers decrease. Reportable.

• Blastomycosis:

  • Etiology: Mold in soil/water.
  • Example exposure: Lumberjacking/woodcutting injuries.
  • Pathophysiology: Inhalation of spores, skin trauma.
  • Incubation period: 30-45 days.
  • Endemic regions: Ohio River Basin, Mississippi River Basin, Great Lakes, St. Lawrence River.
  • Symptoms: Pulmonary (initially asymptomatic in 50%): fever, sweating, cough, nocturnal joint pain. Dissemination to bone, nervous system, lungs, liver, spleen, kidneys possible.
  • Imaging: Chest X-ray, possible osteolytic lesions.
  • Labs: Microscopy (broad-based budding), skin biopsy, bone marrow aspirate.
  • Treatment: Itraconazole PO x 6-12 months. Severe cases: Amphotericin B. Not reportable.

Molds

• Aspergillus:

  • Pathophysiology: Produces aflatoxin, grows into surrounding tissue, can form an aspergilloma ("fungus ball"). Invasive aspergillosis commonly affects the lungs, but can spread to sinuses, CNS, eyes, etc.
  • Diagnosis: Common in respiratory tree. Positive cultures alone are insufficient. Galactomannan antigen detection test needed.
  • Allergic bronchopulmonary aspergillosis: Hypersensitivity to spores causing bronchiole inflammation and eosinophilia.
  • Treatment: Allergic forms: Itraconazole and prednisone, or voriconazole. Invasive: Voriconazole, surgical debridement of sinusitis/focal lesions. Not reportable.

• Mucormycosis ("Black Fungus"):

  • Risk factors: DM, cancer, immunosuppression, steroids.
  • Signs/symptoms: Commonly infects sinuses, eyes, and brain, often leading to tissue death due to vessel invasion.
  • Diagnosis: Biopsy, culture, imaging.
  • Treatment: Amphotericin B IV, surgical debridement. Poor prognosis (over 50% fatality). Not reportable.

Fungus/Protozoa

• Pneumocystis:
  • Etiology: Classified as both a protozoan and a fungal species.
  • Risk factors: HIV with CD4 <200, solid organ/stem cell transplant recipients, high-dose corticosteroids (chemotherapy, rheumatology).
  • Symptoms: Initial: fever, malaise, non-productive cough, progressing to sputum production, chest pain, chills, exertional dyspnea with hypoxia.
  • Imaging: Chest X-ray: diffuse bilateral interstitial infiltrates, "batwinging" appearance.
  • Diagnosis: Sputum sample, PCR, blood test (Beta-D-glucan). Not reportable.

Antifungal Medications

• Amphotericin B:

  • Mechanism: Binds sterols (primarily ergosterol), creating pores that leak cellular components. Targets not fungi-specific; humans have sterols too leading to side effects. Broad-spectrum; covers most yeasts, all dimorphic endemic fungi, and molds.
  • Side effects: Kidney injury (>20%), low electrolytes common.

• Azoles (e.g., Fluconazole, Itraconazole, Voriconazole, Posaconazole, Isavuconazole):

  • Mechanism: Inhibiting a cytochrome P450 enzyme needed for ergosterol synthesis.
  • Fluconazole: Good yeast coverage, CSF penetration, bioavailability. QTc prolongation possible.
  • Itraconazole: Yeast and dimorphics, no molds. PO only. Inconsistent bioavailability, no CSF penetration. QTc prolongation possible.
  • Voriconazole: Yeast, dimorphics, molds (aspergillus, not mucor). Good CSF penetration. QTc prolongation possible. Visual hallucinations (high levels) possible.
  • Posaconazole: Yeast, dimorphics, molds; oral absorption issues. QTc prolongation possible.
  • Isavuconazole: Similar spectrum to posaconazole, better bioavailability, QTc shortening.
  • Side effects: Significant drug-drug interactions, hepatotoxicity (monitor ALT, AST), prolonged QTc (except isavuconazole), and voriconazole visual hallucinations.
  • Best uses: Fluconazole (Candida albicans), Itraconazole (dimorphic endemic fungi), Voriconazole (aspergillus). Fungins: Invasive candidiasis, empiric fungal coverage (neutropenic fever). No dimorphics.