Histoplasmosis

Clinical Features

• Acute Pulmonary:
  • Flu-like syndrome: Fever, chills, nonproductive cough, substernal chest pain.
  • Extrapulmonary hypersensitivity signs: Erythema nodosum, erythema multiforme, polyarthralgias.
• Chronic Cavitary Pulmonary:
  • Mimics TB: Chronic productive cough, hemoptysis, night sweats, weight loss (predominantly in underlying COPD/emphysema).
• Disseminated Histoplasmosis (Immunocompromised): H. capsulatum is an intracellular parasite of the monocyte-macrophage system, will disseminate via blood/lymphatics and deposit
  • Systemic: High fevers, severe weight loss, night sweats.
  • Reticuloendothelial system: Hepatosplenomegaly, generalized lymphadenopathy.
  • Mucocutaneous: Painful oral mucosal ulcers / tongue erosions, petechiae. c
  • Endocrine: Adrenal insufficiency (flank pain, hypotension, hyponatremia, hyperkalemia).

Diagnose

• Initial / Screening Test:
  • Urine and Serum Histoplasma Antigen ELISA (rapid, highest sensitivity for acute pulmonary and disseminated disease).
• Confirmatory / Gold Standard:
  • Fungal Culture (sputum, blood, bone marrow, tissue) or Histopathology.
  • Histopathology (Wright-Giemsa or Silver stain): Small (2-5 µm) intracellular oval yeasts inside macrophages (“Histo Hides in macrophages”).
• Key Labs:
  • Cytopenias (pancytopenia secondary to bone marrow infiltration).
  • ↑ LFTs (alkaline phosphatase, total bilirubin).
  • ↑ LDH and ↑ Ferritin (marked elevation in severe disseminated disease).
• Imaging:
  • CXR / Chest CT:
    • Acute: Patchy/reticulonodular infiltrates with hilar/mediastinal lymphadenopathy.
    • Chronic/Old: Buckshot calcifications (calcified pulmonary granulomas and splenic calcifications).
    • Chronic Cavitary: Apical cavity lesions.

Differential Diagnostics

• Tuberculosis (TB):
  • Diff by (+) PPD / IGRA, acid-fast bacilli (AFB) on stain, cavitary lesions typically apical, no fungal antigen.
• Blastomycosis:
  • Diff by large broad-based budding yeast, endemic to Great Lakes/Ohio River, prominent verrucous/ulcerative skin lesions and osteolytic bone lesions.
• Coccidioidomycosis:
  • Diff by large spherules containing endospores, Southwest US (San Joaquin Valley/Arizona), desert dust exposure, peripheral eosinophilia.
• Sarcoidosis:
  • Diff by non-caseating granulomas, ↑ ACE levels, bilateral hilar lymphadenopathy without infectious etiology or fungal antigen; improves with steroids (steroids worsen untreated histoplasmosis).
• Pneumocystis jirovecii Pneumonia (PJP):
  • Diff by diffuse bilateral ground-glass infiltrates, silver stain showing cup-shaped cysts, lack of hepatosplenomegaly or oral ulcers.