Infectious Disease · Pulmonary Mycoses
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Histoplasma capsulatum is associated with bird or bat droppings in the Ohio and Mississippi River valleys and presents with calcified hilar lymph nodes.
Coccidioides immitis is endemic to the desert Southwest and causes Valley fever, characterized by arthralgias, erythema nodosum, and erythema multiforme.
Blastomyces dermatitidis is found in decaying wood and soil and is characterized by broad-based budding yeast and verrucous skin lesions.
Cryptococcus neoformans is acquired via pigeon droppings and is the most common cause of fungal meningitis in patients with advanced HIV/AIDS.
Aspergillus fumigatus presents as an aspergilloma in pre-existing lung cavities or as invasive aspergillosis in neutropenic patients with septate hyphae branching at 45-degree angles.
Pneumocystis jirovecii pneumonia (PCP) presents with diffuse bilateral interstitial infiltrates and is diagnosed via silver stain of bronchoalveolar lavage fluid.
Mucor and Rhizopus species cause rhinocerebral mucormycosis in patients with diabetic ketoacidosis and present with black eschar on the nasal turbinates.
Vignette unlocked
A 45-year-old male with a history of poorly controlled diabetes mellitus presents to the emergency department with fever, facial pain, and nasal congestion. Physical examination reveals a necrotic black eschar on the nasal septum. The patient is currently in diabetic ketoacidosis. Microscopic examination of a biopsy from the lesion reveals broad, pauciseptate (sparsely septate) ribbon-like hyphae with wide-angle branching.
What is the most appropriate next step in management?
Urgent surgical debridement plus intravenous liposomal amphotericin B (≥5 mg/kg/day)
The vignette describes rhinocerebral mucormycosis, a life-threatening infection in DKA patients; the key is recognizing the association with non-septate hyphae and the necessity of urgent surgical intervention combined with antifungal therapy.
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Etiology / Epidemiology
Endemic fungi (Histoplasma, Coccidioides, Blastomyces) affect immunocompetent travelers; opportunistic fungi (Aspergillus, Cryptococcus) target immunocompromised hosts.
Clinical Manifestations
Subacute cough, fever, and weight loss. Valley fever (Coccidioides) presents with erythema nodosum; fungus ball (Aspergillus) shows cavitary lesions.
Diagnosis
Culture is the reference standard for most endemic and opportunistic mycoses, but *Pneumocystis* cannot be cultured and Mucorales are often culture-negative — for both, histopathology/stain is definitive. Antigen testing is the rapid diagnostic of choice — urine (± serum) Histoplasma antigen and serum cryptococcal antigen (CrAg).
Treatment
Itraconazole for mild-moderate histoplasmosis/blastomycosis; fluconazole for mild-moderate coccidioidomycosis; liposomal amphotericin B for severe/disseminated disease.
Prognosis
High mortality in neutropenic patients; dissemination to CNS or bone indicates poor outcomes.
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Epidemiology & Etiology
Histoplasma capsulatum is found in the Ohio/Mississippi River valleys (bird/bat droppings). Coccidioides immitis is endemic to the Southwestern US (desert soil). Blastomyces dermatitidis is associated with decaying wood and soil in the Great Lakes/Ohio River regions. Aspergillus is ubiquitous, causing disease primarily in patients with neutropenia or structural lung disease.
Pertinent Anatomy
Fungal spores are inhaled into the alveoli. Dissemination occurs via the hematogenous route, frequently targeting the CNS, skin, and bone. Cavitary lesions often localize to the lung apices.
Pathophysiology
Inhalation of conidia leads to a granulomatous inflammatory response. In immunocompromised hosts, the lack of T-cell mediated immunity allows for unchecked fungal proliferation. Aspergillus specifically exhibits angioinvasion, leading to tissue infarction and necrosis.
Clinical Manifestations
Patients present with chronic, non-resolving pneumonia. Valley fever (Coccidioides) is marked by erythema nodosum and arthralgias. Fungus ball (Aspergillus) presents with hemoptysis and a mobile mass on imaging. Respiratory failure and meningitis are critical red flags requiring immediate intervention.
Diagnosis
Culture is the reference standard for most endemic and opportunistic mycoses (*Pneumocystis* cannot be cultured; Mucorales are often culture-negative). Antigen testing provides rapid, high-sensitivity results — urine (± serum) Histoplasma antigen and serum cryptococcal antigen (CrAg). Galactomannan assay is the diagnostic marker for invasive aspergillosis.
Treatment
Itraconazole is the preferred azole when antifungal treatment is indicated; per IDSA 2025, mild acute pulmonary histoplasmosis in immunocompetent hosts is generally observed without antifungals, and moderate disease is treated selectively. Fluconazole (400–1,200 mg daily, lifelong) is the preferred initial therapy specifically for coccidioidal meningitis. CNS histoplasmosis and cryptococcal meningitis require liposomal amphotericin B–based induction first — azoles are used only for consolidation. Amphotericin B is reserved for severe, life-threatening infections; invasive aspergillosis is treated first-line with voriconazole or isavuconazole, not amphotericin B. Nephrotoxicity is the primary dose-limiting side effect of amphotericin B deoxycholate; liposomal formulations are substantially less nephrotoxic.
Prognosis
Prognosis depends on the host's immune status. Disseminated disease carries a high mortality rate. Long-term monitoring for relapse is required in patients with chronic underlying lung disease.
Differential Diagnosis
Tuberculosis: apical cavitation with night sweats
Bacterial pneumonia: acute onset with lobar consolidation
Lung cancer: persistent mass with weight loss and smoking history
Sarcoidosis: bilateral hilar adenopathy without fever
Pneumocystis jirovecii: diffuse ground-glass opacities in HIV