A 47-year-old woman comes to the physician because of a 3-day history of fever, fatigue, loss of appetite, cough, and chest pain. Physical examination shows diffuse inspiratory crackles over the left lung field. An x-ray of the chest shows hilar lymphadenopathy and well-defined nodules with central calcifications. Urine studies show the presence of a polysaccharide antigen. A biopsy specimen of the lung shows cells with basophilic, crescent-shaped nuclei and pericellular halos located within macrophages. This patient's history is most likely to show which of the following?

Previous mycobacterial infection

Treatment with inhaled glucocorticoids

A 43-year-old type 1 diabetic woman who is poorly compliant with her diabetes medications presented to the emergency department with hemorrhage from her nose. On exam, you observe the findings shown in figure A. What is the most likely explanation for these findings?

Gram negative bacterial infection

A 58-year-old man presents with a high-grade fever, throbbing left-sided headache, vision loss, and left orbital pain. He says that his symptoms started acutely 2 days ago with painful left-sided mid-facial swelling and a rash, which progressively worsened. Today, he woke up with complete vision loss in his left eye. His past medical history is significant for type 2 diabetes mellitus, diagnosed 5 years ago. He was started on an oral hypoglycemic agent which he discontinued after a year. His temperature is 38.9°C (102.0°F), blood pressure is 120/80 mm Hg, pulse is 120/min, and respiratory rate is 20/min. On examination, there is purulent discharge from the left eye and swelling of the left half of his face including the orbit. Oral examination reveals extensive necrosis of the palate with a black necrotic eschar and purulent discharge. Ophthalmic examination is significant for left-sided ptosis, proptosis, and an absence of the pupillary light reflex. Laboratory findings are significant for a blood glucose level of 388 mg/dL and a white blood cell count of 19,000 cells/mm³. Urinary ketone bodies are positive. Fungal elements are found on a KOH mount of the discharge. Which of the following statements best describes the organism responsible for this patient’s condition?

Histopathological examination shows non-septate branching hyphae

It appears as a narrow-based budding yeast with a thick capsule

It has budding and filamentous forms

Histopathological examination shows acute angle branching hyphae

A 29-year-old woman comes to the military physician because of a 2-day history of fever, joint pain, dry cough, chest pain, and a painful red rash on her lower legs. Two weeks ago, she returned from military training in Southern California. She appears ill. Her temperature is 39°C (102.1°F). Physical examination shows diffuse inspiratory crackles over all lung fields and multiple tender erythematous nodules over the anterior aspect of both legs. A biopsy specimen of this patient's lungs is most likely to show which of the following?

Spherules filled with endospores

Septate hyphae with acute-angle branching

Encapsulated yeast with narrow-based budding

Oval, budding yeast with pseudohyphae

Clinical presentations of dimorphic fungal infections for USMLE Step 2 CK: High-Yield Microbiology Lessons

Dimorphic Fungi - Two-Faced Pathogens

Histoplasma: Bird/bat droppings. Mimics TB (calcified granulomas). Hepatosplenomegaly in disseminated disease (immunocompromised).
Blastomyces: Pulmonary disease. Extrapulmonary: skin (verrucous lesions), bone (osteomyelitis).
Coccidioides: "Valley Fever" - flu-like illness, erythema nodosum, arthralgias.
Paracoccidioides: Latin America. Pulmonary; mucocutaneous ulcers (oral/nasal).
Sporothrix schenckii: "Rose gardener's disease" - local pustule/nodule with ascending lymphangitis.

⭐ Blastomycosis is notorious for skin and bone lesions. Think "B" for Broad-based budding, Blasto, Bone, and Bad skin.

Histo & Coccidio - The Dust Devils

Transmission: Inhalation of spores from soil disturbed by construction, farming, or dust storms.
Immunity: Primarily T-cell mediated (CD4+); infections are worse in immunocompromised.

Feature	Histoplasmosis (Histo)	Coccidioidomycosis (Coccidio)
Geography	Mississippi & Ohio River Valleys	Southwestern US, Northern Mexico
Source	Bird/bat droppings (caves, coops)	Dust, soil (earthquakes, dust storms)
Primary	Most asymptomatic. Flu-like illness, pneumonia.	"Valley Fever": flu-like, arthralgias, erythema nodosum.
Disseminated	Immunocompromised (AIDS < 100 CD4). Hepatosplenomegaly, pancytopenia, palatal/tongue ulcers.	Any patient. Skin, bone/joint, meningitis.
Imaging (CXR)	Hilar lymphadenopathy, calcified granulomas (like TB).	Often normal; can show nodules, infiltrates, or thin-walled cavities.
Microscopy	Small, oval yeast within macrophages.	Large spherules containing endospores.

⭐ Erythema nodosum (painful nodules on shins) is a classic sign of an acute Coccidioidomycosis infection, indicating a robust immune response.

Blasto & Para - Broad Buds & Captain's Wheels

Blastomycosis (Blastomyces dermatitidis)
- Microscopy: Large yeast with Broad-Based Budding.
- Geography: Eastern/Central US (Ohio & Mississippi River Valleys, Great Lakes).
- Presentation:
  - Pulmonary: Acute or chronic pneumonia; can mimic TB or malignancy.
  - Disseminated:
    - Skin: Verrucous (wart-like) or ulcerative lesions.
    - Bone: Osteomyelitis.
    - GU: Prostatitis.
- 📌 Mnemonic: Blasto Buds Broadly.
Paracoccidioidomycosis (Paracoccidioides brasiliensis)
- Microscopy: Large yeast with multiple buds; "Captain's Wheel" appearance.
- Geography: Central & South America.
- Presentation:
  - Pulmonary: Often asymptomatic or chronic cough.
  - Mucocutaneous: Painful ulcers in the mouth & nose.
  - Lymphadenopathy: Common.

Paracoccidioides brasiliensis 'captain's wheel' yeast

⭐ In Blastomycosis, skin and bone involvement are the most common sites of extrapulmonary dissemination, often presenting as painless verrucous lesions or lytic bone lesions.

Sporothrix - Rose Gardener's Curse

Source: Associated with trauma from rose thorns, sphagnum moss, or hay.
Primary Lesion: Begins as a painless papule or nodule at the inoculation site.
Lymphocutaneous Spread: The hallmark presentation.
- Nodules develop sequentially along lymphatic channels, creating a linear, cord-like distribution.
- These may ulcerate over time.
Disseminated: Rare; can affect joints, lungs, or CNS in immunocompromised individuals.

⭐ Histology: Look for asteroid bodies and cigar-shaped budding yeasts.

Lymphocutaneous sporotrichosis with linear nodules

High‑Yield Points - ⚡ Biggest Takeaways

Dimorphic fungi exist as mold in the cold (environment) and yeast in the heat (body).

Infection is primarily via inhalation of spores, often leading to asymptomatic or flu-like pulmonary illness.

Disseminated disease is a major risk in immunocompromised patients.

Histoplasma is found within macrophages and is associated with bird and bat droppings.

Blastomyces is known for broad-based budding and dissemination to skin and bone.

Coccidioides forms spherules containing endospores and is endemic to the Southwestern US.

Paracoccidioides has a distinctive "captain's wheel" budding appearance.

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