STEPTRACKERMICROBIOLOGY + PULMONOLOGY | SYSTEMIC MYCOSES | HIGH-YIELD REVIEW

Systemic Dimorphic Mycoses

Fungi that are molds in the soil and yeasts (or spherules) in the body — inhaled spores, a geographic clue, granulomas, and disease that mimics TB.

FOCUS ON
Dimorphism: mold at environmental temperature, yeast at 37 °C — except Coccidioides, which forms spherules filled with endospores. Histoplasma: Ohio/Mississippi River valleys, bird and bat droppings (caves), small yeast inside macrophages. Blastomyces: east of the Mississippi and Great Lakes, broad-based budding yeast, lung + skin + bone. Coccidioides: Southwest US desert dust, earthquakes → valley fever, erythema nodosum. Paracoccidioides: Latin America, "ship's wheel" budding. Mild disease → itraconazole/fluconazole; severe → amphotericin B.
FUNGUS
GEOGRAPHY · SOURCE
DISEASE
TISSUE FORM · TREATMENT
Histoplasma capsulatum
Ohio and Mississippi River valleys; bird or bat droppings (caves, chicken coops, demolition)
Mostly asymptomatic or flu-like pneumonia; hilar nodes, calcified granulomas; chronic cavitary in COPD; disseminated in AIDS (pancytopenia, oral ulcers, hepatosplenomegaly)
Small oval yeast within macrophages · urine/serum antigen · itraconazole; amphotericin if severe
Blastomyces dermatitidis
Eastern US, Great Lakes, Ohio/Mississippi valleys; moist soil, woods, rivers
Pneumonia (can mass-like mimic cancer) → verrucous skin lesions, lytic bone lesions, prostatitis
Large yeast with thick double-contoured wall, broad-based budding · itraconazole
Coccidioides immitis / posadasii
Southwest US (Arizona, California's San Joaquin Valley), Mexico; dust storms, construction, earthquakes
Valley fever: pneumonia, fatigue, arthralgia ("desert rheumatism"), erythema nodosum; dissemination to skin, bone, meninges
Spherules with endospores · fluconazole · ↑ dissemination in pregnancy, Filipino/Black patients, immunosuppression
Paracoccidioides brasiliensis
Central and South America; agricultural workers
Chronic lung disease, oral mucosal ulcers, lymphadenopathy
Yeast with multiple buds ("ship's wheel") · itraconazole
Sporothrix schenckii
Thorn prick (rose gardening), sphagnum moss, hay; cat scratches
Papule at inoculation → nodules ascending along lymphatics (lymphocutaneous); rarely lung
Cigar-shaped yeast · itraconazole (or potassium iodide)
Talaromyces marneffei
Southeast Asia; bamboo rats
Disseminated disease in AIDS: fever, umbilicated skin papules
Mimics molluscum · amphotericin
Granulomatous response
Macrophages + Th1 (IFN-γ) contain yeast
Caseating or non-caseating granulomas, calcify when healed
Dissemination when T-cell immunity falls (AIDS, TNF-α inhibitors, steroids)
Diagnosis
Culture is slow; mold phase is a lab biohazard (Coccidioides)
Antigen tests, serology, histology (silver, PAS stains)
Histoplasma antigen cross-reacts with Blastomyces
Treatment ladder
Severity and host decide
Mild: observe or azole · severe/disseminated/CNS: amphotericin B then azole
Coccidioidal meningitis: lifelong fluconazole

Picture it — what each one looks like in tissue

tiny yeast inside a macrophage
HistoplasmaSmall oval yeasts packed inside macrophages.
broad basethick double wall, broad-based bud
BlastomycesLarge yeast with a thick, refractile wall and a broad-based bud.
spherule full of endospores
CoccidioidesLarge spherule that ruptures to release endospores — not a yeast.
many buds — ship's wheel
ParacoccidioidesMother cell ringed by many small buds.

Schematic diagrams, not to scale.

Mechanism — why these cause disease in healthy people

Inhaled conidia (mold)
→
Body heat → yeast/spheruleToo big or protected for easy killing
→
Macrophage + Th1 granulomas
→
Contained · or disseminate if T cells fail

Tell them apart

FUNGUS
REGION
TISSUE FORM
EXTRAPULMONARY
Histoplasma
Ohio/Mississippi
Small yeast in macrophages
Oral ulcers, adrenal, marrow
Blastomyces
East + Great Lakes
Broad-based bud
Skin, bone, prostate
Coccidioides
Southwest desert
Spherule + endospores
Skin, bone, meninges
Paracoccidioides
Latin America
Multiple buds
Mouth, nodes

How it's tested

COMMON CONFUSIONHilar adenopathy with calcified granulomas may be histoplasmosis, sarcoidosis or old TB — the cave or bird-roost exposure points to Histoplasma.
THE TRAPErythema nodosum in valley fever is a good sign (strong cell-mediated immunity), not a sign of dissemination.
YOUR APPROACHExposure + geography → fungus → tissue form on biopsy → host immunity → azole vs amphotericin.

If you see… think…

Spelunker from Kentucky with pneumonia and hilar nodes → Histoplasma
Small yeast packed inside macrophages → Histoplasma
AIDS patient with pancytopenia, oral ulcers, ⁺ urine antigen → disseminated histoplasmosis
Pneumonia + warty skin lesions in Wisconsin → Blastomyces
Thick-walled yeast with broad-based bud → Blastomyces
Arizona construction worker with pneumonia and erythema nodosum → Coccidioides
Spherules full of endospores → Coccidioides
Yeast with many buds like a ship's wheel → Paracoccidioides
Rose gardener with nodules climbing the arm → Sporothrix
Disseminated dimorphic infection after starting infliximab → loss of TNF-α–dependent granulomas