A 24-year-old male presented with a 4-day cough, fever, chills, sweats, and muscle pain. Physical exam found decreased breath sounds bilaterally and a rash on his legs. Chest X-ray and bronchoalveolar lavage found small budding yeast forms, diagnosing histoplasmosis. Histoplasma capsulatum is a dimorphic fungus endemic to the Mississippi and Ohio valleys. It can cause asymptomatic or self-limited infection but disseminated disease in immunocompromised individuals. Treatment involves antifungals like itraconazole or amphotericin B depending on severity.

1. Case Presentation
A 24 year old white male presented to the ED in
Indianapolis, IN with a persistent cough for the
past 4 days. Upon further questioning, he states
that he has also had a mild fever (101), chills,
sweats, and muscle pain. He has also noticed a
rash on his lower legs.

2. History
• Meds: None
• Allergies: Penicillin
• PMHx: community acquired pneumonia 4 years ago – outpatient
• PSHx: Appendectomy 2 years ago
• Social Hx: Computer programmer for IBM, denies drugs and tobacco, significant
EtOH when IU basketball dominates a big ten foe, enjoys taking pictures of bats in
caves
• Family Hx: mom – HTN, CAD, and Type I DM; dad – HTN and prior CVA

3. Physical Exam
• GENERAL APPEARANCE: alert, talkative, actively coughing, in no distress
• VITAL SIGNS: T - 97.5, BP 110/60, respirations 22, and HR 88
• HEENT: Head is normocephalic and atraumatic. Extraocular muscles are intact.
Pupils are equal, round, and reactive to light and accommodation. Nares appeared
normal. Mucous membranes are moist. Posterior pharynx clear of any exudate or
lesions.
• NECK: Supple. No carotid bruits. No lymphadenopathy or thyromegaly.
• LUNGS: mild tachypnea, decreased breath sounds and dullness to percussion
bilaterally in middle and lower lobes, no wheeze appreciated
• HEART: Regular rate and rhythm without murmur.
• ABDOMEN: Soft, non-tender, and non-distended. Normal bowel sounds. No
hepatosplenomegaly or palpable masses were noted.
• NEUROLOGIC: Cranial nerves II through XII are grossly intact, 5/5 strength in UE
and LE, DTR normal
• SKIN: Erythematous, tender macules diffusely on both lower extremities; otherwise
normal

5. Differential Diagnosis?
• Tuberculosis
• Pneumonia (bacterial vs viral vs fungal)
• Pneumocystis carinii pneumonia
• Histoplasmosis
• Blastomycosis
• Malignancy

6. Evaluation
• What labs, imaging, or procedures would be appropriate?

7. Labs
• CBC: WBC 13,000 cells/mm3, Hgb. 13.4, PLTS 350,000/mm3
• BMP: Na 140, K 4.5, Cl 101, HCO3 23, BUN 20, Cr 1.5, Glucose 101
• ABG: pH 7.4, pCO2 31, pO2 85
• Blood cultures: pending
• Sputum stain: No organisms seen on stain,
• Cultures pending

8. Chest PA Radiograph

9. Bronchoalveolar Lavage
Small (2–5 nm) narrow
budding yeast forms
(Grocott's methenamine
silver stain)

10. Diagnosis?
Histoplasma capsulatum
(picture shows
environmental form)

11. Etiology and Epidemiology
• Thermal, dimorphic fungus that exist as microconidia and macroconidia
• Microconidia (2–4 um) are small enough to reach alveoli
• Shortly after infection host, conidia transform into yeast-like forms
• Yeast forms are 2–5 mcg, with NARROW WAISTED BUDDING
• Most prevalent endemic mycosis in
North America
• Most prevalent in Mississippi and
Ohio valleys
• This geographic pattern is due to
humid and acidic nature of soil
• Soil enriched with bird and bat
droppings promotes growth and
sporulation of histoplasma
• Spelunking, excavation, cleaning of
chicken coops, demolition and
remodeling of old buildings are
activities with high level of exposure

12. Pathogenesis
• Inhaled microconidia reach alveoli and are phagocytosed by alveolar
macrophages within which they transform into yeast forms. Transformation is a
requisite for pathogenesis
• Yeasts replicate within macrophages within which they are disseminated
hematogenously
• Yeasts utilize the macrophage’s phagosome as a vehicle to translocate to
hilar/mediastinal lymph nodes
• Histoplasma specific cellular immunity develops in immunocompetent at 2
weeks.
• Cells produce IFN gamma to assist macrophages in killing the organism
• In immunocompotent hosts, macrophages, lymphocytes, and epithelial cells
organize and form granulomas that contain the organism, which typically fibrose
and calcify

13. A, Laminated Histoplasma granuloma of the lung.
B, Histoplasma capsulatum yeast forms fill phagocytes in the lung of a patient with
disseminated histoplasmosis (silver stain)

14. Manifestations in
Immunocompetent Host
• Most common is no manifestation = completely asymptomatic
• Of adults residing in endemic areas, 50–80% have skin-test and/or radiographic
evidence of previous infection without clinical manifestations (incidental CXR
finding is ~ 95%)
• Radiographs can demonstrate normal architecture OR an infiltrate with
hilar/mediastinal adenopathy with focal calcifications (typically a late
manifestation)
• Non-specific febrile illness
• Rheumatologic s/x
– Mild joint infl., ± erythema nodosum/multiforme (5-10%)
• Back/chest pain
• Weight loss if ill > 2wks
• Majority are self-limited

15. Manifestations in
Immunocompromised Host
• In patient with an underlying cellular immunity deficiency (HIV and
immunosuppressive medications), patient will not recover and can develop
progressive disseminated histoplasmosis (PDH)
• Common risk factors include AIDS (CD4+ T cell count <200/L), extremes of age,
and the use of immunosuppressive medications such as prednisone, methotrexate,
and anti-TNF- agents (listen to TV commercials about rheumatoid arthritis meds…
“be sure to tell your doctor if you live in areas with certain fungal infections”)
• Common manifestations: weight loss, fever, hepatosplenomegaly, brain lesions,
oral mucosal ulcerations, GI ulcers, adrenal insufficiency, and death

16. Treatment
• Most patients will recover without therapy, however, itraconazole should be
considered if the patient’s condition has not improved after 1 month
• In patients with a moderate to severe case of acute pulmonary histoplasmosis and
PDH, a lipid emulsion of amphotericin B with glucocorticoids is given for 1- 2
weeks, then intraconazole for 12 weeks
• Be sure to monitor renal and hepatic function for medication side effects