A 47-year-old man comes to the emergency department due to 3 weeks of malaise, nonproductive cough, fatigue, and shortness of breath. Last night, he sweat through his pajamas and had to get out of bed to change his clothes. The patient smokes cigarettes and has no recent travel or sick contacts. He works on a farm in rural Mississippi. Temperature is 38.1 C (100.5 F). Cardiopulmonary examination is normal. There are several erythematous, tender nodules approximately 2-3 cm in diameter over both shins. Chest x-ray reveals bilateral, patchy opacities and enlarged mediastinal and hilar lymph nodes. Tuberculin skin testing and HIV testing are negative. Transbronchial biopsy of one of the lymph nodes shows noncaseating granulomas. No organisms are seen. The patient is diagnosed with pulmonary sarcoidosis, and high-dose corticosteroids are initiated. However, he deteriorates rapidly over 48 hours and requires intubation and mechanical ventilation; a chest x-ray reveals progression of the pulmonary infiltrates. Which of the following is the most likely diagnosis?
Epidemiology and extrapulmonary clinical manifestations of endemic mycoses | ||
Syndrome | Epidemiology | Clinical clues |
Blastomycosis | Mississippi/Ohio River Valley Midwestern United States |
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Histoplasmosis | Mississippi/Ohio River Valley Central & South America |
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Coccidioidomycosis | Southern Arizona/California Northern Mexico |
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This patient was treated for pulmonary sarcoidosis with high-dose corticosteroids due to the presence of erythema nodosum, pulmonary infiltrates, hilar/mediastinal lymphadenopathy, and biopsy evidence of noncaseating granulomas. However, treatment resulted in a rapid deterioration in pulmonary status, which suggests an infectious etiology that worsened due to steroid-induced immune suppression. Common causes of granulomatous pulmonary infections include tuberculosis, blastomycosis, and histoplasmosis.
This patient's vocation as a farmer in rural Mississippi puts him at risk for Histoplasma capsulatum, a dimorphic fungus that proliferates in soil contaminated by bird or bat droppings. H capsulatum is endemic to temperate areas worldwide but is found primarily in the central/southern United States and parts of South America, Asia, and Africa. In patients from these regions, pulmonary histoplasmosis should be considered in the setting of community-acquired pneumonia with mediastinal/hilar lymphadenopathy, arthralgias, and/or erythema nodosum. Although Histoplasma urinary antigen testing is the most rapid method of diagnosis, tissue biopsy is sometimes required; histopathologic samples may reveal caseating (most common) or noncaseating granulomas.
(Choice A) Aspergillosis can cause pulmonary infiltrates and mediastinal lymphadenopathy in immunocompromised patients (eg, prolonged neutropenia) but is quite uncommon in those with intact immunity. In addition, histopathology typically shows septate hyaline hyphae with dichotomous acute angle branching.
(Choice B) Although Coccidioides can cause pulmonary infiltrate with hilar/mediastinal lymphadenopathy and erythema nodosum, it is endemic to the southwestern United States, the deserts of Mexico, and South/Central America; it is not common in Mississippi. Given that this patient has no history of travel, it is unlikely that he was exposed to Coccidioides.
(Choice D) Hypersensitivity pneumonitis is common in farmers and can cause pulmonary symptoms, malaise, and noncaseating granulomas. However, almost all cases would improve, not worsen, with corticosteroid therapy.
(Choice E) Although tuberculosis (TB) can present similarly and would likely worsen with corticosteroids, this patient had negative tuberculin skin testing and noncaseating granulomas on histopathology (TB causes caseating granulomas). This makes TB less likely than H capsulatum.
Educational objective:
Histoplasmosis can mimic the presentation of sarcoidosis and should be considered when a patient with suspected sarcoidosis deteriorates after immunosuppressive therapy. In endemic regions, dimorphic fungi (eg, Histoplasma, Blastomyces, Coccidioides) should be excluded before immunosuppression is initiated.