A 47-year-old African American farmer from Mississippi has a 3-week history of malaise, nonproductive cough, fatigue, and shortness of breath. He is seeking care as he "sweat right through" his shirt the previous night. He is an active smoker with no recent travel or sick contacts. His temperature is 38.1 C (100.5 F). Cardiopulmonary examination is normal. The patient has several erythematous, tender nodules approximately 2-3 cm in diameter over both shins. Chest x-ray shows bilateral patchy opacities and enlarged mediastinal and hilar lymph nodes. Tuberculin skin testing and HIV testing are negative, and serial sputum samples are negative for acid-fast bacilli. Transbronchial biopsy of one of the lymph nodes shows non-caseating granulomas. No organisms are seen with Gram staining and staining for acid-fast bacilli. The patient is diagnosed with pulmonary sarcoidosis, and high-dose corticosteroids are initiated. However, he deteriorates rapidly over the subsequent 48 hours. He is intubated and mechanically ventilated; a chest x-ray reveals progression of the pulmonary infiltrates. Which of the following is the most likely diagnosis?

Question

A 47-year-old African American farmer from Mississippi has a 3-week history of malaise, nonproductive cough, fatigue, and shortness of breath.  He is seeking care as he "sweat right through" his shirt the previous night.  He is an active smoker with no recent travel or sick contacts.  His temperature is 38.1 C (100.5 F).  Cardiopulmonary examination is normal.  The patient has several erythematous, tender nodules approximately 2-3 cm in diameter over both shins.  Chest x-ray shows bilateral patchy opacities and enlarged mediastinal and hilar lymph nodes.  Tuberculin skin testing and HIV testing are negative, and serial sputum samples are negative for acid-fast bacilli.  Transbronchial biopsy of one of the lymph nodes shows non-caseating granulomas.  No organisms are seen with Gram staining and staining for acid-fast bacilli.  The patient is diagnosed with pulmonary sarcoidosis, and high-dose corticosteroids are initiated.  However, he deteriorates rapidly over the subsequent 48 hours.  He is intubated and mechanically ventilated; a chest x-ray reveals progression of the pulmonary infiltrates.  Which of the following is the most likely diagnosis?

Quizplus · Accepted Answer

Histoplasmosis is the most likely diagnosis in this patient from Mississippi who was initially thought to have sarcoidosis (cough, hilar adenopathy, erythema nodosum, and non-caseating granulomas in an African American individual) but deteriorated following high-dose corticosteroid therapy. The patient's rapid decompensation suggests untreated infection; given the granulomas, infections such as tuberculosis (TB) or one of the TB-mimicking diseases (eg, histoplasmosis, blastomycosis) are possibilities. In regions where these organisms are endemic, infection must be excluded before immunosuppressive therapy is initiated. non-caseating granulomas Histoplasma capsulatum (present as mold in soil and in bird and bat droppings) is endemic to the Mississippi and Ohio River basins. In an appropriate epidemiologic setting, pulmonary histoplasmosis should be considered when pulmonary symptoms are accompanied by mediastinal or hilar lymph nodes (or masses) or by arthralgias and erythema nodosum. Disseminated histoplasmosis in immunocompromised patients can present with lymphadenopathy, pancytopenia, and hepatosplenomegaly as the organism targets histiocytes and the reticuloendothelial system. Caseating granulomas are most common, but non-caseating granulomas (as seen in this patient) may be the only finding. Careful fungal tissue stains and culture, along with Histoplasma urinary antigen testing, are used for diagnosis. Mississippi and Ohio River basins Blastomyces (associated with contact with soil or rotting wood, with dissemination in immunocompromised hosts presenting as skin lesions, osteolytic bone lesions, or prostate involvement) is also present in Mississippi and should be excluded in this patient. However, hilar adenopathy is more suggestive of histoplasmosis. (Choice A) Aspergillosis can cause pulmonary infiltrates and mediastinal adenopathy in immunocompromised patients; it is a leading cause of pneumonia in patients with prolonged neutropenia. Aspergillosis is not a likely cause of pulmonary infection in an immunocompetent individual. (Choice B) Coccidioides is found in the southwestern United States, not in Mississippi. Given that this patient has no history of travel, it is unlikely that he was exposed to Coccidioides. (Choice D) Hypersensitivity pneumonitis can form non-caseating granulomas in time, but symptoms caused by a hypersensitivity reaction should improve with corticosteroid therapy rather than worsen. (Choice E) A thorough workup that included skin testing, serial sputum testing, and lymph node biopsy with acid-fast bacilli staining was negative, making TB less likely. Educational objective: Histoplasmosis closely mimics 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. References: Overview of histoplasmosis. (http://www.ncbi.nlm.nih.gov/pubmed/12507161) Endemic mycoses: overlooked causes of community acquired pneumonia. (http://www.ncbi.nlm.nih.gov/pubmed/22386326) Role of histology in the diagnosis of infectious causes of granulomatous lung disease. (http://www.ncbi.nlm.nih.gov/pubmed/21346573)

A 47-Year-Old African American Farmer from Mississippi Has a 3-Week