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4. Histoplasma
Histoplasma is a dimorphic fungus that causes one of the most common respiratory fungal illnesses worldwide. Highly endemic regions in the United States include the Ohio and Mississippi river valleys and around the world including parts of South America, Central and Southern Africa, and Western Asia. Respiratory symptoms develop after inhalation of Histoplasma and conversion from the ambient environmental mycelial form to the yeast-like form, which can take several hours to days. The differential for yeast organisms includes Blastomyces, Cryptococcus, and Coccidioses. Severity of infection depends on the immune status of the individual, number of spores inhaled, and virulence of the particular strain. Most illnesses are self-limited and asymptomatic but it can progress to severe, life-threatening illness particularly in susceptible individuals. Symptomatic histoplasmosis typically presents as a flu-like illness with symptoms including fevers, chills, malaise, headache, myalgias, non-productive cough, and chest pain. A small proportion of patients can present with arthritis and arthralgias with characteristic erythema multiforme or erythema nodosum, as well as pericarditis, rarely. Mediastinal lymph nodal disease is common - ranging from mediastinal adenitis (early in disease) to mediastinal granuloma and fibrosing mediastinitis as two distinct, but late complications. Disseminated disease is more common in individuals with malignancy, immunosuppression, corticosteroid use, or HIV. Pathogenesis of disease in this sub-group of patients usually involves tempered cellular immune response from blunted T-cell number and or function secondary to either low CD4 counts (such as in HIV/AIDS), use of corticosteroids, calcineurin inhibitors, or TNF-blocking agents.
Gold standard for diagnosis is made with culture although growth can be slow (up to 1 month) or negative in up to 50% of respiratory cultures. Serology techniques that detect antibodies or antigen is available for rapid detection however, cross-reactivity exists between Histoplasma and other endemic fungal diseases.
The patient was started on therapy which included itraconazole. Over the next few weeks, he developed initially improved symptoms but then had worsening shortness of breath, orthopnea, and lower extremity edema. He then was readmitted to the hospital.
Which of the following diagnostic tests would be indicated to evaluate for a potentially rare, but serious side effect of itraconazole? (Click on the correct answer to be directed to the seventh and final page)