Correct!
3. Transthoracic Echocardiogram
A potentially rare, but serious side effect of itraconazole therapy is development of itraconazole-induced cardiotoxicity in the form of acute or acute-on-chronic congestive heart failure. The exact mechanism remains unclear however negative inotropy through mitochondrial dysfunction has been implicated in animal models. Multiple case reports have detailed this rare side effect that largely improves after cessation of drug therapy.
Our patient demonstrated a moderately reduced ejection that was new compared to 3 months prior. He underwent cardiac catheterization which ruled out ischemic heart disease. After careful review of his recent medical history, itraconazole was implicated as a cause of his new heart failure. He was stopped on this medication and switched to isavuconazole which has demonstrated in vitro activity in treating Histoplasma. Other azoles, including fluconazole, ketoconazole, posaconazole, and voriconazole all have some variable rates of efficacy against Histoplasma; however, none have been adequately studied in robust clinical trials. Second line therapy should be selected with the expert guidance of Infectious Disease specialist.
Clinical Pearls
Patient Course
Our patient was identified as having acute disseminated histoplasma on basis of pathological review of his CT-guided biopsy of his omentum which showed rare yeast with narrow based budding. On further questioning, he identified that he had lived in the Ohio River Valley many years ago. Further, he had cleaned the roof of his house which was full of bird droppings approximately 2 years prior to presentation.
Additional workup and expert consultation were sought for his pathology slides which demonstrated PCR+ for histoplasma. A urine antigen for histoplasma came back elevated, eventually.
While undergoing first line treatment with itraconazole, he developed non-ischemic cardiomyopathy and congestive heart failure requiring change of medication to a second-line therapy, isavuconazole, under the expert guidance of Infectious Disease. He continued isavuconazole for a year and repeat CT chest showed complete resolution of his tree-in-bud opacities. His urinary histoplasma antigen has remained negative.
References