A copy of the winning poster in the Iowa Society of Hospital Medicine Poster Competition

1. Kody Kasten, OMS-IV1; Matthew Fabiszak, DO1; Aneesa Afroze, MD, MPH, FACP2
Conclusion
Infective endocarditis is an uncommon manifestation of infection with Histoplasma
capsulatum. The diagnosis is frequently missed, and outcomes historically have
been poor. It is unusual for Histoplasma to be observed in both morphologies as a
mold and a yeast form in the human host with the rare exception of on heart
valves, as found in this patient. Histoplasma endocarditis is a serious condition that
requires hospitalization and a team-based approach involving both medical and
surgical teams.
A Rare, but Hearty, Case of Dimorphic Histoplasmosis in Vivo
Figure 2 – Pathology slides showed abundant fungal hyphae consistent with Candida by
PAS and GMS stains.
Figure 3 – Second request to evaluate given previous bone marrow findings concerning
for Histoplasma. Slide additionally shows small intracellular pill shaped yeast suggestive of
Histoplasma by PAS and GMS stains.
Case Presentation
HPI
Histories
• PMH: Dementia, HTN, HLD, coronary artery disease, osteoarthritis
• PSH: Aortic valve replacement in 2011, pacemaker, hip replacement,
cervical spine fusion, L2-L5 decompression
• SH: Former smoker, no alcohol abuse, Married and lives with his wife,
farmer with exposure to cattle, sheep, and frequent gardening
Outside
Hospital
• MRI Head: Multiple small bihemispheric punctate infarcts consistent with
embolic source
• TTE: Large aortic valve vegetation (1.1 x 1.6 cm) on the prosthetic valve
• Pancytopenia  Bone marrow biopsy: Granulomatous inflammation and
yeast forms consistent with Histoplasma
• Initiated on Liposomal Amphotericin B for disseminated histoplasmosis
Transfer
• Accepted transfer for prosthetic valve endocarditis
• Liposomal Amphotericin B continued
• Cleared by Neurology for valve replacement
POD 0
• Undergoes redo sternotomy, explantation of the bioprosthetic aortic
valve, debridement of the ascending aorta graft, and repeat aortic valve
replacement
• Significant postoperative bleeding requiring PRBC transfusion
POD 1
• Intraoperative cultures and smear return with Pathology read concerning
for both Candida and Histoplasma
• Postoperative cardiogenic shock requiring epinephrine and dobutamine
POD 3
• Weaned off of pressor support
• Chest tube removed
POD 12
• Discharged to acute rehabilitation facility
Plan
• Liposomal Amphotericin B 5 mg/kg IV daily for 6 weeks from time of
aortic valve replacement
• Itraconazole 200 mg PO TID x 3 days, then 200 mg PO BID for 1 year
• Lifelong suppression with Itraconazole 200 mg PO Daily
Discussion
• Histoplasma capsulatum is a thermally dimorphic fungus that grows as a
mold in the soil and as a yeast in animal and human hosts.
• Apart from Antarctica, it is found worldwide with a focus in the Ohio and
Mississippi river valleys.1
• According to Ledtke et. al, “Endovascular infection is an uncommon but
devastating manifestation of histoplasmosis, which is often diagnosed late
in disease.”
• Our patient presented with pancytopenia and was subsequently diagnosed
with histoplasmosis via bone marrow biopsy that showed granulomatous
inflammation and yeast forms. However, the patient had a vegetation on his
prosthetic aortic valve that, upon first look by the pathologist, appeared to
be a Candida infection due to its mold morphology. Given the patient’s
recent diagnosis of histoplasmosis, it was requested that the sample be
reexamined. Upon second look the pathologist found yeast forms on the
valve consistent with Histoplasma.
• “H. capsulatum endovascular infections are clinically characterized by a
subacute febrile illness with negative bacterial cultures in patients with
prosthetic endographs or valves.”4
• “H. capsulatum is a rare cause of infectious endocarditis, with only 58
previously described cases.”6 85% of cases were in men.5
• Diagnosis of Histoplasma endocarditis is challenging because the
automated blood culture systems that are commonly used do not favor the
growth of this organism.5
• Combination testing of both urine and serum for Histoplasma antigen should
be performed to increase their usefulness.5
• “Men who have prosthetic heart valves and who present with culture
negative endocarditis should be considered high risk of having Histoplasma
endocarditis.”5
• Limited data to guide H. capsulatum treatment and no specific
recommendations in 2007 IDSA Histoplasmosis Guidelines or the 2015 joint
IDSA/AHA Infective Endocarditis Scientific Statement.5
• Expert recommendations include initial period with Liposomal Amphotericin
B 5mg/kg per day for 4-6 weeks with step-down therapy to Itraconazole for
at least 12 months.5
• Isuvaconazole was used off label in one study because it doesn’t appear to
have an interaction with warfarin, and it causes QTc interval shortening
instead of lengthening like other azole drugs. Isuvaconazole also does not
require renal dosing adjustment.6
References:
1. Armstrong PA, Jackson BR, Haselow D, et al. Multistate Epidemiology of Histoplasmosis, United States, 2011–20141.
Emerging Infectious Diseases. 2018;24(3):425-431. doi:10.3201/eid2403.171258.
2. Benedict K, Thompson GR, Deresinski S, Chiller T. Mycotic Infections Acquired outside Areas of Known Endemicity, United
States. Emerging Infectious Diseases. 2015;21(11):1935-1941. doi:10.3201/eid2111.141950.
3. Biology of Histoplasmosis. https://www.cdc.gov/fungal/diseases/histoplasmosis/causes.html. Accessed October 5, 2018.
4. Ledtke C, Rehm SJ, Fraser TG, et al. Endovascular Infections Caused by Histoplasma capsulatum: A Case Series and Review
of the Literature. Archives of Pathology & Laboratory Medicine. 2012;136(6):640-645. doi:10.5858/arpa.2011-0050-oa.
5. Riddell J, Kauffman CA, Smith JA, et al. Histoplasma capsulatum Endocarditis: Multicenter Case Series with Review of
Current Diagnostic Techniques and Treatment. Medicine. 2014;93(5):186-193. doi:10.1097/MD.0000000000000034.
6. Wiley Z, Woodworth MH, Jacob JT, et al. Diagnostic Importance of Hyphae on Heart Valve Tissue in Histoplasma Endocarditis
and Treatment With Isavuconazole. Open Forum Infectious Diseases. 2017;4(4):ofx241. doi:10.1093/ofid/ofx241.
Figure 1 – CDC3
• 70-year-old Caucasian male presented for evaluation with confusion and
a fall
• Family reports being chronically ill for approximately one year with
relatively negative outpatient evaluation