Rare Case of Disseminated Histoplasmosis Mitral Valve Endocarditis in Florida

Introduction

Histoplasma capsulatum is prevalent in the mid-eastern part of the United States, primarily in the Ohio and Mississippi River Valleys, and is a dimorphic fungus [1–3]. It causes infection by the inhalation of its spores. The fungus requires an environment that will support its growth, which commonly includes areas with large amounts of bird or bat excrement or typically under chicken coops. The fungi can survive for years once they contaminate the soil in an area [2]. The majority of individuals who are infected remain asymptomatic or have mild symptoms, which typically do not require hospitalization. Immunocompromised patients are at the highest risk for disseminated histoplasmosis. Pulmonary symptoms or disseminated infections, such as endocarditis, which can affect native and prosthetic valves, will develop in only about 1% of patients infected [1].

Case Report

A 61-year-old man with a history of diabetes mellitus type II, essential hypertension, and atrial fibrillation presented with an 8- to-10-month history of fatigue, low-grade fevers, night sweats, and unexplained weight loss of 22.7 kg. The patient worked as a commercial residential building supervisor in Central Florida, where he owned a 16-acre farm and raised bull calves as a hobby. He denied any recent travel outside of Florida. On arrival at the Emergency Department, his physical examination was unrevealing of cardiac murmurs, and his lungs were clear. He did not have any palpable lymphadenopathy. He had tachycardia on arrival, with an electrocardiogram revealing atrial flutter, which responded to rate control therapy.

His initial laboratory test results were relatively benign, with no leukocytosis noted on his complete blood count and with no overt electrolyte disturbances on his basic metabolic panel. His inflammatory markers were elevated, including a sedimentation rate of 59 mm/h. A fourth-generation HIV antigen/ antibody testing was negative. Additionally, testing for an immunocompromised state, including tuberculosis, antinuclear antibody, and hepatitis panel were all negative. The Cardiology Service was consulted for his atrial fibrillation and atrial flutter. An echocardiogram revealed an ejection fraction of 65%, trace mitral regurgitation, with no patent foramen ovale or atrial septal defect, and an anterior leaflet of the mitral valve with a large mass. Two sets of blood cultures were obtained, and he was started on empiric antibiotics. The Infectious Disease Service was consulted for further recommendations for presumed endocarditis. A transesophageal echocardiogram confirmed a sessile echo density on the atrial surface of the mitral valve (Figure 1). Due to his extensive unintentional weight loss, a computed tomography scan of his chest, abdomen, and pelvis was completed, which revealed large bilateral adrenal masses, measuring 5.2 cm on the right and 5.0 cm on the left (Figure 2), in addition to splenomegaly and enlarged lymph nodes (Figure 3). The patient’s initial blood cultures were negative; however, the etiology of his infection was documented when his microbial Karius cell-free DNA test from his blood sample was positive, at 254 molecules per μL (reference interval <10 mpm) for H. capsulatum. Both his quantitative (120 pg/mL with reference range typically less than 60 pg/mL) and qualitative fungitell results were positive, indicating beta-DGlucan was detected. His Histoplasma antibodies testing was also positive, with titers over 1: 2048 and immunodiffusion testing revealing H and M bands, which is suggestive of active disease. The patient was immediately given intravenous liposomal amphotericin at a dose of 3 mg/kg/day for a total of 200 mg for 14 days. The patient underwent an adrenal biopsy, with pathological analysis revealing histoplasmosis.

The Cardiothoracic Surgery team was brought on board for the patient to be evaluated for surgery, as a recent left heart catheterization was revealed for multivessel coronary artery disease, in addition to his newly diagnosed endocarditis. He was deemed an appropriate risk and underwent a successful St. Jude Epic 31-mm mitral valve replacement with a tissue valve, along with a coronary artery bypass graft surgery to 4 of his vessels. Mitral valve replacement was preferred, owing to the surgeon’s experience and concern for anti-fungal re-infection. Concomitantly, he underwent a maze procedure and left atrial appendage ligation to help with his persistent atrial fibrillation and atrial flutter. The patient completed anti-fungal therapy and underwent surgical intervention within 5 weeks of his initial diagnosis. The diagnosis of mitral valve endocarditis from disseminated histoplasmosis was confirmed by pathological analysis (Figure 4). His postoperative period was complicated by a 6-day Intensive Care Unit stay, which included treatment for acute blood loss anemia and worsening renal indices, due to acute tubular necrosis. He was discharged home on long-term itraconazole maintenance treatment. Additionally, soil samples from his bull farm were requested to be collected by the Department of Health, as this remained the leading culprit of exposure. At the time of this discussion, the reports from the health department remained pending. Most recently, the patient continued to be asymptomatic, with down-trending Histoplasma antibodies titers at his follow-up in the Infectious Disease Clinic.

Discussion

The geographic area in which a physician is practicing will heavily influence the differential diagnosis in a patient with a suspected infectious etiology. The diagnosis of histoplasmosis is particularly challenging in a region where it is typically not prevalent. The majority of individuals who are infected remain asymptomatic or have mild complaints, which typically do not require hospitalization. Immunocompromised patients are at the highest risk for disseminated histoplasmosis. Patients with disseminated histoplasmosis present with fever, fatigue, and weight loss, which can progress to systemic manifestations including shock, respiratory failure, and even multi-organ failure. A recent systematic literature review from 1940 to 2020 revealed 60 cases of endocarditis caused by Histoplasmosis [1]. Although histoplasmosis has been seen in northern parts of Florida, there are no reported cases in the state of Florida of disseminated histoplasmosis endocarditis [3]. A thorough history is vital in the diagnosis of this fungal infection, as risk factors, including occupation, travel, or recent exposure, all play a role in contracting the disease.

Once there is a high suspicion of histoplasmosis, the confirmation of diagnosis is typically through histopathology [4]. This should be performed in tissues. In our case, we performed an adrenal biopsy and mitral valve tissue biopsy. Samples can be taken from any site of infection, including the bone marrow, blood, cerebrospinal fluid, liver, or skin. Pathology will be revealing of small narrow-based H. capsulatum yeast, which confirms the diagnosis in nearly 100% of cases. Antibody testing plays an important role, with a titer above 1: 32 suggesting infection. The assay testing for the presence of M and H bands, as seen in our patient, can also tell more of the story. An M band occurs during acute infection and also persists chronically. The presence of an H band is rarer and occurs in the presence of an M band, which can indicate a severe acute infection of histoplasmosis.

After diagnosis, immediate and appropriate treatment is life-saving for all patients [5]. H. capsulatum infective endocarditis is a fatal diagnosis without combined surgical intervention and anti-fungal treatment [1]. For individuals receiving anti-fungal therapy alone, mortality for native or prosthetic valve endocarditis is 50% [1]. The patient presented in this case received anti-fungal treatment and surgical intervention and had a 0% mortality for both native and prosthetic valve endocarditis.

Conclusions

We present a case of a 61-year-old man who initially was presumed to have culture-negative endocarditis; however, due to a thorough history being obtained, the appropriate imaging and testing were ordered, which led to our diagnosis of histoplasmosis mitral valve endocarditis. Anti-fungal treatment in combination with surgical treatment was ultimately the lifesaving intervention for this patient. A thorough history is particularly important when evaluating a patient with an unknown infectious source, especially assessing for risk factors, including exposure to environmental factors, workplace, and animals. The patient’s history of exposure can explain an infection that has never been seen in the state of Florida.