Recurrent Invasive Aspergillosis in Immunocompetent Patient

Abstract

Invasive cardiac aspergillosis is a rare form of disseminated Aspergillus infection which carries a very high mortality rate even with aggressive treatment. Importantly, patients with pre-existing cardiac lesions, prosthetic valves, stents, coronary bypass grafts, and implanted devices are at greater risk. A case of fatal, recurrent, disseminated Aspergillus infection in an immunocompetent patient with invasion of a structurally normal heart in the context of multiorgan involvement is presented.

Supplemental material is available for this article.

Keywords: CT, Echocardiography, Infection

© RSNA, 2021

Summary

In patients with a history of Aspergillus infection, the detection of new skin, cardiac, brain, or renal lesions is suggestive of invasive aspergillosis and should prompt aggressive treatment.

Key Points

• ■ Disseminated fungal infection should be included in the differential diagnosis when multiple myocardial masses and large valvular vegetations are seen at imaging, even in immunocompetent hosts.

• ■ The potential need for follow-up of patients with previous aspergillosis and the importance of early detection and treatment of recurrence should be recognized.

Introduction

Disseminated aspergillosis is a rare infection that mostly affects immunocompromised patients (1,2). Invasive aspergillosis (IA) infection can affect the kidneys, the heart, the brain, and the skin. Cardiac involvement has been reported in patients with underlying cardiac abnormalities such as prosthetic valves, cardiac devices, and heart transplants, but only rarely in structurally normal hearts of immunocompetent patients (3). Herein, we report a case of severe recurrent, disseminated IA in an immunocompetent patient with a structurally normal heart.

Case Report

History of Presentation

A 22-year-old male patient was admitted through the emergency department with syncopal attacks, fatigue, and weight loss of 8 kg over 2 months. His physical examination was remarkable for multiple subcutaneous masses ranging between a few millimeters to 4 cm, involving the chest wall and upper and lower limbs. In addition, there was bilateral axillary lymphadenopathy.

Past Medical History

The patient’s past medical history was positive for Aspergillus flavus necrotizing granulomatous encephalitis at the age of 12, for which he had undergone craniotomy and resection of the right occipital lobe. He was discharged and prescribed voriconazole (6 mg/kg twice a day). Six-week postoperative MRI showed evidence of a residual fungal brain lesion. A repeat resection was performed with culture confirming Aspergillus flavus infection. His immunologic investigations were normal, including lymphocyte markers, serum immunoglobulin levels, complement level, blastogenic response, polymorphonuclear leukocyte chemotaxis, and oxidative burst. HIV test was also negative. His thoracic and abdominal CT angiography (CTA) and echocardiography were also reported as normal. He continued to take oral voriconazole for another 8 months. Follow-up MRI 1 month after discharge and every 6 months for 2 years showed resolution of the brain parenchymal abnormalities. The patient did well after the surgery for 10 years until this presentation.

Investigations

His initial laboratory results were a total white blood cell count of 13.3 × 10³/µL (reference range, 3.50–10.0 × 10³/µL), lymphocyte count of 3.48 × 10³/µL (reference range, < 3 × 10³/µL), eosinophils of 1.46 × 10³/µL (reference range, < 0.5 × 10³/µL), erythrocyte sedimentation rate of 16 mm/h (reference range, < 10 mm/h), C-reactive protein level of 184 mg/L (reference range, < 3.3 mg/L), C3 level of 1.52 g/L (reference range, 0.841–1.67 g/L), and C4 level of 0.201 g/L (reference range, 0.164–0.313 g/L). HIV enzyme-linked immunosorbent assay test was negative. CTA of the brain, thorax, and abdomen showed the resection cavity in the right occipital lobe as well as hypoattenuating lesions with surrounding edema within bilateral frontal and parietal lobes. In addition, there were multiple nodular lesions involving both kidneys and the heart (Figs 1–2). Transthoracic echocardiography showed multiple giant masses attached to the mitral valve, the left ventricular free wall, the septum, the right ventricle, and the pericardium with a mild pericardial effusion (Movies 1–3). Biopsy was taken from the subcutaneous nodules (Fig 3), which confirmed the diagnosis of Aspergillus infection.

Figure 1:

CT findings. (A) Axial contrast-enhanced CT image depicts bilateral hypoattenuating renal parenchymal lesions (arrowheads). (B) Axial nonenhanced CT image demonstrates postsurgical resection changes from prior Aspergillosis infection (white asterisk). (C) Axial fluid-attenuated inversion recovery MR image shows mild cortical and subcortical hyperintense signal in the left temporal lobe, insula, and the lentiform nucleus extending to the atrium of the left lateral ventricle (arrows). (D) Axial nonenhanced CT image demonstrates intracranial hemorrhage (black asterisks) with surrounding edema.

Figure 2:

Axial contrast-enhanced images from nongated CT of the chest at the level of the (A) mitral valve and (B) coronary sinus reveal multiple hypoattenuating lesions in the septum (white arrows), wall of the right and left ventricle (black arrows), and the pericardium (white arrowhead). (C) Four-chamber view echocardiogram demonstrates multiple left ventricular masses involving the septum (white arrows), lateral wall protruding into the left ventricular cavity (black arrows), and pericardial space (white arrowhead), as well as a pericardial effusion (PE).

Figure 3:

Clinical photograph shows subcutaneous mass at the left upper limb.

Movie 1.

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Transthoracic echocardiography: Parasternal long-axis view shows large masses attached to the mitral valve leaflets and left ventricle endocardium that protrudes into left ventricle cavity.

Movie 2.

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Transthoracic echocardiography: Apical four-chamber view shows multiple masses in the left ventricle cavity, right ventricle cavity, and interventricular septum as well as mild pericardial effusion.

Movie 3.

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Transthoracic echocardiography: Apical long-axis view shows multiple large masses involving the mitral valve, left ventricular free wall, the septum, right ventricular free wall, and the pericardium.

Differential Diagnoses

Lymphoma, tuberculosis, and fungal infections including aspergillosis were differential diagnoses, with the histopathologic examination of the subcutaneous mass biopsy confirming the diagnosis of aspergillosis (Fig 4).

Figure 4:

Histopathologic findings. Subcutaneous mass microscopic picture. (A) Hematoxylin-eosin–stained tissue shows multiple giant cells along with areas of necrosis (black arrow). (Original magnification, ×20.) (B) Special periodic acid–Schiff stain revealed dark magenta–stained fungal hyphae. (Original magnification, ×40.) (C) Gomori methenamine silver staining shows branching fungal hyphae (white arrow). (Original magnification, ×40.)

Management

Given the biopsy finding, the patient was given intravenous voriconazole (4 mg/kg twice a day) for aspergillosis (4). However, 2 days later, he became unresponsive, necessitating intubation, mechanical ventilation, and admission to the intensive care unit. An emergent brain CT showed a large intracranial hemorrhage, possibly due to the hemorrhagic transformation of massive embolic stroke (Fig 1D). The patient was treated conservatively and, unfortunately, died the following day.

Discussion

IA is a fungal infection that typically affects immunocompromised hosts including those with hematologic malignancies, those who have undergone bone marrow/solid organ transplantation, or those with AIDS. IA carries a high mortality rate of 22% that may exceed 90% with central nervous system involvement (2,5).

Cardiac involvement in IA is commonly seen in patients with previous cardiac lesions, intravenous drug users, and patients with indwelling central venous catheters and typically manifests as infective endocarditis. Aspergillus species account for approximately 25% of all fungal endocarditis (6). The mitral valve is the most frequently affected structure with IA. Importantly, Gumbo et al (7) reported that two-thirds of native valve Aspergillus endocarditis were reported in immunosuppressed patients, and 78% of all cases had vegetations at echocardiography. Our patient presented with pancarditis (involvement of the endocardium, myocardium, and pericardium), which has a worse prognosis.

The recommended treatment of cardiac aspergillosis is surgical intervention with aggressive medical therapy (1,2). However, despite early management, the prognosis is poor, with an overall mortality of 50%–95% (1,8,9). Mortality in cardiac aspergillosis is primarily related to embolic phenomena and heart failure due to valvular regurgitation (7).

A late diagnosis of IA increases the risk of therapeutic failure, with greater complications and subsequently mortality rate (5). The present case emphasizes the importance of regular follow-up in patients with a previous history of IA. It also highlights the value of regular cardiac screening in patients with Aspergillus infection with directed multimodality imaging including echocardiography, cardiac MRI, and CTA as appropriate to assess disease extent and severity. Unfortunately, in this case, the patient was lost to follow-up for 5 years prior to his presentation with advanced disease.

Conclusions

To our knowledge, this is the first case of recurrent invasive cerebral aspergillosis in an immunocompetent patient with dissemination to subcutaneous tissues, the kidneys, and a previously structurally normal heart with involvement of all cardiac layers: endocardium, myocardium, and pericardium.