Mucormycosis is caused by various genera of the order Mucorales of the class Zygomycetes, and the terms mucormycosis and zygomycosis are often used interchangeably . Cunninghamella can also cause infection in humans, which affect multiple organ systems, including the rhinocerebral, pulmonary, cutaneous, and gastrointestinal systems, and cause severe infections . In this case of mucormycosis after LDLT, the brain, lung, heart, gastrointestinal tract, liver, and kidneys were involved, and progression was rapid.
Mucormycosis is uncommon in developed countries . Diabetes mellitus is the most common risk factor, followed by hematologic malignancies and solid organ or hematopoietic cell transplantation . A review of mucormycosis in 116 organ transplant patients found that mucormycosis was caused by C. bertholletiae only in 6% of the cases . To the best of our knowledge, only one case of C. bertholletiae invading multiple organs after liver transplantation has been reported since 1988 , wherein the diagnosis of C. bertholletiae infection was obtained only by a microscopic finding in autopsy; however, there were no representative images of multiple organ dissemination. Our study is the first to report detailed information, including several images on mucormycosis with multiple organ dissemination caused by C. bertholletiae after liver transplantation.
The initial right lung lesion was resected and used to diagnose mucormycosis. However, by that time, other symptoms such as altered consciousness and decreased ejection fraction rate (probably associated with the cerebral and cardiac invasions) had appeared. Pulmonary lesions are common in immunocompromised patients, including solid organ transplant recipients with mucormycosis [4, 10, 12]. Mucorales are ubiquitous in nature, and infection usually begins in a nasal turbinate or alveolus in susceptible individuals . Pulmonary and rhino-orbital-cerebral mucormycosis are acquired by spore inhalation. Mucormycosis develops after a median of 5 months following solid organ transplantation, with a significantly earlier occurrence in liver transplant recipients . Mucormycosis agents such as C. bertholletiae penetrate vasculature, resulting in mycotic thrombi, which can cause infarction with hemorrhagic necrosis . Our case confirmed that the pulmonary lesion pathologically contained hemorrhagic necrosis caused by fungal emboli.
Cardiac mucormycosis caused Takotsubo myocarditis and an ultimately fatal cardiac infarction. Multiple myocardial infarctions due to fungal emboli were pathologically proven in autopsy specimens. The myocardia were most commonly affected in patients with disseminated pulmonary mucormycosis following solid organ transplantation .
Autopsy also revealed fibrin-containing hyphae covering the endothelium in all heart chambers, suggesting fungal endocarditis. Multiple organ infarctions occurred in quick succession; dissemination to multiple organs may have occurred originating from fungal endocarditis. Zhang et al. reported a case of endocarditis caused by C. bertholletiae infection after kidney transplantation .
Previous solid organ transplantation was associated with an increased risk of pulmonary, gastrointestinal, or disseminated infection in patients with mucormycosis . An underlying hematological malignancy increases the risk of organ dissemination [3, 15], which occurs more frequently in the distant organs of immunosuppressed patients . Our patient had infection-promoting factors, such as organ transplantation, bone marrow dysfunction, and immunosuppression. Prophylaxis might be needed against fungal infection, especially in the case of induced immunosuppression before transplantation, although the selection of anti-fungal reagents is complicated.
Previous use of voriconazole is a significant risk factor for mucormycosis development [16, 17]. We transitioned the patient to voriconazole when an Aspergillus infection was suspected before diagnosing mucormycosis. Jeong et al. reported that prior antifungal prophylaxis, including voriconazole and fluconazole, was administered to 11% of patients with mucormycosis . Dissemination might have expanded to include multiple organs during the administration of voriconazole.
The risk of mortality is approximately 11-fold higher in patients with disseminated mucormycosis than in those with localized disease . Mucorales were grown on culture, and histopathological features contributed to a definitive diagnosis of mucormycosis . The presence of broad, aseptate, or pauci-septate hyphae with wide-angle branching with tissue invasion provides evidence of mucormycosis . However, early diagnosis of C. bertholletiae infection is difficult and may only be confirmed on autopsy . Modern molecular-based methods are required for species identification and diagnosis because serologic tests are not available yet . We suspected mucormycosis after culturing the operative specimen; C. bertholletiae was ultimately identified by PCR, detecting specific fungal DNA sequences.
Patient mortality increases if AmB-based therapy is delayed . High-dose conventional AmB at a dose of 10 mg/kg/day for 6 months was reported to contribute to the successful treatment of disseminated mucormycosis after stem cell transplantation . Surgical intervention with debridement of necrotic tissue and debulking improves survival in patients with pulmonary infections . Surgery plus AmB produces superior results than those of AmB administration alone . Discontinuation or reduction in immunosuppression was associated with a better survival rate in patients after solid organ transplantation . AmB was administered after removing the pulmonary lesion; however, the treatment was not completed in our patient because of brain and heart involvement. AmB should be administered as quickly as possible to LDLT recipients with suspected fungal infection.