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Aspergillus Infection of the Thoracolumbar Vertebral Body in a Chronic Hepatitis B-Related Hepatocellular Carcinoma Patient: A Case Report

Liu, Jing1; Gao, Yi-Dan1; Jiang, Yan-Ming1; Wang, Jie1; Li, Ge1; Zhou, Xiang1; Zhu, Qian-Ru2; Chen, Gong-Ying1

Editor(s): Chen, Zhi

Author Information
Infectious Microbes & Diseases: June 2022 - Volume 4 - Issue 2 - p 75-78
doi: 10.1097/IM9.0000000000000087
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Aspergillus is a conditional pathogen, which infection is affected by the physiological state of the body. Generally, infection occurs in immunocompromised patients, such as posttransplantation patients, and patients with acquired immune deficiency syndrome (AIDS) or leukemia,1-4 while it is occasionally seen in healthy people. Aspergillus infections occur most commonly in the lungs, followed by paranasal sinuses, the external auditory canal, and the skin, whereas spine infections are rare. Vertebral aspergillosis, quite a rare condition, may cause osteolysis, intervertebral disc involvement, and epidural space collections, resulting in painful conditions that include neurological symptoms and deformities. The mortality rate is high, partially due to the high cost and poor efficacy of treatment.

Therefore, early diagnosis and early antifungal therapy are important for the control and treatment of this disease. However, since the initial symptoms of fungal spondylitis are generally nonspecific and easy to be confused with tumor metastasis in tumor patient, the possibility of fungal infection should be highly suspected for unexplained spinal infections. This report describes a rare case of Aspergillus infection of the thoracolumbar vertebral body in a patient with chronic hepatitis B (CHB)-related hepatocellular carcinoma.

Case description

In March 2018, a 48-year-old patient with CHB-related hepatocellular carcinoma presented with a 3-month history of lumbago after liver transcatheter arterial chemoembolization (TACE). He had hepatitis B-related cirrhosis and had not been treated. In December 2017, he underwent an abdomen B-ultrasound and an enhanced computed tomographic (CT) scan, which showed hepatic space-occupying lesions that were considered malignant. Then he went to a provincial hospital for diagnosis and treatment, where he was diagnosed with hepatocellular carcinoma according to histopathological analysis and then underwent liver TACE. In the subsequent period, he visited the provincial hospital several times due to unresolved lower back pain, which was symptomatically treated with diclofenac sodium to relieve the pain. Magnetic resonance imaging (MRI) enhancement of the spine suggested an abnormal signal in the T12 and L1-3 vertebral bodies and an increased T2 weighted image sequence signal of the soft tissue surrounding the spinous process. Swelling and T12 vertebral compression changes indicated endplate inflammation. He received empirical anti-infective treatment with cefoperazone sodium and sulbactam sodium. A lumbar puncture was recommended for diagnosis, but the patient refused. Oxycodone sustained release tablets and celecoxib capsules were used, which failed to control the pain, so he came to our hospital. Admission diagnoses were: (1) hepatocellular carcinoma (after TACE); (2) chest and lumbar lesions; (3) CHB-related cirrhosis.

Following admission, a chest CT scan indicated bronchiectasis in the lower lungs with infection, small nodules in the right middle lobe, balloon lumen in the main bronchi, and sputum in the lower bronchus (Figure 1A and 1B). Lumbar enhanced MRI showed an abnormal signal in the T12 and L1-4 vertebral, indicating metastasis, and an increased T2WI sequence signal of soft tissue surrounding the spinous process. MRI also suggested swelling, changes in T12 vertebral compression, and L5/S1 disc herniation (Figure 1E-G). Abdominal ultrasound showed cirrhosis, multiple calcifications in the liver, and splenomegaly. Abdominal ultrasound also found a high echo area in the right lobe of the liver, which was considered liver cancer after TACE. A Mycobacterium tuberculosis antibody test was weakly positive, a purified protein derivative skin test was positive, but a smear was negative for acid-fast bacilli and a T-spot test showed <2.00 pg/ mL. Importantly, a (1,3)-b-D-glucan test (G-test) showed 839.8 pg/mL, while a galactomannan antigen (GM) test was positive, pointing to a fungal infection. In order to diagnose the patient's lumbar lesions, a bone marrow biopsy was recommended, but the patient still refused. Given the patient's lung disease, pulmonary fiberoptic bronchoscopy and alveolar lavage were conducted, but no growth of pathogens was detected in the lavage culture. However, direct metagenomics next-generation sequencing identified Aspergillus fumigatus. Aspergillus-specific IgG levels were 135 AU/mL, the Aspergillus antigen signal was positive, but the GeneXpert MTB/RIF test was negative. Based on these results, the patient was suspected to have pulmonary and thoracolumbar vertebral aspergillosis. Therefore, he was treated with anti-Aspergillus therapy under the condition of informed consent.

Figure 1:
Computed tomographic (CT) scan changes in lung lesions and enhanced magnetic resonance imaging (MRI) changes in thoracolumbar vertebral body lesions before and after anti-Aspergillus treatment. A: Lung window of lung CT scan before treatment. B: Mediastinal window of lung CT scan before treatment. C: Lung window of lung CT scan after 1 year of itraconazole treatment. D: Mediastinal window of lung CT scan after 1 year of itraconazole treatment. E, F, G: Enhanced MRI of thoracic and lumbar before treatment; H, I, J: Enhanced MRI of thoracic and lumbar after 1 year of itraconazole treatment.

We first selected itraconazole 200 mg intravenously for 4 weeks, and then changed to itraconazole oral solution 200 mg every 12 hours for 4 weeks. Subsequently, treatment consisted of 5 cycles of injection and oral solution (itraconazole injection 200 mg every day for 1 week and itraconazole oral solution 200 mg every 12 hours for 3 weeks), and finally treatment consisted of itraconazole oral solution 200 mg every 12 hours for 6 months. Blood G-tests, blood routine, lung CT scans, thoracolumbar CT scans, and enhanced MRI were performed to evaluate treatment efficacy, and myocardial zymogram, BNP, echocardiography, and electrocardiogram were checked to detect side effects every 2 months. The G-test showed a linear decline after treatment (Figure 2A) and Aspergillus-specific IgG became negative (Figure 2B). After 2 months of treatment, the lumbago was relieved, and therefore the painkiller was reduced from oxycodone sustained release tablets 20 mg every 12 hours and celecoxib capsules to oxycodone sustained release tablets 20 mg every 12 hours only. After 6 months of treatment, lumbago was further relieved, so the painkiller was further reduced to 10 mg every 12 hours. After 1 year of treatment, the patient occasionally experienced lumbago and he irregularly took oxycodone sustained-release tablets. A lung CT scan showed that exudative lesions disappeared (Figure 1C and 1D). Furthermore, enhanced MRI showed that lesions in the lumbar and thoracic vertebral bodies and surrounding soft tissues were significantly reduced (Figure 1H-J). Liver enhanced MRI also detected no new tumor lesion. In order to determine a suitable follow-up treatment course, we communicated with the patient again, and a vertebral biopsy was performed under the condition of informed consent of the patient. Histopathology showed focal fibroplasia with lymphocytic infiltration, and no fungus was found in the tissue culture. Therefore, itraconazole oral solution was discontinued. Final diagnosis of this case were: (1) Aspergillus infection of thoracolumbar vertebral body; (2) pulmonary A. fumigatus infection; (3) hepatocellular carcinoma (after TACE); (4) CHB-related cirrhosis; (5) after cholecystectomy.

Figure 2:
Dynamic changes of levels of (1,3)-b-D-glucan in the G-test and Aspergillus -specific IgG during Anti- Aspergillus treatment. A: Dynamic changes of (1,3)-b-D-glucan levels during treatment; B: Dynamic changes of Aspergillus-specific IgG levels during treatment.

The data reported on this case were all obtained from the patient's clinical data. Ethical approval was exempted by the Ethical and Scientific Committees of the Affiliated Hospital of Hangzhou Normal University. Written consent for case publication was obtained from the patient involved in this article.


Vertebral aspergillosis may cause osteolysis, intervertebral disc involvement, and epidural space collections, resulting in painful conditions including neurological symptoms and deformities. It is quite a rare condition that is often misdiagnosed and requires long-term antibiotic therapy, and sometimes, surgical treat-ments.5 Therefore, early diagnosis, by blood cultures or direct sampling, and a proper medical therapy represent the key points in vertebral aspergillosis management. The patient had a basis of hepatitis B virus-related cirrhosis and hepatocellular carcinoma, with long-term neutropenia, so he was at high risk of Aspergillus infections. A. fumigatus, the main pathogenic Aspergillus,6 was detected in the bronchoalveolar lavage fluid, suggesting the presence of pulmonary aspergillosis, which is considered a risk factor for vertebral aspergillosis.

Diagnosis of aspergillosis is divided into 3 levels: determined diagnosed, diagnosed, and suspected.7 Current diagnostic methods include microscopy, culture, histopathology, imaging, GM test, G test, and nucleic acid detection (PCR). The determined diagnosis of Aspergillus infection requires histopathological evidence in addition to detection of the pathogen.8 The final diagnosis of this case is a pulmonary Aspergillus infection, which disseminated to cause a thoracolumbar infection. However, the pulmonary fungal infection site of the patient was located in the lower lobe of the lung, and there was no obvious cough symptom; at the same time, the imaging manifestation of fungal infection in this patient was not typical, so early diagnosis was difficult. Because the patient had low platelet counts, poor coagulation functions, and special location of lung lesions, and he rejected vertebral biopsy, no histopathological evidence of lung and spine vertebral tissue was obtained before diagnostic treatment. However, according to the changes in imaging before and after treatment, symptom improvement, and the final histopathological results of the spine vertebral, the final diagnosis was confirmed to be pulmonary and vertebral Aspergillus infections. Therefore, diagnostic antifungal therapy can be used clinically when the fungal infection is highly suspected while histopathological results are difficult to obtain.

Spinal vertebral fungal infections are currently only reported in cases, without official guidelines for treatment. For patients with simple vertebral or intervertebral space infections without spinal nerve involvement, conservative treatment with antifungal drugs alone is mostly effective. Surgical treatment is mainly performed for the stability of the spine when the spinal nerve is involved. Spinal cord compression is relieved by surgery to correct the kyphosis and restore stability. However, current antifungal treatment of spinal vertebral fungal infections mainly refers to the treatment guidelines for pulmonary fungal infections,8 while spinal vertebral body infections have characteristics such as low penetration of treatment drugs and a high recurrence rate of infection, so it is appropriate to extend the course of medication in clinical practice. There is no unified consensus on the formulation of drug courses and drug dose selection for spinal vertebral fungal infections, and further clinical experience and studies with large samples are needed.

There are some limitations in this case report. Because the patient refused any form of lung and pyramidal biopsy before treatment, we were unable to obtain pre-treatment histological evidence sufficient for the determined diagnosis of invasive pulmonary and thoracolumbar vertebral aspergillosis. Although Aspergillus was found in the bronchoalveolar lavage fluid, only a clinical diagnosis of Aspergillus infection could be made, and diagnostic antifungal therapy was used. A tissue biopsy was finally performed after 1 year of antifungal therapy when the patient's condition was relieved, and the results were negative for Aspergillus.

In conclusion, diagnostic antifungal therapy is of great significance for patients with clinically suspected Aspergillus infections when it is difficult to obtain tissue specimens for determined diagnosis.


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thoracolumbar vertebral body; Aspergillus; hepatocellular carcinoma

Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.