British Journal of Neurosurgery, 2014; Early Online: 1–3 © 2014 The Neurosurgical Foundation ISSN: 0268-8697 print / ISSN 1360-046X online DOI: 10.3109/02688697.2014.957648
SHORT REPORT
Lumbar Aspergillus osteomyelitis mimicking pyogenic osteomyelitis in an immunocompetent adult Kyeong-Wook Yoon & Young-Jin Kim
Br J Neurosurg Downloaded from informahealthcare.com by University of Ulster at Jordanstown on 03/06/15 For personal use only.
Department of Neurosurgery, Dankook University College of Medicine, Cheonan, Chungnam, Republic of Korea
Clinical details
Abstract Spinal Aspergillus osteomyelitis is rare and occurs mostly in immunocompromised patients, but especially very rare in immunocompetent adult. This report presents a case of lumbar vertebral osteomyelitis in immunocompetent adult. A 53-year-old male who had no significant medical history was admitted due to complaints of back pain radiating to the flank for the last 3 months, followed by a progressive motor weakness of both lower limbs. Lumbar magnetic resonance imaging (MRI) demonstrated osteomyelitis and diskitis, suspected to be a pyogenic condition rather than a tuberculosis infection. Despite antibiotic treatment for several weeks, the symptoms worsened, and finally, open surgery was performed. Surgical biopsy revealed an Aspergillus infection and medical treatment with amphotericin B was started. It can be diagnosed early through an MRI; biopsy is very important but difficult, and making the correct differential diagnosis is essential for avoiding unexpected complications. The authors report a case of lumbar Aspergillus osteomyelitis in an immunocompetent adult and reviewed previously described cases of spinal aspergillosis.
A 53-year-old male visited the emergency room with motor weakness (Grade 4), paresthesia, and pain radiating down the legs. He had a history of a couple of spinal block procedures for back pain at a local clinic and no past medical history which was suspicious of an immunosuppressed condition. The patient had no fever, and initial laboratory findings showed a C-reactive protein (CRP) level of 0.86 mg/ dl and white blood cell count (WBC) of 5540/μl (differential count: neutrophils, 64.0%; lymphocytes, 22.2%). Chest radiography showed no active lung lesion. Radiologic study was performed and we found an osteolytic lesion in the inferior endplate of L2 and superior endplate of L3. It was suspected as infectious spondylodiskitis rather than tuberculosis infection (Fig. 1A–C). Antibiotic treatment with vancomycin (2.0 g ⫻ 2 times/ day) was started for the patient and the treatment was continued for 4 weeks. However, the symptoms worsened and the motor grade decreased to grade 3 in both legs. We performed lumbar magnetic resonance imaging (MRI), which revealed that the lesion had become worse. Finally, we decided to perform surgery (total laminectomy of L2 and biopsy). The result of the biopsy was chronic inflammation with granulation tissue and no evidence of malignancy. Vancomycin treatment was continued for another 2 weeks, but the motor weakness increased to grade 2. Another operation for corpectomy and fusion with biopsy was scheduled. The patient underwent surgery and a surgical biopsy was performed. The frozen biopsy revealed aspergillosis in d-PAS (diastase–periodic acid–Schiff ) and GMS (Gomori methenamine silver) staining, and hyphae were identified (Fig. 2). AFB (acid-fast bacilli) staining was negative. We changed the vancomycin to amphotericin B (25 mg/day for 30 days) to treat the Aspergillus infection. The motor grade recovered to grade 4⫹; however, the hypesthesia was still present when he was discharged from the hospital. Seven months after discharge, the patient recovered motor power of both legs and he no longer complained of hypesthesia. A follow-up radiologic study showed no recurrence (Fig. 1D and E).
Keywords: Aspergillus; lumbar spine; spine osteomyelitis
Introduction Aspergillus is a rare and lethal opportunistic infection in immunocompromised patients. Its infection of the lumbar spine is very rare and is transmitted directly from primary lung lesions in children or is hematogenously spread to the lumbar spine in adult groups. Diagnosis of Aspergillus infection is difficult because hyphae should be confirmed in pathologic findings, and small amount of specimen is prone to skip hyphae. Polymerase chain reaction (PCR) assay is a rapid and highly sensitive method to diagnose Aspergillus infection, but is currently a challenging and investigational status.1 The authors present a case of lumbar Aspergillus osteomyelitis that was mistaken for pyogenic osteomyelitis in an immunocompetent middle-aged patient.
Correspondence: Young-Jin Kim, MD, PhD, Department of Neurosurgery, Dankook University College of Medicine, 201 Manghyang-ro Dongnam-gu, Cheonan 330-715, Chungnam Republic of Korea. Tel: ⫹ 82-41-550-3979. Fax: ⫹ 82-41-552-6870. E-mail: [email protected] Received for publication 5 January 2014; accepted 19 August 2014
1
Br J Neurosurg Downloaded from informahealthcare.com by University of Ulster at Jordanstown on 03/06/15 For personal use only.
2
K.-W. Yoon & Y.-J. Kim
Fig. 1. Initial MR T2W sagittal image (A), T1W gadolinium-enhanced image (B), and CT sagittal image (C) showing osteolytic lesion in the inferior endplate of L2 and superior endplate of L3. Post-operative MR T2WI (D) and plain lateral X-ray (E) after 7 months showing no recurrence in previous lesion.
Discussion Invasive aspergillosis occurs most commonly in the lungs. Indiscreet use of broad-spectrum antibiotics and steroids has caused an increase in opportunistic infections. More than 350 species of Aspergillus have been identified; however, only a few species are pathogenic in humans.1 Invasion is common in the respiratory and gastrointestinal systems, and rare in the central nerve system and the bone. It is very rare for these pathogens to cause problems in immunocompetent patients. There was no evidence of immunosuppression in our patient, such as organ transplantation, acquired immune deficiency syndrome, leukemia, and other immunodeficient conditions. Generally, hyphae are not easy to obtain from specimen. Several reports presented that they could obtain hyphae in a couple of biopsy trials. In our case, we barely detected hyphae in two slides among over one hundred slides. When hyphae of Aspergillus are detected, the diagnosis is complete, and in our case, we confirmed hyphae in the pathologic examination, although the subtype was not confirmed. Enzyme immunoassay of galactomannan provides good sensitivity and has been proved for diagnosis of Aspergillus. PCR assay of Aspergillus DNA also provides high sensitivity and species-specific diagnosis. Furthermore, it may be
Fig. 2. Pathologic finding demonstrating acute-angle branching and septate Aspergillus hyphae. (PAS stain, ⫻ 400).
performed using cerebrospinal fluid to detect Aspergillus in the central nervous system.1 The origin of the pathogen in our patient is still unknown. The origin is usually the lung from which it spreads hematogenously. The only possible cause was that the patient underwent a couple of nerve blocks at a local clinic. The organism might have invaded the body directly through a needle puncture during the procedure, but the possibility for this organism to invade into a healthy body is very low. Invasive Aspergillus infection commonly occurs in the lungs, and spinal involvement is rare; however, vertebral bodies are the most frequent site for Aspergillus infections in the bone.2 The clinical symptoms of spinal Aspergillus osteomyelitis are back pain, motor weakness of the legs, and weight loss, but these symptoms are not specific for this condition. WBC and CRP are sometimes in the normal range. The typical MRI appearances of spinal osteomyelitis and diskitis are well understood.3 Hypointensity of the vertebral body and the disk on T1-weighted (T1W) images, hyperintensity of the disk on T2W images, and hyperintensity of the involved endplates on T2W images are typical findings of spinal osteomyelitis. Nonpyogenic spondylitis, such as tuberculosis and fungal infection, tend to preserve the disk morphology, relatively. In our patient, the MR T2W showed that the L2–3 disk space was involved and a margin of the endplate was destroyed (Fig. 1A). Furthermore, we did not suspect a fungal infection because our patient was not in an immunocompromised state. Diagnostic MRI is important for deciding whether to perform surgery or give conservative treatment. However, in the case of Aspergillus osteomyelitis, the clinical laboratory findings and radiologic features are similar to those of tuberculous spondylitis. It is very difficult to distinguish Aspergillus from tuberculous spondylitis, especially in a tuberculosis endemic area such as Korea. Therefore, performing a surgical biopsy is essential for making the differential diagnosis. Invasive Aspergillus is often fatal without proper treatment. Some large randomized control studies have reported that amphotericin B and voriconazole are the treatment of choice for Aspergillus infections.1 The dosage and period of administration of amphotericin B are reported in various protocols proposed by several studies and we choose the dose of 0.35 mg/kg/day for 30 days.
Br J Neurosurg Downloaded from informahealthcare.com by University of Ulster at Jordanstown on 03/06/15 For personal use only.
Lumbar Aspergillus osteomyelitis Histological examination and culture are the gold standard diagnostic methods of invasive Aspergillus infection. However, these diagnostic modalities tend to take a long time and have low sensitivity. Early detection of the pathogen is very important for the proper management of the patient. In our case, the diagnosis was late and the neurologic deficit became aggravated. As a consequence, the patient underwent evitable surgery. Surgery for Aspergillus spondylitis involves the anterior and posterior approaches. The anterior approach is better than the posterior approach in achieving good postoperative vertebral alignment and sufficient decompression. In this case, we performed posterior decompression and first open biopsy but it failed to make an accurate diagnosis. Finally, we could get more abundant diagnostic specimen and good outcome using anterior decompression and fusion with surgical biopsy. Vertebral osteomyelitis caused by Aspergillus infection is very rare. Early diagnosis is difficult especially in the case
3
when the MRI findings are obscure and the patient is immunocompetent as in our case. We conclude that surgery should be performed at an appropriate time and that amphotericin B is effective for treating Aspergillus osteomyelitis. Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Tew CW, Han FC, Jureen R, Tey BH. Aspergillus vertebral osteomyelitis and epidural abscess. Singapore Med J 2009;50: e151–4. 2. Hummel M, Schuler S, Weber U, et al. Aspergillosis with Aspergillus osteomyelitis and diskitis after heart transplantation: surgical and medical management. J Heart Lung Transplant 1993; 12:599–603. 3. Williams RL , Fukui MB, Meltzer CC, et al. Fungal spinal osteomyelitis in the immunocompromised patient: MR findings in three cases. AJNR Am J Neuroradiol 1999;20:381–5.
SHORT REPORT
Lumbar Aspergillus osteomyelitis mimicking pyogenic osteomyelitis in an immunocompetent adult Kyeong-Wook Yoon & Young-Jin Kim
Br J Neurosurg Downloaded from informahealthcare.com by University of Ulster at Jordanstown on 03/06/15 For personal use only.
Department of Neurosurgery, Dankook University College of Medicine, Cheonan, Chungnam, Republic of Korea
Clinical details
Abstract Spinal Aspergillus osteomyelitis is rare and occurs mostly in immunocompromised patients, but especially very rare in immunocompetent adult. This report presents a case of lumbar vertebral osteomyelitis in immunocompetent adult. A 53-year-old male who had no significant medical history was admitted due to complaints of back pain radiating to the flank for the last 3 months, followed by a progressive motor weakness of both lower limbs. Lumbar magnetic resonance imaging (MRI) demonstrated osteomyelitis and diskitis, suspected to be a pyogenic condition rather than a tuberculosis infection. Despite antibiotic treatment for several weeks, the symptoms worsened, and finally, open surgery was performed. Surgical biopsy revealed an Aspergillus infection and medical treatment with amphotericin B was started. It can be diagnosed early through an MRI; biopsy is very important but difficult, and making the correct differential diagnosis is essential for avoiding unexpected complications. The authors report a case of lumbar Aspergillus osteomyelitis in an immunocompetent adult and reviewed previously described cases of spinal aspergillosis.
A 53-year-old male visited the emergency room with motor weakness (Grade 4), paresthesia, and pain radiating down the legs. He had a history of a couple of spinal block procedures for back pain at a local clinic and no past medical history which was suspicious of an immunosuppressed condition. The patient had no fever, and initial laboratory findings showed a C-reactive protein (CRP) level of 0.86 mg/ dl and white blood cell count (WBC) of 5540/μl (differential count: neutrophils, 64.0%; lymphocytes, 22.2%). Chest radiography showed no active lung lesion. Radiologic study was performed and we found an osteolytic lesion in the inferior endplate of L2 and superior endplate of L3. It was suspected as infectious spondylodiskitis rather than tuberculosis infection (Fig. 1A–C). Antibiotic treatment with vancomycin (2.0 g ⫻ 2 times/ day) was started for the patient and the treatment was continued for 4 weeks. However, the symptoms worsened and the motor grade decreased to grade 3 in both legs. We performed lumbar magnetic resonance imaging (MRI), which revealed that the lesion had become worse. Finally, we decided to perform surgery (total laminectomy of L2 and biopsy). The result of the biopsy was chronic inflammation with granulation tissue and no evidence of malignancy. Vancomycin treatment was continued for another 2 weeks, but the motor weakness increased to grade 2. Another operation for corpectomy and fusion with biopsy was scheduled. The patient underwent surgery and a surgical biopsy was performed. The frozen biopsy revealed aspergillosis in d-PAS (diastase–periodic acid–Schiff ) and GMS (Gomori methenamine silver) staining, and hyphae were identified (Fig. 2). AFB (acid-fast bacilli) staining was negative. We changed the vancomycin to amphotericin B (25 mg/day for 30 days) to treat the Aspergillus infection. The motor grade recovered to grade 4⫹; however, the hypesthesia was still present when he was discharged from the hospital. Seven months after discharge, the patient recovered motor power of both legs and he no longer complained of hypesthesia. A follow-up radiologic study showed no recurrence (Fig. 1D and E).
Keywords: Aspergillus; lumbar spine; spine osteomyelitis
Introduction Aspergillus is a rare and lethal opportunistic infection in immunocompromised patients. Its infection of the lumbar spine is very rare and is transmitted directly from primary lung lesions in children or is hematogenously spread to the lumbar spine in adult groups. Diagnosis of Aspergillus infection is difficult because hyphae should be confirmed in pathologic findings, and small amount of specimen is prone to skip hyphae. Polymerase chain reaction (PCR) assay is a rapid and highly sensitive method to diagnose Aspergillus infection, but is currently a challenging and investigational status.1 The authors present a case of lumbar Aspergillus osteomyelitis that was mistaken for pyogenic osteomyelitis in an immunocompetent middle-aged patient.
Correspondence: Young-Jin Kim, MD, PhD, Department of Neurosurgery, Dankook University College of Medicine, 201 Manghyang-ro Dongnam-gu, Cheonan 330-715, Chungnam Republic of Korea. Tel: ⫹ 82-41-550-3979. Fax: ⫹ 82-41-552-6870. E-mail: [email protected] Received for publication 5 January 2014; accepted 19 August 2014
1
Br J Neurosurg Downloaded from informahealthcare.com by University of Ulster at Jordanstown on 03/06/15 For personal use only.
2
K.-W. Yoon & Y.-J. Kim
Fig. 1. Initial MR T2W sagittal image (A), T1W gadolinium-enhanced image (B), and CT sagittal image (C) showing osteolytic lesion in the inferior endplate of L2 and superior endplate of L3. Post-operative MR T2WI (D) and plain lateral X-ray (E) after 7 months showing no recurrence in previous lesion.
Discussion Invasive aspergillosis occurs most commonly in the lungs. Indiscreet use of broad-spectrum antibiotics and steroids has caused an increase in opportunistic infections. More than 350 species of Aspergillus have been identified; however, only a few species are pathogenic in humans.1 Invasion is common in the respiratory and gastrointestinal systems, and rare in the central nerve system and the bone. It is very rare for these pathogens to cause problems in immunocompetent patients. There was no evidence of immunosuppression in our patient, such as organ transplantation, acquired immune deficiency syndrome, leukemia, and other immunodeficient conditions. Generally, hyphae are not easy to obtain from specimen. Several reports presented that they could obtain hyphae in a couple of biopsy trials. In our case, we barely detected hyphae in two slides among over one hundred slides. When hyphae of Aspergillus are detected, the diagnosis is complete, and in our case, we confirmed hyphae in the pathologic examination, although the subtype was not confirmed. Enzyme immunoassay of galactomannan provides good sensitivity and has been proved for diagnosis of Aspergillus. PCR assay of Aspergillus DNA also provides high sensitivity and species-specific diagnosis. Furthermore, it may be
Fig. 2. Pathologic finding demonstrating acute-angle branching and septate Aspergillus hyphae. (PAS stain, ⫻ 400).
performed using cerebrospinal fluid to detect Aspergillus in the central nervous system.1 The origin of the pathogen in our patient is still unknown. The origin is usually the lung from which it spreads hematogenously. The only possible cause was that the patient underwent a couple of nerve blocks at a local clinic. The organism might have invaded the body directly through a needle puncture during the procedure, but the possibility for this organism to invade into a healthy body is very low. Invasive Aspergillus infection commonly occurs in the lungs, and spinal involvement is rare; however, vertebral bodies are the most frequent site for Aspergillus infections in the bone.2 The clinical symptoms of spinal Aspergillus osteomyelitis are back pain, motor weakness of the legs, and weight loss, but these symptoms are not specific for this condition. WBC and CRP are sometimes in the normal range. The typical MRI appearances of spinal osteomyelitis and diskitis are well understood.3 Hypointensity of the vertebral body and the disk on T1-weighted (T1W) images, hyperintensity of the disk on T2W images, and hyperintensity of the involved endplates on T2W images are typical findings of spinal osteomyelitis. Nonpyogenic spondylitis, such as tuberculosis and fungal infection, tend to preserve the disk morphology, relatively. In our patient, the MR T2W showed that the L2–3 disk space was involved and a margin of the endplate was destroyed (Fig. 1A). Furthermore, we did not suspect a fungal infection because our patient was not in an immunocompromised state. Diagnostic MRI is important for deciding whether to perform surgery or give conservative treatment. However, in the case of Aspergillus osteomyelitis, the clinical laboratory findings and radiologic features are similar to those of tuberculous spondylitis. It is very difficult to distinguish Aspergillus from tuberculous spondylitis, especially in a tuberculosis endemic area such as Korea. Therefore, performing a surgical biopsy is essential for making the differential diagnosis. Invasive Aspergillus is often fatal without proper treatment. Some large randomized control studies have reported that amphotericin B and voriconazole are the treatment of choice for Aspergillus infections.1 The dosage and period of administration of amphotericin B are reported in various protocols proposed by several studies and we choose the dose of 0.35 mg/kg/day for 30 days.
Br J Neurosurg Downloaded from informahealthcare.com by University of Ulster at Jordanstown on 03/06/15 For personal use only.
Lumbar Aspergillus osteomyelitis Histological examination and culture are the gold standard diagnostic methods of invasive Aspergillus infection. However, these diagnostic modalities tend to take a long time and have low sensitivity. Early detection of the pathogen is very important for the proper management of the patient. In our case, the diagnosis was late and the neurologic deficit became aggravated. As a consequence, the patient underwent evitable surgery. Surgery for Aspergillus spondylitis involves the anterior and posterior approaches. The anterior approach is better than the posterior approach in achieving good postoperative vertebral alignment and sufficient decompression. In this case, we performed posterior decompression and first open biopsy but it failed to make an accurate diagnosis. Finally, we could get more abundant diagnostic specimen and good outcome using anterior decompression and fusion with surgical biopsy. Vertebral osteomyelitis caused by Aspergillus infection is very rare. Early diagnosis is difficult especially in the case
3
when the MRI findings are obscure and the patient is immunocompetent as in our case. We conclude that surgery should be performed at an appropriate time and that amphotericin B is effective for treating Aspergillus osteomyelitis. Declaration of interest: The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Tew CW, Han FC, Jureen R, Tey BH. Aspergillus vertebral osteomyelitis and epidural abscess. Singapore Med J 2009;50: e151–4. 2. Hummel M, Schuler S, Weber U, et al. Aspergillosis with Aspergillus osteomyelitis and diskitis after heart transplantation: surgical and medical management. J Heart Lung Transplant 1993; 12:599–603. 3. Williams RL , Fukui MB, Meltzer CC, et al. Fungal spinal osteomyelitis in the immunocompromised patient: MR findings in three cases. AJNR Am J Neuroradiol 1999;20:381–5.
