International Journal of Rheumatic Diseases 2014; 17: 229–231
CORRESPONDENCE
Candida glabrata vertebral osteomyelitis in an immunosuppressed patient Dear Editor, A 47-year-old Caucasian man presented in early 2012 with an acute exacerbation of chronic low back pain associated with radiating bilateral leg pain of somatic nature. His gait was normal, midline lumbar tenderness was present with palpation, and movement of the lumbar spine in all planes was painful. Neurological examination showed no abnormalities of sensation and no weakness. Deep tendon reflexes were present and physiological. The plantar responses were physiological. There was no saddle anesthesia or loss of anal tone. An L3 lytic area had been previously identified on magnetic resonance imaging (MRI) in 2010 with two previous radiologically guided biopsies negative for tumor and sterile on culture, showing only fibrous tissue. Serial imaging had shown no change in the appearance of the L3 lesion. A repeat MRI of the lumbar spine prompted by these new symptoms showed a progression of the changes at L3/4 with features of discitis and vertebral signal abnormality extending to the pedicles (Fig. 1). Vertebral osteomyelitis was suspected and a further fine-needle aspirate retrieved two brown pus droplets. Cultures of the aspirate identified Candida glabrata. Blood cultures were negative. Bone scan and gallium scans identified increased uptake of radioisotope in the left sacroiliac joint, left ilium, acetabulum and ischium, consistent with hemipelvic osteomyelitis in addition to the L3/4 discitis. A surgical assessment was obtained at presentation, and in the absence of demonstrable instability or neurological complications, non-operative management was advised. The patient, who suffers from psoriatic arthritis treated with long-term immunosuppression experienced an esophageal perforation in 2009 while being treated with oral corticosteroids and oral non-steroidal anti-inflammatory drugs (NSAIDs) complicated by mediastinitis. This necessitated prolonged treatment in intensive care during which he developed central venous catheter thrombosis and Candida septicaemia in 2009 which was treated with fluconazole. His psoriatic
Figure 1 Magnetic resonance image of lumbar spine – increased signal abnormality in the vertebral bodies extending to the pedicles with fluid in the disc space at L3/4.
arthritis was treated with long-term prednisone 9 mg daily, leflunomide 20 mg daily and methotrexate 25 mg weekly without evidence of lymphopenia or neutropenia on long-term monitoring. Due to the refractory nature of his polyarthritis, two doses of etanercept (50 and later 25 mg) had been administered in mid-2011 after extensive cross-consultation and informed patient consent. Etanercept was discontinued due to intolerance (polyarthralgia after each injection). A right orchidectomy had been performed and radiotherapy was administered in 2008 for a classic seminoma. In late 2011 a left testicular seminoma developed and he was treated with an orchidectomy, and a single cycle of chemotherapy (carboplatin) had been completed 1 month prior to presentation.
© 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
Correspondence
Fluconazole was initially recommenced, but he was subsequently treated with intravenous caspofungin 50 mg daily for 4 weeks, and oral maintenance therapy of posaconazole thereafter. At the time of reporting, after 3 months treatment with posaconazole, the patient continues to suffer from low back pain. His most recent imaging showed ongoing changes with signal loss and gas seen in the L3/4 disc, marked irregularity of the vertebral endplates, without disruption of the posterior elements, segmental instability or any changes in the bony pelvis on CT. A progress surgical opinion was obtained, and in the absence of new signs, continued non-operative management was advised. The patient was reviewed in February 2013. He had been symptom-free with no back pain or neurological symptoms or signs after 2 months treatment with posaconazole after the cessation of caspofungin. Radiographs showed no segmental instability and evolving bony ankylosis of the L3/4 disc space. Candidiasis is a common nosocomial infection, with an increasing incidence and recognition of non-albicans Candida species infections over recent years.1 C. glabrata, formerly known as Torulopsis glabrata, represents an uncommon cause of vertebral osteomyelitis with only 11 previously published cases in the last 3 decades.2 There is a recognized global shift toward invasive candidiasis due to non-albicans Candida species, in particular C. glabrata. The importance of this trend is the increasing variability in susceptibility to anti-fungal drugs,3 and a higher mortality rate associated with these emerging species.4 A previous review found that 14% of cases of Candida osteomyelitis can be attributed to C. glabrata.5 This yeast, a ubiquitous human saprophyte, generally requires the presence of several risk factors to cause invasive disease. Previous reports have noted the correlation of invasive candidal infection with immunosuppression, ethanol abuse, broad spectrum antibacterial drugs, malignancy and intravenous catheterization.6,7 In our patient, three risk factors were present: intravenous catheterization, immunosuppression and malignancy. C. glabrata is relatively resistant to anti-fungal therapy, including azoles, caspofungin and amphotericin B.6 Recommendations for the management of candidiasis from the Infectious Diseases Society of America in 2009 favor initial therapy with an echinocandin anti-fungal.8 However, there are also reports of reduced susceptibility of C. glabrata to echinocandin agents after prolonged therapy.9 In the 12 previous reported cases of C. glabrata vertebral osteomyelitis,
230
the majority have involved use of amphotericin B with limited success. In eight of 11 cases, definitive resolution proved elusive without surgery,2 and early surgical debridement in combination with prolonged anti-fungal therapy has been recommended as the optimal strategy.10 The C. glabrata isolated from the vertebrae of our patient was sensitive to fluconazole, and consequently initial and ongoing therapy consisted of the azole anti-fungal. However, with limited response after several months, the importance of monitoring for changes in susceptibility and the development of resistance is emphasized. In five of 12 cases of C. glabrata vertebral osteomyelitis a preceding fungemia of the same species were noted. The remaining patients were culture-negative but reported symptoms consistent with fungemia.10 However, the onset of symptoms is widely variable, and can range from days to years. Lower back pain is universal and six of 12 cases were associated with lower limb neurological symptoms which ranged from progressive paresthesia to radiculopathy and paraplegia.2 Our case emphasizes the importance of a high clinical suspicion for discitis with atypical micro-organisms in a patient with multiple risk factors. Two prior biopsies had been performed to investigate the possibility of sepsis and malignancy, with false negative results and it seems clear that the condition had remained indolent until increased immunosuppression had facilitated the development of invasive candidiasis. Heightened vigilance for non-albicans Candida species is also of particular importance, with increasing levels of resistance to standard anti-fungal therapy, and poor treatment outcomes. Early detection and prompt institution of therapy are crucial in C. glabrata osteomyelitis to prevent long-term negative outcomes, such as previously documented cases of paraplegia and decreased mobility.2 In summary, we describe a case of C. glabrata discitis/ vertebral osteomyelitis in a patient with multiple risk factors for nosocomial infection, in whom invasive candidiasis remained clinically dormant until further immunosuppression was administered.
ACKNOWLEDGEMENTS The authors are grateful for the patient’s consent in reporting his case.
COMPETING INTERESTS The authors declare no conflict of interest.
International Journal of Rheumatic Diseases 2014; 17: 229–231
Correspondence
Aaron C. TAN,1Nicholas PARKER2 and Mark ARNOLD1,2 Royal North Shore Hospital, and 2Northern Clinical School, University of Sydney, Sydney, NSW, Australia
5
Correspondence: Associate Professor Mark Arnold, email: [email protected]
6
1
7
REFERENCES 1 Burton MJ, Shjah P, Swialto E (2011) Misidentification of Candida parapsilosis as C famata in a clinical case of vertebral osteomyelitis. Am J Med Sci 341, 71–3. 2 Dailey NJM, Young EJ (2011) Candida glabrata spinal osteomyelitis. Am J Med Sci 341, 78–82. 3 Andes DR, Safdar N, Baddley JW et al. (2012) Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patientlevel quantitative review of randomized trials. Clin Infect Dis 54, 1110–22. 4 Fidel PL, Vazquez JA, Sobel JD (1999) Candida glabrata: review of epidemiology, pathogenesis and clinical disease
International Journal of Rheumatic Diseases 2014; 17: 229–231
8
9
10
with comparison to C. albicans. Clin Microbiol Rev 12, 80–96. Miller DJ, Mejicano GC (2001) Vertebral osteomyelitis due to Candida species: case report and literature review. Clin Infect Dis 33, 523–30. Owen PG, Willis BK, Benzel EC (1992) Torulopsis glabrata vertebral osteomyelitis. J Spinal Disord 5, 370–3. Krogh-Madsen M, Arendup MC, Heslet L, Knudsen JD (2006) Amphotericin B and caspofungin resistance in Candida glabrata isolates recovered from a critically ill patient. Clin Infect Dis 42, 938–44. Pappas PG, Kauffman CA, Andes D et al. (2009) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48, 503–35. Thompson GR 3rd, Wiederhold NP, Vallor AC et al. (2008) Development of caspofungin resistance following prolonged therapy for invasive candidiasis secondary to Candida glabrata infection. Antimicrob Agents Chemother 52, 3783–5. Hendrickx L, Van Wijngaerden E, Samson I, Peetermans WE (2001) Candidal vertebral osteomyelitis: report of 6 patients, and a review. Clin Infect Dis 32, 527–33.
231
Copyright of International Journal of Rheumatic Diseases is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Copyright of International Journal of Rheumatic Diseases is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
CORRESPONDENCE
Candida glabrata vertebral osteomyelitis in an immunosuppressed patient Dear Editor, A 47-year-old Caucasian man presented in early 2012 with an acute exacerbation of chronic low back pain associated with radiating bilateral leg pain of somatic nature. His gait was normal, midline lumbar tenderness was present with palpation, and movement of the lumbar spine in all planes was painful. Neurological examination showed no abnormalities of sensation and no weakness. Deep tendon reflexes were present and physiological. The plantar responses were physiological. There was no saddle anesthesia or loss of anal tone. An L3 lytic area had been previously identified on magnetic resonance imaging (MRI) in 2010 with two previous radiologically guided biopsies negative for tumor and sterile on culture, showing only fibrous tissue. Serial imaging had shown no change in the appearance of the L3 lesion. A repeat MRI of the lumbar spine prompted by these new symptoms showed a progression of the changes at L3/4 with features of discitis and vertebral signal abnormality extending to the pedicles (Fig. 1). Vertebral osteomyelitis was suspected and a further fine-needle aspirate retrieved two brown pus droplets. Cultures of the aspirate identified Candida glabrata. Blood cultures were negative. Bone scan and gallium scans identified increased uptake of radioisotope in the left sacroiliac joint, left ilium, acetabulum and ischium, consistent with hemipelvic osteomyelitis in addition to the L3/4 discitis. A surgical assessment was obtained at presentation, and in the absence of demonstrable instability or neurological complications, non-operative management was advised. The patient, who suffers from psoriatic arthritis treated with long-term immunosuppression experienced an esophageal perforation in 2009 while being treated with oral corticosteroids and oral non-steroidal anti-inflammatory drugs (NSAIDs) complicated by mediastinitis. This necessitated prolonged treatment in intensive care during which he developed central venous catheter thrombosis and Candida septicaemia in 2009 which was treated with fluconazole. His psoriatic
Figure 1 Magnetic resonance image of lumbar spine – increased signal abnormality in the vertebral bodies extending to the pedicles with fluid in the disc space at L3/4.
arthritis was treated with long-term prednisone 9 mg daily, leflunomide 20 mg daily and methotrexate 25 mg weekly without evidence of lymphopenia or neutropenia on long-term monitoring. Due to the refractory nature of his polyarthritis, two doses of etanercept (50 and later 25 mg) had been administered in mid-2011 after extensive cross-consultation and informed patient consent. Etanercept was discontinued due to intolerance (polyarthralgia after each injection). A right orchidectomy had been performed and radiotherapy was administered in 2008 for a classic seminoma. In late 2011 a left testicular seminoma developed and he was treated with an orchidectomy, and a single cycle of chemotherapy (carboplatin) had been completed 1 month prior to presentation.
© 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
Correspondence
Fluconazole was initially recommenced, but he was subsequently treated with intravenous caspofungin 50 mg daily for 4 weeks, and oral maintenance therapy of posaconazole thereafter. At the time of reporting, after 3 months treatment with posaconazole, the patient continues to suffer from low back pain. His most recent imaging showed ongoing changes with signal loss and gas seen in the L3/4 disc, marked irregularity of the vertebral endplates, without disruption of the posterior elements, segmental instability or any changes in the bony pelvis on CT. A progress surgical opinion was obtained, and in the absence of new signs, continued non-operative management was advised. The patient was reviewed in February 2013. He had been symptom-free with no back pain or neurological symptoms or signs after 2 months treatment with posaconazole after the cessation of caspofungin. Radiographs showed no segmental instability and evolving bony ankylosis of the L3/4 disc space. Candidiasis is a common nosocomial infection, with an increasing incidence and recognition of non-albicans Candida species infections over recent years.1 C. glabrata, formerly known as Torulopsis glabrata, represents an uncommon cause of vertebral osteomyelitis with only 11 previously published cases in the last 3 decades.2 There is a recognized global shift toward invasive candidiasis due to non-albicans Candida species, in particular C. glabrata. The importance of this trend is the increasing variability in susceptibility to anti-fungal drugs,3 and a higher mortality rate associated with these emerging species.4 A previous review found that 14% of cases of Candida osteomyelitis can be attributed to C. glabrata.5 This yeast, a ubiquitous human saprophyte, generally requires the presence of several risk factors to cause invasive disease. Previous reports have noted the correlation of invasive candidal infection with immunosuppression, ethanol abuse, broad spectrum antibacterial drugs, malignancy and intravenous catheterization.6,7 In our patient, three risk factors were present: intravenous catheterization, immunosuppression and malignancy. C. glabrata is relatively resistant to anti-fungal therapy, including azoles, caspofungin and amphotericin B.6 Recommendations for the management of candidiasis from the Infectious Diseases Society of America in 2009 favor initial therapy with an echinocandin anti-fungal.8 However, there are also reports of reduced susceptibility of C. glabrata to echinocandin agents after prolonged therapy.9 In the 12 previous reported cases of C. glabrata vertebral osteomyelitis,
230
the majority have involved use of amphotericin B with limited success. In eight of 11 cases, definitive resolution proved elusive without surgery,2 and early surgical debridement in combination with prolonged anti-fungal therapy has been recommended as the optimal strategy.10 The C. glabrata isolated from the vertebrae of our patient was sensitive to fluconazole, and consequently initial and ongoing therapy consisted of the azole anti-fungal. However, with limited response after several months, the importance of monitoring for changes in susceptibility and the development of resistance is emphasized. In five of 12 cases of C. glabrata vertebral osteomyelitis a preceding fungemia of the same species were noted. The remaining patients were culture-negative but reported symptoms consistent with fungemia.10 However, the onset of symptoms is widely variable, and can range from days to years. Lower back pain is universal and six of 12 cases were associated with lower limb neurological symptoms which ranged from progressive paresthesia to radiculopathy and paraplegia.2 Our case emphasizes the importance of a high clinical suspicion for discitis with atypical micro-organisms in a patient with multiple risk factors. Two prior biopsies had been performed to investigate the possibility of sepsis and malignancy, with false negative results and it seems clear that the condition had remained indolent until increased immunosuppression had facilitated the development of invasive candidiasis. Heightened vigilance for non-albicans Candida species is also of particular importance, with increasing levels of resistance to standard anti-fungal therapy, and poor treatment outcomes. Early detection and prompt institution of therapy are crucial in C. glabrata osteomyelitis to prevent long-term negative outcomes, such as previously documented cases of paraplegia and decreased mobility.2 In summary, we describe a case of C. glabrata discitis/ vertebral osteomyelitis in a patient with multiple risk factors for nosocomial infection, in whom invasive candidiasis remained clinically dormant until further immunosuppression was administered.
ACKNOWLEDGEMENTS The authors are grateful for the patient’s consent in reporting his case.
COMPETING INTERESTS The authors declare no conflict of interest.
International Journal of Rheumatic Diseases 2014; 17: 229–231
Correspondence
Aaron C. TAN,1Nicholas PARKER2 and Mark ARNOLD1,2 Royal North Shore Hospital, and 2Northern Clinical School, University of Sydney, Sydney, NSW, Australia
5
Correspondence: Associate Professor Mark Arnold, email: [email protected]
6
1
7
REFERENCES 1 Burton MJ, Shjah P, Swialto E (2011) Misidentification of Candida parapsilosis as C famata in a clinical case of vertebral osteomyelitis. Am J Med Sci 341, 71–3. 2 Dailey NJM, Young EJ (2011) Candida glabrata spinal osteomyelitis. Am J Med Sci 341, 78–82. 3 Andes DR, Safdar N, Baddley JW et al. (2012) Impact of treatment strategy on outcomes in patients with candidemia and other forms of invasive candidiasis: a patientlevel quantitative review of randomized trials. Clin Infect Dis 54, 1110–22. 4 Fidel PL, Vazquez JA, Sobel JD (1999) Candida glabrata: review of epidemiology, pathogenesis and clinical disease
International Journal of Rheumatic Diseases 2014; 17: 229–231
8
9
10
with comparison to C. albicans. Clin Microbiol Rev 12, 80–96. Miller DJ, Mejicano GC (2001) Vertebral osteomyelitis due to Candida species: case report and literature review. Clin Infect Dis 33, 523–30. Owen PG, Willis BK, Benzel EC (1992) Torulopsis glabrata vertebral osteomyelitis. J Spinal Disord 5, 370–3. Krogh-Madsen M, Arendup MC, Heslet L, Knudsen JD (2006) Amphotericin B and caspofungin resistance in Candida glabrata isolates recovered from a critically ill patient. Clin Infect Dis 42, 938–44. Pappas PG, Kauffman CA, Andes D et al. (2009) Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis 48, 503–35. Thompson GR 3rd, Wiederhold NP, Vallor AC et al. (2008) Development of caspofungin resistance following prolonged therapy for invasive candidiasis secondary to Candida glabrata infection. Antimicrob Agents Chemother 52, 3783–5. Hendrickx L, Van Wijngaerden E, Samson I, Peetermans WE (2001) Candidal vertebral osteomyelitis: report of 6 patients, and a review. Clin Infect Dis 32, 527–33.
231
Copyright of International Journal of Rheumatic Diseases is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Copyright of International Journal of Rheumatic Diseases is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
