Only eight patients (18.2%) with BS underwent surgery. Culturing was found to be unnecessary because of the positive results of standard tube agglutination test. In 31 patients (72.1%) with TS, the spinal specimens were obtained by open surgery. Although all biopsy specimens of patients with TS were examined histologically, only 19 were sent for culturing. In the remaining 12 patients with tuberculosis, surgeons had assumed that the macroscopic appearance of the involved tissues was analogous to the tissue with tuberculosis, and such specimens were found unnecessary to be sent for culturing. The overall results of the spinal biopsies in TS were as follows: positive histopathologic findings in 77.4% (24/31 patients), positive AFB culture in 57.9% (11/19 patients), and positive AFB smear on Ziehl-Neelsen staining in 47.4% (9/19 patients). Tuberculous spondylitis was diagnosed based on imaging study evidence of a spinal tuberculous focus in conjunction with positive bacteriologic and/or histological findings from a specimen taken at an extraspinal skeletal site in 12 patients who did not undergo surgery. In 3 patients having fistula over the affected vertebrae and right iliac region, specimen of discharge grew M. tuberculosis. Two patients also had a meningeal involvement; one of them had a positive cerebrospinal fluid culture, and the other patient had positive CSF smears for AFB. Of the remaining 7 patients, 2 had a positive sputum culture for M. tuberculosis, and 5 had only positive smears for AFB. Resistance to antituberculous drugs was detected in 23.5% ofthe patients.
Standard tube agglutination testing was positive for antibodies to Brucella (≥1/160) in all patients with brucellosis. This serological test was negative in cases with TS. Blood culture was taken in only 10 patients with BS, and 3 (30%) of them were positive.
All patients received medical treatment with a combination of agents. Although the treatment was medical alone in 36 patients (81.8%) with BS and 12 (27.9%) with TS, 31 patients with TS and 8 patients with BS had an additional surgery (P = 0.0001). The mean duration of medical treatment was significantly longer in TS (12.30 ± 5.40 months; range, 1-28 months) than in BS (4.75 ± 2.33 months; range, 2-11 months) (P = 0.0001). There was no severe adverse event needing cessation of therapy in TS patients, whereas in BS patients, 3 of the treatments were revised. Streptomycin and anti-inflammatory drugs were stopped in one of the patient who developed acute renal failure, and rifampicin was changed to ciprofloxacin in 2 patients with hepatotoxicity.
Five patients with tuberculosis died, whereas in the BS group, no mortality was seen. Only 1 patient with BS had a relapse. Sequelae were mild or moderate in 19 patients (43.2%) in BS and 17 (39.5%) in TS. Unfavorable outcome was in only 3 patients (6.8%) with BS versus in 11 (25.6%) with TS (P = 0.021).
Brucellosis and tuberculosis are both relatively common causes of vertebral osteomyelitis in many endemic areas of the world such as the Mediterranean basin.1-5,18 The frequency of spondylitis in brucellosis ranges from 2% to 58%.1,19-23 Spondylitis is the most common site of skeletal involvement of tuberculosis, comprising in most series approximately 50% of cases.24,25 Recently, an incidence of 51% has been reported from Turkey.26
Tuberculous spondylitis usually affects adults in the fourth decade, and BS affects those older than 50 years. In both forms, men are predominantly affected.10,11,14,18,27-29 On the contrary, in our series, in concordance with other reports from Turkey, the majority of our cases were females.13,22
In vertebral osteomyelitis, early diagnosis is essential because it can be complicated by potentially devastating neurological conditions.7,11,29,30 Unfortunately, diagnosis is easily missed despite the availability of good diagnostic tools, and treatment is often unnecessarily delayed. Cordero and Sanchez10 and Solera et al18 reported that the mean time to diagnosis in BS was 72 and 100 days, respectively. In TS, it was found to vary across studies, from 120 to 231 days.10,11,27-29 In our series, the mean diagnostic delay was significantly shorter in BS (118 days) than in TS (355 days). This fact could be explained by the availability of serological test for brucellosis in Turkey.
A high degree of clinical suspicion of TS allows early diagnosis and treatment. Medical history such as a previous history of tuberculosis or brucellosis or contact with tuberculosis-infected patients or family history for both diseases is valuable clues for the diagnosis.18,26,28,29 The frequency of these clues about medical history has been found to vary across studies, from 8% to 42% of patients with tuberculosis26,27 and 23% in BS,11 which was similar (46.5%) to that reported in our series.
The PPD skin test remains an important diagnostic tool,but several reports notice variable percentages of PPD-negative patients.11,25,27,28 Our data support the fact that a negative tuberculin test does not rule out TS.
Routine laboratory data reported in most studies have been of little diagnostic value.11,27,29 However, in this series, some findings were found to be useful in distinguishing the 2 etiologies. In this respect, high values of ESR and CRP levels and low hemoglobin concentration should point to tuberculosis with compatible clinical and imaging findings for TS.30 Erythrocyte sedimentation rate and CRP levels, although nonspecific, may be useful in evaluating response to treatment and disease activity for both diseases.7,9,30
Vertebral osteomyelitis encompasses a range of clinicalmanifestations. Both infections typically manifest with nonspecific symptoms of discomfort with a slow or insidious onset that may be difficult to distinguish from neck or back pain due to other causes. Patients present with a combination of systemic manifestations such as weight loss, low-grade fever, sweating, malaise, and fatigue, as well as localized back pain.30-32 Fever was more common in BS (range, 60%-85%) than in tuberculosis (range, 32%-58%), which was similar to the reported 63.7% to 37.2% rates in our series, respectively.10,27-29 Localized back pain which is the earliest sign of spondylitis is present in nearly all cases with both diseases,31,32 as seen in this series. In addition to localized back pain and fever, arthralgia and night sweating were more important clinical findings in our cases with brucellosis.
Spondylitis may be complicated by potentially devastating neurological defects that must be considered carefully in endemic areas.31,32 In reported previous series, this rate ranges from 23% to 76% in TS and 10% to 43% in brucellosis.11,18,19,27,28 The larger diagnostic delay partially explains this fact. As expected, neurological involvement was significantly more frequent in TS in our series (44.2% in TS vs 13.6% in BS) similar with the reported studies.
Tuberculous spondylitis most commonly affects the lower thoracic and upper lumbar regions of the spine, both of which comprise 80% to 90%.11,27-29 In some previous reports, the thoracic and lumbar segments were nearly equally affected.1,12,28,33-35 In our case series, the lumbar spine was the most commonly involved region, accounting for 72.1%, followed by the thoracic spine (53.5%), which was similar to the reported 66% and 47% by Pertuiset et al,28 respectively. However, thoracic involvement was more frequent in TS than in BS in our case series (P = 0.030). As for BS, the lumbar spine is frequently reported as the most common site of involvement, followed by thoracic and cervical locations. Lumbar involvement was detected in 79.5% of our patients, which was similar to the reported 45% to 83% rates.10,11,18,19,22,27 Multilevel involvement is more frequent in patients of TS in some of the previously reported studies.11,28,30 However, it has been reported to account for 1% to 24% in cases of tuberculosis28,33,36 and 5%to 21% in cases of brucellosis.11,20,27,28 Similarly, we found a slightly increased number of multilevel involvement in TS group, although it is not statistically significant.
Sacroiliitis, together with spondylitis, is the most frequent osteoarticular involvement in adult patients with brucellosis,18,20,33,37 accounting for 29.5% of our series. Sacroiliac tuberculosis is often associated with tuberculous lesions elsewhere, such as psoas abscess and TS. Approximately 10% of skeletal tuberculosis occurs in sacroiliac joint as seen in our study.38 In our series, sacroiliac joint involvement was not statistically significantly different in both groups (P = 0.062).
The radiological diagnoses of BS and TS are based on the findings of MRI and CT, although radiographs of the spine and bone scan also provide some information. Plain radiographic films do not detect vertebral involvement until at least 50% of a vertebra is destroyed. The bone scan is very sensitive in early stage, but it is scarcely specific.33-35 Therefore, CT and MRI yielding positive findings in the early stage have become the radiological modalities of choice in the diagnosis of both diseases.34,39 It was not the purposes of our study to analyze the yield of the different imaging techniques in both groups. However, we detected that some findings may be helpful in distinguishing the 2 etiologic groups. In this respect, destruction and compression of vertebral body (30.2% and 34.9%, respectively), paraspinal abscesses (67.4%), root and cord compression (20.9% each one), and kyphosis (11.6%) should point to tuberculosis, as described by other authors.1,11,28,29 However, characteristic MRI findings of BS include primarily intact vertebral architecture despite the evidence of diffuse vertebral osteomyelitis, disk space involvement, diskitis, minimal associated paraspinal soft-tissue involvement, and the absence of kyphosis.10,11,18 In our series, 79.5% of the cases with brucellosis showed disk involvement, which is similar to the reported 66% to 78% rates by previous studies Cordero and Sanchez10 and Colmenero et al.11 A kyphotic deformity, frequently described as a feature of TS, may be evident due to collapse and anterior wedging of vertebral bodies.29,40 In our series, it was significantly more frequent in the TS group (P = 0.011).
Bacteriological diagnosis is considered to be a gold standard in BS and TS. Confirmation by culture is highly desirable and leaves no doubt about diagnosis.4,6,11 Collection of a spinal or paraspinal specimens is not absolutely necessary in TS if an extraspinal skeletal focus such as pulmonary, lymph node, and discharge of fistula can be sampled.7,28,31 In some cases, the organism will not be seen on smear or culture, but caseating granuloma, which is a sufficient evidence to begin therapy, will be demonstrated on histological examination,28,30,41 as seen in the present case series. Histological studies of spinal biopsies provided proof of tuberculosis in 77.4% of our patients and in 59% to76% of cases in previous reports.28,29,42 In several studies, the frequency of bacteriologic proof in patients with TS was reported as 47% to 84%,11,28-30 whereas in our series, spinal and extraspinal specimens had a yield of 39.5% and 48.8% for acid-fast smear and culture, respectively. Some surgeons assume that histopathologic examination for TS is sufficient and does not routinely send for M. tuberculosis culturing,1,12,35 as seen in our study. This inappropriate clinical practice could be a major factor threatening the success of tuberculosis control programs in developing countries where antituberculous drug resistance is prevalent. The rate of antituberculous drug resistance in Turkey has been reported as 29.9% to 55.3%.43,44 Our resistance rate was 23.5%; therefore, clinicians and surgeons should be aware of the patterns of antituberculous drug resistance in their geographic area.
Brucella can be cultured from blood during a bacteremic episode, from involved lymph nodes, or from granuloma later in the course of the disease. The presumptive diagnosis of BS can be made serologically.4,18 Brucella agglutination test is quite reliable: 97% of infected persons become positive within 3 weeks of exposures.4 In our study, a spinal biopsy was obtained from only 8 patients with brucellosis because all of the cases had positive results of standard tube agglutination testing.
The management decision should be based on the goals of treatment for each individual case, depending on the stage of the vertebral osteomyelitis.6,7,42,45 Although the rational modality for treatment is combination of both surgical and medical treatments in TS,1,11,12,27,28 antibiotics are the mainstay of the treatment of brucellosis. Antibiotic combination is the norm in both tuberculosis and brucellosis.4,13,18 Although there is no preferred combination for the treatment of spinal brucellosis, the most widely used antibiotic combination for therapy is doxycycline and rifampicin or aminoglycoside. In addition, the problem lies in deciding on the appropriate duration of chemotherapy in both groups.45 This is an area where there is no consensus in tuberculosis. The American Thoracic Society and the Centers for Diseases Control and Prevention clearly indicated that bone and joint tuberculosis requires a minimum of 12 months of therapy,46,47 where there are reported shorter courses, such as 6 or 9 months, which may be appropriate for TS.11,29,46 The preferred duration of therapy for BS should be continued for at least for 3 months or longer4 because of high relapse rates. In our study, whereas half of cases with brucellosis received therapy for more than 3 months, duration of medical treatment were at least 9 months in survivors in TS. Duration of therapy varied according to clinical response and presence of abscess for both diseases.
Surgery is necessary as an adjunct to antibiotic therapy if the vertebral infection produces an abscess, vertebral collapse, or neurological compression.1,6,7,12 The proportion of patients who received surgical treatment varied widely across recent studies from 7% to 55% in TS1,8,11,29 and 3% to 33% in BS.11,13-15,18,19 Need for surgical treatment in 72.1% of our cases with tuberculosis was higher than previously reported rates. This could be explained by advanced stages of tuberculosis in most of our cases; 18.2% of our BS cases were operated on the provided belief of cord compression because of paraspinal soft-tissue involvement similar with the previous reports.
The prognosis in general is good with adequate treatment sustained for an appropriate length of time for both diseases. The diversity of criteria used for evaluation of treatment in each one may cause variations in the results obtained by different researcher. Our series showed a 93.2% favorable outcome in brucellosis and a 74.4% in tuberculosis, which are similar with previously reported rates.10,11,13-15,27-29 The higher rate of unfavorable outcome and death in our cases with tuberculosis than in brucellosis may partially be explained by larger diagnostic delay and more destructive process.20 In the present study, relapse rate was 2.3% in BS, occurring in 4% to 55% according to various studies.11,13,18,22 No relapse was seen in our cases with tuberculosis. This is similar to the study reported by Alothman et al.29 This fact may possibly reflect to be given the adequate treatment duration as we stated above.
Regarding to the outcome, it is important to have a high level of clinical suspicion, especially in patients in countries with a high prevalence of tuberculosis or brucellosis. Our study confirmed that documented history, clinical presentation, laboratory and histological examination, and radiographic imaging can be highly suggestive of spinal tuberculosis and brucellosis. Once the diagnosis of spondylitis is made, even in the absence of positive culture, serum agglutination test, history of fever, night sweating, arthralgia, and the radiological findings of disk involvement will be helpful for the diagnosis of brucellosis, whereas history of contact with active pulmonary tuberculosis or recently or formerly diagnosed tuberculosis, malaise, neurological complaints, higher ESR and CRP, and radiological findings of vertebral destruction and compression, epidural and paravertebral soft-tissue involvement, and abscess and thoracic vertebra involvement with or without kyphosis can be used for the early diagnosis of tuberculosis. In endemic areas, this may be sufficient for empirical treatment for both diseases. A good outcome is expected if the diagnosis is made in early stages before the appearance of spinal deformity.
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