Tuberculosis (TB) has a severe effect on human health, especially in developing countries.1–3 Although TB commonly affect the lungs, spinal involvement occurs in approximately 1% of patients.4 Spinal TB can cause spinal cord compression, which may lead to pain, limited activity, kyphosis, paralysis, and even death.5–8 Thus, it is necessary for both surgeons and patients to understand spinal TB. China has the second highest burden of TB in the world, accounting for 17% of global cases.9 Southwest China, an economically undeveloped region, has the highest burden of TB in China.10 Several studies of the characteristics of spinal TB have been conducted in other countries.11–14 However, only 1 study has focused on spinal TB in southwest China, and it had a relatively small sample size (284 cases) and a relatively short time span (2004–2010).9 More information is needed on spinal TB in southwest China. This study retrospectively reviewed the medical data of 921 patients who were treated for spinal TB at a general hospital in southwest China between 2001 and 2016 to gain useful insights into spinal TB.
Materials and Methods
Chongqing City is a municipality in southwest China. According to the Fourth National Tuberculosis Survey, the prevalence rate for TB in Chongqing was 112.5 per 100,000 in 2009.9 The study was performed at a general hospital located in a major urban zone of Chongqing.
This study retrospectively reviewed the medical data of 921 patients who were admitted to the department of orthopedics at the study hospital for spinal TB from 2001 to 2016. This study was approved by the medical ethics committee and the institutional review board of Xinqiao Hospital, Third Military Medical University, in accordance with the ethical standards of the 1964 Declaration of Helsinki, as revised in 2000. Patients received a thorough explanation of the study, and written informed consent was obtained.
The diagnosis of spinal TB was based on clinical symptoms, physical signs, hematologic findings (C-reactive protein [CRP] level and erythrocyte sedimentation rate [ESR]), radiologic findings, pathologic findings, and assessment of a history of pulmonary TB. Empirical anti-TB chemotherapy was administered when it was difficult to obtain a definite diagnosis.
All patients who were diagnosed with spinal TB were routinely treated with anti-TB chemotherapy (rifampicin 450 mg/d, isoniazid 300 mg/d, pyrazinamide 750 mg/d, and ethambutol 750 mg/d) for 12 to 18 months. Kidney function and liver function were monitored during anti-TB chemotherapy. Indications for surgery for spinal TB were as follows: (1) deterioration of spinal stability; (2) progressive or severe neurologic defect; or (3) severe kyphosis.
At the study institution, a research group is specifically responsible for data collection and follow-up. On hospital admission, patient demographic data, clinical manifestations, radiologic findings, laboratory findings, and treatment methods were recorded. Patients who had inadequate demographic, clinical, or examination information were excluded from the study. Follow-up information was obtained by telephone, through e-mail, and during return visits to the outpatient department, which were performed every 3 months for the first year after treatment and every 6 months for the second year. “Cure” was defined as follows: within 2 years after treatment, no recurrence of tuberculous lesions, maintenance of ESR within the normal range, the finding of bone union in the lesion location on radiographic examination, and disappearance of clinical symptoms for 3 months.15
Demographics and Epidemiology
During the 16-year study period, 921 patients were diagnosed with spinal TB at the study hospital. Spinal TB accounted for 93.22% (921 of 988) of the cases of infectious diskitis diagnosed during the study period. The annual incidence of spinal TB increased throughout the study period (22–104 cases per year) (Figure 1). All patients came from provinces or municipalities in southwest China (Chongqing, 71.88%; Szechwan, 18.24%; Guizhou, 9.12%; Yunnan, 0.76%) (Table 1). The incidence of spinal TB was higher in the rural population than in the urban population from 2001 to 2016 (Figure 2). For the entire region of southwest China, during the study period, approximately 56% of the population lived in a rural setting. Among the 921 patients included in this study, the percentage of those living in a rural setting was 72.96%. The male-to-female ratio was 1.39. Mean age was 43.46 years overall, 43.27 years for the 536 men included in the study and 43.73 years for the 385 women. The greatest number of patients were 41 to 50 years old (22.04%). The 3 most common comorbidities were hypertension (4.13%), osteoporosis (3.58%), and diabetes (3.47%) (Table 1). In this study, multifocal TB was present in 227 (24.65%) of 921 patients with spinal TB. The most common involved extraspinal site was the lung (167, 18.13%), followed by the kidney (14, 1.52%), pleura (11, 1.19%), meninx (10, 1.09%), lymph node (5, 0.54%), peritoneum (4, 0.43%), intestine (3, 0.33%), rib (3, 0.33%), testis (3, 0.33%), elbow (2, 0.22%), popliteal space (1, 0.11%), shoulder (1, 0.11%), pubis (1, 0.11%), ankle (1, 0.11%), and tibia (1, 0.11%). The proportional rate (ie, the number of patients with an extraspinal TB site per 227 patients) is presented in Figure 3.
Proportional graph of the annual number of cases of spinal tuberculosis (TB)/non-TB diskitis between 2001 and 2016.
Demographic Characteristics of 921 Patients With Spinal Tuberculosis
Proportional graph of the annual number of rural and urban patients with spinal tuberculosis (TB) between 2001 and 2016.
Proportional graph of the extraspinal sites of patients with spinal tuberculosis.
Local pain was the most common symptom (901, 97.8%), followed by night sweats (342, 37.1%), low-grade fever (297, 32.2%), weight loss (≥5 kg) (259, 28.1%), kyphosis (231, 25.1%), numbness (191, 20.7%), decreased sensation (188, 20.4%), paralysis (decreased muscular strength [0–4 degree] in any 1 muscle group of either lower limb) (183, 19.9%), weakness (164, 17.8%), decreased reflex (96, 10.4%), radicular pain (95, 10.3%), mass (90, 9.8%), positive leg-raising test (71, 7.7%), and sinus (31, 3.4%). Overall mean duration of symptoms was 23.23 months, and there was a significant difference in the duration of symptoms between the rural population (28.40 months) and the urban population (10.17 months) (P=.041) (Table 2).
Clinical Symptoms and Signs and Initial Laboratory and Imaging Findings
Mean ESR was 43.46 mm/h (range, 1–575 mm/h). Patients with ESR of less than 20 mm/h accounted for 32.68% of cases (301 patients), and those with ESR of greater than 100 mm/h accounted for 5.10% of cases (47 patients). Mean CRP value was 35.12 mg/L (range, 0.7–302.4 mg/L). The percentage of patients with a normal CPR level (≤8 mg/L) was 25.84% (238 patients). The TB antibody test was not a routine component of the examination, and only 164 patients had undergone this test. A positive finding on the TB antibody test was reported for 15.85% of cases (26 patients), a weak positive finding was reported for 15.85% of cases (26 patients), and a negative finding was reported for 68.30% of cases (112 patients) (Table 2).
The 921 patients had 2227 lesions: the lumbar spine was the most commonly involved site (997, 44.77%), followed by the thoracic spine (971, 43.60%). The cervical spine (150, 6.74%) and the sacral spine (109, 4.89%) were less commonly involved (Table 2, Figure 4). The mean number of involved vertebrae per patient was 2.42 (range, 1–14). The most common number of involved vertebrae was 2 (572, 62.11%). Multiple-level skip lesions occurred in 42 patients (4.56%) (Table 2).
Proportional graph of the involved spinal level of patients with spinal tuberculosis.
Treatment and Outcomes
Types of treatment are summarized in Table 3. A total of 211 (22.9%) patients received only anti-TB chemotherapy. Surgical methods included debridement, bone grafting, and instrumentation. The surgical approach (single anterior approach, single posterior approach, and a combination of an anterior and a posterior approach) was selected based on the patient's condition. With the development of minimally invasive spine surgical methods, percutaneous instrumentation has been used since 2009.
Treatment and Follow-up Outcomes
Follow-up information was available for 730 of the 921 patients. A total of 714 patients (97.81%) gradually achieved cure within 18 months of hospital admission. All 16 (2.19%) patients who did not achieve cure did not follow the physician's advice about anti-TB chemotherapy (Table 3).
In the current study, 231 (25.1%) patients had kyphotic deformity. Of these patients, 5 had cervical kyphosis, 123 had thoracic kyphosis, and 103 had lumbar kyphosis. Among the 231 patients, 3 (2 patients with thoracic kyphosis and 1 patient with lumbar kyphosis) did not undergo corrective surgery because they could not tolerate the procedure because of diabetes and heart disease. The other 228 patients underwent surgery. In total, 204 patients underwent bone grafting/autogeneic iliac bone/pedicle screw instrumentation, and 24 patients underwent a combination of bone grafting/autogeneic iliac bone/pedicle screw instrumentation and pedicle subtraction osteotomy. All patients who had surgery were satisfied with the effect of kyphosis correction, which was maintained for the follow-up period of 2 years after surgery.
All 183 patients who had paralysis underwent surgery. Only 1 elderly woman (78 years old) who had relatively long duration of paralysis (1 month) did not obtain symptom improvement. All of the other 182 patients obtained symptom improvement of 1 to 2 degrees of muscular strength.
In this study, 5 patients had multidrug-resistant TB. Multidrug-resistant TB was treated with 18 months of administration of an injectable agent, such as kanamycin or amikacin, a fluoroquinolone, and at least 3 other agents with anti-TB biologic activity (ethionamide, cycloserine, and prothionamide). First-line agents (ethambutol and pyrazinamide) with retained activity also were used. Within the follow-up period, these 5 patients were cured and achieved satisfactory symptom improvement.
During the past few decades, great effort has been made to control the spread of TB in China. However, a serious epidemic of multidrug-resistant TB has occurred and is associated with problems with the public health system and the hospital system.1,2 According to the World Health Organization, each year, 1.4 million new cases of TB occur in China and 1.81 million deaths result from TB in Asia.3 In this study, the annual incidence of spinal TB increased throughout the study period (22–104 cases per year). Although spinal involvement occurs only in approximately 1% of patients with TB,4 considering the huge population of China, millions of Chinese patients are affected by spinal TB. Southwest China, as an economically undeveloped region, had the greatest burden of TB in China.10 Little research has been done on spinal TB in southwest China. The current study collected and assessed the data of 921 patients with spinal TB who were treated at a general hospital in southwest China from 2001 to 2016 to obtain useful insights into spinal TB.
This retrospective study showed that spinal TB can affect all age groups. The youngest patient was 1 year old, and the oldest was 88 years old. Most patients were middle-aged and elderly, with 84.26% of patients between 21 and 70 years old. The greatest number of patients were 41 to 50 years old (22.04%). The age group of patients affected by spinal TB was controversial. Previous studies showed that the most commonly affected age groups were young patients (10–19 years old, 27.3%) in Sabah, Malaysia12; young adult patients (31–40 years old, 30.6%) in Chongqing, China9; and elderly patients (older than 70 years, 55%) in Taiwan, China.16
The current study found a higher incidence of spinal TB in rural populations than in urban populations and a higher incidence of spinal TB compared with non-TB diskitis from 2001 to 2016. Based on these results and the authors' experience, diskitis affecting a rural patient is highly suggestive of spinal TB. Additionally, in the current study, the duration of symptoms was significantly longer in rural populations compared with urban populations. This finding may be related to limited finances, isolated location, and poor knowledge about TB among rural populations. A previous study reported that neurologic dysfunction in association with active spinal TB can be prevented with early diagnosis and prompt treatment.17 Therefore, the Chinese government should invest more funds into rural Medicare and Medicaid projects. In addition, hospitals can offer free rural clinics to improve knowledge about TB.
In total, 227 patients (24.65%) had extraspinal TB infection. The most common extraspinal site was the lung (167 cases, 18.13%). In total, 131 patients had pulmonary TB, followed by gradual appearance of spine symptoms. For 36 patients, the primary symptoms involved only the spine, and pulmonary TB was diagnosed simultaneously on hospital admission. In these cases, it was difficult to identify the primary source of infection. It is generally believed that the spine was infected from a primary focus through the vertebral venous system.11 Thus, to prevent spine infection, early diagnosis and prompt treatment are necessary for patients with pulmonary TB.
Consistent with previous studies, in this study, the lumbar spine and the lower thoracic spine were the most commonly involved sites for spinal TB.9,11–13 The sacral spine was the least affected site, accounting for only 4.89% of cases. Local pain was the most common symptom (97.8%).9 The typical general symptoms of TB (night sweats, 37.1%; low-grade fever, 32.2%; weight loss, 28.1%); kyphosis (25.1%); and neurologic deficits (numbness, 20.7%; decreased sensation, 20.4%; paralysis, 19.9%) also were present in patients with spinal TB.
Assessment of ESR among patients with spinal TB is common, with reported mean values of 84.5 mm/h (range, 1–143 mm/h)12 and 41.2 mm/h (range, 1–145 mm/h).9 In this study, ESR was 1 to 575 mm/h, with a mean value of 43.46 mm/h. Of the study patients, 32.68% had a normal ESR (<20 mm/h) and 5.10% had an ESR of greater than 100 mm/h. The ESR is a sensitive but nonspecific test; it is used only to evaluate disease activity. Another commonly used index to assess the state of TB is CRP level, with a reported mean value of 26.4 mg/L (range, 0.7–303 mg/L). In this study, 15.8% of patients had a normal ESR (<8 mg/L).9 In addition, CRP ranged from 0.7 to 302.4 mg/L, with mean value of 35.12 mg/L. Of the study patients, 25.84% had a normal ESR. The TB antibody test was not routinely included in the examination. The current study showed that the positive rate for the TB antibody test was only 31.70% (positive+weak positive), showing that the sensitivity of this test for the diagnosis of spinal TB is low.
In this study, 2.19% of patients did not achieve cure. These patients did not comply with the physician's advice about anti-TB chemotherapy, and they discontinued use of the chemotherapeutic agents after early improvement of their clinical status. The goals of surgery for spinal TB were to maintain spinal stability and correct kyphosis. Anti-TB chemotherapy, the mainstay of treatment for spinal TB, should be continued throughout the treatment period.18,19
Multidrug-resistant TB shows resistance to both rifampicin and isoniazid.20 Multidrug-resistant TB is increasingly common, but there is a large difference between the actual number of cases and the number of diagnosed cases because there is inadequate access to quick and convenient drug susceptibility testing in the quality-assured laboratories.21 Compared with drug-susceptible TB, treatment of multidrug-resistant TB is challenging.22 In this study, patients who had multidrug-resistant TB were offered an individualized regimen according to their pattern of drug resistance.
The current study had some limitations. First, the study was retrospective. Second, the sample was small (921 patients). A prospective randomized controlled trial with a larger sample is necessary to provide more helpful information on the features of spinal TB.