Introduction: tuberculosis (TB) remains a major cause
of morbidity and mortality worldwide. The incidence of TB has increased
since the 1980s. Given the increasing prevalence of TB worldwide,
osteoarticular TB (OATB) is a significant health problem.
Methods: retrospective study of a case series of hospitalized patients with
confirmed OATB by culture or histopathological examination who were seen at
a reference orthopedic hospital in São Paulo, Brazil, from 2014 to 2019.
Results: thirty patients with confirmed bone and joint TB were seen from
2014 to 2019. The main sites of OATB were the spine (83.3 %) and the
appendicular skeleton (26.7 %). Indication of surgical treatment was
significantly related to the need for hospitalization (p=0.009) and the
increased length of hospital stay (p=0.005). Presence of sequelae at the
end of treatment was correlated with the presence of motor deficit at the
time of OATB diagnosis (p=0.035) as well as with initial presence of
functional limitation (p=0.025) and with high value of C-reactive
protein at the end of treatment (p=0.037).
Conclusions: the delay in the onset of clinical and laboratory signs of
cases of osteoarticular infections hinders the early
diagnosis and treatment of the disease, resulting in major complications
sometimes requiring surgical treatment and consequently leading to a
prolonged hospital stay, evidence of high inflammatory activities, and the
presence of neurological deficits.
Introduction
Tuberculosis (TB) is an important public health problem, with serious
medical, social, and financial impacts, especially in developing countries.
The main etiological agent of this disease is the bacterium Mycobacterium tuberculosis. Every year, approximately 3 million people with TB remain
undiagnosed and continue to spread the disease in the community, making it
difficult to control. When TB occurs in organ systems other than the lungs,
it is called extrapulmonary TB (EPTB). Musculoskeletal TB is responsible for
10–15 % of all EPTB cases. Spinal TB is the most common form of
skeletal TB, accounting for approximately 50 % of all cases (Malaviya,
2003).
Clinical and demographic characteristics of 30 patients
with OATB seen between 2014 and 2019.
VariableSexN=30N (%)Male1653.3Female1446.6EthnicityN=30N (%)White1550.0Other826.6Black620.0Ignored13.3Age (years)Mean ± SD41.7 ± 17.3Median (min; max)40 (2; 79)Initial treatment regimenN=30N (%)Inpatient2273.3Outpatient826.6Mean number of days hospitalized (N=22) ± SD36.5 ± 34.3ComorbiditiesN=30N (%)Presence of comorbidities2273.3Types of comorbiditiesN=22N (%)Cardiometabolic diseases731.8Rheumatic diseases29.1Neoplasm29.1Mental disorder14.5Substance abuse627.3Other418.2HIV serology status knownN=30N (%)HIV positive13.3OATB typeN=30N (%)Disseminated TB1240.0Spinal TB2583.3TB in appendicular skeleton826.7Spinal level affectedN=25N (%)Thoracic936.0Thoraco-lumbar728.0Lumbar624.0Lumbosacral28.0Thoracic, lumbar, and sacral14.0Appendicular siteN=8N (%)Knee450.0Hip112.5Tibia112.5Ankle112.5Forearm112.5Culture for mycobacteria performed on bone tissueN=30N (%)Culture positive2376.6
Continued.
VariableHistopathological examination performed on bone tissueN=30N (%)Suggestive of TB2170.0Not suggestive826.6Result not available13.3Ziehl Nielson stain (ZNS) test performedN=30N (%)ZNS positive310.0Pulmonary radiological examination performedN=23N (%)Finding compatible with pulmonary TB1043.5C-reactive protein (CRP) measured at the beginning of treatmentN=30N (%)Elevated2893.3CRP levels at beginning of treatment (mg L-1)Mean ± SD66.5 ± 65.4Median (min; max)45.1 (1.3; 309.6)CRP levels at end of treatment (mg L-1)Mean ± SD10.3 ± 13.2Median (min; max)3.8 (0.7; 42.9)Materials and methods
A retrospective study was conducted on a series of patients with a diagnosis
of OATB confirmed by culture or histological examination seen at the
Instituto de Ortopedia e Traumatologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo from 2014 to 2019. For the analysis of outcomes, remission was defined as
the absence of signs and symptoms of infection activity 6 months after the
end of treatment. The permanence of motor or sensory sequelae related to the
initial onset of OATB was analyzed separately.
Quantitative variables were described using summary measures (mean and
standard deviation or median) and compared between groups using Student's
t-tests or Mann–Whitney tests. Qualitative variables were described using
absolute and relative frequencies. The existence of association between
variables was verified with chi-square tests or exact tests (Fisher's exact
test or likelihood ratio test). IBM-SPSS for Windows version 20.0 software
was used to do the analyses. Data were tabulated using Microsoft Excel 2003
software. The tests were performed at a significance level of 5 %.
(Kirkwood and Sterne, 2006).
Signs and/or symptoms described for the 30 patients with
OATB (*).
Type of deficitN=17N (%)Paraparesis952.9Paraplegia635.3Tetraparesis15.8Unilateral paresis15.8Results
In this survey, 30 patients with confirmed OATB were found from 2014 to 2019
at our hospital. Among them, 73.3 % required hospitalization, mainly for
diagnostic investigation, with a case fatality rate of 3.3 % and an
average length of stay of 36.5 d. Of the patients, 46.6 % had TB in more than one organ
and 40 % had pulmonary TB concomitantly. Main sites of OATB were spine
(83.3 %), with greater involvement of the thoracic spine (36 %). Among
the 30 patients, 26.7 % had TB in the appendicular skeleton, with knee
involvement in 50 %. Diagnosis was confirmed by M. tuberculosis complex isolation in
culture in 76.6 % of patients. Only 10 % had a positive screening for
acid-fast bacilli (AFB) by conventional sputum smear microscopy test. In the
investigation of disseminated TB, 20 patients underwent chest X-ray and
43.4 % of those had signs suggestive of pulmonary TB. Regarding laboratory
tests, 93.3 % had altered C-reactive protein levels, with a mean of 68.4
(normal reference value <5.0 mg mL-1). The mean value of this test at
the end of treatment was 10.3. Table 1 describes the main clinical and
demographic variables of patients.
Type of treatment for the 30 patients with OATB.
TreatmentN=30N (%)Antituberculosis drugs only30100Antituberculosis drugs and surgery1756.6Type of surgical treatmentN=17N (%)Debridement and spinal arthrodesis1164.7Debridement635.3Antituberculous drugs usedPhase 1 medicationN=30N (%)RIPE12480RIP226.7RIE3310IPE413.3Other phase 1 medicationsN=2N (%)Streptomycin150Levofloxacin and streptomycin150Phase 2 medicationN=30N (%)Rifampicin and isoniazid2790Isoniazid13.3Other26.6Other phase 2 medicationsN=2N (%)Levofloxacin and ethambutol150Pyrazinamide + streptomycin150Mean treatment time (days)316.9
RIPE1: rifampicin, isoniazid, pyrazinamide, and ethambutol. RIP2: rifampicin, isoniazid, and pyrazinamide. RIE3: rifampicin, isoniazid, and ethambutol. IPE4: isoniazid, pyrazinamide, and ethambutol.
Outcomes after 6 months of follow-up for the 30 patients
included in the study.
Outcome at 6 monthsN=30N (%)Remission2273.3Death13.3Recurrence00.0Lost to follow-up26.7Has not yet completed follow-up time at the time of analysis516.7
The mean interval between the onset of symptoms to diagnosis was 358 d.
Table 2 demonstrates the main signs and symptoms described for the 30
patients. 17 patients had some type of neurological deficit associated with
the diagnosis of OATB, as described in Table 3.
Type of sequelae present at the end of the follow-up period.
Chi-square test. a Fisher's exact test. b Mann–Whitney test.
All patients received antituberculous treatment as recommended by the
Brazilian Guidelines (Ministério da Saúde, 2022) and 56.6 % of
patients also underwent surgical treatment. Regarding the surgical treatment
used, debridement and spine arthrodesis was performed in 64.71 % of the
patients and debridement was performed in 35.2 % of the patients (Table 4).
Most patients (73.3 %) achieved remission after the 6-month follow-up
period and only one patient died due to cardiac complications after surgical
procedures, as shown in Table 5. Among the patients who went into remission
however, 18 patients (60 %) had some type of sequelae, with chronic pain
being described in 61 % of patients, followed by paraplegia (22 %),
paresis (11 %), and paresthesia (5.5 %) (Table 6). One case had spinal
deformity (kyphosis) in association with lower back pain.
Patient characteristics and development of sequelae.
Chi-squared test. a Fisher's exact test. b Likelihood ratio test. c Student's t-test.
Diagnostic testing and development of sequelae.
VariableSequelae Total (N=30)pNo (N=12)Yes (N=18)Culture, n (%)>0.999aNegative3 (25)4 (22.2)7 (23.3)Positive9 (75)14 (77.8)23 (76.7)TB suggestive histopathological examination, n (%)>0.999aNegative3 (25)5 (29.4)8 (27.6)Positive9 (75)12 (70.6)21 (72.4)TB suggestive radiological findings, n (%)0.128aNegative4 (33.3)1 (5.6)5 (16.7)Positive8 (66.7)17 (94.4)25 (83.3)ZNS test, n (%)>0.999aNegative11 (91.7)16 (88.9)27 (90)Positive1 (8.3)2 (11.1)3 (10)TB suggestive pulmonary radiological findings, n (%)>0.999aNegative3 (25)4 (22.2)7 (23.3)Positive9 (75)14 (77.8)23 (76.7)CRP at the beginning of treatment (mg L-1)0.465bmean ± SD55.6 ± 51.673.8 ± 73.766.5 ± 65.4median (min; max.)36.9 (1.3; 165.4)57.9 (6.9; 309.6)45.1 (1.3; 309.6)CRP at end of treatment (mg L-1)0.037bMean ± SD6.2 ± 12.312.9 ± 13.410.3 ± 13.2Median (min; max.)1.5 (0.7; 42.9)6.4 (1.3; 39.4)3.8 (0.7; 42.9)
Chi-squared test. a Fisher's exact test. b Mann–Whitney test.
When the medical variables were correlated with the need for surgical
treatment, it was found that patients who required surgery had a greater
need for hospitalization and a longer duration of hospital stay (p<0.05) (Table 7). Median number of hospitalization days was 46 d. Median
time of symptoms in the group with surgical treatment was 150 d, while in
the group with clinical treatment, it was 180 d.
There was no statistically significant difference when analyzing the
clinical characteristics of patients and the risk of developing sequelae at
the end of treatment, although patients with comorbidities tended to have
more sequelae at the end of treatment (91.7 versus 61.1, p=0.099), as
shown in Table 8.
In the analysis of the association between the results of diagnostic tests
performed at the beginning and during the treatment and the presence of
sequelae at the end of the treatment, it was found that the high value of
CRP (mg L-1) at the end of treatment was significantly correlated with
sequelae at the end of treatment (median 1.5 versus 6.4, p=0.037), as
shown in Table 9.
Discussion
Diagnosis of OATB can be challenging. The microscopic examination (Ziehl
Neelson stain or ZNS) is less useful for paucibacillary diseases.
Mycobacterial culture has a high sensitivity for the diagnosis of TB
(Forbes et al., 2018). In this study, the presence of M. tuberculosis isolated in culture was
found in 76.67 % of the cases. Only 10 % had a positive ZNS test.
In the investigation of disseminated TB, 43.48 % of the patients in this
study had radiological findings suggestive of pulmonary TB, in contrast to
lower incidences described in literature (Hogan et al., 2019).
Back pain is the most cited symptom in the literature (Ferrer et al., 2012).
In our study, 73.3 % patients had lower back pain. The mean time from
symptoms to diagnosis was 358 d, suggesting a late diagnosis.
The guidelines suggest that surgery should be considered in patients with
Pott's disease with significant neurological deficits and those who do not respond to medical therapy (Hogan et al., 2019; Malaviya,
2003). During the treatment of the patients in our study, 56.6 % of the
patients underwent surgical procedures.
In the current study, 73.3 % of patients had remission of the condition,
but, in spite of that, 60 % had some type of sequelae. This may be related
to the delay in the diagnosis of tuberculosis, leading to irreversible motor
or sensory deficits even with treatment of the infection. The variables that
were statistically relevant when associated with the presence of sequelae
were functional limitation (p=0.026) and motor deficit (p=0.035), as
previously reported (Wang et al., 2016).
Patients requiring surgery were hospitalized for longer periods than those
in the group receiving only antituberculostatic treatment (Medeiros et al.,
2007; Wang et al., 2016).
In several reports, there were increased levels of CRP in the initial phase,
with decreases occurring throughout treatment (Forbes et al., 2018; Mbuh et
al., 2019; Muller et al., 2013). In the present study, there was a
significant association between a higher value of CRP (median = 6.4 mg dL-1)
at the end of treatment and the presence of long-term sequelae (p<0.037).
Conclusion
In a reference hospital for the treatment of osteoarticular diseases, 30
patients with OATB were confirmed from 2014 to 2019. Pulmonary TB with
concomitant OATB was evident in 40 % of patients. The main sites of OA
infection were the spine (83.3 %) and 26.6 % had TB in the appendicular
skeleton.
The need for surgical treatment was significantly correlated with the need
for hospitalization (p=0.009) and the increased length of hospital stay
(p=0.005). The presence of sequelae at the end of treatment was
correlated with the presence of motor deficit at the beginning of treatment
(p=0.035) as well as with the initial presence of functional limitation
(p=0.025) and with the high value of CRP at the end of treatment (p=0.037).
Data availability
Data is available under the following DOI: 10.17605/OSF.IO/Y4Q6R (de Oliveira, 2022).
Author contributions
CTP, PRDdO, and ALLML planned the campaign; CTP performed the measurements;
CTP, PRDdO, and ALLML analyzed the data; CTP and PRDdO wrote the paper
draft; and CTP, PRDdO, ALLML, VCdC, AMdA, and VFAdM reviewed and edited the
paper.
Competing interests
The contact author has declared that none of the authors has any competing interests.
Ethical statement
This study was approved by the Ethics and Research Committee, CAPPesq,
through the Brazil Platform. CAAE: 30921420200000068.
Disclaimer
Publisher’s note: Copernicus Publications remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Acknowledgements
The authors with to thank the hospital infection control team that
contributed with administrative support and data collection for this study.
Review statement
This paper was edited by Gina Suh and reviewed by three anonymous referees.
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