Unusual presentations of osteoarticular tuberculosis: experience from a tertiary center in Liguria

To study the characteristics of bone or joint tuberculosis (TB) accompanied by TB in other organs (especially the lung), and to study patients' and doctors' delay in detecting bone or joint TB. A retrospective study was conducted on 33 patients with bone or joint TB concurrent with TB of other organs, especially the lung, who were admitted to our hospital between 1981 and 2005. The patients were divided into the following three groups according to the organ of concurrent TB : (1) miliary TB group (N = 10), (2) pulmonary TB group (N = 19), and (3) other TB site group (N = 4). The relationship between bone/joint TB and TB of other organs was studied by comparing the three groups with respect to the time of appearance of musculo-skeletal symptoms or signs such as swelling and pain and that of symptoms or signs originating from other organs, such as cough, sputum, miliary pattern on chest radiograph and superficial lymph node swelling. The mean age (SD) of patients was 50.5 (18.9) yr, and the male to female ratio was 23 : 10. Among 33 patients, bone TB (including 18 spinal TB) was detected in 24 patients, joint TB in 14, and abscess in 3 (concurrent lesions in some patients). The mean intervals from onset of symptoms to consultation (patients' delay), from consultation to diagnosis (doctors' delay) and from symptom onset to diagnosis (total delay) were 5.5 (13.9), 3.4 (5.2) and 8.9 (13.9) months, respectively. (1) Bone/joint TB concurrent with miliary TB (N = 10) In 8 patients with mean age of 61.0 (17.4) yr, musculo-skeletal symptoms/signs preceded respiratory symptoms or appearance of miliary pattern on chest radiograph by 7.8 (7.2) (range; 1-24) months. The patients', doctors' and total delays were 0.4 (0.5), 7.3 (7.8), and 7.7 (7.6) months, respectively. In most cases, bone/joint TB was diagnosed after the onset of miliary pattern on chest radiograph. In one patient with simultaneous onset of musculo-skeletal and respiratory symptoms/signs (age 21 yr), the interval of total delay was 1 month, and in one patient with musculoskeletal symptoms which appeared six months later than respiratory symptoms (age 28 yr), the interval of total delay was 2 months. (2) Bone/joint TB concurrent with active pulmonary TB (N = 19). In this group, the mean age was 52.2 (17.1) yr, and males were predominant (M/F = 15/4). Active pulmonary TB was diagnosed by positive sputum culture in 13 patients, by positive sputum smear or PCR results in 4 patients, and by the clinical course in 2 patients. Ten patients (53%) had a previous TB history. Cavitary lesion was observed in 15 patients, and the upper lobes were predominantly involved on chest radiograph in 19 patients, indicating that the pulmonary TB was probably post-primary (reactivation) in all patients. In 9 patients with mean age of 49.7 (15.7) yr, musculo-skeletal symptoms/signs preceded respiratory symptoms by 14.1 (14.0) (range; 4-48) months. The patients', doctors' and total delays were 13.3 (17.8), 3.8 (6.6), and 17.1 (16.1) months, respectively. On the other hand, in 10 patients with mean age of 54.5 (18.7) yr, musculo-skeletal symptoms/signs and respiratory symptoms/signs appeared simultaneously, and the total delay was 2.7 (1.9) months. Twelve of 19 patients (63%) had complications such as diabetes mellitus, steroid use, and liver diseases. In cases with miliary or pulmonary tuberculosis, the total delay in diagnosis (Y) correlates positively with the time lag from onset of musculo-skeletal symptoms to respiratory symptoms/signs (X), and the regression line (Y = 0.94X + 2.3, r = 0.98, p < 0.001) was almost linear (Y = X), indicating that the diagnosis of bone/joint TB was made just after the diagnosis of miliary or pulmonary TB. (3) Bone/joint TB concurrent with TB of other sites (N = 4) In 2 female cases (21 and 28 yrs) with cervical lymph node TB, musculo-skeletal symptoms/signs and cervical lymph node swelling appeared simultaneously. In a 54-yr male patient, musculo-skeletal symptoms/signs appeared 5 years after appearance of testicular enlargement, and testicular TB was diagnosed by biopsy simultaneously. In a 33 year-old male patient, musculo-skeletal symptoms/signs appeared 7 months after the drainage of pleural and pericardial effusions (TB was not diagnosed initially), and then the diagnosis of bone/joint, pleural, and pericardial tuberculosis was made for the first time. In middle-aged or elderly patients with active bone/joint TB, miliary TB is sometimes caused by bacillemia originating from the infected bone/joint lesions. In cases with bone/joint TB and concurrent pulmonary TB, bone/joint TB and pulmonary TB are probably reactivated independently as a result of decreased systemic immunocompetence.

BACKGROUND AND OBJECTIVES:Tuberculosis (TB) continues to be a major concern for health care workers. The number of reported cases of extrapulmonary tuberculosis, particularly osteoarticular tuberculosis, is increasing. This fact is attributed to different factors such as underestimating the disease and difficulty in diagnosis, which requires tissue sampling and can lead to a delay in the diagnosis, and can result in significant morbidity and mortality. The aim of this study was to highlight the difficulties and delay in diagnosis of articular tuberculosis, raising the need to create awareness about the importance of early diagnosis to avoid major complications of joint destruction.DESIGN AND SETTING:Retrospective review of patients presenting to a tertiary care center between 2003 and 2009.PATIENTS AND METHODS:We reviewed cases who presented with monoarticular joint pain and swelling that failed to respond to treatment elsewhere and were eventually diagnosed as having articular tuberculosis. We collected the demographic data, history, data on clinical examination and the relevant laboratory investigations, in addition to the data on radiological studies. All patients were treated medically with antituberculosis chemotherapy and surgically according to the severity of joint destruction.RESULTS:Thirteen patients had a mean age was 40 years (range, 17-70 years). The average delay in diagnosis was 2 years. Only 1 patient had pulmonary TB. The hip, knee and elbow were the most common joints involved. Bacteriology was positive in 69% of the cases; and histopathology, in 92%. Fifteen percent of the patients had arthrodesis. None showed recurrence after follow-up of 4 years.CONCLUSION:A high level of clinical suspicion is essential for early diagnosis and treatment of osteoarticular TB to reduce its significant morbidity.

Delays in diagnosis of osteoarticular tuberculosis

Background:Concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) is associated with poor treatment outcomes yet its epidemiology in Uganda is unknown. The purpose of this study was to determine the prevalence, associated factors, and treatment outcomes of concurrent PTB and EPTB among patients at a national tuberculosis (TB) treatment center located at Mulago National Referral Hospital in Kampala, Uganda.Methods:We conducted a retrospective review of charts for people with TB who were enrolled in care between January 2015 and December 2019. Eligible charts were for people with pulmonary bacteriologically confirmed TB enrolled into care in the period under study. Concurrent PTB and EPTB was defined as PTB and bacteriological, histopathological, and/or radiological features of TB at another noncontiguous sites.Results:Overall, 400 patient charts were eligible, of whom 240 (60.0%) were aged 15–34 years and 205 (51.3%) were female. The prevalence of concurrent PTB and EPTB was 8.5% (34/400) [95% confidence interval (CI): 6.0–11.7%]. People with concurrent PTB and EPTB were more likely to have at least one comorbidity (82.4% versus 37.2%, p < 0.001), of which HIV was the most frequent. Furthermore, people with concurrent PTB and EPTB were more likely to have empyema (15% versus 2.6%, p = 0.028) but less likely to have bronchopneumonic opacification (0.0% versus 15.3%, p = 0.043) on chest x-ray imaging. People with concurrent PTB and EPTB had higher mortality (26.5% versus 6.37%) and a lower cure rate (41.2% versus 64.8%), p = 0.002.Conclusion:Our findings highlight the need for early detection of TB before dissemination particularly among people who use alcohol and people with HIV.

P09 Uncommon cause of back pain

Purpose: Till date, a number of primers have been described for the diagnostic polymerase chain reaction (PCR) assays for tuberculosis (TB). However, most investigators have evaluated PCR's clinical utility using only one primer specific for Mycobacterium tuberculosis. The purpose of this study was to evaluate the efficacy of PCR tests targeting two different DNA sequences – insertion sequence 6110 (IS6110) and protein antigen b (Pab), in the same set of clinical samples from osteoarticular TB cases, and to evaluate if the sensitivity of the assay is improved. Materials and Methods: Twenty clinical samples obtained from osteoarticular TB cases were subjected to two different PCR assays - 123 base pair (bp) sequence coding for IS6110 and 419 bp sequence coding for Pab. Ten clinical samples from cases of proven septic arthritis were studied as controls. Results: The sensitivity of IS6110 PCR and Pab PCR were found to be 75% and 80%, respectively, and the specificity of both IS6110 PCR and Pab PCR was 100%. No significant difference was found between two PCR assays (P > 0.05). However, there were two cases which were negative by IS6110 PCR but were positive by Pab PCR. There was one case which was positive by IS6110 but was negative by Pab PCR. Seventeen out of 20 samples showed concordance between the results of two PCR tests, increasing the sensitivity to 85%. Conclusion: The diagnostic yield of the PCR test can be improved with the simultaneous amplification of two or more gene targets.

Tuberculosis (TB) remains endemic in South Africa. The spine, hip, and knee joints are common extra-pulmonary TB sites. Sound history taking, clinical examination, and basic laboratory and pathological tests remain key important steps in osteoarticular TB diagnosis. In our resources-stricken context cost is everything, if we can make a diagnosis cheaply that would go a long way. The diagnostic yield of standard laboratory tests compared to a real-time polymerase chain reaction (PCR) for osteoarticular TB diagnosis in a single orthopaedic unit has not been analysed. We conducted a retrospective record review of extra-spinal osteoarticular TB infection at our hospital from 01 June 2016 to 31 December 2021. Patient demographics, clinical history, and laboratory test results were analysed. A total of 34 cases were identified, with 32 of the cases being articular and two osseous involvement. The knee was the most common joint affected followed hip joint. Acid Fast Bacilli were detected in 32% of cases with microscopy, while TB culture was positive in 29% of samples. Histopathological examination and real-time PCR diagnosed TB in 66% and 63% of the cases, respectively. Our findings suggest that in the right context of a suggestive history and examination, histological analysis is as good as PCR for diagnosing osteoarticular TB.

An atypical presentation of tuberculous gumma heralding a diagnosis of lymph node tuberculosis: Hindsight is 20/20

During the last two decades, the resurgence of tuberculosis (TB) has been documented in both developed and developing nations, and much of this increase in TB burden coincided with human immunodeficiency virus (HIV) epidemics. Since then, the disease pattern has changed with a higher incidence of extrapulmonary tuberculosis (EPTB) as well as disseminated TB. EPTB cases include TB lymphadenitis, pleural TB, TB meningitis, osteoarticular TB, genitourinary TB, abdominal TB, cutaneous TB, ocular TB, TB pericarditis and breast TB, although any organ can be involved. Diagnosis of EPTB can be baffling, compelling a high index of suspicion owing to paucibacillary load in the biological specimens. A negative smear for acid-fast bacilli, lack of granulomas on histopathology and failure to culture Mycobacterium tuberculosis do not exclude the diagnosis of EPTB. Novel diagnostic modalities such as nucleic acid amplification (NAA) can be useful in varied forms of EPTB. This review is primarily focused on the diagnosis of several clinical forms of EPTB by polymerase chain reaction (PCR) using different gene targets.

Introduction: Tuberculosis (TB) of bones and joints is a relatively rare manifestation of the disease. Biopsy is the key to diagnosing it, while chemotherapy is the cornerstone of treatment. Some patients need surgery in addition to anti‐TB drugs. We present a series of eight cases of bone and joint TB.Method: The files of the patients with TB diagnosed and treated at the Pulmonary Department of Aristotle University of Thessaloniki (A.U.Th.) between 2013 and 2022 were reviewed. Patients with a bone or joint infection due to M. tuberculosis were selected.Cases Presentation: During these ten years, 307 cases of TB were found. Eight of them were TB of bones and joints (2.6%). Six patients were men and two women, with a mean age of 53.5 years and a standard deviation of 18.2 years. Half of them were native Greeks. The spine was involved in 4 cases, while two of the patients also had pulmonary TB. In seven cases, M. tuberculosis DNA was detected by PCR. Chemotherapy with anti‐TB drugs was administered to all eight patients, with three of them undergoing surgery in addition to anti‐TB medication. The minimum treatment duration was twelve months. Six out of eight cases had a good outcome.Conclusions: TB is a rare cause of infection of bones and joints; however, it should be included in the differential diagnosis of bone lesions. PCR for M. tuberculosis seems to have significantly good results in microbiological confirmation of osteoarticular TB.

To the Editor: The concurrence of active pulmonary tuberculosis (TB) and influenza in immunocompetent hosts is rarely reported. Such concurrence could distract clinicians from diagnosing TB during an influenza epidemic. We describe 7 cases of concurrent active pulmonary TB and influenza A(H1N1)pdm09 virus infection in South Korea. At 2 teaching hospitals in Seoul, medical records were reviewed retrospectively. Among the 12,196 patients for whom A(H1N1)pdm09 infection was confirmed by real-time reverse transcription PCR from May 2009 through May 2011, a total of 7 (0.06%) were co-infected with newly diagnosed active pulmonary TB (Table). Patients who had a history of TB diagnosis were excluded. Table Case summary of concurrent active pulmonary TB and influenza A(H1N1)pdm09 infection* Among the 7 co-infected patients, 6 (85.7%) were <30 years of age. All but 1 patient, who had colon cancer, had been previously healthy. No patients had diabetes mellitus or HIV infection. One patient was a current smoker. For 5 patients, pulmonary TB was diagnosed within 1 week from the date of influenza diagnosis; initial chest radiographic findings were suggestive of active TB or pneumonia. Another 2 patients, for whom radiographic examination was not performed at the first visit, experienced worsening cough and blood-tinged sputum after improvement of influenza; laboratory tests for TB were performed, and pulmonary TB was diagnosed 17 days after the date of influenza diagnosis. For 4 patients, computed tomography of the chest was performed, and multiple nodular lesions, cavities, and tree-in-bud appearance were found. Lymphopenia at initial visit was detected in 2 patients. All Mycobacterium tuberculosis isolates were sensitive to anti-TB drugs, and clinical outcomes were good for all patients. For persons infected with M. tuberculosis, lifetime risk for development of active TB is 5%–10%; this risk increases for those with immunocompromising conditions (1). One study reported that pulmonary TB was a risk factor for A(H1N1)pdm09 infection (2). However, the concurrence of influenza and pulmonary TB has been reported only a few times, and the findings have been mostly descriptive and somewhat contradictory. An old report, from 1919, describes TB diagnoses for patients who were not recovered completely from influenza pneumonia (3). During 1957–1958, Lofgren and Callans (4) observed 46 patients with newly detected TB that had been diagnosed shortly after Asian influenza; among them, 4 had a history of typical influenza. In South Africa, among 72 patients who died of A(H1N1)pdm09 infection, 7 also had active TB (5). In Taiwan, TB and A(H1N1)pdm09 infection in a lung cancer patient was reported (6). In Japan, a fatal case of influenza pneumonia combined with Streptococcus pneumoniae and M. tuberculosis infection in a patient with diabetes mellitus was reported (7). Although the 2 patients from Taiwan and Japan had concurrent illnesses, 6 of the 7 patients in our study had been healthy (6,7). Radiographic abnormalities for the patients reported here were similar to those reported for other patients, but more cavitary lesions were found for the patients reported here. Although it is not clear whether influenza accelerates emergence of TB, some animal studies suggest that influenza-associated TB is possible. In mouse studies, simultaneous injection of tubercle bacilli into the peritoneum and intranasal inoculation with influenza A virus (PR8) resulted in more rapid and extensive development of pulmonary tuberculous lesions than did infection with tubercle bacilli only (8). In a mouse model of chronic infection with M. bovis BCG, acute infection with influenza virus moderately increased the load of acid-fast bacilli in the liver, although this change was not significant (9). It is possible that temporary suppression of T-cell immunity by A(H1N1)pdm09 virus might alter the course of M. tuberculosis infection. Among influenza patients, CD4+ T cells were depleted and a subset of Th17 cells were preferentially lost at an early stage of infection; Th17 cells that produce proinflammatory cytokine interleukin-17 are associated with a protective immune response (10). Among 4 patients for whom laboratory examination was conducted at initial visit, 2 were lymphopenic. However, individual lymphocyte subsets were not checked, and a functional assay of lymphocytes was not conducted. Further studies of serial quantification and functional assay of lymphocytes at the acute stage of influenza and its effect on host susceptibility to TB in animals and humans are needed. The concurrence of TB and influenza could be a simple overlap. In 2009, the case notification rate of pulmonary TB in South Korea was 58.2 cases per 100,000 population; in 2010, it was 56.5. However, if influenza actually amplifies TB, TB might be underestimated and missed in influenza patients. Thus, large-scale observational epidemiologic studies on the changing incidence of TB during the influenza postpandemic era are needed. Especially in TB-endemic areas, physicians should consider a concurrent pulmonary TB diagnosis for influenza patients with radiologic abnormalities consistent with TB or with prolonged respiratory symptoms.

Profile of osteoarticular tuberculosis in children

Extrapulmonary tuberculosis (TB) involving the musculoskeletal system occurs in approximately 1% to 3% of patients with extrapulmonary TB. Concurrent pulmonary or intrathoracic TB is present in less than 50% of cases.1 Spine is the most frequent site of osseous tuberculous involvement. Other affected sites include the hip, knee, foot, elbow, hand, and bursal sheaths.2 Tuberculosis of the foot and ankle remains an uncommon site of the infection, present in 8% to 10% of osteoarticular infection. The diagnosis of osteoarticular tuberculosis is often delayed due to a lack of familiarity with the disease.3 We describe a patient with foot pain and swelling without any respiratory symptom as initial presentation of pulmonary and osteoarticular tuberculosis

Immunodeficiency in end-stage renal disease (ESRD) can be aggravated by haemodialysis (HD). This results in an increased incidence of reactivation of tuberculosis (TB) in HD patients. The tuberculin skin test to detect a latent TB infection (LTBI) has its limitations in these patients because of a high rate of false negative results due to anergy of T cells. Data on the influence of HD on the performance of interferon-gamma release assays are limited. The aim of this study was to determine the effect of HD on the performance of the QuantiFERON-TB Gold (QFT-G) assay in ESRD patients before, during and after the HD session. In HD patients older than 18 years without immunosuppressive medication or other immunocompromising conditions, the QFT-G assay was performed just before starting HD, 30 minutes after start and immediately after the finish of the HD session. Twenty patients were included. No statistically significant differences were found in interferon-gamma production in the nil- and antigen tubes between pre-HD, during and after HD. In 1 patient the predialysis result was indeterminate (one of 60 samples, 1.67%). In all 3 patients with a history of LTBI, the QFT-G test tube results were positive at all time points. In the other 16 patients, all test tubes showed negative results. The QFT-G assay could be a useful test for the evaluation of the immunological response against Mycobacterium tuberculosis in HD patients. The time point of blood sampling does not seem to affect the interpretation of test results.

We investigated the agreement between the tuberculin skin test (TST) and the QuantiFERON-TB gold (QFT-G) assay in the diagnosis of latent tuberculosis infection (LTBI) in patients with systemic lupus erythematosus (SLE). Furthermore, we evaluated the factors associated with indeterminate results in the QFT-G assay in patients with SLE. We enrolled 136 patients with SLE prospectively, and compared them to 66 patients with rheumatoid arthritis (RA). In addition to the TST, QFT-G assay, patients' medications, and Bacillus Calmette-Guérin (BCG) vaccination status were also investigated. A positive TST or QFT-G assay result without an active tuberculosis lesion on chest x-ray was considered to indicate a diagnosis of LTBI. The prevalence of LTBI was 26.5% in patients with SLE and 30.3% in patients with RA. The agreement between the TST and QFT-G assay was fair in SLE patients, but poor in RA patients. BCG vaccination was one factor associated with discordance between TST and QFT-G. Older age and higher SLE Disease Activity Index (SLEDAI) score were associated with a negative TST/positive QFT-G result in patients with SLE. Higher SLEDAI score and increased glucocorticoid dose were associated with an indeterminate result in the QFT-G assay for patients with SLE. Agreement between the QFT-G assay and TST in patients with SLE was found to be fair. However, BCG vaccination status, age, and SLEDAI score are all factors that could result in discordance between the two tests. Indeterminate results from the QFT-G assay may be caused by a higher SLEDAI score or increased glucocorticoid dose.