Performance of adenosine deaminase in synovial fluid for the diagnosis of tuberculous arthritis: A systematic review and meta-analysis.

OBJECTIVES: Adenosine deaminase (ADA) activity has shown good performance in diagnosing pleural, peritoneal, and meningeal tuberculosis. This meta-analysis aimed to evaluate the performance of measuring ADA activity in synovial fluid for the early diagnosis of joint tuberculosis. METHODS: We searched published information in MEDLINE, Embase, Cochrane Library, Web of Science, and MedRxiv databases, as well as unpublished information in the American College of Rheumatology and European League Against Rheumatism for conference abstracts (2012-2021). We also scanned the reference lists of articles. Two reviewers independently applied the criteria for selection, assessed quality, and extracted data (PROSPERO number CRD42021284472). RESULTS: Seven independent studies (N=305 subjects) that compared ADA activity in synovial fluid with a composite reference diagnostic method for tuberculosis were included. Overall, the risk of bias was judged low. Studies were classified as high quality (n=3; 148 subjects) and low quality (n=4; 157 subjects). Pooled sensitivity and specificity of ADA activity was 94% (95% confidence interval [CI], 0.89-98; I2=23%) and 88% (95% CI, 83-92; I2=83%), respectively. The random-effects model for pooled diagnostic Odds ratio was 67.1 (95%CI, 20.3-222.2; I2=30%). The receiver operating characteristic curve area was 0.96 (95% CI, 0.92-0.99). Meta-regression did not identify the quality of the study, country of publication, or the type of assay as a source of heterogeneity. CONCLUSIONS: Measuring ADA activity in synovial fluid demonstrates good performance for the early diagnosis of joint tuberculosis.

Extrapulmonary, Chronic Septic Arthritis From Mycobacterium tuberculosis in the Ankle and Subtalar Joints.

In the United States, rates of Mycobacterium tuberculosis infection have been declining for decades. Osteoarticular tuberculosis of the ankle is rarely observed. We present the case of a 65-year-old man who immigrated to the United States from India 24 years before the onset of symptoms. The patient initially reported atraumatic swelling and pain of the left ankle and foot and was treated for venous insufficiency. Later, the patient was referred to a nonsurgical orthopaedic clinic for additional workup and was found to have elevated inflammatory markers. MRI showed septic arthritis and osteomyelitis of the talus, distal tibia, and calcaneus. Joint aspiration revealed elevated white blood cell counts with predominately PMNs. The patient was then referred to an orthopaedic foot and ankle surgeon and underwent extensive irrigation and débridement. The patient was discharged on empiric antibiotics. Culture results from the original joint aspirate returned 14 days after surgery as positive for acid-fast bacillus, later identified as M tuberculosis by sequencing. Empiric antibiotics were discontinued, and the patient was started on appropriate antituberculotic therapy. This case report illustrates the challenge in the diagnosis of skeletal tuberculosis and the importance of including this condition on the differential for patients with atypical foot and ankle presentations.

Diagnosing osteoarticular tuberculosis and detecting rifampicin resistance: A comparative analysis of Truenat MTB Plus vs GeneXpert Ultra.

SETTING: Diagnosing osteoarticular tuberculosis (OATB) and detecting drug resistance is a challenge in an endemic country like India. OBJECTIVE: Truenat MTB Plus assay (TruPlus), a chip-based portable machine, was compared with GeneXpert Ultra (GxUltra) for diagnosing drug-resistant OATB. DESIGN: 115 synovial fluid and pus specimens [22 culture-positive confirmed, 58 culture-negative clinically-suspected, 35 non-TB controls] processed between 2017 and 2023 were subjected to TruPlus, GxUltra and multiplex-PCR for diagnosing OATB. They were further screened for rifampicin resistance using TruRif chip. The performance was evaluated against composite reference standard, phenotypic drug susceptibility testing and rpoB gene sequencing. RESULTS: TruPlus, GxUltra and MPCR detected 77.5 %, 71.25 %, and 83.75 %, cases of OATB, respectively. TruPlus detected five additional cases missed by GxUltra. The performance of TruPlus was comparable to GxUltra (p = 0.074) and to MPCR (p = 0.074), while performance of GxUltra was significantly inferior to MPCR (p = 0.004). The overall agreement with reference standard was substantial for TruPlus and MPCR and moderate for GxUltra. Both TruRif and GxUltra reported 4 cases as rifampicin resistant. CONCLUSION: TruPlus along with TruRif offers better sensitivity than GxUltra. Its compact and portable platform allows wider application in peripheral settings, thus making it a pragmatic solution for diagnosing OATB and its drug resistance.

Pediatric Multidrug-Resistant Disseminated Tuberculosis Presenting as Small Finger Tuberculous Osteomyelitis: A Case Report.

CASE: We report a case in the United States of a 12-year-old girl with multidrug-resistant tuberculous (MDR-TB) osteomyelitis of the hand managed with surgical debridement and second-line anti-TB therapy. The disease course was complicated by dissemination and multifocal progression. CONCLUSION: Despite early intervention, multidrug resistance makes TB treatment challenging and facilitated progression to disseminated disease in this case. We review the difficulties in diagnosis and treatment of pediatric MDR-TB.

White plague among the "forgotten people" from the Barbaricum of the Carpathian Basin-Cases with tuberculosis from the Sarmatian-period (3rd-4th centuries CE) archaeological site of Hódmezovásárhely-Kenyere-ér, Bereczki-tanya (Hungary).

Tuberculosis (TB) is a bacterial infection that is well-known in the palaeopathological record because it can affect the skeleton and consequently leaves readily identifiable macroscopic alterations. Palaeopathological case studies provide invaluable information about the spatio-temporal distribution of TB in the past. This is true for those archaeological periods and geographical regions from when and where no or very few TB cases have been published until now-as in the Sarmatian period (1st-5th centuries CE) in the Barbaricum of the Carpathian Basin. The aim of our paper is to discuss five newly discovered TB cases (HK199, HK201, HK225, HK253, and HK309) from the Sarmatian-period archaeological site of Hódmezovásárhely-Kenyere-ér, Bereczki-tanya (Csongrád-Csanád county, Hungary). Detailed macromorphological evaluation of the skeletons focused on the detection of bony changes likely associated with different forms of TB. In all five cases, the presence of endocranial alterations (especially TB-specific granular impressions) suggests that these individuals suffered from TB meningitis. Furthermore, the skeletal lesions observed in the spine and both hip joints of HK225 indicate that this juvenile also had multifocal osteoarticular TB. Thanks to the discovery of HK199, HK201, HK225, HK253, and HK309, the number of TB cases known from the Sarmatian-period Carpathian Basin doubled, implying that the disease was likely more frequent in the Barbaricum than previously thought. Without the application of granular impressions, the diagnosis of TB could not have been established in these five cases. Thus, the identification of TB in these individuals highlights the importance of diagnostics development, especially the refinement of diagnostic criteria. Based on the above, the systematic macromorphological (re-)evaluation of osteoarchaeological series from the Sarmatian-period Carpathian Basin would be advantageous to provide a more accurate picture of how TB may have impacted the ancestral human communities of the Barbaricum.

Unveiling foot tuberculosis as an under-recognized source of foot pain.

PURPOSE: Foot tuberculosis is a rare form of osteoarticular tuberculosis, accounting for less than 1% of cases. It presents unique diagnostic challenges due to its nonspecific clinical features and overlapping symptoms with other conditions. This study aimed to investigate the clinical presentation, radiographic findings, and prognosis of foot tuberculosis, with the goal of improving early recognition and appropriate intervention. METHODS: A prospective study was conducted between November 2016 and July 2021, involving 39 patients diagnosed with foot tuberculosis. Clinical examinations, laboratory tests, X-rays, and MRI evaluations were performed to aid in the diagnosis. Biopsy was conducted on patients with radiological lesions. Patients were treated with an 18-month course of antitubercular therapy (ATT). Foot Function Index (FFI) scores were recorded before and after treatment. Statistical analysis was conducted to assess factors impacting prognosis. RESULTS: Unilateral foot involvement was observed in all patients, with a male predominance (61.5%) and a mean age of 31.3 years. The most common symptoms were pain and edema, with sinus tracts present in 17.9% of patients. Radiographic findings showed cystic and sclerotic lesions, with the "spina ventosa" appearance primarily affecting the metatarsal bones. MRI played a valuable role in early detection. Histopathological examination confirmed tuberculosis in all cases, and acid-fast bacilli were found in 23% of patients. Most patients (79.4%) responded well to ATT without requiring surgery. Factors such as high initial ESR, delayed ATT initiation, multiple lesions, and tarsal involvement were associated with unfavourable outcomes. CONCLUSION: Foot tuberculosis presents with nonspecific symptoms, leading to misdiagnosis and delays in appropriate treatment. Clinical examination, radiographic evaluation, and biopsy are essential for accurate diagnosis. Early initiation of ATT is crucial for favourable outcomes. Factors such as high initial ESR, delayed treatment initiation, multiple lesions, and tarsal involvement negatively impact prognosis. This study highlights the importance of recognizing foot tuberculosis and provides insights into its clinical presentation, radiographic features, and treatment outcomes, facilitating timely intervention and improved patient management.

Indolent ulcer and discharging sinus on the eyelid of healthy Indian children and an adult: Orbital tuberculosis, a spot-diagnosis.

Five cases of tuberculous osteomyelitis of the fronto-zygomatic (F-Z) region presented with a non-healing ulcer or discharging sinus in the eyelid skin in healthy children and an adult. Lack of awareness about peri-ocular manifestations of extra-pulmonary tuberculosis and delayed referral to specialists, along with poor compliance to long-term ATT, could be the reason for its underreporting in India.

Extraspinal osteoarticular tuberculosis: A diagnostic and therapeutic challenge.

Tuberculosis (TB) is a major cause of morbidity and mortality, representing a challenge for health-care providers worldwide. Extraspinal osteoarticular tuberculosis (ESOTB) represents a rare location of TB. We aim to describe ESOTB focusing on clinical, diagnostic, and therapeutic characteristics of this entity. We report a retrospective case series of patients diagnosed with ESOTB, treated, and followed up between 2015 and 2022. The diagnosis was based either on bacteriological results (culture and polymerase chain reaction [PCR]) or histological analysis. Five patients with confirmed ESOTB, three women and two men, with a mean age of 46.4 (16-72), were enrolled in study. The affected sites were the elbow (one case), the shoulder (one case), the greater trochanter (one case), the second metatarsal (one case), and the distal interphalangeal joint (one case). The mean delay to diagnosis was 5.8 months (3-10)]. The most common symptoms on presentation were pain (all cases), swelling (all cases), and limited joint range of motion (all cases). One case presented with a draining sinus (20%). Radiological findings were soft tissue swelling (two cases) and periarticular bone destruction (all cases). Four patients presented with pathognomonic histology. PCR was performed in two patients and was positive in both of them. All cases were cured after 9-12 months of oral TB treatment without relapse for the 12-18 months of follow-up. Only one patient underwent surgery for abscess drainage to gain local infection control. ESOTB is a mysterious condition that must not be overlooked and should be suspected in cases of long-standing bone and joint pain and swelling.

Tubercular osteomyelitis of calcaneum in an immunocompetent adult.

Tuberculosis (TB) affecting calcaneum is relatively rare in immunocompetent adults. Due to its nonspecific presentation and the absence of constitutional symptoms of TB, diagnosis is often delayed. The authors present a case of TB of calcaneum in a young male. A 20-year-old male presented with persistent pain and mild swelling of the right heel for 6 months. Upon evaluation with radiographs, a lytic lesion was noted in the posteromedial aspect of the right calcaneum. Magnetic resonance imaging was done and was reported as subacute osteomyelitis with Brodie's abscess. An open biopsy was performed and the obtained tissue was sent for histopathological examination. Histopathology showed features suggestive of Koch's etiology. All the microbiological investigations, including polymerase chain reaction for TB were negative. The patient was started on antitubercular therapy (ATT) based on weight. After 4 months of ATT, the patient developed multiple discharging sinuses over a previous open biopsy scar for which repeat debridement was done. After 12 months of ATT, the patient was asymptomatic, and radiologically, the lesion was healed. Early diagnosis and treatment with ATT will prevent massive destruction and collapse of the calcaneal body and further spread into the subtalar joint. Repeated debridements may be needed in case of nonhealing discharging sinuses to decrease the local infection load.

Mycobacterium tuberculosis infectious monoarthritis in a paediatric patient.

Mycobacterium tuberculosis is uncommon in the USA, and when it is diagnosed, it is usually in adult patients with identifiable risk factors presenting with pulmonary manifestations of the disease. Paediatric tuberculosis is rare, and a minority of those cases can present with isolated extrapulmonary infection. When the musculoskeletal system is involved, there are often no constitutional symptoms, and it can resemble other infectious and inflammatory processes. Diagnosis is challenging, and delay leads to irreversible destructive osteoarticular changes. A prompt diagnosis requires a high index of suspicion. This report presents a case of successfully diagnosed paediatric M. tuberculosis monoarthritis of the knee to highlight these challenges.

"Tuberculosis on the spot" - Discussion of a probable sternal tuberculosis from a late medieval cemetery from Hungary.

Investigations of non-adult remains are particularly suitable for finding epidemic periods in past populations. This study presents a probable unique example of osseous manifestation of tuberculosis on a child's skeletal remains from medieval Hungary. Between 2009 and 2011 the Field Service for Cultural Heritage excavated the exceptional cemetery of Perkáta - Nyúli-dulo in Hungary, with around 5000+ graves. The analysed skeleton (SNR 948) was located in the medieval (10-16th century) part of the cemetery. Besides the standard macroscopic pathological observation, we also performed radiographic analysis. The remains of the child (13-14 year-old) showed numerous skeletal lesions: the ribs have proliferative lesions (dense nodules) on the visceral surface of the shaft, lytic lesions with rounded edges occurred on the thoracic and lumbar vertebral bodies, and on the facies auricularis of the left ilium we can see pitting and new bone formation. What makes this pathological case exceptional is the significant change in the manubrium. It shows extensive osteolytic lesions, probably due to tuberculous osteomyelitis, which is a unique phenomenon in an archaeological context. This rare type of extra-spinal tuberculous osteomyelitis appears in less than 1% of cases with skeletal TB, and even less in case of children, according to modern medical literature. Although some cases of slight lesions on the manubrium have been described from an archaeological context, no such cases showing advanced lesions have been published so far. In the future, biomolecular analyses should be conducted as well, in order to confirm the presence of TB in this individual.

Changes in mortality by tuberculosis in non-industrialized Coimbra (Portugal): Trends between 1861 and 1914.

Considering that before antibiotics and vaccination the course of tuberculosis depended mostly on the patient's immune response, this study tested the hypothesis that the mortality profile remained similar during the transition from the 19th to 20th century. The biographical data of the individuals buried in the Coimbra Municipal Cemetery of Conchada were analysed, and the records of those who were born in the city and had tuberculosis registered as the cause of death were analysed using SPSS. The years of death were grouped: 1861-1870 (n = 124, 22.5%), 1871-1880 (n = 234, 42.4%), and 1910-1914 (5 years, n = 194, 35.1%). Mortality by tuberculosis has increased over the years. A total of 552 individuals, 242 females (43.8%) and 310 males (56.2%) died of tuberculosis (p < 0.05). The mean age at death (min = 11 days, max = 86 years) decreased over time, respectively 51.8, 53.1, and 35.8 years-old for individuals >20. Deaths by pulmonary tuberculosis (n = 38, 1861-1870; n = 115, 1910-1914) and meningeal tuberculosis (n = 0, 1861-1870; n = 48, 1910-1914) increased over time, whereas scrofula decreased (n = 23, 1861-1870; n = 3, 1910-1914). Only a 12 years-old male (0.2%) died of bone tuberculosis. Infant (0-3 years-old) mortality occurred mainly (50.5%,48/95) between July and October. The hypothesis tested was not confirmed. Death by tuberculosis has increased, which may be a consequence of population growth, deterioration of the living conditions, and/or changes in bacterial virulence and/or in the host immune system.

More than one millennium (2nd-16th century CE) of the White Plague in the Carpathian Basin - New cases, expanding knowledge.

The causative agent of tuberculosis is still a widespread pathogen, which caused the death of ca. 1.6 million people globally in 2021. The paleopathological study of human remains revealed the antiquity of the disease and its continuous presence throughout the history of humankind. The Carpathian Basin has always been a biocultural melting pot, since it has seen several migrations over the centuries, and served as a location of admixture and interaction for numerous populations of different cultures. Thus, this geographical territory is ideal for the examination of the coevolutionary processes of hosts and their pathogens. We aimed to reveal the spatial and temporal distribution of tuberculosis cases excavated inside the borders of Hungary between the 2nd and 16th centuries CE. We established a comprehensive database by collecting 114 already published cases and introducing 39 new cases. The involved cases include those that have been confirmed by different molecular methods, as well as possible infections that were identified based on the presence of macromorphological and radiological alterations. The progress of future molecular and paleopathological studies can be facilitated by our dataset, as it presents spatial and temporal information concerning the spread of the disease in the Carpathian Basin, as well as the biological profile and detailed paleopathological description of lesions illustrated by photo- and radiographs.

Tuberculosis in prehistory in Eastern Central Europe (Hungary) - Chronological and geographical distribution.

Tuberculosis (TB) has long been a major scourge of humankind. Paleopathological and paleomicrobiological studies have revealed the past presence of the disease on a large spatial and temporal scale. The antiquity of the disease has extensively been studied in the Carpathian Basin, given its dynamic population and cultural changes since prehistory. These studies, however, have mainly focused on the populations living during the Common Era. The aim of this paper is to present the published and the recently discovered cases of prehistoric TB, from the Neolithic (6000-4500/4400 BCE) to the Bronze Age (2600/2500-800 BCE) Central Carpathian Basin (Hungary). We summarize 18 published cases and present new cases dating to the Neolithic period and introduce 3 newly discovered Bronze Age cases of TB. Despite extensive research, TB has not yet been identified from the Copper and Iron Ages in the Carpathian Basin. Considering the state of TB research, and supplemented by our prehistoric dataset, the spatio-temporal pattern of the disease can be further elucidated, thus advancing future molecular and paleopathological studies. Our dataset offers comprehensive spatial and temporal information on the spread of the disease in the Carpathian Basin, along with a detailed biological profile of the demonstrated cases and extensive paleopathological descriptions of the observed lesions, complemented by photographic evidence. This invaluable resource paves the way for enhanced understanding and progress in the field.

Bacille Calmette-Guérin Vaccine-Induced Tuberculous Elbow Osteomyelitis in an Infant: A Case Report.

CASE: We report a case of Bacillus Calmette-Guérin (BCG) vaccine-induced osteomyelitis of the distal end of the right humerus in a 1-year and 8-month-old girl. The patient was treated with debridement and a 12-month antituberculosis drug. After 3 years of follow-up, no growth disturbances or sequelae were observed. CONCLUSION: BCG osteomyelitis is difficult to diagnose because of its rarity. It is important to suspect BCG osteomyelitis based on symptoms and blood tests and to perform PCR testing. Long-term follow-up after treatment is necessary to monitor for recurrence and avoid growth disturbances until epiphyseal line closure occurs.

Clinical characteristics and treatment outcomes of tuberculous tenosynovitis of the hand and wrist.

Objective: Vietnam is endemic with tuberculosis (TB), which is highly prevalent in the community. TB tenosynovitis of the wrist and hand is uncommon. Because of its insidious progression and atypical presentations, it is often difficult to diagnose, leading to treatment delays. This study investigates the characteristics of clinical and subclinical signs and treatment outcomes of patients with TB tenosynovitis in Vietnam. Patients and Methods: This prospective longitudinal cross-sectional study included 25 TB tenosynovitis patients in the Rheumatology Clinic at University Medical Center Ho Chi Minh City. The diagnosis was made based on a tuberculous cyst in histopathological specimens. The data were collected through medical history, physical examination, and medical records, including demographics, signs, symptoms, condition duration, and related laboratory tests and imaging. The outcomes of all participants were assessed after 12 months of treatment. Results: The most common symptom of TB tenosynovitis was swelling of the hand and wrist, which was present in all patients. Its other symptoms included mild pain and numbness of the hand in 72% and 24% of patients, respectively. It can affect any site on the hand. Hand ultrasound findings included thickening of the synovial membrane (80%), peritendinous effusion (64%), and soft tissue swelling (88%). Most patients (18/22) had a good outcome after the treatment with anti-tubercular drugs. Conclusions: TB tenosynovitis progression is often insidious. Its most common symptoms are swelling of the hand and mild pain. Ultrasound is a useful tool to support the diagnosis. A histological examination confirms the diagnosis. Most cases respond and have a good outcome after 9-12 months of anti-tuberculosis treatment.

Carpal Tunnel Syndrome Secondary to Tuberculous Tenosynovitis With Rice Bodies: A Case Report.

CASE: We report the case of a 34-year-old African man who presented with severe symptoms of recurrent left carpal tunnel syndrome (CTS) and left hand swelling after previous open decompression. Considering the recurrent unilateral affection of the left hand in a patient working in a slaughterhouse in an area with a moderate burden for tuberculosis, tuberculous infection was suspected. Open surgery and biopsy revealed tuberculous tenosynovitis of flexor tendon sheath and shiny white rice bodies. CONCLUSION: Tuberculous tenosynovitis should be considered as a differential diagnosis of the CTS when there is evidence of proliferative tenosynovitis in patients from an endemic area for tuberculosis.