Single-cell transcriptomic analysis reveals a decrease in the frequency of macrophage-RGS1high subsets in patients with osteoarticular tuberculosis.

BACKGROUND: Cell subsets differentially modulate host immune responses to Mycobacterium tuberculosis (MTB) infection. However, the nature and functions of these subsets against osteoarticular tuberculosis (OTB) are unclear. Here, we aimed to understand the phenotypes and functions of immune cell subsets in patients with OTB using single-cell RNA sequencing (scRNA-Seq). METHODS: Pathological and healthy adjacent tissues were isolated from patients with OTB and subjected to scRNA-Seq. Unsupervised clustering of cells was performed based on gene expression profiles, and uniform manifold approximation and projection was used for clustering visualization. RESULTS: Thirteen cell subsets were identified in OTB tissues. scRNA-seq datasets of patients and healthy controls (HCs) showed that infection changed the frequency of immune cell subsets in OTB tissues. Myeloid cell examination revealed nine subsets. The frequency of macrophage-RGS1high subsets decreased in OTB tissues; this increased MTB susceptibility in an SLC7A11/ferroptosis-dependent manner. Immunohistochemistry assays and flow cytometry for patients with OTB and osteoarticular bacterial infection (OBI) and HCs verified that the frequency of macrophage-RGS1high subset decreased in OTB tissues and blood samples, thereby distinguishing patients with OTB from HCs and patients with OBI. CONCLUSION: The macrophage-RGS1high subset levels were decreased in patients with OTB, and would be up-regulated after effective treatment. Therefore, the clinical significance of this study is to discover that macrophage-RGS1high subset may serve as a potential biomarker for OTB diagnosis and treatment efficacy monitoring.

Beyond the norm: Primary multidrug-resistant extrapulmonary tuberculosis unveiled in a case series.

Tuberculosis is a preventable and generally curable infectious disease caused by Mycobacterium tuberculosis. It mostly affects the lungs causing pulmonary tuberculosis; however, it may also involve non-pulmonary organs resulting in extrapulmonary tuberculosis (EPTB). Diagnosis of tuberculosis was based on the constitutional symptoms, organ-specific radiographs, and biological specimen examination. However, diagnosis of extrapulmonary tuberculosis can be difficult when the lungs are not affected and constitutional signs and symptoms of tuberculosis that can help to identify the disease are absent. Although multi-drug-resistant extrapulmonary tuberculosis is not uncommon, primary drug-resistant extrapulmonary tuberculosis in certain areas such as the extraspinal osteoarticular joint, tympanic membrane, and central nervous system is still rare. In this piece, we present three cases of primary multidrug-resistant extrapulmonary tuberculosis with an unusual presentation.

Disseminated tuberculosis in an immunocompetent 15-year-old adolescent.

Tuberculosis is one of the oldest known diseases and it remains one of the main causes of morbidity and mortality, especially in developing countries. It is associated with social inequalities and affects different age groups. Tuberculosis in children and adolescents should be considered a sentinel event, since it is linked to a recent infection through contact with bacilliferous adults. We report an immunocompetent 15-year-old adolescent with tuberculosis, exhibiting pulmonary, osteoarticular, and cutaneous involvement. Conventional treatment with tuberculostatic drugs for a year had satisfactory results without sequelae.

Serum Protein Electrophoresis Patterns in Patients with Osteoarticular Tuberculosis.

CONTEXT AND AIMS: Tuberculosis (TB) is a leading cause of infectious disease deaths in India. It is also one of the most challenging diseases to diagnose and treat effectively. TB can occur both in the lungs and in extrapulmonary locations through hematogenous spread. Osteoarticular TB is a type of extrapulmonary characterized by atypical presentation. If diagnosed early, it can be treated effectively with reduced risk of mortality. SUBJECTS AND METHODS: At Nalanda medical college and hospital, an 18-month prospective research was undertaken. The study included a total of 120 patients with osteoarticular TB. Serum electrophoresis of blood samples was performed at baseline, 2 months, and 4 months following antitubercular medication administration. The fractions of albumin, α1, α2, ß, and γ globulins were estimated and compared with the baseline value. RESULTS: It was observed that as the disease progressed and became more chronic, there was a decrease in albumin and an increase in α1, α2, ß, and γ globulin percentages of serum proteins. Upon follow-up, the serum electrophoresis revealed that these values observed during baseline could be reversed by the administration of antitubercular drugs. CONCLUSIONS: This study suggests that analyzing serum protein fractions could be a cost-effective strategy to determine the presence of osteoarticular TB and also aid in initiating antitubercular treatment.

RésuméContexte et objectifs: La tuberculose (TB) est l'une des principales causes de décès par maladies infectieuses en Inde. C'est également l'une des maladies les plus difficiles à diagnostiquer et à traiter efficacement. La tuberculose peut survenir à la fois dans les poumons et dans des localisations extrapulmonaires par propagation hématogène. La tuberculose ostéoarticulaire est un type de tuberculose extrapulmonaire caractérisée par une présentation atypique. Si elle est diagnostiquée tôt, elle peut être traitée efficacement avec un risque de mortalité réduit. Sujets et méthodes: À la faculté de médecine et à l'hôpital de Nalanda, une recherche prospective de 18 mois a été entreprise. L'étude a inclus un total de 120 patients atteints de tuberculose ostéoarticulaire. L'électrophorèse sérique des échantillons de sang a été réalisée au départ, 2 mois et 4 mois après l'administration de médicaments antituberculeux. Les fractions d'albumine, a1, a2, b et g globulines ont été estimées et comparées à la valeur de base. Résultats: Il a été observé qu'à mesure que la maladie progressait et devenait plus chronique, il y avait une diminution de l'albumine et une augmentation des pourcentages de globulines a1, a2, b et g des protéines sériques. Lors du suivi, l'électrophorèse sérique a révélé que ces valeurs observées au départ pouvaient être inversées par l'administration de médicaments antituberculeux. Conclusions : Cette étude suggère que l'analyse des fractions protéiques sériques pourrait constituer une stratégie rentable pour déterminer la présence d'une tuberculose ostéoarticulaire et également faciliter l'initiation d'un traitement antituberculeux.

Ulnar bone tuberculosis in children: Case report and literature review.

RATIONALE: Tuberculosis of the long tubular bones in children's extremities is infrequent, particularly in the ulna. Early diagnosis poses significant challenges. This report presents a case involving a 2-year-old child with tuberculosis of the ulnar bone, accompanied by a comprehensive review of pertinent literature. The purpose of this study is to share diagnostic and therapeutic experiences and provide potentially valuable insights. PATIENT CONCERNS: In this case, the patient exhibited complete destruction and expansion of the ulnar bone, resulting in a forearm size considerably greater than normal. Concerns were raised about the irreversible deformation of the ulna, the potential for a malignant bone tumor, and its impact on forearm function, potentially endangering the patient's life. DIAGNOSES: The diagnosis was confirmed as tuberculosis of the ulnar bone. INTERVENTIONS: The patient underwent surgery to remove the affected ulnar tissue and received anti-tuberculosis medication. OUTCOMES: Subsequent to treatment, the destruction and expansion of the ulnar bone resolved, with the return of normal ulnar morphology and bone structure. LESSONS: Even in the absence of typical symptoms like fever, weight loss, and loss of appetite, extensive destruction and expansion of a long tubular bone should prompt vigilant consideration of bone tuberculosis.

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.

Bilateral hand dactylitis: An unusual presentation of the great imitator: Tuberculosis.

The incidence of tuberculosis in developed countries has decreased over the years due to the use of effective tuberculosis drugs and improvements in socio-economic conditions. However, with the ease of global transport and increased travel to countries with high tuberculosis prevalence, the reduction in extrapulmonary tuberculosis cases has been less significant compared with the overall decrease in tuberculosis cases. Extrapulmonary tuberculosis can manifest in a variety of ways. Tuberculous dactylitis, a rare form of tuberculous osteomyelitis, was first described by Rankin in 1886. It mainly affects the short tubular bones in the hands and feet of children and is sometimes called 'spina ventosa'. A 42-year-old male patient initially presented to an external centre reporting swelling and pain in the hand joints of one year's duration. Despite one year of treatment with leflunomide and methylprednisolone (16 mg) and a history of methotrexate use during this period, he experienced no improvement. The patient's condition worsened after the start of sulfasalazine. Dermatological examination was performed due to the presence of haemorrhagic crusted papules and plaques on the ventral surface of both hands. A wound culture was taken, but no bacterial growth was observed. One week after the initial evaluation, the patient complained of persistent foul-smelling nasal discharge, which led to an evaluation by the infectious disease department. At this time, the Quantiferon test was positive. Mycobacterial culture on Days 1 and 3 showed growth of the Mycobacterium tuberculosis complex.

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.

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.

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.

Several potential serum proteomic biomarkers for diagnosis of osteoarticular tuberculosis based on mass spectrometry.

BACKGROUND: Osteoarticular tuberculosis is one of the extrapulmonary tuberculosis (EPTB) diseases, which is mainly caused by infection of Mycobacterium tuberculosis (MTB) in bone and joints. The limitation of current clinical test methods is leading to a high misdiagnosis rate and affecting the treatment and prognosis. This study aims to search serum biomarkers that can assist in the diagnosis of osteoarticular tuberculosis. METHODS: Proteomics can serve as an important method in the discovery of disease biomarkers. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze proteins in 90 serum samples, which were collected from June 2020 to December 2021, then evaluated by statistical analysis to screen potential biomarkers. After that, potential biomarkers were validated by enzyme-linked immunosorbent assay (ELISA) and diagnostic models were also established for observation of multi-index diagnostic efficacy. RESULTS: 118 differential expressed proteins (DEPs) were obtained in serum after statistical analysis. After the diagnostic efficacy evaluation and clinical verification, inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2), complement factor H-related protein 2 (CFHR2), complement factor H-related protein 3 (CFHR3), and complement factor H-related protein 5 (CFHR5) were found as potential biomarkers, with 0.7167 (95 %CI: 0.5846-0.8487), 0.8600 (95 %CI: 0.7701-0.9499), 0.8150 (95 %CI: 0.6998-0.9302), and 0.9978 (95 %CI: 0.9918-1.0040) AUC value, respectively. The remaining DEPs except CFHR5 were constructed as diagnostic models, the diagnostic model contained CFHR2 and CFHR3 had good diagnostic efficacy with 0.942 (95 %CI: 0.872-0.980) AUC value compared to other models. CONCLUSION: This study provides a reference for the discovery of serum protein markers for osteoarticular tuberculosis diagnosis, and the screened DEPs can also provide directions for subsequent pathogenesis research.

An extensor tenosynovitis complicated with extensor tendon rupture revealing a hand tuberculosis.

Tuberculous hand tenosynovitis is a rare localization of tuberculosis. It is dominated by flexor tendon involvement; tenosynovitis of the extensor tendons is exceptional. The diagnosis is usually delayed and sometimes overlooked because of the paucity and the chronicity of the symptoms and signs with the patients often seen at the stage of tendon rupture. We, hereby, report the case of a tuberculous tenosynovitis of the extensors of the left hand having evolved into a ruptured extensor tendons to the 4th and 5th digits. The surgical treatment in conjunction with the antituberculous drugs resulted in the healing of this condition.

Tuberculous Osteomyelitis of The Pubic Symphysis - a Case Report of a Rare Entity Mimicking Spondyloarthritis.

Tuberculosis (TB) osteomyelitis of the pubic symphysis is an extremely rare diagnosis. Axial spondyloarthritis (SpA) is characterized by inflammatory back pain and enthesitis, and involvement of pubic symphysis is very unusual at presentation. A 36-year-old female patient with a history of inflammatory back and pubic pain was referred to Rheumatology. She had a pelvic magnetic resonance imaging (MRI) suggestive of osteitis pubis. She was started on etoricoxib 90mg/day as axial spondyloarthritis was suspected, with no improvement. Pelvic MRI was repeated and showed osteomyelitis of the iliopubic branches. An ultrasound-guided biopsy was performed, and culture was positive for Mycobacterium tuberculosis. Further imaging studies revealed small cavitations and several centrilobular micronodules with a tree-in-bud pattern in the upper lung lobes and in the upper segment of the lower left lobe. She was started on anti-tuberculous treatment for 1 year and had a good clinical and radiological response. TB osteomyelitis of the pubic symphysis is a rare entity and has seldom been reported. However, this is the first case, to our knowledge, where the clinical picture mimicked an itself unusual presentation of SpA.

Clinical utility of tuberculosis RNA in the rapid diagnosis of bone and joint tuberculosis.

OBJECTIVES: To evaluate the diagnostic accuracy of tuberculosis RNA (TB-RNA) for the rapid diagnosis of bone and joint tuberculosis (BJTB). METHODS: We conducted a retrospective study to evaluate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of TB-RNA and acid-fast bacillus (AFB) smear against the final clinical diagnosis. RESULTS: A total of 268 patients were included. The overall sensitivity, specificity, PPV, NPV, and AUC of AFB smear for BJTB were 0.7%, 100.0%, 100.0%, 49.3%, and 0.50, respectively, whereas those of TB-RNA were 59.6%, 100.0%, 100.0%, 70.6%, and 0.80, respectively; for cases of confirmed (culture-positive) BJTB, these values were 82.8%, 99.4%, 99.7%, 89.2%, and 0.91, respectively. CONCLUSIONS: The diagnostic accuracy of TB-RNA in the rapid diagnosis of BJTB was relatively good, especially in culture-positive BJTB. The use of TB-RNA could be an effective technique for the rapid diagnosis of BJTB.