Clinical performance of quantitative PCR for the molecular identification of skeletal tuberculosis from formalin-fixed paraffin-embedded tissues.

BACKGROUND: At present, skeletal tuberculosis (TB) diagnosis is mostly by histopathology, but the positivity rate is low. There is a need to develop new methods for the molecular identification of this disorder. Therefore, we aimed to investigate the clinical utility of quantitative PCR (qPCR)-based diagnosis of skeletal TB from formalin-fixed paraffin-embedded (FFPE) tissues and its comparative evaluation with acid-fast bacillus staining (AFS). METHODS: We detected Mycobacterium tuberculosis (M. tuberculosis/MTB) DNA using qPCR and AFS in FFPE tissue samples from 129 patients suspected of having skeletal TB. The sensitivity, specificity as well as area under the curve (AUC) of qPCR and AFS were calculated. Meanwhile, some factors potentially affecting qPCR and AFS results were investigated. RESULTS: Overall, qPCR outperformed AFS in detecting M. tuberculosis. The AUC of qPCR was higher than that of AFS (0.744 vs.0.561, p < 0.001). Furthermore, decalcification of bone tissues did not affect the sensitivity and specificity of qPCR tests. Whereas it impacted the performance of AFS, decalcification increased AFS's specificity and decreased its sensitivity (p < 0.05). Moreover, qPCR had a significantly larger AUC than AFS in decalcified and non-decalcified groups (0.735/0.756 vs. 0.582/0.534, p < 0.001) respectively. Similarly, the AUC of PCR was more extensive than that of AFS regardless of skeletal TB patients with concomitant pulmonary TB or not (0.929 vs. 0.762; 0.688 vs. 0.524, p < 0.01). CONCLUSIONS: Our data demonstrate that qPCR offers superior accuracy for the detection of mycobacteria in FFPE tissues compared to traditional AFS, indicating its clinical value in osteoarticular TB diagnosis.

Poncet's Disease: A Case Report.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB). It spreads from one person to the another through the air while coughing, spitting, speaking or sneezing. TB most commonly affects lungs but it can affect any organ system. Diagnosis of TB is made on the basis of microbiological evidence of MTB on microscopic examination, cultures and chest X-rays. Poncet's disease is a separate entity in which joints are involved in the form of joint pain and swelling without any microbiological evidence of MTB. It usually occurs in the background setting of pulmonary TB. This case focuses on importance of considering Poncet's disease in the differential diagnosis of paediatric polyarticular arthritis in TB endemic regions or if there is a history suggestive of TB exposure and infection.

The Epidemiology of Skeletal Tuberculosis in Northeast of Iran: A Review of 229 Cases.

BACKGROUND: The incidence of tuberculosis (TB) has increased in recent years in both developed and developing countries. Skeletal tuberculosis occurs in approximately 1% of patients with tuberculosis. The present study aimed to evaluate the epidemiology of skeletal tuberculosis in Golestan province in northeastern Iran during 2005-2014. METHODS: In the present retrospective study, the epidemiology of skeletal tuberculosis was studied in 229 skeletal tuberculosis patients who were diagnosed during 2005-2014. The prevalence rate of skeletal TB has been reported according to demographic and clinical features. RESULTS: Over the 10-year period of this study, 229 known skeletal TB cases were identified in which 56.3% were male. The mean age of the patients was 44.0±17.7 (range 7-87). All of the patients were new cases. Most of the patients (56.8%) were from the rural areas and most were diagnosed by the private healthcare system (63.8%). The highest rate of skeletal TB was seen in 2013 (15.3%). Spinal TB (81.2%) scored the highest rate and pain (96.9%) was the most prevalent symptom of skeletal TB. CONCLUSION: The findings suggest that skeletal tuberculosis in northeastern Iran should always be considered as a differential diagnosis for fever and pain on the spinal column. Due to the high level of tuberculosis in the Golestan province (Iran), further research on continued awareness of skeletal TB is stressed.

Tuberculosis of the Cuboid: A Case Report and Review of the Literature.

Tuberculosis (TB) remains a major global health problem. According to a recent World Health Organization report, it ranks as the second leading cause of death from an infectious disease worldwide. According to the "UK Health Protection Agency Tuberculosis in the UK: 2012 Report," 8963 cases were reported in the United Kingdom in 2011. London had the greatest proportion of cases in the United Kingdom and the greatest rate of disease. TB affecting the foot is rare, affecting about 10% of all skeletal TB cases. However, owing to the current patterns of global immigration, with significant volumes of people migrating out of endemic countries, it has become a disease that physicians and surgeons in developed countries should be more aware of in today's practice. To the best of our knowledge, we present the first adult case of TB of the cuboid in the United Kingdom and the first adult case documented outside of India. We present the case details and the results of a thorough review of the literature. TB of the foot and ankle poses a diagnostic challenge because of the propensity of TB to mimic other pathologic entities radiologically. Tissue diagnosis and antitubercular medication is the mainstay of diagnosis and treatment, respectively.

Multifocal Skeletal Tuberculosis - A Case Report.

Introduction: Tuberculosis (TB) remains a pervasive infectious disease, and extrapulmonary manifestations account for a significant proportion of cases. Skeletal involvement is observed in about 10% of extrapulmonary TB instances. While spinal TB is relatively common, sacroiliac (SI) joint TB is a rare occurrence, particularly in immunocompetent individuals. Case Report: This case report discusses an unusual presentation in a 19-year-old immunocompetent lady where the spine, acetabulum, and SI joint were concurrently affected. The patient, initially undergoing alternative medicine, exhibited severe pain, weight loss, and restricted mobility. Radiological evaluations, including X-rays and magnetic resonance imaging, revealed extensive vertebral and pelvic destruction with abscess formation. Surgical debridement and stabilization, alongside antitubercular treatment, led to significant improvement. Conclusion: This case emphasizes the challenges in diagnosing multifocal skeletal TB, highlights the importance of early intervention, and underscores the impact of alternative medicine on treatment delays. A multidisciplinary approach involving histopathological and microbiological examinations is crucial for optimal management.

Chronic multifocal tubercular osteomyelitis in a young Nepalese boy: A rare case presentation.

This study presents a rare case of chronic multifocal tubercular osteomyelitis in a 13-year-old boy from Nepal, a high-burden country for tuberculosis (TB). He presented with chronic pain in the lower extremities and had no pre-existing comorbidities. The patient's clinical presentation, diagnostic process, and treatment plan are described. Multifocal skeletal TB, though infrequent, poses diagnostic challenges due to its variable manifestations. This case emphasizes the importance of considering TB in differential diagnoses, especially in endemic regions, necessitating a high index of suspicion. Early detection and treatment align with WHO's "End TB" strategy and Nepal's TB management guidelines, promoting improved outcomes in high-risk populations.

Calvarial Tuberculosis With Skin Tuberculosis in a Child: A Rare Case Report.

Calvarial tuberculosis (TB) is an uncommon form of skeletal TB. Early diagnosis can be challenging as they may exhibit diagnostic dilemmas. Another rare kind of skin TB is called TB verrucosa cutis. In this case, both of these uncommon forms were observed simultaneously and were effectively treated with first-line antitubercular therapy.

Imaging of musculoskeletal tuberculosis.

Extra-pulmonary tuberculosis (TB) of the musculoskeletal system usually manifests with non-specific clinical features, mimicking a variety of diseases. Diagnosis and treatment of spinal and extra-spinal musculoskeletal TB are often challenging. Imaging has an important role in detecting this disease, aiding diagnosis, identifying complications, and monitoring disease progression. Radiographs and magnetic resonance imaging are the key imaging modalities utilized. Radiologists should aim to be familiar with the spectrum of imaging features of TB affecting spinal and extra-spinal locations in the musculoskeletal system.

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.

Isolated Tuberculosis of the First Metatarsal of the Left Foot With Congenital Hallux Valgus Without Pulmonary Involvement: A First of Its Type Case.

Osteomyelitis caused by Mycobacterium tuberculosis is a rare entity. This clinical condition is even rarer when the bones of extremities like the foot are involved. There is a paucity of literature on the isolated tubercular involvement of the bones of the foot. Further, congenital hallux valgus is an infrequently reported condition. A case of tuberculosis of the first metatarsal of the left foot with congenital hallux valgus without pulmonary involvement is never reported in the literature. We herein present a first of its type case where tuberculous osteomyelitis of the first metatarsal of the left foot with congenital hallux valgus was diagnosed with the help of radiology, cartridge-based nucleic acid amplification test, and pus culture. The patient was initiated on anti-tubercular treatment but was ultimately lost to follow-up.

Odd presentations of skeletal tuberculosis: A case series.

Tuberculosis has been afflicting mankind since times immemorial and yet can still present itself in such a disguised manner that even the bests of experts may be duped. Any site from head to toe can be affected but certain sites are far less common than the others. We came across three inconspicuous manifestations at atypical sites-parapharyngeal abscess, wrist joint and foot ulcer. No other primary site could be identified in any case. Two cases were diagnosed microbiologically and one with radiological evidence. All the three cases were medically managed and depicted positive response.

Probable cases of tuberculosis in Early Medieval pastoralists of Eastern Europe.

Two anthropological collections of the 8-9th century AD from the forest-steppe area of the southern Eastern Europe has been the subject of analysis of the osteo-articular alterations concerning tuberculosis related lesions. According to archaeological data, the Mayaki and Dmitrievka groups are from the territory of Khazar Khaganate, which is well-known by historical data. It was a traditional population with settled pastoral farming. There were studied 292 adult human remains by macroscopic morphological and radiological methods. The completeness of the skeletons could have been better due to the intentional selection of their parts for the museum funds, so there were limitations for the differential diagnosis of TB by morphological criteria. In general, 31 individuals (20 men, 11 women) were marked as possible candidates with skeletal TB. The number of skeletons with possible specific infections from the two series is comparable, but according to sex distribution, there are some significant differences. If in the Dmitrievka group, there was approximately the same distribution of the number of cases of possible infected men and women; in the Mayaki group then there was a significant difference in the prevalence of the male sample. Various reasons can explain the observed differences. Firstly, we cannot rule out an error in the diagnosis of tuberculosis only by morphological methods since the preservation of the skeletons leaves much to be desired. Secondly, as it is known, only a few percent of tuberculosis patients show skeletal alterations, so the direct quantitative comparison cannot be adequate in paleopathological studies. The ambiguity of morphological criteria, particularly for destructive lesions of bone other than vertebrae, does not allow asserting that all identified cases result from TB. However, the results of differential diagnosis can underline that at least half of the skeletons have skeletal alterations most likely related to TB. The final analysis of the remains by aDNA methods will permit more certain confirmation of the diagnosis.

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.

Multifocal Tuberculous Spondylitis and Extensive Extraspinal Tubercular Osteomyelitis without Immunocompromise: Case Report and Literature Review.

Multifocal extensive spinal and extraspinal tuberculosis is very rare. So far, fewer than 10 cases have been reported. We hereby report two such cases to highlight their rarity, the diagnostic and therapeutic challenges they presented, and the overall prognosis of the condition. The two patients (a 19-year-old woman and another 20-year-old woman) had multifocal extensive tuberculosis involving spine and appendicular skeleton with neurological deficit. Both patients presented with back and neck pain and gradual neurological deficit. The insidious onset and malignancy-like spread pattern mimicked neoplasm. After thorough investigations with magnetic resonance imaging, positron emission tomography scan, and biopsy, antitubercular drug therapy was started, and debridement and fixation were done for significant thoracic and cervical vertebral lesions, respectively. Both patients showed excellent neurological recovery after the procedure. Early surgical treatment of the cases with large abscesses helped provide decompression and stabilization and prevented neurological deterioration and deformity. In patients with noncontiguous spinal tuberculosis, high percentage of surgical treatment may be required due to the aggressive behavior of the disease.

Tuberculosis of the Lateral Condyle of the Femur: A Case Report.

Tuberculosis in India has been a constant health issue. The revised national tuberculosis control program has suggested antitubercular drug regimens according to WHO guidelines for pulmonary and extrapulmonary tuberculosis. Here is an uncommon case of an adult presenting with a single lytic lesion of the lateral condyle of the femur; he had no history of primary foci of pulmonary tuberculosis and curettage of the lesion and histopathological examination of the bone tissue showed tubercular etiology. The patient, hence, was started on antitubercular drugs and at a six-month follow-up, resolution of the lesion was noticed.

Primary Rifampicin Mono-Resistant Extrapulmonary Tuberculosis of the Knee Without Pulmonary Involvement: One of the First Cases of Its Type in an Immunocompetent Male.

Tuberculosis presentation at sites other than the lungs is relatively infrequent, and isolated knee involvement without a pulmonary focus is exceptionally rare. Furthermore, there have been no reported cases of primary rifampicin mono-resistant extrapulmonary tuberculosis of the knee in males. In this case, a 24-year-old male patient presented with pain and swelling in his left knee after a fall five years ago. Given the absence of a history of tuberculosis, arriving at a diagnosis posed a significant challenge. However, the diagnosis was ultimately established through cartridge-based nucleic acid amplification tests and clinical link-up with radiometric techniques. Management was based on the latest national guidelines for anti-tuberculous treatment, which were tailored to his weight. To date, he has completed nine months of treatment with a significant improvement in his symptoms. This rare presentation emphasizes the need for a high degree of suspicion even in extrapulmonary tuberculosis cases.

Unusual sites of tuberculosis mimicking skeletal metastases: A case report.

The incidence of skeletal tuberculosis is about 1%-5% of all tuberculous infections. The most common sites are the spine, hip, knee, foot, elbow, hand, and shoulder, whereas the sternum, ribs, sternoclavicular joint, and calvaria are rarely affected. Because of the emergence of skeletal tuberculosis in therapeutic management, radiologists need to be aware of the imaging findings in pulmonary and extrapulmonary tuberculosis. Conventional X-ray plays an important role in diagnosing pulmonary and skeletal tuberculosis. Tuberculosis is known as the 'great mimicker', however, thus computed tomography and magnetic resonance imaging may provide additional details that assist the radiologist in distinguishing this tubercular infection from others. We report the case of a young male patient with skeletal tuberculosis who presented with general weakness, paraplegia, and a calvarial mass.

The humble wrist pain could be "early" tuberculosis and a high index of suspicion may help nip it in the bud: A case report.

Osteoarticular tuberculosis of the wrist is a very rare subset of skeletal Tuberculosis. Diagnosing the tuberculosis wrist in its early stage poses a major challenge to the clinicians because of its atypical and vague presentations and a close resemblance to many relatively benign pathologies. Clinicians from developed parts of the world having less exposure to the myriad forms of osteoarticular tuberculosis are more likely to miss it. We hereby report one such case who presented with wrist pain of short duration, which after thorough examination and investigations, turned out to be tuberculous. It was successfully managed with anti-tuberculosis drugs alone without any debridement or synovectomy. Familiarity with the clinical profile of this entity, in its early stages, is valuable for primary care physicians, rheumatologists, internal medicine specialists, and orthopaedicians alike, who may confuse it with one of the many more common inflammatory, degenerative, or traumatic causes of wrist pain. Within normal range or near normal erythrocyte sedimentation rate and C-reactive protein, and normal looking X-ray does not preclude the diagnosis of tuberculosis wrist. The role of a high index of suspicion and a low threshold for getting higher radiological investigation like MRI in non-responding cases of wrist joint pain cannot be overstated.

Tuberculosis of the Shoulder Joint: A Series of Three Cases.

Introduction: Tuberculosis (TB) involving the shoulder joint is rare. Early diagnosis is difficult but essential to prevent severe joint damage. In this report, we present variable presentation and management of TB of shoulder joint in three patients. Case Report: This report includes three patients. First patient was a 58-year-old male with severe muscle wasting around the shoulder with restriction of all movements had dry form of TB. Second patient was 55-year-old female with pain and swelling in the shoulder had wet form of TB with submuscular bursitis with rice bodies. A 50-year-old female presented with pain in the right shoulder with restricted active movements only was diagnosed with mobile form of TB was our third patient. Shoulder TB was diagnosed on the basis of histopathological examination in all three patients and was treated with 12 months of anti-tubercular therapy (ATT). All patients had good recovery and were back to their routine activities. Conclusion: TB of the shoulder has variable presentation; histopathological examination is the gold standard for diagnosis. Early diagnosis and treatment with ATT help in prevention of the severe joint damage.

A Case Report of Rare Presentation and Delay in the Diagnosis of Neuropathic Abdominal Pain Secondary to Asymptomatic Pott's Spine in Elderly Patients.

The presence of vertebral tuberculosis (TB) in developing countries and Southeast Asia is well known, but developed nations such as the USA and UK also claim a good share because of immigrants and the HIV population. We present a unique case series of two patients with chronic abdominal pain where various differentials and arduous investigation were employed. Finally, after a few months, we could locate the lower thoracic Pott's spine and commenced the treatment with successful resolution of symptoms. Surgeons and gastroenterologists should rule out the spinal cause of abdominal pain and also be aware of other atypical presentations before labeling it functional or irritable bowel syndrome (IBS) or somatoform disorders. Extensive investigation, cost, delay in diagnosis, and emotional disturbances could be the end product commonly encountered in a neuropathic abdominal pain patient if a high level of suspicion is not kept at the initial presentation. Above all, potential bony deformity, neurological deficits, and their irreversible sequelae such as paraparesis can also be thwarted.