Search Results (52)

Background: Systematic infectious screening is recommended before initiation of biologic therapies in chronic inflammatory rheumatic diseases (CIRDs), yet the clinical impact of this strategy in low-prevalence settings remains insufficiently characterized. This study aimed to evaluate the proportion of abnormal findings and their impact on treatment management. Methods: We conducted a retrospective single-center study including adult patients with CIRDs who underwent systematic pre-biologic infectious screening between January 2019 and June 2025. Screening included HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), interferon-γ release assay (IGRA), and chest radiography. The primary outcome was the proportion of abnormal results and their impact on biologic initiation. Results: A total of 418 patients was included (mean age 48.2 ± 14.6 years; 69.1% female). No active HIV, HBV, or HCV infections were detected. Past HBV infection markers were identified in 2.6% of patients, and anti-HCV antibodies in 0.7%, all without detectable viremia. None of these findings required modification of biologic therapy. IGRA positivity was observed in 4.3% of patients and indeterminate results were seen in 3.1%. Preventive antituberculous therapy was initiated in most newly identified IGRA-positive cases, leading to delayed biologic initiation in several patients. Chest radiography yielded limited additional diagnostic value. Conclusions: In this population, systematic pre-biologic infectious screening identified few clinically actionable viral infections, whereas latent tuberculosis screening represented the main determinant of therapeutic modification. These findings support continued emphasis on tuberculosis risk assessment and warrant further prospective studies to evaluate optimized and potentially targeted screening strategies incorporating cost-effectiveness analyses. Full article

Introduction: Tuberculous aneurysm of the thoracic aorta (TBAA) is an extremely rare but potentially fatal manifestation of tuberculosis (TB). Clinical presentation may include hemoptysis in the absence of parenchymal lung abnormalities. Case report: We presented a 62-year-old male with cough, chest pain, and minimal hemoptysis. Diagnostic evaluation confirmed an aneurysm of the descending thoracic aorta at a site previously treated with endovascular repair, with no imaging findings suggestive of pulmonary TB. Bronchoscopy revealed blood in the main bronchi without an identifiable endobronchial source. The diagnosis of TB was established by polymerase chain reaction (PCR) testing of bronchial aspirate obtained during bronchoscopy. Emergency surgical intervention was recommended because of an impending aortic rupture, but the patient declined surgery. Standard antituberculous therapy was initiated, and the patient subsequently developed drug-induced liver injury, prompting temporary cessation of treatment. The clinical course was later complicated by the development of an aortoesophageal fistula (AEF), with significant implications for prognosis. Conclusions: Early recognition of TBAA, along with a multidisciplinary approach that integrates advanced diagnostic modalities, timely vascular intervention, and carefully managed antituberculous therapy, is essential to reduce mortality and optimize treatment outcomes. Full article

Background and Clinical Significance: Extrapulmonary tuberculosis (TB) remains a diagnostic challenge, particularly when affecting rare sites such as the oral cavity and digestive tract. We report the case of a 55-year-old woman with disseminated (miliary) tuberculosis presenting with atypical oral lesions initially suspected to represent a malignant tumor. Case Presentation: The patient had a history of recurrent depressive disorder, cognitive impairment, sleep disturbances, and nicotine/alcohol dependence. She presented with painful ulcerations of the oral cavity, dysphagia, odynophagia, and glossodynia. Otolaryngologic examination revealed reduced tongue mobility and an ulceroinfiltrative lesion involving the floor of the mouth and the lower alveolar ridge. Fibroscopic evaluation confirmed infiltrative ulcerative lesions, and biopsy samples were obtained. Histopathologic examination revealed a chronic necrotizing granulomatous inflammation with multinucleated giant cells, consistent with a mycobacterial infection. Further investigations confirmed disseminated (miliary) tuberculosis with oral and digestive involvement. Antituberculous therapy was initiated; however, despite temporary stabilization, the patient’s condition progressively worsened and the outcome was fatal. Conclusions: Oral and digestive tuberculosis, although rare, should be considered in the differential diagnosis of ulceroinfiltrative lesions of the oral cavity, particularly in patients with systemic symptoms or risk factors for TB. Early histopathologic confirmation and initiation of specific therapy are essential for favorable outcomes and prevention of misdiagnosis as malignant disease. Full article

Pulmonary tuberculosis (TB) produces systemic alterations that can be reflected in biochemical parameters beyond microbiological resolution. Early characterization of the biochemical response to treatment could provide additional criteria for following up with hospitalized patients. A retrospective observational study was conducted focusing on patients with pulmonary TB from a tertiary care hospital, based on biochemical parameters upon admission (“before”) and between 2 and 10 days after starting anti-tuberculosis treatment (“after”). The patients were grouped into three clusters according to the results of the clinical tests: mild (70.1%), inflammatory (26.7%), and severe (3.2%). After the start of treatment, 30% of the patients migrated toward the most biochemically compromised phenotype (Cluster 3). Sixty-one percent showed deterioration in at least one of the three key parameters; only 12.8% improved simultaneously. Significant associations were identified between unfavorable biochemical evolution and HIV (p = 0.004) or patients with public health coverage (p = 0.01). Overall, after antituberculous therapy, a reduction in CRP and leukocytes was observed (p < 0.001), and progressive anemia (ΔHb: −1.7 g/dL) and renal deterioration (ΔCr: +0.52 mg/dL) were identified. The identification of dynamic phenotypes in patients with pulmonary TB can be used to establish early risk markers and contribute to individualized clinical surveillance. Full article

A 30-year-old previously healthy man presented with fever and headache. HIV tests yielded negative results. Cerebrospinal fluid (CSF) analysis revealed pleocytosis (619/µL), elevated protein (210.3 mg/dL) and adenosine deaminase levels, and decreased glucose levels. A positive CSF culture for tuberculosis confirmed the patient had tuberculous meningitis (TBM). He was treated with methylprednisolone, isoniazid, rifampicin, pyrazinamide, and ethambutol (all highly sensitive). His compliance with medication was good. After six weeks of treatment, he was discharged in stable condition. Eight weeks after onset, he was readmitted with vertigo and right deafness. CSF examination showed worsened pleocytosis (819/µL) and protein levels (4296.1 mg/dL). Contrast-enhanced MRI revealed enhancement of meninges in the brainstem and spinal cord as well as the right vestibulocochlear nerve. No brain abscesses were observed. Based on these findings, a paradoxical reaction (PR) with vestibulocochlear neuritis following antituberculous therapy initiation was suspected. He received oral prednisolone, leading to rapid resolution of vestibulocochlear symptoms within two days. Although cranial nerve enhancement due to PR has been mentioned in the literature, specific imaging demonstrating it is scarce. This case highlights PR as a cause of cranial neuropathy in TBM and provides clear radiological evidence of direct inflammatory spread to the vestibulocochlear nerve, bridging a gap in the current literature. Full article

Background: Lymphomatoid granulomatosis (LYG) is a rare and atypical EBV-induced B-cell lymphoproliferative disorder. Clinical manifestations are mainly respiratory, with nodular infiltrates, varying in number and size, being responsible for respiratory distress. Cutaneous, hepatic, or neurological involvement is also possible. Although pathogenesis is not clearly elucidated, quantitative or qualitative cellular immunodepression is thought to be a main factor. Here, we report a case of concomitant LYG and pulmonary tuberculosis. Case presentation: An 80-year-old female patient presented to the emergency unit for steadily increasing dyspnea, with workup revealing bilateral pulmonary nodules and mediastinal lymph node enlargement on chest imaging. Empiric antibiotic therapy was initially started with amoxicillin-clavulanate, which was later combined with azithromycin following respiratory deterioration. A CT-guided lung biopsy showed grade 2 LYG. Treatment with corticosteroids and weekly rituximab was initiated, leading to rapid improvement of respiratory symptoms. After the second dose of rituximab, sputum cultures that were initially collected were found to be positive for Mycobacterium tuberculosis. Rituximab was suspended, and antituberculous treatment was initiated. Rituximab was restarted once tuberculosis was controlled. Follow-up imaging later showed adequate control of both tuberculosis and LYG, with at least a partial remission of the latter. Conclusions: Our case highlights the importance of a complete diagnostic workup when a diagnosis of LYG is made, to avoid missing a concomitant pulmonary disease, such as tuberculosis, even when definite pathologic and clinical features of the former are present. Full article

Coinfection with HIV, active tuberculosis, and COVID-19 is rare but markedly increases mortality risk and complicates treatment due to the interactions between these infections. Management requires a multidisciplinary approach that integrates antiretroviral therapy, antituberculous drugs, antibiotics, and supportive care for COVID-19. We report the case of a 28-year-old male with HIV (viral load 30 copies, CD4 count 303), active tuberculosis, and a history of resolved syphilis, who presented with severe respiratory decompensation and hypoxemia (SpO₂ 55%), requiring orotracheal intubation. Initial treatment included broad-spectrum antibiotics, antiretrovirals, and antituberculous therapy. Despite the critical illness, the patient demonstrated progressive clinical improvement, was successfully extubated after a spontaneous breathing trial, and continued recovery under supplemental oxygen. This case underscores the clinical complexity of triple coinfection and highlights the potential for favorable outcomes when management is timely and multidisciplinary. Full article

Objective: To analyze trends in resistance to antituberculous drugs over a 31-year period (1991–2022) at a hospital in Barcelona and to identify associated epidemiological determinants. Methods: This study included culture-confirmed tuberculosis cases diagnosed between 1991 and 2022. Drug susceptibility testing was conducted with clinical data from hospital records and epidemiological data from the Barcelona Public Health Agency. The primary outcome was resistance to first-line drugs. A subset of isolates was tested for second-line drugs. Trends were compared between the periods 1991–2000 and 2001–2022, aligning with increased immigration. Factors associated with resistance were examined using multivariate regression analysis. Results: Among the 2448 patients included, tuberculosis cases peaked in the 1990s and subsequently declined, while drug resistance increased. Overall, 12.2% of isolates showed resistance to at least one drug: 8.5% were monoresistant, 2.3% multiresistant, and 1.4% polyresistant. The 2001–2022 period had a higher resistance rate (OR 1.63; 95%CI 1.28–2.09) but lower multiresistance (OR 0.40; 95%CI 0.23–0.69). Resistance among new cases doubled from 6.4% to 12.8%, while rates among previously treated cases remained stable. The predictors of resistance were foreign-born (OR 1.52; 95%CI 1.21–1.91) and previous tuberculosis treatment (OR 2.88; 95%CI 2.17–3.81). A total of 90% of isolates remained susceptible to fluoroquinolones and aminoglycosides. Conclusions: Although tuberculosis incidence has declined over the past three decades, antibiotic resistance has increased, driven by foreign-born and retreatment cases. Ongoing drug susceptibility testing, access to second-line therapies, and targeted public health interventions for high-risk populations are essential to maintain control in low-incidence settings. Full article

Objective: We present the case of a 26-year-old male with severe spinal tuberculosis of the thoracolumbar region. The patient suffered from worsening back pain over five years, initially responding to over-the-counter analgesics. Despite being proposed surgery in 2019, the patient refused the intervention and subsequently experienced significant disease progression. Methods: Upon re-presentation in 2022, mild involvement of the T12-L1 vertebrae was recorded by imaging, leading to a percutaneous needle biopsy which confirmed tuberculosis. Despite undergoing anti-tuberculous therapy for one year, the follow-up in 2024 revealed extensive infection from T10 to S1, with large psoas abscesses and a pseudo-tumoral mass of the right thigh. The patient was ultimately submitted to a two-stage surgical intervention: anterior resection and reconstruction of T11-L1 with an expandable cage, followed by posterior stabilization from T8-S1. Results: Postoperative recovery was uneventful, with significant pain relief and no neurological deficits. The patient was discharged on a continued anti-tuberculous regimen and remains under close surveillance. Conclusions: This paper presents details on the challenges of diagnosis and management of severe spinal tuberculosis, with emphasis on the importance of timely intervention and multidisciplinary care. Full article

Tuberculous meningitis (TBM) presents a critical neurologic emergency characterized by high mortality and morbidity rates, necessitating immediate therapeutic intervention, often ahead of definitive microbiological and molecular diagnoses. The primary hurdle in effective TBM treatment is the blood–brain barrier (BBB), which significantly restricts the delivery of anti-tuberculous medications to the central nervous system (CNS), leading to subtherapeutic drug levels and poor treatment outcomes. The standard regimen for initial TBM treatment frequently falls short, followed by adverse side effects, vasculitis, and hydrocephalus, driving the condition toward a refractory state. To overcome this obstacle, intrathecal (IT) sustained release of anti-TB medication emerges as a promising approach. This method enables a steady, uninterrupted, and prolonged release of medication directly into the cerebrospinal fluid (CSF), thus preventing systemic side effects by limiting drug exposure to the rest of the body. Our review diligently investigates the existing literature and treatment methodologies, aiming to highlight their shortcomings. As part of our enhanced strategy for sustained IT anti-TB delivery, we particularly seek to explore the utilization of nanoparticle-infused hydrogels containing isoniazid (INH) and rifampicin (RIF), alongside osmotic pump usage, as innovative treatments for TBM. This comprehensive review delineates an optimized framework for the management of TBM, including an integrated approach that combines pharmacokinetic insights, concomitant drug administration strategies, and the latest advancements in IT and intraventricular (IVT) therapy for CNS infections. By proposing a multifaceted treatment strategy, this analysis aims to enhance the clinical outcomes for TBM patients, highlighting the critical role of targeted drug delivery in overcoming the formidable challenges presented by the blood–brain barrier and the complex pathophysiology of TBM. Full article

Behçet’s disease (BD) is a systemic vasculitis that frequently presents with a relapsing–remitting pattern. CNS involvement (Neuro-Behçet) is rare, affecting approximately 10% of patients. Its etiological mechanisms are not yet fully understood. The most commonly accepted hypothesis is that of a systemic inflammatory reaction triggered by an infectious agent or by an autoantigen, such as heat shock protein, in genetically predisposed individuals. Mycobacterium tuberculosis is known to be closely interconnected with BD, both affecting cell-mediated immunity to a certain extent and probably sharing a common genetic background. We present the case of a 34-year-old Caucasian woman who had been diagnosed with tuberculous meningitis 15 months prior, with significant neurological deficits and lesional burden on MRI with repeated relapses whenever treatment withdrawal was attempted. These relapses were initially considered as reactivation of tuberculous meningoencephalitis, and symptoms improved after a combination of antituberculous treatment and corticosteroid therapy. After the second relapse, the diagnosis was reconsidered, as new information emerged about oral and genital aphthous lesions, making us suspect a BD diagnosis. HLA B51 testing was positive, antituberculous treatment was stopped, and the patient was started on high doses of oral Cortisone and Azathioprine. Consequently, the evolution was favorable, with no further relapses and slow improvements in neurological deficits. To our knowledge, this is the first report of Neuro-Behçet’s disease onset precipitated by tuberculous meningitis. We include a review of the available literature on this subject. Our case reinforces the fact that Mycobacterium tuberculosis infection can precipitate BD in genetically predisposed patients, and we recommend HLA B51 screening in patients with prolonged or relapsing meningoencephalitis, even if an infectious agent is apparently involved. Full article

Four sets of previously synthesized 4-methyl-7-substituted coumarin derivatives were screened for their in vitro anti-inflammatory and anti-tubercular activities. The anti-inflammatory potential of 3a–t, 5a–o, 6a–n, and 7a–f synthesized compounds was evaluated by an anti-denaturation assay using diclofenac sodium as the reference standard. Evaluation of the anti-tuberculous activity of the mentioned compounds was performed by the Resazurin test method against four different TB strains using rifampicin and isoniazid as reference drugs. Based on the anti-inflammatory results, compounds 3o, 5f, 6c, and 7d proved to be the most active compounds in their respective series. Additionally, compounds 3k–n, 5b–d, 6d–f, 6k, 7a, and 7f were found to be the most potent anti-tuberculous agents. In fact, most of the screened compounds exhibited promising activity profiles compared to the respective standard drugs. The structure–activity connections revealed a few intriguing aspects, indicating that the presence of electron-donating and nitrogen-rich fragments boost the anti-inflammatory effects of the examined compounds. However, the presence of electron-withdrawing substituents was required to boost the anti-tubercular activity of the evaluated compounds. Full article

To investigate how structural modifications affect tuberculostatic potency, we synthesized seven new piperidinothiosemicrabazone derivatives 8–14, in which three of them had a pyrazine ring replacing the pyridine ring. Derivatives 8–9 and 13–14 exhibited significant activity against the standard strain (minimum inhibitory concentration (MIC) 2–4 μg/mL) and even greater activity against the resistant M. tuberculosis strain (MIC 0.5–4 μg/mL). Additionally, the effects of compounds 8–9 were entirely selective (MIC toward other microorganisms ≥ 1000 μg/mL) and non-toxic (IC50 to HaCaT cells 5.8 to >50 μg/mL). The antimycobacterial activity of pyrazine derivatives 11–12 was negligible (MIC 256 to >500 μg/mL), indicating that replacing the aromatic ring was generally not a promising line of research in this case. The zwitterionic structure of compound 11 was determined using X-ray crystallography. Absorption, distribution, metabolism, and excretion (ADME) calculations showed that all compounds, except 11, could be considered for testing as future drugs. An analysis of the structure–activity relationship was carried out, indicating that the higher basicity of the substituent located at the heteroaromatic ring might be of particular importance for the antituberculous activity of the tested groups of compounds. Full article

Background: We describe a case of EBV aseptic meningitis in a patient with HIV with an extensive history of prior infections and exposures. Detailed Case Description: A 35-year-old man with a history of HIV, syphilis, and partially treated tuberculosis presented with headache, fever, and myalgias. He reported recent exposure to dust from a construction site and had sexual contact with a partner with active genital lesions. An initial workup revealed mildly elevated inflammatory markers, significant pulmonary scarring from tuberculosis with a classic “weeping willow sign”, and lumbar puncture findings consistent with aseptic meningitis. An extensive evaluation was conducted to identify causes of bacterial and viral meningitis, including syphilis. Immune reconstitution inflammatory syndrome and isoniazid-induced aseptic meningitis were also considered based on his medications. EBV was ultimately isolated through PCR from the patient’s peripheral blood. The patient’s condition improved, and he was discharged on his home antiretroviral and anti-tuberculous treatment. Conclusion: Central nervous system infections represent unique challenges in patients with HIV. EBV reactivation can present with atypical symptoms and should be considered as a cause of aseptic meningitis in this population. Full article

A more effective vaccine against tuberculosis than Bacille Calmette-Guérin (BCG) is urgently needed. BCG derived recombinant VPM1002 has been found to be more efficacious and safer than the parental strain in mice models. Newer candidates, such as VPM1002 Δpdx1 (PDX) and VPM1002 ΔnuoG (NUOG), were generated to further improve the safety profile or efficacy of the vaccine. Herein, we assessed the safety and immunogenicity of VPM1002 and its derivatives, PDX and NUOG, in juvenile goats. Vaccination did not affect the goats’ health in regards to clinical/hematological features. However, all three tested vaccine candidates and BCG induced granulomas at the site of injection, with some of the nodules developing ulcerations approximately one month post-vaccination. Viable vaccine strains were cultured from the injection site wounds in a few NUOG- and PDX- vaccinated animals. At necropsy (127 days post-vaccination), BCG, VPM1002, and NUOG, but not PDX, still persisted at the injection granulomas. All strains, apart from NUOG, induced granuloma formation only in the lymph nodes draining the injection site. In one animal, the administered BCG strain was recovered from the mediastinal lymph nodes. Interferon gamma (IFN-γ) release assay showed that VPM1002 and NUOG induced a strong antigen-specific response comparable to that elicited by BCG, while the response to PDX was delayed. Flow cytometry analysis of IFN-γ production by CD4⁺, CD8⁺, and γδ T cells showed that CD4⁺ T cells of VPM1002- and NUOG-vaccinated goats produced more IFN-γ compared to BCG-vaccinated and mock-treated animals. In summary, the subcutaneous application of VPM1002 and NUOG induced anti-tuberculous immunity, while exhibiting a comparable safety profile to BCG in goats. Full article