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BMC Neurology Apr 2024Monogenic autoinflammatory disorders result in a diverse range of neurological symptoms in adults, often leading to diagnostic delays. Despite the significance of early...
BACKGROUND
Monogenic autoinflammatory disorders result in a diverse range of neurological symptoms in adults, often leading to diagnostic delays. Despite the significance of early detection for effective treatment, the neurological manifestations of these disorders remain inadequately recognized.
METHODS
We conducted a systematic review searching Pubmed, Embase and Scopus for case reports and case series related to neurological manifestations in adult-onset monogenic autoinflammatory diseases. Selection criteria focused on the four most relevant adult-onset autoinflammatory diseases-deficiency of deaminase 2 (DADA2), tumor necrosis factor receptor associated periodic fever syndrome (TRAPS), cryopyrin associated periodic fever syndrome (CAPS), and familial mediterranean fever (FMF). We extracted clinical, laboratory and radiological features to propose the most common neurological phenotypes.
RESULTS
From 276 records, 28 articles were included. The median patient age was 38, with neurological symptoms appearing after a median disease duration of 5 years. Headaches, cranial nerve dysfunction, seizures, and focal neurological deficits were prevalent. Predominant phenotypes included stroke for DADA2 patients, demyelinating lesions and meningitis for FMF, and meningitis for CAPS. TRAPS had insufficient data for adequate phenotype characterization.
CONCLUSION
Neurologists should be proactive in diagnosing monogenic autoinflammatory diseases in young adults showcasing clinical and laboratory indications of inflammation, especially when symptoms align with recurrent or chronic meningitis, small vessel disease strokes, and demyelinating lesions.
Topics: Young Adult; Humans; Adult; Hereditary Autoinflammatory Diseases; Neurologists; Adenosine Deaminase; Intercellular Signaling Peptides and Proteins; Familial Mediterranean Fever; Cryopyrin-Associated Periodic Syndromes; Fever; Phenotype; Meningitis
PubMed: 38632524
DOI: 10.1186/s12883-024-03621-3 -
Reumatologia Clinica Mar 2024Adenosine deaminase (ADA) activity has shown good performance in diagnosing pleural, peritoneal, and meningeal tuberculosis. This meta-analysis aimed to evaluate the... (Meta-Analysis)
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; I=23%) and 88% (95% CI, 83-92; I=83%), respectively. The random-effects model for pooled diagnostic Odds ratio was 67.1 (95%CI, 20.3-222.2; I=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.
Topics: Humans; Adenosine Deaminase; Synovial Fluid; Sensitivity and Specificity; Tuberculosis, Osteoarticular; Arthritis
PubMed: 38494302
DOI: 10.1016/j.reumae.2024.02.002 -
Cellular & Molecular Biology Letters Jan 2024Rheumatoid arthritis (RA) is an autoimmune disease involving T and B lymphocytes. Autoantibodies contribute to joint deterioration and worsening symptoms. Adenosine...
Rheumatoid arthritis (RA) is an autoimmune disease involving T and B lymphocytes. Autoantibodies contribute to joint deterioration and worsening symptoms. Adenosine deaminase (ADA), an enzyme in purine metabolism, influences adenosine levels and joint inflammation. Inhibiting ADA could impact RA progression. Intracellular ATP breakdown generates adenosine, which increases in hypoxic and inflammatory conditions. Lymphocytes with ADA play a role in RA. Inhibiting lymphocytic ADA activity has an immune-regulatory effect. Synovial fluid levels of ADA are closely associated with the disease's systemic activity, making it a useful parameter for evaluating joint inflammation. Flavonoids, such as quercetin (QUE), are natural substances that can inhibit ADA activity. QUE demonstrates immune-regulatory effects and restores T-cell homeostasis, making it a promising candidate for RA therapy. In this review, we will explore the impact of QUE in suppressing ADA and reducing produced the inflammation in RA, including preclinical investigations and clinical trials.
Topics: Humans; Adenosine; Adenosine Deaminase; Arthritis, Rheumatoid; Inflammation; Quercetin; Adenosine Deaminase Inhibitors
PubMed: 38225555
DOI: 10.1186/s11658-024-00531-7 -
Tuberculosis and Respiratory Diseases Jan 2024Tuberculous pleural effusion (TPE) and parapneumonic effusion (PPE) are often difficult to differentiate owing to the overlapping clinical features. Observational...
BACKGROUND
Tuberculous pleural effusion (TPE) and parapneumonic effusion (PPE) are often difficult to differentiate owing to the overlapping clinical features. Observational studies demonstrate that the ratio of lactate dehydrogenase to adenosine deaminase (LDH/ADA) is lower in TPE compared to PPE, but integrated analysis is warranted.
METHODS
We conducted a systematic review to evaluate the diagnostic accuracy of the LDH/ADA ratio in differentiating TPE and PPE. We explored the PubMed and Scopus databases for studies evaluating the LDH/ADA ratio in differentiating TPE and PPE.
RESULTS
From a yield of 110 studies, five were included for systematic review. The cutoff value for the LDH/ADA ratio in TPE ranged from <14.2 to <25. The studies demonstrated high heterogeneity, precluding meta-analysis. Quality Assessment of Diagnostic Accuracy Studies Tool 2 assessment revealed a high risk of bias in terms of patient selection and index test.
CONCLUSION
LDH/ADA ratio is a potentially useful parameter to differentiate between TPE and PPE. Based on the limited data, we recommend an LDH/ADA ratio cutoff value of <15 in differentiating TPE and PPE. However, more rigorous studies are needed to further validate this recommendation.
PubMed: 37726943
DOI: 10.4046/trd.2023.0107 -
Infection & Chemotherapy Jun 2023Tuberculous peritonitis is difficult to diagnose due to its non-specific clinical manifestations and lack of proper diagnostic modalities. Current meta-analysis was...
BACKGROUND
Tuberculous peritonitis is difficult to diagnose due to its non-specific clinical manifestations and lack of proper diagnostic modalities. Current meta-analysis was performed to find the overall diagnostic accuracy of adenosine deaminase (ADA) in diagnosing tuberculous peritonitis.
MATERIALS AND METHODS
PubMed, Google Scholar, and Cochrane library were searched to retrieve the published studies which assessed the role of ascitic fluid ADA in diagnosing tuberculous peritonitis from Jan 1980 to June 2022. This meta-analysis included 20 studies and 2,291 participants after fulfilling the inclusion criteria.
RESULTS
The pooled sensitivity was 0.90 (95% confidence interval [CI]: 0.85 - 0.94) and pooled specificity was 0.94 (95% CI: 0.92 - 0.95). The positive likelihood ratio was 15.20 (95% CI: 11.70 - 19.80), negative likelihood ratio was 0.10 (95% CI: 0.07 - 0.16) and diagnostic odds ratio was 149 (95% CI: 86 - 255). The area under the summary receiver operating characteristic curve was 0.97. Cut- off value and sample size were found to be the sources of heterogeneity in the mete-regression analysis.
CONCLUSION
Ascitic fluid ADA is a useful test for the diagnosis of tuberculous peritonitis with good sensitivity and specificity however, with very low certainty of evidence evaluated by Grading of Recommendations, Assessment, Development and Evaluation approach. Further well- designed studies are needed to validate the diagnostic accuracy of ascitic fluid ADA for tuberculous peritonitis.
PubMed: 37407244
DOI: 10.3947/ic.2023.0014 -
Cureus Jun 2023Tuberculous meningitis is the most serious complication of tuberculosis. Early diagnosis is crucial to start relevant treatment to prevent death and disability.... (Review)
Review
Tuberculous meningitis is the most serious complication of tuberculosis. Early diagnosis is crucial to start relevant treatment to prevent death and disability. Electronic databases PubMed, Google Scholar, and Cochrane Library were used to find relevant articles from January 1980 to June 2022. The random-effect model in terms of pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence interval was adopted to derive the diagnostic efficacy of cerebrospinal fluid (CSF) adenosine deaminase (ADA) for the diagnosis of tuberculous meningitis (TBM) in adult patients. A total of 22 studies (20 prospective and two retrospective data) have been included in this meta-analysis, having 1927 participants. We perceived acceptable pooled sensitivity, specificity, summary receiver operating characteristics (SROCs), and diagnostic odds ratio (DOR) of 0.85 (95% CI: 0.77-0.90), 0.90 (95% CI: 0.85-0.93), 0.94 (95% CI: 0.91-0.96) and 48 (95% CI: 26-86), respectively, for CSF-ADA for differentiating TBM from non-TBM in adult patients. To ascertain the certainty of evidence for CSF-ADA as a diagnostic marker for TBM, Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) analysis was used. CSF-ADA is an auspicious diagnostic test with a high degree of specificity and acceptable sensitivity for the diagnosis of tuberculous meningitis, however, with very low certainty of evidence.
PubMed: 37404432
DOI: 10.7759/cureus.39896 -
Orphanet Journal of Rare Diseases May 2023Deficiency of adenosine deaminase 2 (DADA2) is a rare monogenic autoinflammatory disease, whose clinical phenotype was expanded since the first cases, originally... (Review)
Review
INTRODUCTION
Deficiency of adenosine deaminase 2 (DADA2) is a rare monogenic autoinflammatory disease, whose clinical phenotype was expanded since the first cases, originally described as mimicker of polyarteritis nodosa, with immunodeficiency and early-onset stroke.
METHODS
A systematic review according to PRISMA approach, including all articles published before the 31st of August 2021 in Pubmed and EMBASE database was performed.
RESULTS
The search identified 90 publications describing 378 unique patients (55.8% male). To date 95unique mutations have been reported. The mean age at disease onset was 92.15 months (range 0-720 months), 32 (8.5%) showed an onset of the first signs/symptoms after 18 years old and 96 (25.4%) after 10 years old. The most frequent clinical characteristics described were cutaneous (67.9%), haematological manifestations (56.3%), recurrent fever (51.3%), neurological as stroke and polyneuropathy (51%), immunological abnormalities (42.3%), arthralgia/arthritis (35.4%), splenomegaly (30.6%), abdominal involvement (29.8%), hepatomegaly (23.5%), recurrent infections (18.5%), myalgia (17.9%), kidney involvement (17.7%) etc. Patients with skin manifestations were older than the others (101.1 months SD ± 116.5, vs. 75.3 SD ± 88.2, p 0.041), while those with a haematological involvement (64.1 months SD ± 75.6 vs. 133.1 SD ± 133.1, p < 0.001) and immunological involvement (73.03 months SD ± 96.9 vs. 103.2 SD ± 112.9, p 0.05) are younger than the others. We observed different correlations among the different clinical manifestations. The use of anti-TNFα and hematopoietic cell stems transplantation (HCST) has improved the current history of the disease.
CONCLUSION
Due to this highly variable phenotype and age of presentation, patients with DADA2 may present to several type of specialists. Given the important morbidity and mortality, early diagnosis and treatment are mandatory.
Topics: Male; Female; Humans; Adenosine Deaminase; Intercellular Signaling Peptides and Proteins; Phenotype; Stroke; Mutation
PubMed: 37179309
DOI: 10.1186/s13023-023-02721-6 -
Tropical Medicine & International... Mar 2023To comprehensively evaluate the diagnostic efficacy of adenosine deaminase in cerebrospinal fluid (CSF) for tuberculous meningitis (TBM), and the potential influence of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To comprehensively evaluate the diagnostic efficacy of adenosine deaminase in cerebrospinal fluid (CSF) for tuberculous meningitis (TBM), and the potential influence of patients' age groups and cutoffs of measured adenosine deaminase.
METHODS
Systematic review and meta-analysis of relevant studies retrieved from PubMed, Embase, and Web of Science databases. Pooled sensitivity and specificity were calculated with a random-effect model.
RESULTS
Overall, 43 studies with 1653 patients with TBM and 3417 controls without were included. Pooled results showed that adenosine deaminase in CSF is associated with satisfactory diagnostic efficacy for TBM, with a pooled sensitivity of 0.86 (95% confidence interval [CI]: 0.82-0.90), specificity of 0.89 (95% CI: 0.86-0.91), positive likelihood ratio of 7.70 (95% CI: 6.16-9.63), and negative likelihood ratio of 0.15 (95% CI: 0.12-0.20). The pooled receiver operating characteristic (AUC) was 0.94 (95% CI: 0.91-0.96), suggesting good performance. Subgroup analyses showed good diagnostic efficacies of adenosine deaminase in CSF for both adults (AUC 0.95) and children (AUC 0.96) with TBM. AUCs indicating the diagnostic accuracies of adenosine deaminase in CSF for TBM were 0.93 for studies with cutoffs <10 U/L and and 0.94 for a cutoff =10 U/L, but only 0.90 for studies with cutoffs >10 U/L.
CONCLUSIONS
Measuring adenosine deaminase of CSF shows satisfactory diagnostic efficacy for TBM in children and adults, particularly if using a cutoff ≤10 U/L.
Topics: Adult; Child; Humans; Adenosine Deaminase; Cerebrospinal Fluid; ROC Curve; Sensitivity and Specificity; Tuberculosis, Meningeal
PubMed: 36591905
DOI: 10.1111/tmi.13849 -
Annals of Medicine Dec 2022Paediatric pleural tuberculosis (TB) is a paucibacillary disease, which increases the difficulty of examination. We aimed to assess the performance of pleural fluid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Paediatric pleural tuberculosis (TB) is a paucibacillary disease, which increases the difficulty of examination. We aimed to assess the performance of pleural fluid adenosine deaminase (ADA) in the detection of paediatric pleural TB.
METHODS
PubMed, Web of Science Core Collection, Embase and Cochrane Library databases were searched up to 20 December 2021. We used the bivariate and hierarchical summary receiver operating characteristic models to compute pooled estimates for the overall diagnostic accuracy parameters of ADA for diagnosing paediatric pleural TB.
RESULTS
Eight studies, including 290 pleural fluid samples, met the inclusion criteria. The pooled sensitivity of ADA was 0.85 (95% CI: 0.78-0.90, I: 55.63% < 75%) for detecting patients with paediatric pleural TB. A total of 262 pleural fluid samples from four studies were included to differentiate patients with paediatric pleural TB from controls. At a unified cut-off value of 40 U/L, the pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the summary receiver operating characteristic curve of ADA were 0.89, 0.58, 2.09, 0.20, 10.48 and 0.89, respectively.
CONCLUSIONS
At a cut-off value of 40 U/L, the overall performance of ADA was good for detecting paediatric pleural TB, with relatively high sensitivity and low specificity. Key messageAccurate identification of paediatric pleural TB will help eliminate TB in children. At a cut-off value of 40 U/L, the overall performance of ADA was good for detecting paediatric pleural TB, with relatively high sensitivity and low specificity.
Topics: Humans; Child; Tuberculosis, Pleural; Adenosine Deaminase; Pleural Effusion; Sensitivity and Specificity; ROC Curve
PubMed: 36345981
DOI: 10.1080/07853890.2022.2140452 -
Frontiers in Public Health 2022Abdominal tuberculosis (TB) is a common type of extrapulmonary TB with an insidious onset and non-specific symptoms. Adenosine deaminase (ADA) levels increase rapidly in... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Abdominal tuberculosis (TB) is a common type of extrapulmonary TB with an insidious onset and non-specific symptoms. Adenosine deaminase (ADA) levels increase rapidly in the early stages of abdominal TB. However, it remains unclear whether ADA serves as a diagnostic marker for abdominal TB.
METHODS
We performed a systematic literature search for relevant articles published in PubMed, Web of Science, Cochrane Library, and Embase up to April 2022. First, we used the Quality Assessment of Diagnostic Accuracy Studies tool-2 (QUADAS-2), to evaluate the quality of the included articles. Bivariate and hierarchical summary receiver operating characteristic (HSROC) models were then utilized to analyze pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve (AUROC). In addition, we explored a subgroup analysis for potential heterogeneity and publication bias among the included literature.
RESULTS
Twenty-four articles (3,044 participants, 3,044 samples) which met the eligibility criteria were included in this study. The pooled sensitivity and specificity of ADA for abdominal TB detection were 93% [95% confidence interval (CI): 0.89-0.95] and 95% (95% CI: 0.93-0.96), respectively. PLR and NLR were 18.6 (95% CI: 14.0-24.6) and 0.08 (95% CI: 0.05-0.12), respectively. DOR and AUROC were 236 (95% CI: 134-415) and 0.98 (95% CI: 0.96-0.99), respectively. Furthermore, no heterogeneity or publication bias was found.
CONCLUSIONS
Our meta-analysis found ADA to be of excellent diagnostic value for abdominal TB and could be used as an auxiliary diagnostic tool.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier: CRD42022297931.
Topics: Adenosine Deaminase; Humans; ROC Curve; Sensitivity and Specificity; Tuberculosis
PubMed: 36211645
DOI: 10.3389/fpubh.2022.938544