Current Rheumatology Reviews - Online First
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Clodronate: The Influence on ATP Purinergic Signaling
Authors: Sergio Rosini, Stefano Rosini, Gianantonio Saviola and Luigi MolfettaAvailable online: 03 January 2025More LessATP is involved in numerous physiological functions, such as neurotransmission, modulation, and secretion, as well as in cell proliferation, differentiation, and death. While ATP serves an essential intracellular role as a source of energy, it behaves differently in the extracellular environment, where it acts as a signaling molecule capable of activating specific purinergic receptors (P2YRs and P2XRs) that modulate the response to ATP. Extracellular ATP signaling is a dynamic area of research, with particular interest in ATP’s effects on inflammatory conditions and pain modulation. Clodronate differs from other bisphosphonates that contain an amino group in their structure (N-BPs), and it is metabolized within osteoclasts into a toxic ATP analog, AppCCl2p, which causes mitochondrial dysfunction and osteoclast apoptosis. This characteristic differentiates Clodronate from N-BPs, as the latter act by interfering with the mevalonate pathway. Clodronate has demonstrated anti-inflammatory and analgesic activity in various bone and musculoskeletal diseases through mechanisms involving macrophages, neutrophils, peripheral nociceptors, and the central nervous system.
ATP produced inside cells is accumulated within transport vesicles, where it penetrates via a VNUT channel and is then released extracellularly, playing an active role in acute and chronic inflammatory processes, neurotransmission of pain, and liver disease regulation. Clodronate influences these processes due to its strong inhibitory effect on VNUT-mediated ATP release.
The aim of this review is to highlight the therapeutic potential offered by appropriate modulation of cellular ATP release and the inhibitory effects of Clodronate on the channel through which ATP penetrates transport vesicles.
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Updates on Recent Advances in the Therapy of Adult Psoriatic Disease
Authors: Fadi Kharouf and Dafna D GladmanAvailable online: 01 January 2025More LessPsoriatic arthritis (PsA) is a heterogeneous inflammatory disease with various joint and skin manifestations and multiple associated comorbidities. The management of PsA is important not only in controlling disease activity and preventing subsequent damage but also in improving the quality of life and reducing mortality. Over the years, numerous drugs have been introduced into the therapeutic armamentarium of the disease. While non-steroidal anti-inflammatory drugs (NSAIDs) and conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) have contributed to management, it was not until the advent of biologics (and later on targeted synthetic DMARDs) that therapy was revolutionized, with the achievement of significantly better clinical and radiographic outcomes. Several drugs and treatment approaches are currently being tested in clinical trials at different phases. Despite all the success, there are still various challenges and unmet needs in the field of PsA, reflected by difficult-to-treat disease course, secondary failure of therapy, and lack of consensus on accepted treatment withdrawal protocols, among others. In this review, we have discussed the most recent advances in the therapy of psoriatic disease, with a particular focus on phase III studies completed (or ongoing) since 2020. We also mentioned the challenges and unmet needs in our clinical practice, which we expect current and future research to provide answers to.
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De novo Presentation of Systemic Lupus as Bullous Erythematosus: A Case Report
Available online: 09 December 2024More LessBackgroundSystemic Lupus Erythematosus (SLE) (C1) is a disease with multi-organ involvement that can have a variety of cutaneous manifestations in 76% of cases during the disease. Less than 1% of these patients are diagnosed with confirmed bullous systemic lupus erythematosus (C1). Given the wide differential diagnosis of a bullous lesion, it is imperative to reach a conclusive diagnosis as it can have a direct impact on the course of management of the disease. Here, we present a case of SLE with a de novo presentation of bullous lesions. Throughout the length of the report, we will go through the protracted clinical course of the patient, followed by a clinically relevant discussion of the condition.
Case PresentationThe case describes the presentation of a young African female of low socio-economic status with first-ever eruption of bullous lesions on her trunk and groin. The lesions progressed to involve the face. A biopsy was taken, and the patient was started on dapsone and hydroxychloroquine. She initially responded well but soon developed Steven Johnson syndrome in reaction to dapsone. In the meantime, a biopsy and hematological work-up confirmed a diagnosis of Bullous SLE. The patient was started on methotrexate, to which she initially responded well but developed methotrexate-induced cytopenia. This was followed by initiation of mycophenolate, to which the patient responded very well and was subsequently discharged on the same. At the time of discharge, all lesions healed, and the hematological workup remarkably improved.
ConclusionAll patients with bullous lesions should be evaluated for bullous SLE. A definitive diagnosis will chart the course of management. Multiple drug options are available, and there is no single hierarchy of medicines that will suit all. Sometimes, multiple modalities need to be tried before the patient achieves clinical remission and then can be continued on the same.
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Expression of CD68+ Cells in Synovial Tissue from Patients with PsA and its Association with Disease Activity Indices: A Clinical Pilot Study
Available online: 03 December 2024More LessIntroductionInvestigating CD68+ positive cells in the synovial tissue is crucial for understanding the pathogenesis of psoriatic arthritis (PsA) and developing targeted treatment strategies. The role of CD68+ positive cells in the synovial tissue of patients with PsA for joint destruction has not been fully studied.
ObjectiveThe objective of the study was to examine the presence of CD68+ cells in the synovial tissue of patients with PsA, particularly those with high inflammatory activity.
MethodsSynovial tissue samples were collected during knee joint replacement surgeries from patients with PsA (16 patients) and gonarthrosis (25 patients). Immunohistochemical methods were employed to detect CD68+ cell expression in the tissue samples. The results were analyzed by histologists, and the staining intensity and percentage of positively stained cells were evaluated. The data were then divided into three groups for statistical analysis: negative, weakly positive, and strongly positive histological samples. Routine indices for disease activity, VAS, DAPSA, PASDAI, and mCPDAI were used to assess PsA activity in all patients and to assess correlations with CD68+ positive cells in the synovial tissue. Statistical analysis was performed using SPSS version 26.0 (SPSS Inc., Chicago, IL, USA).
ResultsThe expression of CD68+ positive cells was significantly higher in patients with PsA compared to those with activated gonarthrosis (p < 0.001). The indices for disease activity, VAS, DAPSA, PASDAI, mCPDAI, and mCPDAI showed a significant positive relationship with the expression of CD68 + cells on synovial tissue in patients with PsA (p < 0.01)
ConclusionThe findings of the study confirm the increased numbers of CD68+ cells in PsA vs. gonathrosis synovium. This suggests the need to explore therapeutic approaches aimed at suppressing or blocking CD68+ cells to potentially mitigate joint damage.
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Upadacitinib and Cardiovascular Adverse Events in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis
Authors: Fatemeh Omidi, Parisa Delkash, Mohammad Javad Nasiri and Mehdi MirsaeidiAvailable online: 07 November 2024More LessBackgroundUpadacitinib, a Janus kinase (JAK) inhibitor used in rheumatoid arthritis treatment, has prompted safety concerns due to potential cardiovascular adverse events. However, current evidence does not provide a definitive conclusion.
MethodsWe conducted a comprehensive systematic review of the literature up until March 15, 2024, utilizing databases like PubMed/Medline, Embase, and Cochrane CENTRAL. A meta-analysis approach was used to derive pooled odds ratios (OR) along with their 95% confidence intervals (CI) to assess the cardiovascular risk associated with upadacitinib. Publication bias was evaluated using Begg's and Egger's tests.
ResultsOur meta-analysis included six studies with a total of 4,202 participants. For the 15 mg dosage of Upadacitinib, the pooled OR was 1.20 (95% CI: 0.3-4.3), indicating a nominal, non-significant increase in the risk of cardiovascular adverse events. Analysis of the 30 mg dosage presented a pooled OR of 2.37 (95% CI: 0.6-9.1), pointing to a higher, yet statistically insignificant, potential risk. The absence of publication bias was confirmed through Begg's and Egger’s tests.
ConclusionThe analysis suggests a potential heightened cardiovascular risk associated with Upadacitinib, more so with the 30 mg dosage. Nevertheless, the lack of statistical significance and the wide confidence intervals necessitate a prudent approach to these findings. Tailored treatment strategies, rigorous monitoring, and further empirical studies are crucial for refining the safety profile of upadacitinib and ensuring optimal patient outcomes.
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Sjögren’s Syndrome and Ankylosing Spondylitis Association: A Case-Based Review
Authors: Maroua Slouma, Takwa Mehmli, Emna Hannech, Rim Dhahri, Islam Mejri, Meriem Affes and Imen GharsallahAvailable online: 05 November 2024More LessIntroductionUnlike restrictive pulmonary function and apical fibrobullous disease, diffuse interstitial lung disease is scarce in patients with ankylosing spondylitis (AS). We present a systematic review of the association between AS and SS. We also report a new case of SS revealed by interstitial lung disease in AS patients treated with tumor necrosis factor (TNF) inhibitors.
Materials and methodsThe systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the MEDLINE and SCOPUS databases and included case reports and case series describing the association between AS and SS.
ResultsThere were sixty-three patients, including our case: 16 males and 47 females. The mean age was 49.2 years. The mean SpA duration was 14.1 years. The mean delay between SpA and SS was 12.8 years (0-27). SS was diagnosed after SpA in 62% of cases (n=39). It preceded SpA in 36.5% (n=23) and was concomitant with SpA in 1 case. All patients had sicca symptoms. MSGB showed focal sialadenitis grade III or grade IV in the Chisholm classification in 20 patients. Anti-nuclear antibody was positive in 75.8% of cases. Among them, anti-SSA and anti-SSB were positive in 44.4% and 35.3% of cases. Except for our patient, no patient had interstitial lung disease. SS extra glandular manifestations were reported in 12 cases.
ConclusionThe occurrence of Sjögren’s syndrome is uncommon in patients with ankylosing spondylitis. This association has been reported in the literature, suggesting a pathogenetic link between these two diseases. This association should be considered in ankylosing spondylitis patients with diffuse interstitial lung disease. Knowing this association is necessary for therapeutic adjustment.
Our study has some limitations. Publication bias was the major bias in our study. Indeed, we only included case reports and case series describing the association between SpA and SS. We did not search for unpublished work. Moreover, the follow-up was not specified in most included articles.
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Unmasking the Hidden Peril: A Case Report of Ankylosing Spondylitis Revealing a Giant Aortic Aneurysm
Available online: 31 October 2024More LessBackgroundAnkylosing Spondylitis is a chronic inflammatory rheumatic disease with both articular and extra-articular features. While cardiovascular involvement in Ankylosing spondylitis is rare, it can be life-threatening. This condition is typically associated with the HLA-B27 antigen and often presents in the advanced stages of the disease.
This case is particularly uncommon as cardiovascular involvement was identified at the time of diagnosis in a patient who tested negative for HLA-B27.
Case PresentationHere, we present an uncommon case of a 37-year-old male with 3 years of evolving Ankylosing Spondylitis negative for HLA-B27, who was incidentally found to have a giant aortic aneurysm during cardiovascular screening at the time of his rheumatic disease diagnosis. The patient underwent surgical intervention using the Tyron-David procedure. Subsequent post-operative follow-ups revealed satisfactory outcomes without complications,
ConclusionEven in the absence of clinical signs, and even in the early stages of Ankylosing spondylitis, it is necessary to screen for this condition, at least with transthoracic ultrasound. Early screening ensures prompt treatment, which will save the patient’s life.
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The Ability of Indigenous Plants in Alleviating Rheumatoid Arthritis: A Comprehensive Review
Authors: Aslam Khan, Avijit Mazumder, Bhavani Pentela, Rashmi Mishra and Sachin Kumar SinghAvailable online: 30 October 2024More LessRheumatoid Arthritis is a long-lasted, inflammatory, systemic autoimmune disease that predominantly manifests in people between the ages of 30 and 50 Rheumatoid arthritis is characterized by more than a half-hour of morning stiffness in the affected joints, fever, soreness, swelling, weight loss, tiredness, warm joints, and subcutaneous rheumatoid nodules. Hormonal, genetic, epigenetic, reproductive, and neuroendocrine risk factors, as well as comorbid host variables, are the categories of host-related risk factors associated with the evolution of RA. Additional risk variables that have been linked to RA include food, environmental variables, socioeconomic status, smoking, microbiome, infection agents, and other airborne exposures. The objective of RA therapies is to minimise joint deformity and destruction, minimise discomfort and inflammation in the joints, and maximise joint function.Growing data suggests that the course of Rheumatoid Arthritis is affected by the minimisation of disease activity caused by disease-modifying medications, and that patients may benefit from early antirheumatic medication delivery that modifies illness. While numerous herbs have been explored for their anti-inflammatory properties, it is important to note that not all herbs have been thoroughly researched. This review focuses on seventeen native plant species that have shown either promising or established anti-arthritic effects based on preclinical and clinical studies where available. The review highlights the biochemical and immunological attributes of these herbs, summarizing their therapeutic potential for RA management while also acknowledging the limitations and gaps in current research. This examination provides insights into the potential of these herbal treatments for RA and calls for further research to explore their efficacy and safety in greater depth.
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Promising Anti-Inflammatory Properties of Ursolic Acid Isolated from Atylosia goensis
Authors: Leemol Varghese and Shanaz BanuAvailable online: 24 October 2024More LessIntroductionIndigenous plants are plant species that are native to a specific region and have evolved naturally and adapted to local environmental conditions over a long period.
AimThis study aimed to explore the anti-arthritic effects of Atylosia goensis, an indigenous plant species in the Western Ghats of India.
MethodologyAn ethanolic extract of Atylosia goensis was obtained using the Soxhlet extraction method, which revealed a diverse array of phytochemicals through liquid chromatography-mass spectroscopy (LC-MS). Key compounds, including fatty acids, sterols, and potential health-beneficial compounds, were identified, and one prominent phytoconstituent, ursolic acid, was spectroscopically characterized using 1H NMR, 13C NMR, and mass spectrometry. The research also examined the anti-inflammatory activity and in-vitro and in-vivo anti-arthritic activity of ethanolic extract.
ResultsThe ethanol extract exhibited notable inhibition of Cox-2, indicating potential anti-inflammatory effects. The in vivo anti-arthritic activity of ursolic acid was evaluated at different doses (200 and 400 mg/kg) over a 24-day period. Ursolic acid significantly reduced joint edema, particularly at higher doses, thereby emphasizing its anti-inflammatory properties. Biomarker analysis revealed dose-dependent attenuation of disease-associated biomarker levels, supporting the potential therapeutic efficacy of ursolic acid in arthritis management. Moreover, the hepatoprotective potential of ursolic acid was evident in biochemical parameters, including SGPT, SGOT, and ALP levels. Both doses of ursolic acid effectively mitigated liver dysfunction induced in the disease control group, demonstrating its protective role in liver health. Histopathological assessments corroborated these findings, indicating a reduction in inflammatory areas following ursolic acid treatment, especially at higher doses.
ConclusionThis experimental work provides valuable information on the therapeutic potential of Atylosia goensis and ursolic acid, emphasizing their roles in anti-inflammatory and hepatoprotective applications. This study contributes to the understanding of plant-derived compounds for potential pharmaceutical use in the management of inflammatory and arthritic conditions.
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Familial Mediterranean Fever
Authors: Esra Baskin and Umit Saatci
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Metabolic Syndrome in Behçets Disease Patients: Keep an Eye on the Eye
Authors: Suzan S. ElAdle, Eiman A. Latif, Yousra H. Abdel-Fattah, Emad El Shebini, Iman I. El-Gazzar, Hanan M. El-Saadany, Nermeen Samy, Reem El-Mallah, Mohamed N. Salem, Nahla Eesa, Rawhya El Shereef, Marwa El Khalifa, Samar Tharwat, Samah I. Nasef, Maha Emad Ibrahim, Noha M. Khalil, Ahmed M. Abdalla, Mervat I. Abd Elazeem, Rasha Abdel Noor, Rehab Sallam, Amany El-Bahnasawy, Amira El Shanawany, Soha Senara, Hanan M. Fathi, Samah A. El Bakry, Ahmed Elsaman, Amany El Najjar, Usama Ragab, Esraa A. Talaat, Nevin Hammam, Aya K. El-Hindawy, Tamer A. Gheita and Faten Ismail
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