Search Results (297)

Chikungunya virus (CHIKungunya Virus, CHIKV) is a mosquito-borne plus-stranded RNA virus. Adaptive mutations such as A226V in the E1 envelope protein of CHIKV significantly enhance the transmission efficiency of the virus in Aedes albostriae, leading to multiple rounds of epidemics around the world including the large-scale outbreak in Guangdong Province in 2025. After a viral infection, a significant proportion of patients will progress from acute arthralgia to chronic arthritis that persists. The pathogenesis of the disease involves the persistence of the virus in joint tissues, the persistent inflammatory response with IL-1β, IL-6 and IL-17 as the core mediated by macrophages, possible autoimmune cross-reactions, and individual genetic susceptibility. At present, there is no specific antiviral drug, but important progress has been made in vaccine development against the virus. Vaccines based on live attenuated virus (VLA1553) and virus-like particle (VLP) platforms have been approved for the market and provide a tool to prevent and control this important public health threat. This review synthesizes current knowledge on CHIKV-induced chronic arthritis pathogenesis and recent vaccine advances, providing a framework for understanding disease mechanisms and guiding future prevention strategies. Full article

Background/Objectives: Understanding the relationship between reactogenicity and immunogenicity after repeated BNT162b2 vaccination is critical for optimizing vaccination strategies. This study quantified their progressive dissociation across four vaccine doses. Methods: We conducted a prospective longitudinal cohort study among Croatian healthcare workers vaccinated with BNT162b2 from January 2021 to January 2024. Anti-SARS-CoV-2 IgG antibodies were measured at 16 timepoints using chemiluminescent immunoassay. Local (pain, erythema, swelling) and systemic (fever, fatigue, headache, myalgia, arthralgia, nausea) reactions were recorded for 7 days using FDA toxicity scale. Correlations were analyzed with Spearman’s method and Bonferroni correction. Fourth-dose responses were predicted by exponential modeling. Results: Of 631 participants, 524 completed primary immunization, 418 received a third dose (173 with complete data), and 56 received a fourth dose (22 with complete paired data). Local reactions declined from 82.4% after the first dose to 42.9% after the fourth (p < 0.001). Systemic reactions peaked at 44.8% after the second dose, then decreased to 26.0% after the third and 19.6% after the fourth. In contrast, median antibody levels rose from 9910 AU/mL after the primary series to 29,002 AU/mL after the third and 38,274 AU/mL after the fourth. Correlations between reactions and antibody titer progressively weakened: r = 0.37 (95% CI 0.29–0.44, p < 0.001) after the primary series, r = 0.08 (95% CI −0.07 to 0.23, p = 0.30) after the third, and r = 0.04 (95% CI −0.39 to 0.45, p = 0.86) after the fourth dose. Conclusions: Progressive dissociation between reactogenicity and immunogenicity was observed across four BNT162b2 doses. Booster doses maintain robust antibody responses despite reduced reactogenicity, reinforcing that minimal side effects are consistent with sustained humoral responses. Full article

Objectives: To quantitatively assess masticatory function with instrumental measures in a group of patients suffering from temporomandibular joint (TMJ) arthralgia, and to compare the results with symptom-free controls. Methods: Data of bite force, variance-of-hue-based (VOH) chewing efficiency, chewing frequency, the bilateral pressure pain threshold (PPT) of the temporalis and masseter muscles, and mandibular range of motion (RoM) were collected in a sample of TMJ arthralgia patients (n = 14) and controls (n = 19). The diagnosis of arthralgia was obtained following the DC/TMD protocol. Comparison between the groups was conducted using independent samples t-tests (level of significance α = 0.05). Associations within the arthralgia group were assessed using Pearson’s correlation coefficient. Results: In comparison to the controls, arthralgia patients showed significantly restricted pain-free and maximum unassisted mouth opening (p < 0.001, p = 0.022 respectively) as well as a significant decrease in both bite force (p < 0.001) and chewing frequency (p = 0.01). The average chewing efficiency for the arthralgia group was 0.14 ± 0.08 VOH. The PPT for both masseter muscles did not show significant differences in comparison to the control group. Conclusions: In patients with TMJ arthralgia, functional markers such as RoM, bite force, and chewing frequency exhibited significant limitations compared to the control group. The employment of instrumental measurements in the documentation of symptoms in clinical practice provides an objective basis for the assessment of functional limitations. Hence, we recommend integrating them into the longitudinal patients’ observation during therapy. Full article

Background/Objectives: Severe infusion-related reactions to rituximab are rare; we aim to extend our knowledge about them in children, focusing on rituximab-induced serum sickness (RISS) and anaphylaxis. Methods: We conducted a monocentric retrospective study on children and adolescents who received rituximab. Patients were defined as having RISS if they had fever and at least rash and/or arthralgia, 1 to 30 days following infusion, and without another diagnosis to explain symptoms. Anaphylaxis was defined according to the diagnostic criteria proposed by the World Allergy Organization. Results: 1534 rituximab infusions in 391 patients were analyzed. Seven patients developed RISS; all received rituximab for an autoimmune disease, including four for immune thrombocytopenia (ITP). Six patients had fever, rash, and arthralgia. C-reactive protein or sedimentation rate was increased in all patients, and complement was decreased in 83%. Evolution was favorable within a few days with corticosteroids and/or intravenous immunoglobulins. Rituximab was reinfused in one patient, which resulted in an immediate anaphylactoid reaction. Lower doses of rituximab were less likely to induce RISS. RISS was associated with a greater chance of achieving ITP remission. Seven patients developed anaphylaxis; five successfully received further infusions using desensitization protocols. Conclusions: RISS in children is a severe complication of rituximab infusion. Our study suggests that it may be more frequent in individuals treated for autoimmune conditions, especially ITP. The classical triad of fever, rash, and arthralgia appeared to be frequently present, and biological inflammation and/or low complement can further support the diagnosis. In contrast to anaphylaxis, where rituximab may be safely rechallenged upon desensitization protocol, treatment alternatives should be pursued in patients experiencing RISS, given the higher risk of severe RISS recurrence. Full article

Background/Objectives: Childhood-onset Sjögren disease (cSjD) is a rare autoimmune disorder with heterogeneous manifestations and ongoing diagnostic challenges, as there are no validated paediatric criteria. Our study aims to characterise the clinical, laboratory, and imaging features of children diagnosed with cSjD at a single Romanian paediatric rheumatology centre between 2015 and 2025 and contextualise these findings within the most recent literature. Methods: A retrospective review of 15 consecutive cSjD patients was conducted, including clinical features, autoantibodies, imaging, biopsy findings, treatment, and outcomes. Results: Our cohort showed a significant female predominance (80%) and a broad age range at disease onset (3–15 years). Extraglandular manifestations were more common at presentation than glandular phenotypes (53.3% vs. 40%). Lupus-like extraglandular presentations frequently led to initial misdiagnosis as childhood-onset systemic lupus erythematosus (SLE) in our cohort. Sicca symptoms were present at diagnosis in only 3 of 15 patients (20%) and developed later during follow-up in an additional 4 patients (26.7%). Notably, the cohort included novel findings, such as an unprecedented presentation with acute exudative pericarditis complicated by cardiac tamponade. Anti-SSA antibodies and salivary gland ultrasound abnormalities were highly prevalent (86.7% and 100%, respectively). Anti-SSB antibodies were detected in seven patients (46.7%), with titres showing more variability than those of anti-SSA, ranging from just above the positivity threshold to mildly elevated levels. The association with macro-creatine kinase type I was another distinctive feature of this series. Chronic musculoskeletal pain and dryness were our patients’ most frequently reported symptoms at the last assessment, affecting up to 5/15 (33.3%) in each domain. One patient showed irreversible ocular damage during our study. Conclusions: Extraglandular presentations of cSjD are highly heterogeneous and diagnostically challenging, often occurring without glandular symptoms. Lupus-like systemic features—including facial vasculitic purpura, with or without arthralgia, and occasional pericarditis, as observed in our cohort—may contribute to frequent initial diagnostic misattribution to SLE. Early salivary gland ultrasonography, targeted autoantibody testing, and selective biopsy are essential for timely diagnosis, underscoring the urgent need for paediatric-specific validated classification criteria. Full article

Background/Objectives: Temporomandibular disorders (TMDs) are a group of multifactorial conditions affecting the temporomandibular joints (TMJs), masticatory muscles, and associated structures. TMDs are identified as the main cause of non-dental orofacial pain in children and adolescents. This scoping review aims to explore recent evidence on prevalence, clinical presentation, associated factors, and treatment approaches of TMDs in children and adolescents. Methods: A systematic search was conducted across PubMed, Scopus and Embase for studies published between 2015 and 2025, following PRISMA-ScR guidelines. Results: Thirty-eight studies were included. TMD prevalence in children and adolescents ranged from 16.9% to 40% through clinical examination, with painful TMD rates ranging from 16.2% to 25.5%, while symptom-based surveys reported prevalences of 9–35.3%. The most frequent diagnoses were myofascial pain, myalgia, arthralgia and disc displacement with reduction. Female sex and increasing age were consistent risk factors. Psychosocial variables, such as anxiety and depression, showed strong associations with pain-related TMDs. Structural and systemic conditions such as musculoskeletal alterations, joint hypermobility, respiratory conditions and headaches/migraines were also frequently reported. Evidence on treatment appears to be limited. In juvenile idiopathic arthritis (JIA), TMJ involvement is prevalent (32.6–64%), particularly in the persistent oligoarticular subtype. Conclusions: TMDs in children and adolescents are prevalent and multifactorial conditions, mainly of muscular origin, presenting more frequently in adolescents and females. Psychosocial factors, functional habits, clenching, mouth breathing and systemic conditions may be associated with TMD presence or severity. Substantial heterogeneity persists in diagnostic criteria, assessment tools and outcome measures. Research on therapeutic interventions is scarce and often limited to small samples. Standardized diagnostic protocols, improvements in research consistency, longitudinal cohorts and RCTs are needed to clarify etiological pathways, validate diagnostic criteria and establish effective, evidence-based strategies for the management of TMDs in children and adolescents. Full article

Background: Poly(ADP-ribose) polymerase inhibitor (PARPi) treatment in ovarian cancer patients after first-line chemotherapy and following the response to platinum-based chemotherapy at relapse is associated with survival benefits. Maintenance therapies can be administered over extended periods, making treatment tolerability assessment essential in optimizing patient outcomes. This cohort study aimed to evaluate the agreement between physician and patient reporting of PARP inhibitor-related toxicities and the rate of underestimation of each symptom considered. Methods: Patients treated with PARPis in the first-line or recurrent setting were included. A specific Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) questionnaire was generated and administered to the cohort. For each toxicity, agreement between patients and physicians was assessed using Cohen’s kappa and Gwet’s AC1; in addition, the rate of toxicity under-reporting by physicians was calculated. Results: Seventy-seven ovarian cancer patients were included; 39 (50.6%) received PARPis in the first-line setting, while 38 (49.4%) were treated for recurrence. Cohen’s kappa values for agreement between patients and physicians across 12 reported toxicities ranged from 0 to 0.15, indicating poor agreement (κ < 0.20) for all assessed toxicities, with the lowest levels of agreement for decreased appetite (κ = 0), rash (κ = 0.02), headache (κ = 0.00), arthralgia (κ = 0.03), insomnia (κ = 0.03), and fatigue (κ = 0.04). When agreement was assessed using Gwet’s AC1, agreement remained poor to moderate for the majority of the symptoms evaluated. Physician under-reporting rates were higher for nausea (51.9%), rash (57.1%), headache (49.3%), arthralgia (70.2%), insomnia (48.1%), and fatigue (67.5%). Conclusions: Our results underscore the importance of systematically integrating patient-reported outcomes into clinical practice, including in maintenance settings, to ensure an accurate assessment of treatment-related toxicities. Full article

Objective: The oral cavity is the beginning of the digestive tract and the composition of saliva could indicate immune events in the gut and joints. The objective of this research was to evaluate the diagnostic accuracy of salivary interleukin (IL)-17A for temporomandibular joint (TMJ) internal derangements (IDs) in patients with spondyloarthritis (SpA). Methods: SpA disease activity was assessed using the Bath Ankylosing Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS) and Disease Activity Index for Psoriatic Arthritis (DAPSA). Salivary cytokines were analyzed using enzyme-linked immunosorbent assay. TMJ conditions were evaluated using The Diagnostic Criteria for Temporomandibular Disorder (DC/TMD) protocol. A symptomatic TMJ-ID group with intracapsular arthralgia (n = 64) and asymptomatic TMJ-ID group without intracapsular arthralgia (n = 50), regardless of joint sounds, were compared with controls (healthy TMJs, n = 86). Results: Women were more prevalent and salivary IL-17A concentration was higher in both ID groups than in controls. Salivary IL-17A levels positively correlated with erythrocyte sedimentation rate, anti-streptolysin-O titer, salivary IL-12/23 p40 and matrix metalloproteinase-3 levels, sore and swollen joint counts, BASDAI, chronic TMJ pain and anxiety. IL-17A demonstrated diagnostic accuracy for currently symptomatic (cutoff, 11 pg/mL) and asymptomatic (cutoff, 11.6 pg/mL) TMJ-ID vs. controls. Patients with IL-17A levels above these cutoffs more frequently exhibited disc displacement with reduction and degenerative TMJ disease, higher self-reported spinal pain and higher SpA activity, as assessed by ASDAS, than patients with IL-17A levels ≤ cutoffs. TMJ-related headache and somatization contributed to greater TMJ pain in those with IL-17A > cutoffs, when compared with dichotomous controls. Conclusions: Salivary IL-17A concentration provides an accurate laboratory marker of SpA activity and enables the diagnosis of both currently symptomatic and asymptomatic TMJ-IDs in patients with SpA. Full article

This prospective, single-center, case-control study investigated circulating autoantibodies (AAbs) targeting G protein-coupled receptors (GPCRs) in Long COVID (LC) patients to identify potential diagnostic biomarkers and therapeutic targets. Fifteen participants were enrolled at the LC clinic in Rome: eleven with severe LC—defined as >4 persistent symptoms (fatigue, cognitive impairment, poor exercise tolerance, dyspnea, arthralgia, or dysautonomic manifestations) >3 months post-infection—and four asymptomatic post-COVID (APC) individuals. Fatigue was assessed using the Fatigue Assessment Scale (FAS ≥ 22; severe ≥ 35). Auto-Abs against AT1R, endothelin receptor A, adrenergic (α1, α2, β1, β2), and muscarinic (M1–M5) receptors were quantified, along with blood cortisol and ACTH levels. SARS-CoV-2-specific T-cell responses to Spike and Nucleocapsid proteins were evaluated by ELISpot assay. In our small cohort, LC patients were younger, had fewer comorbidities (p = 0.03), fewer vaccine doses (p = 0.03), and higher FAS scores (33 vs. 12; p = 0.001). Mean GPCR AAbs levels were higher in LC than in APC (8.88 vs. 5.45 Units/mL; p = 0.17), indicating a coherent autoimmune signature in LC that correlates with symptom development. Morning cortisol was lower in LC (12.7 vs. 17 mg/dL; p = 0.01), and T-cell responses tended to be weaker. These findings suggest GPCR AAbs may serve as biomarkers and therapeutic targets for a subset of patients, guiding diagnosis and treatments with IV immunoglobulin or immunoadsorption. Full article

The dried leaves of Turpinia arguta (Lindl.) Seem, a traditional Chinese medicinal herb, have been used for the treatment of tonsillitis, sore throat, throat arthralgia, and novel coronavirus pneumonia. This plant possesses significant medicinal, economic, and ecological values. Assessing its distribution patterns and its response to global climate change is critical for the conservation and sustainable use of its resources. This study used GIS technology and ENMTools v1.3 to select 247 distribution records of T. arguta and employed the kuenm R package (running on R v4.4.3, package version 2.0.1) to optimize the MaxEnt model parameters. Based on current and future climate data, this study predicted the current and future potential suitable areas of T. arguta in China during the periods of the 2050s (2041–2060), 2070s (2061–2080), and 2090s (2081–2100) under three SSP emission scenarios (SSP126, SSP245, and SSP585). Additionally, it identified the key environmental variables driving its distribution patterns and conducted a quality suitability regionalization analysis using sample chemical content data. The results show that under current climatic conditions, the highly suitable areas for T. arguta are mainly distributed across five provinces: Jiangxi, Guangdong, Guangxi, Fujian, and Hunan. The distribution of T. arguta is primarily influenced by precipitation and temperature. The suitable ranges of key environmental variables are as follows: average temperature in September > 26 °C (optimal range: 28–32 °C), precipitation in April 175–250 mm, precipitation in September 100–160 mm, annual mean temperature 20–30 °C (optimal range > 22.5 °C), and annual precipitation 1500–2000 mm (peak value: 1750 mm). Quality analysis reveals a positive correlation between ligustroflavone content and the mean diurnal temperature range, as well as between rhoifolin content and soil sand content. Compared with current suitable areas, the total suitable areas of T. arguta are projected to contract by varying degrees across all scenarios in the future. This study will provide a robust scientific basis for guiding the sustainable development/utilization of its resources and optimizing artificial cultivation practices. Full article

Visceral leishmaniasis (VL) is an endemic zoonotic disease in southern Europe with increasing clinical relevance among immunocompromised populations; however, detailed clinical data remain scarce. This retrospective multicentre cohort study analysed patients with confirmed VL treated at seven hospitals in Greece over a 26-year period. Clinical, treatment, and outcome data were collected with a minimum follow-up of 18 months to assess cure, treatment failure, relapse, and mortality. A total of 144 patients were enrolled (59% male; mean age 41.8 years, range 0.1–84 years), most of whom were Greek nationals (85%) and resided in rural areas (61%). Fever was the primary reason for hospital admission in 95% of patients. At diagnosis, 42 patients (29%) were immunocompromised. These patients were significantly older than immunocompetent individuals and more likely to present with diarrhoea and arthralgia, whereas hepatomegaly was less frequent. Liposomal amphotericin B was administered to 90% of patients. Treatment failure occurred in 14 patients (10%) and was significantly associated with immunosuppression and leukaemia. Relapse within 18 months occurred in 5.5% of patients. Overall mortality was relatively low (7 patients, 5%), with one death directly attributable to VL. This study demonstrates that VL remains endemic in Greece, affects patients across all age groups, and is primarily autochthonous. Immunosuppression is associated with distinct clinical features and poorer treatment outcomes in VL, underscoring the need for heightened clinical vigilance, combined diagnostic approaches, and extended follow-up in vulnerable populations. Full article

Background/Objectives: Intra-articular polynucleotide (PN) has emerged as an alternative to hyaluronic acid (HA) for treating knee osteoarthritis (OA), with randomized controlled trials (RCTs) reporting similar or greater pain reduction. Real-world evidence on both single- and repeated-cycle outcomes remains limited. This study evaluated PN’s real-world effectiveness and safety and whether its pain reduction falls within ranges reported in previous PN–HA RCTs, and evaluated repeated-cycle outcomes. Methods: Clinical data from 1048 PN-treated OA patients were retrospectively reviewed. The safety set comprised 1024 patients with follow-up visits. The efficacy set included 975 patients who completed 3–5 weekly PN injections with evaluable VAS, CGI, and PGI data at baseline, 3, and 6 months. A repeated-treatment subgroup (n = 45) received a second PN cycle 6 months later. First-cycle outcomes were compared with PN–HA RCTs. Results: In the first-cycle (n = 975), VAS decreased from 50.30 mm to 23.02 and 22.43 mm at 3 and 6 months (−27.28 and −27.87 mm; p < 0.0001), showing a comparable magnitude to RCT-reported ranges (~27–41 mm). CGI improvement was 81.0% and 79.6%, and PGI improvement 78.8% and 78.1% at 3 and 6 months. In the repeated-treatment subgroup (n = 45), despite a lower second-cycle baseline VAS of 31.00 mm (vs. 50.30 mm at first-cycle baseline), VAS decreased to 14.07 mm and 17.33 mm at 3 and 6 months (−16.93 and −13.67 mm; p < 0.001), achieving comparable absolute post-treatment pain levels. Among 1024 patients, three mild-to-moderate arthralgia events (0.29%) occurred, with no serious device-related adverse events in either cycle. Conclusions: PN provided meaningful 6-month pain reduction in a comparable magnitude to previous RCTs and showed consistent benefit with repeated administration without new safety concerns. Full article

Bruton’s tyrosine kinase (BTK) inhibitors have revolutionized the treatment landscape for patients with indolent lymphoid malignancies such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). The most common adverse events include cardiac arrhythmia, bleeding, infection, diarrhea, arthralgias, hypertension, and skin changes. Second-generation BTK inhibitors, e.g., acalabrutinib and zanubrutinib and the non-covalent BTK inhibitor pirtobrutinib, are less toxic than the first-generation BTK inhibitor ibrutinib. The most common toxic skin symptoms related to BTKi treatment include hemorrhage, bleeding events, bruising, skin ecchymoses, and contusion; they are particularly common in patients treated with ibrutinib. Other dermatologic symptoms include rash, cellulitis, skin infections, subcutaneous abscesses and peripheral edema. This article discusses the development of skin symptoms in patients with ibrutinib and newer BTK inhibitors, and summarizes their clinical and pathological characteristics. A literature search was performed using PubMed, Web of Science, and Google Scholar for articles published in English. Additional relevant publications were obtained by reviewing the references from the chosen articles. Full article

Introduction: The addition of immunotherapy to neoadjuvant treatment for early triple-negative breast cancer (TNBC) has been adopted in clinical practice in France since March 2022, with little real-world data published on the topic. The aim of this study was to evaluate real-world data on treatment feasibility, efficacy, and related toxicities, with a specific focus on immune-related adverse events (irAEs). Methods: We conducted a retrospective analysis of patients who completed at least the neoadjuvant sequence of pembrolizumab combined with chemotherapy for early-stage TNBC at Montpellier Cancer Institute from April 2022 to July 2024. Adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. The pathological complete response (pCR) was defined as the absence of residual invasive disease in the breast and axillary lymph nodes (ypT0/Tis ypN0). Results: We reviewed data from 92 patient records. The median age at diagnosis was 50 years (range: 27–76). The history of autoimmune disease was noted in 3.2% of patients. Grade 3–4 irAEs were observed in 20% of patients and included hepatitis (8.6%), colitis (3.3%), skin toxicity (2.1%), myocarditis (2%), arthralgia (1%), autoimmune hemolytic anemia (1%), hypothyroidism (1%), and adrenal insufficiency (1%). No treatment-related deaths were reported. Immunotherapy was discontinued due to irAEs in 29.3% of patients in the study population. The pCR rate was 61,1%, with no significant association between the number of neoadjuvant pembrolizumab cycles and the pCR rate (p = 0.7). Patients experiencing grade 3–4 irAEs had a pCR rate of 80%, compared to 56.7% in those without such toxicities (p = 0.079). Initial positivity of antinuclear antibodies (ANA) was not associated with an increased incidence of irAEs. Conclusions: The immune-related adverse events and efficacy data observed in our cohort were broadly comparable to those reported in the KEYNOTE-522 trial, with no treatment-related deaths. Patients with grade 3–4 irAEs tended to have higher pCR rates. Full article

Oropouche virus (OROV) has emerged as a significant arboviral pathogen in South America, responsible for recurrent outbreaks of febrile illness. In the Loreto region of Peru, more than 600 cases were reported in 2024, markedly exceeding expected incidence rates. We conducted a retrospective observational study using clinical–epidemiological records of all RT-qPCR-confirmed cases of Oropouche fever from the Regional Health Directorate of Loreto between October 2024 and March 2025. A total of 100 confirmed cases were identified. The most frequent symptoms were fever (88%), headache (78%), and myalgia (72%). No atypical or neurological presentations were reported. No severe cases or deaths occurred. Eight patients required hospitalization, mainly due to severe abdominal pain, persistent vomiting, arthralgia, and pregnancy. Six pregnant women were identified; three experienced pregnancy complications, though no fetal malformations or miscarriages were observed. This outbreak represents a new OROV epidemic in the region, with fewer cases than in 2024 and predominantly mild clinical courses. Although outcomes were generally favorable, the occurrence of complications in pregnant women underscores the importance of continued molecular surveillance and targeted public health interventions. Full article