Search Results (27)

Human T-lymphotropic virus 1 (HTLV-1) infection has been associated with inflammatory, autoimmune, and lymphoproliferative diseases with a wide spectrum of clinical manifestations. Among patients with inflammatory rheumatological disease manifestations, cases of rheumatoid arthritis, Sjögren’s syndrome, polymyositis, and fibromyalgia, among others, have been reported. Another common feature of rheumatological diseases is the presence of joint manifestations, such as arthralgia and arthritis. In the present study, we sought to determine the laboratory profile and clinical rheumatological manifestations of people living with HTLV-1/2 residing in a metropolitan area in the Brazilian Amazon. A total of 957 individuals were screened for HTLV-1/2 infection by enzyme-linked immunosorbent assay (ELISA), and samples from seropositive individuals were subjected to infection confirmation by Western blotting or quantitative polymerase chain reaction (qPCR). Individuals with confirmed HTLV-1 and HTLV-2 infection were clinically evaluated for signs and symptoms of rheumatological diseases. Of the 957 individuals tested, 69 were positive for HTLV-1/2 infection, with 56 confirmed cases of HTLV-1 infection (5.9%), 12 of HTLV-2 infection (1.2%), and 1 classified as undetermined (0.1%). After clinical screening, 15 infected individuals with complaints suggestive of rheumatological disease were selected for evaluation by a rheumatologist (11 with HTLV-1 infection (1.1%) and 4 with HTLV-2 infection (0.4%)). The predominant pain pattern was symmetrical polyarthralgia, with large joints predominantly being affected. The diseases diagnosed were psoriatic arthritis, osteoarthritis, fibromyalgia, and regional pain syndromes. Antinuclear antibody (ANA) positivity was observed in two patients. Our findings confirm that HTLV-1 infection is associated with rheumatological disease manifestations and highlight the novel finding of cases of HTLV-2 infection in patients with rheumatoid arthritis symptoms. Full article

We used the Queensland acute rheumatic fever (ARF) and rheumatic heart disease (RHD) register to describe the clinical phenotype and the characteristics of individuals diagnosed with ARF in Far North Queensland, Australia, between January 2012 and December 2023. There were 830 episodes of ARF in 740 individuals during the study period; 785/830 (95%) episodes occurred in First Nations Australians and 696/824 occurred in areas of socioeconomic disadvantage. There was no significant change in the overall incidence of ARF during the study period (Spearman’s rho = 0.51, p = 0.09). The median (interquartile range) age of the cohort was 15 (10–23) years, although 276/830 (33%) episodes of ARF occurred in individuals ≥ 20 years. Individuals with carditis, polyarthritis, an abnormal electrocardiogram, fever and elevated inflammatory markers were more likely to have confirmed ARF. The presence of polyarthralgia, monoarthritis or skin manifestations was not associated with a diagnosis of confirmed ARF. Individuals with monoarthralgia were less likely to have confirmed ARF. At the end of the study period, 264/706 (37%) individuals who had access to echocardiography had confirmed RHD. Individuals who did not have echocardiography documented as a component of their initial episode of care were more likely to have severe RHD at the end of the study (25/339 (7%) versus 7/401 (2%), p < 0.0001). ARF and RHD continue to be diagnosed in First Nations Australians in tropical Australia. It seems unlikely that Australia will achieve its stated aim of eliminating RHD by 2031. Full article

Chikungunya fever (CHIKF), caused by the Chikungunya virus (CHIKV), manifests as acute febrile illness often associated with polyarthritis and polyarthralgia. Although the acute symptoms resolve within two weeks, many patients experience prolonged joint pain and inflammation, resembling rheumatoid arthritis (RA). This study aimed to identify molecular markers related to joint pain and chronicity in CHIKV-infected individuals by analyzing blood transcriptomes using bulk RNA sequencing. B- and T-cell receptor (BCR and TCR) diversity was assessed through computational analysis of RNA-seq data, revealing a significant reduction in CDR3 diversity in CHIKV-infected individuals compared to healthy controls. This reduced diversity was associated with the upregulation of genes involved in osteoclast differentiation and activation, particularly through the RANK/RANKL signaling pathway. These findings suggest a potential link between immune dysregulation and enhanced osteoclast activity, which may contribute to the persistence of joint pain in chronic CHIKF. Targeting osteoclast-related pathways could offer therapeutic strategies for managing chronic symptoms in CHIKF patients. Full article

Uncaria tomentosa (UT) is a medicinal plant popularly known as cat’s claw belonging to the Rubiaceae family that has been reported to display antiviral and anti-inflammatory activities. The chikungunya virus (CHIKV) outbreaks constitute a Brazilian public health concern. CHIKV infection develops an abrupt onset of fever, usually accompanied by a skin rash, besides incapacitating polyarthralgia. There is no vaccine available or treatment for CHIKV infection. The present study evaluates the hydroalcoholic extract of UT bark as a potential antiviral against CHIKV. The in vitro antiviral activity of the UT extract against the Brazilian CHIKV strain was assessed using quantitative reverse transcription polymerase chain reaction, flow cytometry, and plaque assay. Results obtained demonstrated that UT inhibits CHIKV infection in a dose-dependent manner. At the non-cytotoxic concentration of 100 µg/mL, UT exhibited antiviral activity above 90% as determined by plaque reduction assay, and it reduced the viral cytopathic effect. Similarly, a significant virucidal effect of 100 µg/mL UT was observed after 24 and 48 h post-infection. This is the first report on the antiviral activity of UT against CHIKV infection, and the data presented here suggests UT as a potential antiviral to treat CHIKV infection. Full article

Mycoplasma pneumoniae is a self-propagating microorganism that commonly causes respiratory tract infections. It can also cause a variety of extrapulmonary symptoms with or independently of respiratory symptoms, such as skin lesions, arthralgia, myalgia, hemolysis, cardiac lesions, gastrointestinal symptoms, and central nervous system lesions, which are rare manifestations reported in approximately 0.1% of cases. In this study, we present a unique case of Mycoplasma-related abducens nerve palsy, polyarthritis, and erythema multiforme without respiratory disease. The patient was a 69-year-old woman who presented to our hospital with a skin rash, fever, arthralgia, and diplopia without respiratory symptoms. Brain magnetic resonance imaging showed optic neuritis on the right side, suggesting the diplopia was caused by right abducens nerve palsy. However, the etiologies of abducens nerve palsy were not revealed by the physical examination, blood biochemistry tests, or bacteriological examinations, including the cerebrospinal fluid examination obtained at admission. Mycoplasma infection was suspected from erythema multiforme revealed by a skin biopsy and polyarthralgia, and it was finally diagnosed according to elevated Mycoplasma particle agglutination (PA) antibodies in paired serum. Though minocycline did not improve her diplopia, the daily administration of 30 mg of prednisolone gradually improved her symptoms, and the Mycoplasma PA antibody titer, which was regularly measured in the clinical course, also decreased, suggesting a relationship between Mycoplasma infection and abducens nerve palsy. This is the first case of isolated abducens nerve palsy, which was reported as the only central neurological symptom in an adult patient with Mycoplasma infection. The mechanism or pathogenesis of CNS manifestations caused by Mycoplasma pneumoniae remains to be elucidated, and further investigation is needed. Hence, Mycoplasma infection is a common disease. Clinicians should be aware of the diverse manifestations, including abducens nerve palsy, of Mycoplasma infection and should consider Mycoplasma infection even in the absence of typical respiratory symptoms. Full article

O’nyong-nyong virus (ONNV) is a member of the reemerging arthritogenic alphaviruses that cause chronic debilitating polyarthralgia and/or polyarthritis via their tropism for the musculoskeletal system. Thus, the discovery of dual antiviral and anti-inflammatory drugs is a great challenge in this field. We investigated the effects of the common plant-derived alkaloids berberine (isoquinoline), matrine (quinolizidine), and tabersonine (indole) at a non-toxic concentration (10 μM) on a human fibroblast cell line (HS633T) infected by ONNV (MOI 1). Using qRT-PCR analyses, we measured the RNA levels of the gene coding for the viral proteins and for the host cell immune factors. These alkaloids demonstrated multifocal effects by the inhibition of viral replication, as well as the regulation of the type-I interferon antiviral signaling pathway and the inflammatory mediators and pathways. Berberine and tabersonine proved to be the more valuable compounds. The results supported the proposal that these common alkaloids may be useful scaffolds for drug discovery against arthritogenic alphavirus infection. Full article

Bowel-associated arthritis–dermatosis syndrome (BADAS) is a rare neutrophilic dermatosis that was first described in 1971 in patients who underwent bypass surgery for obesity. Over the years, the number of reported cases associated with medical gastroenterological conditions, particularly inflammatory bowel disease (IBD), has progressively increased. To date, there are no systematic reviews in the literature on BADAS. The design of an a priori protocol was based on PRISMA guidelines, and a search of PubMed and Scopus databases was conducted for articles published between 1971 and 2023 related to the topic. Fifty-one articles including 113 patients with BADAS were analyzed in this systematic review. Bariatric surgery and IBD were the most frequently reported causes of BADAS, accounting for 63.7% and 24.7% of all cases, respectively. A total of 85% of cases displayed the typical dermatological presentation, including urticarial maculopapular lesions centered by a vesicopustule, with the majority of lesions located on the upper limbs (73.5%). Polyarthralgia or localized arthritis were always present. Atypical presentations included cellulitis-like, erythema-nodosum-like, Sweet-syndrome-like and pyoderma-gangrenosum-like manifestations. Gastrointestinal symptoms were frequently observed in IBD-related cases (67.9%). The histopathology showed a neutrophilic infiltrate (96.6%). The most commonly used treatment regimens consisted of systemic corticosteroids, metronidazole and tetracyclines, either alone or in combination. A relapsing–remitting course was observed in 52.1% of patients. In conclusion, BADAS is a neutrophilic dermatosis that presents with a wide variety of cutaneous manifestations, both typical and atypical. Gastrointestinal symptoms are frequently observed, particularly in cases related to IBD. The histopathology is clear but not specific compared with other neutrophilic dermatoses. The diagnosis can be challenging, but the relapsing–remitting course and the strong association with polyarthralgia and gastrointestinal disease can aid in the diagnosis. Full article

Chikungunya virus is an arthropod-borne infectious agent that causes Chikungunya fever disease. About 90% of the infected patients experience intense polyarthralgia, affecting mainly the extremities but also the large joints such as the knees. Chronic disease symptoms persist for months, even after clearance of the virus from the blood. Envelope proteins stimulate the immune response against the Chikungunya virus, becoming an important therapeutic target. We inactivated the Chikungunya virus (iCHIKV) and produced recombinant E2 (rE2) protein and three different types of anti-rE2 monoclonal antibodies. Using these tools, we observed that iCHIKV and rE2 protein induced mechanical hyperalgesia (electronic aesthesiometer test) and thermal hyperalgesia (Hargreaves test) in mice. These behavioral results were accompanied by the activation of dorsal root ganglia (DRG) neurons in mice, as observed by calcium influx. Treatment with three different types of anti-rE2 monoclonal antibodies and absence or blockade (AMG-9810 treatment) of transient receptor potential vanilloid 1 (TRPV1) channel diminished mechanical and thermal hyperalgesia in mice. iCHIKV and rE2 activated TRPV1+ mouse DRG neurons in vitro, demonstrating their ability to activate nociceptor sensory neurons directly. Therefore, our mouse data demonstrate that targeting E2 CHIKV protein with monoclonal antibodies and inhibiting TRPV1 channels are reasonable strategies to control CHIKV pain. Full article

Chikungunya (CHIKV) is an arthritogenic alphavirus that causes a self-limiting disease usually accompanied by joint pain and/or polyarthralgia with disabling characteristics. Immune responses developed during the acute phase of CHIKV infection determine the rate of disease progression and resolution. Annexin A1 (AnxA1) is involved in both initiating inflammation and preventing over-response, being essential for a balanced end of inflammation. In this study, we investigated the role of the AnxA1-FPR2/ALX pathway during CHIKV infection. Genetic deletion of AnxA1 or its receptor enhanced inflammatory responses driven by CHIKV. These knockout mice showed increased neutrophil accumulation and augmented tissue damage at the site of infection compared with control mice. Conversely, treatment of wild-type animals with the AnxA1 mimetic peptide (Ac_2–26) reduced neutrophil accumulation, decreased local concentration of inflammatory mediators and diminished mechanical hypernociception and paw edema induced by CHIKV-infection. Alterations in viral load were mild both in genetic deletion or with treatment. Combined, our data suggest that the AnxA1-FPR2/ALX pathway is a potential therapeutic strategy to control CHIKV-induced acute inflammation and polyarthralgia. Full article

Background: Immune checkpoint inhibitors (ICIs) have been a major advance in treating non-small-cell lung cancer (NSCLC). Programmed cell death protein-1/programmed death-ligand 1 blockade enhances immune function, mediating anti-tumor activity, yet causing immune-related adverse events (irAEs). We investigated the prognostic role of Grade 3–4 irAEs on overall survival (OS). Methods: This observational study recruited advanced NSCLC patients who received ICIs at Bichat-Claude Bernard University Hospital and in a community hospital, Saint-Joseph Foundation (Paris), between 1 January 2016 and 31 December 2019. Immunotherapy as a single-agent or double-drug combination was applied in the first and later lines. Univariable and multivariable analyses were instrumental in evaluating the prognostic impact of irAEs. Results: Overall, 201 consecutive ICI-treated patients were enrolled. High-grade irAEs (Grades 3–4) occurred in 36 patients (17.9%), including 11 (30.5%) cases of pneumonitis, 8 (22.2%) of colitis, 4 (11.1%) hepatic, 3 (8.3%) dermatological, 2 (5.5%) neurological events, and 2 cases (5.5%) of poly-arthralgia. The median OS was 10.4 ± 1.36 months (95% CI:7.7–13.1), being significantly higher in patients with high-grade irAEs than those without, 27.8 months vs. 8.1 months, respectively (HR = 2.5; p < 0.0001). Multivariable analysis revealed an independent association between high-grade irAEs and longer OS (HR = 0.29, 95% CI: 0.2–0.6, p < 0.0001). Conclusions: Our real-life study confirms that high-grade irAEs predict longer OS in advanced NSCLC. Full article

Mayaro virus (MAYV) is an emerging alphavirus causing acute febrile illness associated with chronic polyarthralgia. Although MAYV is currently restricted to tropical regions in South America around the Amazon basin, it has the potential to spread globally by Aedes species mosquitoes. In addition, there are currently no specific therapeutics or licenced vaccines against MAYV infection. We have previously shown that an adenovirus based Mayaro vaccine (ChAdOx1 May) was able to provide full protection against MAYV challenge in vaccinated A129 mice and induced high neutralising antibody titres. In this study, we have constructed a replication deficient simian adenovirus (ChAdOx2) and a Modified Ankara Virus (MVA) based vaccine expressing the MAYV structural cassette (sMAYV) similar to ChAdOx1 May, and characterised recombinant MAYV E2 glycoprotein expressed in a mammalian system for immune monitoring. We demonstrate that ChAdOx2 May was able to induce high antibody titres similar to ChAdOx1 May, and MVA May was shown to be an effective boosting strategy following prime vaccination with ChAdOx1 or ChAdOx2 May. In order to measure MAYV neutralising ability, we have developed a virus replicon particle-based neutralisation assay which effectively detected neutralising antibodies against MAYV. In summary, our study indicates the potential for further clinical development of the viral vectored MAYV vaccines against MAYV infections. Full article

The co-circulation of chikungunya virus (CHIKV), dengue virus (DENV) and Zika virus (ZIKV) in Rio de Janeiro (RJ), Brazil, caused a challenging triple epidemic, as they share similar clinical signs and symptoms and geographical distribution. Here, we aimed to investigate the clinical and laboratorial aspects of chikungunya suspected cases assisted in RJ during the 2018 outbreak, focusing on the differential diagnosis with dengue and zika. All suspected cases were submitted to molecular and/or serological differential diagnostic approaches to arboviruses. A total of 242 cases suspected of arbovirus infection were investigated and 73.6% (178/242) were molecular and/or serologically confirmed as chikungunya. In RT-qPCR confirmed cases, cycle threshold (Ct) values ranged from 15.46 to 35.13, with acute cases presenting lower values. Chikungunya cases were mainly in females (64%) and the most frequently affected age group was adults between 46 to 59 years old (27%). Polyarthralgia affected 89% of patients, especially in hands and feet. No dengue virus (DENV) and Zika virus (ZIKV) infections were confirmed by molecular diagnosis, but 9.5% (23/242) had serological evidence of DENV exposure by the detection of specific anti-DENV IgM or NS1, and 42.7% (76/178) of chikungunya positive cases also presented recent DENV exposure reflected by a positive anti-DENV IgM or NS1 result. A significantly higher frequency of arthritis (p = 0.023) and limb edema (p < 0.001) was found on patients with CHIKV monoinfection compared to dengue patients and patients exposed to both viruses. Lastly, phylogenetic analysis showed that the chikungunya cases were caused by the ECSA genotype. Despite the triple arboviruses’ epidemic in the state of RJ, most patients with fever and arthralgia investigated here were diagnosed as chikungunya cases, and the incidence of CHIKV/DENV co-detection was higher than that reported in other studies. Full article

A 79-year-old female patient with no pre-existing rheumatological conditions presented with severe functional impairment secondary to polyarthralgia, most likely an adverse reaction following her first dose of Oxford/AstraZeneca ChAdOx1 nCov-19 vaccination against SARS-CoV-2, the causative agent of Coronavirus Disease 2019 (COVID-19). The presentation mimicked clinical features of polymyalgia rheumatica and was distinctive in its pattern and delayed onset. Its severity in an elderly patient was significant against trial findings of decreasing reactogenicity of ChAdOx1 nCov-19 vaccine with increasing age, and traumatic to the patient. Acute phase reactants were elevated, consistent with recent similar reports among mostly elderly, female patients. New onset rheumatological conditions and flares of pre-existing, well-controlled conditions had been well established in COVID-19 and, to a lesser extent, post-vaccination. Viral arthralgias as a distinct clinical entity in COVID-19 is only beginning to be recognized. It could be that this case report represents a similar entity which occurs following vaccination against SARS-CoV-2. Despite this, the benefits of vaccination continue to outweigh such risks, although this case report is important for providing understanding of clinical progression when such reactions occur, aiding in patient discussions and clinical decisions to weigh up further investigations or empirical treatment against reassurance and close monitoring. Full article

There is a need to develop a highly effective vaccine against the emerging chikungunya virus (CHIKV), a mosquito-borne Alphavirus that causes severe disease in humans consisting of acute febrile illness, followed by chronic debilitating polyarthralgia and polyarthritis. In this review, we provide a brief history of the development of the first poxvirus vaccines that led to smallpox eradication and its implications for further vaccine development. As an example, we summarize the development of vaccine candidates based on the modified vaccinia virus Ankara (MVA) vector expressing different CHIKV structural proteins, paying special attention to MVA-CHIKV expressing all of the CHIKV structural proteins: C, E3, E2, 6K and E1. We review the characterization of innate and adaptive immune responses induced in mice and nonhuman primates by the MVA-CHIKV vaccine candidate and examine its efficacy in animal models, with promising preclinical findings needed prior to the approval of human clinical trials. Full article