Chronic Arthralgia Research Articles

Chikungunya on Kidney Transplant Recipients: Is It the Same?

Chikungunya virus (CHIKV) infection is an acute febrile illness with polyarthralgia and arthritis. There are few data about CHIKV infection in kidney transplant recipients (KTR). We report the largest case series of CHIKV infection in this population. We retrospectively analyzed 32 cases of CHIKV infection in KTR between January 2016 and December 2017 at Hospital Universitário Walter Cantídio of Federal University of Ceará. All patients had been in endemic areas before the beginning of the symptoms. All presented arthralgia, 15 (46.9%) with joint inflammatory symptoms and 14 (43.8%) evolved to chronic arthralgia. Seven (21.9%) showed acute kidney injury (AKI) by Kidney Disease: Improving Global Outcomes criteria during the acute phase. Acute kidney injury was not related to prednisone use (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.04-2.61, P = 0.3) nor chronic arthralgia (OR, 1.2; 95% CI, 0.2-8.4, P = 0.8) as well as male sex, chronic kidney disease and older than 60 years (OR, 1.7; 95% CI, 0.3-10.3, P = 0.58; OR, 0.4; 95% CI, 0.1-2.7, P = 0.4; and OR, 2.1; 95% CI, 0.3-14.9, P = 0.45, respectively). Hospitalization was associated to AKI (OR, 44.0; 95% CI, 3.8-503.1; P = 0.002), probably due to diarrhea or dehydration. One patient died throughout the study, possibly unassociated with CHIKV infection. KTR with CHIKV infection have a clinical presentation and evolution similar to those seen in the general population. Kidney function is generally well preserved, with transitory graft dysfunction without negative impact after 3 months from the beginning of the symptoms. Previous costicosteroids use did not relate with AKI or chronic arthralgia.

Beyond Members of the Flaviviridae Family, Sofosbuvir Also Inhibits Chikungunya Virus Replication.

Chikungunya virus (CHIKV) causes a febrile disease associated with chronic arthralgia, which may progress to neurological impairment. Chikungunya fever (CF) is an ongoing public health problem in tropical and subtropical regions of the world, where control of the CHIKV vector, Aedes mosquitos, has failed. As there is no vaccine or specific treatment for CHIKV, patients receive only palliative care to alleviate pain and arthralgia. Thus, drug repurposing is necessary to identify antivirals against CHIKV. CHIKV RNA polymerase is similar to the orthologue enzyme of other positive-sense RNA viruses, such as members of the Flaviviridae family. Among the Flaviviridae, not only is hepatitis C virus RNA polymerase susceptible to sofosbuvir, a clinically approved nucleotide analogue, but so is dengue, Zika, and yellow fever virus replication. Here, we found that sofosbuvir was three times more selective in inhibiting CHIKV production in human hepatoma cells than ribavirin, a pan-antiviral drug. Although CHIKV replication in human induced pluripotent stem cell-derived astrocytes was less susceptible to sofosbuvir than were hepatoma cells, sofosbuvir nevertheless impaired virus production and cell death in a multiplicity of infection-dependent manner. Sofosbuvir also exhibited antiviral activity in vivo by preventing CHIKV-induced paw edema in adult mice at a dose of 20 mg/kg of body weight/day and prevented mortality in a neonate mouse model at 40- and 80-mg/kg/day doses. Our data demonstrate that a prototypic alphavirus, CHIKV, is also susceptible to sofosbuvir. As sofosbuvir is a clinically approved drug, our findings could pave the way to it becoming a therapeutic option against CF.

Circulation of Chikungunya virus East-Central-South Africa genotype during an outbreak in 2016-17 in Piaui State, Northeast Brazil.

ABSTRACTChikungunya virus (CHIKV) is an arbovirus that emerged in the Americas in 2013. Infection with CHIKV is symptomatic in most of the cases and patients can develop chronic arthralgia that lasts from months to years in over 40% of the cases. The East-Central-South Africa (ECSA) genotype was introduced in Brazil in 2014, in Bahia State. Here we report the circulation of the CHIKV ECSA genotype in Piaui State, Northeast Brazil, during the years 2016-2017. The phylogenetic analysis revealed a single introduction of this lineage probably in 2015 and its maintenance at least until 2017. This analysis has also demonstrated the proximity of this genotype with isolates from neighboring States, and its partial nucleotide sequence of the viral E1 gene revealed a synapomorphy synonyms. This finding highlights the spread of the ECSA genotype in Brazil and supports its circulation in the Brazilian Northeast.

Neuromodulation treats Chikungunya arthralgia: a randomized controlled trial

The Chikungunya (CHIK) virus is epidemic in Brazil, with 170,000 cases in the first half of 2016. More than 60% of patients present relapsing and remitting chronic arthralgia with debilitating pain lasting years. There are no specific therapeutic agents to treat and rehabilitee infected persons with CHIK. Persistent pain can lead to incapacitation, requiring long-term pharmacological treatment. Advances in non-pharmacological treatments are necessary to promote pain relief without side effects and to restore functionality. Clinical trials indicate transcranial direct current stimulation (tDCS) can treat a broad range of chronic pain disorders, including diffuse neuromuscular pain and arthralgia. Here, we demonstrate that the tDCS across the primary motor cortex significantly reduces pain in the chronic phase of CHIK. High-resolution computational model was created to analyze the cortical electric field generated during tDCS and a diffuse and clustered brain current flow including M1 ipsilateral and contralateral, left DLPFC, nucleus accumbens, and cingulate was found. Our findings suggest tDCS could be an effective, inexpensive and deployable therapy to areas lacking resources with a significant number of patients with chronic CHIK persistent pain.

Pain, balance, grip strength and gait parameters of older adults with and without post-chikungunya chronic arthralgia.

To compare the levels of pain, grip strength, balance and gait in older adults with and without post-Chikungunya chronic arthralgia (PCCA). Sixty-two older adults, 30 with and 32 without PCCA participated in the study. Pain level was assessed using a Visual Analogue Scale (VAS). Gait during a 10-m walk was assessed using inertial sensors. Semi-static balance was assessed during an eyes-closed bipedal balance test on a force platform, and grip strength was assessed using a hand dynamometer. Participants with PCCA presented severe levels of pain (VAS>7.5), poorer balance, lower grip strength, walked slower, with lower cadence and stride length and higher stride time and stride length variability than participants without PCCA (P<0.001 for all variables). Older adults with PCCA had high levels of pain, impaired balance and gait and lower grip strength compared to older adults without PCCA.

The Methyltransferase-Like Domain of Chikungunya Virus nsP2 Inhibits the Interferon Response by Promoting the Nuclear Export of STAT1.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that has evolved effective mechanisms to counteract the type I interferon (IFN) response. Upon recognition of the virus, cells secrete IFNs, which signal through transmembrane receptors (IFNAR) to phosphorylate STAT proteins (pSTAT). pSTAT dimers are transported into the nucleus by importin-α5 and activate the transcription of IFN-stimulated genes (ISGs), increasing cellular resistance to infection. Subsequently, STAT proteins are shuttled back into the cytoplasm by the exportin CRM1. CHIKV nonstructural protein 2 (nsP2) reduces ISG expression by inhibiting general host cell transcription and by specifically reducing the levels of nuclear pSTAT1 via an unknown mechanism. To systematically examine where nsP2 acts within the JAK/STAT signaling cascade, we used two well-characterized mutants of nsP2, P718S and KR649AA. Both mutations abrogate nsP2's ability to shut off host transcription, but only the KR649AA mutant localizes exclusively to the cytoplasm and no longer specifically inhibits JAK/STAT signaling. These mutant nsP2 proteins did not differentially affect IFNAR expression levels or STAT1 phosphorylation in response to IFNs. Coimmunoprecipitation experiments showed that in the presence of nsP2, STAT1 still effectively bound importin-α5. Chemically blocking CRM1-mediated nuclear export in the presence of nsP2 additionally showed that nuclear translocation of STAT1 is not affected by nsP2. nsP2 putatively has five domains. Redirecting the nsP2 KR649AA mutant or just nsP2's C-terminal methyltransferase-like domain into the nucleus strongly reduced nuclear pSTAT in response to IFN stimulation. This demonstrates that the C-terminal domain of nuclear nsP2 specifically inhibits the IFN response by promoting the nuclear export of STAT1.IMPORTANCE Chikungunya virus is an emerging pathogen associated with large outbreaks on the African, Asian, European, and both American continents. In most patients, infection results in high fever, rash, and incapacitating (chronic) arthralgia. CHIKV effectively inhibits the first line of defense, the innate immune response. As a result, stimulation of the innate immune response with interferons (IFNs) is ineffective as a treatment for CHIKV disease. The IFN response requires an intact downstream signaling cascade called the JAK/STAT signaling pathway, which is effectively inhibited by CHIKV nonstructural protein 2 (nsP2) via an unknown mechanism. The research described here specifies where in the JAK/STAT signaling cascade the IFN response is inhibited and which protein domain of nsP2 is responsible for IFN inhibition. The results illuminate new aspects of antiviral defense and CHIKV counterdefense strategies and will direct the search for novel antiviral compounds.

Effect of surgical scope on postoperative fibrosis of knee joints

Knee arthrofibrosis is a common complication after surgery, which is one of the key factors affecting the surgical outcome. It often causes the decrease of joint activity, chronic arthralgia, degeneration of cartilage tissues and joint disuse change, which seriously affects the daily life of the patients. How to reduce the occurrence of knee arthrofibrosis is the key to improve the expected effect of surgery, which is also an important problem to solve in clinical medicine; with our team's previous and recent research, we found that the degree of knee arthrofibrosis is closely related to the rang of the surgical. The use of minimally invasive and arthroscopic treatment can reduce the damage to synovial, cartilage and fat pad tissue, at the same time, combining with early postoperative rehabilitation training is the future effective prevention of postoperative arthrofibrosis of knee.

The Interplay of Viral and Host Factors in Chikungunya Virus Infection: Targets for Antiviral Strategies.

Chikungunya virus (CHIKV) has re-emerged as one of the many medically important arboviruses that have spread rampantly across the world in the past decade. Infected patients come down with acute fever and rashes, and a portion of them suffer from both acute and chronic arthralgia. Currently, there are no targeted therapeutics against this debilitating virus. One approach to develop potential therapeutics is by understanding the viral-host interactions. However, to date, there has been limited research undertaken in this area. In this review, we attempt to briefly describe and update the functions of the different CHIKV proteins and their respective interacting host partners. In addition, we also survey the literature for other reported host factors and pathways involved during CHIKV infection. There is a pressing need for an in-depth understanding of the interaction between the host environment and CHIKV in order to generate potential therapeutics.

Antiobesity Effect of Astilbe chinensis Franch. et Savet. Extract through Regulation of Adipogenesis and AMP-Activated Protein Kinase Pathways in 3T3-L1 Adipocyte and High-Fat Diet-Induced C57BL/6N Obese Mice.

Astilbe chinensis Franch. et Savat. (AC) has been used in traditional medicine for the treatment of chronic bronchitis, arthralgia, and gastralgia. In this study, we investigated the antiobesity effect of AC extract on 3T3-L1 preadipocytes and high-fat-diet-fed C57BL/6N obese mice. We found that AC extracts dramatically decreased the lipid content of 3T3-L1 cells in a concentration-dependent manner without cytotoxicity. The action mechanism of AC extract was demonstrated to be the inhibition of lipid accumulation and dose-dependent decrease in the expression of CCAAT/enhancer-binding protein α (C/EBPα), peroxisome proliferator-activated receptor-γ (PPAR-γ), and sterol regulatory element-binding protein 1 (SREBP1). Furthermore, AC extract increased the mitochondrial phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), mitochondrial biogenesis, and lipolysis-related factors. In amice model of high-fat-diet-induced obesity, the mice administered AC extract experienced significant decrease of 64% in weight gain, 55% in insulin resistance index, 22% in plasma triglycerides (TG), 56% in total cholesterol (TC), and 21% in nonesterified fatty acid (NEFA) levels compared with those in the high-fat diet-fed control mice. Collectively, these results indicated that AC extract exerted antiobesogenic activity through the modulation of the AMPK signaling pathway, inhibition of adipogenesis, decreased lipid content, and reduced adipocyte size.

The time course analysis of morphological changes induced by Chikungunya virus replication in mammalian and mosquito cells

Chikungunya virus (CHIKV), are-emerging Alphavirus, causes chronic myalgia and arthralgia in infected individuals. However, the exact pathophysiology remains undefined till date. Virus induced time course changes in host cells at the ultrastructural level and host cytoskeleton have been reported for other alphaviruses such as Sindbis and Semliki Forest virus. Few studies have tried to delineate the same for CHIKV leading to some understanding of the replication process. Selective CHIKV infection of progenitor cells involved in muscle repair has been proposed as acause of myalgia; albeit the outcome of infection on these cells has not been reported. With this background, we investigated CHIKV-induced time course changes in two cell lines-Aedes albopictus (C6/36) and murine myoblasts (C2C12) by transmission electron microscopy (TEM). CHIKV infection of C2C12 cells resulted in cell death, with cells exhibiting well defined apoptotic features. In contrast, mature virions were released from infected C6/36 cells without cytolysis. Double labelling of C2C12 cytoskeletal proteins-such as actin, tubulin and CHIKV revealed that viral nucleocapsids co-localized with these proteins during replication. As the infection progressed, CHIKV disrupted the normal organisation of these cell proteins. CHIKV-induced plasma membrane extensions were observed in infected cells, which so far have been reported only for Sindbis virus. This is afirst report describing the time course of morphological changes occurring in host cells as aresult of infection with CHIKV at the ultrastructural level. Apoptosis of myoblasts due to CHIKV infection could also be an important factor contributing to the recurrence of myalgia in CHIKV patients. Keywords: Chikungunya; electron microscopy; confocal microscopy; C6/36; C2C12; actin; α-tubulin.

The Identification of Risk Factors for Chronic Chikungunya Arthralgia in Grenada, West Indies: A Cross-Sectional Cohort Study.

BackgroundChikungunya virus (CHIKV) is a re-emerging arboviral pathogen. In 2014, an explosive CHIKV outbreak occurred in Grenada, West Indies, infecting approximately 60% of the population. In approximately 50% of cases, CHIKV infection transitions to painful arthralgia that can persist for years. Elucidation of the risk factors for chronic disease is imperative to the development of effective risk management strategies and specific therapeutics.MethodsWe conducted a cross-sectional study of 240 people who were tested for CHIKV during the outbreak. We administered questionnaires to examine demographic, behavioral, psychological, social, and environmental factors to identify associations with chronic disease. Physical examinations were performed and persistent symptoms were recorded.ResultsEthnicity and socioeconomic status were not associated with risk of chronic joint pain. Female sex increased risk, and age was demonstrated to be predictive of chronic CHIKV sequelae. Mosquito avoidance behaviors did not reduce risk. Patients suffering joint pains, generalized body ache, and weakness in the extremities during acute infection were more likely to develop chronic arthralgia, and an increased duration of acute disease also increased risk.ConclusionsThese data demonstrate that chronic CHIKV affects people across the ethnic and socioeconomic spectrum, and it is not reduced by vector avoidance activity. Increased duration of acute symptoms, in particular acute joint pain, was strongly correlated with the risk of persistent arthralgia, thus effective clinical management of acute CHIKV disease could reduce burden of chronic CHIKV.

Disruption of the Opal Stop Codon Attenuates Chikungunya Virus-Induced Arthritis and Pathology.

ABSTRACTChikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for several significant outbreaks of debilitating acute and chronic arthritis and arthralgia over the past decade. These include a recent outbreak in the Caribbean islands and the Americas that caused more than 1 million cases of viral arthralgia. Despite the major impact of CHIKV on global health, viral determinants that promote CHIKV-induced disease are incompletely understood. Most CHIKV strains contain a conserved opal stop codon at the end of the viral nsP3 gene. However, CHIKV strains that encode an arginine codon in place of the opal stop codon have been described, and deep-sequencing analysis of a CHIKV isolate from the Caribbean identified both arginine and opal variants within this strain. Therefore, we hypothesized that the introduction of the arginine mutation in place of the opal termination codon may influence CHIKV virulence. We tested this by introducing the arginine mutation into a well-characterized infectious clone of a CHIKV strain from Sri Lanka and designated this virus Opal524R. This mutation did not impair viral replication kinetics in vitro or in vivo. Despite this, the Opal524R virus induced significantly less swelling, inflammation, and damage within the feet and ankles of infected mice. Further, we observed delayed induction of proinflammatory cytokines and chemokines, as well as reduced CD4+ T cell and NK cell recruitment compared to those in the parental strain. Therefore, the opal termination codon plays an important role in CHIKV pathogenesis, independently of effects on viral replication.

Association Between Polymorphisms in the Genes of Estrogen Receptors and the Presence of Temporomandibular Disorders and Chronic Arthralgia

The high prevalence of painful temporomandibular disorders (TMDs) in women suggests that estrogen and its receptors play a fundamental etiologic role in the development of this joint pathology through complex action mechanisms. The aim of this study was to evaluate the possible association between polymorphisms in the ESR1 (estrogen receptor-1) and ESRRB (estrogen-related receptor-β) genes and the risk of simultaneous development of TMDs and pain in other joints in the body. All participants were clinically evaluated for the presence of TMD (Research Diagnostic Criteria for TMD) and asked about the presence of chronic joint pain. The control group consisted of 72 patients without TMD and without pain. Participants with arthralgia were divided into 3 groups: with muscular TMD (n=42), with articular TMD (n=16), and without TMD and with systemic arthralgia (n=82). Eight single-nucleotide polymorphisms in the ESR1 (rs12154178, rs1884051, rs2273206, rs7774230) and ESRRB (rs1676303, rs4903399, rs10132091, rs7151924) genes were investigated. The χ2 test and Student t and Mann-Whitney tests were used to assess the relevance of nominal and continuous variables, respectively. A P value less than .05 was considered significant. The TT (timin/timin) genotype for the ESR1 (rs2273206) gene was strongly associated with the risk of developing muscle TMDs and temporomandibular joint pain (P=.04). For the ESRRB (rs1676303) gene, an association was observed between the CC (cytosine/cytosine) genotype and the presence of articular TMDs associated with other chronic arthralgia (P=.02). These results were confirmed by the increased risk of developing articular TMDs associated with the C allele (P=.04). This study supports the hypothesis that changes in the ESR1 and ESRRB genes influence the presence of TMDs associated with chronic joint pain.

An Unusual Case of Whippleʼs Disease Discovered During Screening Endoscopy

Introduction: Whipple's Disease is a rare disease that results in a chronic systemic infection. The bacterial culprit responsible is a gram positive bacillus known as Tropheryma whipplei. The classic initial presentation is a constellation of gastrointestinal symptoms of diarrhea, weight loss, and abdominal pain; however, not all cases present with such findings. Despite a multitude of advances in diagnostic fields, Whipple's Disease remains elusive and difficult to diagnose. We present a rare case of Whipple's Disease in a patient undergoing screening for esophageal varices. Case: We present a case of a 77 year old Caucasian male with past medical history of diabetes, hypertension, and alcoholic cirrhosis. The diagnosis of alcoholic cirrhosis was made approximately 5 years ago at a different institution. During his initial office visit, he reported no complaints, except for nonspecific chronic arthralgia. The patient had not undergone screening for esophageal varices, and was scheduled for endoscopy in an outpatient setting. The EGD revealed a Schatzki's ring, pale friable eroded mucosa in the distal esophagus, a 3mm polyp in the gastric body (Figure 1), and an 8mm eroded polyp in the gastric cardia. The gastric cardia polyp and distal esophageal mucosa were biopsied and results were unremarkable. The 3mm gastric body polyp demonstrated gastric mucosa with numerous PAS positive histiocytes (Figure 2) in the lamina propria containing vacuoles, which in turn contained bacteria undergoing lysis according to electron microscopy exam (Figure 3). These findings were strongly suggestive of Whipple's Disease. As his only symptom was non-specific chronic arthralgia, treatment for Whipple's Disease was deferred. Plans are made for follow-up EGD to evaluate and take random biopsies of the small bowel for pathologic examination.Figure: Body of stomach lesion where Whipple's was found.Figure: PAS-D eosinophilic structures within the histiocytes.Figure: A) Numerous phagocytized bacteria within lysosomes B) Intact bacterium with recognizable cell wall present within the cytoplasm of the histiocyte.Discussion:Tropheryma whipplei is a bacterium known to cause a rare illness in humans, Whipple's Disease. This disease typically involves multiple organ systems, including but not limited to the gastrointestinal tract, joints, and central nervous system. A brief review of the literature suggests that there are only few cases of Whipple's Disease diagnosed each year. Our case describes a patient presenting for screening of esophageal varices found to have Whipple's Disease based off biopsy of a gastric polyp. Endoscopic visualization may be helpful in considering diagnosis in the future.

Clinical manifestations of chikungunya among university professors and staff in Santo Domingo, the Dominican Republic

ABSTRACTObjective.To further characterize chikungunya virus infection and its associated clinical manifestations, using a sample of university professors and staff in Santo Domingo, the Dominican Republic.Methods.A cross-sectional study with quota sampling by department was performed to obtain a convenience sample of professors (n = 736) and staff (n = 499) at the Universidad Autónoma de Santo Domingo. Surveys were used to collect demographic and infection data during the fall term of 2014. Univariate and bivariate analyses were carried out to quantify infection and clinical manifestation prevalence and to assess relationships of these outcomes with age, sex, and acute phase duration.Results.Of 1 236 participants, 49% reported infection (professors = 41%; staff = 61%). Of these, 53% also reported the presence of chronic effects, largely arthralgia (48%). Significant relationships were observed between reported infection and sex (P = 0.023), age (P < 0.001), and occupation (P < 0.001). More headache (P = 0.008) and edema (P < 0.001) in females, more headache (P = 0.005) in younger subjects, and more myalgia (P = 0.006) in those with longer acute symptoms were found. Additionally, more chronic arthralgia (P < 0.001; P = 0.003) and chronic edema (P < 0.001; P = 0.001) in females and older subjects, and more chronic myalgia (P = 0.041) and chronic edema (P = 0.037) in those with longer acute symptoms were observed.Conclusions.To the authors knowledge, this is the first population-based chikungunya prevalence study in the Dominican Republic, and the first to explore clinical manifestations in a university setting. The findings reflect results from studies following the 2005 – 2006 Reunion Island outbreak: prevalence of infection and chronic arthralgia, as well as associations with sex, age, and acute intensity. Longitudinal research can provide further insight into these effects.

Chikungunya virus and autoimmunity.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus. Fever, rash and severe arthralgia are the hallmarks of chikungunya fever (CHIKF), the disease caused by this virus. The acute course of the disease usually lasts few weeks to months. Chronic, relapsing or persistent arthralgia and arthritis have been described mimicking rheumatoid arthritis (RA), requiring immunosuppressive drugs.The purpose of this review is to characterize both the chronic clinical course of CHIKF-associated arthritis and the immunological pathogenic mechanisms involved. The effect of postepidemic chronic persistent rheumatic course on the functional status of affected individuals, affecting large populations, has been studied. One-third of affected individuals had persistent pain months to years postepidemic and the identified risk factors for functional disability were identified.Inflammatory biomarkers associated with disease severity of RA such as interleukin 6 (IL6), and relevant chemokines have been found to correlate with the severity of postepidemic chronic disease. There are conflicting reports on antinuclear antibodies (ANAs) as well as rheumatoid factor and anti-citrullinated peptide antibody (ACPA) sero-positivity during infections.According to a recent study, eight out of 10 infected individuals developed chronic persistent rheumatic course and met classification criteria for seronegative RA.In a flow cytology analyses, these eight patients, similar to a group of RA patients, had a greater percentage of activated and effector CD4 and CD8 T cells than healthy controls. Patients with CHKV infections may have a chronic persistent course of musculoskeletal disease, overlapping clinical and immunologic features with RA patients. In the appropriate setting and awareness, CHIKV infection should be considered when a patient is evaluated with a new symmetric polyarthritis.The question to be raised: Is it possible that in genetic prone individuals and in a particular environmental and infectious setting, such as CHIKF outbreak, an autoimmune disease will emerge?

Haplotypes of the RANK and OPG genes are associated with chronic arthralgia in individuals with and without temporomandibular disorders

The aim of this study was to evaluate the association between genetic polymorphisms and the comorbid presence of chronic systemic arthralgia in patients with articular temporomandibular disorders (TMD). Subjects were evaluated for the presence of TMD and asked about the presence of chronic joint pain. Four groups were included in the study: articular TMD and systemic arthralgia (n=85), no articular TMD and systemic arthralgia (n=82), articular TMD and no systemic arthralgia (n=21), no articular TMD and no systemic arthralgia (control, n=72). A total of 14 single nucleotide polymorphisms in the OPG, RANK, and RANKL genes were investigated. In the statistical analysis, a P-value of <0.05 was considered significant. For the OPG gene, an association was observed between the group with chronic arthralgia and joint TMD and the control group (P=0.04). There was also a tendency towards an association of the haplotype CGCCAA with an increased risk of developing chronic joint pain, even in the absence of TMD (P=0.06). For the RANK gene, the AGTGC haplotype was associated with the lowest risk of presenting chronic joint pain in individuals without TMD (P=0.03). This study supports the hypothesis that changes in the OPG and RANK genes influence the presence of chronic joint pain in individuals with and without TMD.

Persistent arthralgia and related risks factors in laboratory-confirmed cases of Chikungunya virus infection in Mexico

ABSTRACTObjective.To estimate the cumulative incidence of persistent arthralgia at 6 months from acute Chikungunya virus (CHIKV) infection and to evaluate the association of clinical markers with the risk of long-term arthralgia.Methods.This multicenter retrospective cohort study was conducted in the Mexican state of Colima. A total of 136 individuals aged 15 years and older with serologically confirmed CHIKV infection were enrolled. Participants were interviewed at 6 months from the onset of symptoms, and self-reported persistent arthralgia (PA) was the main binary outcome. A self-report numeric rating scale (NRS) ranging from 0 to 10 was used to estimate the severity of articular pain.Results.The cumulative incidence of PA was 41.9%. Severe pain (NRS ≥ 7) presented in 36.8% of participants with PA. In multiple analysis, individuals aged 40 years and older (risk ratio (RR) = 1.60; 95% confidence interval (CI), 1.03-2.48) and those with articular pain at 3 months post-infection (RR = 3.95; 95% CI, 1.95-8.01) had a significantly increased risk of PA at 6 months from CHIKV infection.Conclusions.To the best of our knowledge, this is first report of a CHIKV-associated longterm outcome in Mexico, where the incidence of the infection has been high. This is also the first study in Latin America evaluating several factors associated with the risk of PA. Our findings may be useful in health care settings to stratify the risk of chronic arthralgia secondary to CHIKV infection and to identify patients who would benefit clinically from early medical intervention.

Suppression of Arthritis Progression with Lutein Extracted from Tagetes erecta in Collagen-Induced Arthritis Model Rats

Background: Chronic arthralgia and arthritis are the most common causes of activity limitation and disability among middle-aged and older adults. Rheumatoid arthritis is a persistent inflammation of the synovium of the joints, leading to destruction of the surrounding bone and cartilage and ultimately joint de formities. Several studies reported that carotenoid intake, including lutein, was associated with a decreased risk of rheumatoid arthritis. We examined the effects of lutein extract (LE) from Tagetes erecta on inflammatory suppression in the collagen-induced arthritis (CIA) model rat. Keywords: Arthritis, inflammation, lutein, rheumatoid, synovial cell, xanthophyll.

Hyperferritinemia is a potential marker of chronic chikungunya: A retrospective study on the Island of Curaçao during the 2014–2015 outbreak

BackgroundRecently Chikungunya virus (CHIKV) outbreaks have been reported in the Carribean. There is no data regarding the outbreak in Curaçao. In addition, to date there is no biomarker that could be used to predict chronic infection. ObjectivesTo characterize the first CHIKV outbreak in Curaçao and to identify potential biomarkers for chronic infection. Study designA serological test and quantitative polymerase chain reaction (qPCR) were used on samples collected in Curaçao to confirm infection. Subsequently, six samples with high viral load were selected for phylogenetic analysis. Furthermore we investigated the association of macrophage-related biomarkers during CHIKV infection with chronic arthralgia/arthritis. Results116 patients in Curacao were diagnosed with CHIKV infection based on ELISA and 77% were tested positive for CHIKV by qPCR. Phylogenetic analysis showed that an Asian genotype was the cause of the outbreak. Elevated levels of ferritin and CRP were significantly associated with viraemia. In addition, elevated ferritin levels were significantly associated with chronic arthralgia. ConclusionsThe results showed that the presence of an Asian genotype of CHIKV in Curaçao for the first time. Moreover, we found an association between ferritin levels with chronic arthralgia.