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Infection with mosquito-borne arthritogenic alphaviruses, such as Ross River virus (RRV) and Barmah Forest virus (BFV), can lead to long-lasting rheumatic disease. Existing mouse models that recapitulate the disease signs and immunopathogenesis of acute RRV and BFV infection have consistently shown relevance to human disease. However, these mouse models, which chiefly model hindlimb dysfunction, may be prone to subjective interpretation when scoring disease. Assessment is therefore time-consuming and requires experienced users. The DigiGait system provides video-based measurements of movement, behavior, and gait dynamics in mice and small animals. Previous studies have shown DigiGait to be a reliable system to objectively quantify changes in gait in other models of pain and inflammation. Here, for the first time, we determine measurable differences in the gait of mice with infectious arthritis using the DigiGait system. Statistically significant differences in paw area and paw angle were detected during peak disease in RRV-infected mice. Significant differences in temporal gait parameters were also identified during the period of peak disease in RRV-infected mice. These trends were less obvious or absent in BFV-infected mice, which typically present with milder disease signs than RRV-infected mice. The DigiGait system therefore provides an objective model of variations in gait dynamics in mice acutely infected with RRV. DigiGait is likely to have further utility for murine models that develop severe forms of infectious arthritis resulting in hindlimb dysfunction like RRV. IMPORTANCE Mouse models that accurately replicate the immunopathogenesis and clinical disease of alphavirus infection are vital to the preclinical development of therapeutic strategies that target alphavirus infection and disease. Current models rely on subjective scoring made through experienced observation of infected mice. Here, we demonstrate how the DigiGait system, and interventions on mice to use this system, can make an efficient objective assessment of acute disease progression and changes in gait in alphavirus-infected mice. Our study highlights the importance of measuring gait parameters in the assessment of models of infectious arthritis.

Aim: Andrographolide, the major bioactive compound of the plant Andrographis paniculata, exerts anti-inflammatory, cyto-, neuro- and hepato-protective effects. Traditional remedies for infectious diseases include A. paniculata for maladies like fever, pain, rashes which are associated with chikungunya and other arboviral diseases. Since andrographolide and A. paniculata have potent antiviral properties, the present review aims to provide a comprehensive report of symptoms and immunological molecules involved in chikungunya virus (CHIKV) infection and the therapeutic role of andrographolide in the mitigation of chikungunya and associated symptoms., Materials and Methods: Studies on the therapeutic role of A. paniculata and andrographolide in chikungunya and other viral infections published between 1991 and 2021 were searched on various databases., Results and Discussion: The havoc created by chikungunya is due to the associated debilitating symptoms including arthralgia and myalgia which sometimes remains for years. The authors reviewed and summarized the various symptoms and immunological molecules related to CHIKV replication and associated inflammation, oxidative and unfolded protein stress, apoptosis and arthritis. Additionally, the authors suggested andrographolide as a remedy for chikungunya and other arboviral infections by highlighting its role in the regulation of molecules involved in unfolded protein response pathway, immunomodulation, inflammation, virus multiplication, oxidative stress, apoptosis and arthritis., Conclusion: The present review demonstrated the major complications associated with chikungunya and the role of andrographolide in alleviating the chikungunya associated symptoms to encourage further investigations using this promising compound towards early development of an anti-CHIKV drug. Chemical Compound studied: andrographolide (PubChem CID: 5318517)., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Most studies on chronic chikungunya virus (CHIKV) arthritis include patients treated with disease-modifying antirheumatic drugs (DMARDs), likely altering the expression of clinical manifestations and outcome. Therefore, we sought to evaluate the clinical features and correlates in DMARD-naive patients with chronic CHIKV arthritis. We conducted a case-control study in adult patients with serologically confirmed CHIKV infection in Puerto Rico. Demographic features, clinical manifestations, comorbidities, disease activity (per Clinical Disease Activity Index [CDAI]), functional status (per Health Assessment Questionnaire Disability Index [HAQ-DI]), and pharmacologic treatment were ascertained. Patients with and without chronic CHIKV arthritis were compared. Furthermore, a sub-analysis was performed among patients with chronic CHIKV who presented with mild disease activity versus moderate-to-high disease activity at study visit. In total, 61 patients were studied; 33 patients had chronic arthritis and 28 had resolved arthritis. Patients with chronic arthritis had significantly more diabetes mellitus, chronic back pain, and fever, tiredness, and myalgias on the acute phase. The mean (SD) HAQ score was 0.95 (0.56), and 57.6% had moderate-to-high disease activity. Patients with moderate-to-high disease activity had higher scores in overall HAQ-DI and HAQ-DI categories (dressing and grooming, arising, hygiene, reaching, and activities) than in those with mild activity. In conclusion, in this group of DMARD-naive patients with chronic CHIKV arthritis, nearly 58% had moderate-to-high disease activity and had substantial functional disability. Diabetes mellitus, chronic back pain, and some manifestations on acute infection were associated with chronic CHIKV arthritis.

Emerging and re-emerging arthritogenic alphaviruses, such as Chikungunya virus (CHIKV) and O'nyong nyong virus, cause acute and chronic crippling arthralgia associated with inflammatory immune responses. Approximately 50% of CHIKV-infected patients suffer from rheumatic manifestations that last 6 months to years. However, the physiological functions of individual immune signaling pathways in the pathogenesis of alphaviral arthritis remain poorly understood. Here, we report that a deficiency in CXCL10, which is a chemoattractant for monocytes/macrophages/T cells, led to the same viremia as wild-type animals, but fewer immune infiltrates and lower viral loads in footpads at the peak of arthritic disease (6-8 days post infection). Macrophages constituted the largest immune cell population in footpads following infection, and were significantly reduced in Cxcl10 -/- mice. The viral RNA loads in neutrophils and macrophages were reduced in Cxcl10 -/- compared to wild-type mice. In summary, our results demonstrate that CXCL10 signaling promotes the pathogenesis of alphaviral disease and suggest that CXCL10 may be a therapeutic target for mitigating alphaviral arthritis.

Objective: Arthritogenic alphaviruses, such as Ross River virus (RRV) and chikungunya virus (CHIKV), particularly affect joints of the extremities and can lead to debilitating and potentially chronic polyarthritis/polyarthralgia. The innate immune response of the host plays a crucial role in inducing proinflammatory host factors, leading to tissue destruction and bone loss in the joints. This study was performed to assess how the inhibition of interleukin-1β (IL-1β) signaling using the clinical rheumatoid arthritis drug anakinra influences bone loss in mice with arthritogenic alphavirus infections., Methods: Mice (n = 5 per group) were infected with RRV or CHIKV and then treated with anakinra. Weight gain and disease severity were measured, tissue viral titers were determined, and histologic changes in joint tissues were assessed., Results: Anakinra therapy reduced RRV- and CHIKV-induced bone loss in this murine model (P < 0.001 and P < 0.05, respectively). Histologic analysis of the knee joint showed that treatment with anakinra decreased epiphyseal growth plate thinning, loss of epiphyseal bone volume, and osteoclastogenesis in the tibia. Importantly, pharmacologic IL-1 receptor (IL-1R) blockade did not improve other clinical features, including disease score, weight loss, or viremia., Conclusion: The present findings suggest that anakinra therapy may reduce bone loss in experimental murine models of RRV and CHIKV. Further investigations are needed to assess the potential therapeutic benefits of anakinra in patients with arthritogenic alphavirus disease., (© 2019, American College of Rheumatology.)

Introduction: Chikungunya virus infection causes arthralgia and arthritis in the acute phase of the disease but, in more than half of the cases, musculoskeletal manifestations can be prolonged over time and, in some cases, become chronic. Although polyarthralgia is the most frequent chronic manifestation, forms with polyarthritis, tenosynovitis and enthesopathy are also common., Objective: To analyze the clinical characteristics of patients with persistent articular manifestations after infection with the Chikungunya virus., Patients: Report of 3 cases of chronic arthritis after infection with chikungunya virus diagnosed at outpatient care in a university hospital of Catalonia, all of them imported after exposure in areas of epidemic infection between 2013-2015., Results: All three patients had inflammatory joint pain for more than one year after acute disease (3, 2 and 1 years, respectively). In all cases, it appeared as polyarthritis with involvement of small joints of hands and feet (pseudorheumatoid arthritis-like). Laboratory tests showed a slight elevation of acute phase reactants, and analyses for immune markers were negative. Two of the patients required treatment with glucocorticoids and hydroxychloroquine. The course led to slow clinical improvement, but only one of them came to be completely asymptomatic., Conclusion: In the differential diagnosis of chronic polyarthritis, Chikungunya virus disease should also be considered in areas in which it is not endemic., (Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Background/objective: Although mortality rates related with chikungunya (CHIK) outbreaks in Latin America's (LA's) dengue-endemic rural and new urban regions are low, dealing with symptoms and sequelae can both produce a significant burden of disease and diminish quality of life-from many months to years-after the acute phase of the infection, with a significant impact on public and individual health.The aim of this work was to establish Pan-American League of Associations for Rheumatology-Central American, Caribbean and Andean Rheumatology Association (ACCAR) consensus-conference endorsements and recommendations on the diagnosis and treatment of CHIK-related inflammatory arthropathies transmitted by Aedes aegypti and Aedes albopictus in LA., Methods: Based on the Consensus Development Conference format, a panel of ACCAR rheumatologist voting members (n = 10) took part in this Pan-American League of Associations for Rheumatology initiative. Experts voted from a previous content analysis of the medical literature on CHIK, 4 subsequent topic conferences, and a workshop. Consensus represents the majority agreement (≥80%) achieved for each recommendation., Results: The experts' panel reached 4 overarching principles: (1) CHIK virus (CHIKV) is a re-emergent virus transmitted by 2 species of mosquitoes: A. aegypti and A. albopictus; (2) CHIKV caused massive outbreaks in LA; (3) chronic CHIKV infection produces an inflammatory joint disease that, in some cases, can last for several months to years, and (4) currently, there are no vaccines or antivirals licensed for CHIKV infections., Recommendations: Pan-American League of Associations for Rheumatology-ACCAR achieved 13 endorsements and recommendations on CHIK categorized in 3 groups: (1) epidemiology and clinical manifestations, (2) diagnosis, and (3) treatment, representing the consensus agreement from the panel's members.

Background: Atherosclerosis, inflammation and coronary plaque destabilization are linked to each other. Infections due to various microbes may trigger Acute Coronary Syndrome (ACS) by systemic inflammation cascade., Methods: We have evaluated the prevalence of Post Chikungunya Chronic Arthritis (PCCA) among 400 consecutive ACS patients (Case group) and compared with control group subjected to elective surgery by the prospective case-control observational study. Cases were excluded if standard criteria of ACS were not satisfied and in the control group if the patient suffered a Myocardial Infarction (MI) within 28 days of elective surgery. PCCA duration more than two years or serum IgM anti-CCP positive patients were also excluded from the case as well as a control group., Results: The case and control groups were similar except, less number of heart failure (O.R.7.3, 95% C.I. 3.3-15.9) and chronic kidney injury patients (O.R. 0.5, 95% C.I. 0.3-0.9) in the elective surgery (control) group. PCCA was present in 24 out of 400 ACS cases and 8 out of 400 control group. Among ACS case-patients, those suffering from PCCA tended to be younger and more often women, with more diabetes, hypertension, chronic kidney injury and high mean CRP. In unadjusted analysis PCCA was three times more common in the case versus control (O.R. 3.0, 95% C.I. 1.4- 6.4); results were indistinguishable after multidiscipline adjustment (O.R. 3.0, 95% C.I. 1.3-6.8)., Conclusion: PCCA is common among patients with ACS and post-infective systemic inflammation of PCCA may trigger plaque destabilization., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Viral Arthritis (VA), a disease caused by Avian Reovirus (ARV), has emerged as a significant cause of economic losses in broiler chicken flocks in Western Canada. These outbreaks were characterized by 4-13% morbidity, followed by a spike in mortality/culling that in extreme cases required total flock depopulation. From 2012-2017, 38 ARV isolates were recovered. Molecular characterization of a partial segment of the sigma (σ)C gene shows all six previously known ARV clusters in Western Canadian broiler chickens. The most numerous clusters were Cluster#4 and Cluster #5 while the most variable clusters were Cluster#1 (76.7-100% identity), Cluster#2 (66-99.3%), and Cluster#4 (62-100%). This variation suggests that an autogenous vaccine may not protect against a same-cluster challenge virus. This is the first publication showing the wide genetic diversity of ARV Cluster#4, the circulation of all six worldwide reported ARV clusters in Canada, and important differences in ARV Cluster classification among researchers., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose of Review: To review the emergence, clinical features, pathogenesis, and treatment of acute chikungunya (CHIK) fever and chronic CHIK arthritis., Recent Findings: Since 2004, CHIK, an arboviral infection, has spread throughout the world, infecting millions of people. The illness occurs in two phases: an acute viremic infection followed by chronic arthritis. In less developed countries, there are limited resources and effective treatment. For acutely ill CHIK fever patients, management is symptomatic. The treatment of chronic CHIK arthritis should be determined by an understanding of pathogenesis. Is chronic CHIK arthritis a persistent viral infection or a postinfectious inflammatory process? Multiple proinflammatory cytokines, chemokines, and growth factors have been identified in chronic CHIK arthritis. Attempts to isolate CHIK virus from synovial fluid have been unsuccessful. Given pathogenetic similarities (as well as differences) compared with rheumatoid arthritis and the painful, disabling nature of the arthritis, it is not surprising that disease-modifying antirheumatic drugs such as methotrexate have begun to be used., Summary: CHIK infection has emerged with major arthritic epidemics for which evidence-based therapy is limited. But there is an opportunity to improve the treatment of chronic CHIK arthritis and, from this disease, to gain understanding of the pathogenesis and treatment of inflammatory arthritis more generally.

In the past decade, arboviruses-arthropod-borne viruses-have been the focus of public health institutions worldwide following a spate of devastating outbreaks. Chikungunya virus, an arbovirus that belongs to the alphavirus genus, is a reemerging arthritogenic virus that has caused explosive outbreaks since 2006, notably on Réunion Island, and more recently in the Caribbean, South America, India, and Southeast Asia. The severity of arthritic disease caused by chikungunya virus has prompted public health authorities in affected countries to develop specific guidelines to tackle this pathogen. Chikungunya virus disease manifests first as an acute stage of severe joint inflammation and febrile illness, which later progresses to a chronic stage, during which patients may experience debilitating and persisting articular pain for extended periods. This review aims to provide a broad perspective on current knowledge of chikungunya virus pathogenesis by identifying key clinical and experimental studies that have contributed to our understanding of chikungunya virus to date. In addition, the review explores the practical aspects of treatment and management of both acute and chronic chikungunya virus based on clinical experience during chikungunya virus outbreaks. Finally, recent findings on potential therapeutic solutions-from antiviral agents to immunomodulators-are reviewed to provide both viral immunologists and clinical rheumatologists with a balanced perspective on the nature of a reemerging arboviral disease of significant public health concern, and insight into future therapeutic approaches to better address the treatment and management of chikungunya virus., (© 2017, American College of Rheumatology.)

Objective: To determine if chikungunya virus persists in synovial fluid after infection, potentially acting as a causative mechanism of persistent arthritis., Methods: We conducted a cross-sectional study of 38 Colombian participants with clinical chikungunya virus infection during the 2014-2015 epidemic who reported chronic arthritis and 10 location-matched controls without chikungunya virus or arthritis. Prior chikungunya virus infection status was serologically confirmed, and the presence of synovial fluid chikungunya virus, viral RNA, and viral proteins was determined by viral culture, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and mass spectrometry, respectively. Biomarkers were assessed by multiplex analysis., Results: Patients with serologically confirmed chikungunya arthritis (33 of 38 [87%]) were predominantly female (82%) and African Colombian (55%) or white Colombian (33%), with moderate disease activity (mean ± SD Disease Activity Score in 28 joints 4.52 ± 0.77) a median of 22 months after infection (interquartile range 21-23 months). Initial symptoms of chikungunya virus infection included joint pain (97%), swelling (97%), stiffness (91%), and fever (91%). The most commonly affected joints were the knees (87%), elbows (76%), wrists (75%), ankles (56%), fingers (56%), and toes (56%). Synovial fluid samples from all patients with chikungunya arthritis were negative for chikungunya virus on qRT-PCR, showed no viral proteins on mass spectrometry, and cultures were negative. Case and control plasma cytokine and chemokine concentrations did not differ significantly., Conclusion: This is one of the largest observational studies involving analysis of the synovial fluid of chikungunya arthritis patients. Synovial fluid analysis revealed no detectable chikungunya virus. This finding suggests that chikungunya virus may cause arthritis through induction of potential host autoimmunity, suggesting a role for immunomodulating agents in the treatment of chikungunya arthritis, or that low-level viral persistence exists in synovial tissue only and is undetectable in synovial fluid., (© 2017, American College of Rheumatology.)

Objective: To estimate the frequency of chronic joint pain after infection with chikungunya virus in a Latin American cohort., Methods: A cross-sectional follow-up of a prospective cohort of 500 patients from the Atlántico Department, Colombia who were clinically diagnosed as having chikungunya virus during the 2014-2015 epidemic was conducted. Baseline symptoms and follow-up symptoms at 20 months were evaluated in serologically confirmed cases., Results: Among the 500 patients enrolled, 485 had serologically confirmed chikungunya virus and reported joint pain status. Patients were predominantly adults (mean ± SD age 49 ± 16 years) and female, had an education level of high school or less, and were of Mestizo ethnicity. The most commonly affected joints were the small joints, including the wrists, ankles, and fingers. The initial virus symptoms lasted a median of 4 days (interquartile range [IQR] 3-8 days). Sixteen percent of the participants reported missing school or work (median 4 days [IQR 2-7 days]). After 20 months, one-fourth of the participants had persistent joint pain. A multivariable analysis indicated that significant predictors of persistent joint pain included college graduate status, initial symptoms of headache or knee pain, missed work, normal activities affected, ≥4 days of initial symptoms, and ≥4 weeks of initial joint pain., Conclusion: This is the first report to describe the frequency of chikungunya virus-related arthritis in the Americas after a 20-month follow-up. The high frequency of chronic disease highlights the need for the development of prevention and treatment methods., (© 2017, American College of Rheumatology.)

Arthritis and arthralgia during a viral infection are often polyarticular and symmetric and can mimic rheumatoid arthritis. Depending on germs, others signs and symptoms as fever, cutaneous rash (Parvovirus B19) or jaundice (hepatitis) can be present. Worldwide most common germs are Parvovirus B19, hepatitis B and C, HIV and alphavirus. There are significant differences throughout the world and epidemiology continues to evolve with a progression of vector-borne infections. Diagnosis of viral arthritis is often difficult and is based on epidemiological, clinical and serological data., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Introduction: Chikungunya (CHIK) is a tropical arbovirus, transmitted by the female mosquito Aedes aegypti and Aedes albopictus. In Brazil, there have been cases reported since 2014. The initial manifestations of this virus are sudden onset high fever, headache, chills, rashes, myalgia and intense joint pain. Usually, CHIK presents the acute and chronic phases, the latter characterized by bilateral polyarthralgia, which can last for months or even years. During this period, autoimmune diseases can be triggered, making the picture even more complicated., Method: A systematic review was performed on the PubMed and Scielo databases in January 2017. Clinical trials, cohorts, case-control and case reports were included in the study. Expert opinions, societal consensuses and literary reviews were exclusion criteria. Studies were conducted in English, Spanish and Portuguese. The studies were descriptively analyzed and the data was grouped according to methodological similarity., Results: Twenty-four (24) articles were selected and, in compliance with the inclusion and exclusion criteria, 18 were eliminated, with six studies remaining in the present review: five clinical trials and one case report., Conclusion: When the manifestations of CHIK become chronic and, the longer they last, more complications arise. Polyarthralgia can be immaterial, distancing individuals from their daily-life activities. Anti-inflammatory drugs (either steroid or not), in addition to immunosuppressants, homeopathy and physiotherapy are measures of treatment that, according to the literature, have been successful in relieving or extinguishing symptoms. However, it is fundamental that studies of CHIK treatment be further developed.

Objective: To determine whether the seasonal distribution of Kingella kingae osteoarticular infections is similar to that of common respiratory viruses., Study Design: Between October 2009 and September 2016, we extracted the results of K kingae-specific real-time polymerase chain reaction analyses performed for bone or joint specimens in patients from 2 pediatric tertiary care centers in Paris. We used data of respiratory virus detection from the Réseau National des Laboratoires network with coordination with the National Influenza Center of France. The Spearman rank correlation was used to assess a correlation between weekly distributions, with P < .05 denoting a significant correlation., Results: During the 7-year study period, 322 children were diagnosed with K kingae osteoarticular infection, and 317 testing episodes were K kingae-negative. We observed high activity for both K kingae osteoarticular infection and human rhinovirus (HRV) during the fall (98 [30.4%] and 2401 [39.1%] cases, respectively) and low activity during summer (59 [18.3%] and 681 [11.1%] cases, respectively). Weekly distributions of K kingae osteoarticular infection and rhinovirus activity were significantly correlated (r = 0.30; P = .03). In contrast, no significant correlation was found between the weekly distribution of K kingae osteoarticular infection and other respiratory viruses (r = -0.17, P = .34 compared with respiratory syncytial virus; r = -0.13, P = .34 compared with influenza virus; and r = -0.22, P = .11 compared with metapneumovirus)., Conclusion: A significant temporal association was observed between HRV circulation and K kingae osteoarticular infection, strengthening the hypothesis of a role of viral infections in the pathophysiology of K kingae invasive infection., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Chikungunya virus (CHIKV) belongs to a group of mosquito-borne alphaviruses associated with acute and chronic arthropathy, with peripheral and limb joints most commonly affected. Using a mouse model of CHIKV infection and arthritic disease, we show that CHIKV replication and the ensuing foot arthropathy were dramatically reduced when mice were housed at 30°C, rather than the conventional 22°C. The effect was not associated with a detectable fever, but was dependent on type I interferon responses. Bioinformatics analyses of RNA-Seq data after injection of poly(I:C)/jetPEI suggested the unfolded protein response and certain type I interferon responses are promoted when feet are slightly warmer. The ambient temperature thus appears able profoundly to effect anti-viral activity in the periphery, with clear consequences for alphaviral replication and the ensuing arthropathy. These observations may provide an explanation for why alphaviral arthropathies are largely restricted to joints of the limbs and the extremities.

Objectives: The objectives of this study were to determine the prevalence of hepatitis C virus-associated inflammatory arthritis, to describe its clinical and immunologic correlates, and to identify features that are characteristic of arthritis in chronic hepatitis C., Methods: Participants with chronic hepatitis C infection enrolled in a population-based cohort study in Alaska and who had not received anti-viral treatment for hepatitis C were recruited. In a cross-sectional study, we assessed joint symptoms and signs, performed autoantibody and cytokine testing, and abstracted medical records for features of hepatitis C and arthritis., Results: Of the 117 enrolled participants, 8 (6.8%) had hepatitis C-associated arthritis. The participants with arthritis were younger than those without (median age: 45 vs. 52, p = 0.02). Rheumatoid factor was commonly present among patients with hepatitis C-associated arthritis. The only studied autoantibody found more commonly in patients with HCV arthritis than those without arthritis was anti-nuclear antibody (63% vs. 23%, p = 0.026). The only joint symptom significantly more common in hepatitis C arthritis was self-reported joint swelling (75% vs. 26%, p = 0.007). Features of fibromyalgia were more common and functional status was worse in those with arthritis than those without. No cytokines differed in patients with and without arthritis. There were no associations of arthritis or autoantibodies with liver-related outcomes., Conclusions: In this study of a cohort of individuals with chronic HCV infection, HCV-associated arthritis was present in less than 10%. Few serologic features distinguished participants with or without arthritis, but self-reported joint swelling was more common in those with arthritis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Epidemiological studies suggest a viral etiology in approximately 1% of patients presenting with acute arthritis. The arthritogenic effect of viral infections may be related to viral invasion of synovial cells, the cellular and humoral immune response to viral antigens or by induction of autoimmunity. Viral arthritis can mimic rheumatoid arthritis by presenting as a symmetrical polyarticular disease often accompanied by a rash and influenza-like symptoms. Serological testing for pathogen-specific IgM and IgG antibodies is frequently performed for establishing a viral etiology of arthritis. Virus isolation from the joints or detection of viral nucleic acids in the synovium or synovial fluid is only rarely successful and does not always provide proof of a viral origin of arthritis. While viral arthritis in most cases is self-limiting, protracted disease can occur.

Avian reoviruses are the causative agent of viral arthritis/tenosynovitis in chickens and turkeys. Clinical signs of disease include swelling of the hock joints accompanied by lesions in the gastrocnemius and digital flexor tendons causing lameness in addition to hydropericardium. The economic impact is significant as it results in poor weight gain, increased feed conversion ratios and condemnations at the processing plant. Vaccination with both live attenuated and inactivated oil emulsion vaccines have been used successfully for decades to control the disease. Current commercial vaccine strains belong to the same serotype and are antigenically and serologically distinct from circulating variant field viruses isolated from clinical cases of tenosynovitis. Since 2012, there has been a dramatic increase in the number of clinical cases of tenosynovitis in commercial poultry and commercial vaccines are unable to provide adequate levels of protection against disease. Producers have elected to use custom inactivated vaccines in the absence of any commercially available homologous vaccines. Identification and selection of field isolates for use in autogenous vaccines can be difficult especially when multiple reoviruses are co-circulating among flocks. In addition, field data suggests that in some cases the custom vaccines are providing adequate protection against disease but as new genetic variants emerge, new vaccines are needed., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In a proportion of patients, chikungunya arthritis (CA) might run into a chronic persistent phase. The treatment for this phase is not very clear. In this randomized parallel group open label study of 24 weeks duration, we evaluated the efficacy of DMARD combination in persistent CA. Consecutive 139 patients with persistent CA (persistent arthritis for >1 year after the chikungunya fever either in 2008 or 2009 fulfilling epidemiological criteria for CA) were screened. Of these patients who were already taking hydroxychloroquine (HCQ) and had active arthritis were randomized to receive either fixed-dose combination therapy (methotrexate 15 mg/day, sulfasalazine 1 g/day, and HCQ 400 mg/day) or continue with HCQ 400 mg/day (dose optimized) monotherapy. Both groups received oral prednisolone up to 6 weeks. Assessments at every 4 weeks were carried out for primary efficacy (disease activity score; DAS ESR 28) and secondary efficacies, HAQ-Indian version and pain VAS100mm. Seventy-two patients were randomized (37 combination therapy, 35 monotherapy). Both groups were well matched in all respects. At 24 weeks, the combination therapy group showed significant improvement in both disease activity (mean ± SD DAS28; 3.39 ± 0.87 vs. 4.74 ± 0.65, p < 0.0001) and disability (mean ± SD HAQ; 1.4 ± 0.31 vs. 1.88 ± 0.47, p < 0.0001). At the study end, pain VAS was significantly less in the combination therapy group (46 ± 6.13 vs. 60.8 ± 11.6, p < 0.0001). Three patients withdrew from the combination group (inefficacy; 2, adverse event; 1) and seven from monotherapy (inefficacy; 7). This study provide evidence that for chronic persistent CA combination DMARD therapy with methotrexate, sulfasalazine and HCQ is superior to monotherapy with HCQ.

In 2013, chikungunya virus (CHIKV) transmission was documented in the Western Hemisphere, and the virus has since spread throughout the Americas with more than 1.8 million people infected in more than 40 countries. CHIKV targets the joints, resulting in symmetric polyarthritis that clinically mimics rheumatoid arthritis and can endure for months to years. At present, no approved treatment is effective in preventing or controlling CHIKV infection or disease. We treated mice with eight different disease-modifying antirheumatic drugs and identified CLTA4-Ig (abatacept) and tofacitinib as candidate therapies based on their ability to decrease acute joint swelling. CTLA4-Ig reduced T cell accumulation in the joints of infected animals without affecting viral infection. Whereas monotherapy with CTLA4-Ig or a neutralizing anti-CHIKV human monoclonal antibody provided partial clinical improvement, therapy with both abolished swelling and markedly reduced levels of chemokines, proinflammatory cytokines, and infiltrating leukocytes. Thus, combination CTLA4-Ig and antiviral antibody therapy controls acute CHIKV infection and arthritis and may be a candidate for testing in humans., (Copyright © 2017, American Association for the Advancement of Science.)

Viral arthritis and vasculitis are important differential diagnoses primarily in patients with acute polyarticular arthritis in association with fever and rash, in populations specially at risk and in returning travellers. Parvovirus B19 is the most frequent cause of viral arthritis in Europe, whereas rubella, hepatitis B and C viruses have become less common. Due to worldwide tourism arthritogenic alphaviruses, which are transmitted by mosquito vectors have come into the focus of tropical medicine and rheumatology. Viral arthritis is typically self-limiting but due to severe pain often requires symptomatic therapy with nonsteroidal antirheumatic drugs; however, arthritis and vasculitis may also be a manifestation of an important treatable viral infection, such as hepatitis B, C and human immunodeficiency viruses (HIV).

Acute-onset arthritis is a common clinical problem facing both the general clinician and the rheumatologist. A viral aetiology is though to be responsible for approximately 1% of all cases of acute arthritis with a wide range of causal agents recognised. The epidemiology of acute viral arthritis continues to evolve, with some aetiologies, such as rubella, becoming less common due to vaccination, while some vector-borne viruses have become more widespread. A travel history therefore forms an important part of the assessment of patients presenting with an acute arthritis. Worldwide, parvovirus B19, hepatitis B and C, HIV and the alphaviruses are among the most important causes of virally mediated arthritis. Targeted serological testing may be of value in establishing a diagnosis, and clinicians must also be aware that low-titre autoantibodies, such as rheumatoid factor and antinuclear antibody, can occur in the context of acute viral arthritis. A careful consideration of epidemiological, clinical and serological features is therefore required to guide clinicians in making diagnostic and treatment decisions. While most virally mediated arthritides are self-limiting some warrant the initiation of specific antiviral therapy., (© 2016 Royal College of Physicians.)

The present study is the first investigation of the association between single nucleotide polymorphisms (SNPs - rs8099917, rs12979860 and rs8103142) of the IL28B gene and the development of human T-lymphotropic virus (HTLV)-associated arthropathy (HAA). Individuals with HAA exhibited low interleukin (IL) 6 (p<0.05) and high IL-10 (p<0.05) levels compared with asymptomatic patients. TNF-α/CD4(+) T cell count, TNF-α/CD8(+) T cell count and IFN-γ/proviral load positively correlated in asymptomatic patients. The allelic and genotypic frequencies did not differ between patients with HAA and asymptomatic patients. Seven haplotypes were detected in the investigated population, with haplotype CCT (p<0.05) being the most frequent among the HTLV-infected individuals, while haplotype TTG (p<0.05) was detected in the group with HAA only. Compared with asymptomatic patients, individuals with HAA and genotype TT (rs8099917) exhibited larger numbers of CD8(+) T cells (p<0.05) and higher proviral load levels (p<0.05). Those patients with HAA and genotypes CC (rs12979860) and TT (rs8103142) exhibited high TNF-β (p<0.05) and IFN-γ (p<0.05) levels. Those patients with HAA and genotype CT/TT (rs12979860) exhibited high IL-10 levels (p<0.05). These results suggest that haplotypes CCT and TTG might be associated with susceptibility to HTLV infection and progression to HAA, respectively. Genotype TT (rs8099917) might be a risk factor for elevation of the proviral load and CD8(+) T cell count. In addition, genotypes CC (rs12979860) and TT (rs8103142) seem to be associated with increased TNF-β and IFN-γ levels., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recent concerning facts of Chikungunya virus (CHIKV); a Togaviridae family alphavirus has proved this as a worldwide emerging threat which causes Chikungunya fever and devitalizing arthritis. Despite severe outbreaks and lack of antiviral drug, a mere progress has been made regarding to an epitope-based vaccine designed for CHIKV. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites by using various immunoinformatics and docking simulation tools. Initially, whole proteome of CHIKV was retrieved from database and perused to identify the most immunogenic protein. Structural properties of the selected protein were analyzed. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell were checked for the selected protein. The peptide region spanning 9 amino acids from 397 to 405 and the sequence YYYELYPTM were found as the most potential B cell and T cell epitopes respectively. This peptide could interact with as many as 19 HLAs and showed high population coverage ranging from 69.50% to 84.94%. By using in silico docking techniques the epitope was further assessed for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post therapeutic strategy, three dimensional structure was predicted along with validation and verification that resulted in molecular docking study to identify the potential drug binding sites and suitable therapeutic inhibitor against targeted protein. Finally, pharmacophore study was also performed in quest of seeing potent drug activity. However, this computational epitope-based peptide vaccine designing and target site prediction against CHIKV opens up a new horizon which may be the prospective way in Chikungunya virus research; the results require validation by in vitro and in vivo experiments., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Arthritogenic alphaviral infection begins as a febrile illness and often progresses to joint pain and rheumatic symptoms that are described as polyarthritis. Alphaviral arthritis and classical arthritides share many similar cellular and immune mediators involved in their pathogenesis. Recent in vitro and in vivo evidence suggests that bone loss resulting from increased expression of bone resorption mediators may accompany alphaviral infection. In addition, several longitudinal studies have reported more severe and delayed recovery of alphaviral disease in patients with pre-existing arthritic conditions. This review aims to provide insights into alphavirus-induced bone loss and focuses on aspects of disease exacerbation in patients with underlying arthritis and on possible therapeutic targets., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Human T cell leukemia virus type 1 or HTLV-1 infection is a public health problem in endemic regions like Japan, Central America or Africa. Although the majority of HTLV-1 carriers remain asymptomatic throughout their lives, some patients could develop neurological disorder, inflammatory arthropathy also called HTLV-1-associated arthropathy or T-cell malignancy, the adult T-cell leukemia/lymphoma or ATL with a very poor prognosis. Described to be very close to rheumatoid arthritis, HTLV-1-associated arthropathy patients have few or no response to the first line therapy with corticosteroids and disease modifying antirheumatic drugs or DMARDs. The use of anti-TNF-α agents in these patients is an interesting alternative but asks the question of risk of developing an adult T-Cell leukemia/lymphoma. We reported an exceptional case of a smoldering ATL patient with an HTLV-1-associated arthropathy, refractory to corticosteroid, DMARDs and rituximab therapy, treated successfully with etanercept, without progression to aggressive ATL after 5 years., (Copyright © 2013 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Chronic virus C hepatitis records high prevalence, almost 170 million people worldwide being infected. Systemic involvement is frequent and the implication of the osteoarticular system raises various problems in properly diagnosing and treating it. Rheumatoid arthritis is the most frequent type of inflammatory polyarthritis, with a prevalence of 0.8% in the general population. The rheumatoid factor recorded high values at virus C hepatitis patients (19-80%) even in the absence of articular manifestations, its sensitivity and specificity being reduced for the rheumatoid arthritis diagnosed simultaneous with virus C hepatitis. We report a case of chronic virus C hepatitis patient which, after 30 years of evolution, presents the onset of senile rheumatoid polyarthritis. The authors discuss the usefulness dosage of anti-cyclic citrullinated peptide antibodies for establishing the differential diagnosis between rheumatoid arthritis and hepatitis C-related arthropathy and the particularities of the specific treatment when there is a hepatitis C virus associated infection.

The complement system plays an important role in both the innate and adaptive immune system. Patients with inherited complement deficiencies have an increased risk of systemic bacterial infections. Deficiencies of the terminal complement pathway are especially associated with invasive meningococcal disease. Here, we report a case of a boy that presented with arthritis and recurrent bacterial and viral infections. Extensive analyses revealed decreased complement activity of both classical and alternative pathway, indicating a deficiency of C3 or one of the factors of the terminal complement pathway. Mutational analysis of the C6 gene identified two compound heterozygous mutations. An unknown missense aberration was found that involves the loss of a cysteine, possibly affecting the 3D structure of the protein. Furthermore, a known splice site variation was identified that results in a 14% shorter protein, due to transcription of amino acids that are normally intronic until a stop codon is reached (exon-intron boundary defect). It is known that the protein with this latter aberration is still functionally active when present with other C6 mutations and therefore, the consequences of the combination of the identified variations have been studied. Quantitative ELISAs showed that at least one allele produced a circulating C6 molecule that can be incorporated in the membrane attack complex, likely the truncated protein. In the present case we observed relapsing bacterial and viral infections, but no meningococcal disease. The reduced complement activity can be explained by the identified genetic variations in C6, as recombinant C6 supplementation corrected complement function in vitro., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Arthralgia is a common presentation to general practice, and many cases will not require any specific treatment. It is important to differentiate viral arthritis from other causes as early intervention in inflammatory arthritis has been shown to improve long-term outcome., Objective: This article provides a review of the different causes of viral arthritis, with an emphasis on recognising the clues to a viral cause, and summarises appropriate investigations and management., Discussion: Viral arthritis is typically self-limiting and requires no specific intervention, although in rare cases symptoms can be prolonged. Some viruses have a predilection for the joints, and arthritis is one of the common presenting signs of infection. It may also be a manifestation of important treatable viral infections such as hepatitis and human immunodeficiency virus (HIV). Early systemic inflammatory arthritis can be difficult to differentiate from viral arthritis and should be actively considered in all patients. Comprehensive testing for viral aetiologies is of limited utility.

Arthritogenic alphaviruses, including Ross River virus (RRV), Chikungunya virus (CHIKV), Sindbis virus (SINV), Mayaro virus (MAYV), O'nyong-nyong virus (ONNV), and Barmah Forest virus (BFV), cause incapacitating and long lasting articular disease/myalgia. Outbreaks of viral arthritis and the global distribution of these diseases point to the emergence of arthritogenic alphaviruses as an important public health problem. This review discusses the molecular mechanisms involved in alphavirus-induced arthritis, exploring the recent data obtained with in vitro systems and in vivo studies using animal models and samples from patients. The factors associated to the extension and persistence of symptoms are highlighted, focusing on (a) virus replication in target cells, and tissues, including macrophages and muscle cells; (b) the inflammatory and immune responses with recruitment and activation of macrophage, NK cells and T lymphocytes to the lesion focus and the increase of inflammatory mediators levels; and (c) the persistence of virus or viral products in joint and muscle tissues. We also discuss the importance of the establishment of novel animal models to test new molecular targets and to develop more efficient and selective drugs to treat these diseases.

Parvovirus B19 infection is highly prevalent in children and the most common manifestation is a facial rash. In adults, acute polyarthritis and skin rash are often the presenting features. We report three patients with the disease. A 40-year-old female presenting with fever, myalgias and painful swelling of elbows, knees, wrists and feet, with functional limitation, after having a respiratory infection. Additionally, an erythematous skin rash appeared in both extremities. IgM antibodies against Parvovirus B19 were positive. The skin biopsy disclosed a leukocytoclastic vasculitis. The patient was treated with anti-inflammatory drugs and antihistaminics. A 40-year-old female, presenting with skin rash and pain in wrists and hands. IgM antibodies against parvovirus were positive. The patient was treated successfully with acetaminophen. A 38-year-old male with psoriasis, presenting with generalized and progressive polyarthralgia. A Parvovirus viral load determination found 239000 copies of the virus and IgM antibodies were positive. He was successfully treated with non-steroidal anti-inflammatory drugs.

Objective: Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes a chronic debilitating polyarthralgia/polyarthritis, for which current treatments are often inadequate. To assess whether new drugs being developed for rheumatoid arthritis (RA) might find utility in the treatment of alphaviral arthritides, we sought to determine whether the inflammatory gene expression signature of CHIKV arthritis shows any similarities with RA or collagen-induced arthritis (CIA), a mouse model of RA., Methods: Using a recently developed animal model of CHIKV arthritis in adult wild-type mice, we generated a consensus CHIKV arthritis gene expression signature, which was used to interrogate publicly available microarray studies of RA and CIA. Pathway analyses were then performed using the overlapping gene signatures., Results: Gene set enrichment analysis showed that there was a highly significant overlap in the differentially expressed genes in the CHIKV arthritis model and in RA. This concordance also increased with the severity of RA, as measured by the inflammation score. A highly significant overlap was also seen between CHIKV arthritis and CIA. Pathway analysis revealed that the overlap between these arthritides was spread over a range of different inflammatory processes. Involvement of T cells and interferon-γ (IFNγ) in CHIKV arthritis was confirmed in studies of MHCII-deficient mice and IFNγ-deficient mice, respectively., Conclusion: These results suggest that RA, a chronic autoimmune arthritis, and CHIKV disease, usually a self-limiting viral arthropathy, share multiple inflammatory processes. New drugs and biologic therapies being developed for RA may thus find application in the treatment of alphaviral arthritides., (Copyright © 2012 by the American College of Rheumatology.)

Mosquito-transmitted alphaviruses causing human rheumatic disease are globally distributed and include chikungunya virus, Ross River virus, Barmah Forest virus, Sindbis virus, o'nyong-nyong virus and Mayaro virus. These viruses cause endemic disease and, occasionally, large epidemics; for instance, the 2004-2011 chikungunya epidemic resulted in 1.4-6.5 million cases, with imported cases reported in nearly 40 countries. The disease is usually self-limiting and characterized by acute and chronic symmetrical peripheral polyarthralgia-polyarthritis, with acute disease usually including fever, myalgia and/or rash. Arthropathy can be debilitating, usually lasts weeks to months and can be protracted; although adequate attention to differential diagnoses is recommended. The latest chikungunya virus epidemic was also associated with some severe disease manifestations and mortality, primarily in elderly patients with comorbidities and the young. Chronic alphaviral rheumatic disease probably arises from inflammatory responses stimulated by the virus persisting in joint tissues, despite robust antiviral immune responses. Serodiagnosis by ELISA is the standard; although international standardization is often lacking. Treatment usually involves simple analgesics and/or NSAIDs, which can provide relief, but better drug treatments are clearly needed. However, the small market size and/or the unpredictable and rapid nature of epidemics present major hurdles for development and deployment of new alphavirus-specific interventions.

In humans, chikungunya virus (CHIKV) infection causes fever, rash, and acute and persisting polyarthralgia/arthritis associated with joint swelling. We report a new CHIKV disease model in adult mice that distinguishes the wild-type CHIKV-LR strain from the live-attenuated vaccine strain (CHIKV-181/25). Although eight-week old normal mice inoculated in the hind footpad developed no hind limb swelling with either virus, CHIKV-LR replicated in musculoskeletal tissues and caused detectable inflammation. In mice deficient in STAT1-dependent interferon (IFN) responses, CHIKV-LR caused significant swelling of the inoculated and contralateral limbs and dramatic inflammatory lesions, while CHIKV-181/25 vaccine and another arthritogenic alphavirus, Sindbis, failed to induce swelling. IFN responses suppressed CHIKV-LR and CHIKV-181/25 replication equally in dendritic cells in vitro whereas macrophages were refractory to infection independently of STAT1-mediated IFN responses. Glycosaminoglycan (GAG) binding may be a CHIKV vaccine attenuation mechanism as CHIKV-LR infectivity was not dependent upon GAG, while CHIKV-181/25 was highly dependent., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Nonbacterial arthritis is a rare but well-recognized complication of acute varicella in children. Reported cases usually described monoarthritis of the knee that occurs at the onset of the rash or shortly after. Herein, we describe a case of arthritis of the hip that occurred in a 4-year-old girl 6 days before the onset of rash. The presence of varicella-zoster virus DNA in synovial fluid was confirmed by real-time polymerase chain reaction. A review of the literature reported 26 previous cases of aseptic arthritis due to varicella infection among children.

Chikungunya virus (CHIKV) is associated with outbreaks of infectious rheumatic disease in humans. Using a mouse model of CHIKV arthritis and myositis, we show that tumor necrosis factor-α, interferon-γ, and monocyte chemotactic protein 1 (MCP-1) were dramatically induced in tissues from infected mice. The same factors were detected in the serum of patients with CHIKV-induced polyarthralgia and polyarthritis, with MCP-1 levels being particularly elevated. Bindarit (MCP inhibitor) treatment ameliorated CHIKV disease in mice. Histological analysis of muscle and joint tissues showed a reduction in inflammatory infiltrate in infected mice treated with bindarit. These results suggest that bindarit may be useful in treating CHIKV-induced arthritides in humans.

Animal models, which mimic human disease, are invaluable tools for understanding the mechanisms of disease pathogenesis and development of treatment strategies. In particular, animal models play important roles in the area of infectious arthritis. Alphaviruses, including Ross River virus (RRV), o'nyong-nyong virus, chikungunya virus (CHIKV), mayaro virus, Semliki Forest virus and sindbis virus, are globally distributed and cause transient illness characterized by fever, rash, myalgia, arthralgia and arthritis in humans. Severe forms of the disease result in chronic incapacitating arthralgia and arthritis. The mechanisms of how these viruses cause musculoskeletal disease are ill defined. In recent years, the use of a mouse model for RRV-induced disease has assisted in unraveling the pathobiology of infection and in discovering novel drugs to ameliorate disease. RRV as an infection model has the potential to provide key insights into such disease processes, particularly as many viruses, other than alphaviruses, are known to cause infectious arthritides. The emergence and outbreak of CHIKV in many parts of the world has necessitated the need to develop animal models of CHIKV disease. The development of non-human primate models of CHIKV disease has given insights into viral tropism and disease pathogenesis and facilitated the development of new treatment strategies. This review highlights the application of animal models of alphaviral diseases in the fundamental understanding of the mechanisms that contribute to disease and for defining the role that the immune response may have on disease pathogenesis, with the view of providing the foundation for new treatments.

Chikungunya virus (CHIKV) is an emerging alphavirus responsible for several infectious outbreaks in the world. After an acute stage of illness characterised by a fever-arthralgia syndrome and rash, joint disorders due to CHIKV infection can sometimes persist for several months or years. Chronic arthritis after this emerging disease is well documented, and similarities to rheumatoid arthritis have been described. Knowledge of the geographical epidemiology of CHIKV infection is crucial for better control of the disease. Thus, recent outbreaks have led to several studies, which have highlighted the need for a better understanding of the clinical features of Chikungunya (CHIK) and beginning knowledge of the pathophysiogenesis, which can lead to further research., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Chikungunya fever (CHIKF) is currently distributed in Africa and in South and Southeast Asia; outbreaks have occurred periodically in the region over the past 50 years. After a large outbreak had occurred in countries in the western Indian Ocean region in 2005, several countries reported cases of CHIKF from travelers who had visited affected areas. In Japan, there have been only 15 cases of CHIKF patients so far, according to the National Institute of Infectious Diseases. Therefore, to evaluate the clinical and radiological features associated with the disease, we describe 6 imported cases of CHIKF. All of the patients had had prolonged arthralgia on admission to our hospital, and diagnosis was confirmed with specific antibodies by using an IgM-capture enzyme-linked immunoassay and a plaque reduction neutralizing antibody assay. Magnetic resonance imaging (MRI) of one patient revealed erosive arthritis and tenosynovitis during the convalescence stage. Clinicians should be aware of the late consequences of infection by the chikungunya virus (CHIKV) and recognize the possible association of subacute and chronic arthritis features. In addition, competent vectors of CHIKV, Aedes aegypti, can now be found in many temperate areas of the eastern and western hemispheres, including Japan. This fact raises concern that the virus could be introduced and become established in these areas. This necessitates an increased awareness of the disease, because imported cases are likely to contribute to the spread of CHIKV infection wherever the competent mosquito vectors are distributed.

Viral infections may manifest as acute or chronic arthritis. Joint involvement arises from either direct infection of the joint, through an immunological response directed towards the virus or autoimmunity. Epidemiological clues to the diagnosis include geographic location and exposure to vector-borne, blood-borne or sexually transmitted viruses. Although not always possible, it is important to diagnose the pathogenic virus, usually by serology, nucleic acid tests or rarely, viral culture. In general, viral arthritides are self-limiting and treatment is targeted at symptomatic relief. This article focuses on the causes, clinical features, diagnosis and treatment of viral arthritides.

Osteomyelitis variolosa is an infection of bone and joints by smallpox virus variola major, most commonly in the elbows, wrists, ankles, hands, and feet. We report one such case in a 70-year-old woman who presented with deformities of the right knee, both elbows and ankles, and the left hand, and a history of childhood fever with rashes. Her lateral femoral condyle of the right knee was hypoplastic with patella baja. Her right elbow was ankylosed and her left elbow was dislocated with multidirectional instability. Her third and fourth metacarpals on the left hand were shortened. Both ankles were stiff with valgus deformity; both taluses were destroyed.

Background: Although many viruses produce musculoskeletal symptoms during an acute infection, a long-term inflammatory arthritis remains an unusual consequence. When evaluating arthritis in a patient with a chronic or latent viral infection, serologic testing and therapeutic options are significantly altered., Results: The example of hepatitis C reveals how chronic infection can complicate the diagnosis of rheumatoid arthritis. Determination of rheumatoid factor is of limited utility, whereas the anticyclic citrullinated peptide has become a new test with improved specificity. Therapeutic options are severely constrained because of potential hepatotoxicity of oral agents such as methotrexate and leflunomide. Antitumor necrosis factor alpha biologics have demonstrated initial safety in the setting of hepatitis C virus but may be associated with reactivation of hepatitis B virus. Biologics such as abatacept and rituximab have been inadequately studied in this population to date. Prevention of viral infections by influenza and herpes zoster vaccines in rheumatoid arthritis patients needs improved administration rates and careful planning to maximize efficacy., Conclusions: Chronic viral infections complicate the diagnosis and therapy of inflammatory arthritis. The antitumor necrosis factor alpha biologics have become important therapeutic options for patients with hepatitis C. Vaccination against influenza and herpes zoster are underused in health maintenance of arthritis patients.