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Objectives: Reactive arthritis (ReA) provides a unique opportunity to comprehend how a mucosal infection leads to inflammatory arthritis at a distant site without the apparent invasion of the pathogen. Unfortunately, conventional stool cultures after ReA provide limited information, and there is a dearth of metagenomic studies in ReA. The objective of this study was to identify gut microbiota associated with the development of ReA., Methods: Patients with ReA or undifferentiated peripheral spondyloarthritis (UpSpA) were included if they presented within 4 weeks of the onset of the current episode of arthritis. Metagenomic DNA was extracted from the stools of these patients and of 36 age- and sex-similar controls. Sequencing and analysis were done using a standard 16S ribosomal pipeline., Results: Of 55 patients, there was no difference between the gut microbiota of postdiarrheal ReA (n = 20) and of upSpA (n = 35). Comparing the gut microbiota of patients vs healthy controls, the patients had significantly higher alpha and beta diversity measures. After stringency filters, Proteobacteria had high abundance while Firmicutes had lesser as compared with the controls. Six families were overexpressed in patients, while another five were overexpressed in controls. Sixteen genera and 18 species were significantly different between patients and controls. At the species level there was strong association of Staphylococcus aureus, Clostridium septicum Klebsiella pneumoniae, Escherichia coli, Empedobacter brevis, Roseburia hominis, Bacillus velezensis and Crassaminicella with ReA., Conclusion: The microbiota of classical gut-associated ReA and upSpA is similar. Patients have higher diversities in their gut microbiota compared with healthy controls. Both known and previously unreported species associated with ReA/upSpA were identified., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Poncet disease (PD) is a rare form of reactive polyarthritis associated with acute tuberculosis (TB). Multiple TB foci are rare in PD, particularly on the hands. Herein, we describe a case of PD with foci in the trapezium and spine of a 76-year-old man. His medical history included knee arthritis as well as hand and lumbar pain. Radiography and magnetic resonance imaging revealed lytic lesions in the trapezium and spine, which were suspected to be caused by TB infection. An open biopsy of the trapezium and spine was performed. The biopsy results revealed dry necrosis and epithelioid granulation. The diagnosis of PD was made, and the patient was referred to a TB specialty hospital. Our results highlight the importance of considering PD in older patients with multiple TB foci, especially on the hands. Level of Evidence: Level V (Therapeutic).

Reactive arthritis (ReA) is defined as arthritis resulting from infections in other body parts, such as the gastrointestinal and urogenital tracts. The primary clinical manifestations involve acute-onset and self-limiting asymmetric large joint inflammation in the lower limbs. Although bacterial or chlamydia infections have long been recognized as playing a pivotal role in its pathogenesis, recent studies suggest that antibiotic treatment may perpetuate rather than eradicate chlamydia within the host, indicating an involvement of other mechanisms in Reactive arthritis. Reactive arthritis is currently believed to be associated with infection, genetic marker (HLA-B27), and immunologic derangement. As an autoimmune disease, increasing attention has been given to understanding the role of the immune system in Reactive arthritis. This review focuses on elucidating how the immune system mediates reactive arthritis and explores the roles of intestinal dysbiosis-induced immune disorders and stress-related factors in autoimmune diseases, providing novel insights into understanding reactive arthritis., Competing Interests: Declarations. Conflict of interest: T. He and W. Qian declare that they have no competing interests. For this article no studies with human participants or animals were performed by any of the authors. All studies mentioned were in accordance with the ethical standards indicated in each case., (© 2024. The Author(s).)

Background: The incidence of pediatric inflammatory bowel disease is increasing. tumor necrosis factor alpha inhibitors medicines improved the prognosis of affected subjects. Nonetheless, a proportion of patients do not respond or lose response to treatment. Newer biologics, like ustekinumab, have been approved for adults. The pediatric off-label use of these drugs is increasing, despite limited safety evidence. We report a case of disseminated mycobacterial infection (MI) presenting with reactive polyarthritis (Poncet's disease, PD) in a girl with Crohn's disease receiving various immunosuppressants, including ustekinumab., Case Report: A 12-year-old girl with Crohn's disease was admitted for acute-onset migratory polyarthritis of large and small joints and opioid-resistant pain. She had recently received adalimumab and methotrexate and was currently under treatment with ustekinumab. She was vaccinated with Bacillus Calmette-Guérin and screened for tuberculosis before starting immunosuppressants. Interferon-gamma release assay, Mantoux test and chest computed tomography scan were negative. Disseminated MI with PD was diagnosed following positive cultures for Mycobacterium tuberculosis complex in blood and intestinal biopsies (with negative in synovial fluid and gastric aspirate). Whole-exome sequencing did not identify any genetic susceptibility to MI. Antituberculosis treatment eradicated MI., Conclusions: Children with inflammatory bowel disease receiving combination immunosuppressive treatments including tumor necrosis factor alpha inhibitors and anti-IL-12/23 agents are at higher risk for MI. Disseminated MI should be considered and ruled out in these patients when presenting with pulmonary, extrapulmonary or unusual clinical manifestations, like PD. The collection of multiple specimens (including intestinal biopsies) for mycobacterial culture is recommended when mycobacterial disease is suspected., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Reactive arthritis is included in the spectrum of seronegative spondyloarthritides, occurring secondary to triggers of genitourinary and gastrointestinal tract infections. We describe two cases of sexually acquired reactive arthritis secondary to genital infection by Chlamydia trachomatis, diagnosed by in-house polymerase chain reaction performed on the first void urine. Both patients were managed with a combined approach of short course antibiotics, immunosuppressive agents, biologicals and surgical intervention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Objective: To compare the diversity and composition of the gastrointestinal microbiome of patients with SpA., Methods: MiSeq sequencing of the V3-V4 region of the 16S ribosomal RNA gene was performed on DNA isolated from stool. Patients with concurrent SpA and IBD were excluded. Differences were assessed for richness and diversity indices by QIIME 2™. Differences between means >0,2% with a p-value<0,05 were assumed significant. Institutional Ethics Committee endorsement., Results: 69 individuals included, 49 with SpA (ankylosing spondylitis-AS 72,9%, psoriatic arthritis-PsA 18,8%, reactive arthritis-ReA 8,3%) 5 positive controls-dysbiosis and 15 controls-eubiosis. Conventional treatment in 42,9%, anti-IL-17 16,3% and anti-TNF 40,8%. By subtype, statistically significant differences in favour of AS were found for the diversity indices. AS vs PsA there was a difference in favour of AS for Clostridium clostridioforme (p=0,002), Gemmiger formicilis (p=0,009), Roseburia inulivorans (p=0,008) and Lachnospira pectinoschiza . AS vs ReA there was a difference in favour of AS for L. pectinoschiza (p=0,009), Ruminococcus callidus (p=0.006), Clostridium ruminantium (p=0.031); G. formicilis (p=0,034). Diversity and richness showed differences in patients with high activity for Simpson's and Pielou's indices. In high activity, lower enrichment of Bacteroides eggerthii (p= 0,0003), C. ruminantium (p= 0,026) and Alistipes putredinis (p=0,035) was found. The number of ASV was higher in the anti-IL-17 vs conventional group (p=0.025) and a trend between anti-IL-17 vs anti-TNF (p=0.09). In anti-TNF there was a lower proportion for C. clostridioforme (p=0.023), G. formicilis (p=0.030) and R. callidus (p= 0.003). In anti IL-17, Alistipes indistinctus (p= 0.012) was decreased., Conclusions: There are differences in microbial diversity for SpA subtypes. The level of disease activity is plausible to influence the composition of the faecal microbiota. Anti-TNFα treatment may influence the microbiome environment favouring restoration of the gut microbiota, while anti-IL-17 may maintain an inflammatory environment.

Reactive arthritis Abstract. Reactive Arthritis is a sterile, inflammatory arthritis that is typically preceded by a bacterial gastrointestinal or urogenital infection occurring one to four weeks previously. The typical pattern is an asymmetric oligoarthritis most common affecting the lower extremities. Similar to other spondyloarthropathies, enthesitis, dactylitis, and sacroiliitis can occur as well as extra-articular manifestations, such as conjunctivitis, anterior uveitis, oral ulcers, circinate balanitis, and keratoderma blennorrhagicum. The treatment of "triggering" infection with antibiotics is the first therapeutic goal, especially for Chlamydia trachomatis. For arthritis NSAIDs are the treatment of first choice, followed by intraarticular or oral glucocorticosteroids. DMARDs (Sulfasalzine, TNF-alpha inhibitors) are reserved for refractory cases. Over 50% of the patients have a self-limited course lasting two to six months, 30% have recurrent episodes, and 10-20% have a chronic course requiring immunosuppressive therapy.

The introduction of the term reactive arthritis (ReA) for the joint inflammation observed after infection with Yersinia enterocolitica, in which "a causative pathogen cannot be isolated from the synovial fluid", and the association with the HLA-B27 were the historical milestones for a new classification and assignment to the spondylarthritides (SpA). The division into postinfectious and reactive arthritis proposed in 1976 was put into perspective in the 1990s because of investigations with the newly available molecular biological method of the polymerase chain reaction. Microbial products could be identified from joint samples of patients with ReA. Therefore, it was proposed to abandon the distinction between the two groups of diseases and to prefer the term ReA for both. This created a terminological and nosological issue. On the one hand, there are generally accepted classification and diagnostic criteria for the classical HLA-B27-associated ReA that are assigned to SpA. On the other hand, an increasing number of bacterial pathogens, viruses, amoebas, helminths as well as antiviral and antibacterial vaccinations are described as triggers of arthritis, which have been published under the term ReA. Since the beginning of the SARS-CoV‑2 pandemic, cases of acute post-COVID-19 arthritis have been described, which were also classified as ReA because of comparable clinical features., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Reactive arthritis (ReA) is a form of sterile arthritis that occurs secondary to an extra-articular infection in genetically predisposed individuals. The extra-articular infection is typically an infection of the gastrointestinal tract or genitourinary tract. Infection-related arthritis is a sterile arthritis associated with streptococcal tonsillitis, extra-articular tuberculosis, or intravesical instillation of bacillus Calmette-Guérin (iBCG) therapy for bladder cancer. These infection-related arthritis diagnoses are often grouped with ReA based on the pathogenic mechanism. However, the unique characteristics of these entities may be masked by a group classification. Therefore, we reviewed the clinical characteristics of classic ReA, poststreptococcal ReA, Poncet's disease, and iBCG-induced ReA. Considering the diversity in triggering microbes, infection sites, and frequency of HLA-B27, these are different disorders. However, the clinical symptoms and intracellular parasitism pathogenic mechanism among classic ReA and infection-related arthritis entities are similar. Therefore, poststreptococcal ReA, Poncet's disease, and iBCG-induced ReA could be included in the expanding spectrum of ReA, especially based on the pathogenic mechanism.

Reactive arthritis is an extremely rare spondyloarthritis that affects the peripheral joints and spine, resulting in common symptoms such as arthritis, urethritis, conjunctivitis, and mucocutaneous lesions. On rare occasions, oral lesions such as circinate erosions on the hard and soft palate, gums, tongue, and cheeks may occur. Reactive arthritis may develop during or after genitourinary or gastrointestinal bacterial infections such as Shigella, Salmonella, Yersinia, and Chlamydia. A 36-year-old man presented with circinate balanitis, urethral discharge, oligoarthralgia, conjunctivitis, lymphadenopathy, pharyngitis, and erythematous lesions on the palate. Culture examination showed presence of Neisseria gonorrhoeae and antibiotic treatment resulted in improvement of conjunctivitis and the lesions on the penis. However, severe oligoarthralgia, palatal erosions that increased in severity and size, and depilated areas on the tongue were observed. The definitive diagnosis was reactive arthritis. The prevalence of sexually transmitted infections is increasing, highlighting the need to increase awareness of associated risks such as reactive arthritis. Moreover, consideration of non-specific oral manifestations in a systemic context may aid in effective diagnosis and treatment, suggesting the need for multidisciplinary teams.

Purpose of Review: This article presents a comprehensive narrative review of reactive arthritis (ReA) with focus on articles published between 2018 and 2020. We discuss the entire spectrum of microbial agents known to be the main causative agents of ReA, those reported to be rare infective agents, and those reported to be new candidates causing the disease. The discussion is set within the context of changing disease terminology, definition, and classification over time. Further, we include reports that present at least a hint of effective antimicrobial therapy for ReA as documented in case reports or in double-blind controlled studies. Additional information is included on microbial products detected in the joint, as well as on the positivity of HLA-B27., Recent Findings: Recent reports of ReA cover several rare causative microorganism such as Neisseria meningitides, Clostridium difficile, Escherichia coli, Hafnia alvei, Blastocytosis, Giardia lamblia, Cryptosporidium, Cyclospora cayetanensis, Entamoeba histolytica/dispar, Strongyloides stercoralis, β-haemolytic Streptococci, Mycobacterium tuberculosis, Mycoplasma pneumoniae, Mycobacterium bovis bacillus Calmette-Guerin, and Rickettsia rickettsii. The most prominent new infectious agents implicated as causative in ReA are Staphylococcus lugdunensis, placenta- and umbilical cord-derived Wharton's jelly, Rothia mucilaginosa, and most importantly the SARS-CoV-2 virus. In view of the increasingly large spectrum of causative agents, diagnostic consideration for the disease must include the entire panel of post-infectious arthritides termed ReA. Diagnostic procedures cannot be restricted to the well-known HLA-B27-associated group of ReA, but must also cover the large number of rare forms of arthritis following infections and vaccinations, as well as those elicited by the newly identified members of the ReA group summarized herein. Inclusion of these newly identified etiologic agents must necessitate increased research into the pathogenic mechanisms variously involved, which will engender important insights for treatment and management of ReA.

Purpose of the Review: This topical review attempts to build the concepts of PSRA as an independent entity and discuss prevalent diagnostic criteria. It utilizes a search strategy to collate all clinical features of PSRA reported from across the world and also discusses laboratory and treatment options in brief., Recent Findings: There are several immune-mediated diseases described after acute streptococcal infections. Post-streptococcal reactive arthritis (PSRA) is a sterile, self-limiting arthritis that occur as an immune sequelae to streptococcal infection. Though PSRA resembles the arthritis of acute rheumatic fever superficially, it is a separate entity in its own right. It is different from classical reactive arthritis too. It was being recognized worldwide and more frequently in the recent past, possibly due to heightened awareness amongst clinicians. However, research on this enigmatic immune phenomenon is limited. Most acceptable hypotheses suggest molecular mimicry sensitizing the immune system towards synovial peptides such as keratin, vimentin and laminin, leading to arthritis in a genetically predisposed individual. There is still much to be learnt from this unique disease about the vagaries of the immune system.

Reactive Arthritis (ReA), a rare seronegative inflammatory arthritis, lacks exquisite classification under rheumatic autoimmunity. ReA is solely established using differential clinical diagnosis of the patient cohorts, where pathogenic triggers linked to enteric and urogenital microorganisms e.g. Salmonella, Shigella, Yersinia, Campylobacter, Chlamydia have been reported. Inflammatory Bowel Disease (IBD), an idiopathic enteric disorder co-evolved and attuned to present gut microbiome dysbiosis, can be correlated to the genesis of enteropathic arthropathies like ReA. Gut microbes symbolically modulate immune system homeostasis and are elementary for varied disease patterns in autoimmune disorders. The gut-microbiota axis structured on the core host-microbe interactions execute an imperative role in discerning the etiopathogenesis of ReA and IBD. This study predicts the molecular signatures for ReA with co-evolved IBD through the enveloped host-microbe interactions and microbe-microbe 'interspecies communication', using synonymous gene expression data for selective microbes. We have utilized a combinatorial approach that have concomitant in-silico work-pipeline and experimental validation to corroborate the findings. In-silico analysis involving text mining, metabolic network reconstruction, simulation, filtering, host-microbe interaction, docking and molecular mimicry studies results in robust drug target/s and biomarker/s for co-evolved IBD and ReA. Cross validation of the target/s or biomarker/s was done by targeted gene expression analysis following a non-probabilistic convenience sampling. Studies were performed to substantiate the host-microbe disease network consisting of protein-marker-symptom/disease-pathway-drug associations resulting in possible identification of vital drug targets, biomarkers, pathways and inhibitors for IBD and ReA.Our study identified Na (+) /H (+) anti-porter (NHAA) and Kynureninase (KYNU) to be robust early and essential host-microbe interacting targets for IBD co-evolved ReA. Other vital host-microbe interacting genes, proteins, pathways and drugs include Adenosine Deaminase (ADA), Superoxide Dismutase 2 (SOD2), Catalase (CAT), Angiotensin I Converting Enzyme (ACE), carbon metabolism (folate biosynthesis) and methotrexate. These can serve as potential prognostic/theranostic biomarkers and signatures that can be extrapolated to stratify ReA and related autoimmunity patient cohorts for further pilot studies.

Case: A 59-year-old man with previously well-functioning partial knee replacement was admitted with a warm, swollen, and painful knee. The clinical presentation was consistent with prosthetic joint infection (PJI), but the synovial fluid analysis was negative for microbial growth. Further discussion revealed earlier Campylobacter jejuni enterocolitis that subsequently provoked reactive arthritis (ReA) mimicking PJI. The patient was treated with oral naproxen and intra-articular injection of triamcinolone and recovered completely without antibiotics or surgery. After 29 months, the knee is functioning normally., Conclusion: ReA is rare but should be included in the differential diagnosis of PJI.

Introduction: Post-Streptococcal Reactive Arthritis (PSRA) is defined as inflammatory arthritis of ≥1 joint associated with a recent group A streptococcal infection in a patient who does not fulfill the Jones criteria for the diagnosis of Acute Rheumatic Fever (ARF)., Methods: In this narrative review, we conducted a systematic search on MEDLINE, EMBASE, Cochrane Library and Google Scholar using the words poststreptococcal reactive arthritis. The search covered the time period between 1982 and 2016. The purpose of this review is to summarize the current state of knowledge of PSRA with respect to the definition, epidemiology, clinical presentation and treatment. We also summarize the key differences between PSRA, reactive arthritis (ReA) and ARF., Results: PSRA has a bimodal age distribution at ages 8-14 and 21-37 years with an almost equal male to female ratio. Clinically, it causes acute asymmetrical non-migratory polyarthritis, however, tenosynovitis and small joint arthritis may occur. This disease entity can be associated with extraarticular manifestations, including erythema nodosum, uveitis and glomerulonephritis. The frequency of HLA-B27 in PSRA does not differ from that of the normal population, which suggests that it is a separate entity from ReA. Involvement of the axial skeleton, including sacroiliitis, is uncommon in PSRA. PSRA tends to occur within 10 days of a group A streptococcal infection, as opposed to the 2 to 3 weeks delay for ARF. PSRA can be associated with prolonged or recurrent arthritis, in contrast to ARF, in which arthritis usually lasts a few days to 3 weeks. Treatment usually involves NSAIDs or corticosteroids., Conclusion: We summarize clinical features that help differentiate PSRA from ARF and ReA. First-line treatment options include NSAIDs and corticosteroids. Most cases resolve spontaneously within a few weeks, but some cases are recurrent or prolonged. There are no published randomized controlled trials of PSRA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Diagnosis of postenteritic reactive arthritis (ReA) is a challenge and might have a broad range of differential diagnoses. A 50-year-old man was referred to our attention because of persistent inflammatory low back pain and asymmetric oligoarthritis. The clinical history was positive for diarrhoea in the previous 3 months. Inflammatory bowel disease, Whipple and celiac diseases were carefully excluded. In addition, serology, stool cultures, biopsies from the upper gastrointestinal tract yielded negative results for infections. A presumptive diagnosis of ReA was done and a non-steroidal anti-inflammatory drug trial prescribed. Persistence of symptoms prompted us for a second look of the colon. Biopsy collected from the terminal ileum were cultured and surprisingly colonies of Hafnia alvei, a rod-shaped Enterobacteriaceae, were detected. Treatment with ciprofloxacin leads to fast symptoms resolution. Although enterocolitis from H. alvei has been rarely reported, the culture of intestinal specimens might be recommended in the work-up of patients with suspected postenteritic ReA., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Objectives: : Shiga toxin (Stx) is produced by Shigella dysenteriae, a Gram-negative, facultative anaerobic bacillus that causes shigellosis, haemolytic uraemic syndrome (HUS) and Reiter's syndrome. The detection methods for shiga toxin needs to be rapid, accurate, reliable and must be extensively evaluated under field conditions. The aim of this study was to develop rapid, sensitive and specific detection method for Stx., Methods: : Mice and rabbits were immunized with purified recombinant Shiga toxin B (rStxB). Using these antibodies dot ELISA, sandwich ELISA and flow through assay were developed., Results: : The high-titre antibodies specifically reacted with purified rStxB. Dot-ELISA, sandwich ELISA and flow-through assay were developed and standardized that could detect StxB with limit of detection (LOD) of 9.75, 9.7 ng/ml and 0.46 μg/cassette, respectively., Interpretation & Conclusions: : The rStxB was used to produce antibodies to avoid handling of pathogen. The Flow through assay 'developed was specific, rapid and field amenable., Competing Interests: None

Objective: Salmonella enterica infections can lead to Reactive Arthritis (ReA), which can exhibit an association with human leucocyte antigen (HLA)-B*27:05, a molecule prone to misfolding and initiation of the unfolded protein response (UPR). This study examined how HLA-B*27:05 expression and the UPR affect the Salmonella life-cycle within epithelial cells., Methods: Isogenic epithelial cell lines expressing two copies of either HLA-B*27:05 and a control HLA-B*35:01 heavy chain (HC) were generated to determine the effect on the Salmonella infection life-cycle. A cell line expressing HLA-B*27:05.HC physically linked to the light chain beta-2-microglobulin and a specific peptide (referred to as a single chain trimer, SCT) was also generated to determine the effects of HLA-B27 folding status on S. enterica life-cycle. XBP-1 venus and AMP dependent Transcription Factor (ATF6)-FLAG reporters were used to monitor UPR activation in infected cells. Triacin C was used to inhibit de novo lipid synthesis during UPR, and confocal imaging of ER tracker stained membrane allowed quantification of glibenclamide-associated membrane., Results: S. enterica demonstrated enhanced replication with an altered cellular localisation in the presence of HLA-B*27:05.HC but not in the presence of HLA-B*27:05.SCT or HLA-B*35:01. HLA-B*27:05.HC altered the threshold for UPR induction. Salmonella activated the UPR and required XBP-1 for replication, which was associated with endoreticular membrane expansion and lipid metabolism., Conclusions: HLA-B27 misfolding and a UPR cellular environment are associated with enhanced Salmonella replication, while Salmonella itself can activate XBP-1 and ATF6. These data provide a potential mechanism linking the life-cycle of Salmonella with the physicochemical properties of HLA-B27 and cellular events that may contribute to ReA pathogenesis. Our observations suggest that the UPR pathway maybe targeted for future therapeutic intervention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Reactive arthritis after Group A streptococcal infection (poststreptococcal reactive arthritis: PSRA) that does not meet the Jones criteria for acute rheumatic fever (ARF) has been reported as a new entity for over a decade. In Japan there are few reports of PSRA. We encountered four children with arthritis accompanied with Group A streptococcal infection in our department. We investigated our cases and the recent Japanese literature. Japanese cases of PSRA are frequently accompanied with uveitis and erythema nodosum, and tonsillectomy resolved their symptoms in some cases. There were overlap cases between ARF, juvenile idiopathic arthritis, and PSRA., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Invasive meningococcal disease (IMD) caused by the serogroup W (MenW) sequence type-11 complex strain has recently emerged worldwide. Meningococcal infections due to this strain are associated with high case fatality and often atypical clinical manifestations. However, the annual IMD incidence was low, and MenW is rare in Japan. We described the first Japanese case of meningococcal meningitis and meningococcemia caused by this strain in a previously healthy 27-year-old woman. This case showed various neurological complications such as abducens palsy, cerebellitis, and cerebellar infarction, and reactive arthritis. This case provides useful information on the possibility of spreading IMD strains and the cause of various complications., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Reactive arthritis is usually regarded as a form of spondylarthritis. Patients generally present with an acute asymmetrical oligoarthritis following an episode of diarrhea or urethritis. The most frequent involved pathogens are Salmonella, Shigella, Campylobacter and Chlamydia trachomatis. Additional causative pathogens have been described. Non-steroidal anti-inflammatory drugs are the first line treatment for reactive arthritis, associated with physiotherapy. Occasionally, a short course of glucocorticoids or an intra-articular injection is needed. Chlamydia induced reactive arthritis should be treated with antibiotics. Some patients experience chronic persistent arthritis. These patients could benefit from a treatment with DMARDs such as sulfasalazine. In refractory cases, TNF-inhibitors are sometimes used., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Objective: Reactive arthritis (ReA) is a sterile arthritis following an extra-articular infection, usually of the gastrointestinal or genitourinary tract. The aim of this study was to assess the incidence and the clinical and therapeutic characteristics of ReA and to compare them with those of a historical cohort. We hypothesised that improved hygiene together with prevention and treatment of sexually transmitted infections may have decreased the incidence of ReA., Methods: All patients with ReA diagnosed in the University Hospital Centres of Lyon Sud and Besançon from January 2002 to December 2012 were included in the study retrospectively and were compared with ReA patients diagnosed from January 1986 to December 1996 in the same two hospitals. Medical records were reviewed, clinical features, treatments and outcomes were analysed and diagnoses were compared with international diagnostic criteria., Results: Twenty-seven patients were included between 2002 and 2012 compared with 31 between 1986 and 1996. The overall incidence of ReA in patients hospitalised in the rheumatology department did not change, although the current evolution is more severe with development of chronic disease in the form of more frequent spondyloarthritis. While the incidence of Chlamydiae trachomatis has decreased, new microbes are now found to be involved., Conclusions: ReA still exists and its incidence has been stable over the last 30 years. However, ReA currently more often progress to spondyloarthritis. Our study also highlights the need for diagnostic criteria that accurately detect ReA., (Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objective: Reactive arthritis (ReA) is an inflammatory disorder occurring several weeks after gastrointestinal or genitourinary tract infections. HLA-B27 positivity is considered a risk factor, although it is not necessarily predictive of disease incidence. Among nongenetic factors, the intestinal microbiome may play a role in disease susceptibility. The objective of this study was to characterize the gut microbiota and host gene interactions in ReA and postinfectious spondyloarthritis., Methods: Adult subjects with peripheral spondyloarthritis and control subjects with preceding infections who did not develop arthritis were prospectively recruited from a geographic region with a high prevalence of ReA. Clinical variables, HLA status, and 16S ribosomal RNA gene sequencing of intestinal microbiota were analyzed., Results: Subjects with ReA showed no significant differences from controls in gut bacterial richness or diversity. However, there was a significantly higher abundance of Erwinia and Pseudomonas and an increased prevalence of typical enteropathogens associated with ReA. Subjects with ultrasound evidence of enthesitis were enriched in Campylobacter, while subjects with uveitis and radiographic sacroiliitis were enriched in Erwinia and unclassified Ruminococcaceae, respectively; both were enriched in Dialister. Host genetics, particularly HLA-A24, were associated with differences in gut microbiota diversity irrespective of disease status. We identified several co-occurring taxa that were also predictive of HLA-A24 status., Conclusion: This is the first culture-independent study characterizing the gut microbial community in postinfectious arthritis. Although bacterial factors correlated with disease presence and clinical features of ReA, host genetics also appeared to be a major independent driver of intestinal community composition. Understanding of these gut microbiota-host genetic relationships may further clarify the pathogenesis of postinfectious spondyloarthritides., (© 2017, American College of Rheumatology.)

Competing Interests: Competing interests: KK, TM and YMo received scholarship donations from AbbVie, Actelion, Astellas, Bristol-Myers, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, Japan Blood Products Organization, Mitsubishi-Tanabe, MSD, Pfizer, Shionogi, Takeda, Teijin and UCB. YMi received scholarship donations from Asahi Kasei, Astellas, Daiichi Sankyo, Kissei, Nippon Shinyaku, Ono, Pfizer and Takeda.

We report here on four cases of patients with strongly positive anti-citrullinated cyclic peptides (anti-CCP) antibodies and clinical features of seronegative spondyloarthritis (SpA) and reactive arthritis. The four patients had various clinical presentations: one had an initial diagnosis of seropositive rheumatoid arthritis (RA) with involvement of the sacroiliac joints (similar to previous reports of the association of two diseases); one had a clinical picture of reactive arthritis following an episode of an Escherichia coli positive urinary tract infection; and two had asymmetrical sacroiliitis (SII), but no evidence of peripheral joint involvement (never reported before). In all cases, high titers of anti-CCP antibodies were found. We present a comparison of the clinical manifestations, radiographic features and treatment regimens of these cases. Our report supports previous literature data of possible overlap existing between RA and SpA, but also presents for the first time the association of high titers of anti-CCP antibodies with SII and reactive arthritis in patients with no peripheral small joint involvement., (© 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

BACKGROUND The aim of this study was to explore the correlation between HLA-B27 and the intracellular elimination, replication, and trafficking of Salmonella enteritidis (S. enteritidis) collected from patients with reactive arthritis. MATERIAL AND METHODS Confocal microscopy, flow cytometry, and sandwich enzyme-linked immunosorbent assay (ELISA) were employed in this study to evaluate the localization of proteins of interest, to assess the intracellular trafficking of S. enteritidis, and to measure the production of cytokines of interest. RESULTS HLA-B27 was negatively associated with intracellular S. enteritidis elimination in healthy human monocytes/macrophages. In S. enteritidis infected monocytes/macrophages, HLA-27B was also negatively correlated with bacteria elimination but positively related to bacteria replication. S. enteritidis did not co-localize with NRAMP1 and LAMP1/2 in HLA-B27 cells. S. enteritidis did not co-exist with transferrin or dextran within HLA-B27 and A2 cells. CONCLUSIONS HLA-B27 is closely associated with the intracellular elimination and replication of S. enteritidis. Replicated bacteria in HLA-B27 monocytic cells were located within unique vacuoles rather than disturbing host endocytosis.

Yersinia enterocolitica (YE) biotype 1A is generally considered non-pathogenic, and the role of it in causing reactive musculoskeletal complications is unclear. We evaluated the capability of YE biotype 1A to induce reactive arthritis (ReA) and other reactive musculoskeletal symptoms. Analysis of self-reported musculoskeletal symptoms was supplemented with a telephone interview (with a permission to acquire copies of patient files from a local physician or hospital) and/or clinical examination of subjects with recent musculoskeletal symptoms after a positive stool culture for YE. The diagnoses of ReA and reactive tendinitis and enthesitis (ReTe) were defined as "definite" when based on clinical examination and/or on interview by phone and "probable" when based solely on the questionnaire. Of 120 subjects, who reported musculoskeletal symptoms, 100 were included in the final analysis. Among these 100 patients, 68% had YE biotype 1A, 16% YE bio/serotype 4, and 1% biotype 2 infection; the remaining 15% had different YE-like strains or a non-biotypable strain. Of the 21 patients with ReA and of the 14 patients with ReTe, the diagnosis was definite in 9 and 7 patients and probable in 12 and 7 patients, respectively. The clinical picture of ReA caused by YE biotype 1A was similar with other bio/serotypes of YE. The definite ReA due to YE biotype 1A occurred in middle-aged adults (5 men, 4 women) with the most frequently affected joints being the knees and ankles. We suggest that YE biotype 1A should be taken into account as a new trigger of ReA.

Introduction: Reactive arthritis due to Clostridium difficile infection is uncommon., Case Reports: We report two cases of reactive arthritis associated with C. difficile infection that occurred in a 40-year-old woman and a 47-year-old man. The literature review between 1976 (date of first reported case) and 2016 retrieved 54 observations (including our two cases). Reactive arthritis occurs most frequently in young subjects after a variable time frame according to C. difficile infection, involving one or several articulations. The issue is generally favourable with or without anti-inflammatory treatment., Conclusion: The increasing incidence of C. difficile infection makes more likely the occurrence of this related reactive arthritis. Therefore physicians should consider it in differential diagnosis of bacterial infections capable of causing reactive arthritis., (Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Reactive arthritis is classified as a spondyloarthropathy. Current concepts of disease suggest an infectious trigger, followed by inflammatory arthritis. Several mechanisms have been proposed to explain the interaction of host susceptibility and microorganism. Diagnosis relies on a compatible clinical syndrome and microbiologic confirmation of the pathogen. Antibiotic therapy seems useful in Chlamydia-triggered arthritis. The role of antibiotics in arthritis triggered by enteric pathogens is less clear. The role of tumor necrosis factor alpha inhibitors in therapy is evolving. Many patients have a course limited to a few months, but others experience extraarticular disease and more prolonged courses., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: One of the rare presentations of active pulmonary or even extrapulmonary tuberculosis is polyarthropathy which is the involvement of multiple large and small joints in the body; a reactive constellation known as Poncet's disease. This may sometimes be the sole manifestation of the disease before more obvious features develop. The pain experienced during polyarthritis can be crippling thereby limiting the mobility and activities of patients. Polyarthritis as a symptom of active tuberculosis can be easily misinterpreted for more common causes of polyarthritis such as rheumatological diseases that present similarly., Case Presentation: We describe the case of a 25-year-old Asian woman and a 45-year-old Asian man who presented with active tuberculosis where polyarthralgia was the first and only symptom for many months followed by pulmonary and pleural manifestations. Both patients showed dramatic improvement with anti-tuberculous therapy. The total duration of therapy was 6 months., Conclusions: Based on our observations, we propose that tuberculosis be included among the differentials for patients with unusual presentation of joint pains, especially in endemic regions and/or susceptible populations.

The following review summarizes the evidence on reactive arthritis (ReA), focussing on the latest relevant work on epidemiology, diagnosis, pathogenesis, and treatment. ReA is a joint inflammation that develops after a primary, extra-articular infection; the infection often involves the urogenital or gastrointestinal system, and less frequently the respiratory tract. The microbial agent causing the primary infection and triggering the arthritis cannot be cultured from the synovial compartment by standard methods; however, bacterial antigens or nucleic acids originating from Chlamydia trachomatis and other microbes can be detected within joint material. ReA occurs worldwide with a prevalence of 40/100,000 and an incidence of 5/100,000. The arthritis develops within days or weeks after the primary infection and usually affects the lower extremities. A dactylitis of the toes is highly typical, while axial or extra-articular manifestations are less common. The disease subsides in many cases within weeks or months, however relapses can occur and chronic forms are described in 30 % of patients.Antibiotic treatment is recommended for the active primary infection. Treatment of ReA focuses on alleviation of signs and symptoms. Severe and chronic forms require the use of immunomodulatory agents.

Aim: Poncet's disease is a well recognized form of reactive arthritis in the presence of extra-articular tuberculosis. There are very limited case reports even from countries where tuberculosis is common and there are no accepted diagnostic criteria for Poncet's disease. In the present study we are describing clinical features of Poncet's disease from a tuberculosis-endemic region along with a proposal of a new diagnostic criteria., Methods: All patients diagnosed as having Poncet's disease were included. The clinical details, demographic features, pattern of joint involvement, investigation findings, treatment details and clinical outcomes were recorded on a structured pro forma., Results: Twenty-three patients with Poncet's disease were identified during the study period. Thirteen patients had oligoarthritis and the rest had polyarthritis with ankle joint involvement being most common. The duration of joint symptoms varied from 3 days to 6 years. All patients had non-erosive and non-deforming arthritis. Systemic symptoms were absent in 48% of patients. Mantoux was positive in most cases (81%). Tuberculosis was extrapulmonary in most cases, lymph node tuberculosis being most common. All patients had complete resolution of joint symptoms with anti-tubercular treatment. All the factors contributing to eventual diagnosis of Poncet's disease were carefully analyzed and diagnostic criteria are proposed. In the proposed criteria, there are two essential, two major and three minor criteria. According to these criteria 19 patients had definite and three had probable Poncet's disease., Conclusion: The most common presentation of Poncet's is in the form of oligoarthritis. The proposed criteria can be used for diagnosing Poncet's disease., (© 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

We report the first case of reactive arthritis associated with lymphogranuloma venereum (LGV) in an Italian human immunodeficiency virus-negative woman with urogenital and rectal Chlamydia trachomatis L2 serovar infection. The LGV-associated arthritis has to be considered even when classic symptoms of arthritis are missing and in case of asymptomatic or cryptic LGV localizations.

Reactive arthritis is an under-studied complication of genital Chlamydia trachomatis infection (chlamydia). We assessed trends and risk factors for reactive arthritis in a large urban sexual health clinic. Using a case-control design, data on reactive arthritis cases and controls at the Sydney Sexual Health Centre over the period 1992-2012 were extracted and multivariate analyses were performed. Trend analyses were performed on reactive arthritis diagnoses. Over the 1992-2012 study period, 85 reactive arthritis cases were diagnosed at Sydney Sexual Health Centre. The rate of reactive arthritis diagnoses decreased over time (23 in 1992-1996 to one in 2007-2011 and none in 2012), while chlamydia diagnoses increased (770 in 1992-1996 to 2257 in 2007-2011). In multivariate analysis, factors independently associated with a reactive arthritis diagnosis were: being male (adjusted odds ratio [aOR] 3.27; 95% confidence interval [CI] 1.04-10.32; p = 0.043) or born overseas (aOR 2.69; 95% CI 1.27-5.70; p = 0.010), while a past sexually transmitted infection other than chlamydia or non-gonococcal urethritis was protective (aOR 0.21; 95% CI 0.10-0.45; p < 0.001). Reactive arthritis was not associated with current or recent chlamydia infection (p = 0.184) but was marginally associated with past non-gonococcal urethritis (p = 0.080). This study found a decline in reactive arthritis diagnoses despite an increase in chlamydia diagnoses., (© The Author(s) 2015.)

A 35-year-old man presented with polyarthritis and constitutional symptoms, and a recent history of multiple tick bites and skin rash on trekking holiday. He did not respond to oral doxycycline and cephalexine for presumed Lyme's disease. Further investigation confirmed strongly positive streptococcal serology. There was absence of clinical or echocardiography evidence of heart involvement and immunological screening for inflammatory arthritis was negative. In the absence of other major Jones criteria for acute rheumatic fever, besides polyarthritis and the serological evidence of a recent streptococcal infection, a diagnosis of post-streptococcal reactive arthritis (PSRA) was also made. He responded well to penicillin therapy and has been started on oral penicillin prophylaxis as per available guidance. As streptococcal infections in the adult population are increasingly reported, it is a timely opportunity to revisit PSRA, and develop comprehensive treatment and antibiotic prophylaxis guidelines., (2016 BMJ Publishing Group Ltd.)

In developing countries, one-third of patients with reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA) are triggered by Salmonella typhimurium. Synovial fluid mononuclear cells (SFMCs) of patients with ReA and uSpA proliferate to low molecular weight fractions (lmwf) of outer membrane proteins (Omp) of S. typhimurium. To characterize further the immunity of Omp of Salmonella, cellular immune response to two recombinant proteins of lmwf, OmpA and OmpD of S. typhimurium (rOmpA/D-sal) was assessed in 30 patients with ReA/uSpA. Using flow cytometry, 17 of 30 patients' SF CD8(+) T cells showed significant intracellular interferon (IFN)-γ to Omp crude lysate of S. typhimurium. Of these 17, 11 showed significantly more CD8(+) CD69(+) IFN-γ T cells to rOmpA-sal, whereas only four showed reactivity to rOmpD-sal. The mean stimulation index was significantly greater in rOmpA-sal than rOmpD-sal [3·0 (1·5-6·5) versus 1·5 (1·0-2·75), P < 0·005]. Similarly, using enzyme-linked immunospot (ELISPOT) in these 17 patients, the mean spots of IFN-γ-producing SFMCs were significantly greater in rOmpA-sal than rOmpD-sal [44·9 (3·5-130·7) versus 19·25 (6-41), P < 0·05]. SFMCs stimulated by rOmpA-sal produced significantly more proinflammatory cytokines than rOmpD-sal: IFN-γ [1·44 (0·39-20·42) versus 0·72 (0·048-9·15) ng/ml, P < 0·05], interleukin (IL)-17 [28·60 (6·15-510·86) versus 11·84 (6·83-252·62) pg/ml, P < 0·05], IL-23 [70·19 (15-1161·16) versus 28·25 (> 15-241·52) pg/ml, P < 0·05] and IL-6 [59·78 (2·03-273·36) versus 10·17 (0·004-190·19) ng/ml, P < 0·05]. The rOmpA-sal-specific CD8(+) T cell response correlated with duration of current synovitis (r = 0·53, P < 0·05). Thus, OmpA of S. typhimurium is a target of SF CD8(+) T cells and drives SFMC to produce increased cytokines of the IL-17/IL-23 axis which contribute to the pathogenesis of Salmonella-triggered ReA., (© 2016 British Society for Immunology.)

In the differential diagnostics of autoimmune-mediated rheumatic diseases, rheumatologists often have to consider infections (e. g. Lyme arthritis) or reactive diseases (e. g. reactive arthritis after urogenital bacterial infections). Furthermore, infections with an atypical presentation or caused by atypical pathogens (opportunistic infections) can complicate the immunosuppressive therapy of autoimmune diseases. For this purpose not only conventional microbiological culture methods but also PCR-based methods are increasingly being applied for the direct detection of pathogens in clinical specimens. The aim of this overview is to present commonly used PCR methods in the clinical practice of rheumatology and to describe their benefits and limitations compared to culture-based detection methods.

Background: Deaths due to tuberculosis have reached 2.5 million cases per year worldwide. Poncet's disease is an infrequent form of tuberculosis characterised by a clinical picture of polyarthritis., Clinical Case: A 24-year-old male presented with morning stiffness, arthralgias, bilateral symmetric arthritis of the proximal interphalangeal joints, wrists, knees, ankles, and shoulders, and adenomegalies at the cervical, submandibular, left supraclavicular, axillary and inguinal levels, without fever. Laboratory results were as follows: ESR 44mm/h, C-reactive protein 4.35, normal levels of complement C3 and C4, negative rheumatoid factor and anticyclic citrullinated peptide antibodies, positive antinuclear antibodies with fine speckled pattern (1:320) and cytoplasm (1:160) pattern and negative anti-Smith, -double-stranded DNA, Sjogren's syndrome-antigen A and Sjogren's syndrome-antigen B. Histological report of cervical node tissue revealed granulomatous lesions compatible with tuberculosis. Rheumatoid arthritis and systemic lupus erythematosus were ruled out. Anti-tuberculosis agents were initiated that resolved the clinical picture. Diagnosis of Poncet's disease was confirmed., Conclusion: The differential diagnosis between tuberculosis and autoimmune inflammatory joint diseases is a clinical challenge., (Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.)

Current molecular genetic understanding of the metabolically active persistent infection state of Chlamydia trachomatis and Chlamydia pneumoniae in the synovium in patients with arthritis and spondyloarthritis favors a causal relationship. Here, we examine how adequately the accepted criteria for that etiologic relationship are fulfilled, emphasizing the situation in which these microorganisms cannot be cultivated by standard or other means. We suggest that this unusual situation of causality by chlamydiae in rheumatic disease requires establishment of a consensus regarding microorganism-specific terminology as well as the development of new diagnostic and classification criteria. Recent studies demonstrate the value of molecular testing for diagnosis of reactive arthritis, undifferentiated spondyloarthritis, and undifferentiated arthritis caused by C. trachomatis and C. pneumoniae in clinical practice. Data regarding combination antibiotic therapy is consistent with the causative role of chlamydiae for these diseases. Observations of multiple intra-articular coinfections require more research to understand the implications and to respond to them.

Diabetes insipidus is a disease in which large volumes of dilute urine (polyuria) are excreted due to vasopressin (AVP) deficiency [central diabetes insipidus (CDI)] or to AVP resistance (nephrogenic diabetes insipidus). In the majority of patients, the occurrence of CDI is related to the destruction or degeneration of neurons of the hypothalamic supraoptic and paraventricular nuclei. The most common and well recognized causes include local inflammatory or autoimmune diseases, vascular disorders, Langerhans cell histiocytosis (LCH), sarcoidosis, tumors such as germinoma/craniopharyngioma or metastases, traumatic brain injuries, intracranial surgery, and midline cerebral and cranial malformations. Here we have the opportunity to describe an unusual case of female patient who developed autoimmune CDI following ureaplasma urealyticum infection and to review the literature on this uncommon feature. Moreover, we also discussed the potential mechanisms by which ureaplasma urealyticum might favor the development of autoimmune CDI.