Enteric Infection-Associated Reactive Arthritis: A Systematic Review and Meta-Analysis.

Background. The objective of this systematic review and meta-analysis was to estimate the proportions of individuals infected with Campylobacter, Escherichia, Salmonella, Shigella, or Yersinia who develop reactive arthritis. Methods. A systematic review was conducted, encompassing English-language articles published before January 2024, sourced from the Embase, PubMed, Scopus, and Web of Science databases. This review included observational studies that reported the occurrence of reactive arthritis (ReA) among patients with Campylobacter, Escherichia, Salmonella, Shigella, or Yersinia infections. Data extraction was carried out independently by two reviewers. Subsequently, a random-effects meta-analysis was performed, with heterogeneity assessed using the I2 value. Additionally, meta-regression was employed to investigate the potential influence of study-level variables on the observed heterogeneity. Results. A total of 87 studies were identified; 23 reported on ReA development after Campylobacter infection, 7 reported on ReA after Escherichia infection, 30 reported ReA onset after salmonellosis, 14 reported ReA after shigellosis, and 13 reported ReA after Yersinia infection. The proportion of Campylobacter patients who developed ReA was 0.03 (95% CI [0.01, 0.06], I2 = 97.62%); the proportion of Escherichia patients who developed ReA was 0.01 (95% CI [0.00, 0.06], I2 = 92.78%); the proportion of Salmonella patients was 0.04 (95% CI [0.02, 0.08], I2 = 97.67%); the proportion of Shigella patients was 0.01 (95% CI [0.01, 0.03], I2 = 90.64%); and the proportion of Yersinia patients who developed ReA was 0.05 (95% CI [0.02, 0.13], I2 = 96%). Conclusion. A significant proportion of Salmonella, Shigella, and Yersinia cases resulted in ReA. Nonetheless, it is important to interpret the findings cautiously due to the substantial heterogeneity observed between studies.

Looking back on 51 years of the Carol Nachman Prize in Rheumatology-significance for the field of spondyloarthritis research.

The city and casino of Wiesbaden, capital of the German state Hessen, have endowed the Carol Nachman Prize to promote research work in the field of rheumatology since 1972. The prize, endowed with 37,500 €, is the second highest medical award in Germany and serves to promote clinical, therapeutic, and experimental research work in the field of rheumatology. In June 2022, the 50-year anniversary was celebrated. In the symposium preceding the award ceremony, an overview was given on the significance of spondyloarthritis for the work of the awardees in the past 30 years. This overview has now been put together to inform the interested community of the work performed, including the opinion of the awardees regarding what they consider to be their most important contribution.

Distinguishing Acute Rheumatic Fever From Post-streptococcal Reactive Arthritis.

We report an initial episode of post-streptococcal reactive arthritis (PRSA) in a 61-year-old male with group A streptococcal (GAS) bacteremia. The disease is commonly reported in young children and young adults. Additionally, this patient exemplifies the nonlinear boundaries of acute rheumatic fever (ARF) and PRSA, bringing into question whether they are truly distinct disease entities. These two conditions oftentimes present in similar fashions, making it difficult for clinicians to determine a specific diagnosis. We highlight the importance of recognizing ARF versus PRSA as an incorrect diagnosis can lead to the development of harmful complications including rheumatic heart disease (RHD).

Chronic sexually acquired reactive arthritis secondary to Chlamydiatrachomatis.

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.

Reactive Arthritis as a Consequence of Infection by Clostridium difficile in a Pediatric Patient.

Reactive arthritis (RA) is the development of a sterile inflammatory arthritis usually associated with a previously known infection, most commonly from the gastrointestinal or urogenital tract. The diagnosis is clinical, based on the presence of acute oligoarticular arthritis of larger joints developing within two to four weeks of the infection. However, in some cases where the infection is not clear, the diagnosis is a challenge, like in the case presented here. We must always rule out past infections as a cause of arthritis by directly asking about the presence of symptomatology associated with it, presented in the past few weeks. It's important to emphasize that human leukocyte antigen B27 (HLA-B27) should not be used as a diagnostic tool, and it always needs to be correlated with the clinical features. There is no confirmed evidence in the literature that is in favor of prescribing antibiotic therapy during an acute presentation of RA as it usually presents after the infection is cured.

Reactive Arthritis After mpox Vaccination.

Autoimmune inflammatory reaction after vaccination is a rare clinical entity. Reactive arthritis has been described after various vaccinations, but not after mpox vaccination. Here we present a case of recently diagnosed reactive arthritis after mpox vaccination that presented in the context of unrelenting fever and diarrhea complicated by migratory arthritis and anterior uveitis. We have reported this case to the Vaccine Adverse Event Reporting System (VAERS).

16s RNA-based metagenomics reveal previously unreported gut microbiota associated with reactive arthritis and undifferentiated peripheral spondyloarthritis.

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.

Immunologic derangement caused by intestinal dysbiosis and stress is the intrinsic basis of reactive arthritis.

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.

Spondyloarthropathies and arthritis post-infection: a historical perspective.

The spondyloarthropathies are a group of conditions characterised by spinal joint pain and have related clinical, epidemiological and genetic-related features. Ankylosing spondylitis, reactive arthritis, the spinal form of psoriatic arthritis and Crohn's and colitis enteropathic arthritis are the major clinical entities of the spondyloarthropathies, and principally occur in HLA-B27 positive individuals. Ankylosing spondylitis is much more common in males than females. Patients are usually seronegative for rheumatoid factor, and extra-articular features including iridocyclitis, mucous membrane and skin lesions: aortitis, may occur in some patients. The reactive arthritis form classically occurs following an infection of the gastrointestinal or genitourinary tract. The Crohn's and colitis enteropathic arthritis forms often have an associated large joint asymmetrical arthritis. Also discussed are acute rheumatic fever and Lyme disease which are conditions where the individual develops arthritis after an infection.

Reactive arthritis following COVID-19: clinical case presentation and literature review.

Reactive arthritis (ReA) is a clinical condition typically triggered by extra-articular bacterial infections and often associated with the presence of HLA-B27. While ReA has traditionally been associated with gastrointestinal and genitourinary infections, its pathogenesis involves immune and inflammatory responses that lead to joint affections. The emergence of COVID-19, caused by SARS-CoV-2, has prompted studies of plausible associations of the virus with ReA. We present a case of ReA in a patient who survived COVID-19 and presented with joint affections. The patient, a 31-year-old man, presented with lower limb joints pain. SARS-CoV-2 was confirmed by PCR testing during COVID-19-associated pneumonia. Following a thorough examination and exclusion of all ReA-associated infections, a diagnosis of ReA after COVID-19 was confirmed. In addition, this article encompasses a study of similar clinical cases of ReA following COVID-19 reported worldwide.

Reactive arthritis as a rare complication of intravesical bacillus Calmette-Guérin treatment: Report of two cases.

Intravesical bacillus Calmette-Guérin (BCG) immunotherapy is recommended for non-muscle-invasive bladder cancer after transurethral resection. BCG-associated musculoskeletal adverse events are rare. We report two cases of BCG reactive arthritis that were unusually severe and refractory. These describe two male patients who presented with polyarthritis after BCG exposure. Ultrasonography-guided glucocorticoid injections, high-dose systemic glucocorticoids and the institution of sulfasalazine were required for achievement of remission. Bacillus Calmette-Guérin reactive arthritis can present as polyarthritis of small and medium joints or as mono-oligoarthritis of asymmetrical ankles and knees, frequently associated with tenosynovitis and enthesitis. The mechanism by which BCG promotes arthralgia and arthritis is poorly understood. The most well-accepted theory is that the BCG antigens migrate to different peripheral tissues, including the joints. There is also a lack of knowledge regarding risk factors, with possible genetic factors playing a role. As the two presented cases show, BCG-induced reactive arthritis should be considered in the differential diagnosis of arthritis and refractory tenosynovitis in BCG-exposed patients.

COVID-associated arthritis after severe and non-severe COVID-19: A systematic review.

AIM: Since the coronavirus outbreak became a global health emergency in 2020, various immune-based effects, such as inflammatory arthritis (IA), have been recorded. This study aimed to determine the role of COVID-19 severity on post-COVID arthritis. METHODS: We systematically reviewed 95 patients who developed arthritis after severe and non-severe COVID-19 infection by searching the databases, including PubMed, SCOPUS, and EMBASE. We used the term "COVID-associated arthritis" because there was no definite diagnostic method for classifying arthritides after COVID-19 infection, and the diagnosed arthritis types were based on the authors' viewpoints. RESULTS: After evaluating the data between the two severe and non-severe COVID-19-infected groups of patients, the results showed that the COVID-19 severity may affect the pattern of joint involvement in IA. In both groups, combination therapy, including oral nonsteroidal anti-inflammatory drugs with different types of corticosteroids, was the most common treatment. In addition, the mean age and comorbidities rate was higher in the severe COVID-19 group. Even though the patients in the severe COVID-19 group developed more serious COVID-19 symptoms, they experienced milder arthritis with better outcomes and more delayed onsets that required less aggressive therapy. CONCLUSION: We conclude that there may be an inverse relationship between COVID-19 severity and arthritis severity, possibly due to weaker immunity conditions following immunosuppressant treatments in patients with severe COVID-19.

Return to Play After the Diagnosis of Reactive Arthritis in a Professional Football Player.

In professional football, most of the injuries are traumatic; however, these athletes may suffer from rheumatologic diseases, that may present as sports-related injuries. Reactive arthritis (ReA) is classified as a sub-group of the spondyloarthritis family and is relatively rare. In this article, we highlight the successful return to play (RTP) process after the ReA diagnosis in an elite football player in the Portuguese first league. The athlete was able to RTP four months and one week after the diagnosis, had no ReA recurrence nor re-injury >8 months after RTP, and is playing at an elite level.

Spondyloarthritides.

The spondyloarthritides are a diverse group of distinct yet interrelated disease processes with overlapping clinical features. They are ankylosing spondylitis, reactive arthritis, inflammatory bowel disease-associated arthritis, and psoriatic arthritis. Genetically, these disease processes have been linked by the presence of HLA-B27. They manifest with axial and peripheral symptoms, such as inflammatory back pain, enthesitis, oligoarthritis, and dactylitis. The onset of symptoms can begin before the age of 45; however, because of the wide range of signs and symptoms, diagnosis can be delayed, leading to unchecked inflammation, structural damage, and later, restriction in physical mobility.

Systemic exposure to bacterial amyloid curli alters the gut mucosal immune response and the microbiome, exacerbating Salmonella-induced arthritis.

The Salmonella biofilm-associated amyloid protein, curli, is a dominant instigator of systemic inflammation and autoimmune responses following Salmonella infection. Systemic curli injections or infection of mice with Salmonella Typhimurium induce the major features of reactive arthritis, an autoimmune disorder associated with Salmonella infection in humans. In this study, we investigated the link between inflammation and microbiota in exacerbating autoimmunity. We studied C57BL/6 mice from two sources, Taconic Farms and Jackson Labs. Mice from Taconic Farms have been reported to have higher basal levels of the inflammatory cytokine IL - 17 than do mice from Jackson Labs due to the differences in their microbiota. When we systemically injected mice with purified curli, we observed a significant increase in diversity in the microbiota of Jackson Labs mice but not in that of the Taconic mice. In Jackson Labs, mice, the most striking effect was the expansion of Prevotellaceae. Furthermore, there were increases in the relative abundance of the family Akkermansiaceae and decreases in families Clostridiaceae and Muribaculaceae in Jackson Labs mice. Curli treatment led to significantly aggravated immune responses in the Taconic mice compared to Jackson Labs counterparts. Expression and production of IL - 1ß, a cytokine known to promote IL - 17 production, as well as expression of Tnfa increased in the gut mucosa of Taconic mice in the first 24 hours after curli injections, which correlated with significant increases in the number of neutrophils and macrophages in the mesenteric lymph nodes. A significant increase in the expression of Ccl3 in colon and cecum of Taconic mice injected with curli was detected. Taconic mice injected with curli also had elevated levels of inflammation in their knees. Overall, our data suggest that autoimmune responses to bacterial ligands, such as curli, are amplified in individuals with a microbiome that promote inflammation.

A case of reactive arthritis caused by a perianal abscess.

Reactive arthritis is an immune-mediated aseptic arthritis resulting from either genitourinary or intestinal tract in a genetically susceptible host. Reactive arthritis is not uncommon, and the most common infectious agents are Chlamydia trachomatis, Salmonella, Yersinia, and Shigella, some new infectious agents include Staphylococcus lugdunensis, Rothia mucilaginosa, and umbilical cord-derived Wharton's jelly, as well as the SARS-CoV-2 virus, which has been more studied in recent years. We found that reactive arthritis caused by infection of perianal abscesses is very rare and few cases have been described in the medical literature. We report a 21-year-old man with polyarticular swelling and pain, and subcutaneous hematoma at his right ankle joint; he was considered reactive arthritis. After treating with non-steroidal anti-inflammatory drugs, sulfasalazine, surgery, and antibiotics, the patient's arthralgia gradually improved and the symptoms largely disappeared at the 1-month follow-up.

Reactive Arthritis Following Coronavirus 2019 Infection in a Pediatric Patient: A Rare Case Report.

Reactive arthritis (ReA) following Coronavirus 2019 (COVID-19) infection has been described mainly in adults, and only two pediatric cases have been reported. We report a third case where ReA was found to be a sequela following COVID-19 infection. A 15-year-old right-handed Caucasian girl presented with severe left-wrist pain. She was experiencing fever, rash, and migratory oligoarthritis, and laboratory work-up showed elevated inflammatory markers and a positive COVID-19 IgG antibody test. Imaging revealed inflammatory arthropathy with wrist synovitis. The patient was diagnosed with ReA following COVID-19 infection and was treated surgically by wrist arthroscopic synovectomy after the failure of conservative management. It has been 1 year after her surgery, and she is doing well. Emerging case reports are linking ReA as a delayed response to COVID-19 infection; therefore, ReA should be included in the list of differential diagnoses in all patients with joint pain following COVID-19 infection.

Acute arthritis following SARS-CoV-2 infection: About two cases.

Joint involvement in COVID-19 may occur at different stages of the disease and maybe represented by non-specific arthralgia or by acute arthritis. We report two cases of COVID-19 infection that were complicated by postviral reactive arthritis. Case 1: A 47-year-old male was presented 20 days after a COVID-19 infection with acute right knee arthritis. On biologic data, erythrocyte sedimentation rate and C-reactive protein were normal, and immunologic data were negative. A joint puncture was performed showing a turbid fluid. Testing for microcrystals was negative, as well as the synovial fluid culture. An infectious investigation was conducted, which was negative. The patient's complaints improved significantly, with analgesics and non-steroidal anti-inflammatory drugs (NSAID). Case 2: A 33-year-old female presented with acute left knee arthritis evolving for 48 h, free of fever, after a COVID-19 infection treated 15 days ago. On examination, besides knee arthritis, the osteoarticular examination was normal. A biological inflammatory syndrome was noted in laboratory tests. A yellow fluid with multiple PNN was detected in the joint fluid aspiration, with a negative culture. The patient was treated by analgesics and NSAID. The follow-up was highlighted by the arthritis resolution. Conclusion: Both of our cases are consistent with what has already been reported in the literature confirming the development of PostCOVID arthritis and strengthen the impending necessity of wider studies to identify rheumatologic manifestations in the short- and long-terms after surviving COVID-19.

Reactive arthritis after COVID-19 vaccination: 17 cases.

OBJECTIVES: The aim of the study is to report a series of 17 cases of ankle bi-arthritis that occurred shortly after coronavirus disease 2019 RNA vaccination, and to discuss the potential role of these vaccines in the pathogenesis of this rheumatological manifestation. METHODS: All patients were examined in the same department and received a full work-up to investigate the usual causes of ankle bi-arthritis. No rheumatic inflammatory disease occurred after 9 months of follow-up. A post-vaccination serological follow-up in search of anti-Spike antibodies was requested for all patients. RESULTS: All patients recovered with low dose of prednisolone within <2 months, except one who could not be weaned off CS. The level of antibodies found was very high in all patients. CONCLUSION: The ankle bi-arthritis occurrence chronology, the follow-up and the similar clinical presentation might suggest a pathogenic role of RNA vaccination.