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.
UNASSIGNED: Reaktive Arthritis (ReA) ist definiert als Arthritis, die das Resultat von Infektionen in anderen Körperteilen darstellt, z. B. im Gastrointestinal- und Urogenitaltrakt. Zu den primären klinischen Manifestationen gehören selbstlimitierende asymmetrische Entzündungen großer Gelenke in den unteren Extremitäten mit akutem Beginn. Zwar galten bakterielle oder Chlamydieninfektionen lange als entscheidend in der Pathogenese, aber aktuellen Studien zufolge führt eine antibiotische Behandlung möglicherweise eher zur Aufrechterhaltung als zur Eradikation der Chlamydieninfektion im Wirt, was auf die Beteiligung anderer Mechanismen an der Reactive arthritis hinweist. Derzeit wird davon ausgegangen, dass Reactive arthritis mit Infektionsprozessen, einem genetischen Marker (HLA-B27) und immunologischen Störungen einhergeht. Als Autoimmunerkrankung ist dem Verständnis der Rolle des Immunsystems bei Reactive arthritis zunehmend Aufmerksamkeit gewidmet worden. Der Fokus der vorliegenden Arbeit liegt auf der Erläuterung der Mediationsvorgänge des Immunsystems bei Reactive arthritis und auf der Darstellung der Bedeutung von durch intestinale Dysbiose induzierte Immunkrankheiten und stressbedingte Faktoren bei Autoimmunerkrankungen, was neue Einsichten in das Verständnis der Reactive arthritis vermittelt.

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 (ReA) is uncommon. The present case is a Chinese man who has been treated with adalimumab and leflunomide to control ankylosing spondylitis (AS). During the treatment, the patient developed a range of symptoms, including fever, fatigue, pustular rash, suppurative urethritis, genital ulcers, oral ulcers, bilateral uveitis, heel pain and swelling and pain of the knee and ankle joints. The laboratory studies revealed the presence of HLA-B27, and urethral secretions were positive for Ureaplasma urealyticum. The patient was eventually diagnosed with ReA. The development of ReA may be related to the combination of adalimumab and leflunomide, which reduces immune function and triggers activation of potential U. urealyticum. The patient received 3 weeks of antibiotics, corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs), resulting in a significant improvement. The dose of corticosteroids was gradually reduced, and adalimumab was reintroduced. The patient was followed up for 3 months without recurrence.

Streptococcus gordonii (S. gordonii) belongs to the alpha-hemolytic Streptococcus group. It is a symbiotic bacterium found in the human oral mucosa which is present in large quantities on the surface of the teeth. It is generally considered nonpathogenic or weakly pathogenic and is known to cause subacute endocarditis; however, there are few reports of reactive arthritis (ReA) caused by S. gordonii. Herein, we report a case of ReA complicated by subacute infective endocarditis caused by S. gordonii and explore the possible pathogenic mechanism of ReA caused by S. gordonii.

BACKGROUND: Fibrinogen to albumin ratio (FAR) is a newly investigated indicator for inflammation. The study aimed to explore the potential ability of FAR in assessing the severity of inflammation in spondyloarthritis.
METHODS: The clinical data of 196 spondyloarthritis (SpA) patients, 66 osteoarthritis (OA) patients, and 81 healthy controls (HC) were collected in this retrospective study. The SpA group included 69 psoriatic arthritis patients, 47 reactive arthritis patients and 80 ankylosing spondylitis patients. Chi-square test and Mann-Whitney U test, Spearman\'s correlation test, regression analysis, and ROC analyses were used for the analysis of FAR.
RESULTS: FAR level in group SpA was higher than in OA or HC. In the SpA group, the reactive arthritis group was characterized by the highest FAR level. After matching the erythrocyte sedimentation rate, a significant difference occurred between groups SpA and OA, but not in SpA subgroups. The FAR level was significantly related to erythrocyte sedimentation rate and C-reactive protein. After regression and receiver operating characteristics analysis, FAR was considered the most potential pointer to evaluate inflammation in SpA with the area under curve of 0.95. The recommended cut-off value of FAR was 9.44 for serious inflammation and 8.34 for mild conditions.
CONCLUSIONS: FAR is closely related to inflammatory biomarkers and can be a potential indicator in the assessment of inflammation in spondyloarthritis.

The severe acute respiratory syndrome coronavirus 2-induced coronavirus disease 2019 (COVID-19) has had a global spread. Vaccines play an essential role in preventing the spread. However, almost all types of vaccines have been reported to be associated with adverse events. Reactive arthritis (ReA) after vaccination has been reported; however, ReA after COVID-19 vaccination has not been reported. We reported a 23-year-old woman who suffered from an acute ReA on her left knee joint after COVID-19 vaccination and discussed the etiology and preventive strategy. She presented with swollen, painful left knee joint for 18 d. She had been inoculated 0.5 ml CoronaVac vaccine on 0 d and the 14th day with deltoid intramuscular injection. Finally, she was diagnosed as ReA after CoronaVac vaccination and was administered a single intra-articular injection of 1 ml compound betamethasone. The swelling and pain nearly disappeared after 2 d. On 1month follow-up, her condition was normal. ReA after COVID-19 vaccination is rare. The benefits of vaccination far outweigh its potential risks and vaccination should be administered according to the current recommendations. Further attentions should be put to determine which individual is at higher risk for developing autoimmune diseases after COVID-19 vaccination. More versatile and safer vaccines should be explored.

The pathogenesis of reactive arthritis (ReA) has not been fully elucidated. In recent years, many researchers have confirmed that multiple cytokines are involved in the occurrence and development of ReA. Although ReA is self-limiting, it is still incurable for some patients who have no or a weak response to traditional drugs, such as non-steroidal anti-inflammatory agents, glucocorticoids and immunosuppressive agents. This is called refractory reactive arthritis. Currently, there is insufficient evidences for the treatment of refractory ReA with biological agents, though biological agents against cytokines have been developed over the past few years. This review summarizes the current development of clinical treatments of ReA with biological agents, which provides future investigations on refractory ReA with more evidence and references.

BACKGROUND: Reactive arthritis (ReA) is sterile arthritis triggered by bacterial gastrointestinal or urogenital infections. Although the pathogenesis of ReA remains unclear, genetic factors seem to play an important role. Different killer cell immunoglobulin-like receptors (KIRs) and their corresponding specific histocompatibility leukocyte antigen-C (HLA-C) ligand genotypes have been implicated in susceptibility and resistance to infections and autoimmune diseases but have, thus far, not been investigated in ReA.
METHODS: This study was conducted in 138 ReA patients (65 females, 73 males); aged 18-69 years (mean, 37 years) and 151 randomly selected healthy control individuals matched for ethnicity, age and sex. These subjects were genotyped for KIR genes and HLA-C alleles by polymerase chain reaction with sequence-specific primers.
RESULTS: The frequencies of inhibitory KIR2DL2 and KIR2DL5 were significantly lower in the ReA patients than in the controls (p = .005 and p = .033, respectively). The presence of more than seven inhibitory KIR genes was protective (p = .016). Moreover, we found that activating KIR2DS1 alone or in combination with the HLA-C1C1 genotype (which indicates the absence of the HLA ligands for their homologous inhibitory receptor KIR2DL1) is associated with susceptibility to ReA (p = .039 and p = .011, respectively), whereas KIR2DL2 in combination with the HLA-C1 ligand is associated with protection against ReA (p = .039).
CONCLUSIONS: These observations indicate that high levels of activating and low levels of inhibitory KIR signals may affect the functions of NK cells and T cells. This imbalance enables the innate and adaptive immune responses of the host to be easily triggered by pathogens, resulting in the overproduction of local and systemic cytokines that contribute to the pathogenesis of ReA.