Treatment of Reactive Arthritis with Biological Agents.

PURPOSE OF THE REVIEW: Reactive arthritis (ReA) is an inflammatory joint condition triggered by an infection elsewhere in the body, and this review aims to provide a comprehensive synthesis of recent studies including case reports and case series to determine whether biologics are a treatment option. RECENT FINDINGS: Recent studies indicate that biological agents, including anti-TNF agents (infliximab, adalimumab, etanercept), anti-IL17 (secukinumab), and anti-IL6 (tocilizumab), are effective in treating refractory cases of ReA. Evidence suggests these agents are associated with significant clinical improvement. Notably, the data reveal that these biologics are generally well-tolerated, with a low incidence of major adverse events, which supports their safety profile for use in ReA. Biological agents, including anti-TNF, anti-IL17, and anti-IL6 therapies, can be safely and effectively used in the treatment of ReA when conventional therapies fail. It further emphasizes the need for a well-designed controlled trial to provide scientific basis for better informed clinical decisions in cases not responding to conventional treatment.

Bacterial amyloid curli activates the host unfolded protein response via IRE1α in the presence of HLA-B27.

Salmonella enterica serovar Typhimurium (STm) causes gastroenteritis and can progress to reactive arthritis (ReA). STm forms biofilms in the gut that secrete the amyloid curli, which we previously demonstrated can trigger autoimmunity in mice. HLA-B27 is a genetic risk factor for ReA; activation of the unfolded protein response (UPR) due to HLA-B27 misfolding is thought to play a critical role in ReA pathogenesis. To determine whether curli exacerbates HLA-B27-induced UPR, bone marrow-derived macrophages (BMDMs) isolated from HLA-B27 transgenic (tg) mice were used. BMDMs treated with purified curli exhibited elevated UPR compared to C57BL/6, and curli-induced IL-6 was reduced by pre-treating macrophages with inhibitors of the IRE1α branch of the UPR. In BMDMs, intracellular curli colocalized with GRP78, a regulator of the UPR. In vivo, acute infection with wild-type STm increased UPR markers in the ceca of HLA-B27tg mice compared to C57BL/6. STm biofilms that contain curli were visible in the lumen of cecal tissue sections. Furthermore, curli was associated with macrophages in the lamina propria, colocalizing with GRP78. Together, these results suggest that UPR plays a role in the curli-induced inflammatory response, especially in the presence of HLA-B27, a possible mechanistic link between STm infection and genetic susceptibility to ReA.

A toddler with transient synovitis and COVID-19 infection.

Transient synovitis of the hip is a common medical emergency in children. Although reactive arthritis in adults may occur 1-4 weeks after COVID-19 infection or post-vaccination, few reports of transient synovitis in children associated with acute COVID-19 infection have been made. Transient synovitis of the hip occurs most frequently in children 3-8 years of age with a recent upper respiratory infection, bacterial infection, or trauma. This case report presents a unique case of an otherwise healthy 15-month-old girl with right hip pain and the refusal to ambulate associated with COVID-19 infection.

A novel approach with tofacitinib for the management of keratoderma blennorrhagicum in reactive arthritis: a case report.

Reactive arthritis(ReA), a form of arthritis occurring post-infection, manifests with antecedent infection symptoms, arthritis, and extra-articular manifestations, categorizing it as spondyloarthritis. "Keratoderma blennorrhagicum" (characterized by pustular hyperkeratosis on palms and soles, resembling pustular psoriasis) represents the most typical skin manifestation of ReA, occurring in acute or chronic phases. Severe lesions necessitate systemic disease modifying anti-rheumatic drugs (DMARDs) or biologic therapies. This article reports a case of ReA with sacroiliitis and widespread pustular eruptions following a urinary tract infection. Treatment with sulfasalazine and thalidomide significantly improved sacroiliitis, but the skin rash remained persistent and recurring. Subsequent use of adalimumab and secukinumab resulted in worsening skin rash, prompting a switch to tofacitinib, leading to a remarkable improvement in pustular eruptions after 20 days of treatment. This case demonstrates successful application of tofacitinib in treating severe keratoderma blennorrhagicum refractory to conventional DMARDs and biologics, offering insights into JAK inhibition for challenging rheumatic diseases with skin involvement.

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 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.