[Faecal microbiota study reveals specific dysbiosis in spondyloarthritis according to subtype, disease activity and treatment]. / Estudio de microbiota fecal revela disbiosis específica en espondiloartritis, según subtipo, actividad de la enfermedad y tratamiento.

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.

OBJETIVO: Comparar la diversidad y composición del microbioma gastrointestinal de pacientes con EspA. MÉTODOS: La secuenciación MiSeq de la región V3-V4 del gen ARN ribosomal 16, se realizó en ADN aislado de heces. Se excluyeron pacientes con EspA y EII simultánea. Se evaluaron diferencias para los índices de riqueza y diversidad por medio de QIIME 2™. Las diferencias entre medias> 0,2%, con un valor de p< 0,05, se asumieron significativas. Aval del Comité de Ética Institucional. RESULTADOS: 69 individuos incluidos, 49 con EspA (espondilitis anquilosante-EA 72,9%, artritis psoriásica-APs 18,8%, artritis reactiva-ARe 8,3%), cinco controles positivos-disbiosis y 15 controles-eubiosis. El tratamiento convencional en 42,9%, anti-IL-17 16,3%, y anti-TNF 40,8%. Por subtipo-EasP, se encontraron diferencias estadísticamente significativas a favor de EA para los índices de diversidad. Entre EA vs APs, hubo diferencia a favor de EA para Clostridium clostridioforme (p=0,002), Gemmiger formicilis (p=0,009), Roseburia inulivorans (p=0,008) y Lachnospira pectinoschiza. Entre EA vs ARe hubo diferencia a favor de EA para L. pectinoschiza (p=0,009), Ruminococcus callidus (p = 0,006), Clostridium ruminantium (p=0,031); G. formicilis (p=0,034). La diversidad y riqueza mostraron diferencias en pacientes con alta actividad para los índices de Simpson y Pielou. En alta actividad, se encontró menor enriquecimiento de Bacteroides eggerthii (p=0,0003), C. ruminantium (p= 0,026) y Alistipes putredinis (p= 0,035). El número de ASV fue superior en el grupo de anti IL-17 vs convencional (p=0.025), y una tendencia entre anti IL-17 vs anti-TNF (p=0,09). En anti TNF hubo menor proporción para C. clostridioforme (p=0,023), G. formicilis (p=0,030) y R. callidus (p= 0,003). Y en anti IL-17, Alistipes indistinctus (p= 0,012), estuvo disminuida. CONCLUSIONES: Existen diferencias en la diversidad microbiana para los subtipos de EspA. El nivel de actividad de la enfermedad es plausible para influir en la composición de microbiota fecal. El tratamiento con anti-TNFα, puede influenciar el ambiente del microbioma favoreciendo la restauración de la microbiota intestinal, mientras los anti IL-17 podrían mantener un ambiente inflamatorio.

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.

Disseminated Mycobacterial Infection With Reactive Polyarthritis (Poncet's Disease) During Immune-suppressive Treatment Including Ustekinumab for Pediatric Crohn's Disease.

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.

Diagnostic considerations in the clinical management of sudden swelling of the knee: a case report and review of the literature.

BACKGROUND: Reactive arthritis and septic arthritis rarely present concomitantly in the same joint and patient. Reactive arthritis presenting after coronavirus disease 2019 is also exceedingly rare, with less than 30 cases reported thus far. Less common pathogens such as Clostridium difficile have been reported to cause reactive arthritis, especially in patients with a positive human leukocyte antigen B27, and therefore should be considered in diagnostic algorithms. The aim of this case report is to highlight the difficulties and precautions in discerning and diagnosing patients presenting with sudden swelling of the knee. CASE PRESENTATION: We report the case of a 70-year-old Caucasian male with a recent history of coronavirus disease 2019 upper respiratory infection and diarrhea and negating trauma, who presented with a swollen and painful knee. Pain and swelling worsened and inflammatory parameters increased after an intraarticular corticosteroid injection. The patient was therefore treated with arthroscopic lavage and intravenous antibiotics for suspected septic arthritis. Synovial fluid and synovium samples were taken and sent for microbiological analysis. Synovial fluid cytology showed increased leukocytes at 10,980 × 106/L, while polymerase chain reaction and cultures came back sterile. Clostridium difficile toxin was later detected from a stool sample and the patient was treated with oral vancomycin. The patient was tested for the presence of human leukocyte antigen B27, which was positive. We present a review of the literature about the challenges of distinguishing septic from reactive arthritis, and about the mechanisms that predispose certain patients to this rheumatological disease. CONCLUSIONS: It is still a challenge to differentiate between septic and reactive arthritis of the knee, and it is even more challenging to identify the exact cause of reactive arthritis. This case report of a human leukocyte antigen-B27-positive patient highlights the necessity of contemplating different, less common causes of a swollen knee joint as a differential diagnosis of an apparent septic infection, especially in the coronavirus disease 2019 era. Treating the patient for septic arthritis prevented any possible complications of such a condition, while treating the C. difficile infection contributed to the substantial relief of symptoms.

Reactive arthritis: the convoluted history of Reiter's disease.

Reactive arthritis, previously known as Reiter's Syndrome or Disease was a post-dysenteric, asymmetrical acute large joint polyarthritis, with fever, conjunctivitis, iritis, purulent urethral discharge, rash and penile soft tissue swelling. Although the eponym was given to Hans Reiter, various forms of the condition have been recorded in history a few hundred years before Reiter. Two French doctors, Noel Fiessinger (1881-1946) and Edgar Leroy (d. 1965), presented a paper at la Societe des Hopitaux-in Paris on the 8th December 1916 on dysentery in 80 soldiers on the Somme, and four of whom developed a "syndrome conjunctivo-uretro-synovial". Their paper was given 4 days before Reiter's presentation on 12th December 1916 at the Society of Medicine in Berlin, on a German army officer with an illness similar to those described by Fiessinger and Edgar Leroy. It is documented that Hans Reiter was one of a number of University professors who signed an oath of allegiance to Adolf Hitler in 1932. For socio-ethical reasons and for clinical utility, Reiter's syndrome is now known as reactive arthritis.

Poncet's disease and tubal tuberculosis: A case report.

A 25-year-old female patient was admitted to the hospital with abdominal pain, loss of appetite, and weight loss for the last 5 months. The patient underwent paracentesis five times and was referred to our clinic after peritonitis findings were detected. Tubal tuberculosis was detected during her hospitalization. The patient, who also developed joint pain, was diagnosed with Poncet's disease. She was given quadruple antituberculosis treatment. After the treatment, the patient's joint pain regressed, and the adnexal mass due to tubal tuberculosis disappeared. In this case report, we wanted to present a rare case of Poncet's disease with tubal tuberculosis.

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.

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.

Role of ultrasound and inflammatory factors in the management of pediatric hip joint effusion.

BACKGROUND: Septic arthritis is an important differential diagnosis of hip joint pain. Joint aspiration analysis is a necessary diagnostic measure for septic arthritis. In order to reduce the need for joint aspiration, we compared the combination of ultrasound findings and laboratory findings to separate septic arthritis from reactive arthritis. METHODS: Children aged < 14 years who were referred to Akbar pediatric hospital in 2020-2022 with hip pain or limping were included in this longitudinal study. Participants underwent ultrasound examinations of the hip and blood samples were obtained from them. After confirming an effusion, dependent on patient status and clinical diagnosis, one of the following approaches was recommended; the close follow-up, or the ultrasound-guided aspiration of the hip joint effusion, and or arthrotomy. The various ultrasound and laboratory were documented. Data were analyzed and P < 0.001 being considered statistically significant. RESULTS: Overall, 115 patients with a mean age of 3.43 ± 5.76 years, 46 of whom were girls, were studied. The final diagnosis in 23 cases (20.0%) was septic arthritis and 92 (80.0%) had reactive arthritis. C-reactive protein (CRP) and The erythrocyte sedimentation rate (ESR) unlike aspirate volume, effusion volume measured on ultrasound, capsule thickness, total thickness, and recorded capsule-to-effusion ratio were significantly higher in patients with septic arthritis (P < 0.001). There was a significant agreement between the volume of measured fluid in the anterior recess and the volume of aspirated fluid (2.5 times, P < 0.001). Septic arthritis was not observed in any of the patients with effusion volume in anterior recess less than 0.5 cc and ESR less than 40 mm/hr or CRP less than 15 mg/L. CONCLUSION: Since septic arthritis was not observed in any of the patients with effusion volume < 0.5 cc and normal inflammatory factors (ESR or CRP), conservative management and close follow-up can be recommended in these patients instead of joint fluid aspiration.

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.

Azacitidine as a rare cause of reactive arthritis in a patient with acute myeloid leukemia.

INTRODUCTION: Azacitidine (AZA), a demethylating agent, is one of the mainstay treatments for patients with myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML) who are ineligible for curative allogeneic stem-cell transplantation and is recommended as first-line treatment in multiple countries. While arthralgia and myalgia have been commonly reported as side effects, the incidence of drug-induced reactive arthritis has only been reported twice so far. CASE REPORT: We present a retrospective overview of a clinical case of a 71-year-old patient that developed new cytopenias on a background of Chronic Lymphocytic Leukaemia and was diagnosed with therapy-associated AML. His treatment included an indefinite course of AZA to induce remission and optimise long-term survival which resulted in a satisfactory haematological response. However, after his ninth AZA cycle, he presented to the emergency department with knee swelling and erythema and conjunctivitis. MANAGEMENT AND OUTCOMES: Arthrocentesis of the knee revealed reactive arthritis with no crystal or organism growth. His symptoms were managed effectively with conservative management including NSAIDs, analgesia and temporary immobilization for joint rest. The adverse drug reaction probability score in our study was calculated as six and adverse drug reaction was thus assigned to the "probable" category. CONCLUSION: We report a case that points to AZA as a probable cause of arthritis flares in MDS patients. The current limitation of this study is the lack of available data, future reviews and research will aid in providing stronger evidence of a correlation between arthritis and AZA treatment.

Inflammatory Arthritis After COVID-19: A Case Series.

BACKGROUND Some patients who have recovered from acute infection with SARS-CoV-2 develop persistent symptoms that have been termed post-COVID syndrome (PoCoS). PoCoS can affect the musculoskeletal system, with arthralgia and myalgia being common. Preliminary evidence suggests that PoCoS is an immune-mediated condition that not only predisposes but also precipitates pre-existing inflammatory joint diseases such as rheumatoid arthritis and reactive arthritis. Here, we describe a series of patients who presented to our Post-COVID Clinic and were found to have inflammatory arthritis (reactive and rheumatoid arthritis). CASE REPORT We present 5 patients who developed joint pain several weeks after recovery from acute SARS-CoV-2 infection. These patients were seen in our Post-COVID Clinic and came from locations across the United States. All 5 patients were women, with age of diagnosis of COVID-19 disease between 19 and 61 years (mean 37.8 years). All patients presented with joint pain as the primary concern to the Post-COVID Clinic. Abnormal joint imaging was present in all patients. Treatments varied and included non-steroidal anti-inflammatory drugs, acetaminophen, corticosteroids, immunomodulators (golimumab), methotrexate, leflunomide, and hydroxychloroquine. CONCLUSIONS COVID-19 disease is a potential cause of inflammatory arthritis, with both rheumatoid arthritis and reactive arthritis demonstrated in our PoCoS population. Care must be taken to identify these conditions, as there are treatment ramifications.

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.

Autoimmune disorders caused by intravesical bacillus Calmette-Guerine treatment: A systematic review.

Intravesical bacillus Calmette-Guérin (BCG) is a common and highly effective treatment for non-muscle invasive urothelial carcinoma of the urinary bladder. BCG may cause an autoimmune reaction in some patients. One hundred and fifty-eight papers were analyzed, for a total of hundred and thirty patients with reactive arthritis, sixty patients with ocular manifestations and eighteen patients with other rheumatologic diseases. Among 130 subjects with reactive arthritis, an autoimmune symptom occurred after 5 instillations of intravesical BCG (IQR 4-6), which represents 5 weeks in most cases. Fifty-one patients had concurrent ocular involvement. The resolution of symptoms was achieved in a median of 32.5 days (IQR 14-90). Forty-two men and twenty women had ocular manifestations, most commonly conjunctivitis. Patients with HLA-B27 typing had earlier presentation of ocular symptoms related to the number of instillations (4.5 vs 6 [p < 0.05]. Resolution of symptoms was achieved at a median of 128 days (IQR 21-150). Among patients treated with NSAIDs (either with or without steroids), the duration of the disease was significantly shorter in both the articular and the ocular groups (28 vs. 120 [p < 0.05] and 30 vs.105 [p < 0.05], respectively). Other autoimmune manifestations included general autoimmune diseases, such as vasculitis, psoriasis and myasthenia gravis.