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: 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.

Reactive arthritis occurring after COVID-19 infection: a narrative review.

PURPOSE: Reactive arthritis is acute aseptic arthritis occurring 1 to 4 weeks after a distant infection in a genetically predisposed individual. It may occur after COVID-19 infection. We summarize, in this article, the current findings of reactive arthritis following COVID-19 infection. METHODS: A literature search has been performed from December 2019 to December 2021. We included case reports of reactive arthritis occurring after COVID-19 infection. We collected demographic, clinical, and paraclinical data. RESULTS: A total of 22 articles were reviewed. There were 14 men and 11 women with a mean age of 44.96 + 17.47 years. Oligoarticular involvement of the lower limbs was the most frequent clinical presentation. The time between arthritis and COVID infection ranged from 6 to 48 days. The diagnosis was based on clinical and laboratory findings. The pharmacological management was based on non-steroidal anti-inflammatory drugs in 20 cases. Systemic or local steroid therapy was indicated in 13 patients. Sulfasalazine was indicated in two cases. Alleviation of symptoms and recovery were noted in 22 cases. The mean duration of the clinical resolution was 16 + 57 days. CONCLUSION: The diagnosis of reactive arthritis should be considered in patients with a new onset of arthritis following COVID-19 infection. Its mechanism is still unclear.

Reactive arthritis following COVID-19: cause for concern.

Low-quality evidence suggests that COVID-19 may trigger reactive arthritis one to four weeks after the infection. Post COVID-19 reactive arthritis resolves within a few days, and no additional treatment is required. Established diagnostic or classification criteria for reactive arthritis are missing, and a deeper understanding of the immune mechanism related to COVID-19 prompt us to further investigate the immunopathogenic mechanisms capable of promoting or contrasting the development of specific rheumatic diseases. Caution should be exerted when managing post-infectious COVID-19 patient with arthralgia.

[Reactive arthritis]. / Reaktive Arthritis.

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.

Quo vadis reactive arthritis?

PURPOSE OF REVIEW: We provide an overview of recent articles which describe new thinking regarding HLA-B27-associated reactive arthritis (ReA), including those additional infection-related arthritides triggered by microbes that often are grouped under the term ReA. RECENT FINDINGS: With the advent and continuation of the pandemic, an increasing number of cases and case series of post-COVID-19 arthritis have been reported and classified as ReA. Further, arthritis after COVID-19 vaccination is a new entity included within the spectrum of ReA. New causative microorganisms identified in case reports include Clostridium difficile, Mycoplasma pneumoniae, Giardia lamblia, Leptospira , and babesiosis. SARS-CoV-2 is emerging as a significant etiologic agent for apparent ReA. SUMMARY: It is now clear that comprehensive clinical and laboratory investigations, synovial fluid analyses, and close follow-up of patients all are essential to differentiate ReA from diseases that may present with similar clinical attributes. Further, and importantly, additional research is required to define the wide diversity in causative agents, epidemiology, and rare case presentations of these arthritides. Finally, new classification and diagnostic criteria, and updated treatment recommendations, are essential to the advancement of our understanding of ReA.

Surgically treated reactive arthritis of the ankle after COVID-19 infection: A case report.

A 37-year-old man developed right ankle pain and swelling six days after being diagnosed with coronavirus disease (COVID-19). Despite conservative treatment, his ankle symptoms persisted. Magnetic resonance imaging and computed tomography showed synovial hypertrophy and bone erosion in the ankle. Following arthroscopic synovectomy, performed 69 days after the COVID-19 diagnosis, the pain improved significantly. The clinical course was consistent with that of reactive arthritis following severe acute respiratory syndrome coronavirus 2 infection. The pathological findings resembled rheumatoid nodules. The bone erosion may have originated from the inflammatory pathway, which resembles the mechanism of rheumatoid arthritis.

Clinical profiles of post-infectious arthritis and transient synovitis of the hip in children.

BACKGROUND: Acute inflammatory arthritides can present as a result of immune reaction following infections. Post-infectious arthritis and transient synovitis of the hip in children are included in this disease entity. The aim of this study was to describe the clinical profiles of post-infectious arthritis and transient synovitis of the hip in Thai children. METHODS: A retrospective review was performed at a tertiary care hospital in Bangkok, Thailand from January 2005 to July 2017. RESULTS: Eighty-six patients (56 boys and 30 girls) were included in this study. Mean age was 8.4 ± 4.8 years. Reactive arthritis was diagnosed in two patients (2.3%) following Salmonella spp. and Chlamydia trachomatis infections. Post-streptococcal reactive arthritis was present in 10 patients (11.6%). Transient synovitis of the hip was found in 30 patients (34.9%). Forty-four patients (51.2%) were clinically diagnosed with post-infectious arthritis. Mono/oligoarthritis was the most common clinical profile (84.9%). The distribution of lower-extremity involvement was as follows: hip, 47.6%; knee, 46.5%; and ankle joints, 30.2%. The documented preceding illness consisted mostly of upper respiratory tract symptoms (30.2%). Non-steroidal anti-inflammatory drugs were prescribed for 70 patients (81.4%). CONCLUSION: Mono/oligoarthritis of the lower extremity was the main clinical profile. Preceding viral illness was documented in one-third of children. Reactive arthritis was rarely seen.

Knowledge and Perceptions of Reactive Arthritis Diagnosis and Management Among Healthcare Workers During the COVID-19 Pandemic: Online Survey.

BACKGROUND: Reactive arthritis (ReA) is an often neglected disease that received some attention during the coronavirus disease 2019 (COVID-19) pandemic. There is some evidence that infection with severe acute respiratory syndrome coronavirus 2 can lead to "reactive" arthritis. However, this does not follow the classical definition of ReA that limits the organisms leading to this condition. Also, there is no recommendation by any international society on the management of ReA during the current pandemic. Thus, a survey was conducted to gather information about how modern clinicians across the world approach ReA. METHODS: An e-survey was carried out based on convenient sampling via social media platforms. Twenty questions were validated on the pathogenesis, clinical presentation, and management of ReA. These also included information on post-COVID-19 arthritis. Duplicate entries were prevented and standard guidelines were followed for reporting internet-based surveys. RESULTS: There were 193 respondents from 24 countries. Around one-fifth knew the classical definition of ReA. Nearly half considered the triad of conjunctivitis, urethritis and asymmetric oligoarthritis a "must" for diagnosis of ReA. Other common manifestations reported include enthesitis, dermatitis, dactylitis, uveitis, and oral or genital ulcers. Three-fourths opined that no test was specific for ReA. Drugs for ReA were non-steroidal anti-inflammatory drugs, intra-articular injections, and conventional disease-modifying agents with less than 10% supporting biological use. CONCLUSION: The survey brought out the gap in existing concepts of ReA. The current definition needs to be updated. There is an unmet need for consensus recommendations for the management of ReA, including the use of biologicals.

Reactive Arthritis After Intravesical Bacillus Calmette-Guérin Therapy.

ABSTRACT: Reactive arthritis (ReA) is a sterile arthritis that occurs in genetically predisposed individuals secondary to an extra-articular infection, usually of the gastrointestinal or genitourinary tract. Sterile arthritis associated with instillation of intravesical bacillus Calmette-Guérin (iBCG) therapy used for bladder cancer can also be included under ReA based on the pathogenic mechanism. Similar to spondyloarthritis, HLA-B27 positivity is a known contributor to the genetic susceptibility underlying iBCG-associated ReA. Other genetic factors, such as HLA-B39 and HLA-B51, especially in Japanese patients, can also be involved in the pathophysiology of iBCG-associated ReA. The frequencies of ReA- and ReA-related symptoms are slightly different between Japanese and Western studies. Proper understanding of possible complications, their epidemiology and pathogenesis, and their management is important for the rheumatologist when noting symptomatic patients using iBCG. Herein, we will review the most current information on ReA after iBCG therapy.

Reactive, infectious, or postinfectious arthritis?

The issue of reactive arthritis belongs to one of the most complex problems in rheumatology. Although the original concept of reactive arthritis as a „sterile arthritis“ has already been overcome, much remains unclear. Non-uniform terminology, classification and diagnostic criteria as well as treatment guidelines leave room for different interpretations of this issue. Therefore it is difficult for non-rheumatologists (internal medicine physicians and general practitioners) to find their way around this topic. Our comprehensive report discusses the latest findings from etiology to treatment of reactive arthritis. It also addresses the aforementioned controversies from terminology to the latest list of causative pathogens, including viruses, parasites and vaccines.

NMR-Based Metabolomics Revealed the Underlying Inflammatory Pathology in Reactive Arthritis Synovial Joints.

Reactive arthritis (ReA) is an aseptic synovitis condition that often develops 2-4 weeks after a distant (extra-articular) infection with Chlamydia, Salmonella, Shigella, Campylobacter, and Yersinia species. The metabolic changes in the synovial fluid (SF) may serve as indicative markers to both improve the diagnostic accuracy and understand the underlying inflammatory pathology of ReA. With this aim, the metabolic profiles of SF collected from ReA (n = 58) and non-ReA, i.e., rheumatoid arthritis (RA, n = 21) and osteoarthritis (OA, n = 20) patients, respectively, were measured using NMR spectroscopy and compared using orthogonal partial least-squares discriminant analysis (OPLS-DA). The discriminatory metabolic features were further evaluated for their diagnostic potential using the receiver operating characteristic (ROC) curve analysis. Compared to RA, two (alanine and carnitine), and compared to OA, six (NAG, glutamate, glycerol, isoleucine, alanine, and glucose) metabolic features were identified as diagnostic biomarkers. We further demonstrated the impact of ReA synovitis condition on the serum metabolic profiles through performing a correlation analysis. The Pearson rank coefficient (r) was estimated for 38 metabolites (profiled in both SF and serum samples obtained in pair from ReA patients) and was found significantly positive for 71% of the metabolites (r ranging from 0.17 to 0.87).

EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors.

BACKGROUND: Rheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance for rheumatologists addressing them, a European League Against Rheumatism task force was convened to harmonise expert opinion regarding their identification and management. METHODS: First, the group formulated research questions for a systematic literature review. Then, based on literature and using a consensus procedure, 4 overarching principles and 10 points to consider were developed. RESULTS: The overarching principles defined the role of rheumatologists in the management of irAEs, highlighting the shared decision-making process between patients, oncologists and rheumatologists. The points to consider inform rheumatologists on the wide spectrum of musculoskeletal irAEs, not fulfilling usual classification criteria of rheumatic diseases, and their differential diagnoses. Early referral and facilitated access to rheumatologist are recommended, to document the target organ inflammation. Regarding therapeutic, three treatment escalations were defined: (1) local/systemic glucocorticoids if symptoms are not controlled by symptomatic treatment, then tapered to the lowest efficient dose, (2) conventional synthetic disease-modifying antirheumatic drugs, in case of inadequate response to glucocorticoids or for steroid sparing and (3) biological disease-modifying antirheumatic drugs, for severe or refractory irAEs. A warning has been made on severe myositis, a life-threatening situation, requiring high dose of glucocorticoids and close monitoring. For patients with pre-existing rheumatic disease, baseline immunosuppressive regimen should be kept at the lowest efficient dose before starting immunotherapies. CONCLUSION: These statements provide guidance on diagnosis and management of rheumatic irAEs and aim to support future international collaborations.

NMR-based clinical metabolomics revealed distinctive serum metabolic profiles in patients with spondyloarthritis.

Spondyloarthritis (SpA) is a common rheumatic disorder of the young, marred by delay in diagnosis, and paucity of biomarkers of disease activity. The present study aimed to explore the potential of serum metabolic profiling of patients with SpA to identify biomarker for the diagnosis and assessment of disease activity. The serum metabolic profiles of 81 patients with SpA were compared with that of 86 healthy controls (HCs) using nuclear magnetic resonance (NMR)-based metabolomics approach. Seventeen patients were followed up after 3 months of standard treatment, and paired sera were analyzed for effects of therapy. Comparisons were done using the multivariate partial least squares discriminant analysis (PLS-DA), and the discriminatory metabolic entities were identified based on variable importance in projection (VIP) statistics and further evaluated for statistical significance (p value < 0.05). We found that the serum metabolic profiles differed significantly in SpA as compared with HCs. Compared with HC, the SpA patients were characterized by increased serum levels of amino acids, acetate, choline, N-acetyl glycoproteins, Nα-acetyl lysine, creatine/creatinine, and so forth and decreased levels of low-/very low-density lipoproteins and polyunsaturated lipids. PLS-DA analysis also revealed metabolic differences between axial and peripheral SpA patients. Further metabolite profiles were found to differ with disease activity and treatment in responding patients. The results presented in this study demonstrate the potential of serum metabolic profiling of axial SpA as a useful tool for diagnosis, prediction of peripheral disease, assessment of disease activity, and treatment response.

Poncet's Disease: A Case Report.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB). It spreads from one person to the another through the air while coughing, spitting, speaking or sneezing. TB most commonly affects lungs but it can affect any organ system. Diagnosis of TB is made on the basis of microbiological evidence of MTB on microscopic examination, cultures and chest X-rays. Poncet's disease is a separate entity in which joints are involved in the form of joint pain and swelling without any microbiological evidence of MTB. It usually occurs in the background setting of pulmonary TB. This case focuses on importance of considering Poncet's disease in the differential diagnosis of paediatric polyarticular arthritis in TB endemic regions or if there is a history suggestive of TB exposure and infection.

[Post-Corona-Virus-Disease­19 arthritis. Manifestation under the clinical picture of a reactive arthritis]. / Post-COVID­19-Arthritis. Manifestation unter dem klinischen Bild einer reaktiven Arthritis.

A total of 13 case reports of reactive arthritis reported in the literature in connection with coronavirus disease 2019 (COVID­19) are reviewed. Men were affected more frequently than women. The arthritis was manifested 4-44 days after the infection or the occurrence of the COVID­19 symptoms. Acute arthritis was monoarticular or oligoarticular. Only 1 out of 7 patients examined was human-leucocyte-antigen(HLA)-B27 positive. A direct viral infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could not be detected in the synovial fluid and was not investigated in the synovial membrane. The arthritis was successfully treated with nonsteroidal anti-inflammatory drugs and/or intra-articular or systemic corticosteroids. The pathogenesis of post-COVID­19 reactive arthritis is unknown.

[Postinfectious reactive arthritis after chlamydia infection in competitive sports : Clinical management and current literature review]. / Postinfektiöse reaktive Arthritis nach Chlamydieninfektion im Leistungssport : Klinisches Management und aktuelle Literaturübersicht.

BACKGROUND: Reactive arthritis following infection with chlamydia is a rare but important differential diagnosis in atraumatic joint swelling. A delayed diagnosis often leads to prolonged periods of absence from physical activity. This can have serious consequences, especially for the career of competitive athletes. OBJECTIVES: Recommendation for the clinical management of postinfectious reactive arthritis for rapid diagnosis and targeted treatment in the symptomatic clinical course. MATERIALS AND METHODS: Review of the literature on the topics "chlamydia", "reactive arthritis", "postinfectious arthritis" and "sexually acquired reactive arthritis", including presentation of two clinical cases of postinfectious reactive arthritis after chlamydia infection from competitive sports. RESULTS AND CONCLUSION: Reactive arthritis following chlamydia infection in competitive athletes is a rare entity. However, it can be accompanied by far-reaching individual consequences, especially with regard to possible downtime in sports. Long-term consequences such as chronic joint damage in maintained synovitis must also be considered. In order to make a diagnosis, a specific anamnesis and the direct detection of the pathogen in the specimen of synovial fluid by polymerase chain reaction is essential. This allows a reliable diagnosis to be made with immediate initiation of therapy. However, a prolonged course of the disease cannot be excluded even if therapy is started in due time.

REACTIVE ARTHRITIS IN CHILDREN (REVIEW).

Reactive arthritis is an aseptic inflammatory arthritis that is associated with intestinal, urogenital, and nasopharyngeal infections, and represents a systemic clinical presentation of these infections. Reactive arthritis among children still remains an issue in pediatric rheumatology. The variety of the clinical manifestations makes it difficult to diagnose and detect reactive arthritis. Moreover, there is a risk that reactive arthritis without a proper treatment can lead to chronic destructive joint diseases. As the articles' analysis has shown, this topic in pediatrics has been neglected over the past 10 years. Thus, the paper presents data on the epidemiology, pathophysiology, clinical presentation and diagnosis of this disease, as well as recommendations for further studies.

Reactive Arthritis: Treatment Challenges and Future Perspectives.

PURPOSE OF THE REVIEW: Reactive arthritis is synovitis related to an infection away from the joint. The evolution is variable, frequently self-limited, but with the possible evolution to a prolonged form, generating functional incapacity and sequelae. RECENT FINDINGS: New microbiological families have been incriminated and pathophysiological links have been clarified, highlighting the role of the mucous membranes (gut in particular), specific cell populations, and the production of pro-inflammatory cytokines. First-line pharmacological treatment is based on NSAIDs. In case of failure, synthetic and more recently biological DMARDs are indicated. Only open data are available for biological DMARDs but suggest good efficacy and safety. Reactive arthritis has not disappeared. The diagnosis must be mentioned by the clinic and history to allow the rapid introduction of an appropriate treatment.