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Background: It has been over a year since the first documented case of the COVID-19 virus was recorded. Since then, our understanding of this virus has continually evolved, however, its wide-ranging effects are still unfolding. Similar to previously studied viral infections, severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) has been shown to lead to a degree of autoimmunity in patients who are recovering from its effects. Due to its effects on the innate im-mune system, such as the toll-like receptors and complement system, a varying degree of pro-inflammatory markers can become widespread in those who continue to recover from the virus. This case series offers a unique perspective on how COVID-19 has had dramatic effects on those already suffering from inflammatory rheumatic conditions, such as rheumatoid arthritis, systemic lupus erythematosus, or fibromyalgia. As the ever-lasting effects of COVID-19 are still unfolding, this case series is one of few to discuss the development and changes of patients with rheumatic conditions. This study hopes to encourage larger studies to be conducted on the effects of COVID-19 on autoimmune conditions. Case presentation: Seven patients were identified with new manifestations of rheumatic conditions, which included 3 cases of rheumatoid arthritis, 2 cases of polymyalgia rheumatica, 1 case of reac-tive arthritis, and 1 case of cutaneous lupus. Post-COVID syndrome was also diagnosed in 7 other patients. Patients with rheumatoid arthritis presented with symptoms 4-5 weeks after being diagnosed with COVID-19. Symptoms of polyarticular joint pain, swelling, and morning stiffness were reported in this group. These patients were treated with disease-modifying anti-rheumatic drugs and experi-enced an improvement in symptoms on follow-up. Two cases of polymyalgia rheumatica were identified in patients that were previously diagnosed with COVID-19 six weeks prior. One patient had no significant past medical history and the other patient had a history of rheumatoid arthritis, which was well controlled. These patients experienced weakness and tenderness in the proximal joints with elevated levels of ESR and CRP. They were treated with prednisone and showed improvement. Reactive arthritis was diagnosed in 1 patient who presented with swelling in both hands and wrists 2 days after being diagnosed with COVID-19. This patient began to experience symptoms of reac-tive arthritis 2 days after resolution of initial COVID-19 symptoms and this persisted for 3 months. The patient was managed with methylprednisolone injections and NSAIDs, which improved her symptoms. Post-COVID syndrome was identified in 7 patients. All patients were female and had a history of well-controlled fibromyalgia. Patients generally experienced fatigue, headaches, and memory fog, which had variable onset from a few days and up to 4 weeks after being diagnosed with COVID-19. One patient had a complete recovery of her symptoms at follow-up 3 months after the initial presen-tation. The other 6 patients continued to report symptoms of post-COVID syndrome at follow-up. Patients were managed with lifestyle modifications and their previous fibromyalgia treatment. Conclusion: While cases of COVID-19 continue to rise, complications of this disease are still being discovered. Those who initially recover from COVID-19 may experience new-onset rheumatic con-ditions, worsening of previously diagnosed rheumatic conditions, or post-COVID syndrome. As we continue to learn more about the effects of COVID-19, the awareness of these manifestations will play a key role in the appropriate management of these patients.

A 20-year-old Caucasian man with a history of psoriasis presented to the emergency department due to a 2-week history of severe polyarthralgia and a 3-week history of non-bloody diarrhoea. The initial workup 2 days prior in an urgent care clinic returned negative for all enteric pathogens including Clostridioides difficile nucleic acid amplification test. Investigations revealed colitis on CT and pseudomembranous colitis on colonoscopy. The aspirate returned positive for C. difficile toxin. Tissue biopsies of the ascending, transverse, sigmoid colon and rectum were negative for chronicity to suggest inflammatory bowel disease with extraintestinal manifestation as the aetiology of polyarthralgia, which had been the most likely differential diagnosis until that point. The biopsy confirmed the diagnosis of reactive arthritis in the setting of C. difficile colitis. The patient improved on treatment with naproxen and was referred to rheumatology where he was found to be HLA-B27 positive.

We present the case of a 19-year-old male patient who developed symmetrical distal polyarthritis which was diagnosed as a reactive atypical arthritis caused by SARS-COV-2 infection after dismissing other causes of arthritis.

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.

Controversy has arisen among the overall benefit and potential risks in the use of corticosteroids for the treatment of pediatric bacterial meningitis. This systematic review and meta-analysis aims to provide evidence of the use of corticosteroids in the treatment of bacterial meningitis in children.Electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, and other databases) were searched from inception until March 9, 2021. Randomized clinical trials focused on corticosteroids as adjuvant therapy in pediatric bacterial meningitis were considered eligible. The primary outcomes were hearing loss and neurologic sequelae. Secondary outcomes were mean days before resolution of fever, mortality, secondary fever, and reactive arthritis. Fixed- or random-effects models were used to evaluate the association between corticosteroids therapy and outcomes by calculating risk ratios (RRs) and mean differences (MDs) with corresponding 95% CIs. Two independent reviewers completed citation screening, data extraction, and risk assessment.Twenty-nine studies with 3433 patients were included. An obvious benefit was found in the treatment of corticosteroids in hearing loss (RR = 0.62; 95% CI, 0.47-0.81; I² = 17%; P = 0.0006). No benefit was found in the rate of neurologic sequelae. However, obvious benefit was found in the low-dosage subgroup (0.6 mg/kg per day) (RR = 0.60; 95% CI, 0.47-0.77; I² = 0%; P0.0001) but not in the high-dosage subgroup (0.8 mg/kg per day). An increasing rate of secondary fever was found when using corticosteroids (RR = 1.29; 95% CI, 1.10-1.51; I² = 13%; P = 0.001). Corticosteroids could significantly decrease the mean days before resolution of fever (MD = -1.48; 95% CI, -1.79 to -1.17; I² = 84%, P0.00001). No difference was found in the rate of mortality and reactive arthritis.The findings of this study suggest that the administration of corticosteroids is associated with reduced hearing loss and neurologic sequelae especially in children using a low dose of corticosteroids. Benefits also included a reduction in the mean number of days before resolution of fever.

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).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 19 (COVID-19) pandemic, which is deeply affecting the whole world. In this new case for the scientific world, scientists are investigating the etiopathogenesis of viral infection-induced damage and have started to focus on the short and long-term immune system effects and alterations after SARS-CoV-2 infection. The case is here reported of a 53-year-old female patient with acute monoarthritis after SARS-CoV-2 infection, who responded adequately to 150 mg/day diclofenac treatment, and the available case reports are comprehensively reviewed. With the focus on arthritis after SARS-CoV2 infection, which emerges as a new pathological condition associated with COVID-19, it was aimed to examine the possible immunological mechanisms of post-COVID-19 arthritis based on the current data on SARS-CoV-2 and the known pathogenetic background of viral arthritis.

The objective of this systematic review and meta-analysis was to estimate the proportion of postinfectious reactive arthritis (ReA) after bacterial enteric infection from one of four selected pathogens. We collected studies from PubMed, Web of Science, and Embase, which assessed the proportion of postinfectious ReA published from January 1, 2000 to April 1, 2018. Papers were screened independently by title, abstract, and full text; papers in English, Spanish, and Portuguese utilizing a case-control (CC) or cohort study design, with a laboratory confirmed or probable acute bacterial enteric infection and subsequent ReA, were included. The proportion of ReA cases was pooled between and across pathogens. Factors that can induce study heterogeneity were explored using univariate meta-regression, including region, sample size, study design, and ReA case ascertainment. Twenty-four articles were included in the final review. The estimated percentage of cases across studies describing

Reactive arthritis (ReA) is a form of inflammatory arthritis triggered by a remote antecedent infection, usually in the genitourinary or gastrointestinal tract. It is part of the spondyloarthropathy (SpA) spectrum, an umbrella term for a group of distinct conditions with shared clinical features. Typically, it presents with an asymmetric oligoarthritis of the lower limb joints, and patients may also have sacroiliitis, enthesitis and dactylitis. Other features often seen include anterior uveitis, urethritis and skin manifestations such as pustular lesions on the plantar areas. Although ReA was characterised initially as a sterile arthritis, the detection of metabolically active Chlamydia species in the joint fluid of some affected patients has generated further questions on the pathophysiology of this condition. There are no formal diagnostic criteria, and the diagnosis is mainly clinical. HLA-B27 can support the diagnosis in the correct clinical context, and serves as a prognostic indicator. The majority of patients have a self-limiting course, but some develop chronic SpA and require immunomodulatory therapy.

The issue of reactive arthritis belongs to one of the most complex problems in rheumatology. Although the original concept of reactive arthritis as a#8222;sterile arthritis#8220; 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.

Reactive arthritis (ReA) is defined as inflammatory arthritis secondary to an extra-articular infection with a key genetic background, HLA-B27. However, to date, the diagnosis and classification remain incomplete. The study focused on the similarities and differences in clinical manifestation, imaging features, and laboratory inspection between HLA-B27 negative patients and HLA-B27 positive patients in order to provide a reference for future development of diagnostic and classification criteria. Twenty-five ReA (19 HLA-B27 negative patients and 6 HLA-B27 positive patients) were included in this retrospective study. Clinical data, including demographics, clinical symptoms, imaging features, and laboratory inspection, were collected. The chi-square test and Mann-Whitney U test were used in the analysis. HLA-B27 negative group showed more involvement of upper extremities and small joints, while HLA-B27 positive group performed more axial symptoms. No significant difference was found in imaging features (ultrasound and magnetic resonance imaging) or laboratory inspection (microbes culture and infection-related indicators) between the 2 groups. ReA patients with different genetic backgrounds show various manifestations, although they encounter similar infections.

A total of 13 case reports of reactive arthritis reported in the literature in connection with coronavirus disease 2019 (COVID‑19) are reviewed. Men were affected more frequently than women. The arthritis was manifested 4-44 days after the infection or the occurrence of the COVID‑19 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-COVID‑19 reactive arthritis is unknown.Es werden 13 Fallberichte einer reaktiven Arthritis im Zusammenhang mit einer Coronavirus-Krankheit-2019 (COVID‑19) referiert. Männer sind häufiger betroffen als Frauen. Die Arthritis manifestiert sich 4 bis 44 Tage nach der Infektion bzw. dem Auftreten der COVID‑19-Symptome. Die akute Arthritis ist monoartikulär oder oligoartikulär. Nur einer von 7 untersuchten Patienten war Humanes-Leukozyten-Antigen(HLA)-B27-positiv. Eine direkte virale Infektion des Gelenkes mit „severe acute respiratory syndrome coronavirus 2“ (SARS-CoV‑2) wurde in der Synovialflüssigkeit nicht nachgewiesen und in der Synovialis nicht untersucht. Die Arthritis wurde mit nichtsteroidalen Antirheumatika und/oder intraartikulären oder systemischen Kortikosteroiden erfolgreich behandelt. Die Pathogenese der post-COVID‑19-reaktiven Arthritis ist ungeklärt.

Background Although, preliminary reports of Severe Acute Respiratory Syndrome (SARS)-CoV-2 infection suggest that the infection causes a less severe illness in children, there is now growing evidence of other rare or even serious complications of disease. Case presentation During the recent COVID-19 pandemic in Kerman, Iran, two children (an 8 year-old boy and a 6 year-old girl) were referred to outpatient Clinic of Pediatric Rheumatology with complaints of limping. Both children had experienced fever and mild respiratory tract infection. At the beginning of the second week of infection, they developed joint effusion. They both tested positive for coronavirus infection and were therefore diagnosed with post Coronavirus reactive arthritis. Both children were treated successfully with rest and Non-Steroidal Anti-Inflammatory Drugs (NSAID). They did not have any medical problems in the two months fallow up. Conclusions These two cases suggest that COVID-19 may be rheumatogenic. Highlighting the need for awareness of physicians, especially pediatricians, regarding the pathogenesis margins of this virus, as late presentations are of great importance.

The patient was a 70-year-old woman who underwent transurethral resection of bladder tumor in May 2020. She was diagnosed with urothelial carcinoma (high grade, pT1 by pathology). We started bacillus Calmette-Guerin (BCG) intravesical infusion (80 mg Tokyo strain) in August of the same year after a second transurethral resection. Pain during urination persisted during the administration of BCG, and it worsened after the completion of six doses. The patient was hospitalized with back and neck pain and difficulty in physical movement. At the time of admission, bilateral conjunctivitis was observed. The patient was diagnosed with reactive arthritis associated with BCG intravesical injection therapy, as three typical symptoms were observed (bilateral conjunctivitis, urethritis, polyarthritis). The patient was treated with prednisolone and non-steroidal anti-inflammatory drugs for arthritis, but the symptoms did not improve. We administered salazosulfapyridine and her reactive arthritis improved.

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.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.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.

The introduction of the term reactive arthritis (ReA) for the joint inflammation observed after infection with Yersinia enterocolitica, in which "a causative pathogen cannot be isolated from the synovial fluid", and the association with the HLA-B27 were the historical milestones for a new classification and assignment to the spondylarthritides (SpA). The division into postinfectious and reactive arthritis proposed in 1976 was put into perspective in the 1990s because of investigations with the newly available molecular biological method of the polymerase chain reaction. Microbial products could be identified from joint samples of patients with ReA. Therefore, it was proposed to abandon the distinction between the two groups of diseases and to prefer the term ReA for both. This created a terminological and nosological issue. On the one hand, there are generally accepted classification and diagnostic criteria for the classical HLA-B27-associated ReA that are assigned to SpA. On the other hand, an increasing number of bacterial pathogens, viruses, amoebas, helminths as well as antiviral and antibacterial vaccinations are described as triggers of arthritis, which have been published under the term ReA. Since the beginning of the SARS-CoV‑2 pandemic, cases of acute post-COVID-19 arthritis have been described, which were also classified as ReA because of comparable clinical features.Die Einführung der Bezeichnung reaktive Arthritis (ReA) für die nach Infektion mit Yersinia enterocolitica beobachtete Gelenkentzündung, bei der „ein ursächlicher Erreger nicht aus der Gelenkflüssigkeit isoliert werden kann“, und die Assoziation mit dem HLA-B27 waren die historischen Wegmarken für eine neue Klassifikation und Zuordnung zu den Spondyloarthritiden (SpA). Die 1976 vorgeschlagene Unterteilung in postinfektiöse und reaktive Arthritiden erfuhr in den 1990er-Jahren durch Untersuchungen mit der neu verfügbaren molekularbiologischen Methode der Polymerasekettenreaktion eine Relativierung. Aus Gelenkproben von Patienten mit ReA konnten mikrobielle Produkte identifiziert werden. Deshalb wurde vorgeschlagen, die Unterscheidung zwischen den beiden Erkrankungsgruppen aufzugeben und für beide den Begriff „ReA“ vorzuziehen. Daraus ist eine terminologische und nosologische Problematik entstanden. Einerseits existieren Klassifikations- und Diagnosekriterien für die klassische HLA-B27-assoziierte ReA, die der SpA zugeordnet und allgemein akzeptiert sind. Andererseits sind eine zunehmende Zahl von bakteriellen Erregern, Viren, Amöben, Helminthen, aber auch antivirale und antibakterielle Impfungen als Auslöser einer Arthritis beschrieben, die unter der Bezeichnung ReA publiziert wurden. Seit dem Beginn der SARS-CoV-2-Pandemie werden Fälle einer akuten Post-COVID-19-Arthritis beschrieben, die wegen der vergleichbaren klinischen Merkmale ebenfalls als ReA klassifiziert wurden.

ObjectivesIn August 2016, Campylobacter spp contaminated an untreated reticulated water supply resulting in a large-scale gastroenteritis outbreak affecting an estimated 8320 people. We aimed to determine the incidence of probable reactive arthritis (ReA) cases in individuals with culture-confirmed campylobacteriosis (CC), self-reported probable campylobacteriosis (PC) and those reporting no diarrhoea (ND).DesignWe conducted a retrospective cohort study to identify incidence of probable ReA cases. We identified cases with new ReA symptoms using an adapted acute ReA (AReA) telephone questionnaire. Those reporting ≥1 symptom underwent a telephone interview with the study rheumatologist. Probable ReA was defined as spontaneous onset of pain suggestive of inflammatory arthritis in ≥1 previously asymptomatic joint for ≥3 days occurring ≤12 weeks after outbreak onset.SettingPopulation-based epidemiological study in Havelock North, New Zealand.ParticipantsWe enrolled notified CC cases with gastroenteritis symptom onsets 5 August 2016–6 September 2016 and conducted a telephone survey of households supplied by the contaminated water source to enrol PC and ND cases.ResultsOne hundred and six (47.3%) CC, 47 (32.6%) PC and 113 (34.3%) ND cases completed the AReA telephone questionnaire. Of those reporting ≥1 new ReA symptom, 45 (75.0%) CC, 13 (68.4%) PC and 14 (82.4%) ND cases completed the rheumatologist telephone interview. Nineteen CC, 4 PC and 2 ND cases developed probable ReA, resulting in minimum incidences of 8.5%, 2.8% and 0.6% and maximum incidences of 23.9%, 12.4% and 2.15%.DiscussionWe describe high probable ReA incidences among gastroenteritis case types during a very large Campylobacter gastroenteritis outbreak using a resource-efficient method that is feasible to employ in future outbreaks.

Reactive arthritis (ReA) is a form of sterile arthritis that occurs secondary to an extra-articular infection in genetically predisposed individuals. The extra-articular infection is typically an infection of the gastrointestinal tract or genitourinary tract. Infection-related arthritis is a sterile arthritis associated with streptococcal tonsillitis, extra-articular tuberculosis, or intravesical instillation of bacillus Calmette–Guérin (iBCG) therapy for bladder cancer. These infection-related arthritis diagnoses are often grouped with ReA based on the pathogenic mechanism. However, the unique characteristics of these entities may be masked by a group classification. Therefore, we reviewed the clinical characteristics of classic ReA, poststreptococcal ReA, Poncet’s disease, and iBCG-induced ReA. Considering the diversity in triggering microbes, infection sites, and frequency of HLA-B27, these are different disorders. However, the clinical symptoms and intracellular parasitism pathogenic mechanism among classic ReA and infection-related arthritis entities are similar. Therefore, poststreptococcal ReA, Poncet’s disease, and iBCG-induced ReA could be included in the expanding spectrum of ReA, especially based on the pathogenic mechanism.

Background Inflammatory arthritis is the most common late manifestation of untreated Lyme disease in the United States. While antimicrobial therapy is effective in resolving swelling and pain for 90% of patients, many patients have persistent inflammation, termed postinfectious Lyme arthritis (PILA). Current outcome measures for Lyme arthritis have several limitations, as improvement is considered a dichotomous outcome based solely on physical examination. There is growing interest in the use of ultrasonography to better define outcomes in inflammatory arthritis, and this is particularly relevant for conditions such as late Lyme arthritis and PILA, which are monoarticular or oligoarticular. We describe results from a series of 5 patients who underwent ultrasound evaluations leading to a diagnosis of PILA. Methods This is a case series describing 5 patients with PILA who were referred for evaluation and treatment of symptomatic joints. Results Musculoskeletal ultrasound showed significant joint pathology, even in cases with minimal clinical findings. Synovitis, effusions, enthesitis/tendinopathy, and bone erosions were seen and helped confirm the presence of ongoing inflammatory arthritis. Conclusions Marked inflammatory change-with synovitis, enthesitis and erosions-can be seen in selected patients with PILA. Systematic sonographic evaluation of patients with PILA is needed to further evaluate pathology and treatment response.

BackgroundFibrinogen 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.MethodsThe 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.ResultsFAR 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.ConclusionFAR is closely related to inflammatory biomarkers and can be a potential indicator in the assessment of inflammation in spondyloarthritis.

The current COVID-19 pandemic raises several clinical challenges. Cases of COVID-19-associated arthritis have been reported, and inconsistently described as either COVID-19 viral arthritis or COVID-19 reactive arthritis. We aimed to review all the reported cases of ‘COVID-19-associated arthritis’, which we propose, is a better term to define the entire spectrum of new-onset arthritis believed to be associated with SARS-CoV-2 infection. We performed a systematic literature review using MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews to search for articles published up to 13 December 2021. We included cohort studies, case series and case reports describing patients diagnosed with COVID-19 reactive or viral arthritis by a physician, irrespective of fulfilment of classification criteria. To identify relevant studies, medical subject headings and keywords related to ‘COVID-19/SARS-CoV-2 infection’ and ‘reactive arthritis’ were used. Our search retrieved 419 articles, of which 31 were included in the review. A total of 33 cases were reported in these 31 articles, the majority being adults (28/33=85%) with peripheral joint involvement (26/33=79%). Most of the patients responded well to treatment and the disease was self-limiting. These 33 case reports describe a possible causal relationship between exposure to SARS-CoV-2 and the onset of arthritis. However, since these cases were reported during a pandemic, other aetiologies cannot be fully excluded. The exact mechanism through which SARS-CoV-2 might trigger arthritis is not fully understood and robust epidemiological data to support a causal relationship are still lacking.

To identify a panel of serum biomarkers that could specifically identify imminent cases of rheumatoid arthritis (RA) before diagnosis.Serum samples were collected at 4 time points from active component US military personnel, including 157 anti-citrullinated protein antibody (ACPA)-seropositive and 50 ACPA-seronegative RA subjects, 100 reactive arthritis (ReA) subjects, and 76 healthy controls. The cohorts were split into 2 phases, with samples tested on independent proteomic platforms for each phase. Classification models of RA diagnosis based on samples obtained within 6 months prior to diagnosis were developed both in univariate analyses and by multivariate random forest modeling of training sample sets and testing sample sets from each phase.Increases in serum analytes, including C-reactive protein levels, serum amyloid A, and soluble programmed cell death 1 (PD-1), were observed in seropositive RA subjects at the time point closest to diagnosis, up to several years before diagnosis. Only a small fraction of RA subjects had levels above the 95th percentile of healthy control levels until the time period within 6 months of diagnosis. For classification of RA diagnosis using samples obtained within 6 months prior to diagnosis, soluble PD-1 provided superior specificity compared to ReA cases (89%), with a sensitivity of 48% for RA classification. An 8-analyte model provided superior sensitivity (69%), with comparable specificity relative to ReA (82%).Our findings demonstrate that imminent RA diagnosis could be classified with high specificity, relative to healthy controls and ReA cases, using a panel of cytokines measured in serum samples collected within 6 months before actual diagnosis.

Zeidler and Hudson1 break a lance on the entity of reactive arthritis when dealing with classification criteria for spondyloarthritis (SpA), axial or peripheral. We would like to thank our colleagues for their insightful comments and reassure them that we do not forget reactive arthritis as an entity or put it aside. It is important to make clear that Zeidler and Hudson argue about a causal pathophysiological relationship: an infection that …