Acute Reactive Arthritis Research Articles

Acute Rheumatic Fever or Post-streptococcal Reactive Arthritis: Two Different Entities

Acute Rheumatic Fever or Post-streptococcal Reactive Arthritis: Two Different Entities

To the 100th anniversary of the birth of academician V.A. Nasonova. Infections and rheumatic diseases: from the past to the future

In rheumatology, the problem of infectious pathology is quite acute. This is primarily due to the participation of various infectious agents in the development of immuno-inflammatory rheumatic diseases (IIRD), in which microorganisms play a trigger role, triggering the immunopathological mechanisms of inflammation. Vivid examples of such diseases are acute rheumatic fever and reactive arthritis. The infectious etiology of Lyme disease has been proven. An equally difficult task is the fight against comorbid infection (CI), which often complicates the course of many IIRD due to a violation of the immune status caused by both the background disease and the use of immunosuppressive drugs. The predominance of respiratory tract lesions in the structure of CI in patients with IIRD makes it necessary to use influenza and pneumococcal vaccines in them, since the risk of deaths from these infections among these patients is quite high. During the development of the COVID-19 pandemic, which has become a challenge to all mankind, a large number of new fundamental and medical problems have been revealed concerning the relationship between viral infection and many widespread chronic non-communicable diseases, among which IIRDs occupy an important position. As one of the methods of combating the current COVID-19 pandemic, great hopes are pinned on the widespread use of vaccination. The possibility of using mo noclonal antibodies for pre-exposure prophylaxis of COVID-19, including in patients with IIRD, is discussed.

Assessing the Diagnostic Significance of Herpes Virus Infections’ Serological Markers in Children: Overdiagnosis or Clinically Relevant Studies? Retrospective Study

Background. Nowadays, population generally has high contamination with herpes virus infections. Infection commonly is asymptomatic, and the virus persists in the human body over a lifetime. Excessive diagnosis of herpes virus infections as well as overestimation of their role in the genesis of various diseases in immunocompetent people are common in Russian pediatrics.Objective. The aim of the study is to assess the frequency and efficacy of serological testing in the suspected correlation of herpes virus infections and infectious and somatic diseases in a multidisciplinary hospital.Methods. The study included patients hospitalized in the multidisciplinary hospital in Moscow, who were assigned serological examination for herpes viruses. The laboratory study was carried out by enzyme-linked immunosorbent assay with the revealing the markers of herpes simplex virus type 1 and 2, Epstein-Barr virus, and cytomegalovirus. The results of the examination were analyzed according to the nosology and their role in diagnosis and management.Results. The identification of herpes virus infections’ markers was performed for 996 patients undergoing medical treatment in 17 different hospital departments within 2 months. Most commonly the examination was prescribed in infectious disease, pediatric, and hematological departments and covered more than 140 different nosologies. Acute respiratory infection, reactive arthritis, thrombocytopenia, infectious mononucleosis, acute tonsillitis, gastrointestinal pathology, acute bronchitis, and pneumonia were the most common nosologies. Positive markers of acute infection were revealed in 1.71% of cases for HSV-1/HSV-2, in 4.89% — for EBV, in 3.81% — for CMV. Moreover, positive results of serological examination were mostly noted in the cases of infectious diseases: infectious mononucleosis, tonsillitis, or acute respiratory infections. Tests were assigned for all three infections at the same time in most cases.Conclusion. Widespread examination for herpes virus infections is the typical variant of overdiagnosis and it is usually less informative. Generally positive markers are observed in typical course of herpes virus infections when clinical picture is enough for diagnosis verification.

Reactive arthritis incidence in a community cohort following a large waterborne campylobacteriosis outbreak in Havelock North, New Zealand

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...

Post COVID Vaccination Reactive Arthritis: A Contemporary Assailant

The severe acute respiratory syndrome coronavirus 2-induced coronavirus disease 2019 (COVID-19) has had a global spread. While most patients with coronavirus disease 2019 (COVID-19) present with mild or moderate symptoms, 15% may develop severe pneumonia, 5% develop acute respiratory distress syndrome (ARDS), septic shock, and multiple organ failure. Some patients may also experience arthralgia or arthritis. Cases of reactive arthritis have been reported during or after COVID-19. Vaccines play an essential role in preventing the spread. However, almost all types ofvaccines have been reported to be associated with adverse events. With the approval of the use of COVID-19 vaccines, the vaccination program was started in our country and is still continuing. Reactive arthritis (ReA) after vaccination has been reported; however, ReA after COVID-19 vaccination has not been reported widely. We reported a 26-year’sold woman who suffered from an acute ReA on her left knee, left ankle and right wrist joint 8 days after COVID-19 vaccination anddiscussed the etiology and preventive strategy. She presented with oligoarthritic for 12 days eight days after COVID vaccination. Finally, she was diagnosed as ReA after COVID vaccination and was administered systemic steroid. The swelling and pain nearly disappeared after 7 days. On 1month follow-up, her condition was normal. ReA after COVID-19 vaccination is rare. The benefits ofvaccination far outweigh its potential risks and vaccination should be administered according to the currentrecommendations. Further attentions should be put to determine which individual is at higher risk fordeveloping autoimmune diseases after COVID-19 vaccination. More versatile and safer vaccines should beexplored.

MRI and Sonography of the Knee in Acute Reactive Arthritis: An Observational Cohort Study.

Reactive arthritis (ReA) is a unique subgroup of spondyloarthritis with acute presentation and tendency to develop chronicity. Magnetic resonance imaging (MRI) has enabled identification of sensitive markers of response to therapy. A longitudinal pilot study of acute ReA with knee joint involvement satisfying the Braun's criteria was undertaken. Magnetic resonance imaging of the knee was assessed at baseline, and agreement with ultrasonography was assessed. Clinical details were recorded using a detailed and structured case record form. Patients were followed up, and MRI predictors of transition to chronic arthritis were looked for. In 25 patients with ReA, synovial thickening was the most common feature. Enthesitis was observed on MRI in 20%. Urethritis-related and HLA-B27-positive ReA had higher synovial thickening scores (p = 0.007). Agreement was poor between MRI and ultrasonography (synovial hypertrophy: k = 0.04). On follow-up, 34% (n = 7/21 for >12 months) continued to have active disease. None of the clinical or radiological features were predictive of chronicity. Posturethritis and B27-positive ReA was more severe than postenteritis ReA and RA on MRI. One third develop chronic disease on follow-up. Magnetic resonance imaging is superior to sonography, although baseline imaging is not predictive of chronicity. The results of this pilot exploratory study argue for larger studies on MRI in ReA.

Optimization of the method for predicting clinical outcomes of reactive arthritis in children

The comparative analysis of content of cytokine and significant local antimicrobial factors (IL-6, IL-8, IL-17, INF-γ, TNF-α, IL-10, CRP, lysozyme, lactoferrin) in the coprofiltrates and serum of patients with acute and chronic reactive arthritis (ReA) made it possible to determine the markers predicting the course and outcomes of arthritis. It is established that the method of predicting ReA involving the analysis of the parameters characterizing coprofiltrates of children is the more accurate and effective method.

Hypertrophic osteoarthropathy mimicking a reactive arthritis: a case report and review of the literature

BackgroundHypertrophic osteoarthropathy (HOA) is a syndrome characterized by abnormal proliferation of skin and periosteal tissues of the extremities. It can be a rare hereditary disease (pachydermoperiostosis) or can be secondary to various diseases, though mostly lung malignancies. Here, we report an unusual clinical presentation of HOA.Case presentationA 77-year-old man presented with fever, diarrhea, and an oligoarthritis involving the left knee and the ankles. Since left knee synovial fluid aspiration revealed an aseptic synovitis and Clostridium Difficile toxin was detectable in stool samples, a reactive arthritis secondary to a Clostridium Difficile induced colitis was initially suspected. However, the presence of a worsened digital clubbing and the lack of a good clinical response to steroid therapy led us to perform a radionuclide bone scanning, which revealed HOA. This turned out to be associated with a lepidic predominant lung adenocarcinoma, which was clinically and radiologically difficult to distinguish from a relapse of pneumonia.ConclusionConsistent with the literature, HOA tends to have a variable clinical presentation, mimicking that of various rheumatic diseases. This clinical case shows that HOA can present as a presumptive acute reactive arthritis, and it highlights the importance of patient’s follow-up in the differential diagnosis of inflammatory arthritis, especially when a worsened digital clubbing is present.

A retrospective study: Acute rheumatic fever and post-streptococcal reactive arthritis in Japan

BackgroundAcute rheumatic fever (ARF) and post-streptococcal reactive arthritis (PSRA) are immune-mediated consequences of group A streptococcal pharyngitis. ARF has declined in developed nations. No prevalence survey of PSRA has been conducted. This study evaluated the incidence and characteristics of ARF and PSRA in Japanese children. MethodsFrom 2010 to 2015, ARF and PSRA were evaluated using clinical data retrospectively collected by chart review from 528 hospitals. ResultsFrom 323 hospitals (61% response rate), 44 cases of ARF and 21 cases of PSRA were reported. Patients with ARF and/or PSRA were mainly from large cities in Japan. The mean age of ARF occurrence was 8.5 years, and the ratio of female/male patients was 16:28. Major manifestations in the acute phase included carditis, 27 cases (61.4%); polyarthritis, 22 cases (50%); erythema marginatum, 7 cases (15.9%); Sydenham chorea, 3 cases (6.8%); and subcutaneous nodules, 1 case (2.3%). Twenty-one (58.3%) patients had migratory arthritis. During the follow-up period, 6 patients (13.6%) showed mild carditis. For PRSA, the mean age was 8.2 years, and the ratio of female/male patients was 12:9. Six (28.6%) patients had monoarthritis, and 4 (19%) patients had migratory arthritis. No patient had carditis. ConclusionsAlthough ARF and PSRA are rare in the Japanese pediatric population, substantial numbers of patients with both conditions were identified in this study. We observed a high incidence of arthritis and carditis in ARF patients. No PSRA case was complicated with carditis. General pediatricians need to have updated information about ARF and PSRA, even in industrialized countries.

Алгоритм ультразвуковой дифференциальной диагностики острого и хронического течения реактивного артрита

Алгоритм ультразвуковой дифференциальной диагностики острого и хронического течения реактивного артрита

Concurrent peritonsillar abscess and poststreptococcal reactive arthritis complicating acute streptococcal tonsillitis in a young healthy adult: a case report

BackgroundStreptococcus pyogenes is responsible for 5-15% and 20-30% of acute pharyngitis/tonsillitis in adults and children, respectively. It not only causes acute illness but also can give rise to local suppurative complications such as peritonsillar abscess as well as trigger the postinfectious syndromes of glomerulonephritis, acute rheumatic fever and poststreptococcal reactive arthritis. Here, we report a case of a young healthy adult in whom both peritonsillar abscess and poststreptococcal reactive arthritis developed as a complication of acute streptococcal tonsillitis. To the best of our knowledge, such a coincidence of poststreptococcal sequelae has not been reported previously.Case presentationA 32-year-old previously healthy woman was diagnosed with acute tonsillitis by her family doctor and treated empirically with amoxicillin/clavulanic acid (875/125 mg) twice daily for 5 days. Four days after completing antibiotic therapy, peritonsillar abscess of left tonsil developed. Needle aspiration followed by incision and drainage were performed by otolaryngologist at the Emergency Department. Next, the patient was discharged home on a 10-day course of cefuroxime and metronidazole. The symptoms of peritonsillar abscess were subsiding during treatment, however on the last day of antibiotic therapy, swelling and pain of the left ankle appeared. Five days later the patient was consulted by rheumatologist. Cultures of throat swabs and abscess aspirate collected 2 weeks before revealed the presence of Streptococcus pyogenes. Antistreptolysin O (ASO) titer was evaluated and proved to be 412 IU/ml (normal 0–200 IU/ml). The level of C-reactive protein was 13,0 mg/L (normal <5,0 mg/L). There was no known cardiac involvement. Poststreptococcal reactive arthritis was diagnosed. Left ankle arthralgia persisted for about 5–6 weeks. Six months after the presentation at the Emergency Department, the patient was well, with ASO titer reaching 262 IU/ml.ConclusionsClinicians should be aware that appropriate choice of antibiotic, proper dose as well as duration of therapy of acute GAS pharyngitis/tonsillitis are crucial to prevent poststreptococcal sequelae.

HLA-B27 and human β2-microglobulin affect the gut microbiota of transgenic rats.

The HLA-B27 gene is a major risk factor for clinical diseases including ankylosing spondylitis, acute anterior uveitis, reactive arthritis, and psoriatic arthritis, but its mechanism of risk enhancement is not completely understood. The gut microbiome has recently been shown to influence several HLA-linked diseases. However, the role of HLA-B27 in shaping the gut microbiome has not been previously investigated. In this study, we characterize the differences in the gut microbiota mediated by the presence of the HLA-B27 gene. We identified differences in the cecal microbiota of Lewis rats transgenic for HLA-B27 and human β2-microglobulin (hβ2m), compared with wild-type Lewis rats, using biome representational in situ karyotyping (BRISK) and 16S rRNA gene sequencing. 16S sequencing revealed significant differences between transgenic animals and wild type animals by principal coordinates analysis. Further analysis of the data set revealed an increase in Prevotella spp. and a decrease in Rikenellaceae relative abundance in the transgenic animals compared to the wild type animals. By BRISK analysis, species-specific differences included an increase in Bacteroides vulgatus abundance in HLA-B27/hβ2m and hβ2m compared to wild type rats. The finding that HLA-B27 is associated with altered cecal microbiota has not been shown before and can potentially provide a better understanding of the clinical diseases associated with this gene.

FRI0023 Enzymatic dnase and hyaluronidase serum activity in patients with early arthritis

BackgroundEarly arthritis (EA) is one of the most important problems of modern rheumatology. Searching the new pathogenic mechanism of recently-onset joints inflammation caused by different factors is needed. Enzymatic serum...

Rheumatic Fever and Post-Group A Streptococcal Arthritis in Children

There are several diseases associated with group A beta hemolytic streptococcal infection; the two most common are acute rheumatic fever (ARF) and poststreptococcal reactive arthritis (PsRA). Epidemiological and clinical data for both diseases are described, as well as current recommendations for treatment and prevention. There is an ongoing debate as to whether these two are different diseases or are parts of the spectrum of the same disease. There are some reports of carditis developing after PsRA, suggesting that PsRA may be part of the spectrum of ARF. However, since there are substantial clinical, immunological, and genetic differences between PsRA and ARF, we believe PsRA to be a distinct entity.

Selected Reaction Monitoring to Differentiate and Relatively Quantitate Isomers of Sulfated and Unsulfated Core 1 O-Glycans from Salivary MUC7 Protein in Rheumatoid Arthritis

Rheumatoid arthritis is a common and debilitating systemic inflammatory condition affecting up to 1% of the world's population. This study aimed to investigate the immunological significance of O-glycans in chronic arthritis at a local and systemic level. O-Glycans released from synovial glycoproteins during acute and chronic arthritic conditions were compared and immune-reactive glycans identified. The sulfated core 1 O-glycan (Galβ1-3GalNAcol) was immune reactive, showing a different isomeric profile in the two conditions. From acute reactive arthritis, three isomers could be sequenced, but in patients with chronic rheumatoid arthritis, only a single 3-Gal sulfate-linked isomer could be identified. The systemic significance of this glycan epitope was investigated using the salivary mucin MUC7 in patients with rheumatoid arthritis and normal controls. To analyze this low abundance glycan, a selected reaction monitoring (SRM) method was developed to differentiate and relatively quantitate the core 1 O-glycan and the sulfated core 1 O-glycan Gal- and GalNAc-linked isomers. The acquisition of highly sensitive full scan linear ion trap MS/MS spectra in addition to quantitative SRM data allowed the 3- and 6-linked Gal isomers to be differentiated. The method was used to relatively quantitate the core 1 glycans from MUC7 to identify any systemic changes in this carbohydrate epitope. A statistically significant increase in sulfation was identified in salivary MUC7 from rheumatoid arthritis patients. This suggests a potential role for this epitope in chronic inflammation. This study was able to develop an SRM approach to specifically identify and relatively quantitate sulfated core 1 isomers and the unsulfated structure. The expansion of this method may afford an avenue for the high throughput investigation of O-glycans.

Reactive arthritis

Reactive arthritis (ReA) can be defined as the development of sterile inflammatory arthritis as a sequel to remote infection, often in the gastrointestinal or urogenital tract. Although no generally agreed-upon diagnostic criteria exist, the diagnosis is mainly clinical, and based on acute oligoarticular arthritis of larger joints developing within 2-4 weeks of the preceding infection. According to population-based studies, the annual incidence of ReA is 0.6-27/100,000. In addition to the typical clinical picture, the diagnosis of ReA relies on the diagnosis of the triggering infection. Human leucocyte antigen (HLA)-B27 should not be used as a diagnostic tool for a diagnosis of acute ReA. In the case of established ReA, prolonged treatment of Chlamydia-induced ReA may be of benefit, not only in the case of acute ReA but also in those with chronic ReA or spondylarthropathy with evidence of persisting chlamydia antigens in the body. In other forms of ReA, there is no confirmed evidence in favour of antibiotic therapy to shorten the duration of acute arthritis. The outcome and prognosis of ReA are best known for enteric ReA, whereas studies dealing with the long-term outcome of ReA attributable to Chlamydia trachomatis are lacking.

Acute rheumatic fever and poststreptococcal reactive arthritis reconsidered

The incidence of acute rheumatic fever (ARF) in the United States and Western Europe is decreasing and postStreptococcal reactive arthritis (PSRA) is more prevalent. It is not clear whether PSRA is a forme fruste of ARF or a separate disease entity. Therefore, this review explores similarities and dissimilarities in initial symptoms and signs, disease course and underlying pathophysiologic mechanisms. ARF and PSRA present differently. PSRA patients are generally older, have a longer interval between group A streptococcus infection and symptom onset, and respond less dramatically to salicylates than ARF patients. The course of ARF may be complicated by carditis and valvular heart disease. Echocardiographic studies in Caucasian adults with PSRA have revealed no increase in valvular heart disease. The course of PSRA is characterized by arthritis that, in contrast to ARF, is additive, nonmigratory and is frequently chronic. Factors of the host, the Streptococcus and the immune response involved in the development of PSRA are scarcely explored, hampering comparisons with ARF. On the basis of the differences in clinical presentation and disease course, ARF and PSRA are separate disease entities. Development of validated diagnostic criteria for PSRA is mandatory to proceed with studies on pathophysiological mechanisms and treatment in PSRA.

Toll‐like receptor 2 variants are associated with acute reactive arthritis

We previously reported a recent outbreak of salmonellosis in which some individuals developed complications of the enteric infection. The objective of this study was to identify genetic variants that might predispose infected individuals to develop articular and/or extraarticular sequelae after Salmonella enteritidis infection. The entire exposed cohort was invited to participate in the study by sending a saliva sample for DNA analysis. Seventy-five Salmonella-infected subjects for whom there was clinical information agreed to participate and were stratified into 4 groups. Group 1 patients had arthritis and extraarticular features, group 2 patients had arthritis alone, group 3 patients had extraarticular features alone, and group 4 patients had neither. DNA samples from an uninfected cohort of 91 normal subjects were also genotyped. Genotyping was performed using 2 Toll-like receptor 2 (TLR-2) (rs5743708 and rs5743704) and 2 TLR-4 (rs4986790 and rs4986791) single-nucleotide polymorphisms (SNPs). Statistical analyses were carried out using chi-square tests. There was no association of TLR-4 exonic variants with any clinical events that were reported as accompanying the Salmonella infection. In contrast, compared with normal controls, one of the rare TLR-2 SNPs (rs5743708, R753Q) was associated with the development of arthritis and extraarticular features (P = 0.015 by chi-square test). The TLR-2 variant 753Q was not detected in any of the infected individuals with an uncomplicated course. Another TLR-2 variant, 631H, was associated with articular symptoms in infected males (P = 0.03 by chi-square test). In this outbreak, genetic variants of TLR-2, but not TLR-4, were associated with acute reactive arthritis following infection with S enteritidis.

Can we differentiate between acute rheumatic fever and post-streptococcal reactive arthritis?

Acute rheumatic fever has some clinical overlap with post-streptococcal reactive arthritis. In fact, some have considered post-streptococcal arthritis to be part of the spectrum of acute rheumatic fever. Barash et al retrospectively evaluated 68 patients with acute rheumatic fever and 159 patients with post-streptococcal reactive arthritis. They found significant differences in erythrocyte sedimentation rate, C-reactive protein, duration of joint symptoms after starting anti-inflammatory treatment, and relapse of joint symptoms after cessation of treatment. Thus, it appears that the two are separate entities that can be distinguished with clinical and laboratory variables.

In vivo inhibition of human neutrophil collagenase (MMP-8) activity during long-term combination therapy of doxycycline and non-steroidal anti-inflammatory drugs (NSAID) in acute reactive arthritis.

We studied the in vivo effect of long-term doxycycline treatment combined with NSAID on human interstitial collagenases, other matrix metalloproteinases, serine proteinases, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and lactoferrin from saliva and serum during the course of acute reactive arthritis (ReA). Collagenase activity and serine proteases (elastase-like, cathepsin G-like and trypsin-like activities) of saliva (n = 10) and gelatinase, lactoferrin and TIMP-1 of saliva (n = 10) and serum (n = 10) samples before and after 2 months doxycycline treatment, combined with NSAID, were studied by quantitative SDS-PAGE assay, ELISA assay and by spectrophotometric assay. The cellular source and molecular forms of salivary collagenase were characterized by immunoblotting using specific antisera. We found that activities of total and endogenously active interstitial collagenase reduced significantly. The salivary collagenase was found to originate from neutrophils. No fragmentation of either pro 75-kD and active 65-kD MMP-8 was detected after 2 months doxycycline treatment. However, during 2 months doxycycline and NSAID treatment no reduction of salivary and serum gelatinase, lactoferrin and TIMP-1-levels and salivary serine protease activities were detected. The in vivo inhibition of collagenase (MMP-8) activity during long-term doxycycline therapy in human saliva containing inflammatory exudate of ReA patients may contribute to the reduced tissue destruction observed in recent clinical and animal model studies in arthritides during long-term doxycycline/tetracycline treatment.