Persistent Arthritis Research Articles

Clinical outcome of ultrasonographic detected undifferentiated synovitis in patients with arthralgia

BackgroundIn the early stages of rheumatic diseases, individuals may present with nonspecific musculoskeletal symptoms (such as arthralgia) in the absence of clinical synovitis. Ultrasound (US) looks potentially helpful, particularly in the absence of symptomatic arthritis. This research aims to study the clinical outcomes of undifferentiated synovitis detected by ultrasound in patients who complain of arthralgia and their predicting factors.ResultsFrom 174 patients with arthralgia, 42% of cases went into remission, and 58% remained as persistent inflammatory arthritis (PIA) (26.4% persisted as undifferentiated arthritis, 31.6% differentiated into specific rheumatic diseases of whom 9.2% became rheumatoid arthritis, 6.3% developed spondyloarthropathy, and other diseases) after 2 years of follow-up. Regression analysis showed that patients with Power Doppler (PD) grade (I or II), grayscale (GS) synovitis grade (II or III), and GS synovitis ≥ grade II in one wrist were significant predictors for PIA in undifferentiated arthralgia’s patients.ConclusionsApproximately 60% of patients with arthralgia developed inflammatory arthritis (IA) after 2 years of follow-up, with 77% of them having US synovitis at the onset of the study. A positive PD signal, grade (II or III) GS synovitis, or ≥ grade II at one wrist were all independently related to the development of PIA in arthralgia patients.

New Highly Selective Antivirals for Chikungunya Virus identified from the Screening of a Drug-Like Compound Library.

Chikungunya fever is a mosquito-borne disease caused by Chikungunya virus (CHIKV). Treatment of CHIKV infections is currently supportive and does not limit viral replication or symptoms of persistent chronic arthritis. Although there are multiple compounds reported as antivirals active against CHIKV in vitro, there are still no effective and safe antivirals. Thus, active research aims at the identification of new chemical structures with antiviral activity. Here, we report the screen of the Pandemic Response Box library of small molecules against a fully infectious CHIKV reporter virus. Our screening approach successfully identified previously reported CHIKV antiviral compounds within this library and further expanded potentially active hits, supporting the use of reporter-virus-based assays in high-throughput screening format as a reliable tool for antiviral drug discovery. Four molecules were identified as potential drug candidates against CHIKV: MMV1634402 (Brilacidin) and MMV102270 (Diphyllin), which were previously shown to present broad-spectrum antiviral activities, in addition to MMV1578574 (Eravacycline), and the antifungal MMV689401 (Fluopicolide), for which their antiviral potential is uncovered here.

Harnessing the Power of Nature: Nyctanthes arbortristis as an Alternative Medicine

The Nyctanthes arbortristis, frequently referred to as Night-flowering Jasmine or Parijat, has a longstanding presence in traditional medicine. In this study, our objective was to assess its potential as an alternative therapy by analyzing its therapeutic uses and the scientific data that supports it. Nyctanthes arbortristis, a plant widely used in Ayurveda for its anti-inflammatory, antipyretic, and analgesic qualities, has shown promise in the treatment of several health disorders such as persistent fever, arthritis, parasite infections, and respiratory ailments. Recent studies have found several bioactive chemicals in this plant, including alkaloids, flavonoids, essential oils, and glycosides. These substances contribute to the pharmacological effects of the plant. This report consolidates current research results on the many health advantages of the plant and proposes potential topics for future investigations on the most effective ways to use it for therapeutic purposes. By incorporating Nyctanthes arbortristis into contemporary healthcare, it will be possible to create treatment plans that are both natural and sustainable, while also complementing current practices.

Features Associated With Different Inflammatory Phenotypes of Calcium Pyrophosphate Deposition Disease: Study Using Data From the International American College of Rheumatology/EULAR Calcium Pyrophosphate Deposition Classification Criteria Cohort.

The study objective was to examine the disease, demographic, and imaging features associated with different inflammatory phenotypes of calcium pyrophosphate deposition (CPPD) disease, ie, recurrent acute calcium pyrophosphate (CPP) crystal arthritis, chronic CPP crystal inflammatory arthritis, and crowned dens syndrome (CDS). Data from an international cohort (assembled from 25 sites in 7 countries for the development and validation of the 2023 CPPD classification criteria from the American College of Rheumatology/EULAR) that met the criteria were included. Three cross-sectional studies were conducted to determine the phenotypic characteristics of recurrent acute CPP crystal arthritis, chronic CPP crystal inflammatory arthritis, and CDS. Multivariable logistic regression analysis was used to calculate adjusted odds ratio (aOR) and 95% confidence interval (CI) to examine the association between potential risk factors and the inflammatory phenotype. Among the 618 people included (56% female; mean age [standard deviation] 74.0 [11.9] years), 602 (97.4%) had experienced acute CPP crystal arthritis, 332 (53.7%) had recurrent acute arthritis, 158 (25.6%) had persistent inflammatory arthritis, and 45 (7.3%) had had CDS. Recurrent acute CPP crystal arthritis associated with longer disease duration (aOR 2.88 [95% CI 2.00-4.14]). Chronic CPP crystal inflammatory arthritis was associated with acute wrist arthritis (aOR 2.92 [95% CI 1.81-4.73]), metacarpophalangeal joint osteoarthritis (aOR 1.87 [95% CI 1.17-2.97]), and scapho-trapezo-trapezoid (STT) joint osteoarthritis (aOR 1.83 [95% CI 1.15-2.91]), and it was negatively associated with either metabolic or familial risk for CPPD (aOR 0.60 [95% CI 0.37-0.96]). CDS was associated with male sex (aOR 2.35 [95% CI 1.21-4.59]), STT joint osteoarthritis (aOR 2.71 [95% CI 1.22-6.05]), and more joints affected with chondrocalcinosis (aOR 1.46 [95% CI 1.15-1.85]). CPPD disease encompasses acute and chronic inflammatory phenotypes, each with specific clinical and imaging features that need to be considered in the diagnostic workup.

Synthesis of a Borrelia burgdorferi-Derived Muropeptide Standard Fragment Library.

The interplay between the human innate immune system and bacterial cell wall components is pivotal in understanding diseases such as Crohn's disease and Lyme arthritis. Lyme disease, caused by Borrelia burgdorferi, is the most prevalent tick-borne illness in the United States, with a substantial number of cases reported annually. While antibiotic treatments are generally effective, approximately 10% of Lyme disease cases develop persistent arthritis, suggesting a dysregulated host immune response. We have previously identified a link between the immunogenic B. burgdorferi peptidoglycan (PG) and Lyme arthritis and showed that this pathogen sheds significant amounts of PG fragments during growth. Here, we synthesize these PG fragments, including ornithine-containing monosaccharides and disaccharides, to mimic the unique composition of Borrelia cell walls, using reproducible and rigorous synthetic methods. This synthetic approach allows for the modular preparation of PG derivatives, providing a diverse library of well-defined fragments. These fragments will serve as valuable tools for investigating the role of PG-mediated innate immune response in Lyme disease and aid in the development of improved diagnostic methods and treatment strategies.

Explorations on the antiviral potential of zinc and magnesium salts against chikungunya virus: implications for therapeutics.

Chikungunya virus (CHIKV), which causes chikungunya fever, is an arbovirus of public health concern with no approved antiviral therapies. A significant proportion of patients develop chronic arthritis after an infection. Zinc and magnesium salts help the immune system respond effectively against viral infections. This study explored the antiviral potential of zinc sulphate, zinc acetate, and magnesium sulphate against CHIKV infection. The highest non-toxic concentration of the salts (100 µM) was used to assess the prophylactic, virucidal, and therapeutic anti-CHIKV activities. Dose-dependent antiviral effects were investigated to find out the 50% inhibitory concentration of the salts. Entry bypass assay was conducted to find out whether the salts affect virus entry or post entry stages. Virus output in all these experiments was estimated using a focus-forming unit assay, real-time RT-PCR, and immunofluorescence assay. Different time- and temperature-dependent assays revealed the therapeutic antiviral activity of zinc and magnesium salts against CHIKV. A minimum exposure of 4 hours and treatment initiation within 1 to 2 hours of infection are required for inhibition of CHIKV. Entry assays revealed that zinc salt affected virus-entry. Entry bypass assays suggested that both salts affected post-entry stages of CHIKV. In infected C57BL6 mice orally fed with zinc and magnesium salts, a reduction in viral RNA copy number was observed. The study results suggest zinc salts exert anti-CHIKV activity at entry and post entry stages of the virus life cycle, while magnesium salt affect CHIKV at post entry stages. Overall, the study highlights the significant antiviral potential of zinc sulphate, zinc acetate, and magnesium sulphate against CHIKV, which can be exploited in designing potential therapeutic strategies for early treatment of chikungunya patients, thereby reducing the virus-associated persistent arthritis.

P128 Predicting Persistent Inflammatory Arthritis in patients with Palindromic Rheumatism: Development of Scores for Risk Stratification

Abstract Background/Aims Palindromic rheumatism (PR) is a recognised precursor of rheumatoid arthritis (RA). Up to 50% of PR patients will progress to persistent inflammatory arthritis (PIA) but risk factors for progression remain unclear. Analysis of this large UK prospective PR cohort has been used to develop the first risk stratification tool to predict progression to PIA. Methods The Leeds PR cohort was recruited from regional primary and secondary care referrals. PR was defined as ‘a confirmed history/physical examination consistent with episodes of joint pain and swelling that returned to normal in the absence of an alternative diagnosis’. Clinical, serological and immunogenetic parameters were assessed at baseline and three monthly for the first year, then six monthly. Progression to PIA was defined as clinical synovitis persisting for >3 weeks as confirmed by a rheumatologist. Prediction models were developed by performing a Cox regression analysis, then applying LASSO to select the most important risk variables (using R). Results 161 PR patients were followed between July 2008 and January 2023. 33% (53/161) developed PIA and 91% of progressors met criteria for RA. 90% of patients were DMARD naive at baseline. Female gender, anti-cyclic citrullinated peptide (anti-CCP) positivity, rheumatoid factor (RF) positivity, age>40, smoking (ever) and a typical interval between attacks of < 1 month were all associated with progression (Table 1). Cox regression analysis showed female gender (HR 2.2CI1.1-4.7, p = 0.03) and anti-CCP>3x upper limit of normal (HR 5.9, CI 2.0-17.4, p = 0.002) were strongly associated with progression. 'Ever’ and 'Two-year’ prediction models were created to calculate risk of developing PIA (Table 1). Patients could be stratified into high, moderate and low risk groups, with progression rates of 53% (34/64), 25% (19/77) and 0% respectively in the ‘Ever’ model and 37% (27/ 73), 16% (11/69) and 0% respectively in the ‘Two-year’ model. Conclusion In patients with PR, female gender, positive anti-CCP, positive RF, age >40, smoking and a typical interval between attacks of < 1 month were predictive of progression to PIA. Combining these factors allows feasible risk stratification in clinical practice. High and moderate risk groups should be monitored in secondary care and considered for interventional trials. Disclosure R. Chowdhury: None. F. Shuweihdi: None. N. Sidhu: None. L. Duquenne: None. L. Garcia-Montoya: None. J. Nam: None. A. Di Matteo: None. K. Harnden: None. D. Sahin-Eroglu: None. P. Emery: Consultancies; BMS, AbbVie, MSD, Pfizer, Novartis, and Roche. Honoraria; Abbvie, Gilead, Lilly, Novartis. Grants/research support; AbbVie, BMS, Lilly, Samsung. K. Mankia: Honoraria; Abbvie, Lilly, UCB, Galapagos. Grants/research support; Gilead, Lilly.

Traumatic Ulnar Carpal Translocation, Distal Radioulnar Joint Subluxation with Occult Perilunate Injury

Abstract Background Perilunate injuries pose a significant treatment challenge, particularly when initially missed or underestimated. These injuries have a multitude of variations as propagation of the injury may be through ligaments and/or bone, with more recent appreciation given to nondislocated perilunate injuries. Case Description We present a new variant of perilunate injuries, not dislocated (PLIND). This occult ligamentous perilunate injury was associated with ulnar carpal translocation, radiocarpal subluxation, and distal radioulnar subluxation. The extent of injury was fully appreciated intraoperatively, with only subtle clues present on preoperative exam and imaging, emphasizing the high index of suspicion required to identify these injuries. Clinical outcome at 1-year follow-up was very satisfactory. Literature Review PLIND consist a distinct subset within the spectrum of perilunate injuries in which there is no observed disruption of the capitolunate relationship. Based on few cases reported in the literature (attributable to their rare occurrence and likely additional lack of awareness surrounding the injury pattern), current recommendations for surgical management include arthroscopic or open approach to appropriately address osseous and ligamentous injuries. Clinical Relevance Recognition of PLIND injuries is challenging given the lack of frank dislocation of the capitate head on the lunate, as observed in classic perilunate injuries. Heightened clinical suspicion in patients with consistent mechanism and presentation, followed by timely surgical management, may limit sequelae of persistent instability and arthritis. Our case contributed to relevant literature by presenting a previously undescribed PLIND variant combined with radiocarpal instability, ulnar carpal translocation, and distal radioulnar subluxation.

Predictors of disease course in systemic juvenile idiopathic arthritis.

The aim of this study was to identify potential predictors of the disease course of systemic juvenile idiopathic arthritis (sJIA) at the time of diagnosis. This retrospective observational study was conducted in patients diagnosed with sJIA in our hospital between April 2009 and October 2023. The relationship between the disease course of sJIA patients and demographic, clinical, laboratory findings and complications was analysed. Of the 51 patients diagnosed with sJIA, 26 (51%) patients had monocyclic, 7 (13.7%) polycyclic, and 18 (35.2%) persistent disease course. The presence of arthritis, polyarticular involvement, and hip involvement at the time of diagnosis were associated with persistent disease course (P = .009, P = .003, P = .003). Serositis and higher white blood cell and neutrophil counts at the time of diagnosis were associated with a monocyclic disease course (P = .034, .002, .008). However, no significant correlation was found between macrophage activation syndrome and disease course (P = 1). sJIA patients with polyarthritis and hip involvement at disease onset may develop a persistent course. Although macrophage activation syndrome is an important complication of sJIA, its effect on the course of the disease was not found in this study.

When should the use of biological agents be considered in persistent oligoarticular juvenile idiopathic arthritis patients?

JADAS10 indicating ongoing severe disease activity at 3rd and 6th months rather than baseline JADAS10 is associated with the addition of bDMARDs. • Oligoarticular JIA patients have the best outcomes among JIA categories and respond favorably to first-line therapies such as non-steroidal anti-inflammatory drugs and intraarticular corticosteroid injections. • Clinically inactive disease rates have increased with the widespread use of biological agents in oligoarticular JIA patients who have not responded to initial therapies. • Approximately one-fifth of patients with persistent oligoarticular JIA on methotrexate may require the addition of a biological disease modifying anti-rheumatic drug during follow-up. • The JADAS10 calculated at 3 and 6months is a valuable tool to identify patients who should be added biological disease modifying anti-rheumatic drugs in persistent oligoarticular JIA.

Emerging Phytochemical Formulations for Management of Rheumatoid Arthritis: A Review.

Rheumatoid arthritis (RA) is a T-cell-mediated chronic inflammatory disorder affecting 0.5-1% of the global population. The disease with unknown etiology causes slow destruction of joints, advancing to significant deterioration of an individual's quality of life. The present treatment strategy comprises the use of disease-modifying anti-rheumatic drugs (DMARDs) coupled with or without nonsteroidal anti-inflammatory drugs or glucocorticoids. Additionally, involves co-therapy of injectable biological DMARDs in case of persistent or recurrent arthritis. The availability of biological DMARDs and the implementation of the treat-to-target approach have significantly improved the outcomes for patients suffering from RA. Nevertheless, RA requires continuous attention due to inadequate response of patients, development of tolerance and severe side effects associated with long-term use of available treatment regimens. An estimated 60-90% of patients use alternative methods of treatment, such as herbal therapies, for the management of RA symptoms. Over the past few decades, researchers have exploring natural phytochemicals to alleviate RA and associated symptoms. Enormous plant-origin phytochemicals such as alkaloids, flavonoids, steroids, terpenoids and polyphenols have shown anti-inflammatory and immunomodulatory activity against RA. However, phytochemicals have certain limitations, such as high molecular weight, poor water solubility, poor permeability, poor stability and extensive first-pass metabolism, limiting absorption and bioavailability. The use of nanotechnology has aided to extensively improve the pharmacokinetic profile and stability of encapsulated drugs. The current review provides detailed information on the therapeutic potential of phytochemicals. Furthermore, the review focuses on developed phytochemical formulations for RA, with emphasis on clinical trials, regulatory aspects, present challenges, and future prospects.

Late Presentation of Early-onset Sarcoidosis: A Case Report

Background: Early-onset sarcoidosis is a rare systemic inflammatory granulomatous disease, distinguished by onset before the age of 4 and notably lacking pulmonary involvement. Unfortunately, the condition often shows clinical features similar to juvenile idiopathic arthritis, resulting in the misdiagnosis of numerous patients. This case report delves into the challenges associated with the delayed diagnosis of early-onset sarcoidosis, with a particular focus on the diagnostic methods employed to address this delayed recognition. Case presentation: A 15-year-old girl presented with a history of recurrent fever since infancy, accompanied by rash, arthritis, and joint deformity. Previously misdiagnosed with juvenile idiopathic arthritis, she underwent management with steroids and methotrexate, yielding no improvement. The diagnosis of early-onset sarcoidosis was made during adolescence based on serial examinations, comprehensive laboratory and radiological evaluations, and subsequent histopathology findings. Presently, the patient is receiving treatment with low-dose steroids and biologic therapy (Tocilizumab) and experiencing no disease progression. Conclusion: This case report underscores the importance of considering early-onset sarcoidosis in the differential diagnosis of pediatric patients exhibiting persistent arthritis from an early age. Early detection and treatment are crucial in averting complications and enhancing the overall quality of life.

Transcriptome analysis of Huh7 cells upon Chikungunya virus infection and capsid transfection reveals regulation of distinct cellular and metabolic pathways

Chikungunya virus (CHIKV) causes persistent arthritis and neurological problems imposing a huge burden globally. The present study aims to understand the interaction mechanism of Chikungunya virus and CHIKV-capsid in Huh7 cells. The RNA-sequencing and qRT-PCR method was used for the transcript and gene profiles of CHIKV virus and CHIKV capsid alone. Transcriptional analysis showed capsid induced 1114 and 956 differentially expressed genes (DEGs) to be upregulated and downregulated respectively, while in virus, 933 genes were upregulated and 956 were downregulated. Total 202 DEGs were common in both capsid and virus; and nine were validated using qRT-PCR. Identified DEGs were found to be associated with metabolic pathways such as Diabetes, cardiac disease, and visual impairment. Further, knock-down study on one of the DEGs (MafA) responsible for insulin regulation showed low viral proteins expression suggesting a reduction in virus-infection. Thus, the study provides insight into the interplay of the virus-host factors assisting virus replication.

Meniscal disruption associated with septic arthritis in three neonatal foals

SummaryThe objective of this study was to report clinical characteristics, surgical management and medium‐term (6–12 months) outcomes of three Arabian neonatal foals with meniscal disruption associated with septic arthritis of the lateral femorotibial joint. The three neonatal Arabian foals with septic arthritis of the lateral femorotibial joint (LFTJ), were diagnosed with disruption of the lateral meniscal (LM). Suspicion of meniscal pathology was based on ultrasonography, computed tomography (in 2 foals) and confirmed during arthroscopy. Treatment included arthroscopic debridement and lavage of the joint with debridement of the meniscal disruption. Postoperative care included systemic and intra‐articular antimicrobials, based on culture and sensitivity results. Two of the foals received intra‐articular injections of autologous mesenchymal stem cells. Marked LM disruption was observed in the LFTJ of the affected joints of all foals, involving the meniscal body (n = 3) and caudal horn (n = 1). Purulent material within the torn tissue was debrided with a synovial resector. Foal 1 was lame‐free as a yearling. Foal 2 was lame at walk at 7.5 months and euthanised due to poor prognosis. Foal 3 showed mild lameness at trot in a straight line at 6 months. Disruption of the LM continued to be visible on US in both foals at these timepoints. It was concluded that meniscal disruption and infection should be considered as a differential in neonatal foals with persistent femorotibial septic arthritis. In such cases, the LM could be the primary nidus of infection.

255. Borrelia-specific antibody profiling in joint fluid distinguishes antibiotic-refractory Lyme arthritis from antibiotic-responsive arthritis

Abstract Background Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States. It drives a multisystem disorder, of which Lyme arthritis is the most common feature of late disseminated disease, seen in approximately 60% of untreated individuals. While most Lyme arthritis resolves with oral or IV antibiotics, termed “antibiotic-responsive” arthritis, a small percentage of individuals develop progressive synovitis despite both oral and IV antibiotic therapy, called “antibiotic refractory” Lyme arthritis (LA), requiring treatment with immunosuppressive, disease modifying antirheumatic drugs (DMARDs). The primary drivers behind antibiotic refractory disease are likely multifactorial and remain incompletely understood. More specifically, it remains unclear whether antibodies, specific for Borrelia or autoantibodies, may act as biomarkers or play a mechanistic role in driving pathogenesis in the joint. Methods We performed a matched, cross-compartmental comparison of antibody profiles from blood and joint fluid of individuals with antibiotic responsive (n = 11) or antibiotic refractory arthritis (n= 31). We used a multiplexed luminex assay to perform biophysical profiling of Borrelia burgdorferi -specific antibodies to B67 lysate, CRASP1, CRASP2, DbpA, DbpB, Arp37, Flagellin, OspA, OspB, OspC, OspE, p27, p35, p39, VlsE, and autoantigen Apolipoprotein B100. Results While serum antibody profiles poorly discriminated responsive from refractory LA patients, a discrete profile of B.burgdorferi-specific antibodies in the joint fluid was able to discriminate antibiotic responsive from refractory LA patients. Cross compartmental comparison of antibody glycosylation, IgA1, and antibody-dependent complement deposition (ADCD) revealed differences across compartments, with more poorly coordinated Lyme-specific humoral responses and increased antibody-dependent complement deposition in antibiotic-refractory arthritis. Conclusion These data demonstrate B.burgdorferi-specific serological markers that may support the early stratification and clinical management of LA, but also point to immune complex driven complement activation as a key mechanism underlying persistent Lyme arthritis. Disclosures Christine Wiggins, B.S., Takeda Pharmaceutical Company: Stocks/Bonds Elizabeth Deriso, PhD, Takeda: Employee Klemen Strle, PhD, Takeda: I am an employee of Takeda. My work at Takeda does not overlap with my academic efforts in Lyme disease. John A. Branda, M.D, Analog Devices Inc.: Grant/Research Support|DiaSorin: Grant/Research Support|Gold Standard Diagnostics: Grant/Research Support|Pfizer Inc: Grant/Research Support|Zeus Scientific: Grant/Research Support Douglas A. Lauffenburger, PhD, Sanofi: Board Member|Sanofi: Honoraria|Sanofi: Honoraria Galit Alter, PhD, Leyden Labs: Ownership Interest|Moderna Therapeutics: Employee|Seromyx Systems: Ownership Interest

EVALUATION OF PERIPHERAL AND CENTRAL ANALGESIC EFFICACIES OF AYURVEDIC NEW FORMULATION FOR AMAVATA DISEASE IN ANIMAL MODEL THROUGH WRITHING TEST AND TAIL -FLICK IMMERSION TEST IN MICEMODEL- AN ANIMAL EXPERIMENTAL STUDY.

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disorder, it is the most common persistent inflammatory arthritis, occurring throughout the world and in all ethnic groups. This is the most marked in those with severe diseases, with a reduction in expected lifespan by 8-15 years. Around 40% of RA pa-tients are registered disable within 3 years, around 80% are moderately to severely disables within 20 years, and 25% will require a large joint replacement. Functional capacity decreases most rapidly at the beginning of disease and the functional status of patients within their 1st year of RA is often predictive of long-term out-come(1). Aim: In research field RA need more attention for deep research due to, firstly its unbearable symptoms and secondary complication and secondly in modern science there are medicines available for temporary manage-ment purpose but with lot of adverse reaction. RA is a non-curable disease, in Ayurveda, RA can be corelated with Amavata disease (Rheumatoid arthritis). Methodology: In this present study It has been taken up to see the efficacy of new combined Ayurvedic formu-lation i,e combination of Stem of Asthishrinkhala (Cissus quadrangularis L), bulb of Sunthi (Zingiber offici-nale Roscoe) and bulb of Rasona (Allium sativum L) with (1:1:1) ration for better management with less side effects. This research firstly done on animal to evaluate central and peripheral activity of research drug, through Writhing Test and Tail -flick immersion test in Mice model.

Baseline predictors of disease severity in immune checkpoint inhibitor-induced inflammatory arthritis.

The objective of this study was to determine baseline risk factors for requiring immunosuppression and having persistent arthritis in patients with immune checkpoint inhibitor-induced inflammatory arthritis (ICI-inflammatory arthritis). Participants were adults with rheumatologist diagnosed ICI-inflammatory arthritis. The primary outcome was requirement of conventional synthetic (cs) or biologic (b) DMARDs; other outcomes were persistence of inflammatory arthritis >6 months after ICI cessation and requirement of CSs. Logistic regression models evaluated associations between clinical features and primary and secondary outcomes, with adjustment for potential confounders, as appropriate. One hundred and twenty-six patients with ICI-inflammatory arthritis were included; 53 patients (42%) required a csDMARD/bDMARD. In the univariate logistic regression analysis, higher clinical disease activity index (CDAI), tenosynovitis, longer symptom duration before first rheumatology visit and longer ICI duration were significantly associated with a higher likelihood of requiring DMARDs; in addition, there was a trend towards those treated with prior chemotherapy being less likely to need DMARDs. After adjustment, tenosynovitis, longer symptom duration and higher CDAI remained associated with requiring DMARDs, while those with prior chemotherapy were significantly less likely to require DMARDs. Combination anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein-4)/PD-1 (Programmed cell death protein-1) therapy and CS use at baseline were associated with a higher risk of persistent inflammatory arthritis. Higher levels of disease activity, tenosynovitis and longer symptom duration prior to rheumatology referral were associated with requiring DMARDs for ICI-inflammatory arthritis, while those treated previously with chemotherapy were less likely to require additional immunosuppression. The presence of risk factors for severe disease at baseline may indicate a role for higher initial CS dose, earlier rheumatology referral, and adoption of immunosuppression beyond CSs to improve outcomes.

Monoarticular juvenile idiopathic arthritis as a distinct clinical entity A proof-of-concept study

BackgroundCurrently, monoarticular Juvenile Idiopathic Arthritis (monoJIA) is included in the ILAR classification as oligoarticular subtype although various aspects, from clinical practice, suggest it as a separate entity.ObjectivesTo describe the clinical characteristics of persistent monoJIA.MethodsPatients with oligoJIA and with at least two years follow-up entered the study. Those with monoarticular onset and persistent monoarticular course were compared with those with oligoJIA. Variables considered were: sex, age at onset, presence of benign joint hypermobility (BJH), ANA, uveitis, therapy and outcome. Patients who had not undergone clinical follow-up for more than 12 months were contacted by structured telephone interview.ResultsOf 347 patients with oligoJIA, 196 with monoarticular onset entered the study and 118 (60.2%), identified as persistent monoJIA, were compared with 229 oligoJIA. The mean follow-up was 11.4 years. The switch from monoarticular onset to oligoarticular course of 78 patients (38.8%) occurred by the first three years from onset. In comparison with oligoJIA, the most significant features of monoJIA were later age at onset (6.1 vs. 4.7 years), lower female prevalence (70.3 vs. 83.4%), higher frequency of BJH (61.9 vs. 46.3%), lower frequency of uveitis (14.4 vs. 34.1%) and ANA+ (68.6 vs. 89.5%) and better long-term outcome.ConclusionsMonoJIA, defined as persistent arthritis of unknown origin of a single joint for at least three years, seems to be a separate clinical entity from oligoJIA. This evidence may be taken into consideration for its possible inclusion into the new classification criteria for JIA and open new therapeutic perspectives.

Systemic-onset Juvenile Idiopathic Arthritis in a young child

We present a 31-month-old female child who was referred by the pediatricians with 1-year history of recurrent high-grade fever associated with polyarthritis and recurrent skin rash, which disappears within 24 hours of resolution of fever. She had lost the ability to walk unsupported because of persistent arthritis. Her Full Blood Count (FBC) was remarkable for marked leucocytosis, thrombocytosis, and a mild normocytic normochromic anemia; Erythrocyte Sedimentation Rate (ESR) and C-reactive Protein (CRP) were both elevated at 110mm/hour and 200mg/L (<7) respectively while serial blood cultures were negative for septicemia and blood films were negative for acute leukemia; HIV, hepatitis B and C virus, tuberculosis, rheumatic fever, rheumatoid arthritis, and connective tissue disease screenings were all negative. Her hemoglobin genotype is AA. She had repeatedly received treatments for malaria and ‘sepsis’ with parenteral and oral antimalarials and antibiotics with no permanent relief, hence the reason for referral to the rheumatologist. An assessment of Systemic-onset Juvenile Idiopathic Arthritis (SoJIA) was made when her serum ferritin came back elevated at 670ng/mL (4.63 – 204) and she was commenced on oral ibuprofen with remarkable improvement evidenced by resolution of fever, joint pain and rash and normalization of ESR, CRP and serum ferritin within 8 weeks of treatment. Although SoJIA is rare, it would be worthwhile to include this disease in the differential diagnoses and subsequent evaluation in any child presenting with unexplained recurrent fever associated with body rash and polyarthritis.

Characteristics of persistent arthritis with refractory Kawasaki disease: a single-center retrospective study

Arthritis is one complication of Kawasaki disease (KD); however, the clinical features of arthritis in KD have not been well clarified. We retrospectively investigated the characteristics of persistent arthritis beyond the subacute phase of KD. In this cohort, 49 of 243 patients (20%) developed arthritis, with 33 patients (14%) experiencing persistent arthritis. Among these 33 patients, 31 (94%) had complete KD. Thirty (91%) were resistant to first intravenous immunoglobulin, and 15 (45%) required additional infliximab. Five patients (15%) developed coronary artery lesions, and 24 (73%) had oligoarthritis, mainly in large lower-extremity joints. Twenty-four patients (73%) complained of arthralgia. At arthritis onset, 16 patients (48%) presented with fever, including recurrent fever in 10 patients. Serum C-reactive protein concentration in patients with active arthritis significantly increased compared with after acute KD treatment (2.4 vs. 0.7 mg/dL, p < 0.001). Serum matrix metalloproteinase-3, a biomarker of arthritis, was significantly higher in patients with active arthritis than in remission (93.7 vs. 20.3 ng/mL, p < 0.001). Thirty (91%) and 14 (42%) patients, respectively, were treated with non-steroidal anti-inflammatory drugs and prednisolone, and they completely recovered. To summarize, persistent arthritis is a common complication in refractory KD, and adequate diagnosis and treatment are necessary.