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ID PMID Title PublicationDate abstract
30533376 A successful treatment of rheumatoid arthritis-related interstitial pneumonia with ninteda 2019 Rheumatoid arthritis-related interstitial pneumonia with a usual interstitial pneumonia (RA-UIP) has a poor prognosis and a new treatment strategy is required. The antifibrotic agent nintedanib reduces the annual rate of decline in forced vital capacity (FVC) in idiopathic pulmonary fibrosis (IPF) patients. Recently, the potential efficacy of antifibrotic agents against chronic progressive fibrotic diseases including RA-UIP has been attracting attention. A 74-year-old man diagnosed with IPF on high-resolution computed tomography (HRCT). His FVC was decreasing over time, and his exertional dyspnea and cough had progressed with progression of reticulation on imaging. He was treated with nintedanib, which resulted in decreased coughing together with a reduction in FVC decline, from -11.6%/year to -5.2%/year. A swollen joint appeared eight months after this intervention, and he was diagnosed with rheumatoid arthritis. In this patient, nintedanib was effective against RA-UIP. This is the first case in which nintedanib was shown to be effective for RA-UIP.
30008722 Interferon-Gamma-Mediated Osteoimmunology. 2018 Osteoimmunology is the interdiscipline that focuses on the relationship between the skeletal and immune systems. They are interconnected by shared signal pathways and cytokines. Interferon-gamma (IFN-γ) plays important roles in immune responses and bone metabolism. IFN-γ enhances macrophage activation and antigen presentation. It regulates antiviral and antibacterial immunity as well as signal transduction. IFN-γ can promote osteoblast differentiation and inhibit bone marrow adipocyte formation. IFN-γ plays dual role in osteoclasts depending on its stage. Furthermore, IFN-γ is an important pathogenetic factor in some immune-mediated bone diseases including rheumatoid arthritis, postmenopausal osteoporosis, and acquired immunodeficiency syndrome. This review will discuss the contradictory findings of IFN-γ in osteoimmunology and its clinical application potential.
29651907 Evidence-based clinical practice guideline for adult Still's disease. 2018 Sep OBJECTIVES: Using an expert- and data-driven methodology, we have constructed the first clinical practice guidelines (CPGs) for adult Still's disease (ASD) after complete systematic review (SR) of the literature based upon the Medical Information Network Distribution Service (Minds) procedure. METHODS: The CPG committee for ASD organized by the Research Team for Autoimmune Diseases, the Research Program for Intractable Disease of the Japanese Ministry of Health, Labour, and Welfare has developed CPG for ASD 2017, according to the procedure proposed by Minds. The CPG development process includes (1) clarification of the purpose of CPG, (2) organization of the steering committee, (3) organization of the CPG committee and secretariat, (4) defining the scope (setting of clinical questions (CQs)), (5) SR, (6) development of recommendations, (7) drafting the CPG, (8) external evaluation and public comments, and (9) release. Because we wanted to construct CPG for ASD to encompass both adult-onset Still's disease (AOSD) and adult patients with systemic juvenile idiopathic arthritis (sJIA), we also included SR data from sJIA in this study. RESULTS: Twenty-six CQs were selected and roughly divided into the following items: (1) clinical findings (CQs 1-4), (2) laboratory findings (CQs 5-8), (3) complications (CQs 9-13), (4) treatment with oral medicine (CQs 14-19), (5) treatment with biological reagents (CQs 20-23), and (6) treatments for sJIA (CQs 25-26). Recommendations and the strength of the recommendations for these CQs were decided by a modified Delphi method. CONCLUSION: We have developed the first published CPG for ASD including AOSD and sJIA, which includes 26 CQs and recommendations. This guideline will help rheumatologists, non-specialized physicians, other healthcare providers, medical and health-related students, and patients and their family members to understand and treat ASD.
30207562 Tofacitinib Versus Non-Tumor Necrosis Factor Biologics for Patients With Active Rheumatoid 2018 Jun OBJECTIVES: This study aims to compare the disease status of patients with active rheumatoid arthritis (RA) after treatment with tofacitinib or non- tumor necrosis factor (TNF) biologics. PATIENTS AND METHODS: The study included a total of 50 RA patients (18 males, 32 females; mean age 68.3±1.3 years; range 42 to 92 years). We prospectively and randomly enrolled 25 patients for treatment with tofacitinib (Tofa group: 10 males, 15 females; mean age 68.3±2.0 years; range, 42 to 92 years) and 25 for treatment with non-TNF biologics (non-TNF group: 8 males, 17 females; mean age 68.3±1.7 years; range 51 to 92 years). Mean disease activity score 28 (DAS28), C-reactive protein (CRP), clinical disease activity index (CDAI), health assessment questionnaire (HAQ)-disability index (DI), and matrix metalloproteinase-3 values were recorded at baseline and at 4, 8, and 12 months. RESULTS: There was a significant difference in the percent changes of DAS28, CRP and CDAI at every time point versus baseline in both treatment groups. HAQ-DI was also significantly different at every time point in both groups except for at four months in the non-TNF group. CONCLUSION: Tofacitinib was well tolerated in active RA patients and exerted effects comparable to those of non-TNF biologics.
30181828 Prevalence of chronic obstructive pulmonary disease (COPD) among rheumatoid arthritis: res 2018 Rheumatoid arthritis (RA) is being increasingly recognized as an important contributor to chronic obstructive pulmonary disease (COPD). Although smoking is a major risk factor, other factors may play a role. We used National Inpatient Sample (NIS) from 2013 to explore this relationship. We used propensity matching with a 1:3 nearest-neighbor-matching algorithm to match 1 RA hospitalization to 3 age- and-sex-matched comparators. In the age- and-sex-matched population, RA had a higher odds of COPD (OR 1.20, 95% CI: 1.17-1.22, p < 0.0001). RA is associated with increased COPD prevalence, independent of smoking. COPD might fall within the spectrum of RA complications, likely due to autoimmune and inflammatory mechanisms.
30013458 Recovery From Rheumatoid Arthritis Following 15 Months of Therapy With Low Doses of Ionizi 2018 Jul Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that occurs commonly in old people. Hot spring radon therapy is widely practiced in Central Europe and Japan for relief from the painful symptoms. The usual duration of a spa treatment is a week or two, and the relief is temporary. This article reports on the near-complete recovery of a patient who had been suffering from RA for 10 years. The patient received 15 months of low-dose radon and γ-radiation therapy in a room that reproduced the conditions of a radon spa. The daily 40-minute exposure in the therapy room was supplemented by ten 6-minute radio-nebulizer treatments. The inflammation markers C-reactive protein and matrix metalloproteinase 3 declined strongly to the normal level of 0.07 mg/dL and the near-normal level of 48.9 ng/mL, respectively. After the patient's return to good health, the frequency of the visits was reduced to twice each month. The patient's protection systems appear to have adapted to stimulated conditions, sufficiently to sustain the recovery from RA. Such a long-term course of treatments and follow-up maintenance could be carried out in any hospital that has these low-dose radiation therapy rooms. The therapy could be scheduled to suit patient availability.
30842793 Evaluation of the Prevalence of Temporomandibular Joint Involvement in Rheumatoid Arthriti 2018 Nov OBJECTIVES: Temporomandibular joint (TMJ) disorders, known as TMDs, are significant public health problems and may result in pain and disability. In order to determine the prevalence of clinical/subjective TMD in rheumatoid arthritis (RA), we used the research diagnostic criteria (RDC)/TMD axes. We assessed the anti-cyclic citrullinated protein (anti-CCP)-related TMD in RA for the first time. MATERIALS AND METHODS: Fifty-two RA patients were compared to 47 healthy controls with regard to complete blood count (CBC), serology, acute phase reactants (APR), and TMJ dysfunction. RESULTS: The anti-CCP antibody showed a significant correlation with the development of clinical TMD (P=0.001, 95% confidence interval (CI)=12.4%-35.6%). A prevalence of 50% was calculated through the RDC/TMD for such disorders. In RA patients, statistically significant differences were observed between the groups with and without clinical TMD regarding psychological depression and physical symptoms. CONCLUSIONS: According to the results, a significant correlation was found between the anti-CCP antibody and TMD. Therefore, when this antibody is detected in the blood serum, the treatment must be initiated. The RDC/TMD used in this study assessed the prevalence of TMJ dysfunction in conformity with RA-associated TMJ findings previously obtained through other conventional methods.
32743356 Spontaneous regression of a renal mass and multiple lung nodules after methotrexate cessat 2018 Nov INTRODUCTION: Methotrexate has been reported to increase the risk of lymphoproliferative disorders. We report a rare case who was clinically diagnosed with methotrexate-associated lymphoproliferative disorders of the kidney. CASE PRESENTATION: A 77-year-old patient with rheumatoid arthritis had taken low-dose methotrexate for 13 years. The patient developed left renal mass 3 cm in size and multiple pulmonary nodules. Initially, renal malignant tumor with lung metastases was considered and the renal biopsy was planned. However, under possible diagnosis of methotrexate-related lymphoproliferative disorder, we withdrew methotrexate treatment at first and then observed spontaneous regression of the tumorous lesions of the kidney and lungs. CONCLUSION: Although methotrexate-related lymphoproliferative disorder in kidneys is very rare, our case advocates the importance of a relevant differential diagnosis of methotrexate-related lymphoproliferative disorder under the setting of long-term treatment of methotrexate for rheumatoid arthritis.
30686971 A Comparison of Co-methylation Relationships Between Rheumatoid Arthritis and Parkinson's 2018 Rheumatoid arthritis (RA) is a complex autoimmune disease. Recent studies have identified the DNA methylation loci associated with RA and found that DNA methylation was a potential mediator of genetic risk. Parkinson's disease (PD) is a common neurodegenerative disease. Several studies have indicated that DNA methylation levels are linked to PD, and genes related to the immune system are significantly enriched in PD-related methylation modules. Although recent studies have provided profound insights into the DNA methylation of both RA and PD, no shared co-methylation relationships have been identified to date. Therefore, we sought to identify shared co-methylation relationships linked to RA and PD. Here, we calculated the Pearson's correlation coefficient (PCC) of 225,239,700 gene pairs and determined the differences and similarities between the two diseases. The global co-methylation change between in PD cases and controls was larger than that between RA cases and controls. We found 337 gene pairs with large changes that were shared between RA and PD. This co-methylation relationship study represents a new area of study for both RA and PD and provides new ideas for further study of the shared biological mechanisms of RA and PD.
30588171 No effect of anti-TNF-α treatment on serum IL-17 in patients with rheumatoid arthritis. 2018 INTRODUCTION: Interleukin 17 (IL-17) and CC-chemokine ligand 20 (CCL20) are increasingly implicated in the pathogenesis of rheumatoid arthritis (RA). A correlation has been reported to exist between serum levels of IL-17 and CCL20 and the disease activity. However, such an effect has not been universally demonstrated. The aim of the present study was to investigate if serum levels of IL-17 and/or CCL20 reflect the disease activity and response to anti-TNF-α therapy in patients with RA. MATERIAL AND METHODS: Twenty-two RA patients qualified to receive anti-TNF-α treatment were prospectively assessed before and after 12 weeks of therapy. Serum concentrations of IL-17 and CCL20 were measured with high-sensitivity immunoassays. Disease activity was assessed by the 28-joint disease activity score (DAS28). RESULTS: Twelve weeks of therapy resulted in a satisfactory therapeutic response in the majority (91%) of patients (reflected both by clinical and standard biochemical criteria). However, serum concentrations of IL-17 and CCL20 did not change significantly over the course of therapy Moreover, they did not correlate with the disease activity, patient characteristics, and their response to therapy. CONCLUSIONS: Serum levels of IL-17 and CCL20 do not reflect changes in the clinical and biochemical status that occur in patients undergoing anti-TNF-α treatment for RA. The lack of such an association indicates that IL-17 signalling is not affected by anti-TNF-α therapy and is thus not critically involved in the disease pathogenesis.
30324023 Effects of rheumatoid arthritis associated transcriptional changes on osteoclast different 2018 BACKGROUND: Osteoclast differentiation in the inflamed synovium of rheumatoid arthritis (RA) affected joints leads to the formation of bone lesions. Reconstruction and analysis of protein interaction networks underlying specific disease phenotypes are essential for designing therapeutic interventions. In this study, we have created a network that captures signal flow leading to osteoclast differentiation. Based on transcriptome analysis, we have indicated the potential mechanisms responsible for the phenotype in the RA affected synovium. METHOD: We collected information on gene expression, pathways and protein interactions related to RA from literature and databases namely Gene Expression Omnibus, Kyoto Encyclopedia of Genes and Genomes pathway and STRING. Based on these information, we created a network for the differentiation of osteoclasts. We identified the differentially regulated network genes and reported the signaling that are responsible for the process in the RA affected synovium. RESULT: Our network reveals the mechanisms underlying the activation of the neutrophil cytosolic factor complex in connection to osteoclastogenesis in RA. Additionally, the study reports the predominance of the canonical pathway of NF-κB activation in the diseased synovium. The network also confirms that the upregulation of T cell receptor signaling and downregulation of transforming growth factor beta signaling pathway favor osteoclastogenesis in RA. To the best of our knowledge, this is the first comprehensive protein-protein interaction network describing RA driven osteoclastogenesis in the synovium. DISCUSSION: This study provides information that can be used to build models of the signal flow involved in the process of osteoclast differentiation. The models can further be used to design therapies to ameliorate bone destruction in the RA affected joints.
30304567 Chemical inhibition of HSP90 inhibits TNF-α mediated proliferation and induces apoptosis 2018 Oct 10 Rheumatoid arthritis fibroblast-like synoviocytes (RAFLS) proliferate abnormally and resist apoptosis. Geldanamycin (GA) and other HSP90 inhibitors have emerged as promising therapeutic agents that inhibited cancer cell growth. In this study, we explored the effects of HSP90 inhibitor, GA, on tumor necrosis factor (TNF)-α-induced proliferation and apoptosis of RAFLS, and the underlying mechanism. Human RAFLS was isolated from the knee joints of patients with RA and subjected to TNF-α treatment in combination of various concentration of GA. We found that GA dose-dependently inhibited TNF-α-induced RAFLS proliferation as measured, but promoted RAFLS apoptosis. Further mechanistic study identified that GA dose-dependently attenuated TNF-α-mediated activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) pathways, both of which are involved in TNF-α-mediated RAFLS proliferation. Moreover, GA-induced apoptosis and mitochondrial damage of RAFLS, as evidenced by increased Bax/Bcl-2 ratio and mitochondrial cytochrome c release, and enhanced cleavages of caspase-3, caspase-9, and poly-(ADP-ribose) polymerase. Collectively, our results revealed that chemical inhibition of HSP90 by GA suppressed TNF-α-induced proliferation of RAFLSs through the MAPK and NF-κB signaling pathways and induces RAFLS apoptosis via mitochondria-dependent pathway. These findings demonstrated for the first time that HSP90 inhibition in RAFLS could be therapeutic beneficial for RA.
30022862 Intestinal tuberculosis in a 55-year-old woman with a 30-year history of rheumatoid arthri 2018 INTRODUCTION: Tuberculosis (TB) is one of the endemic diseases with a challenging diagnosis in the absence of pulmonary disease. On the other hand, rheumatoid arthritis (RA) is a systemic autoimmune disease with extra-articular manifestations that occur at any age after onset, such as nodules, Sjögren's syndrome, anemia of chronic disease, and pulmonary manifestations, which are more frequently seen in patients with severe, active disease. Here we present a case of RA with intestinal TB. CASE REPORT: A 55-year-old woman with a 30-year history of RA using prednisolone and hydroxychloroquine presented with a nonpositional hypogastric pain and a weight loss of 20 kg over 7 months. No history of biological therapy was recorded. Colonoscopy revealed an ulcerated mass that was suspicious for malignancy. The pathobiological assessments confirmed ulceration and granulation tissue formation, foci of necrotizing granulomatous inflammation in lamina propria with adjacent mild crypt regenerative changes. Also, Ziehl-Neelsen staining for acid-fast bacilli in the granulomas was positive though the polymerase chain reaction assay did not detect the Mycobacterium tuberculosis. Anti-TB medication for 2 weeks eliminated the symptoms. CONCLUSIONS: Intestinal TB in patients with vague abdominal symptoms and relevant physical findings such as pain and palpable mass should be considered to prevent late or misdiagnosis.
29881347 A Novel Circulating miRNA-Based Model Predicts the Response to Tripterysium Glycosides Tab 2018 Accumulating clinical evidence show that not all rheumatoid arthritis (RA) patients benefit to the same extent from a Tripterygium wilfordii Hook F (TwHF)-based therapy-Tripterysium glycosides tablets (TG tablets), which emphasizes the need of predictive biomarkers and tools for drug response. Herein, we integrated TG tablets' response-related miRNA and mRNA expression profiles obtained from the clinical cohort-based microarray, miRNA target prediction, miRNA-target gene coexpression, as well as gene-gene interactions, to identify four candidate circulating miRNA biomarkers that were predictive of response to TG tablets. Moreover, we applied the support vector machines (SVM) algorithm to construct the prediction model for the treatment outcome of TG tablets based on the levels of the candidate miRNA biomarkers, and also confirmed its good performance via both 5-fold cross-validation and the independent clinical cohort validations. Collectively, this circulating miRNA-based biomarker model may assist in screening the responsive RA patients to TG tablets and thus potentially benefit individualized therapy of RA in a daily clinical setting.
29853727 Cartilage and bone damage in rheumatoid arthritis. 2018 Rheumatoid arthritis (RA), which is a chronic inflammatory disease with a multifactorial aetiology, leads to partial or permanent disability in the majority of patients. It is characterised by persistent synovitis and formation of pannus, i.e. invasive synovial tissue, which ultimately leads to destruction of the cartilage, subchondral bone, and soft tissues of the affected joint. Moreover, inflammatory infiltrates in the subchondral bone, which can lead to inflammatory cysts and later erosions, play an important role in the pathogenesis of RA. These inflammatory infiltrates can be seen in magnetic resonance imaging (MRI) as bone marrow oedema (BME). BME is observed in 68-75% of patients in early stages of RA and is considered a precursor of rapid disease progression. The clinical significance of synovitis and bone marrow oedema as precursors of erosions is well established in daily practice, and synovitis, BME, cysts, hyaline cartilage defects and bone erosions can be detected by ultrasonography (US) and MRI. A less explored subject is the inflammatory and destructive potential of intra- and extra-articular fat tissue, which can also be evaluated in US and MRI. Finally, according to certain hypotheses, hyaline cartilage damage may trigger synovitis and lead to irreversible joint damage, and MRI may be used for preclinical detection of cartilage biochemical abnormalities. This review discusses the pathomechanisms that lead to articular cartilage and bone damage in RA, including erosion precursors such as synovitis and osteitis and panniculitis, as well as the role of imaging techniques employed to detect early cartilage damage and bone erosions.
29567569 Ipsilateral stress fracture of the proximal fibula after total knee arthroplasty in a pati 2018 INTRODUCTION: Previous studies have reported a lower extremity stress fracture after total knee arthroplasty (TKA). However, a fibular fracture after TKA is quite rare. We report a case of proximal fibula fracture after TKA in a patient with rheumatoid arthritis (RA). PRESENTATION OF CASE: A 45 year old woman with RA had severe knee and foot pain with an antalgic gait disturbance. There was a significant joint deformity in many of lower limb joints. Interval bilateral TKAs were performed two weeks apart. Right TKA was performed using a constraint-type prosthesis, through lateral parapatellar approach. Left TKA was performed using a posterior-stabilized (PS) prosthesis through the more commonly employed, medial parapatellar approach. Seven weeks after the right TKA, the patient was found to have an atraumatic proximal fibular fracture. The fracture went on to heal conservatively. DISCUSSION: The fracture was considered to have occurred after the TKA. The callus appeared eleven weeks after the TKA. The factors that contributed to the fracture were thought to be overload of the fragile bone secondarily to disuse osteopaenia, RA or potentially the significant valgus malalignment correction. The surgical approach, the implant or implantation or the persisting joint deformity, were thought to be contributing factors to the aetiology of the stress fracture. The resultant change in clinical outcome/course is outlined in this case report. CONCLUSION: A stress fracture of the proximal fibula has the potential in the aetiology of may cause other stress fractures, joint other instability, and/or malalignment of the total lower extremity.
30402267 Neutropaenia in early rheumatoid arthritis: frequency, predicting factors, natural history 2018 OBJECTIVES: To determine the frequency, severity and natural history of neutropaenia in early rheumatoid arthritis (RA), explore its associations with clinical features and assess its impact on clinical management. METHODS: The Scottish Early Rheumatoid Arthritis inception cohort prospectively recruited patients with newly diagnosed RA and followed them up every 6 months. Patients with RA who developed at least one episode of neutropaenia (grade 1: <2.0×10^9/L; grade 2: <1.5×10^9/L; grade 3: <1.0×10^9/L; grade 4: <0.5×10^9/L) were compared with those who did not. Comparisons were also made between patients who experienced one or more episodes of neutropaenia and between patients with different neutropaenia grades. RESULTS: 77 neutropaenia episodes were recorded in 58 of 771 (7.5%) patients with RA, who were followed up for a median (range) of 18 (6-48) months. Neutropaenia occurred at a median (range) of 12 (0-120) months after RA diagnosis. The majority had mild neutropaenia (grade 1: n=42; grade 2: n=14; grade 3: n=1; grade 4: n=1). Neutropaenia was transient (single episode) in the majority (44; 75.8%) of cases but led to treatment discontinuation in 14 (24.1%) patients. Patients who developed neutropaenia were more likely to be female (p=0.01) and non-smokers (p=0.007) and had lower baseline neutrophil levels (p<0.0001). Binomial regression analysis confirmed the latter (p<0.0001, B: -0.491) as neutropaenia predictor. The rate of infections did not differ between patients who developed neutropaenia and those who did not (p=0.878). CONCLUSION: Neutropaenia was a common finding in this cohort. It was usually mild, transient and not associated with increased infection rates. Neutropaenia occurrence was associated with non-smoking, female gender and lower baseline neutrophil levels.
29068268 Structural insights into the binding mode of flavonols with the active site of matrix meta 2018 Nov Cartilage degradation in rheumatoid arthritis is mediated principally by the collagenases and gelatinases. Gelatinase B (also called matrix metalloproteinase 9 - MMP-9), is a valid target molecule which is known to participate in cartilage degradation as well as angiogenesis associated with the disease and inhibition of its activity shall prevent cartilage damage and angiogenesis. The focus of this study is to investigate the possibilities of MMP-9 inhibition by flavonol class of bioflavonoids by studying their crucial binding interactions at the active site of MMP 9 using molecular docking (Glide XP and QPLD) and further improvisation by post-docking MM-GBSA and molecular dynamic (MD) simulations. The results show that flavonols can convincingly bind to active site of MMP-9 as demonstrated by their stable interactions at the S1' specificity pocket and favourable binding energies. Gossypin has emerged as a promising candidate with a docking score of -14.618 kcal/mol, binding energy of -79.97 kcal/mol and a stable MD pattern over 15 ns. In addition, interaction mechanisms with respect to catalytic site zinc are also discussed. Further, the drug-like characters of the ligands were also analysed using ADME analysis.
29122658 Endothelium-derived contraction in a model of rheumatoid arthritis is mediated via angiote 2018 Jan A role for endothelium-derived constricting factors (EDCF), and the angiotensin II type 1 receptor (AT1R) pathway, in the vascular impairment found in the rat Freund's complete adjuvant (FCA)-model of rheumatoid arthritis (RA) was examined. FCA arthritis was induced in rats±losartan. Vehicle-treated rats served as controls. Knee-joint swelling and red blood cell (RBC) aggregation were measured as indicators of inflammation and endothelium reactivity assessed by response to acetylcholine (ACh) on aortic rings. Results show that knee-joint swelling and RBC aggregation were elevated in the FCA+vehicle group and restored to control levels in the FCA+losartan-treated animals. ACh-induced relaxation of aortic rings taken from FCA+vehicle animals was significantly impaired compared to vehicle-controls and this vasoreactivity was restored to control levels in the FCA+losartan-treated group. Further examination of aorta from the FCA+vehicle animals revealed an EDCF that was reliant on cyclooxygenase-2 (but not cyclooxygenase-1), generation of superoxide anion generation (but not hydrogen peroxide) and activation of thromboxane-prostanoid receptor. Losartan administration in vivo or ex vivo (to aortic rings) prevented the generation of the EDCF. In summary, this is the first evidence of an EDCF in a model of RA and identifies this mechanism as potentially significant in the cardiovascular disorder associated with the disease.
30016193 Long-Term Effect of Pulsed Nd:YAG Laser in the Treatment of Children with Juvenile Rheumat 2018 Aug OBJECTIVE: The aim of this study was to evaluate the long-term impact of a pulsed neodymium-doped yttrium aluminum garnet (Nd:YAG) laser [high-intensity laser therapy (HILT)] in the treatment of juvenile rheumatoid arthritis (JRA). MATERIALS AND METHODS: A sample of 30 children participated in this study (15 in the laser group and 15 in the placebo group), with a mean age of 10.53 ± 1.25 years. Children who were randomly assigned to the laser group received HILT thrice per week for 4 weeks, plus the exercise program. HILT scanned each knee with 600 J in two phases and 15 J to 10 points for a total of 750 J for each knee. The placebo laser group received placebo HILT plus the same exercise program. The outcomes measured in this study were the pain level by the visual analog scale (VAS) and gait parameters by the GAITRite(®) system. Statistical analysis was performed by ANOVA with repeated measures to compare the differences between the baseline, post-treatment, and 12-week follow-up measurements for both groups. The level of significance was set at p < 0.05. RESULTS: The VAS results significantly decreased post-treatment in the laser group relative to the placebo group and were still improved at the 12-week follow-up. Gait parameters significantly increased in the laser group after 4 weeks of treatment and after 12 weeks compared to the placebo group. CONCLUSIONS: HILT, when combined with an exercise program, appears to be more effective in children with JRA than a placebo laser procedure with exercises.