Thalidomide Is an Adjunct Therapy for the Refractory Systemic Juvenile Idiopathic Arthritis Patients in a Tertiary Hospital Study

Background: Systemic JIA (sJIA) is one of the subtypes of JIA, which is most difficult to treat among all JIA cases. About 50% of sJIA cases did not respond to traditional disease modifying anti-rheumatic drugs (DMARDs)—metho-trexate (MTX). Thalidomide is an immunomodulating and anti-inflammatory drug that induces sustained improvement of refractory sJIA cases. Objectives: To evaluate the efficacy of thalidomide in refractory sJIA patients. Methods: This was a prospective interventional study carried out in the Paediatric Rheumatology and Immunology follow-up clinic run by the Department of Pediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka from January 2019 to July 2020. Twenty-five sJIA patients who were refractory to conventional DMARDs were included in this study. These patients were prescribed thalidomide at a dose of 3 - 5 mg/kg/day for six months and efficacy was assessed by using juvenile arthritis disease activity score (JADAS 27) at 12th and 24th weeks of treatment. Result: Active joint counts and ESR improvement were observed in 90.69%, 97.67% and 69.84%, 100% of sJIA patients respectively at 12th and 24th weeks of treatment. Improvement of physicians and parent global assessment of VAS were 77.56%, 97.43% and 70.62% and 96.04% respectively at 12th and 24th weeks of treatment. Improvement of the total score of JADAS-27 was 77.51% at 12th week and 97.52% at 24th of week follow-up which was statistically significant. Somnolence, constipation and paresthesia were found as common adverse effect in this study. Conclusion: Efficacy of thalidomide was assessed by JADAS 27 criteria showed significant improvement in refractory sJIA patients in this study. It may be concluded that Thalidomide is safe and effective as an adjunct therapy of refractory sJIA patients.

Current Review of Systemic Juvenile Idiopathic Arthritis: What Do Paediatricians Need to Know?

Systemic juvenile idiopathic arthritis is classified as an autoimmune entity and a subtype of juvenile idiopathic arthritis, although it has many features of autoinflammatory-type of diseases. This review article will elaborate on the disease’s pathogenesis and its proposed relation to autoinflammatory diseases including defective innate immunity and phagocytosis response leading excessive cytokine release. It also explains the disease’s epidemiology, clinical phenotype, diagnostic challenges, complications and current advancements in the treatment of systemic juvenile idiopathic arthritis, such as IL-1 and IL-6 antagonists and their impact on the disease trajectory. Care of patients with systemic juvenile idiopathic arthritis requires a comprehensive multidisciplinary team to optimize the care and avoid complications of the disease itself such as growth impairment, macrophage activation syndrome or the complications of immunosuppressant and immunomodulatory treatments.

Operative stabilization of the remaining mobile segment in ankylosed cervical spine in systemic onset- juvenile idiopathic arthritis:A case report

We describe a case of a 19-year-old young man with oligoarthritis type of juvenile idiopathic arthritis, who presented with several month duration of lower neck pain and progressive muscular weakness of all four limbs. X-rays of the cervical spine demonstrated spontaneous apophyseal joint fusion from the occipital condyle to C6 and from C7 to Th2 with marked instability between C6 and C7. Surgical intervention began with anterolateral approach to the cervical spine performing decompression, insertion of cage and anterior vertebral plate and screws, followed by posterior approach and fixation. Care was taken to restore sagittal balance. The condition was successfully operatively managed with multisegmental, both column fixation and fusion, resulting in pain cessation and resolution of myelopathy. Postoperatively, minor swallowing difficulties were noted, which ceased after three days. Patient was able to move around in a wheelchair on the sixth postoperative day. Stiff neck collar was advised for three months postoperatively with neck pain slowly decreasing in the course of first postoperative month.On the follow-up visit six months after the surgery patient exhibited no signs of spastic tetraparesis, X-rays of the cervical spine revealed solid bony fusion at single mobile segment C6-C7. He was able to gaze horizontally while sitting in a wheelchair. Signs of myelopathy with stiff neck and single movable segment raised concerns about intubation, but were successfully managed using awake fiber-optic intubation. Avoidance of tracheostomy enabled us to perform an anterolateral approach without increasing the risk of wound infection. Regarding surgical procedure, the same principles are obeyed as in management of fracture in ankylosing spondylitis or Mb. Forestrier.

Systemic juvenile idiopathic arthritis–associated lung disease: A retrospective cohort study

BACKGROUND Lung damage in systemic juvenile arthritis(sJIA)is one of the contemporary topics in pediatric rheumatology.Several previous studies showed the severe course and fatal outcomes in some patients.The information about interstitial lung disease(ILD)in the sJIA is scarce and limited to a total of 100 cases.AIM To describe the features of sJIA patients with ILD in detail.METHODS In the present retrospective cohort study,information about 5 patients less than 18-years-old with sJIA and ILD were included.The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019.ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement.Macrophage activation syndrome(MAS)was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement.RESULTS The onset age of sJIA ranged from 1 year to 10 years.The time interval before ILD ranged from 1 mo to 3 years.The disease course was characterized by the prevalence of the systemic features above articular involvement,intensive rash(100%),persistent and very active MAS(hScore range:194-220)with transaminitis(100%),and respiratory symptoms(100%).Only 3 patients(60%)developed a clubbing phenomenon.All patients(100%)had pleural effusion and 4 patients(80%)had pericardial effusion at the disease onset.Two patients(40%)developed pulmonary arterial hypertension.Infusion-related reactions to tocilizumab were observed in 3(60%)of the patients.One patient with trisomy 21 had a fatal disease course.Half of the remaining patients had sJIA remission and 2 patients had improvement.Lung disease improved in 3 patients(75%),but 1 of them had initial deterioration of lung involvement.One patient who has not achieved the sJIA remission had the progressed course of ILD.No cases of hyper-eosinophilia were noted.Four patients(80%)received canakinumab and one(20%)tocilizumab at the last follow-up visit.CONCLUSION ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset.Extensive rash,serositis(especially pleuritis),full-blown MAS with transaminitis,lymphopenia,trisomy 21,eosinophilia,and biologic infusion reaction are the main predictors of ILD.The following studies are needed to find the predictors,pathogenesis,and treatment options,for preventing and treating the ILD in sJIA patients.

Systematic review and network meta-analysis of different nonsteroidal anti-inflammatory drugs for juvenile idiopathic arthritis

BACKGROUND Various non-steroidal anti-inflammatory drugs(NSAIDs)have been used for juvenile idiopathic arthritis(JIA).However,the optimal method for JIA has not yet been developed.AIM To perform a systematic review and network meta-analysis to determine the optimal instructions.METHODS We searched for randomized controlled trials(RCTs)from PubMed,EMBASE,Google Scholar,CNKI,and Wanfang without restriction for publication date or language at August,2023.Any RCTs that comparing the effectiveness of NSAIDs with each other or placebo for JIA were included in this network meta-analysis.The surface under the cumulative ranking curve(SUCRA)analysis was used to rank the treatments.P value less than 0.05 was identified as statistically significant.RESULTS We included 8 RCTs(1127 patients)comparing 8 different instructions including meloxicam(0.125 qd and 0.250 qd),Celecoxib(3 mg/kg bid and 6 mg/kg bid),piroxicam,Naproxen(5.0 mg/kg/d,7.5 mg/kg/d and 12.5 mg/kg/d),inuprofen(30-40 mg/kg/d),Aspirin(60-80 mg/kg/d,75 mg/kg/d,and 55 mg/kg/d),Tolmetin(15 mg/kg/d),Rofecoxib,and placebo.There were no significant differences between any two NSAIDs regarding ACR Pedi 30 response.The SUCRA shows that celecoxib(6 mg/kg bid)ranked first(SUCRA,88.9%),rofecoxib ranked second(SUCRA,68.1%),Celecoxib(3 mg/kg bid)ranked third(SUCRA,51.0%).There were no significant differences between any two NSAIDs regarding adverse events.The SUCRA shows that placebo ranked first(SUCRA,88.2%),piroxicam ranked second(SUCRA,60.5%),rofecoxib(0.6 mg/kg qd)ranked third(SUCRA,56.1%),meloxicam(0.125 mg/kg qd)ranked fourth(SUCRA,56.1%),and rofecoxib(0.3 mg/kg qd)ranked fifth(SUCRA,56.1%).CONCLUSION In summary,celecoxib(6 mg/kg bid)was found to be the most effective NSAID for treating JIA.Rofecoxib,piroxicam,and meloxicam may be safer options,but further research is needed to confirm these findings in larger trials with higher quality studies.

Characterization of microbiota in systemic-onset juvenile idiopathic arthritis with different disease severities

BACKGROUND Systemic-onset juvenile idiopathic arthritis (SoJIA) is one of most serious subtypes of juvenile idiopathic arthritis. Although the pathogenesis of SoJIA remains unclear, several studies have suggested a correlation between gut dysbiosis and JIA. Further understanding of the intestinal microbiome may help to establish alternative ways to treat, or even prevent, the disease. AIM To explore alterations in fecal microbiota profiles in SoJIA patients and to evaluate the correlations between microbiota and clinical parameters. METHODS We conducted an observational single-center study at the Pediatric Department of Peking Union Medical College Hospital. Children who were diagnosed with SoJIA at our institution and followed for a minimum period of six months after diagnosis were recruited for the study. Healthy children were recruited as a control group (HS group) during the same period. Clinical data and stool samples were collected from SoJIA patients when they visited the hospital. RESULTS The SoJIA group included 17 active and 15 inactive consecutively recruited children;the control group consisted of 32 children. Firmicutes and Bacteroidetes were the two most abundant phyla among the total sample of SoJIA children and controls. There was a significant difference among the three groups in observed species, which was the highest in the Active-SoJIA group, followed by the Inactive-SoJIA group and then HS group (Active-SoJIA vs HS: P = 0.000;and Inactive-SoJIA vs HS: P = 0.005). We observed a lower Firmicutes/Bacteroidetes ratio in SoJIA patients (3.28 ± 4.47 in Active-SoJIA, 5.36 ± 8.39 in Inactive-SoJIA,and 5.67 ± 3.92 in HS). We also observed decreased abundances of Ruminococcaceae (14.9% in Active-SoJIA, 17.3% in Inactive-SoJIA, and 22.8% in HS;Active-SoJIA vs HS: P = 0.005) and Faecalibacterium (5.1% in Active-SoJIA, 9.9% in Inactive-SoJIA, and 13.0% in HS;Active-SoJIA vs HS: P = 0.000) in SoJIA compared with HS. By contrast, the abundance of Bacteroidaceae was the highest in the Active-SoJIA group, followed by the Inactive-SoJIA and HS groups (16.5% in Active-SoJIA, 12.8% in Inactive-SoJIA, and 9.7% in HS;Active-SoJIA vs HS: P = 0.03). The Spearman correlation analysis revealed a negative correlation between Proteobacteria or Enterobacteriaceae and juvenile arthritis disease activity score on 27 joints (JADAS-27). CONCLUSION The composition of the intestinal microbiota is different in SoJIA patients compared with healthy children. The dysbiosis presents partial restoration in inactive status patients.

Evolution of treatment options for juvenile idiopathic arthritis

A recent study published in World J Clin Cases addressed the optimal non-steroidal anti-inflammatory drugs(NSAIDs)for juvenile idiopathic arthritis(JIA).Herein,we outline the progress in drug therapy of JIA.NSAIDs have traditionally been the primary treatment for all forms of JIA.NSAIDs are symptom-relief medications,and well tolerated by patients.Additionally,the availability of selective NSAIDs further lower the gastrointestinal adverse reactions compared with traditional NSAIDs.Glucocorticoid is another kind of symptom-relief medications with potent anti-inflammatory effect.However,the frequent adverse events limit the clinical use.Both NSAIDs and glucocorticoid fail to ease or pre-vent joint damage,and the breakthrough comes along with the disease-mo-difying antirheumatic drugs(DMARDs).DMARDs can prevent disease pro-gression and reduce joint destruction.Particularly,the emergence of biologic DMARDs(bDMARDs)has truly revolutionized the therapeutics of JIA,compared with conventional synthetic DMARDs.As a newly developed class of drugs,the places of most bDMARDs in the management of JIA remain to be well estab-lished.Nevertheless,the continuous evolution of bDMARDs raises hopes of improving long-term disease outcomes for JIA.

Serum Zinc and Copper Level in Juvenile Idiopathic Arthritis (JIA) Patients and Its Correlation with Disease Duration-A Tertiary Hospital Study

Background: Juvenile Idiopathic Arthritis (JIA) is the most prevalent rheumatic disease in children. It is associated with abnormal levels of serum zinc (Zn) and copper (Cu) as during inflammation serum copper concentration increases and zinc decreases. Objective: To assess the serum Zn and Cu levels in different sub-types of JIA patients and their correlation with the disease duration. Methods: This cross-sectional study was conducted over twelve months at the Pediatric Rheumatology Division, Department of Paediatrics, Bangabandhu Sheikh Mujib Medical University. Sixty-nine JIA cases that fulfilled the International League of Association for Rheumatology (ILAR) criteria were taken as cases and age and sex-matched healthy children were considered as controls. The serum Zn and Cu tests were done using the spectrophotometric method with INDIKO PLUS Drug Analyzer. Data were recorded in a pre-designed questionnaire. Data were checked, verified and analyzed manually where continuous variables were analyzed using unpaired t-test and categorical variables using the ANOVA test. Pearson’s correlation coefficient test was used to see the correlation of serum zinc and copper levels with disease duration. Results: Boys were predominant in both case and control groups, with the majority within the 10 to 16-year-age group. Enthesitis-related arthritis (ERA) was the most common subtype followed by sJIA, Oligo JIA, Poly JIA (RF-) and unclassified subtypes. Disease duration was found less than 12 months in 30.4% of JIA patients. Serum analysis revealed a statistically significant reduction in mean zinc levels and increased copper levels in JIA patients compared to controls. This study observed a negative correlation between serum zinc levels and disease duration, whereas serum copper levels exhibited a positive correlation with disease duration. Conclusion: In conclusion, this study revealed that JIA patients exhibit alterations in serum zinc and copper levels. Serum copper levels showed a positive correlation and serum zinc levels showed a negative correlation with the duration of the disease.

Clinical and laboratory features of juvenile idiopathic arthritis with wrist involvement:Results of a retrospective cohort study

BACKGROUND Previous studies in the pre-biological era showed an association of wrist inflammation in juvenile idiopathic arthritis(JIA)with progressive disease course,polyarticular involvement and failure of methotrexate treatment.AIM To describe features of JIA,associated with wrist arthritis.METHODS Data from about 753 JIA patients were included in this retrospective cohort study.The clinical and laboratory features of patients with and without wrist involvement were analyzed.RESULTS Wrist involvement was found in oligoarthritis(5.8%),RF(−)/RF(+)polyarthritis(44.9%/15.0%),enthesitis-related arthritis(17.7%),and systemic(58.6%)JIA categories.Unilateral wrist involvement was typical for oligoarthritis patients,bilateral involvement was either equal to that of unilateral involvement or was more frequent in other categories.Wrist arthritis was found to be associated with female sex,a low incidence of uveitis,and more indications of systemic inflammation,including elevated levels of C-reactive protein,erythrocyte sedimentation rate,and platelets,as well as involvement of the cervical spine,temporomandibular,shoulder,elbow,metacarpophalangeal,proximal interphalangeal,distal interphalangeal,hip,ankle,and tarsus arthritis.The number of patients with hip osteoarthritis and hip replacement was also higher.Wrist arthritis was associated with a lower probability of achieving remission[hazard ratio(HR)=1.3(95%CI:1.0-1.7),P=0.055],and a higher probability of being treated with biologics[HR=1.7(95%CI:1.3-2.10,P=0.00009)].CONCLUSION Wrist arthritis in JIA patients is a marker of a severe disease course,characterized by more intensive inflammation,unfavorable outcomes,and.requiring more intensive treatment with early administration of biologics.Close monitoring of wrist inflammation with ultrasound and MR assessment with early biological treatment might improve the outcomes.

A Single-Center Experience of Systemic Onset Juvenile Idiopathic Arthritis at a Tertiary Hospital in Jeddah, Saudi Arabia

Background and Objective: Systemic-onset juvenile idiopathic arthritis (JIA) is a major and prevalent subset of arthritis among children and it has a broad spectrum of clinical presentation, course and prognosis. This study described the clinical presentation of systemic-onset JIA in a Saudi-based cohort. Methods: A retrospective chart review was performed of the medical records of children with systemic-onset JIA who were followed up at King Abdul Aziz University Hospital, Jeddah, between January 1997 and December 2013. Patients’ files were reviewed for demographic, clinical, and paraclinical data, which were analyzed using the statistical Package for the Social Sciences. Results: We included 20 patients of both genders (8 boys and 12 girls). The mean age of disease onset was 7 (4.5) years. The most common presenting symptoms were fever (100%), arthritis (100%), and rash (55%). Hepatomegaly (5%), abdominal (5%) and pulmonary manifestations (3%) were less frequent manifestations. Most patients had high white blood cell counts (50%), elevated erythrocyte sedimentation rates (80%) and C-reactive protein levels (90%). The interval between onset of symptoms and diagnosis was 9.4 (12.5) weeks. Patients were treated with non-steroidal anti-inflammatory drugs, methotrexate, steroids, anti-tumor necrosis agents, and disease-modifying anti-rheumatic drugs. Bone marrow biopsy was conducted to exclude malignancy in 20% of the patients. Conclusion: Saudi children with systemic-onset JIA present with prolonged fever and arthritis (mainly oligoarticular rather than polyarticular). Physicians should be aware of the presentation of systemic-onset JIA in our setting in order to make prompt diagnosis and treatment decisions as early as possible. Carful follow-up of febrile patients is paramount to reaching the diagnosis early and initiating treatment.

Vaccination coverage in children with juvenile idiopathic arthritis,inflammatory bowel diseases,and healthy peers:Cross-sectional electronic survey data

BACKGROUND Patients with immune-mediated diseases,such as juvenile idiopathic arthritis(JIA)and inflammatory bowel disease(IBD)are at increased risk of developing infections,due to disease-related immune dysfunction and applying of immunosuppressive drugs.AIM To evaluate vaccine coverage in patients with IBD and JIA,and compare it with healthy children.METHODS In the cross-sectional study we included the data from a questionnaire survey of 190 Legal representatives of children with JIA(n=81),IBD(n=51),and healthy children(HC,n=58).An electronic online questionnaire was created for the survey.RESULTS There were female predominance in JIA patients and younger onset age.Parents of JIA had higher education levels.Employment level and family status were similar in the three studied groups.Patients with JIA and IBD had lower vaccine coverage,without parental rejection of vaccinations in IBD,compare to JIA and healthy controls.The main reason for incomplete vaccination was medical conditions in IBD and JIA.IBD patients had a lower rate of normal vaccine-associated reactions compared to JIA and HC.The encouraging role of physicians for vaccinations was the lowest in JIA patients.IBD patients had more possibilities to check antibodies before immune-suppressive therapy and had more supplementary vaccinations compared to JIA and HC.CONCLUSION JIA and IBD patients had lower vaccine coverage compared to HC.Physicians'encouragement of vaccination and the impossibility of discus about future vaccinations and their outcomes seemed the main factors for patients with immune-mediated diseases,influencing vaccine coverage.Further investigations are required to understand the reasons for incomplete vaccinations and improve vaccine coverage in both groups,especially in rheumatic disease patients.The approaches that stimulate vaccination in healthy children are not always optimal in children with immunemediated diseases.It is necessary to provide personalized vaccine-encouraging strategies for parents of chronically ill children with the following validation of these technics.

Systemic Form of Juvenile Idiopathic Arthritis: Epidemiological, Clinical, Paraclinical and Therapeutic Aspects of 13 Cases in Abidjan

Objective: To describe the epidemiological, clinical, paraclinical and therapeutic aspects of systemic juvenile idiopathic arthritis observed in Abidjan. Materials and Method: This retrospective and descriptive study covered 13 children suffering from systemic juvenile idiopathic arthritis selected in the Rheumatology Department of University Hospital Center of Cocody in Abidjan (Cote d’Ivoire) from January 2005 to December 2015. We were interested to the sociodemographical, clinical, paraclinical and therapeutic aspects. Results: The systemic form of the juvenile idiopathic arthritis represented 0.2% of the 4608 rheumatologic diseases and 70.58% of the JIA. We selected 6 boys and 7 girls, with an average age of 10.8 years and mostly going to school (84.61%). The diagnostic delay was 18 months. The main clinical signs were fever and joint damage observed each in 100% of cases, impaired general condition (92.30%) and tumor syndrome (83.33%). Biological signs were characterized by hyperleukocytosis (69.20%) and the presence of a biologic inflammatory syndrome (on average, erythrocyte sedimentation rate 59.6 mm and C Reactive Protein 56.4 mg/l). The cervical damage was the essential functional complication (38.46%). The major treatment has been a therapeutic combination based on corticotherapy and methotrexate (100%) with 1 death case by macrophage activation syndrome. Conclusion: Systemic juvenile idiopathic arthritis is rarely diagnosed in the rheumatologic practice in Abidjan. It concerns children relatively big, and is characterized by a febrile polyarthritis with impaired general condition and tumor syndrome. This systemic form is treated by corticotherapy and methotrexate.

Anemia in Juvenile Idiopathic Arthritis (JIA) and Other Pediatric Rheumatologic Diseases: A Retrospective Study

Objectives: The present study estimated the prevalence of anemia among children and adolescents with pediatric rheumatological diseases in a referral center, and analyzed the associated clinical and biological parameters. Methods: A retrospective chart review included 49 children with rheumatological diseases, who were diagnosed by a pediatric rheumatologist and classified according to the International League of Associations for Rheumatology (ILAR) guidelines and criteria endorsed by the American College of Rheumatologists. Anemia was defined as hemoglobin level lower than the 5th centile for the corresponding age and gender. Disease activity was indicated by serum levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), where available. Results: Participants were aged 2 - 18 years (mean ± SD = 10.41 ± 4.23 years), 38 (77.6%) of them had JIA, and 8 (16.3%) had systemic lupus erythematosus. The most frequent subtype of JIA was the polyarticular (16 out of 38, 42.1%), followed by systemic (14, 36.8%). The prevalence of anemia was 46.9% (95% CI = 32.5% - 61.7%), with no significant difference between JIA and other diseases or between the different JIA subtypes. Nevertheless, anemia was more frequently observed in younger patients (age 2 - 6 years: 69.2% vs <48%) and those with elevated ESR (68.8% vs 33.3%) or CRP (60.0% versus 45.2%), compared with their counterpart respectively;however, only the association with ESR was statistically significant (p = 0.049). No agreement was found between CRP and ESR (Kappa = 0.140). Conclusion: Anemia is frequent in JIA and other rheumatologic diseases in children, concerning approximately 50% of the patients and responding to anemia of inflammation as the major pathophysiological mechanism. Further research is warranted to provide more accurate insight into the pathophysiological mechanisms and clinical characteristics of anemia in pediatric rheumatological disease and to measure its morbidity, to provide efficient and evidence-based management strategies.

Update on biologic therapies for juvenile idiopathic arthritis-associated uveitis

Juvenile idiopathic arthritis(JIA)is the most common rheumatic disease of childhood,and juvenile idiopathic associated uveitis(JIA-U)is the most frequently noted extra-articular manifestation.JIA-U can present asymptomatically and lead to ocular complications,so regular screening and monitoring are needed to prevent potentially sight-threatening sequelae.Topical glucocorticoids such as prednisolone acetate are usually the first line of treatment for anterior uveitis associated with JIA-U,but long-term use may be associated with cataract,ocular hypertension and glaucoma.Disease modifying anti-rheumatic drugs(DMARDs)such as methotrexate allow tapering of the corticosteroids to prevent long-term complications.Biologic therapies have been increasingly used as targeted therapies for JIA-U,particularly monoclonal antibodies targeting the proinflammatory cytokine TNF-αsuch as adalimumab and infliximab.One recent,multicenter,prospective,randomized clinical trial provided evidence of the efficacy of adalimumab with methotrexate for JIA-U compared to methotrexate alone.Another clinical trial studying the interleukin-6 inhibitor tocilizumab for JIA-U showed promise in tapering topical corticosteroids.Additionally,JAK inhibitors are emerging biologic therapies for JIA-U in patients refractory to TNF-αinhibitors,with a clinical trial assessing the efficacy of baricitinib for JIA-U underway.While clinical trials on these novel biologics are limited,further investigation of these agents may provide additional therapeutic options for JIA-U.

Expression of FLICE-inhibitory Protein in Synovial Tissue and Its Association with Synovial Inflammation in Juvenile Idiopathic Arthritis

Objective To examine the expression of FLICE-inhibitory protein (FLIP) in juvenile idiopathic arthritis (JIA) and analyze its correlation with synovial inflammation. Methods The expression of FLIP was assessed in 11 JIA and 3 normal synovial tissue samples by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. The cell types expressing FLIP were further characterized,and the correlation of FLIP expression with the degree of synovial inflammation,as well as the activity of caspase 8 was then analyzed. Results RT-PCR revealed the expression of FLIP mRNA in all 11 JIA samples,but not in 3 normal synovial tissues. In JIA,FLIP expression could be found in both the lining and sublining layers,mainly in the macrophage-like cells. Moreover,the expression of FLIP in JIA synovial tissues was positively correlated with the degree of synovial inflammation (r=0.563,P<0.05). Conclusion The expression of antiapoptotic FLIP in JIA synovial tissue and its correlation to accumulation of inflammatory cells in synovial tissue suggests that FLIP potentially extends the lifespan of synovial cells and thus contributes to the progression of joint destruction.

A Rare Case of Chronic Recurrent Multifocal Osteomyelitis with Undifferentiated Juvenile Idiopathic Arthritis, Uveitis, and Psoriasis

We report here a 17-year-old boy with a complicated presentation of undifferentiated juvenile idiopathic arthritis, vision-threatening uveitis and chronic recurrent multifocal osteomyelitis (CRMO) in the pelvis. His severe iritis needed subtenon injections and only responded to infliximab after failing multiple biologics. Unfortunately he later developed infliximab-associated psoriasis. A combination of infliximab and ustekinumab induced remission of his arthritis, osteomyelitis, uveitis and psoriasis without experiencing severe infections.

The Relationship between Bone Mineral Density and Dietary Intake in Moroccan Children with Juvenile Idiopathic Arthritis

Background and objective: The aim of this study was to evaluate the association between dietary intake and bone mineral density in children with juvenile idiopathic arthritis (JIA). Methods: A cross-sectional study carried out in Morocco between May 2010 and June 2011, covering out patients with JIA. The characteristics of patients were collected. The nutritional status was assessed by a food questionnaire including data of food intake during 7 consecutive days using 24-hour dietary recall. Food intake was quantified using the software Bilnut (Bilnut version 2.01, 1991). Bone mineral density (BMD in g/cm2) was measured by DXA method (X-ray absorptiometry) on a Lunar Prodigy. Results: The study consisted of 33 patients with JIA (4 - 16 years old). The median age of patients was 10.4 ± 4.3 years. Median disease duration was 2 (1 - 4.5) years. The group of patients with low dietary intake of proteins was associated with low BMD (p = 0.03). Low BMD was related with low intake of magnesium (p = 0.007) and vitamin C (p = 0.04) in children aged between 4 and 9 years. Low intake of vitamin E and folate was associated with high BMD in the other range of children (p < 0.001). Conclusion: This study suggests that low intake of protein and of some micronutrients (magnesium, vitamin C, vitamin E and folate) influence bone mass in children with JIA. Prospective studies with a larger number of patients seem to be necessary in order to confirm our findings.

Current Approach to Treatment of Juvenile Idiopathic Arthritis: Case Report of Hiperimmunglobulin E Syndrome Developed Juvenile Idiopathic Arthritis

Introduction: Juvenile idiopathic arthritis (JIA) represents a heterogeneous group of childhood chronic arthritic conditions. The pathogenesis of JIA remains incompletely understood. This disease can lead to a significant morbidity including joint deformity, growth impairment and a persistence of active arthritis into adulthood. The past two decades have witnessed significant advances in treatment and improved outcomes for affected children. With the current use of biologics, more target-specific, better tolerated, safer and more effective treatments have become possible. However, continuing, comprehensive follow-up is needed to characterize the long-term effects of such treatments. Hyperimmunoglobulin E syndrome (hyper-IgE, or Job’s syndrome) is a rare immune deficiency characterized by high IgE levels, atopic chronic eczema, tendency towards re-current pyogenic infection, neutrophil chemotaxis disorder and varying T-cell function impairment. Case Report: The case of a 17-year-old male patient with hyper-IgE who develops the oligoarticular subtype of JIA over a period of four years is discussed. The course of JIA is unfavorable, causing severe deformity of numerous joints (left elbow, right 3rd metacarpophalangeal, left knee, right ankle) and a fungal infection scar on the left eye. Blood tests show an ESR of 89 mm/h, rheumatoid factor (RF) 8.3 IU/mL (0 - 20) and positive antinuclear antibody (ANA). To improve gait, corrective surgery is performed on the right ankle, followed by rehabilitation and physical therapy. Conclusion: Developments in the near future will be crucial for understanding JIA pathophysiology and improving treatment.

Evaluation of Tuberculin Skin Test Response and Interfering Factors in Patients with Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is the most common rheumatologic disease in pediatric age group. Mycobacterium tuberculosis infection (TB) is an important cause of mortality and morbidity in patients with inflammatory rheumatologic disease. The objective of this study is to determine to what extent active disease and use of drugs in JIA affects response to PPD skin test and thus to investigate the significance of PPD skin test in the diagnosis of latent TB. 77 children diagnosed with JIA according to ILAR diagnostic criteria and routinely followed by our rheumatology clinic were included in the patient group. Patients were grouped according to subtypes of disease, activity status and drugs they used. Control group was formed from 58 healthy children. PPD skin test was applied to each subject and the number of BCG scars of all cases was recorded. We found no significant difference in PPD induration diameters between JIA and control group (p > 0.05). The number of BCG scar is similar in both groups. In the control group, age and number of BCG scars and PPD skin test diameter are positively correlated. But there is no such significant relationship in patients with JIA (p > 0.05). PPD induration diameter of patients with active disease is significantly shorter than patients in remission (p > 0.05). PPD induration diameter of patients treated with steroid and disease modifying anti-rheumatic drug (DMARD) and underwent remission were not significantly different from the control group. When compared with patients using other drugs, patients on remission using steroid and DMARD have shorter PPD induration diameter. Activity of disease and drugs used (steroid, DMARD) affects PPD response. In the diagnosis of latent TB, normal range of PPD diameter in healthy child changes in JIA patient with active disease. That the PPD diameter is shorter than normal range could indicate underlying TB infection. This fact should be considered in the follow-up of the patients with JIA.

A 10-Year Saudi Experience of Using Adalimumab in Treating Juvenile Idiopathic Arthritis

Background: Traditionally, management of Juvenile Idiopathic Arthritis (JIA) involves use of non-steroidal anti-inflammatory drugs (NSAIDS) or disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX) or sulfasalazine;or steroids. However, in several cases, a low therapeutic response or important side effects is encountered. This study reports our experience in using adalimumab in JIA patients by assessing the efficacy and safety of this treatment in this category of patients. Methods: A retrospective study was conducted among 38 patients with JIA at the Pediatric Department, King Abdulaziz Univesrity Hospital, Jeddah, Saudi Arabia, in the period January 2005-March 2016. Patients’ records were reviewed and relevant demographic and clinical data were collected. Data were analyzed using SPSS version 21 and represented using tables. Results: The 38 patients were distributed as 11 (28.9%) males and 27 (71.1%) females;mean ± SD age was 11.91 ± 4.54 (range = 3 - 19) years. Mean ± SD (range) disease duration was 3.26 ± 2.52 (0 - 12) years and most frequent diagnoses included polyarticular rheumatoid factor (RF) negative form 12 (31.6%), followed by systemic and oligoarticular JIA with 9 (23.7%) cases each. Before adalimumab, fever was present in 13 (34.2%) cases, followed by rash in 8 (21.0%) cases;while 21 (55.3%) were asymptomatic. Thirty-one (81.6%) were in failure of MTX, 19 (50%) of steroids, 7 (18.4%) of NSAIDS and 3 (7.9%) had had intraarticular injections. Biologically, ANA, RF and anti-CCP were positive in 22 (57.9%), 8 (21.1%) and 4 (10.5%) of the cases, respectively. Uveitis was present in 11 (28.9%) of the patients. Analysis of adalimumab efficacy showed 10 (52.6%) cases of complete remission, 9 (23.7%) of partial remission and 9 (23.7%) other where treatment was discontinued. Major adverse effects included local pain (4 [10.5%]), new onset uveitis (1 [2.6%]) and rash (1 [2.6%]), responsible of 1case of treatment discontinuation. Predictors for complete remission on adalimumab were oligoarticular form (β = 3.450, p = 0.009) and negative RF (β = 2.381, p = 0.036);while predictors for nonresponse, whether complete or partial, were polyarticular form (β = ?3.784, p = 0.005) and positive anti-CCP (β = ?3.178, p = 0.021). Conclusion: Adalimumab is an efficient and relatively safe alternative in the treatment of JIA with relatively high remission rates and lower rates of adverse effects. Further multicentre experiences are warranted to prove its efficacy and safety in the Saudi patients.