Systemic-onset Juvenile Idiopathic Arthritis Research Articles

A child with systemic onset juvenile idiopathic arthritis and nephrotic syndrome.

Amyloidosis of the kidney is a rare complication in children with juvenile idiopathic arthritis (JIA), more commonly seen with systemic onset juvenile idiopathic arthritis (SOJIA). It usually presents with asymptomatic proteinuria. An 11.5-year-old boy with onset of SOJIA at 6 years of age came to our clinic with anasarca. Urinalysis and serum albumin suggested a diagnosis of nephrotic syndrome (NS) and kidney biopsy confirmed amyloidosis deposits. Treatment with injection tocilizumab was initiated. The proteinuria has decreased, and kidney functions are normal. Children with SOJIA should be monitored for proteinuria so that they can be offered timely appropriate therapy.

Fever of unknown origin in pediatrics: causes and clinical characteristics in a single centre experience

BackgroundFever of unknown origin (FUO) is a common condition worldwide in children that remains a diagnostic challenge. The causes of FUO vary depending on the patient's age, residency, and the time of study. Therefore, this study aimed to identify the common aetiologies of FUO at Alexandria University Children’s Hospital under the current diagnostic abilities and newly emerging diseases.MethodsThe current prospective observational study included all children fulfilling the definition of FUO admitted at Alexandria University Children's Hospital from January 2020 to December 2021 using a steps approach for investigations.ResultsA total of 110 children with fever of unknown origin (FUO) were included in this study; the average duration of fever was 36.76 ± 31.73 days. In most of the enrolled cases 105/110 (95.4%) the definite etiology of FUO was identified. The common causes were collagen vascular diseases (30.9%), infectious diseases (28.2%), miscellaneous conditions (19.1%), and malignancy (17.3%). Among collagen vascular diseases, systemic lupus erythematosus (SLE) (47.1%) and systemic onset juvenile idiopathic arthritis (sJIA) (38.2%) were the most common. In the infectious category, Katayama fever (16.1%), brucellosis (12.9%), and urinary tract infection (UTI) (12.9%) were the most frequently observed. Post-Covid MIS-C (52.4%) was the most common in the miscellaneous category. Children in the infectious category had significantly higher neutrophil [5.76 (2.28–7.92) × 10^3/µl] and lymphocytic counts [ 4.2 (2.04–5.91) × 10^3/µl]; (P < 0.001 and < 0.010 respectively). Moreover, in the collagen category the median lymphocytic count was lower [1.95 (1.47–2.73) × 10^3/µl] with a significantly (P < 0.010) higher neutrophil/ lymphocyte ratio [2.30 (1.53–3.91)].ConclusionCollagen vascular diseases, infectious diseases, miscellaneous, and malignancy were the most common causes of FUO. Katayama fever, urinary tract infections (UTI), and brucellosis were the most common causes in the infectious category. Post-Covid MIS-C and hemophagocytic lymphohistiocytosis were the most common diagnoses in the miscellaneous category.

Diagnostic guidelines for familial hemophagocytic lymphohistiocytosis revisited

AbstractCurrent hemophagocytic lymphohistiocytosis 2004 (HLH-2004)–based diagnostic criteria for familial hemophagocytic lymphohistiocytosis (FHL) are based on expert opinion. Here, we performed a case-control study to test and possibly improve these criteria. We also developed 2 complementary expert opinion–based diagnostic strategies for FHL in patients with signs/symptoms suggestive of HLH, based on genetic and cellular cytotoxicity assays. The cases (N = 366) were children aged <16 years with verified familial and/or genetic FHL (n = 341) or Griscelli syndrome type 2 (n = 25); 276 from the HLH-94/HLH-2004 databases and 90 from the Italian HLH Registry. All fulfilled the HLH-94/HLH-2004 patient inclusion criteria. Controls were 374 children with systemic-onset juvenile idiopathic arthritis (sJIA) and 329 + 361 children in 2 cohorts with febrile infections that could be confused with HLH and sepsis, respectively. To provide complete data sets, multiple imputations were performed. The optimal model, based on 17 variables studied, revealed almost similar diagnostic thresholds as the existing criteria, with accuracy 99.1% (sensitivity 97.1%; specificity 99.5%); the original HLH-2004 criteria had accuracy 97.4% (sensitivity 99.0%; specificity 97.1%). Because cellular cytotoxicity assays here constitute a separate diagnostic strategy, HLH-2004 criteria without natural killer (NK)–cell function was also studied, which showed accuracy 99.0% (sensitivity, 96.2%; specificity, 99.5%). Thus, we conclude that the HLH-2004 criteria (without NK-cell function) have significant validity in their current form when tested against severe infections or sJIA. It is important to exclude underlying malignancies and atypical infections. In addition, complementary cellular and genetic diagnostic guidelines can facilitate necessary confirmation of clinical diagnosis.

Functional status of Indian children with juvenile idiopathic arthritis.

The functional disability status of Indian children with juvenile idiopathic arthritis is unidentified. In this cross-sectional study functional capacity of 60 juvenile idiopathic arthritis patients was assessed by the Childhood Health Assessment Questionnaire. A total of 60 juvenile idiopathic arthritis patients aged ranges from 1 to 12 years were recruited from a teaching hospital in eastern India. A childhood health assessment questionnaire was used to assess the functional health of children. Pain, patient's/parent's global assessment of general well-being, and physician's global assessment were assessed. Childhood health assessment questionnaire disability index for oligoarticular juvenile idiopathic arthritis differed significantly from polyarticular juvenile idiopathic arthritis (P < 0.001), systemic-onset juvenile idiopathic arthritis (P = 0.018) and undifferentiated juvenile idiopathic arthritis (P < 0.001). There was a good to a strong positive correlation between the childhood health assessment questionnaire disability index with pain score, patient's/parent's global assessment score, and physician global assessment score for the total juvenile idiopathic arthritis cohort. regarding juvenile idiopathic arthritis subtypes, significant correlations were noted between the childhood health assessment questionnaire disability index with the patient's/parent's global assessment and physician's global assessment (except for enthesitis-related arthritis). Assessment and documentation of the functional health status of juvenile idiopathic arthritis patients will improve the management of the disease.

Relapses of juvenile idiopathic arthritis in adulthood: A monocentric experience.

Our aim was to describe a monocentric cohort of young adult patients with juvenile idiopathic arthritis (JIA), assessing the risk of relapse after transition to adult care. We conducted a retrospective study and collected clinical, serological, and demographic data of young adult patients (18-30 years old) referred to the Transition Clinic of a single Italian centre between January 2020 and March 2023. Patients with systemic-onset JIA were excluded. Primary outcome was disease relapse, defined by Wallace criteria. Risk factors were analysed by Cox proportional hazards regression. Fifty patients with age 18-30 years old were enrolled in the study and followed for a median 30 months. The median disease duration at transition was 15 years. Twenty (40%) patients were on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and 38 (76%) were on biological DMARDs through adulthood. Twenty-three patients relapsed after transitioning to adult care for a median 9-month follow-up (IQR 0-46.5). Most relapses involved the knees (69.6%). The univariate analysis identified monoarthritis (HR 4.67, CI 1.069-20.41, p value = 0.041) as the main risk factor for relapse within the first 36 months of follow-up. Early onset, ANA positivity, past and ongoing treatment with csDMARDs or bDMARDs, therapeutic withdrawal, and disease activity within 12 months before transition did not significantly influence the risk of relapse. In JIA patients, the risk of relapse after transitioning to adult care remains high, irrespective of disease subtype and treatment. The main risk factor for the early occurrence of articular activity is monoarticular involvement.

Pediatric Rheumatological Diseases in a Tertiary Care Hospital of Central India: A Retrospective Clinico-Epidemiological Profile.

Introduction:Infectious diseases account for the major health problem in developing countries like India. Though non-infectious diseases like rheumatological disorders are not very common, the burden of these disorders as a group is high in society due to the huge population size. The rheumatological disorders have varied presentations which may mimic other infectious pathologies leading to a significant time lag in the diagnosis. There is inadequate data on the exact burden of these diseases. The spectrum of rheumatological disorders in developing countries is different as compared to the Western world.Hence this study was carried out with the aim of studying the clinical, epidemiological, and laboratory profile of rheumatological disorders in the pediatric age group in a tertiary care hospital. Methods:It was a retrospective study. Data of patients admitted with the diagnosis of rheumatological disorder in the age group of one month to 15 years during the period from June 2018 to December 2022 were reviewed. Results:A total of 35 patients were identified with 20 being female. The mean age of the patients was 8.42± 3.95 years. The most common disease was juvenile idiopathic arthritis (JIA)- 10(28.57%) with an equal proportion of polyarticular JIA and systemic-onset JIA, followed by systemic lupus erythematosus (SLE) nine (25.71%) and Kawasaki Disease (KD)- eight (22.85%). The commonest presenting complaint was fever followed by a rash, whereas the most common findings were pallor and rash. Anemia was present in 25 (71.42%). C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were high in 20 (57.14%) and 22 (62.85%), respectively. Antinuclear antibodies (ANA) were positive in 10 (28.57%) and rheumatoid factor (RA) factor in only one (2.85%) case. Conclusions:The most common rheumatological disorder identified was JIA. Fever and rash were the common presenting complaints. Pallor was the commonest sign whereas anemia was the commonest hematological abnormality.

Hearing Loss in Systemic Onset Juvenile Idiopathic Arthritis (Sojia) -A Single Case Study

Juvenile Rheumatoid Arthritis is a common type of arthritis in children under the age of sixteen. Females are more affected than males with ratio of 2:1. Systemic onset Juvenile Idiopathic Arthritis (SoJIA) is an immune driven inflammatory condition that develops in children. Although SoJIA can occur any time during childhood it usually starts before age five. Inflammation of internal organs and MAS (macrophage activation syndrome) is closely associated with SoJIA. Children with SoJIA have high levels of two powerful inflammatory protein (cytokines) called Interleukin -1 and Interleukin-6. The management of SoJIA follows up with NSAIDs, Corticosteroids, DMARDs and inflammatory cytokine blockade. The incudomalleolar and incudostapedial joint are synovial in nature and hence could be involved in inflammatory process. Immune complex mediated vasculitis and ototoxic side effects may cause a pathological inner ear. Thus individuals with SoJIA are at higher risk of hearing impairment.

Systemic onset juvenile idiopathic arthritis associated with Agammaglobulinemia: A brief report

Systemic onset Juvenile Idiopathic Arthritis (SJIA) is defined as a systemic inflammatory disease. Innate immune system dysregulation and systemic inflammation are the autoinflammatory pathogenesis of this disease. The clinical manifestations are fever, arthritis, lymphadenopathy, rash, and serositis. Of the manifestation of immune deficiency is recurrent otitis media. Recurrent otitis media should be evaluated for immune components. In this report, we presented a boy with recurrent otitis media, pain and swelling in both knees, and fever which fever was exacerbated at nights and he had no fever during day. After immune system evaluations, autosomal recessive agammaglobulinemia was observed in genetic test.

A-085 Analytical Performance of BÜHLMANN sCAL® turbo, a New, Reliable and Precise High-Throughput Assay to Assess the Inflammatory Status of Patients

Abstract Background Serum calprotectin plays an important pro-inflammatory role in the innate immune system and is a promising marker with several potential applications in rheumatoid arthritis, juvenile idiopathic arthritis and systemic onset juvenile idiopathic arthritis. Serum calprotectin can be a useful tool to monitor disease activity and predict treatment response in these patients. Methods The aim of this work was to evaluate the analytical performance of BÜHLMANN sCAL® turbo, a new turbidimetric test on clinical chemistry analyzers for the determination of calprotectin levels in serum. Assay characteristics were established according to CLSI guidelines (CLSI C28-A3, EP05-A3, EP07-A3, and EP09-A3). 111 samples were measured using 3 lots over 3 days and compared to another commercially available assay. Results The analytical measuring range from 0.23 to 15 µg/mL, extended to 225 µg/mL with an additional dilution in an automated rerun on a clinical chemistry analyzer, is suitable to address the described pathologies. 160 self-declared healthy adults (m/w) aged 18–83 years exhibit reference limits of 1.77 and 1.10 µg/mL when sampled either in a native tube or a gel separator tube and processed within 3.4 h after collection, respectively. With a within-laboratory precision up to 5.1% and a reproducibility up to 11.1% the method is precise, reliable and suitable for routine use. Tested concentrations of oral and injectable pharmaceuticals showed no interference. Hemolyzed samples are not recommended. It shows good comparison to an existing commercial assay with a bias of 12.5% (Bland-Altman) and a slope of 1.16 (Passing-Bablok). Conclusion A high-throughput test on clinical chemistry analyzers is now available with the turbidimetric BÜHLMANN sCAL® turbo allowing reliable and precise measurements of serum calprotectin levels.

Refractory macrophage activation syndrome in children with systemic onset juvenile idiopathic arthritis treated with canakinumab

Refractory macrophage activation syndrome in children with systemic onset juvenile idiopathic arthritis treated with canakinumab

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 (&lt;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.

Bone mineral density in egyptian children with juvenile idiopathic arthritis: possible correlation to serum RANKL / osteoprotegerin (OPG) ratio and OPG gene polymorphisms

BackgroundChildren with juvenile idiopathic arthritis (JIA) are at higher risk of decreased bone mineral density (BMD) compared with healthy children due to genetic, disease and medication-related causes. This study aims to investigate the possible effects of osteoprotegerin (OPG) gene polymorphisms and serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor κB-ligand (RANKL) and RANKL/OPG ratio on BMD in children with JIA.MethodsOPG gene rs2073617, rs3134069, serum RANKL, OPG and RANKL/OPG ratio were evaluated in 60 JIA children and 100 matched healthy controls. BMD was evaluated by lumbar dual energy X-ray absorptiometry (DEXA) according to which patients were classified in 2 groups (DEXA z-score above and below − 2). Composite disease activity was measured using the Juvenile Arthritis Disease Activity Score (JADAS) 27-joints. Articular damage was scored using the juvenile arthritis damage index (JADI).ResultsPatients aged 12.05 ± 3.2 years, included 38 females and 31% had BMD z-score below-2. Systemic-onset JIA was the most frequent phenotype (38%). Genotypes and alleles frequencies of the 2 studied polymorphisms did not differ between patients and controls (p > 0.05 for all) while serum RANKL and RANKL/OPG ratio were significantly higher in patients compared to controls (p = < 0.001 and 0.03 respectively). Patients with BMD < -2 had significantly greater frequencies of rs2073617 TT genotype and T allele (p < 0.001), higher serum RANKL, RANKL/OPG ratio (p = 0.01, 0.002), female predominance (p = 0.02), higher articular and extra-articular damage index (p = 0.008,0.009) and more frequent steroid usage (p = 0.02) compared to patients with BMD z-score >-2. Multivariate analysis showed rs2073617 TT genotype, RANKL/OPG ratio, long disease duration (above 36 months) and use of steroid to be associated with decreased BMD (p = 0.03,0.04,0.01,0.01 respectively) in JIA children.ConclusionsEgyptian children with JIA have decreased BMD. rs2073617 TT genotype and T allele, RANKL/OPG ratio are possible determinants of reduced BMD in JIA. Our results underline the importance of frequent monitoring of BMD in JIA children and trying to control disease activity to preserve long term bone health.

IFIH1 and DDX58 gene variants in pediatric rheumatic diseases.

The IFIH1 gene codes the MDA5 protein and the DDX58 gene codes the RIG-I receptor. Both proteins are parts of the interferon (IFN) I signaling pathway and are responsible for antiviral defense and innate immune response. IFIH1 and DDX58 polymorphisms are associated with a spectrum of autoimmune diseases. Rare gain-of-function IFIH1 mutations have been found in Singleton-Merten and Aicardi-Goutières syndrome, while DDX58 mutation can cause atypical Singleton-Merten syndrome. To characterize children with pediatric rheumatic diseases (PRD) carrying DDX58 or IFIH1 variants. Clinical exome sequencing was performed on 92 children with different PRD. IFIH1 and DDX58 variants have been detected in 14 children. IFN-I score has been analyzed and the clinical characteristics of patients have been studied. A total of seven patients with systemic lupus erythematosus (SLE) (n = 2), myelodysplastic syndrome with SLE features at the onset of the disease (n = 1), mixed connective tissue disease (MCTD) (n = 1), undifferentiated systemic autoinflammatory disease (uSAID) (n = 3) have 5 different variants of the DDX58 gene. A common non-pathogenic variant p.D580E has been found in five children. A rare variant of uncertain significance (VUS) p.N354S was found in one patient with uSAID, a rare likely non-pathogenic variant p.E37K in one patient with uSAID, and a rare likely pathogenic variant p.Cys864fs in a patient with SLE. Elevated IFN-I score was detected in 6 of 7 patients with DDX58 variants. Seven patients had six different IFIH1 variants. They were presented with uSAID (n = 2), juvenile dermatomyositis (JDM) (n = 1), SLE-like disease (n = 1), Periodic fever with aphthous stomatitis, pharyngitis, and adenitis syndrome (n = 1), and systemic onset juvenile idiopathic arthritis (n = 1). Three patients have VUS p.E627X, one patient has benign variant p.I923V. Rare VUS p.R595H was detected in the JDM patient. Another rare VUS p.L679Ifs*2 and previously not reported variant p.V599Ffs*5 were detected in the patient with uSAID. One patient with uSAID has rare VUS p.T520A. All patients had elevated IFN-I scores. Rare compound-heterozygous IFIH1 variant (p.L679Ifs*2 and p.V599Ffs*5), heterozygous IFIH1 variant (p.T520A) and heterozygous DDX58 variant (p.Cys864fs) are probably disease causative for uSAID and SLE. The majority of patients with different DDX58 and IFI1 variants had hyperactivation of the IFN I signaling pathway.

Tocilizumab-induced hypofibrinogenemia in patients with systemic-onset juvenile idiopathic arthritis

Systemic juvenile idiopathic arthritis (SJIA) is a chronic inflammatory disease of childhood with elevated serum IL-6 levels. As an inhibitor of IL-6R, tocilizumab (TCZ) has been approved to treat SJIA patients. TCZ-induced hypofibrinogenemia has been only reported in adult cases and limited small case series with rheumatoid arthritis or giant cell arteritis. Here, we describe the incidence of TCZ-induced hypofibrinogenemia in SJIA patients and its possible influence on bleeding risk. SJIA patients with TCZ treatment in Shenzhen Children’s hospital were retrospectively reviewed. Only those with the data on serum fibrinogen levels were included. Data on clinical manifestations, laboratory parameters, management, and sJADAS10-ESR score were collected. Laboratory data were extracted following the start of TCZ therapy at 2, 4, 8, 12, and 24 weeks thereafter. Seventeen SJIA patients with TCZ treatment were included. Thirteen (76.47%, 13/17) had hypofibrinogenemia. The lowest serum fibrinogen levels were even below 1.5 g/L in seven (41.17%, 7/17) patients. Among four patients without MTX treatment, two had obvious hypofibrinogenemia. Although five patients had already stopped steroid treatment 24 weeks after TCZ treatment, three of them still had hypofibrinogenemia. Only P14 had mild nasal mucosal bleeding occasionally. Coagulation tests were regularly performed in eight patients, of these, six had hypofibrinogenemia, which occurred following one to four doses of TCZ; continuation of TCZ treatment hadn’t further aggravated hypofibrinogenemia. Serum fibrinogen levels were not decreased consistently with the improvement of sJADAS10-ESR score in more than half of these eight patients. Factor XIII was detected in six patients and none was identified with Factor XIII deficiency. TCZ alone may induce hypofibrinogenemia in SJIA patients. Continuation of TCZ treatment may be safe for most SJIA patients. But for SJIA patients with indications of surgery or complicated with MAS, the risk of hemorrhage should be regularly evaluated during TCZ treatment. The association between TCZ-induced hypofibrinogenemia and factor XIII deficiency remains uncertain.Trial registration: Not applicable; this was a retrospective study.

Childhood rheumatic diseases: bites not only the joint, but also the heart.

Cardiovascular involvement in juvenile rheumatic diseases is the primary manifestation in paediatric vasculitis and a major organ manifestation in paediatric connective tissue diseases. Though coronary vasculitis is the prototypical manifestation of Kawasaki disease, it can also be seen in patients with polyarteritis nodosa. Pericarditis is the most common manifestation seen in juvenile rheumatic diseases like systemic onset JIA, and lupus. Cardiac tamponade, valvular insufficiency, aortic root dilatation and arrhythmias are seen rarely. Cardiac involvement is often recognized late in children. The development of cardiac disease in juvenile systemic sclerosis is associated with a poor outcome. In long term, childhood onset of rheumatic diseases predisposes to diastolic dysfunction and premature atherosclerosis during adulthood. Key Points • Pericarditis is the most common cardiac manifestation in SLE and can lead to tamponade. • Conduction defects are common in juvenile mixed connective tissue disease and systemic sclerosis. • Pulmonary hypertension is a significant contributor to mortality in juvenile systemic sclerosis. • In Kawasaki disease, early treatment can reduce risk of coronary artery aneurysms.

Adult-onset and Juvenile-onset Still's Disease: A Comparative Study of Both Sides.

Adult-onset Still's disease and systemic-onset juvenile idiopathic arthritis constitute two sides of the same continuum disease. We aimed to investigate the similarities and differences between those diseases. We conducted a retrospective study including adult patients affected by still's disease, attending the rheumatology department and patients affected by systemic-onset juvenile idiopathic arthritis attending the pediatric department. We recorded clinical and radiological findings, different therapeutic regimens, and disease patterns. There were 8 adult patients (6 females and 2 males) and 8 juvenile patients (4 females and 4 males). The classical triad of spiking fever, arthritis, and evanescent skin rash was the first clinical presentation observed in 4 adult patients and in 2 juvenile patients. Arthritis was noted in 8 adult patients versus 6 juvenile patients. Joint deformities were seen in adult patients. Non-steroid antiinflammatory drugs and corticosteroids were the most prescribed molecules. csDMARDs and bDMARDs were used in second-line therapy only for adult patients. The monocyclic course was predominant in juvenile patients and the polycyclic course in adult patients. The chronic course was observed only in two adult patients. Remission was noted in 5 adult patients and 6 juvenile patients. There were no significant differences between the two groups regarding clinical findings, different therapeutic regimens, and disease patterns. From the findings of our study, it seems that AOSD and sJIA are the same syndrome continuum expressed in different hosts. This hypothesis is supported by clinical course, molecule evidence, cytokine profile, and treatment response.

Rescue of Pap-Mas in Systemic JIA Using Janus Kinase Inhibitors, Case Report and Systematic Review.

Biological disease-modifying anti-rheumatic drugs (bDMARDs) targeting interleukin (IL)-6 and IL-1β represent a steroid-sparing first-line therapy used in systemic-onset juvenile idiopathic arthritis (sJIA). Recently, the occurrence of pulmonary alveolar proteinosis (PAP) in sJIA patients was reported with early-onset and exposure to bDMARDs as potential risk factors. We report on a new case with longitudinal immunomonitoring successfully treated by Janus Kinase inhibitors (JAKi) and review past clinical descriptions of this new entity. We report one case of pulmonary alveolar proteinosis and macrophage activation syndrome (PAP-MAS) with longitudinal immunomonitoring. We then conducted a review of the literature of seven publications reporting 107 cases of PAP-MAS sJIA, and included the main characteristics and evolution under treatment. Of the seven articles analyzed, the incidence of PAP-MAS among sJIA patients varied from 1.28% to 12.9%. We report here a single case among a cohort of 537 sJIA patients followed in the pediatric department of the Hospices Civils de Lyon over the last 15 years. This child presented with all clinical and immunological characteristics of PAP-MAS. After several lines of treatment, he benefited from JAKi and improved with respect to both systemic symptoms and lung disease. In the literature, strategies with monoclonal antibodies targeting either INF-γ or IL-1β/IL-18 have been tested with variable results. Orally taken JAKi presents the advantage of targeting multiple cytokines and avoiding parenteral injections of monoclonal antibodies that may contribute to the pathogenesis. JAKi represent a promising option in the treatment of lung disease associated with sJIA.

Use of Intravenous Anakinra for Management of Pediatric Cytokine Storm Syndromes at an Academic Medical Center.

Background: Off-label intravenous (IV) route of anakinra is increasingly recognized to enable higher and faster maximal plasma concentrations than subcutaneous route for treatment of cytokine storm syndromes. Objective: To describe off-label indications of IV anakinra, corresponding dosing and safety profiles, particularly during the coronavirus disease 19 (COVID-19) pandemic. Methods: A retrospective, single-cohort study was conducted at an academic medical center to evaluate use of IV anakinra in hospitalized pediatric patients (age ≤21 years). Institutional Review Board review was considered exempt. The primary endpoint was the primary indication(s) for IV anakinra. The key secondary endpoints were dosing of IV anakinra, previous immunomodulatory therapies, and adverse events. Results: Of 14 pediatric patients, 8 (57.1%) received IV anakinra for treatment of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, whereas 3 and 2 were treated for hemophagocytic lymphohistiocytosis (HLH) and flares of systemic onset juvenile idiopathic arthritis (SoJIA), respectively. The initial dosing regimen of IV anakinra for MIS-C associated with COVID-19 was a median dose of 2.25 mg/kg/dose with a median dosing interval of 12 hours for a median initial treatment duration of 3.5 days. Eleven (78.6%) patients received previous immunomodulatory therapies (IV immune globulin [n = 10; 71.4%] and steroids [n = 9; 64.3%]). No adverse drug events were documented. Conclusion: IV anakinra was used off-label for treatment of MIS-C associated with COVID-19, HLH and SoJIA flares in critically ill patients with no adverse drug events documented. This study helped ascertain the off-label indications of IV anakinra and corresponding patient characteristics.

Clinical and Laboratory Profile of Patients with Newly Diagnosed Juvenile Idiopathic Arthritis: An Observational Study from a Tertiary Care Centre, Karnataka, India

Introduction: Juvenile Idiopathic Arthritis (JIA) is the most common rheumatic condition of childhood. It represents a heterogeneous group of childhood arthritis. Aim: To study the clinical profile and laboratory characteristics of all newly diagnosed JIA patients. Materials and Methods: This hospital-based prospective observational study was conducted in the Department of Paediatric Rheumatology in Indira Gandhi Institute of Child Health, Bengaluru, Karnataka, India between December 2017 to April 2019. All children who fulfilled International League of Associations for Rheumatology (ILAR) criteria for the diagnosis of JIA were enrolled in the study, and their clinical and laboratory parameters were evaluated. The analysis between matchedpairs data like the comparison between age of onset and age of presentation in males and females were done by paired t-test. Results: Fifty one children were included in the study with M:F of 1:1.12. Mean age at onset was 8.71±4.02 years and median duration of disease was 13 months (2-96 months). The most common subgroup was polyarticular JIA 18 (35.3%) followed by Systemic Onset Juvenile Idiopathic Arthritis (SOJIA) 14 (27.5%), enthesitis-related arthritis 13 (25.5%) and oligoarticular JIA 4 (7.8%). Knee (94%) was the most common joint involved followed by the ankle (70.5%). Fever was the most common extra-articular feature present in 73% of cases. Hepatomegaly, splenomegaly and lymphadenopathy was present in 33.3%, 9.8% and 21.6% children, respectively. Anaemia, leukocytosis, thrombocytosis and elevated Erythrocyte Sedimentation Rate (ESR) were more common in SOJIA. Macrophage Activation Syndrome (MAS) was diagnosed in 2 cases of SOJIA (14.3%) with no mortality. Conclusion: Polyarticular JIA was the common subtype in the study, followed by SOJIA. Most common joint involved was knee, followed by ankle and fever is the most common extraarticular manifestation.

Ассоциации гена VDR с клиническими проявлениями, осложнениями и обеспеченностью витамином D на фоне ювенильного идиопатического артрита у детей

Objective. To conduct an association search between genetic variants (c.1206T&gt;C, c.152T&gt;C, c.1174+283G&gt;A) of the VDR gene and clinical manifestations of juvenile idiopathic arthritis (JIA), need for genetically engineered biological drugs (GEBDs) and vitamin D status in children. Patients and methods. This study included 150 children (mean age: 9.11 ± 2.21 years) with JIA and 333 healthy controls. The determination of serum calcidiol concentrations was performed in all patients. Polymorphic variants of the VDR gene (c.1206T&gt;C, c.1175-9G&gt;T, c.152T&gt;C, c.1174+283G&gt;A) were tested by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) technique. Results. Carriers of the minor TT genotype of the genetic variant c.1206T&gt;C(A&gt;G) TaqI are 4 time more likely to develop systemic JIA, 5 time more likely to have high disease activity and uveitis, as well as 9.9 times more often require prescription of GEBDs. Carriers of the minor genotype TT of the genetic variant c.152T&gt;C FokI are 7.7 times more likely to develop systemic JIA and 4.3 times – polyarticular JIA, 6.2 times more likely to have high disease activity and 5.6 times – uveitis, 8 times more often have a severe calcidiol deficiency and 4 times more often require prescription of GEBDs. Carrying the minor AA genotype of the BsmlI polymorphism (c.1174+283G&gt;A) increases the risk of systemic-onset JIA by 17 times, high disease activity and uveitis – by 18 times, and need for GEBDs – by 15 times; carrying the AA and GA genotypes increases the risk of calcidiol deficiency by 5 times and severe calcidiol deficiency by 9 times. Conclusion. All studied genetic variants of the VDR gene verifiably affect the development of clinical manifestations, complications, calcidiol levels and response to therapy in JIA. Key words: VDR gene, juvenile idiopathic arthritis, children, vitamin D, autoimmune disease