Systemic-onset Juvenile Idiopathic Arthritis Research Articles

Communicating Calf Swelling in Systemic-Onset Juvenile Idiopathic Arthritis.

Communicating Calf Swelling in Systemic-Onset Juvenile Idiopathic Arthritis.

Multisystem Inflammatory Syndrome in Children and Kawasaki Disease: Two Different Illnesses with Overlapping Clinical Features

Multisystem Inflammatory Syndrome in Children and Kawasaki Disease: Two Different Illnesses with Overlapping Clinical Features

The benefit-risk balance for biological agents in juvenile idiopathic arthritis: a meta-analysis of randomized clinical trials.

To assess the net benefit of biological agents (BA) used in JIA. We systematically searched databases up to March 2019 for randomized controlled trials (RCT) performed in JIA disease. Separate random-effects meta-analyses were conducted for efficacy (ACR paediatric score 30%, ACRpedi30) and serious adverse events for safety. In order to standardize the baseline risk, we performed a meta-analysis of baseline risk in the control group (for both efficacy and safety meta-analysis). The net benefit was determined as the risk difference of efficacy subtracted by the risk difference of safety. We included 19 trials: 11 parallel RCTs (754 patients) and 8 withdrawal RCTs (704 patients). The net benefit ranged from 2.4% (adalimumab) to 17.6% (etanercept), and from 2.4% (etanercept) to 36.7%, (abatacept) in parallel and withdrawal trials assessing non-systemic JIA, respectively. In the systemic JIA category, the net benefit ranged from 22.8% (rilonacept) to 70.3% (canakinumab), and from 32.3% (canakinumab) to 58.2% (tocilizumab) in parallel and withdrawal trials, respectively. The results suggest that a greater number of patients experienced therapeutic success without serious adverse events in the systemic onset JIA category compared with the BAs for non-systemic JIA categories. Baseline risk, design of trial and JIA categories impact the measure of net benefit of BAs in JIA patients.

Rheumatologists' perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets.

The ongoing pandemic coronavirus disease 19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a matter of global concern. Environmental factors such as air pollution and smoking and comorbid conditions (hypertension, diabetes mellitus and underlying cardio-respiratory illness) likely increase the severity of COVID-19. Rheumatic manifestations such as arthralgias and arthritis may be prevalent in about a seventh of individuals. COVID-19 can result in acute interstitial pneumonia, myocarditis, leucopenia (with lymphopenia) and thrombocytopenia, also seen in rheumatic diseases like lupus and Sjogren’s syndrome. Severe disease in a subset of patients may be driven by cytokine storm, possibly due to secondary hemophagocytic lymphohistiocytosis (HLH), akin to that in systemic onset juvenile idiopathic arthritis or adult-onset Still’s disease. In the absence of high-quality evidence in this emerging disease, understanding of pathogenesis may help postulate potential therapies. Angiotensin converting enzyme 2 (ACE2) appears important for viral entry into pneumocytes; dysbalance in ACE2 as caused by ACE inhibitors or ibuprofen may predispose to severe disease. Preliminary evidence suggests potential benefit with chloroquine or hydroxychloroquine. Antiviral drugs like lopinavir/ritonavir, favipiravir and remdesivir are also being explored. Cytokine storm and secondary HLH might require heightened immunosuppressive regimens. Current international society recommendations suggest that patients with rheumatic diseases on immunosuppressive therapy should not stop glucocorticoids during COVID-19 infection, although minimum possible doses may be used. Disease-modifying drugs should be continued; cessation may be considered during infection episodes as per standard practices. Development of a vaccine may be the only effective long-term protection against this disease.Key Points• Patients with coronavirus disease 19 (COVID-19) may have features mimicking rheumatic diseases, such as arthralgias, acute interstitial pneumonia, myocarditis, leucopenia, lymphopenia, thrombocytopenia and cytokine storm with features akin to secondary hemophagocytic lymphohistiocytosis.• Although preliminary results may be encouraging, high-quality clinical trials are needed to better understand the role of drugs commonly used in rheumatology like hydroxychloroquine and tocilizumab in COVID-19.• Until further evidence emerges, it may be cautiously recommended to continue glucocorticoids and other disease-modifying antirheumatic drugs (DMARDs) in patients receiving these therapies, with discontinuation of DMARDs during infections as per standard practice.

P136 Adverse reaction with intravenous immunoglobulin (IVIG) therapy and management of symptoms: a single centre experience

Abstract Background IVIG is a therapeutic preparation comprising of pooled blood donated from large numbers of healthy people. There are different preparations of IVIG available. All should have high levels of IgG (>95%) but vary in concentrations, pH, stabilizing agents and IgA content. In inflammatory conditions, IVIG is often used as an adjunct therapy in patients with poor response to first line therapy and in general well tolerated. However adverse reactions can occur and vary in severity from mild constitutional symptoms to aseptic meningitis. The aim of this study was to identify patients who required IVIG within the paediatric rheumatology department at Great Ormond Street Hospital, the underlying diagnosis of these patients and the indication for starting treatment. The study also looked at the number of adverse drug reactions of patients requiring IVIG, the symptoms they presented with and the management of these symptoms. Methods A retrospective case review, of patients under the care of the paediatric rheumatology team who received IVIG between July 2013 to August 2018. We collected demographics including, age, sex, diagnosis of patients and indication for commencing IVIG, symptoms of any adverse drug reaction and management of symptoms. Results We identified 43 patients who required IVIG over the last 5 years as part of their treatment plan, of which 23 patients had a diagnosis of Juvenile dermatomyositis (JDM). Of the remaining patients 5 had a diagnosis of SLE, 4 with SRP positive mysositis, 2 with necrotising myositis and 2 with atypical systemic onset JIA. The main indication for starting treatment was for active or worsening skin disease, muscle weakness or both. From the 43 patients that required IVIG, 21 patients had an adverse drug reaction and 15/21 patients had a diagnosis of JDM. 5/21 patients had symptoms associated with aseptic meningitis (headache, photophobia and neck stiffness), 2 of which were unable to continue treatment. The remaining 16 patients had milder constitutional symptoms. Symptoms were managed by premedicating patients prior to subsequent IVIG treatment with a combination of paracetamol, chlorphenamine, ondansetron or by reducing the rate of IVIG infusion or reducing the dose of IVIG from 2g/kg to 1g/kg. Conclusion We identified from the study, that half the patients requiring IVIG as part of their treatment plan had an adverse drug reaction of which half had a diagnosis of JDM. However, the majority of patients who had an adverse drug reaction had mild constitutional symptoms, relieved by premedication or by adjusting IVIG rate of infusion or dose. Only 2 patients were unable to continue IVIG treatment. Disclosures S.H.A. Wildman None. M. Al-Obaidi None.

Autoinflammatory diseases in childhood, part 2: polygenic syndromes.

Autoinflammatory diseases are a family of disorders characterized by aberrant stimulation of inflammatory pathways without involvement of antigen-directed autoimmunity. They can be further divided in monogenic and polygenic types. Those without an identified genetic mutation are known as polygenic and include systemic-onset juvenile idiopathic arthritis, idiopathic recurrent acute pericarditis, Behçet syndrome, chronic recurrent multifocal osteomyelitis and inflammatory bowel disease among others. Autoinflammatory diseases are characterized by recurrent flares or persistent systemic inflammation and fever, as well as lymphadenopathy and cutaneous, abdominal, thoracic and articular symptoms. Although these syndromes can mimic infections clinically, the inflammatory lesions in autoinflammatory disorders are aseptic. However, because of their infrequency, varied and nonspecific presentation, and the new genetic identification, diagnosis is usually delayed. In this article, which is Part 2 of a two-part series, the authors review the main polygenic autoinflammatory diseases that can be seen in childhood, with special emphasis wherever applicable on imaging features that may help establish the correct diagnosis. However, the major role of imaging is to delineate organ involvement and disease extent.

Autoinflammatory diseases in childhood, part 1: monogenic syndromes.

Autoinflammatory diseases constitute a family of disorders defined by aberrant stimulation of inflammatory pathways without involving antigen-directed autoimmunity. They may be divided into monogenic and polygenic types. Monogenic autoinflammatory syndromes are those with identified genetic mutations, such as familial Mediterranean fever, tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency or hyperimmunoglobulin D syndrome, cryopyrin-associated periodic fever syndromes (CAPS), pyogenic arthritis pyoderma gangrenosum and acne (PAPA) syndrome, interleukin-10 and interleukin-10 receptor deficiencies, adenosine deaminase 2 deficiency and pediatric sarcoidosis. Those without an identified genetic mutation are known as polygenic and include systemic-onset juvenile idiopathic arthritis, idiopathic recurrent acute pericarditis, Behçet syndrome, chronic recurrent multifocal osteomyelitis and inflammatory bowel disease among others. Autoinflammatory disorders are defined by repeating episodes or persistent fever, rash, serositis, lymphadenopathy, arthritis and increased acute phase reactants, and thus may mimic infections clinically. Most monogenic autoinflammatory syndromes present in childhood. However, because of their infrequency, diverse and nonspecific presentation, and the relatively new genetic recognition, diagnosis is usually delayed. In this article, which is Part 1 of a two-part series, the authors update monogenic autoinflammatory diseases in children with special emphasis on imaging features that may help establish the correct diagnosis.

Drug Reaction and High Fatality Lung Disease in Systemic Onset Juvenile Idiopathic Arthritis (sJIA)

Drug Reaction and High Fatality Lung Disease in Systemic Onset Juvenile Idiopathic Arthritis (sJIA)

The role of serum cytokine level in the evaluation of the efficacy of tocilizumab for the treatment of systemic-onset juvenile idiopathic arthritis

Objective To evaluate the value of serum cytokine level in the efficacy of tocilizumab for the treatment of systemic-onset juvenile idiopathic arthritis. Methods 30 cases with SoJIA hospitalized in Capital Institute of Paediatrics from June 2016 to October 2018 were treated with Interleukin-6 receptor antagonist(tocilizumab) injection. Among them, 20 were males(67%) and 10 were females(33%). The age at diagnosis was between 0.84 to 13years. Whiteblood cell, C-reactive protein, erythrocyte sedimentation rate, serum interleukin(IL-6, IL-2R, IL-8, IL-10, IL-1β) and tumor necrosis factor-alpha levels were observed before treatment, after the 2nd week, after the 6th week and after the 22nd week.Mann-Whitney nonparametric test and Chi-square test were used to analyze the data of cytokines pre and after-treatment. Results All of the 30 cases had fever before medication. The fever disappeared in 28 cases after using tocilizumab. One case stopped using tocilizumab because of allergic reaction and one case stopped because of poor efficacy. Among 28 cases with normal body temperature after medication, the arthritis and rash manifestations were significantly improved. WBC, AESR and CRP were all lower than those before medication. Within these 28 cases, the serum IL-6 level was168.50(67.40-589.25) pg/mL pre-treatment, 107.50(28.03-281.50) pg/mL after the 2nd week. There was no statistical difference between them(Z=-1.754, P>0.05). The serum IL-6 level was 64.05 (19.90-130.75) pg/mL after the 6th week and 24.80 (3.45-95.40) pg/mL after the 22nd week. Compared with pre-treatment, they were all lower than pre-treatment levels(Z=-2.942,-3.334,P 0.05,>0.05,>0.05). Serum IL-8 level was 200.85(95.43-364.00)pg/ml after the 2nd week, 194.50(50.75-433.00)pg/ml after the 6th week, 161.50 (38.98-308.00)pg/ml after the 22nd week. Compared with pre-treatment [96.20(59.75-371.75) pg/ml], there were no statistical difference between after and pre-treatment(Z=-0.86,-0.131,-0.186,P>0.05,>0.05,>0.05). There was no statistical difference between after the 2nd week and pre-treatment in the IL-10 level(χ2=2.33, P>0.05). The IL-10 level after 6th week and after 22nd week were all lower than pre-treatment levels(χ2=4.08, 4.08, P 0.05,>0.05,>0.05)in IL-1β level. Conclusion After treatment with tocilizumab, the levels of serum IL-6 and IL-2R are helpful to assess the activity of SoJIA and the efficacy of therapy. Key words: Cytokine; Tocilizumab; Systemic-onset juvenile idiopathic arthritis

Clinical profile of juvenile idiopathic arthritis from a tertiary care hospital in Northern India

Background: Juvenile idiopathic arthritis (JIA) is the most common rheumatological disorder in children with wide variation in its clinical profile. Objective: The aim is to study the clinical, laboratory, radiological, and treatment profile of children with JIA attending the rheumatology clinic of a tertiary care hospital in Northern India. Methods: In this prospective observational study, we analyzed the clinical, serological, radiological, and treatment profile of 56 consecutive JIA patients attending our hospital between January 2013 to December 2016. Results: Out of 56 children, 38 (67.8%) were boys and 18 (32.2%) were girls. Five (8.9%), 15 (26.8%), 16 (28.5%), and 20 (35.7%) children had oligoarticular, systemic-onset JIA (SOJIA), polyarticular JIA, and enthesitis-related arthritis (ERA), respectively, with male: female ratios being 0.67:1. 6.5:1, 0.45:1 and 9:1, respectively. Mean age at disease onset was 6.7 ± 4.3 (mean ± standard deviation), 6.6 ± 4.5, 6.0 ± 2.6, and 10.4 ± 3.2 years in SOJIA, polyarticular, oligoarticular and ERA, respectively. Arthritis was present in all patients. Fever, lymphadenopathy, hepatosplenomegaly, and rash were exclusive to patients with SOJIA. Uveitis and anti-nuclear antibody (ANA) positivity (3.5% each) were rare findings. Knee was the most common joint involved in all subtypes except SOJIA, where the wrist was most commonly involved. All children with SOJIA and polyarticular JIA required conventional synthetic disease-modifying anti-rheumatic drugs. Seven children with SOJIA, six children with polyarticular JIA and six children with ERA received biological disease-modifying anti-rheumatic drugs, in view of refractory disease. Conclusion: JIA-ERA, followed by polyarticular JIA, were most common subtypes of JIA in our study. The knee is the most common joint to be involved. Uveitis and ANA positivity are rare findings in our subsets of children.

Long-term surveillance of biologic therapies in systemic-onset juvenile idiopathic arthritis: data from the German BIKER registry.

Using data from the German Biologics JIA Registry (BIKER), long-term safety of biologics for systemic-onset JIA with regard to adverse events of special interest was assessed. Safety assessments were based on adverse event reports after first dose through 90 days after last dose. Rates of adverse event, serious adverse event and 25 predefined adverse events of special interest were analysed. Incidence rates were compared for each biologic against all other biologics combined applying a mixed-effect Poisson model. Of 260 systemic-onset JIA patients in this analysis, 151 patients received etanercept, 109 tocilizumab, 71 anakinra and 51 canakinumab. Patients with etanercept had higher clinical Juvenile Arthritis Disease Activity Score 10 scores, active joint counts and steroid use at therapy start. Serious adverse events were reported with higher frequency in patients receiving canakinumab [20/100 patient years (PY)] and tocilizumab (21/100 PY). Cytopenia and hepatic events occurred with a higher frequency with tocilizumab and canakinumab. Medically important infections were seen more often in patients with IL-6 or IL-1 inhibition. Macrophage activation syndrome occurred in all cohorts with a higher frequency in patients with canakinumab (3.2/100 PY) and tocilizumab (2.5/100 PY) vs anakinra (0.83/100 PY) and etanercept (0.5/100 PY). After adjustment only an elevated risk for infections in anakinra-treated patients remained significant. Three definite malignancies were reported in patients ever exposed to biologics. Two deaths occurred in patients treated with etanercept. Surveillance of pharmacotherapy as provided by BIKER is an import approach especially for patients on long-term treatment. Overall, tolerance was acceptable. Differences between several biologics were noted and should be considered in daily patient care.

Population pharmacokinetics of tacrolimus in pediatric patients with systemic-onset juvenile idiopathic arthritis: Initial dosage recommendations.

Pediatric patients with systemic-onset juvenile idiopathic arthritis (SOJIA) may be treated with tacrolimus. However, the therapeutic range for tacrolimus is narrow with considerable inter- and intra-individual variability, making it difficult to formulate an ideal dosage regimen for personalized treatment. The purpose of the present study was to set up a population pharmacokinetics (PPK) model of tacrolimus treatment for SOJIA to determine the optimal initial dosage. Patients with SOJIA were analyzed using non-linear mixed-effects modeling. Different regimens were analyzed using Monte Carlo simulation with concentration profiles. A first-order absorption and elimination one-compartment model was selected as the most appropriate model for SOJIA. Based on initial dosage recommendations, the regimen of 0.5 mg every 24 h (q24h) appeared to be most suitable for subjects with a body weight of 5 kg, while the 0.5 mg q12h regimen was most suitable for subjects with a body weight of 15–25 kg, the 1/0.5 mg q24h regimen was appropriate for the 26–35 kg group and the 1 mg q12h regimen was suitable for the subjects with a body weight of 36–50 kg. To the best of our knowledge, the present study established the first PPK model of tacrolimus treatment that may be used for the selection of the initial dose based on body weight of pediatric patients with SOJIA.

Systemic Onset Juvenile Idiopathic Arthritis (sJIA) or Still's Disease: A Diagnostic Challenge; while Presented as Fever of Unknown Origin. 2 Cases

Systemic-onset juvenile idiopathic arthritis (sJIA) or Still's disease is a chronic inflammatory disease of unknown etiology belongs to the group of Juvenile Idiopathic Arthritis. In contrast to other JIA patients in whom the joint disease usually overshadows the more general symptomatology, in Systemic-onset juvenile idiopathic arthritis (sJIA) extra-articular features such as spiking fever, hepatosplenomegaly, lymphadenopathy, rash, pleurisy, or pericarditis, and vasculopathy are most prominent. Thus the onset of disease can be vary nonspecific and may suggest bacterial or viral infection, malignancy or other rheumatic disease. As it is highly characterized by its extra-articular systemic illness features, in some ways, it resembles a fever of unknown origin. We present 2 cases of fever of unknown origin, initially presented with fever and other extra-articular features, without any arthritis, but after several months develops arthritis and finally diagnosed as Systemic-onset juvenile idiopathic arthritis (sJIA) or Still's disease .
 Anwer Khan Modern Medical College Journal Vol. 10, No. 1: Jan 2019, P 84-88

P14 The Irish National Centre for Paediatric Rheumatology experience of moving from IV to SC tocilizumab (TCZ)

Abstract Background Tocilizumab (TCZ) is a monoclonal antibody that targets the interleukin 6 receptor. It is approved for use in children over the age of 2 years with systemic onset juvenile idiopathic arthritis (SoJIA) and polyarticular juvenile idiopathic arthritis (pJIA) who have not responded to treatment with non-steroidal agents, corticosteroids and methotrexate mono-therapy. Previous studies from our centre have shown a positive response to IV TCZ with high rates of remission. TCZ has recently been licensed for administration via the SC route. The aim of this study is to determine how many patients receiving IV TCZ were successfully changed to SC TCZ in the first 6 months after SC TCZ paediatric licensing was obtained and to document any adverse events. Methods Retrospective review of patients with SoJIA or pJIA who were on IV TCZ and changed to S/C TCZ over a 6 month period from October 2018 to April 2019. Patients were identified from an in-house aseptic pharmacy database Clinichemo®. All patients on IV TCZ were identified and cross checked against the Hibernian patient referral system for home SC TCZ administration. Criteria for changing included fulfilling Wallace Criteria for clinical remission and appropriate JIA subtype. Results were analysed using Microsoft Excel. Results 28 patients receiving IV TCZ in October 2018 were identified. 8 were excluded due to either a diagnosis other than SoJIA/pJIA or changing to an alternative biologic. Of the 20 eligible patients, 10 had successfully changed by April 2019. Of those who did not change, 1 is due to change in May 2019, 2 did not wish to change, indicating personal preference as their reason. A total of 7 were deemed unsuitable for medication change due to ongoing active disease. Of the 10 patients who successfully changed, 2 had SoJIA and 8 had pJIA. All were commenced on a dose of 162mg with frequency varying from 1 to 4 weekly as per Summary of Product Characteristics. There was no significant change in ESR, CRP, LFT or WCC demonstrated pre or post change in administration route. No adverse events were reported. 1 patient subsequently changed back to IV administration due to patient preference. Conclusion Our experience to date has been positive, with 50% of patients changed to SC administration within 6 months of approval. A number of other patients have been identified for a change to SC TCZ within the next 6 months. While 1 patient subsequently elected to change back to IV TCZ, to date, no patient has come off SC TCZ due to an increase in disease activity. We hope to follow this study with a patient questionnaire to determine the patient perspective of changing to SC administration of TCZ. Conflicts of Interest The authors declare no conflicts of interest.

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

BACKGROUNDSystemic-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.AIMTo explore alterations in fecal microbiota profiles in SoJIA patients and to evaluate the correlations between microbiota and clinical parameters.METHODSWe 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.RESULTSThe 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).CONCLUSIONThe composition of the intestinal microbiota is different in SoJIA patients compared with healthy children. The dysbiosis presents partial restoration in inactive status patients.

22. Systemic onset juvenile idiopathic arthritis with multi-organ failure in a teenager

IntroductionSystemic onset juvenile idiopathic arthritis (JIA) is an often severe and potentially life-threatening subtype of chronic arthritis starting under the age of 16 years. It is characterised by fevers, rash and arthritis, although this may not be apparent until later in the disease course, which can add difficulty to making the diagnosis. We present a case of systemic onset JIA with multi-organ impairment to showcase its mimicry of other diseases and highlight importance of awarenessCase descriptionA 15-year-old girl presented with a 7 day history of fever, cough, sore neck, enlarged lymph nodes and widespread macular rash. She had been started on penicillin in the community for presumed scarlet fever, but was hospitalised due to worsening symptoms. Differential diagnoses discussed were lymphadenitis and EBV, due to ongoing fevers, high inflammatory markers, and raised liver function tests. She then developed an acute kidney injury and profound hypotension. She was treated with immunoglobulin for possible Kawasaki disease, broad spectrum antibiotics for possible toxic shock syndrome/sepsis, and transferred to the regional PICU for ongoing inotropic support and management of her multi-system illness.She was found to have a non-dilated cardiomyopathy with poor left ventricular function, low complement and positive anti-streptolysin titres. No postive cultures or focus of infection were found. Antibody tests including dsDNA were negative. She required CPAP for respiratory support and was treated with pulsed methylprednisolone for systemic onset JIA. She then received a weaning course of prednisolone over several months and made an excellent recovery.DiscussionThis was an interesting case for those involved because the initial symptoms, evolving signs and investigation results didn’t easily tie together to give one suitable diagnosis. Several avenues of treatment were explored, including a range of antibiotics and immunoglobulin, before methylprednisolone. The patient also remained remarkably ‘well’ looking despite her multi-organ impairment.Key learning pointsThis case highlighted the importance of awareness of systemic onset JIA and its complications, particularly in a non-typical age group, for the general paediatrician. Early discussion with and involvement of tertiary rheumatology services served to optimise management and outcome, and will hopefully also improve long-term prognosis.Conflicts of interestThe authors have declared no conflicts of interest.

Recurrent inflammatory disease caused by a heterozygous mutation in CD48

Recurrent inflammatory disease caused by a heterozygous mutation in CD48

Evaluation of patients with systemic onset juvenile idiopathic arthritis

GIRIS ve AMAC: Sistemik baslangicli juvenile idiyopatik artrit (JIA) nadir gorulen bir JIA alt tipi olarak kabul edilir ve diger JIA alt gruplarindan farkli olarak otoinflamatuar hastalik grubunda degerlendirilir. Ulkemizde sistemik baslangicli JIA ile ilgili az sayida calisma bulunmaktadir. Bu calismada klinigimizde sistemik baslangicli JIA tanili olgularin klinik ve laboratuvar ozelliklerinin arastirilmasi amaclanmistir. YONTEM ve GERECLER: Klinigimizde takip edilen 303 JIA tanili olgu tarandi ve 18 sistemik baslangicli JIA tanili olgu (%5,9) tespit edildi. Olgularin verileri elektronik dosya kayitlarindan geriye donuk olarak taranarak elde edildi. BULGULAR: Olgularin yaslari ortanca 11,7 yil (5,3-20 yil) ve kiz erkek orani 4/14 idi. Tani yaslari ortanca 4,9 yil (1,5-15,2 yil) ve tanida gecikme suresi ortanca 4 hafta (2 hafta-10,8 yil) olarak saptandi. En sik basvuru yakinmasi olgularin tumunde gorulen ates ve artrit (n=18, %100) idi. Bir olguda monoartrit gorulurken diger olgularda birden fazla eklem tutulumu vardi. En sik gorulen form monosiklik formdu (n=7, %38,8). Olgularda gorulen en sik komplikasyon boy kisaligi (n=4, %22,2) idi ve makrofaj aktivasyon sendromu 2 olguda (%11,1) gelisti. Tedavide en sik steroidler (n=17, %94,4) kullanilirken biyolojik tedavi 7 olguda (%38,8) kullanildi. Bu olgularin son tedavilerine bakildiginda; 5 olgunun tocilizumab, bir olgunun canakinumab aldigi, kalan 1 olgunun ise takibi biraktigi saptandi. Takipten cikan bir olgu disinda tum olgularda remisyon saglandi. TARTISMA ve SONUC: Sistemik baslangicli JIA, diger JIA alt gruplarina kiyasla daha az olarak gorulmektedir. Hastalik enfeksiyon hastaliklari ve diger inflamatuar hastaliklarla karisabildigi icin tani gecikebilmektedir. Kortikosteroid tedavisine cogunlukla olumlu yanit alinmakla birlikte steroide direncli olgularda anti IL-6 ve anti IL-1 ilaclar etkili olabilmektedir

Evaluation of Patients with Systemic onset Juvenile Idiopathic Arthritis

Evaluation of Patients with Systemic onset Juvenile Idiopathic Arthritis

Hemophagocytic Lymphohistiocytosis in Children

Background: Hemophagocytic lymphohistiocytosis (HLH) is a disorder of the immune regulatory system with a high rate of mortality. The clinical presentation of HLH could be similar to those of many other conditions, making its diagnosis difficult. Methods: The current study was conducted on the children with HLH referred to the Pediatric Ward of Imam Reza Hospital, Mashhad, Iran during nine years from 2010 to 2018. The data collection tool included items on clinical presentations, physical examination, laboratory data, treatment strategy, and the disease outcome. The diagnosis of HLH was made based on the HLH-2004 Diagnostic Criteria. Data were analyzed using SPSS version 20. Results: Among the 17 cases with HLH, the mean age at the onset of HLH was 4.671 ± 4.60 years with a male to female ratio of 11:6. Fever and splenomegaly were the most common findings. The study of the etiology revealed that about 30 of the children had the familial form of HLH, 17.5 were previously diagnosed with rheumatologic disorders (i.e., systemic lupus erythematosus and systemic-onset juvenile idiopathic arthritis), and the same rate was affected by infectious diseases. Idiopathic factors, the Chediak-Higashi syndrome, and the Griscelli syndrome were responsible for the occurrence of HLH in 17.5, 12, and 6 of the cases, respectively. According to the obtained results of the study, 35.3 of the patients were cured and about 64.7 died. Conclusions: Due to the high risk of mortality from this disorder, the recognition of HLH symptoms, especially atypical presentations of the disorder, is critical both for pediatricians and subspecialists. © 2019, Author(s).