ObjectiveTo investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA).MethodsIn a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data.ResultsLD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features.ConclusionsA rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.

Objective To investigate characteristics and risk factors of a novel parenchymal lung disease, increasingly detected in systemic juvenile idiopathic arthritis (sJIA). Methods In a multi-center retrospective study, 61 cases were investigated, using physician-reported clinical information and centralized analyses of radiologic, pathologic and genetic data. Results Lung disease (LD) was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the IL-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes +/- ground glass opacities. Predominant pathology (23/36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features, including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. 5-year survival was 42%. Whole-exome sequencing (20/61) did not identify a novel monogenic defect PAP-related or macrophage activation syndrome (MAS)-related mutations as likely primary cause. Trisomy 21 (T21) increased LD risk, as did young sJIA onset. Refractory sJIA was not required for LD development. Exposure to interleukin (IL)-1 and IL-6 inhibitors (46/61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but it was not associated with LD features. Conclusions A rare, life-threatening LD in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.

BackgroundH Syndrome is an autosomal recessive disorder characterized by cutaneous hyperpigmentation, hypertrichosis, and induration with numerous systemic manifestations. The syndrome is caused by mutations in SLC29A3, a gene located on chromosome 10q23, which encodes the human equilibrative transporter 3 (hENT3). Less than 100 patients with H syndrome have been described in the literature, with the majority being of Arab descent, and only a few from North America.Case presentationHere we report five pediatric patients from three medical centers in the United States who were identified to have H syndrome by whole exome sequencing. These five patients, all of whom presented to pediatric rheumatologists prior to diagnosis, include two of Northern European descent, bringing the total number of Caucasian patients described to three. The patients share many of the characteristics previously reported with H syndrome, including hyperpigmentation, hypertrichosis, short stature, insulin-dependent diabetes, arthritis and systemic inflammation, as well as some novel features, including selective IgG subclass deficiency and autoimmune hepatitis. They share genetic mutations previously described in patients of the same ethnic background, as well as a novel mutation. In two patients, treatment with prednisone improved inflammation, however both patients flared once prednisone was tapered. In one of these patients, treatment with tocilizumab alone resulted in marked improvement in systemic inflammation and growth. The other had partial response to prednisone, azathioprine, and TNF inhibition; thus, his anti-TNF biologic was recently switched to tocilizumab due to persistent polyarthritis. Another patient improved on Methotrexate, with further improvement after the addition of tocilizumab.ConclusionH syndrome is a rare autoinflammatory syndrome with pleiotropic manifestations that affect multiple organ systems and is often mistaken for other conditions. Rheumatologists should be aware of this syndrome and its association with arthritis. It should be considered in patients with short stature and systemic inflammation, particularly with cutaneous findings. Some patients respond to treatment with biologics alone or in combination with other immune suppressants; in particular, treatment of systemic inflammation with IL-6 blockade appears to be promising. Overall, better identification and understanding of the pathophysiology may help devise earlier diagnosis and better treatment strategies.

A novel B-Mode and Doppler image acquisition and scoring system for assessing synovitis in the pediatric knee was successfully developed through practical exercises and consensus process. Study results demonstrate overall good to excellent reliability. This article is protected by copyright. All rights reserved.

BackgroundMagnetic resonance imaging (MRI) is often used to diagnose and monitor treatment effects of juvenile spondyloarthropathy (SpA). Our objective was to describe MRI findings in juvenile SpA and determine predictors of active sacroiliitis and response to treatment.MethodsChildren who had MRI of the sacroiliac (SI) joints and were referred to the pediatric rheumatology clinic from 2009 to 2012 were retrospectively studied. The clinical parameters, laboratory studies and findings on MRI were collected and a composite score ratio (CR) was calculated for both SI joints on each MRI study based on a semi-quantitative scale that included evaluation of bone marrow edema (BME), synovial enhancement (SE), and erosions (ER). The findings on MRI were correlated with clinical and laboratory values.Results50 subjects who underwent 76 MRI for suspected or known SpA were included in the study. Sacroiliitis was seen in 48 MRIs in 32 subjects. Of the subjects with sacroiliitis, mean age ± standard deviation was 13.7 ± 2.6 years, 71% were male and 41% were HLA B27 positive. SE without BME was seen in 31% cases of sacroiliitis. In subjects with sacroiliitis, 79% also had hip arthritis and 41% had enthesitis of the pelvic region on MRI. In 38% of subjects with sacroiliitis, physical exam was not indicative of sacroiliitis or hip arthritis. Longitudinal data were available for 13 subjects. Sacroiliitis on MRI improved in 9 subjects with the greatest improvement in MRI composite score ratio after initiation of etanercept therapy. CR improvement was due to improvement of BME and SE components, while the ER score remained the same or worsened in all but 1 subject.ConclusionHistory, physical exam or laboratory data may not predict sacroiliitis in children. Magnetic resonance imaging plays a valuable role in the initial evaluation and later treatment monitoring of children with spondyloarthropathy. Synovial enhancement is significantly reduced after treatment, and unlike adults, synovial enhancement may be detected without accompanying bone marrow edema, which suggests gadolinium contrast may be an important component in the assessment of children with spondyloarthropathy.

We performed a retrospective chart review for all cases of recurrent Stevens Johnson Syndrome (SJS) from March 2013 to March 2016. Nine children had 29 episodes of SJS or incomplete SJS; all children were male and 8 (88%) were white. Episodes affected mucus membranes with minimal skin involvement. Mycoplasma infections and HLA-B27/-B51 were common.

BackgroundTo describe grey-scale sonographic findings in lower extremity entheses in healthy children.MethodsHealthy patients referred to Orthopedic Surgery or Adolescent Medicine outpatient clinics or their siblings ages 5-18 years were recruited. Grey-scale ultrasound was performed on 3 entheseal sites bilaterally, the proximal patellar ligament insertion (PPL), distal patellar ligament insertion (DPL), and Achilles tendon insertion (AT). Entheseal thickness and quality were recorded. Comparison of thickness between contralateral sites was evaluated to determine within subject site variability.Results702 entheses were examined in 117 children. Age had a weak positive correlation with thickness with large variability. Weight had the strongest correlation to thickness. Contralateral sites are comparable in thickness; a difference of 28%, 26%, and 18% between bilateral PPL, DPL, and AT, respectively, falls within the 95th percentile of the healthy pediatric population in this study. The patellar ligament contour evolved with age from a curved to linear contour.ConclusionsWeight is the best predictor of entheseal thickness in children although there is a large degree of variability. Contralateral entheses are comparable in thickness. A difference below 28%, 26%, and 18% between bilateral PPL, DPL, and AT, respectively, falls within the 95th percentile.

Objective The clinical decision-making process in pediatric arthritis lacks an objective, reliable bedside imaging tool. The aim of this study was to develop an ultrasound (US) scanning protocol and assess the reliability of B-Mode and Doppler scoring systems for inflammatory lesions of the pediatric ankle. Methods As part of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) US group, 19 pediatric rheumatologists through a comprehensive literature review developed a set of standardized views and scoring systems to assess inflammatory lesions of the synovial recesses as well as tendons of the pediatric ankle. Three rounds of scoring of still-images were followed by one practical exercise. Agreement among raters was assessed using two-way single score intraclass correlation coefficients (ICC). Results Of the thirty-seven initially identified views to assess the presence of ankle synovitis and tenosynovitis, nine views were chosen for each B-mode and Doppler mode semi-quantitative evaluation. Several scoring exercises and iterative modifications resulted in a final highly reliable scoring system: anterior tibiotalar joint ICC: 0.93 (Confidence Interval, CI, 0.92–0.94), talonavicular joint ICC: 0.86 (CI 0.81–0.90), subtalar joint ICC: 0.91 (CI 0.88–0.93), tendons ICC: 0.96 (CI 0.95–0.97). Conclusion A comprehensive and reliable pediatric ankle US scanning protocol and scoring system for the assessment of synovitis and tenosynovitis were successfully developed. Further validation of this scoring system may allow its use as an outcome measure for both clinical and research applications.