Evidence map›Paper›PMID 31562126›Full record

ArticleAnnals of the rheumatic diseases2019

Emergent high fatality lung disease in systemic juvenile arthritis.

Vivian E Saper, Guangbo Chen, Gail H Deutsch, R Paul Guillerman, Johannes Birgmeier, Karthik Jagadeesh, Scott Canna, Grant Schulert, Robin Deterding, Jianpeng Xu and 63 more

Erratum issuedOpen access · greenAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of the rheumatic diseases, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 113 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed, 5 pooled it
15.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

113 citing papers in PubMed, 5 syntheses or guidelines pooled it, 206 citations in OpenAlex.

  1. Pooled it
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  10. Type I Interferon and Still Disease.Arthritis & rheumatology (Hoboken, N.J.) · 2026
    Article
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53 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

73 authors at 20 institutions in 8 countries.

Vivian E SaperPediatrics, Stanford University, Stanford, California, USA.
Guangbo ChenInstitute for Immunity, Transplantation and Infection, Center for Biomedical Informatics Research, Medicine, Stanford University, Stanford, California, USA.
Gail H Deutsch *Pathology, Seattle Children's Hospital, Seattle, Washington, USA.
R Paul Guillerman *Radiology, Baylor College of Medicine, Houston, Texas, USA.
Johannes Birgmeier *Genetics, Stanford University, Stanford, California, USA.
Karthik Jagadeesh *Genetics, Stanford University, Stanford, California, USA.
Scott Canna *Pediatrics, Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Grant Schulert *Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Robin DeterdingChildren's Hospital Colorado, Aurora, Colorado, USA.
Jianpeng XuPediatrics, Stanford University, Stanford, California, USA.
Ann N LeungRadiology, Stanford University, Stanford, California, USA.
Layla BouzoubaaPublic Health Services, Biostatistics, University of Miami School of Medicine, Miami, Florida, USA.
Khalid AbulabanHelen DeVos Children's Hospital, Grand Rapids, Michigan, USA.
Kevin BaszisPediatrics, Washington University in Saint Louis, Saint Louis, Missouri, USA.
Edward M BehrensPediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
James BirminghamMedicine, Metro Health Hospital, Wyoming, Michigan, USA.
Alicia CaseyBoston Children's Hospital, Boston, Massachusetts, USA.
Michal CidonPediatrics, Children's Hospital of Los Angeles, Los Angeles, California, USA.
Randy Q CronChildren's of Alabama, Birmingham, Alabama, USA.
Aliva DePediatrics, Columbia University Medical Center, New York, New York, USA.
Fabrizio De BenedettiRheumatology, Ospedale Pediatrico Bambino Gesu, Roma, Italy.
Ian FergusonPediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.
Martha P FishmanBoston Children's Hospital, Boston, Massachusetts, USA.
Steven I GoodmanArthritis Associates of South Florida, Delray Beach, Florida, USA.
T Brent GrahamPediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Alexei A GromPediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Kathleen HainesJoseph M Sanzari Children's Hospital, Hackensack, New Jersey, USA.
Melissa HazenBoston Children's Hospital, Boston, Massachusetts, USA.
Lauren A HendersonBoston Children's Hospital, Boston, Massachusetts, USA.
Assunta HoPediatrics, Prince of Wales Hospital, New Territories, Hong Kong.
Maria IbarraChildren's Mercy Hospitals and Clinics, Kansas City, Missouri, USA.
Christi J InmanPediatrics, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
Rita JerathChildren's Hospital of Georgia, Augusta, Georgia, USA.
Khulood KhawajaPediatrics, Al Mafraq Hospital, Abu Dhabi, Abu Dhabi, United Arab Emirates.
Daniel J KingsburyRandall Children's Hospital at Legacy Emanuel, Portland, Oregon, USA.
Marisa Klein-GitelmanPediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Khanh LaiPediatrics, University of Utah Health Sciences Center, Salt Lake City, Utah, USA.
Sivia LapidusJoseph M Sanzari Children's Hospital, Hackensack, New Jersey, USA.
Clara LinChildren's Hospital Colorado, Aurora, Colorado, USA.
Jenny LinChildren's Hospital at Montefiore, Bronx, New York, USA.
Deborah R LiptzinChildren's Hospital Colorado, Aurora, Colorado, USA.
Diana MilojevicJohns Hopkins All Children's Hospital, Saint Petersburg, Florida, USA.
Joy MombourquettePediatrics, Kaiser Permanente Roseville Medical Center, Roseville, California, USA.
Karen OnelPediatrics, Hospital for Special Surgery, New York, New York, USA.
Seza OzenPediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Maria PerezCook Children's Medical Center, Fort Worth, Texas, USA.
Kathryn PhillippiAkron Children's Hospital, Akron, Ohio, USA.
Sampath PrahaladPediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
Suhas RadhakrishnaRady Children's Hospital, San Diego, California, USA.
Adam ReinhardtPediatrics, University of Nebraska Medical Center College of Medicine, Omaha, Nebraska, USA.
Mona RiskallaPediatrics, University of Minnesota Medical School Twin Cities, Minneapolis, Minnesota, USA.
Natalie RosenwasserPediatrics, Hospital for Special Surgery, New York, New York, USA.
Johannes RothChildren's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
Rayfel SchneiderHospital for Sick Children, Toronto, Ontario, Canada.
Dieneke Schonenberg-MeinemaEmma Children's Hospital AMC, Amsterdam, The Netherlands.
Susan ShenoiUniversity of Washington School of Medicine, Seattle, Washington, USA.
Judith A SmithPediatrics, University of Wisconsin Madison School of Medicine and Public Health, Madison, Wisconsin, USA.
Hafize Emine SönmezPediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Matthew L StollChildren's of Alabama, Birmingham, Alabama, USA.
Christopher TowePediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Sara O VargasHarvard Medical School, Boston, Massachusetts, USA.
Richard K VehePediatrics, University of Minnesota Medical School Twin Cities, Minneapolis, Minnesota, USA.
Lisa R YoungPediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Jacqueline YangInstitute for Immunity, Transplantation and Infection, Center for Biomedical Informatics Research, Medicine, Stanford University, Stanford, California, USA.
Tushar DesaiMedicine, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, California, USA.
Raymond BalisePublic Health Services, Biostatistics, University of Miami School of Medicine, Miami, Florida, USA.
Ying LuBiomedical Data Science, Stanford University, Stanford, California, USA.
Lu TianBiomedical Data Science, Stanford University, Stanford, California, USA.
Gill BejeranoGenetics, Stanford University, Stanford, California, USA.
Mark M DavisInstitute for Immunity, Transplantation and Infection, Microbiology and Immunology, Stanford University, Stanford, California, USA.
Purvesh KhatriInstitute for Immunity, Transplantation and Infection, Center for Biomedical Informatics Research, Medicine, Stanford University, Stanford, California, USA.
Elizabeth D MellinsPediatrics, Stanford University, Stanford, California, USA mellins@stanford.edu.ORCID 0000-0003-2577-139X
Childhood Arthritis and Rheumatology Research Alliance Registry Investigators
Stanford University · USBoston Children's Hospital · USChildren's Hospital Colorado · USCincinnati Children's Hospital Medical Center · USChildren's Hospital of Philadelphia · USChildren's of Alabama · USHacettepe University · TRHackensack University Medical Center · USHospital for Special Surgery · USSeattle Children's Hospital · USUniversity of Miami · USUniversity of Minnesota · USUniversity of Utah · USAkron Children's Hospital · USAlbert Einstein College of Medicine · USAugusta University · USBambino Gesù Children's Hospital · ITBaylor College of Medicine · USCarolina Arthritis Associates · USChildren's Hospital of Eastern Ontario · CA

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
Translational Incubator CoreU19AI109662 · NIAID · STANFORD UNIVERSITY · PI GLENN, JEFFREY S · 2014 to 2019
$28.6M
Giant MagnetoResistive (GMR) Sensors for Measuring Influenza VaccineR01AI125197 · NIAID · STANFORD UNIVERSITY · PI UTZ, PAUL JOSEPH, WANG, SHAN X. · 2016 to 2021
$5.0M
Interdisciplinary Training Program in MetabolismT32DK091317 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI SCOTT A SUMMERS · 2011 to 2026
$4.8M
Midcareer Investigator Award in Patient-Oriented Research in Pediatric Rare Lung DiseasesK24HL143281 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI YOUNG, LISA R. · 2018 to 2022
$540k
NHLBI NIH HHS K24 HL143281NIAID NIH HHS R01 AI125197NIAID NIH HHS U19 AI057229NIAID NIH HHS U19 AI109662NIDDK NIH HHS T32 DK091317
6 · The paper itself

Abstract

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.

Indexed as

Arthritis, JuvenileBiopsyChildChild, PreschoolFemaleFollow-Up StudiesHumansIncidenceInfantLungLung DiseasesMalePrognosisRetrospective StudiesSurvival RateTomography, X-Ray Computedadult onset still's diseaseDMARDs (biologic)inflammationjuvenile idiopathic arthritistreatment

Identifiers

PMID31562126
PMCPMC7065839
OpenAlexW2975994788

What OpenQuestion holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.