Retrospective Cohort Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Pediatr. Mar 9, 2024; 13(1): 88912
Published online Mar 9, 2024. doi: 10.5409/wjcp.v13.i1.88912
Systemic juvenile idiopathic arthritis–associated lung disease: A retrospective cohort study
Konstantin E Belozerov, Natalia M Solomatina, Eugenia A Isupova, Alla A Kuznetsova, Mikhail M Kostik
Konstantin E Belozerov, Natalia M Solomatina, Eugenia A Isupova, Alla A Kuznetsova, Mikhail M Kostik, Department of Pediatric, Saint-Petersburg State Pediatric Medical University, Saint-Petersburg 194100, Russia
Konstantin E Belozerov, St. Petersburg State Budgetary Institution of Health Care, Children's City Polyclinic No. 29 of the Kalininsky District of St. Petersburg, St. Petersburg 195274, Russia
Mikhail M Kostik, Research Laboratory of Autoimmune and Autoinflammatory Diseases, World-Class Research Centre for Personalized Medicine, Almazov National Medical Research Centre, St. Petersburg 197341, Russia
Author contributions: Kostik MM and Belozerov KE contributed to the conceptualization, writing, review, editing and original draft preparation; Kostik MM and Kuznetsova AA contributed to the methodology; Belozerov KE contributed to the software and formal analysis; Solomatina NM and Isupova EA contributed to the validation and resources; Belozerov KE, Solomatina NM, and Isupova EA contributed to the investigation; Kuznetsova AA contributed to data curation; Kostik MM contributed to funding, supervision and project administration; All authors read and approve the final manuscript, were involved in drafting the article or revising it critically for important intellectual content.
Supported by the Ministry of Science and Higher Education of the Russian Federation, No. 075-15-2022-301.
Institutional review board statement: The Ethics Committee of Saint Petersburg State Pediatric Medical University (18/01 from 27.10.2022) approved this retrospective study's protocol.
Informed consent statement: Written consent was obtained according to the Declaration of Helsinki. All patients or patient representatives (for patients under the age of 15 years) gave their consent in their case report forms authorizing the anonymous use of their medical information. All patients were appropriately anonymized.
Conflict-of-interest statement: All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Data sharing statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—a checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mikhail M Kostik, MD, PhD, Professor, Department of Pediatric, Saint-Petersburg State Pediatric Medical University, Lytovskaya 2, Saint-Petersburg 194100, Russia. kost-mikhail@yandex.ru
Received: October 14, 2023
Peer-review started: October 14, 2023
First decision: December 23, 2023
Revised: January 3, 2024
Accepted: February 18, 2024
Article in press: February 18, 2024
Published online: March 9, 2024
Processing time: 144 Days and 9.1 Hours
Abstract
BACKGROUND

Lung damage in systemic juvenile arthritis (sJIA) is one of the contemporary topics in pediatric rheumatology. Several previous studies showed the severe course and fatal outcomes in some patients. The information about interstitial lung disease (ILD) in the sJIA is scarce and limited to a total of 100 cases.

AIM

To describe the features of sJIA patients with ILD in detail.

METHODS

In the present retrospective cohort study, information about 5 patients less than 18-years-old with sJIA and ILD were included. The diagnosis of sJIA was made according to the current 2004 and new provisional International League of Associations for Rheumatology criteria 2019. ILD was diagnosed with chest computed tomography with the exclusion of other possible reasons for concurrent lung involvement. Macrophage activation syndrome (MAS) was diagnosed with HLH-2004 and 2016 EULAR/ACR/PRINTO Classification Criteria and hScores were calculated during the lung involvement.

RESULTS

The onset age of sJIA ranged from 1 year to 10 years. The time interval before ILD ranged from 1 mo to 3 years. The disease course was characterized by the prevalence of the systemic features above articular involvement, intensive rash (100%), persistent and very active MAS (hScore range: 194-220) with transaminitis (100%), and respiratory symptoms (100%). Only 3 patients (60%) developed a clubbing phenomenon. All patients (100%) had pleural effusion and 4 patients (80%) had pericardial effusion at the disease onset. Two patients (40%) developed pulmonary arterial hypertension. Infusion-related reactions to tocilizumab were observed in 3 (60%) of the patients. One patient with trisomy 21 had a fatal disease course. Half of the remaining patients had sJIA remission and 2 patients had improvement. Lung disease improved in 3 patients (75%), but 1 of them had initial deterioration of lung involvement. One patient who has not achieved the sJIA remission had the progressed course of ILD. No cases of hyper-eosinophilia were noted. Four patients (80%) received canakinumab and one (20%) tocilizumab at the last follow-up visit.

CONCLUSION

ILD is a severe life-threatening complication of sJIA that may affect children of different ages with different time intervals since the disease onset. Extensive rash, serositis (especially pleuritis), full-blown MAS with transaminitis, lymphopenia, trisomy 21, eosinophilia, and biologic infusion reaction are the main predictors of ILD. The following studies are needed to find the predictors, pathogenesis, and treatment options, for preventing and treating the ILD in sJIA patients.

Keywords: Systemic juvenile arthritis; Interstitial lung disease; Canakinumab; Tocilizumab; Interleukin-6; Interleukin-1

Core Tip: We evaluated 5 patients with systemic juvenile arthritis and interstitial lung disease. This is an ultra-rare, unrecognized, life-threatening and potentially fatal complication of systemic juvenile arthritis. This complication is usually associated with early onset age, systemic features of the disease, especially with pleuritis, severe and long-term macrophage activation syndrome, lymphopenia, trisomy 21 syndrome, and biologic anaphylaxis. The recognition of these symptoms can help in early suspicion of this severe complication.