Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Mar 9;13(1):88912.
doi: 10.5409/wjcp.v13.i1.88912.

Systemic juvenile idiopathic arthritis-associated lung disease: A retrospective cohort study

Konstantin E Belozerov  1   2 , Natalia M Solomatina  1 , Eugenia A Isupova  1 , Alla A Kuznetsova  1 , Mikhail M Kostik  1   3
Affiliations

Systemic juvenile idiopathic arthritis-associated lung disease: A retrospective cohort study

Konstantin E Belozerov et al. World J Clin Pediatr. .

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

PubMed Disclaimer

Conflict of interest statement

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.

Figures

Figure 1
Figure 1
Clubbing of the fingers in patient 2. The changes of the distal phalanges and the nails are apparent.
Figure 2
Figure 2
Chest computed tomography in patient 2 with lipoid pneumonia. A and B: Representative signs of interstitial changes in all lobes of the lungs with damage to the distal parts of the tracheobronchial tree. There are diffuse changes with the presence of multiple intralobular foci, with thickening of the peribronchovascular interstitium.
Figure 3
Figure 3
Brief summary of the pathogenesis of lung involvement in systemic juvenile arthritis. BMPR2: Bone morphogenetic protein receptor type II; GM-CSF: Granulocyte-macrophage colony-stimulating factor; IFN: Interferon; IL: Interleukin; ILD: Interstitial lung disease; MAS: Macrophage activation syndrome; PAH: Pulmonary arterial hypertension; PAP: Pulmonary alveolar proteinosis; sJIA: Systemic juvenile idiopathic arthritis; TNF: Tumor necrosis factor.
See this image and copyright information in PMC

References

    1. Schulert GS, Yasin S, Carey B, Chalk C, Do T, Schapiro AH, Husami A, Watts A, Brunner HI, Huggins J, Mellins ED, Morgan EM, Ting T, Trapnell BC, Wikenheiser-Brokamp KA, Towe C, Grom AA. Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease: Characterization and Risk Factors. Arthritis Rheumatol. 2019;71:1943–1954. - PMC - PubMed
    1. Minoia F, Davì S, Horne A, Demirkaya E, Bovis F, Li C, Lehmberg K, Weitzman S, Insalaco A, Wouters C, Shenoi S, Espada G, Ozen S, Anton J, Khubchandani R, Russo R, Pal P, Kasapcopur O, Miettunen P, Maritsi D, Merino R, Shakoory B, Alessio M, Chasnyk V, Sanner H, Gao YJ, Huasong Z, Kitoh T, Avcin T, Fischbach M, Frosch M, Grom A, Huber A, Jelusic M, Sawhney S, Uziel Y, Ruperto N, Martini A, Cron RQ, Ravelli A Pediatric Rheumatology International Trials Organization; Childhood Arthritis and Rheumatology Research Alliance; Pediatric Rheumatology Collaborative Study Group; Histiocyte Society. Clinical features, treatment, and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a multinational, multicenter study of 362 patients. Arthritis Rheumatol. 2014;66:3160–3169. - PubMed
    1. Saper VE, Chen G, Deutsch GH, Guillerman RP, Birgmeier J, Jagadeesh K, Canna S, Schulert G, Deterding R, Xu J, Leung AN, Bouzoubaa L, Abulaban K, Baszis K, Behrens EM, Birmingham J, Casey A, Cidon M, Cron RQ, De A, De Benedetti F, Ferguson I, Fishman MP, Goodman SI, Graham TB, Grom AA, Haines K, Hazen M, Henderson LA, Ho A, Ibarra M, Inman CJ, Jerath R, Khawaja K, Kingsbury DJ, Klein-Gitelman M, Lai K, Lapidus S, Lin C, Lin J, Liptzin DR, Milojevic D, Mombourquette J, Onel K, Ozen S, Perez M, Phillippi K, Prahalad S, Radhakrishna S, Reinhardt A, Riskalla M, Rosenwasser N, Roth J, Schneider R, Schonenberg-Meinema D, Shenoi S, Smith JA, Sönmez HE, Stoll ML, Towe C, Vargas SO, Vehe RK, Young LR, Yang J, Desai T, Balise R, Lu Y, Tian L, Bejerano G, Davis MM, Khatri P, Mellins ED Childhood Arthritis and Rheumatology Research Alliance Registry Investigators. Emergent high fatality lung disease in systemic juvenile arthritis. Ann Rheum Dis. 2019;78:1722–1731. - PMC - PubMed
    1. Kimura Y, Weiss JE, Haroldson KL, Lee T, Punaro M, Oliveira S, Rabinovich E, Riebschleger M, Antón J, Blier PR, Gerloni V, Hazen MM, Kessler E, Onel K, Passo MH, Rennebohm RM, Wallace CA, Woo P, Wulffraat N Childhood Arthritis Rheumatology Research Alliance Carra Net Investigators. Pulmonary hypertension and other potentially fatal pulmonary complications in systemic juvenile idiopathic arthritis. Arthritis Care Res (Hoboken) 2013;65:745–752. - PMC - PubMed
    1. Proceedings of the 25th European Paediatric Rheumatology Congress (pReS 2018) Pediatr Rheumatol. 2018;16:52.