{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T13:38:09Z","timestamp":1773409089353,"version":"3.50.1"},"reference-count":34,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T00:00:00Z","timestamp":1680566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ANR","award":["ANR-21-CE17-0064"],"award-info":[{"award-number":["ANR-21-CE17-0064"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Introduction: Biological disease-modifying anti-rheumatic drugs (bDMARDs) targeting interleukin (IL)-6 and IL-1\u03b2 represent a steroid-sparing first-line therapy used in systemic-onset juvenile idiopathic arthritis (sJIA). Recently, the occurrence of pulmonary alveolar proteinosis (PAP) in sJIA patients was reported with early-onset and exposure to bDMARDs as potential risk factors. We report on a new case with longitudinal immunomonitoring successfully treated by Janus Kinase inhibitors (JAKi) and review past clinical descriptions of this new entity. Methods: We report one case of pulmonary alveolar proteinosis and macrophage activation syndrome (PAP-MAS) with longitudinal immunomonitoring. We then conducted a review of the literature of seven publications reporting 107 cases of PAP-MAS sJIA, and included the main characteristics and evolution under treatment. Results: Of the seven articles analyzed, the incidence of PAP-MAS among sJIA patients varied from 1.28% to 12.9%. We report here a single case among a cohort of 537 sJIA patients followed in the pediatric department of the Hospices Civils de Lyon over the last 15 years. This child presented with all clinical and immunological characteristics of PAP-MAS. After several lines of treatment, he benefited from JAKi and improved with respect to both systemic symptoms and lung disease. In the literature, strategies with monoclonal antibodies targeting either INF-\u03b3 or IL-1\u03b2\/IL-18 have been tested with variable results. Orally taken JAKi presents the advantage of targeting multiple cytokines and avoiding parenteral injections of monoclonal antibodies that may contribute to the pathogenesis. Conclusions: JAKi represent a promising option in the treatment of lung disease associated with sJIA.<\/jats:p>","DOI":"10.3390\/jcm12072702","type":"journal-article","created":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T01:39:26Z","timestamp":1680658766000},"page":"2702","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Rescue of Pap-Mas in Systemic JIA Using Janus Kinase Inhibitors, Case Report and Systematic Review"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2479-6165","authenticated-orcid":false,"given":"Franck","family":"Zekre","sequence":"first","affiliation":[{"name":"Nephrology, Rheumatology and Dermatology Unit, National Reference Centre for Rare Rheumatic Autoimmune and Systemic Diseases in Children (RAISE), M\u00e8re Enfant Hospital, Hospices Civils de Lyon, 69500 Bron, France"},{"name":"International Center of Infectiology Research (CIRI), INSERM U1111, CNRS, UMR5308, ENS of Lyon, Claude Bernard University Lyon 1, 69007 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5965-4647","authenticated-orcid":false,"given":"Anita","family":"Duncan","sequence":"additional","affiliation":[{"name":"Nephrology, Rheumatology and Dermatology Unit, National Reference Centre for Rare Rheumatic Autoimmune and Systemic Diseases in Children (RAISE), M\u00e8re Enfant Hospital, Hospices Civils de Lyon, 69500 Bron, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"Laurent","sequence":"additional","affiliation":[{"name":"Nephrology, Rheumatology and Dermatology Unit, National Reference Centre for Rare Rheumatic Autoimmune and Systemic Diseases in Children (RAISE), M\u00e8re Enfant Hospital, Hospices Civils de Lyon, 69500 Bron, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maud","family":"Tusseau","sequence":"additional","affiliation":[{"name":"International Center of Infectiology Research (CIRI), INSERM U1111, CNRS, UMR5308, ENS of Lyon, Claude Bernard University Lyon 1, 69007 Lyon, France"},{"name":"Department of Clinical Genetics, Hospices Civils de Lyon, 69500 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7218-3294","authenticated-orcid":false,"given":"R\u00e9mi","family":"Pescarmona","sequence":"additional","affiliation":[{"name":"Immunology Unit, H\u00f4pital Edouard Herriot, 69003 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8604-1089","authenticated-orcid":false,"given":"Sophie","family":"Collardeau-Frachon","sequence":"additional","affiliation":[{"name":"Department of Pathology, M\u00e8re-Enfant Hospital, Hospices Civils de Lyon, 69500 Bron, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camille","family":"Ohlmann","sequence":"additional","affiliation":[{"name":"Service de Pneumologie P\u00e9diatrique, Allergologie et Mucoviscidose, M\u00e8re-Enfant Hospital, Hospices Civils de Lyon, 69500 Bron, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5085-443X","authenticated-orcid":false,"given":"S\u00e9bastien","family":"Viel","sequence":"additional","affiliation":[{"name":"International Center of Infectiology Research (CIRI), INSERM U1111, CNRS, UMR5308, ENS of Lyon, Claude Bernard University Lyon 1, 69007 Lyon, France"},{"name":"Immunology, Allergy and Immunomonitoring Unit, Groupement H\u00f4pitaux du Sud, 69310 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Reix","sequence":"additional","affiliation":[{"name":"Service de Pneumologie P\u00e9diatrique, Allergologie et Mucoviscidose, M\u00e8re-Enfant Hospital, Hospices Civils de Lyon, 69500 Bron, France"},{"name":"UMR CNRS 5558 (\u00e9quipe EMET), Laboratoire de Biom\u00e9trie et Biologie Evolutive (LBBE), Universit\u00e9 Claude Bernard Lyon 1, 69622 Villeurbanne, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9587-3896","authenticated-orcid":false,"given":"Sarah","family":"Benezech","sequence":"additional","affiliation":[{"name":"International Center of Infectiology Research (CIRI), INSERM U1111, CNRS, UMR5308, ENS of Lyon, Claude Bernard University Lyon 1, 69007 Lyon, France"},{"name":"Institute of Hematology and Pediatric Oncology, 69008 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4902-5332","authenticated-orcid":false,"given":"Alexandre","family":"Belot","sequence":"additional","affiliation":[{"name":"Nephrology, Rheumatology and Dermatology Unit, National Reference Centre for Rare Rheumatic Autoimmune and Systemic Diseases in Children (RAISE), M\u00e8re Enfant Hospital, Hospices Civils de Lyon, 69500 Bron, France"},{"name":"International Center of Infectiology Research (CIRI), INSERM U1111, CNRS, UMR5308, ENS of Lyon, Claude Bernard University Lyon 1, 69007 Lyon, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.autrev.2016.07.004","article-title":"Systemic-onset juvenile idiopathic arthritis","volume":"15","author":"Cimaz","year":"2016","journal-title":"Autoimmun. 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