Athénaïs Boucly, Stéphane Mitrovic, Maryvonnick Carmagnat, Laurent Savale, Xavier Jaïs, Jean-Luc Taupin, Estibaliz Lazaro, Emilie Berthoux, Nicolas Schleinitz, Maria-Rosa Ghigna, Joanna Kedra, Xavier Mariette, Céline Roussin, Pierre-Antoine Juge, Marc Humbert, Olivier Sitbon, David Montani, Bruno Fautrel
{"title":"Pulmonary arterial hypertension in adults with Still's disease: another pulmonary manifestation associated with HLA-DRB1*15.","authors":"Athénaïs Boucly, Stéphane Mitrovic, Maryvonnick Carmagnat, Laurent Savale, Xavier Jaïs, Jean-Luc Taupin, Estibaliz Lazaro, Emilie Berthoux, Nicolas Schleinitz, Maria-Rosa Ghigna, Joanna Kedra, Xavier Mariette, Céline Roussin, Pierre-Antoine Juge, Marc Humbert, Olivier Sitbon, David Montani, Bruno Fautrel","doi":"10.1016/j.ard.2025.04.016","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Inflammatory lung disease in Still's disease (SD) has recently been described. Among its manifestations, pulmonary arterial hypertension (PAH) is a rare and life-threatening event, with only a few case reports published. The objective was to report the largest adult cohort of PAH occurring in the context of SD.</p><p><strong>Methods: </strong>We identified 16 adult SD patients with PAH (PAH+) by a call for observations from the CRI-IMIDIATE (Club Rhumatismes & Inflammation - Immune-Mediated Inflammatory Disease Alliance for Translational and Clinical Research) network (https://cri-net.com/recherche/reseau-CRI-Imidiate/) and a search of the French pulmonary hypertension network registry. Patient characteristics and disease evolution were retrospectively compared with those of 111 SD controls without PAH (PAH-) followed in a reference centre.</p><p><strong>Results: </strong>The profile of patients in the PAH+ and PAH- groups differed: 100% versus 69.4% female (P = .006), 75% versus 17.1% Black (P < .0001), more active SD both at diagnosis and throughout the disease course, and more likely to present macrophage activation syndrome (62.5% vs 14.4%, P < .0001) and exhibit eosinophilia during the disease course (68.7% vs 7.2%, P < .0001). For the 84 out of 127 patients with genetic typing, the HLA-DRB1*15 allele was more prevalent in PAH+ than PAH- patients (8/11 [72.7%] vs 22/73 [30.1%], P = .014). PAH+ patients more frequently received canakinumab and immunosuppressants than did PAH- patients and had higher frequency of drug reactions to interleukin 1 (IL-1) and/or IL-6 inhibitors (37.5% vs 7.2%, P = .002). Mortality was higher in PAH+ than PAH- patients (37.5% vs 0.9%, P < .0001), and all deaths were related to SD flare.</p><p><strong>Conclusions: </strong>These results reinforce the association between the HLA-DRB1*15 allele and severe forms of SD and raise the question of therapeutic optimisation in such patients.</p>","PeriodicalId":8087,"journal":{"name":"Annals of the Rheumatic Diseases","volume":" ","pages":""},"PeriodicalIF":20.3000,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of the Rheumatic Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ard.2025.04.016","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objectives: Inflammatory lung disease in Still's disease (SD) has recently been described. Among its manifestations, pulmonary arterial hypertension (PAH) is a rare and life-threatening event, with only a few case reports published. The objective was to report the largest adult cohort of PAH occurring in the context of SD.
Methods: We identified 16 adult SD patients with PAH (PAH+) by a call for observations from the CRI-IMIDIATE (Club Rhumatismes & Inflammation - Immune-Mediated Inflammatory Disease Alliance for Translational and Clinical Research) network (https://cri-net.com/recherche/reseau-CRI-Imidiate/) and a search of the French pulmonary hypertension network registry. Patient characteristics and disease evolution were retrospectively compared with those of 111 SD controls without PAH (PAH-) followed in a reference centre.
Results: The profile of patients in the PAH+ and PAH- groups differed: 100% versus 69.4% female (P = .006), 75% versus 17.1% Black (P < .0001), more active SD both at diagnosis and throughout the disease course, and more likely to present macrophage activation syndrome (62.5% vs 14.4%, P < .0001) and exhibit eosinophilia during the disease course (68.7% vs 7.2%, P < .0001). For the 84 out of 127 patients with genetic typing, the HLA-DRB1*15 allele was more prevalent in PAH+ than PAH- patients (8/11 [72.7%] vs 22/73 [30.1%], P = .014). PAH+ patients more frequently received canakinumab and immunosuppressants than did PAH- patients and had higher frequency of drug reactions to interleukin 1 (IL-1) and/or IL-6 inhibitors (37.5% vs 7.2%, P = .002). Mortality was higher in PAH+ than PAH- patients (37.5% vs 0.9%, P < .0001), and all deaths were related to SD flare.
Conclusions: These results reinforce the association between the HLA-DRB1*15 allele and severe forms of SD and raise the question of therapeutic optimisation in such patients.
期刊介绍:
Annals of the Rheumatic Diseases (ARD) is an international peer-reviewed journal covering all aspects of rheumatology, which includes the full spectrum of musculoskeletal conditions, arthritic disease, and connective tissue disorders. ARD publishes basic, clinical, and translational scientific research, including the most important recommendations for the management of various conditions.