Pulmonary arterial hypertension in adults with Still's disease: another pulmonary manifestation associated with HLA-DRB1*15

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

Pulmonary arterial hypertension in adults with Still's disease: another pulmonary manifestation associated with HLA-DRB1*15

Ann Rheum Dis. 2025 May 15:S0003-4967(25)00905-7. doi: 10.1016/j.ard.2025.04.016. Online ahead of print.

Authors

Athénaïs Boucly¹, Stéphane Mitrovic², Maryvonnick Carmagnat³, Laurent Savale¹, Xavier Jaïs¹, Jean-Luc Taupin³, Estibaliz Lazaro⁴, Emilie Berthoux⁵, Nicolas Schleinitz⁶, Maria-Rosa Ghigna⁷, Joanna Kedra⁸, Xavier Mariette⁹, Céline Roussin¹⁰, Pierre-Antoine Juge¹¹, Marc Humbert¹, Olivier Sitbon¹, David Montani¹, Bruno Fautrel⁸

Affiliations

¹ APHP, Hôpital Bicêtre, DMU Thorinno, Service de Pneumologie, Le Kremlin-Bicêtre, France; Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France; INSERM, UMR S_999, Le Kremlin-Bicêtre, France.
² Sorbonne Université-APHP, Service de Rhumatologie, Hôpital Pitié-Salpêtrière, Paris, France; Centre d'Etude et de Référence sur les Maladies AutoInflammatoires et les Amyloses (CEREMAIA), FAI2R network, Paris, France; INSERM UMRS 959, Immunology-Immunopathology-Immunotherapy (i3), Sorbonne Université, Paris, France. Electronic address: stephane.mitrovic@aphp.fr.
³ Hôpital Saint Louis, APHP, Laboratoire d'Immunologie et Histocompatibilité, Paris, France.
⁴ Hôpital Haut-Lévêque, service de Médecine Interne, CHU Bordeaux, France.
⁵ Hôpital Saint Joseph-Saint Luc, service de Médecine Interne, Lyon, France.
⁶ Hôpital de la Timone, AP-HM, Département de Médecine Interne, Aix-Marseille Université, Marseille, France.
⁷ Hôpital Marie Lannelongue, service d'anatomopathologie, Le Plessis-Robinson, France.
⁸ Sorbonne Université-APHP, Service de Rhumatologie, Hôpital Pitié-Salpêtrière, Paris, France; Centre d'Etude et de Référence sur les Maladies AutoInflammatoires et les Amyloses (CEREMAIA), FAI2R network, Paris, France; Institut d'Epidémiologie et de Santé Publique Pierre Louis, UMR S 1136, Equipe PEPITES, Paris, France.
⁹ Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France; APHP, service de Rhumatologie, Hôpital Bicêtre, Le Kremlin-Bicêtre, Paris.
¹⁰ Centre Hospitalier Ouest Réunion, service de Médecine Interne, La Réunion, France.
¹¹ Université Paris Centre, Service de Rhumatologie, Hôpital Bichat-Claude Bernard, AP-HP, Paris, France.

PMID: 40379524
DOI: 10.1016/j.ard.2025.04.016

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.