[en] [en] IMPORTANCE: Immune-mediated inflammatory diseases are rare but increasingly reported among patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). Systemic lupus erythematosus (LE) and cutaneous LE associated with MDS/CMML have been rarely described, with atypical features and refractory disease.
OBJECTIVE: To provide a comprehensive description of the phenotype and therapeutic responses of LE associated with MDS/CMML and to compare them with idiopathic LE.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective case-control study included nationwide, multicenter data from January 1975 to January 2023. Patients with MDS/CMML who either fulfilled classification criteria for systemic LE or had skin lesions diagnosed as cutaneous LE were included. For MDS/CMML systemic LE, a 2:1 case-control study was conducted with idiopathic systemic LE. Clinical features, centralized skin histopathology, and targeted next-generation sequencing were analyzed. Data were analyzed from May 2022 to June 2025.
MAIN OUTCOMES AND MEASURES: The clinical, pathological, and molecular features of LE occurring in the setting of MDS or CMML compared with idiopathic LE.
RESULTS: Of 24 included patients, 9 (38%) were female, 15 (63%) were male, and the median (range) age at diagnosis was 65 (32-85) years. A total of 19 were diagnosed with systemic LE and 5 with cutaneous LE. The median (range) follow-up was 4.5 (1-31) years. Cutaneous involvement was the most common manifestation of LE (17 [71%]). Chilblain lupus was the predominant subtype (6 [35%]). Compared with idiopathic systemic LE, patients with MDS/CMML-associated LE were older (median [range] age, 65 [32-85] years vs 23 [11-55] years; P < .001), more frequently male (10 [53%] vs 3 [8%]; P = .008), had less kidney involvement (2 [10%] vs 27 [71%]; P < .001), had less articular involvement (7 [36%] vs 37 [97%]; P < .001), and had reduced anti-double-stranded DNA positivity (6 [32%] vs 29 [76%]; P = .001). The underlying hematologic diseases included MDS (16 [66%]) and CMML (8 [34%]), with 22 (92%) classified as lower risk (Revised International Prognostic Scoring System score of 3.5 or less). Centralized histopathological review reclassified 6 skin biopsies (50%) as MDS/CMML cutis. Identical myeloid variants were detected in blood and skin in 6 of 8 patients, supporting a clonal inflammatory process. Standard LE therapies were often poorly effective, while clone-directed therapies (azacitidine or allogeneic hematopoietic stem cell transplant) led to parallel hematologic and LE responses in 5 of 7 patients.
CONCLUSIONS AND RELEVANCE: In this study, MDS/CMML-associated lupuslike manifestations were a distinct entity mimicking systemic LE or cutaneous LE and characterized by clonal inflammation rather than classic autoimmunity in most cases. Early recognition is important, as treatment may require clone-targeting therapies rather than conventional LE therapy.
Disciplines :
Hematology
Author, co-author :
Chauffier, Jeanne; Internal Medicine Department, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris, France
Jachiet, Vincent; Internal Medicine Department, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris, France
Battistella, Maxime; Pathology Department, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, INSERM U1342, Institut de Recherche Saint-Louis, Université Paris Cité, Paris, France
Romero, Pierre; Pathology Department, Centre Hospitalo-Universitaire de Pitié Salpétrière, CIMI, U11-35 Assistance Publique-Hôpitaux de Paris, Paris, France
Fenaux, Pierre; Hematology Department, Hopital Saint Louis, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France
Zakine, Eve; Pathology Department, Centre Hospitalo-Universitaire de Pitié Salpétrière, CIMI, U11-35 Assistance Publique-Hôpitaux de Paris, Paris, France
Zhao, Lin Pierre; Hematology Department, Hopital Saint Louis, Assistance Publique-Hôpitaux de Paris, Université Paris Cité, Paris, France
Mahévas, Thibault; Dermatology Department, Hopital de Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris Cite University, Paris, France
Bouaziz, Jean-David; Dermatology Department, Hopital de Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris Cite University, Paris, France
Hadjadj, Jerome; Internal Medicine Department, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris, France
Amoura, Zahir; Internal Medicine Department, Centre Hospitalo-Universitaire de Pitié Salpetrière, Assistance Publique des Hôpitaux de Paris, Sorbonne Université, Paris, France
Mathian, Alexis; Internal Medicine Department, Centre Hospitalo-Universitaire de Pitié Salpetrière, Assistance Publique des Hôpitaux de Paris, Sorbonne Université, Paris, France
Breillat, Paul; Internal Medicine Department, Centre Hospitalo-Universitaire de Pitié Salpetrière, Assistance Publique des Hôpitaux de Paris, Sorbonne Université, Paris, France
Hirsch, Pierre; Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, CRSA, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Hématologie Biologique, Paris, France
Bourguiba, Rim; Internal Medicine Department, Hôpital FSI, La Marsa, Tunisia
De Voeght, Adrien ; Université de Liège - ULiège > Département des sciences cliniques
Grobost, Vincent; Service de Médecine Interne, Clermont-Ferrand University Hospital, CHU Estaing, Clermont-Ferrand, France
Begon, Edouard; Dermatology Department, Hôpital René Dubos, Pontoise, France
Jandus, Peter; Immunology and Allergology Department, Geneva University Hospital, Geneva, Switzerland
Brenaut, Emilie; Dermatology Department, Centre Hospitalo-Universitaire de Brest, Brest, France
Laumondais, Victoire; Dermatology Department, Centre Hospitalo-Universitaire de Brest, Brest, France
Fain, Olivier; Internal Medicine Department, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris, France
Moguelet, Philippe; Pathology Department, Centre Hospitalo-Universitaire de Pitié Salpétrière, CIMI, U11-35 Assistance Publique-Hôpitaux de Paris, Paris, France
Mekinian, Arsene; Internal Medicine Department, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris, France
Chasset, François; Dermatology Department, Hôpital Tenon and CIMI, U11-35, Assistance Publique-Hôpitaux de Paris, Paris, France
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