TOPLINE:

Lupus-like manifestations in myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) represent a distinct inflammatory syndrome driven by clonal hematopoietic cells rather than classic autoimmunity.

METHODOLOGY:

• Researchers conducted a retrospective case-control study of 24 patients (54% male; median age at diagnosis, 66.5 years) with MDS/CMML who fulfilled classification criteria for systemic lupus erythematosus (LE) or had skin lesions diagnosed as cutaneous LE from January 1975 to January 2023.
• A 2:1 case-control analysis compared 19 patients with MDS/CMML-associated systemic LE with 38 patients with idiopathic systemic LE, examining clinical features, centralized skin histopathology, and targeted next-generation sequencing.
• Skin biopsies from 12 patients were reviewed by pathologists specializing in cutaneous manifestations of MDS/CMML and cutaneous LE.
• Next-generation sequencing from targeted myeloid panels was performed on peripheral blood samples from 14 patients and bone marrow samples from five patients to identify clinically relevant genetic alterations.

TAKEAWAY:

• Compared with patients with idiopathic systemic LE, those with MDS/CMML-associated LE were older (median age, 23 vs 65 years; P < .001), were more often male (8% vs 53%; P = .008), and had reduced kidney involvement (71% vs 10%; P < .001).
• Cutaneous involvement was the most common manifestation of LE, affecting 71% of patients, with chilblain lupus being the most common subtype (35%), and centralized histopathologic review reclassified 50% of skin biopsies as MDS/CMML cutis.
• Identical myeloid variants were detected in both blood and skin samples in six of eight patients, supporting a clonal inflammatory process.
• Standard LE treatments showed limited effectiveness, whereas clone-directed therapies (azacitidine or allogeneic hematopoietic stem cell transplant) led to parallel hematologic and lupus responses in five of seven patients.

IN PRACTICE:

“MDS/CMML-associated LE represents a distinct inflammatory syndrome, likely mediated by clonal hematopoietic cells rather than classic autoimmunity,” the authors concluded. “Recognizing this entity is essential to avoid misdiagnosis and therapeutic failure,” they added.

SOURCE:

The study was led by Jeanne Chauffier, MD, Lariboisiere University Hospital, Paris, France, and was published online on November 19 in JAMA Dermatology.

LIMITATIONS: 

Limitations included the retrospective design, a small sample size, and the possibility of additional variants not detected by the targeted myeloid next-generation sequencing panel.

DISCLOSURES:

The authors did not report any funding source. Several authors declared receiving personal fees, grants, and nonfinancial support from various drug companies, including Innate Pharma, Kyowa Kirin, Recordati Rare Diseases, Bristol Myers Squibb, MSD, Sanofi, Sobi, Janssen, Lilly, Novartis, Almirall, AbbVie, and Johnson & Johnson, outside the submitted work. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.