A NOVEL study suggests that lupus erythematosus (LE) associated with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukaemia (CMML) represents a distinct syndrome, with clinical features and treatment responses differing markedly from idiopathic LE.
Distinct Features of MDS/CMML-Associated Lupus-Like Disease
In a nationwide, multicentre cohort study spanning nearly five decades, researchers analysed 24 patients diagnosed with LE in the setting of MDS or CMML. Of these, 19 had systemic LE and 5 had cutaneous LE. The median age at diagnosis was 65 years, notably older than typical idiopathic LE patients, who are often diagnosed in their 20s. Men were disproportionately affected (63% vs 8% in idiopathic LE), and classic lupus features, including kidney and joint involvement, were significantly less common. Cutaneous manifestations were predominant, with chilblain lupus representing the most frequent subtype.
Centralised histopathology of skin lesions and targeted next-generation sequencing revealed that in several cases, the same myeloid gene variants found in blood were also present in skin tissue. This suggests that clonal haematopoiesis, rather than traditional autoimmune mechanisms, may drive inflammation in MDS/CMML-associated LE.
Standard lupus therapies, such as corticosteroids and immunosuppressants, were often poorly effective. By contrast, treatments targeting the underlying haematologic clone, including azacitidine and allogeneic stem cell transplantation, led to improvements in both blood counts and lupus-like symptoms in a subset of patients.
“These findings highlight a lupus-like syndrome that is biologically distinct from classic LE,” said the study authors. “Recognition of this entity is crucial, as it may require early haematologic evaluation and clone-directed therapy rather than conventional lupus management.”
Early Recognition of Lupus-Like Syndrome Critical for Care
The study emphasises the importance of differentiating MDS/CMML-associated LE from idiopathic lupus to avoid ineffective treatment and guide appropriate care. Future research is needed to further define molecular drivers of this clonal inflammation and to establish evidence-based guidelines for management.
Reference
Chauffier J et al. Lupuslike Manifestations in Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia. JAMA Dermatol.2025;DOI:10.1001/jamadermatol.2025.4586.
