Monogenic Lupus Is a Construct: Insights into the Current Nomenclature and Classification

Monogenic lupus is a rare inherited entity, which has been increasingly recognized over the past decade. Monogenic lupus demonstrates heterogeneity in etiopathogenesis, phenotypes, and outcome compared to sporadic systemic lupus erythematous (SLE). Its distinctive features include early-onset disease, atypical manifestations of underlying diseases such as immunodeficiency, immune dysregulation, and refractory disease course. The term “monogenic lupus” has been used internationally to collectively describe a group of patients presenting with SLE or SLE-like symptoms with a proven underlying pathogenic variant. It has been considered a form of SLE irrespective of the differences observed. To date, there is no standardized definition or criteria to identify monogenic lupus. Therefore, this review highlights the differences between monogenic lupus and sporadic SLE to discuss the challenges related to the current nomenclature and unmet needs in the diagnosis of monogenic lupus. A considerable number of underlying pathogenic variants have recently been uncovered, leading to various pathways’ involvement with significant overlap. This allows us to propose a new definition for monogenic lupus which can be considered as a construct rather than a disease or syndrome.