Neutropenia and Lymphopenia in Systemic Lupus Erythematosus: Distinct Phenotypes and Associated Factors in a Saudi Multicenter Study

Background/Objectives: Neutropenia and lymphopenia are common hematologic manifestations of systemic lupus erythematosus (SLE), but whether they represent distinct phenotypes is not well established. This study evaluated their prevalence, patterns, and associated factors. Methods: This multicenter retrospective study included 353 adults with SLE from three Saudi centers. Cytopenias were defined using prespecified laboratory criteria. Patients were classified as having neither abnormality, isolated neutropenia, isolated lymphopenia, or both. Multivariable logistic regression was used to assess factors associated with ever-neutropenia and ever-lymphopenia. Results: Leukopenia occurred in 141 patients (39.9%). Ever-neutropenia and ever-lymphopenia were each observed in 88 patients (24.9%); 47 (13.3%) had isolated neutropenia, 47 (13.3%) had isolated lymphopenia, and 41 (11.6%) had both abnormalities. Persistent neutropenia and lymphopenia occurred in 22 (6.2%) and 23 (6.5%) patients, respectively. Most neutropenia was mild, and only three patients had severe neutropenia. The four phenotypes differed in age, body mass index, autoimmune hemolytic anemia, platelet count, anti-Smith positivity, and immunosuppressive exposure. No included variable was independently associated with ever-neutropenia. Ever-lymphopenia was independently associated with male sex (aOR 2.66, 95% CI 1.22–5.81), anti-Smith positivity (aOR 2.71, 95% CI 1.40–5.24), and exposure to azathioprine (aOR 2.07, 95% CI 1.16–3.71), mycophenolate mofetil use (aOR 2.79, 95% CI 1.42–5.52), and rituximab use (aOR 3.83, 95% CI 1.50–9.75). Conclusions: Neutropenia and lymphopenia each occurred in one-quarter of patients with SLE, whereas persistent cytopenias were uncommon. No independent associations were identified for ever-neutropenia. The demographic, serologic, and treatment-related associations of ever-lymphopenia support separate evaluation of the two abnormalities in SLE.