Systemic lupus erythematosus associated with paroxysmal nocturnal hemoglobinuria: a case report and literature review highlighting the clinical significance of small PNH clones.

Systemic lupus erythematosus (SLE) and paroxysmal nocturnal hemoglobinuria (PNH) represent distinct disorders linked by complement pathway dysregulation, yet their co-occurrence remains poorly characterized. We present a 42-year-old woman with newly diagnosed SLE exhibiting persistent cytopenia and Coombs-negative hemolysis, in whom high-sensitivity flow cytometry identified GPI-deficient clones consistent with PNH. Following treatment for SLE, she showed clinical improvement with stable small granulocyte PNH clone during more than 2 years of follow-up. Systematic literature review of seven additional cases reveals that SLE-associated PNH manifests heterogeneously, with thrombotic events occurring in 37.5% (3/8) of patients and detectable hemolysis in 87.5% (7/8). Notably, our analysis challenges the conventional view that small PNH clones (<10% granulocytes) are clinically insignificant - two such cases demonstrated biochemical evidence of hemolysis. These findings suggest that even small PNH clones may contribute to clinical hemolysis in SLE patients through autoimmune complement activation. This observation has immediate clinical relevance, as it justifies PNH screening in SLE patients with unexplained cytopenia or Coombs-negative hemolysis, and the management should be guided by clinical phenotype rather than clone size alone.