Refractory autoimmune cytopenias in pediatric Evans syndrome with underlying systemic immune dysregulation

Evans syndrome is a rare but challenging disorder in children; and despite rapidly growing evidence for targetable systemic immune dysregulation driving these “idiopathic” autoimmune cytopenias, precision diagnosis and management remains sub‐optimal among these patients. We analyzed retrospective clinical data for 60 pediatric ES patients followed at 3 large tertiary referral centers in the United States over a recent 6‐year period and found that definable underlying systemic immune dysregulation was identified in only 42% of these patients throughout the course of clinical care. Median time from ES diagnosis to identification of the underlying systemic immune dysregulation disorder was 1.3 years (<1 month for rheumatologic disease, 2.3 years for CVID, 3.4 years for ALPS, and 7.4 years for monogenic disorders of immune regulation). Notably, a significantly higher percentage of patients in whom a definitive immune dysregulation disorder was ultimately identified required ≥3 cytopenia‐directed therapies (92%) and also second‐ and third‐line immunomodulatory agents (84%), vs those in whom no unifying immune dysregulation was diagnosed (65%, and 35%, respectively)—indicating that autoimmune cytopenias as a manifestation of systemic immune dysregulation are more treatment‐refractory and severe. These data underline the importance of identifying the underlying systemic immune dysregulation and providing targeted therapy in pediatric ES.