Beyond eosinophil counts: organ involvement patterns across hypereosinophilic syndrome subtypes in a single-center cohort.

INTRODUCTION: Hypereosinophilic syndrome (HES) is defined by persistent hypereosinophilia Q5 associated with eosinophil-mediated organ damage. However, the relationship between HES etiology and organ-involvement patterns remains incompletely defined, particularly in non-hematological forms. This study aimed to describe organ involvement across HES subtypes and to explore clinical associations with multiorgan disease. METHODS: In this retrospective single-center study, 105 patients referred for hypereosinophilia were classified after a standardized two-tailed diagnostic work-up as reactive HES, single-organ HES, lymphocytic-variant HES (L-HES), overlap HES, idiopathic HES, myeloid HES, or HEus. Demographic data, absolute eosinophil count (AEC) at onset, organ domains, organ burden, and exploratory associations with multiorgan disease were analyzed. RESULTS: Mean age at onset was 54.6 ± 18.9 years, and 60.0% of patients were male. Thirteen patients were classified as HEus and had no detectable organ involvement, whereas all HES categories showed at least one involved organ domain. Among recorded organ domains, lung involvement was the most frequent (39.0%), followed by gastrointestinal (30.5%) and cutaneous involvement (29.5%). Peripheral nervous system involvement occurred in 19.0% of patients, whereas cardiac, renal, thrombotic, and central nervous system involvement occurred in 6.7%, 4.8%, 1.9%, and 1.0%, respectively. Multiorgan involvement occurred in 34 patients (32.4%). DISCUSSION: Organ burden differed significantly across subtypes, with overlap HES, mainly driven by eosinophilic granulomatosis with polyangiitis (EGPA), showing the highest multiorgan burden. L-HES and idiopathic HES were predominantly associated with cutaneous disease, whereas single-organ HES involved only the gastrointestinal tract or lung. AEC correlated with the number of involved organs and was strongly associated with multiorgan involvement. Organ involvement in HES is common, heterogeneous, and unevenly distributed across subtypes. Integrating etiological classification with systematic organ phenotyping may improve risk stratification and guide diagnostic and follow-up strategies.