Case Report: Hypereosinophilic syndrome misdiagnosed as atopic dermatitis due to refractory pruritic rash masking peripheral neuropathy

Background Hypereosinophilic syndrome (HES) is a rare and heterogeneous disorder characterized by persistent eosinophilia and multi-organ involvement. Cutaneous manifestations are common, whereas peripheral neuropathy may be underrecognized, particularly when dermatologic symptoms predominate. Case presentation We report the case of a 49-year-old man with a 10-year history of recurrent pruritic papules initially managed as atopic dermatitis. Laboratory testing revealed marked eosinophilia (absolute eosinophil count: 5.29 × 10 9 /L) and significantly elevated total immunoglobulin E (IgE) (>6,000 IU/mL; reference range: 0–100 IU/mL). One week after initiating upadacitinib for refractory pruritus, the patient’s itch severity decreased substantially, after which he more clearly perceived distal numbness and gait instability. Nerve conduction studies demonstrated a symmetric sensory-predominant axonal polyneuropathy. Skin biopsy showed eosinophilic inflammatory infiltration without evidence of vasculitis. Quantitative intraepidermal nerve fiber density (IENFD) was within the age-adjusted reference range, consistent with preserved small-fiber integrity. After comprehensive exclusion of secondary and clonal causes of eosinophilia, a diagnosis of idiopathic HES with cutaneous and peripheral nervous system involvement was established. Treatment was adjusted to mepolizumab (300 mg subcutaneously every 4 weeks), followed by clinical improvement in neuropathic symptoms and a reduction in eosinophil levels. Conclusion This case highlights the importance of maintaining a high index of suspicion for systemic eosinophilic disorders in patients with chronic refractory pruritus and marked eosinophilia. Severe pruritus may obscure or delay recognition of concurrent neurological symptoms; therefore, early electrophysiological evaluation should be considered when systemic involvement is suspected. Targeted anti-IL-5 therapy represents an effective treatment strategy in selected cases of HES.