Butterfield and Gleich [1] reported that interferon- was efficient in five of six patients with the idiopathic hypereosinophilic syndrome. We report a case of hypereosinophilic syndrome that was refractory to interferon therapy and was successfully treated with oral etoposide.

A 59-year-old man had had defined idiopathic hypereosinophilic syndrome since 1991. High-grade fever and bloody diarrhea with abdominal cramps were temporally associated with high eosinophil counts. Moderate splenomegaly and lower limb dysesthesia caused by axonal polyneuropathy were consistently found. The eosinophil count before any specific treatment was 20 000 cells/mm³. IgE and vitamin B₁₂ levels were normal. Examination of repeated bone marrow biopsy specimens and of karyotype did not show myeloproliferative features. Digestive endoscopy showed widespread mucosal ulcerations. Examination of a biopsy specimen of the small intestine showed pleomorphic eosinophilic infiltrates (10% to 25%) and subtotal villous atrophy.

Oral prednisone (1 mg/kg body weight daily) was started in June 1991 and was initially efficient. In April 1992, hydroxyurea at a dose of 300 mg/d was started because of a relapse of the hypereosinophilic syndrome that occurred when the steroid dose was tapered to 0.5 mg/kg per day. In September 1992, the eosinophil count reached 10 000 cells/mm³, and interferon-2a (Roferon-A; Roche, Nutley, New Jersey) was administered (3 MU three times a week). The hydroxyurea dose was maintained at 200 mg/d, and the prednisone dose was decreased to 15 mg/d.

In April 1993, the interferon- dose was increased (5 MU three times a week) because of further relapse. The eosinophil count decreased to 600 cells/mm³. In June 1994, fever and peripheral facial palsy developed, and the eosinophil count was 2600 cells/mm³. Interferon- was replaced with purinethol (150 mg/d) plus hydroxyurea (100 mg/d). In August 1994, the patient had fever, hematemesis, abdominal pain, and deep venous thrombosis of the left calf. His eosinophil count was 23 000 cells/mm³. Purinethol and hydroxyurea were stopped. Intravenous prednisolone, 1 g/d for 3 days (followed by oral prednisone 1 mg/kg per day), had only a brief effect. Oral etoposide (100 mg/d for 10 days, then 50 mg every other day) was added to the steroids. Clinical and biological variables dramatically improved. The prednisone dose was tapered to 0.3 mg/kg per day. After 3 months, the patient was asymptomatic, and his eosinophil counts were less than 350 cells/mm³.

Etoposide (VP16-213) is a podophyllotoxin derivative used in both myeloproliferative and lymphoproliferative disorders. A long-term response to etoposide has previously been reported in one case of steroid-resistant hypereosinophilic syndrome [2]. Because low-dose oral etoposide might be efficient in patients with interferon-resistant hypereosinophilic syndrome, we suggest that it be tested as a second-line agent in refractory idiopathic hypereosinophilic syndrome.