Comment on: Recurrent skin reaction attributable to darbepoetin alfa in a patient with chronic renal failure

A 90-year-old man was admitted to our department with multiple pruritic erythematous skin lesions on the trunk, face, and limbs of 2 days duration. His medical history was unremarkable except for chronic renal failure (CRF) being treated with candesartan 8 mg/day and clopidogrel 75 mg/day for the last 2 years. His renal function was stable during the last year (serum creatinine: 3–3.5 mg/dL), but 2 months prior to his admission he developed anemia (Ht, 28%; Hb, 9 mg/dL), which after extensive investigation was attributed to his renal dysfunction. Thus, the patient was commenced on darbepoetin alfa (Aranesp) 60 μg/week subcutaneously. The patient reported that after the second injection of darbepoetin he noticed the presence of pruritic skin lesion, particularly over his trunk and arms. The skin lesions significantly improved without any medication after darbepoetin's discontinuation, but the patient experienced a severe exacerbation of his rash after 10 days when he decided to receive a third dose of darbepoetin. On admission, the clinical examination revealed a generalized dermatitis with superficial desquamation covered his face, trunk, upper, and lower limbs (Figure 1), without any other abnormal findings. Laboratory findings included hematocrit, 31.2%; WBC, 11,200/mm³; Cr, 3.2 mg/dL; urea, 95 mg/dL. The patient was commenced on prednisolone 1 mg/kg intravenously and cetirizine 20 mg/day/os. On the following days, the patient's clinical condition gradually improved and he was discharged after 5 days in a good condition with prednisolone 20 mg/os in decreasing dosage. The patient was followed-up in the clinic, prednisolone withdrawn 10 days after his discharge, and the skin lesions completely disappeared 15 days later.

FIGURE 1. Pruritic erythematous skin lesions on the back as part of widespread dermatitis of the patient at the day of admission to our department.

The introduction of erythropoietin has been a significant development in the management of patients with CRF.¹ Darbepoetin alfa is a glycoprotein analog of recombinant human erythropoietin, which contains up to 22 sialic acid molecules giving it higher potency and a longer half-life.² Although well tolerated by most patients (only 3% discontinued treatment due to adverse events), prescribing information reported that skin rash occurred in 7% of patients taking darbepoetin alfa. However, only three cases of generalized skin reaction attributable to darbepoetin alfa are reported in the literature^3–5 and only one of the patients suffered from CRF.⁴ Interestingly, in the latter patient,⁴ the skin lesions were attributed to polysorbate 80, which is used as excipient in many drugs, including darbepoetin alfa. Our patient had used a similar formulation of darbepoetin alfa containing polysorbate 80. Thus, we decided to prescribe a polysorbate 80-free erythropoietin and the patient remains in full remission without any relapse of his skin lesions for 18 months now.

Evangelos Cholongitas, Simos Spyrou,

Chrysa Georgousaki, and Maria Dasenaki

Department of Internal Medicine, General Hospital of

Sitia, Sitia GR-72300, Greece