Late onset of bortezomib-associated cutaneous reaction following herpes zoster

Abstract

Dear Editor, Bortezomib, a proteasome inhibitor, has demonstrated a remarkable activity in multiple myeloma. The most common adverse events are fatigue, gastrointestinal effects, peripheral neuropathy, and thrombocytopenia. Skin rashes have been reported in about 20% of the patients. We report the case of a patient who developed a bortezomib-associated cutaneous reaction in the same area of a recent herpes zoster. A 49-year-old man with a relapsed multiple myeloma started a treatment with bortezomib at the dose of 1.3 mg/m on days 1, 4, 8, and 11 every 21 days. At baseline, serum paraprotein was 6.1 g/dl; renal function and calcemia were normal. The patient achieved partial remission after the first cycle of treatment with bortezomib. At cycle 2, the patient developed a varicella-zoster virus (VZV) infection at the neck and trunk associated with fever treated with intravenous acyclovir. Bortezomib was interrupted for 3 weeks and then restarted at the same dose after complete resolution of the infection. Four weeks later, at day 8 of cycle 4, the patient presented with an itching papular skin rash localized at the same sites of prior VZV infection without constitutional symptoms (Fig. 1). Bortezomib was continued, and the lesions were resolved adding oral prednisone for some days. At day 8 of cycle 5, the lesions recurred with the same features and distribution. The patient underwent cutaneous biopsy demonstrating a perivascular and interstitial infiltrate consisting of T CD3+ lymphocytes and CD68+ histiocytes (Fig. 2). Bortezomib was not discontinued this time, and dexamethasone was added at 20 mg on days 1–2, 4–5, 8–9, and 11–12. After two doses of dexamethasone, the skin rash resolved. Despite the dose reduction and ongoing treatment, however, with dexamethasone at cycle 7, skin lesions recurred during the rest period between 7 and 8 cycles and were successfully treated with oral antihistaminics. The patient completed the planned eight cycles of therapy without further problems, achieving a very good partial remission. Skin rashes typically consistent with hypersensitivity reactions are reported in 20% of the patients under treatment with bortezomib. Recently, more skin rashes have been reported as cutaneous reactions with peculiar clinical and histological features. Three cases were described as Sweet’s syndromes [1, 2], characterized by acute onset of fever and painful erythematous papulo-nodular eruption associated with the histologic evidence of a dermal neutrophilic infiltrate. In the other cases, the rash was not accompanied by constitutional symptoms, and the histologic examination showed the presence of perivascular lymphocytic infiltrates associated sometimes with small vessel vasculitis [3, 4]. Regardless of the histologic picture, these rashes usually occur early within the first 2–3 cycles of therapy. Most commonly, the lesions disappear after the discontinuation of bortezomib but recur after rechallenge. The adoption of systemic corticosteroids is very effective for the cure of the rash and for the prevention of recurrences. Only in the case described by Knoops et al. [1], the rash recurred despite Ann Hematol (2007) 86:301–302 DOI 10.1007/s00277-006-0227-9