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Sweet‐like syndrome induced by bortezomib

An 80-year-old man suffering from multiple myeloma emerging from a monoclonal gammopathy of unclear significance was treated with a combination therapy of bortezomib (days 1, 4, 8, 11, 22, 25, 29, 32) and melphalan (day 1). Additionally, prednisolone was given on days 1–4. On day 30 (after receiving bortezomib for the seventh time), he developed asymptomatic red-livid targetoid and infiltrated plaques on cheeks, upper back and the neck (Figure 1). His mucous membranes were normal and he manifested no signs of infection. The differential blood count revealed an anemia with hemoglobin of 10.9 g/dl, a leucopenia (4 800 leucocytes per μl) with normal neutrophils (60.1 %) and reduced number of lymphocytes (16.2 %). Skin biopsies taken from the neck showed a perivascular accentuated infiltrate of monomorphic cells without atypia and few neutrophils (Figure 2). The majority of the cells were positive for lysozyme, CD68 and myeloperoxidase. CD163, a marker of macrophage activity, was only weakly expressed. Taking account of the medical history, skin findings and histology we diagnosed a Sweet-like syndrome induced by bortezomib. Topical corticosteroids produced marked improvement after several weeks. Subsequent chemotherapy cycles were covered with systemic prednisolone without recurrence of skin lesions. Blood analyses after three Clinical Letter cycles of chemotherapy showed a successful response of the multiple myeloma. Bortezomib is a proteasome inhibitor, which was approved in 2008 to treat progressive multiple myeloma in combination with melphalan and prednisolone. Potential adverse effects include hematological complications (such as thrombocytopenia, neutropenia and anemia), and peripheral neuropathy (especially when administered intravenously) [1]. Moreover, bortezomib can cause cutaneous side effects such as erythema, pruritus, periorbital edema, eczemas and rarely erythema multiforme-like skin changes or vasculitis [2, 3], which appear within a few days or weeks after the therapy is initiated and increase during further chemotherapy cycles [4, 5]. Sweet-like skin lesions induced by bortezomib are very rare and except for this case report only 8 cases have been published in literature since 2005 (Table 1). The occurrence of the first skin lesions varied between a few days to several weeks after bortezomib was given for the first time. Males were affected more frequently than females. The erythematous and edematous monomorphic papules and plaques presented acutely on mainly neck and upper back and sometimes were reported to be painful. The clinical picture alone does not allow a differentiation from the classic Sweet syndrome in which paraneoplastic occurrence (for example with hematological disorders like multiple myeloma) is not uncommon. In contrast to the classic Sweet syndrome, however, the bortezomib-induced Sweet-like syndrome lacks fever and neutrophilia [4, 5]. To clarify drug-induced cutaneous side effects in patients with multiple myeloma, a cutaneous infiltration by the hematological disease itself must be excluded. Apart from the clinical picture the histological features also differ from