LAUSR

Dear Editor, An 81-year-old patient was diagnosed with multiple myeloma (MM) characterized by 30.5% of clonal plasma cells within the bone marrow, an IgG kappa monoclonal protein (M-protein) of 50.7 g/l, bone lesions of the cervical spine, anaemia (Hb: 81 g/l) without hypercalcaemia or renal failure. His medical history included arterial hypertension, dyslipidaemia, benign prostatic hyperplasia and right cardiac insufficiency. Lenalidomide (25 mg orally daily 21/28 days) and systemic steroid therapy (dexamethasone, 20 mg orally weekly) were introduced with good response after 1 month. Unfortunately, after 1.5 months of treatment, the patient was hospitalized for febrile agranulocytosis due to pneumonia and hematologic toxicity of lenalidomide. Clinical examination found the presence of inflammatory skin ulcerations in knees, right tibia and both hands (Fig. 1a). These skin lesions had been evolving over 1 month and were not present at the time of diagnosis of MM. Based on the morphology of the knee lesions, the presumptive clinical diagnosis of pyoderma gangrenosumwasmade and confirmed by a skin biopsy (presence of epidermal/dermal necrosis, neutrophilic infiltrates, micro-abscesses and leukocytoclasia (Fig. 1b). Serum antineutrophil cytoplasmic antibodies were negative, and Doppler sonography was normal. Lenalidomide was stopped due the haematologic toxicity. Usage of G-CSF together with antibiotic therapy (piperacillin/tazobactam) led to favourable clinical outcome in 15 days. Skin ulcerations were managed locally with occlusive dressings and during this period became less inflammatory with healing process. Two weeks after lenalidomide discontinuation, the patient was rechallenged with the same drug followed by recurrence of new skin ulcerations (Fig. 1c). Then, lenalidomide was definitely stopped, and pomalidomide was introduced. Three weeks later, the ulcers had completely healed (Fig. 1d). Lenalidomide belongs to the class of immunomodulators (IMiDS). Its mechanism of action is complex and not yet truly understood. It can modulate cytokine production by increasing the production of anti-inflammatory cytokines and inhibiting the production of pro-inflammatory cytokines [1]. Pyoderma gangrenosum is a rare inflammatory skin condition, and diagnostic criteria have been recently reappraised [2]. PG has been observed in many patients with plasma cell dyscrasia and, for most cases, either preceded or was diagnosed concurrently with these. Its occurrence has described with several pharmaceutical agents [3], but the physiopathological mechanisms remain hypothetical. Nevertheless, a mechanism involving a cytokine disorder is often reported. Some authors have described IMiDS as useful for treatment of PG [4]; nevertheless, in this case, lenalidomidewas clearly responsible for the PG. The inflammatory recurrence and the appearance of new skin lesions at the resumption of lenalidomide and the beginning of healing when stopping lenalidomide are very in favour of the involvement of the lenalidomide which has already been associated with immune-mediated or autoimmune disease [5]. Interestingly, pomalidomide which belongs to the same pharmaceutical class did not induce PG and was introduced for preserving a very effective therapeutic class in multiple myeloma. In conclusion, this is the first report of a histologically proven case of pyoderma gangrenosum induced by lenalidomide, and in our experience, switching to another IMiDS like pomalidomide is possible. * Mathieu Meunier [email protected]