Panniculitis in a patient with chronic myelogenous leukaemia treated with imatinib
Authors: S. Ugurel, T. Lahaye, R. Hildenbrand, E. Glorer, A. Reiter, A. Hochhaus, D. Schadendorf, S. Goerdt
Journal: British Journal of Dermatology (2003)

Sir, The tyrosine kinase inhibitor imatinib (Glivec, formerly STI571; Novartis, Basel, Switzerland) selectively impairs the function of the platelet‐derived growth factor receptor and c‐kit (CD117). Moreover, imatinib inhibits the BCR‐ABL fusion protein1 resulting from the Philadelphia (Ph) translocation t(9;22)(q34;q11) that plays a crucial role in the pathogenesis of chronic myelogenous leukaemia (CML). Imatinib has been shown in various clinical trials in CML and gastrointestinal stromal tumours to be a well‐tolerated oral drug with frequent but mild toxicities.2 We report a 64‐year‐old woman diagnosed as having chronic phase Ph+ CML in October 1995. After haematological failure of interferon alfa‐based therapy oral imatinib 400 mg daily was commenced in August 2001. Complete haematological response was achieved after 2 months of therapy. In January 2002, self‐limiting erythematous skin lesions were first observed on the lower legs. During the following months, similar lesions recurred, some of which persisted, in different locations and with variable intensity on both legs and arms. In September 2002, painful erythematous skin lesions appeared on both arms, accompanied by fever. Under the suspicion of streptococcal cellulitis a variety of antibiotic therapies was administered. In November 2002 the clinical situation had deteriorated, with erythematous, swollen, deeply indurated and very painful skin lesions on the right forearm and the upper and lower left leg (Fig. 1A,B). Further symptoms were a fever of 38·5 °C, night sweats, malaise and fatigue. No associated lymphadenopathy or hepatomegaly were detected. The spleen was slightly enlarged (14 × 6 cm). Laboratory tests showed a C‐reactive protein level of 141 mg L−1 and a hypochromic, normocytic anaemia with a haemoglobin level of 7·6 g dL−1 requiring transfusion. CML was in the accelerated phase (white blood cell count 9·3 × 109 L−1; 12% bands, 81% polymorphonuclear cells, 2% lymphocytes, 3% monocytes and 2% basophils; platelets 741 × 109 L−1). Bone marrow aspiration cytology revealed a hypercellularity of myelo‐ and megakaryopoiesis with 2% blasts; cytogenetic evaluation showed 100% Ph+ metaphases without clonal evolution. Biopsy of lesional skin of the lower left leg showed a mild, nonspecific mononuclear perivascular infiltrate throughout the dermis. In the subcutaneous tissue, however, numerous macrophages, neutrophils and lymphocytes were present between the adipocytes throughout the fatty tissue lobules and in close vicinity to small blood vessels, but not in a septal configuration (Fig. 2). Focal necrotic adipocytes were detected. Based on these histological findings the patient was diagnosed as having panniculitis. After exclusion of a pancreatic disorder, an α1‐antitrypsin deficiency, preceding trauma or infection or a subcutaneous infiltrate from the CML, the panniculitis was considered most probably to be an adverse reaction to imatinib. Imatinib treatment was stopped and the patient received corticosteroids (methylprednisolone, initially 120 mg daily), leading to a rapid improvement of all skin lesions. Hydroxyurea was commenced as an alternative symptomatic treatment for CML but was not able to induce haematological remission. Imatinib therapy in combination with glucocorticosteroids was reintroduced. Mild cutaneous lesions reappeared, without general symptoms.