Sweet’s syndrome in a granulocytopenic patient with acute myeloid leukemia on FLT3 inhibitor

Abstract

Introduction: Gilteritinib is a FLT3 kinase inhibitor approved for FLT3-mutated acute myeloid leukemia (AML). We present a case of febrile neutropenia and neutrophilic dermatosis consistent with Sweet's syndrome (SS). Case history: A 55-year-old woman presented with fever and skin lesions after 4 weeks of initiation of Gilteritinib for AML. She was febrile, pancytopenic and neutropenic with absolute neutrophil count (ANC) of 0.1x10E3/UI. Examination revealed reddish and violaceous rashes on her extremities. Pathology showed superficial dermal edema, widespread epidermal spongiosis and multiple neutrophils in the dermal infiltrate. Rash improved with prednisone 60 mg daily and started to flare with taper. She was still on Gilteritinib all this time. Gilteritinib was finally stopped due to non-response and possible contribution in flaring her SS. Shortly after, the patient succumbed to progressive disease and complications of sepsis. Discussion: There have been reports of SS in neutropenic patients although SS is typically a neutrophilic dermatosis. The pathogenesis of SS in neutropenia remains uncertain. Our study represents an additional medication-associated cutaneous complication of AML therapy. Clinicians need to be aware of potential neutrophilic dermatoses with FLT-3 inhibition, even with peripheral neutropenia.

Bullous Sweet syndrome in a patient with acute myeloid leukemia treated with midostaurin: Rapid response to acitretin and colchicine—A case report

“…FLT3 inhibitorinduced neutrophilic dermatoses have also been reported. [2][3][4] This confirmed the diagnosis of bullous Sweet syndrome, caused by midostaurin treatment. 5 In FLT3 inhibitor-induced neutrophilic dermatosis it has been hypothesized that terminal myeloid differentiation promotes AML blast to become mature neutrophils.…”

From the Deep: Overlap of Neutrophilic Dermatoses Disorders Associated With Acute Myeloid Leukemia

“…Concerning myeloid neoplasm-associated NDs, there's mounting evidence that skin-infiltrating neutrophils may be clonally related to the neoplastic cells and may have differentiated from them [11], with some authors even suggesting that leukaemia cutis and Sweet syndrome (SS) associated with AML may be included in the same disease spectrum. Moreover, NDs, especially SS but also PG and neutrophilic eccrine hidradenitis, may be induced by drugs used to treat AML, in particular FLT3 inhibitors such as gilteritinib [2][3][4][5].…”

“…The dermal neutrophilic infiltrate favoured that diagnosis. FLT-3 inhibitors, such as gilterinib, which was reinitiated by the patient two weeks prior to this admission, have been associated with NDs [ 2 - 5 ]. We can hypothesise the contribution of this drug to the whole clinical picture, supporting the diagnosis of ND 2-4.…”

Considering Sex and Gender in Therapeutics throughout the Product Life Cycle: A Narrative Review and Case Study of Gilteritinib

“…11 Another case report described Sweet syndrome in a 55-year-old female who presented with neutrophilic dermatosis after 4 weeks of gilteritinib therapy for AML. 12 The patient was started on prednisone but experienced flare with tapering. The gilteritinib was eventually stopped because of nonresponse and the drug's potential contribution to the Sweet syndrome flare.…”

“…The patient died shortly afterward, secondary to disease progression and complications of sepsis. 12 The third included study aimed to investigate the clinical benefit of gilteritinib in the treatment of relapsed or refractory FLT3mutated AML in a randomized trial comparing gilteritinib with conventional salvage chemotherapy regimens, also known as the ADMIRAL trial. 13 In the ADMIRAL trial, females accounted for 53% of participants in the gilteritinib arm and 56.5% in the salvage chemotherapy arm.…”