The Possible Role of G-CSF in the Pathogenesis of Sweet's Syndrome

Abstract

Sweet's syndrome (SS) is characterized by the clinical features of fever, leucocytosis, neutrophilia and the sudden onset of asymmetric, often very painful skin lesions and dense dermal infiltrates of mature neutrophils without signs of vasculitis. Apart from idiopathic cases the disease is frequently associated with hematological malignancies, but it may also be observed in patients with solid tumors, mainly tumors of the genito-urinary tract. In the past, numerous theories have been proposed to explain the pathogenesis of this rare disease. SS has been interpreted as a direct response to mechanical and chemical irritants, an infectious disease or a disorder of neutrophilic chemotaxis and/or phagocytosis, but most often it has been described as a hypersensitivity reaction. Each of these theories can account for particular symptoms, but none of them reconciles the dominating clinical and laboratory features of the disease. Furthermore recently published casuistic observations suggest the involvement of certain cytokines in particular G-CSF and Il-6 in the pathogenesis of the disease, which might explain many of the observed clinical and laboratory findings. The following article summarizes these data and gives a review of the current literature.

Inducible deletion of the Blimp-1 gene in adult epidermis causes granulocyte-dominated chronic skin inflammation in mice

“…Inducible expression of PKC family members, such as PKCe or PKCα, in the epidermis leads to the development of systemic neutrophilia and increased levels of chemoattractants for neutrophils and macrophages, including CXCL-1 and G-CSF (18,19), and this situation most resembles the innate immune responses of CKO mice in the present study. Interestingly, CKO mice showed some similar features of an orphan disease known as Sweet syndrome, which involves neutrophilic dermatosis and systemic neutrophilia and is associated with elevated serum G-CSF and IL-6 levels (20)(21)(22). Moreover, some patients with Sweet syndrome also have an inflammatory bowel disease, such as Crohn disease or ulcerative colitis (22).…”

Pyoderma Gangrenosum Following Cytosine Arabinoside, Aclarubicin and Granulocyte Colony-Stimulating Factor Combination Therapy in Myelodysplastic Syndrome.

“…Endogenous G-CSFlevels are increased in MDSpatients associated with Sweet's syndrome (2). The development of Sweet's syndrome or PGhas recently been reported following G-CSF therapy in patients with hematologic malignancies (2, 12, 13).…”

“…Skin lesions, such as Sweet' s syndrome (acute febrile neutrophilic dermatosis), have recently been associated with G-CSF therapy in MDSpatients (2). Pyoderma gangrenosum (PG), a neutrophilic dermatosis with pathological features similar to Sweet' s syndrome, may be associated with systemic diseases (3).…”

Reaktive neutrophile Dermatosen

“…Die Pathogenese beider Erkrankungen ist noch unklar. Doch gibt es Hinweise, dass die immunologische Reaktivität oder Pathergie durch Zytokine wie IL-1, IL-3, IL-6, IL-8, G-CSF und TNFα beeinflusst werden [3,4]. Die häufige Assoziation mit entzündlichen Systemerkrankungen und das gute Ansprechen auf antientzündliche oder immunmodulierende Therapien sind weitere indirekte pathogenetische Hinweise.…”