Progressive Lipo-Lymphedema Associated with Increased Activity of Dermal Fibroblasts in Monoclonal Gammopathy of Undetermined Significance: Is There a Causal Relationship?
Thielitz A, Bellutti M, Bonnekoh B, Franke I, Wiede A, Lotzing M, Reinhold D, Gollnick H; 2012
Synopsis: This study investigates whether a monoclonal gammopathy of unknown significance (MGUS) could be a causal factor in progressive lymphedema.
Abstract: The pathophysiology of skin diseases associated with monoclonal gammopathies is generally unknown. Our aim was to investigate whether a monoclonal gammopathy could be a causal factor in progressive lymphedema. We describe a 75 year old patient with a rapidly progressive lipo-lymphedema and a monoclonal gammopathy of unknown significance (MGUS) suspected as a key etiological factor. Dermal fibroblasts were cultured from lesional lower leg skin and non-lesional abdominal skin and compared to healthy control fibroblasts. We found 10-fold elevated basic fibroblast growth factor 2 (FGF-2) in the patient’s serum and significantly increased basal FGF-2 production of lesional and non-lesional fibroblasts compared to healthy controls. Upon restimulation with patient or healthy control serum, lesional fibroblasts showed significantly increased proliferation rates and FGF-2 production in vitro. Non-lesional abdominal fibroblasts showed an intermediate phenotype between lesional and control fibroblasts. Our findings provide the first evidence that lesional dermal fibroblasts from lipo-lymphedema with plasma cell infiltration show increased proliferation and FGF-2 production and that both local tissue factors and altered FGF-2 serum levels associated with monoclonal gammopathies might contribute to this phenotype. Thus we propose a possible pathophysiologic link between the gammopathy-associated factors and the generation of lymphedema with initial fibrogenesis aggravating pre-existing lipedema.
APA Citation: Thielitz, A., Bellutti, M., Bonnekoh, B., Franke, I., Wiede, A., Lotzing, M., … & Gollnick, H. (2012). Progressive lipo-lymphedema associated with increased activity of dermal fibroblasts in monoclonal gammopathy of undetermined significance: is there a causal relationship?. Lymphology, 45(3), 124-129.
AMA Citation: Thielitz A, Bellutti M, Bonnekoh B, et al. Progressive lipo-lymphedema associated with increased activity of dermal fibroblasts in monoclonal gammopathy of undetermined significance: is there a causal relationship?. Lymphology. 2012;45(3):124-129.