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Progressive lipo-lymphedema associated with increased activity of dermal fibroblasts in monoclonal gammopathy of undetermined significance: is there a causal relationship?

Resource type
Authors/contributors
Title
Progressive lipo-lymphedema associated with increased activity of dermal fibroblasts in monoclonal gammopathy of undetermined significance: is there a causal relationship?
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.
Publication
Lymphology
Volume
45
Issue
3
Pages
124-129
Date
2012 Sep
Journal Abbr
Lymphology
Language
eng
ISSN
0024-7766 0024-7766
Archive
The University of Arizona Libraries
Extra
Place: United States
Citation
Thielitz, A., Bellutti, M., Bonnekoh, B., Franke, I., Wiede, A., Lotzing, M., Reinhold, D., & 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. The University of Arizona Libraries.