PROGRESSIVE LIPO-LYMPHEDEMA ASSOCIATED WITH INCREASED ACTIVITY OF DERMAL FIBROBLASTS IN MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE: IS THERE A CAUSAL RELATIONSHIP?
- A Thielitz
- M Bellutti
- B Bonnekoh
- I Franke
- A Wiede
- M Lotzing
- D Reinhold
- H Gollnick
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 nonlesional 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. Nonlesional 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.
Keywords: fibroblast activity, lipo-lymphedema, monoclonal gammopathy, FGF-2, dermal fibrosis, immunoglobulins
How to Cite:
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.
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