Articles
Authors: A Thielitz ( ) , M Bellutti ( ) , B Bonnekoh ( ) , I Franke ( ) , A Wiede ( ) , M Lotzing ( ) , D Reinhold ( ) , H Gollnick ( )
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).