The University of Arizona

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 diseasesassociated with monoclonal gammopathies isgenerally unknown. Our aim was to investigatewhether a monoclonal gammopathy couldbe a causal factor in progressive lymphedema.We describe a 75 year old patient with arapidly progressive lipo-lymphedema and amonoclonal gammopathy of unknown significance(MGUS) suspected as a key etiologicalfactor. Dermal fibroblasts were cultured fromlesional lower leg skin and non-lesionalabdominal skin and compared to healthycontrol fibroblasts. We found 10-fold elevatedbasic fibroblast growth factor 2 (FGF-2) in thepatient’s serum and significantly increasedbasal FGF-2 production of lesional and nonlesionalfibroblasts compared to healthycontrols. Upon restimulation with patient orhealthy control serum, lesional fibroblastsshowed significantly increased proliferationrates and FGF-2 production in vitro. Nonlesionalabdominal fibroblasts showed anintermediate phenotype between lesional andcontrol fibroblasts. Our findings provide thefirst evidence that lesional dermal fibroblastsfrom lipo-lymphedema with plasma cellinfiltration show increased proliferation andFGF-2 production and that both local tissue factors and altered FGF-2 serum levelsassociated with monoclonal gammopathiesmight contribute to this phenotype. Thus wepropose a possible pathophysiologic linkbetween the gammopathy-associated factorsand the generation of lymphedema with initialfibrogenesis aggravating pre-existing lipedema.

Full Text:

PDF