Progressive lipo-lymphedema associated with increased activity of dermal fibroblasts in monoclonal gammopathy of undetermined significance: is there a causal relationship?
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.
Clinic of Dermatology and Venereology, Otto-von-Guericke-University, Magdeburg, Germany. anja.thielitz@med.ovgu.de
A
A
Thielitz
M
M
Bellutti
B
B
Bonnekoh
I
I
Franke
A
A
Wiede
M
M
Lotzing
D
D
Reinhold
H
H
Gollnick
D000368:Aged; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000097:blood; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008209:Lymphedema / Q000209:etiology*; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000150:complications*; D012867:Skin / Q000166:cytology / Q000378:metabolism
D016222:Fibroblast Growth Factor 2