Study Of Pathology, Diagnosis And Treatment Of Skin Fibrosis In Secondary Lymphedema

[Objective] Skin fibrosis is a clinically serious and irreversible pathological process of secondary lymphedema,and is also a challeng on the diagnosis and treatment.This study explored the pathological change,using of SkinFibroMeter device,imagings of indocyanine green lymphography and treatment effects of complete decongestive therapy,aimed to elaborate these new pathological characteristics of skin fibrosis and technologies of diagnosis and treatment on secondary lymphedema.[Material and Methods] From 2014 November to 2016 February,45 women with secondary unilateral lower limb lymphedema(they were allocated to three groups,namely an LE?,LE?,and LE? group,according to the three-stage scale for classification of lymphedematous limbs)and 15 healthy women volunteers(they were assigned to control group)were enrolled in this study.Full-thickness skin biopsies of lymphedematous limbs from seven patients and control samples from seven healthy controls were harvested.In order to observing the expressions of collagen?chymase and transforming growth factor-?1,the skin samples were assayed by Masson,immunehistochemical,and immunofluorescence staining and were analyzed by westernblot and enzyme-linked immunosorbent assay.The skin stiffness values of affected limbs of 45 patients and 15 healthy limbs of volunteers were measured by using the SkinFibroMeter to diagnose and evaluate fibrotic changes in the skin of patients with stage?-? secondary lymphedema of the lower limb.Then,the indocyanine green lymphographys were provided to these patients and healthy volunreers to analyze the imaging characteristic of lymphedematous and healthy lower limbs.After that,the treatment effects were assessed in these patients using complex decongestive therapy.[Results] Expression of collagen in the skin of lymphedematous lower limb increased in parallel with disease stage from lymphedema stage?to stage ?.It meaned that the affected lower limbs have already suffered skin fibrosis in lymphedema stage?.Increased chymase,transforming growth factor-?1 expression in the lymphedematous skin,and the increased expression of transforming growth factor-?1 on lymphaticvessels,endothelial cells,and interstitial tissues coincided with chymase expression.Using SkinFibroMeter to assess,increasing skin stiffness with increasing severity of secondary lymphedema of the lower limb and these values correlated positively with stage of secondary lymphedema.The indocyanine green lymphography showed different imaging characteristics including dilation of lymphatic vessels?lymph stasis?dermal backflow and abnormal lymph nodes in affected lower limb.Using complex decongestive therapy effectively improved lymph stasis and promote backflow to decreased circumference,interstitial fluid content and chymase concertration of lymphedematous low limb.[Conclusions] Our results demonstrate that the skin fibrosis has been produced in the stage?of secondary lymphedema lower limb,and with the development,the fibrotic degree has became more serious.During this progress,chymase and transforming growth factor-?1expression is significantly increased in the fibrotic skin.We speculate that increased expression of chymase may facilitate the release of latency-associated peptide transforming growth factor-?1 to generate activated transforming growth factor-?1,and the upregulation of active transforming growth factor-?1 can promote fibrosis in the lymphedematous skin.In clinical study,we have showed that the new device--SkinFibroMeter is very sensitive and accurate for detecting skin fibrosis of edematous limb,and the increased skin stiffness can indicate the more severe skin fibrosis.The indocyanine green lymphography can provide the intuitive and instantaneous imaging of lymphatic vessels and nodes,which help us to diagnose and assess the secondary lymphedema.The complex decongestive therapy is an effective treatment method for patients with secondary lower limb lymphedema to improve the swelling and fibrosis of affected limbs.Therefore,this pathological finding may provide a novel means on skin fibrosis and these technologys of diagnosis and treatment have the promising prospect for patients with secondary lower limb lymphedema.