BACKGROUND Lipedema is a chronic, progressive disorder of subcutaneous adipose tissue that usually affects the lower extremities of women. Also known as “two-body syndrome,” the fat accumulations in lipedema are unsightly and painful. The disorder is well-known in Europe but is largely unrecognized and underdiagnosed in the United States. OBJECTIVE To hold the First International Consensus Conference on Lipedema with the purpose of reviewing current European guidelines and the literature regarding the long-term benefits that have been reported to occur after lymph-sparing liposuction for lipedema using tumescent local anesthesia. METHODS International experts on liposuction for lipedema were convened as part of the First International Congress on Lipedema in Vienna, Austria, June 9 to 10, 2017. RESULTS Multiple studies from Germany have reported long-term benefits for as long as 8 years after liposuction for lipedema using tumescent local anesthesia. CONCLUSION Lymph-sparing liposuction using tumescent local anesthesia is currently the only effective treatment for lipedema.

Lipedema is a chronic, progressive disease of adipose tissue with lack of consistent diagnostic criteria. The aim of this study was a thorough comparative characterization of extracellular microRNAs (miRNAs) from the stromal vascular fraction (SVF) of healthy and lipedema adipose tissue. For this, we analyzed 187 extracellular miRNAs in concentrated conditioned medium (cCM) and specifically in small extracellular vesicles (sEVs) enriched thereof by size exclusion chromatography. No significant difference in median particle size and concentration was observed between sEV fractions in healthy and lipedema. We found the majority of miRNAs located predominantly in cCM compared to sEV enriched fraction. Surprisingly, hierarchical clustering of the most variant miRNAs showed that only sEVmiRNA profiles-but not cCMmiRNAs-were impacted by lipedema. Seven sEVmiRNAs (miR-16-5p, miR-29a-3p, miR-24-3p, miR-454-p, miR-144-5p, miR-130a-3p, let-7c-5p) were differently regulated in lipedema and healthy individuals, whereas only one cCMmiRNA (miR-188-5p) was significantly downregulated in lipedema. Comparing SVF from healthy and lipedema patients, we identified sEVs as the lipedema relevant miRNA fraction. This study contributes to identify the potential role of SVF secreted miRNAs in lipedema. Lipedema is a chronic, progressive disease characterized by bilateral, symmetrical, disproportional deposition of adipose tissue in the extremities and buttocks 1. Patients suffer from pain, reduced joint mobility, hematoma, edema and psychological impacts 2. It was first described in 1940 as a connective tissue disorder, characterized by fluid being collected in the interstitium instead of entering into lymphatics 3. This excess fluid in the interstitium potentially leads to growth of adipose tissue and hypoxia, which in turn might enhance angiogenesis of pathologic vessels 4,5. The area of lymphatic vessels and the number of blood vessels were found increased in non-obese lipedema patients compared to controls 6. Examination of adipose tissue from lipedema patients demonstrated hypertrophic adipocytes, crown-like structures and increased number of macrophages 6-8. Besides functioning as an energy storage, white adipose tissue (WAT) responds differentially to physiological and pathological metabolic changes by secreting a large diversity of proteins, hormones, lipids, non-coding ribonucleic acids (RNAs)-including microRNAs (miRNAs)-and extracellular vesicles (EVs) 9,10. Small EVs (sEVs) are a fraction of 70-150 nm sized, membrane-enclosed particles, which contain cell-type specific proteins, enzymes, growth factors, cytokines, lipids, as well as coding and non-coding RNAs. It has been repeatedly reported, that WAT-derived vesicular miRNAs are involved in metabolic regulations 11,12 and adipose tissue is considered a significant source of circulating sEV-miRNAs 11. By acting in an autocrine, paracrine as well as systemic manner, these factors can contribute to metabolic abnormalities, modulation of osteogenic differentiation, inhibition of...

Lipedema is a chronic, progressive disease of adipose tissue with unknown etiology. Based on the relevance of the stromal vascular fraction (SVF) cell population in lipedema, we performed a thorough characterization of subcutaneous adipose tissue, SVF isolated thereof and the sorted populations of endothelial cells (EC), pericytes and cultured adipose-derived stromal/stem cells (ASC) of early-stage lipedema patients. We employed histological and gene expression analysis and investigated the endothelial barrier by immunofluorescence and analysis of endothelial permeability in vitro. Although there were no significant differences in histological stainings, we found altered gene expression of factors relevant for local estrogen metabolism (aromatase), preadipocyte commitment (ZNF423) and immune cell infiltration (CD11c) in lipedema on the tissue level, as well as in distinct cellular subpopulations. Machine learning analysis of immunofluorescence images of CD31 and ZO-1 revealed a morphological difference in the cellular junctions of EC cultures derived from healthy and lipedema individuals. Furthermore, the secretome of lipedema-derived SVF cells was sufficient to significantly increase leakiness of healthy human primary EC, which was also reflected by decreased mRNA expression of VE-cadherin. Here, we showed for the first time that the secretome of SVF cells creates an environment that triggers endothelial barrier dysfunction in early-stage lipedema. Moreover, since alterations in gene expression were detected on the cellular and/or tissue level, the choice of sample material is of high importance in elucidating this complex disease.

Therapeutic options of anogenital warts (AGW) at the urethral meatus are limited and often require effortful and time-consuming procedures under general anesthesia. Here, we present two cases of AGW at the urethral meatus, which we have successfully treated with low-dose topical ingenol mebutate gel.

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