OBJECTIVES:Indocyanine green lymphography (ICGL) has emerged as a potentially powerful tool for the study of the superficial lymphatic system and to support the diagnosis of lymphoedema. However, detailed descriptions of ICGL findings in healthy individuals are limited. In this study, we imaged a series of healthy participants using ICGL, attempting to establish quantitative and qualitative ICGL parameters of the lower limb. METHODS:Sixteen healthy individuals aged 20-55 years were recruited to undergo lower limb ICGL after 0.1 mL injections of 1 g/L ICG were administered intradermally to 5 locations around the foot. Outcome measures included: (1) the drainage routes of contractile lymphatic collectors observed, (2) the number of lymphatic vessels crossing the anterior ankle, and (3) the pumping frequency of lymphatic vessels. Abnormal features, such as highly tortuous or vessels with retrograde lymph flow, were noted. RESULTS:Propulsion of ICG containing lymph could be seen in all individuals, with drainage via the anteromedial and anterolateral drainage pathways predominating (observed in 31/32 and 25/32 limbs, respectively). The number of lymphatic vessels crossing the anterior ankle was 3.4 ± 1.1 with an average rate of 1 propulsion every 66 seconds in the vessels investigated. Isolated cases of highly tortuous and refluxing vessels were observed. CONCLUSIONS:Although limited by absorption and scatter of infrared light, ICGL facilitated the characterization of normal lower limb lymphatic vessels through a rigorous set of objective measures. This in turn will allow better identification of pathological changes. ADVANCES IN KNOWLEDGE:Establishment of normal lower limb lymphatic anatomy and function.

Lipedema is a chronic adipose tissue condition that primarily affects women. Despite increasing recognition of lipedema, the condition remains poorly understood and lacks standardized diagnostic criteria or confirmatory tests. Variability in definitions and measurement across clinical and research settings impedes comparability across studies, constraining the evidence base needed to support future advances in clinical practice and patient care. To address challenges associated with inconsistent definitions and data collection, the Lipedema Foundation (LF) partnered with clinicians, researchers, and biostatisticians to develop a Lipedema Common Case Report Form (CCRF). The CCRF was designed to be a research data harmonization tool and is not intended to define diagnostic standards or guide clinical treatment decisions. Its development involved review of published lipedema clinical guidelines and collaborative work to define data elements and attributes for inclusion. When they existed, validated or standardized measures were incorporated directly. When no suitable standardized measures were available, an iterative and collaborative process was used to develop lipedema-specific Common Data Elements (CDEs). The initial version of the CCRF was piloted in participants with and without lipedema, and updates based on participant and clinician feedback were incorporated into the CCRF. A biostatistical review evaluated data completeness, quality, and structure, leading to additional refinements. The final Version 1 instrument consists of 682 CDEs organized into four classifications: (1) Core, (2) Supplemental Highly Recommended, (3) Supplemental, and (4) Exploratory. The current version is prepared for dissemination in the field. By disseminating the CCRF broadly and encouraging adoption in all lipedema research beginning in 2026, including all newly initiated LF-funded projects, LF intends to evaluate its use with grantees and iterate systematically to achieve consistent and comparable data collection. The CCRF provides a structured framework for harmonized data collection that may facilitate comparability across studies and support future development of standardized diagnostic and research methodologies.

Pathogenic variants in kinesin KIF11 underlie microcephaly-lymphedema-chorioretinopathy (MLC) syndrome. Although well known for regulating spindle dynamics ensuring successful cell division, the association of KIF11(encoding EG5) with development of the lymphatic system and how KIF11 pathogenic variants lead to lymphatic dysfunction and lymphedema remain unknown. Using patient-derived lymphoblastoid cells, we demonstrated that patients with MLC carrying pathogenic stop-gain variants in KIF11 have reduced mRNA and protein levels. Lymphoscintigraphy showed reduced tracer absorption, and intestinal lymphangiectasia was detected in one patient, pointing to impairment of lymphatic function caused by KIF11 haploinsufficiency. We revealed that KIF11 is expressed in early human and mouse development with the lymphatic markers VEGFR3, podoplanin, and PROX1. In zebrafish, single-cell RNA-Seq identified kif11 specifically expressed in endothelial precursors. In human lymphatic endothelial cells, EG5 inhibition with ispinesib reduced VEGFC-driven AKT phosphorylation, migration, and spheroid sprouting. KIF11 knockdown reduced PROX1 and VEGFR3 expression, providing for the first time to our knowledge a link between KIF11 and drivers of lymphangiogenesis and lymphatic identity.

Background: Germline heterozygous variants in the ETS transcription factor, ERG , cause “ERG deficiency syndrome”, characterised by bone marrow failure (BMF), haematological malignancy and primary lymphoedema predisposition. Given the recent discovery of ERG deficiency syndrome and the limited number of reported cases, the full phenotypic spectrum of the disorder remains to be defined. Methods: Through international collaborations, we ascertained germline ERG variants in individuals with aortic/mitral valve abnormalities and/or aortic aneurysm. We conducted explorative genotype/phenotype analysis of population and disease databases, including in-depth analysis of the UK Biobank, to identify additional variants. To assess both variant-level evidence demonstrating a damaging effect on gene function (DNA binding, transactivation) and experimental evidence supporting the role of the gene in related phenotypic features, we performed functional assays and characterised ERG expression during a critical timepoint of murine aortic valve development. Results: We report 10 heterozygous ERG variants (7 likely pathogenic/pathogenic) in 11 patients (including one family) with aortic/mitral valve abnormalities and aortic aneurysm (6 co-segregate with a BMF or lymphoedema), before 50 years of age, broadening the phenotypic landscape of ERG deficiency syndrome. Providing a possible molecular explanation for aortic valve defects, ERG is present at high levels in aortic valves at a critical point of murine aortic valve development. Explorative genotype/phenotype analysis of population and disease databases identified 3 ERG variants, demonstrating that rare pathogenic variants are hidden within such cohorts. Seven variants are predicted to cause premature protein termination and all three missense variants disrupted transactivation and/or DNA-binding in vitro . Further in-depth analysis of the UK Biobank identified two predicted pathogenic ERG missense variants in ostensibly asymptomatic individuals obscured by somatic genetic rescue, a competitive, ERG-deficiency-driven stem cell phenomenon. Conclusion: ERG deficiency syndrome encompasses a broader clinical phenotype than previously recognised, including cardiovascular manifestations; aortic and mitral valve abnormalities and aortic aneurysms. Identification of patients with hidden germline ERG variants and the expansion of clinical features of ERG deficiency will improve genetic diagnosis and direct clinical management to individuals and families.

Lymphatic valves are essential for maintaining tissue fluid homeostasis, and their dysfunction leads to lymphedema, a morbid and disfiguring disease without a cure. Mechanical forces due to lymph flow are required for proper lymphatic valve development, yet it remains unclear how lymphatic endothelial cells (LECs) sense and decode mechanical signals. In this study, we identify the cell guidance semaphorin receptor plexin D1 (PLXND1) as a lymphatic mechanosensor required for lymphatic valve morphogenesis. Conditional genetic ablation of Plxnd1 in LECs caused major defects in lymphatic valve development in 2 different lymphatic vascular beds. Mechanistically, PLXND1 acted as a mechanosensor within a lymphatic mechanocomplex, initiating distinct mechanical signals and activating the lymphatic valve transcriptional program through an unconventional pathway. Screening of patients with primary lymphedema identified PLXND1 missense variants, and functional analysis established 2 pathogenic variants that selectively disrupt the ligand versus mechanosensing functions of this receptor. Variants associated with lymphedema in members of the mechanocomplex disrupted its formation, underscoring the central role of this complex in lymphatic valve biology. Our work uncovers a mechanosensing mechanism guiding lymphatic valve development, and has profound implications for the understanding and treatment of primary lymphedema in humans.

Background Lymphoedema distichiasis syndrome (LDS) is an autosomal dominant inherited form of lymphoedema, typically presenting with lower limb lymphoedema from puberty and distichiasis from birth. For up to 97% of patients, a coding change in FOXC2 is identifiable. However, a number of case studies identifying structural variants (SVs) outside of the FOXC2 locus have been reported.Methods Using a range of approaches, including genome sequencing, we investigated whether we could identify SVs, which may be impacting FOXC2 in a series of unsolved cases. In silico tools were used to annotate these variants for potential insights into regulatory mechanisms.Results We identified five families with SVs impacting FOXC2. One with a mosaic deletion causing a truncated protein, and four with SVs impacting the non-coding portion of the genome downstream of FOXC2, likely causing dysregulation of the gene. A review of 28 patients in the DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources (DECIPHER) database with 16q24 deletions, including the whole of FOXC2, identified only two reported to have lymphoedema or distichiasis.Conclusion These additional cases bolster the evidence supporting FOXC2 as a monogenic cause of LDS. The fact that these SVs are not detected through panel testing underscores the recommendation for employing genome sequencing or array-comparative genomic hybridisation (CGH) in patients with suspected LDS who lack a genetic diagnosis. Public databases of patients with 16q24 deletions, incorporating FOXC2, but without lymphoedema reported, demand caution when interpreting deletions affecting the entirety of FOXC2. Work is required to explore the role of these putative regulatory elements whose dysregulation may cause this syndrome.

Transcription factor networks are crucial for the regulation of endothelial cell gene expression during vascular development and homeostasis. A recent analysis of 269 rare diseases in 77,539 individuals revealed an association between loss-of-function variants in ERG, encoding an ETS transcription factor, with primary lymphoedema. However, the pathogenicity of such variants and possible mechanisms of ERG-associated lymphatic vessel dysfunction remains to be established. Here, we have further identified and characterised lymphoedema-associated ERG genetic variants, revealing pathogenic mechanisms ranging from differential ERG subcellular localisation to altered DNA-binding and impaired transactivation. We confirm a role for ERG in regulating lymphangiogenesis using in vitro assays and a lymphatic endothelium-specific Erg deletion mouse model. Furthermore, we characterise the transcriptional and epigenomic landscape of human dermal lymphatic endothelial cells, identifying a unique role for ERG in regulating lymphatic gene programs, including the establishment of cooperative TF networks with PROX1 and GATA2. Our studies identify ERG as a master regulator of lymphatic endothelial cell transcriptional networks and uncover the mechanisms that underpin a novel causative gene for primary lymphoedema. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Infrastructure support for this research was provided by the NIHR Imperial Biomedical Research Centre (BRC), The Wellcome Trust, Cancer Research UK and the Medical Research Council (MRC). This study received financial support from the British Heart Foundation (BHF) through grants to GMB (PG/20/16/35047, PG/17/33/32990) and AMR (RG/11/17/29256, RG/17/4/32662). Rosetrees Trust (Seedcorn2022\100269) supported GMB & DP; DP is supported by the NIHR Imperial BRC; TV is funded by BHF PhD Studentship FS/4yPhD/F/23/34202 to GMB & IC; DN is funded by a BHF PhD Studentship FS/4yPhD/F/20/34128 to IC, AMR and GMB. IC is recipient of a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (224662/Z/21/Z). AS was jointly funded by EPSRC (EP/L015498/1) and BHF (RE/13/4/30184). SD, ES and PO were supported by the Swiss Federal National Fund for Scientific Research (CRSII5_177191/1). SM-A, SMa, KG, KO, SD and PO were supported by the MRC (MR/P011543/1) and BHF (RG/17/7/33217). DEA was funded by Qatar National Research Fund (QNRF) Graduate Scholarship Research Award (GSRA8-I-1-0210-21001). ADC acknowledges financial support from a UK Research and Innovation (UKRI) Future Leaders Fellowship (MR/S034757/1) and Economic and Social Research Council (ESRC) grant (ES/T013397/1). Computational analyses were performed at the Imperial College Research Computing Service (DOI: 10.14469/hpc/2232). This research was made possible through access to data in the National Genomic Research Library, which is managed by Genomics England Limited (a wholly owned company of the Department of Health and Social Care). The National Genomic Research Library holds data provided by patients and collected by the NHS as part of their care and data collected as part of their participation in research. The National Genomic Research Library is funded by the National Institute for Health Research and NHS England. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: London Brighton and Sussex Research Ethics Committee gave ethical approval for this work (REC Ref: 14/LO/0753). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All source data are available within the article. Upon publication, all sequencing data generated in this study (RNA-seq, ATAC-seq, ChIP-seq) will be publicly available at the NCBI Gene Expression Omnibus as a super-series. Software code developed for this study will be available at GitHub. Any other data are available from the corresponding authors upon reasonable request.

Pathogenic variants in kinesin KIF11 underlie microcephaly-lymphedema-chorioretinopathy (MLC) syndrome. Although well known for regulating spindle dynamics ensuring successful cell division, the association of KIF11 (encoding EG5) with development of the lymphatic system and how KIF11 pathogenic variants lead to lymphatic dysfunction and lymphedema remain unknown. Using patient-derived lymphoblastoid cells, we demonstrated that patients with MLC carrying pathogenic stop-gain variants in KIF11 have reduced mRNA and protein levels. Lymphoscintigraphy showed reduced tracer absorption, and intestinal lymphangiectasia was detected in one patient, pointing to impairment of lymphatic function caused by KIF11 haploinsufficiency. We revealed that KIF11 is expressed in early human and mouse development with the lymphatic markers VEGFR3, podoplanin, and PROX1. In zebrafish, single-cell RNA-Seq identified kif11 specifically expressed in endothelial precursors. In human lymphatic endothelial cells, EG5 inhibition with ispinesib reduced VEGFC-driven AKT phosphorylation, migration, and spheroid sprouting. KIF11 knockdown reduced PROX1 and VEGFR3 expression, providing for the first time to our knowledge a link between KIF11 and drivers of lymphangiogenesis and lymphatic identity.

In vitro modelling relies on the availability of suitable cell types that accurately represent the organs under study. In lymphatic research, human dermal lymphatic endothelial cells represent the “gold standard”, even though they lose their identity and proliferative capacity over time. A recently established immortalised lymphatic endothelial cell line (imLEC) could become a promising new tool for lymphatic disease modelling. We further characterised this cell line by comparing imLECs and HDLECs in terms of the expression of proteins essential for correct lymphatic function, and the proliferation, migration and sprouting responses to vascular endothelial growth factor C (VEGFC). We show similarities in the expression of lymphatic markers and VEGFC-driven cellular responses, supporting imLECs can retain their VEGFC-driven lymphangiogenic capacity without losing their lymphatic identity. RNA sequencing, however, revealed certain transcriptional differences in genes regulating lymphatic function in health and disease, highlighting the need for further validation at single gene level or specific lymphatic-associated signalling pathways. We acknowledge these limitations should be considered in future applications. Nonetheless, we believe that imLECs represent a useful model for the development of gene editing techniques allowing better modelling of lymphatic disease-associated genetic variants, ensuring long-term culture and providing higher reproducibility in genotype–phenotype validation analyses.

PIEZO1 variants have been associated with generalized lymphatic dysplasia (GLD) through mechanisms involving reduced PIEZO1 expression. Here, we report variants where the mechanism involves reduced channel mechanical sensitivity. Two of the variants encode amino acid changes in the channel's cap structure (Ile2270Thr and Arg2335Gln), one in the ninth transmembrane helical unit (THU) below the cap (Gly1978Asp) and one in the fifth THU distant from the cap (Glu829Val). Patch-clamp studies of the cap and sub-cap variant channels revealed abolished or reduced channel mechanical sensitivity with the possibility to activate the channels and partly rescue mechanical sensitivity by the small molecule Yoda1. The potency of Yoda1 at the variant channels was less than at the wild-type channel, but chemical synthesis of Yoda1 analogs revealed a molecule with improved potency. The data suggest cases of GLD in which there is decreased channel mechanical sensitivity and the potential to reduce dysfunction pharmacologically.

OBJECTIVES:This systematic review aims to evaluate the use of indocyanine green lymphography (ICGL) for the investigation of the lymphatics in the lower limbs of primary lymphoedema patients. METHODS:MEDLINE and EMBASE articles from January 1, 2000 to September 1, 2023 were searched for. A total of 11 studies were included in the review after a two-stage screening process. RESULTS:Data on patient demographics, ICG contrast injection technique, imaging protocols, and imaging outcomes were summarized and reviewed in detail. The review highlights the lack of commonality in protocols used. Factors important for good imaging are highly variable, particularly the number of injections, their location, and whether they are delivered intradermally or subcutaneously. CONCLUSIONS:ICGL has strong potential to become a diagnostic tool to diagnose lymphoedema due to its non-ionizing nature and cost-effectiveness. However, due to the lack of thorough phenotyping and genotyping of patients included in the studies, uncertainty still exists as to the value of the described imaging features such as splash, starburst, and diffuse dermal rerouting patterns. Future studies, therefore, should aim to explore the diagnostic utility of ICGL for lymphoedema further through the imaging of primary lymphoedema patients with a confirmed genetic diagnosis and using standardized imaging protocols. ADVANCES IN KNOWLEDGE:ICGL is a strong candidate for advancing the diagnosis and understanding of primary lymphoedema, and monitoring response to treatment, but protocol heterogeneity and a lack of consistency in reporting imaging details and patient phenotyping currently hold it back.

Developmental and functional defects in the lymphatic system are responsible for primary lymphoedema (PL). PL is a chronic debilitating disease caused by increased accumulation of interstitial fluid, predisposing to inflammation, infections and fibrosis. There is no cure, only symptomatic treatment is available. Thirty-two genes or loci have been linked to PL, and another 22 are suggested, including Hepatocyte Growth Factor (HGF). We searched for HGF variants in 770 index patients from the Brussels PL cohort. We identified ten variants predicted to cause HGF loss-of-function (six nonsense, two frameshifts, and two splice-site changes; 1.3% of our cohort), and 14 missense variants predicted to be pathogenic in 17 families (2.21%). We studied co-segregation within families, mRNA stability for non-sense variants, and in vitro functional effects of the missense variants. Analyses of the mRNA of patient cells revealed degradation of the nonsense mutant allele. Reduced protein secretion was detected for nine of the 14 missense variants expressed in COS-7 cells. Stimulation of lymphatic endothelial cells with these 14 HGF variant proteins resulted in decreased activation of the downstream targets AKT and ERK1/2 for three of them. Clinically, HGF-associated PL was diverse, but predominantly bilateral in the lower limbs with onset varying from early childhood to adulthood. Finally, aggregation study in a second independent cohort underscored that rare likely pathogenic variants in HGF explain about 2% of PL. Therefore, HGF signalling seems crucial for lymphatic development and/or maintenance in human beings and HGF should be included in diagnostic genetic screens for PL.

AIM:The aim of this study was to describe the technique of DCMRL to identify central lymphatic abnormalities in patients with primary lymphatic anomalies and discuss utility of the findings. MATERIALS AND METHODS:Twenty-eight patients with primary lymphatic abnormalities underwent dynamic magnetic resonance imaging (MRI) following injection of gadolinium directly into inguinal lymph nodes at a tertiary lymphovascular referral center. RESULTS:Technical success was achieved in 23 patients (82.1%). Pathological imaging findings included obstructed, hypoplastic, or absent lymphatic channels with collateralization/rerouting or reflux of flow, lymphangiectasia, lymphatic pseudoaneurysms, and lymph leaks. Protocol modifications for improved imaging are highlighted including technical aspects of lymph node injection, image acquisition and MRI parameters. In two patients, imaging findings warranted embolization of the abnormal lymphatic channels with subsequent symptomatic improvement. CONCLUSION:DCMRL has been shown to be a safe, reproducible technique in patients with primary lymphatic anomalies enabling imaging of the central lymphatic system.

BACKGROUND:Despite an increased interest in visualizing the lymphatic vessels with magnetic resonance lymphangiography (MRL), little literature is available describing their appearance in nonlymphedematous individuals. To determine lymphatic abnormalities, an understanding of how healthy lymphatic vessels appear and behave needs to be established. Therefore, in this study, MRL of individuals without a history of lymphatic disease was performed. METHODS:A total of 25 individuals (15 women) underwent MRL of their lower limbs using a 3.0 T Philips magnetic resonance imaging scanner (Philips Medical Systems). The first nine participants were recruited to establish the concentration of gadolinium-based contrast agent (GBCA) to administer, with the remainder imaged before and after interdigital forefoot GBCA injections at the optimized dose. Outcomes, including lymphatic vessel diameter, tortuosity, and frequency of drainage via particular drainage routes, were recorded. RESULTS:Healthy lymphatic vessels following the anteromedial pathway were routinely observed in post-contrast T1-weighted images (average tortuosity, 1.09 ± 0.03), with an average of 2.16 ± 0.93 lymphatic vessels with a diameter of 2.47 ± 0.50 mm crossing the anterior ankle. In six limbs, vessels following the anterolateral pathways were observed. No vessels traversing the posterior of the legs were seen. In a subset of 10 vessels, the lymphatic signal, measured at the ankle, peaked 29 minutes, 50 seconds ± 9 minutes, 29 seconds after GBCA administration. No lymphatic vessels were observed in T2-weighted images. CONCLUSIONS:Contrast-enhanced MRL reliably depicts the lymphatic vessels in the legs of healthy controls. Following interdigital contrast injection, anteromedial drainage appears dominant. Quantitative measures related to lymphatic vessel size, tortuosity, and drainage rate are readily obtainable and could be beneficial for detecting even subtle lymphatic impairment.

The genomics era has facilitated discovery of new genes predisposing to bone marrow failure (BMF) and hematological malignancy (HM). We report the discovery of ERG as a novel autosomal dominant BMF/HM predisposition gene. ERG is a highly constrained transcription factor critical for definitive hematopoiesis, stem cell function and platelet maintenance. ERG colocalizes with other transcription factors including RUNX1 and GATA2 on promoters/enhancers of genes orchestrating hematopoiesis. We identified a rare heterozygous ERG missense variant in 3 thrombocytopenic individuals from one family and 14 additional ERG variants in unrelated individuals with BMF/HM including 2 de novo cases and 3 truncating variants. Phenotypes associated with pathogenic germline ERG variants included cytopenias (thrombocytopenia, neutropenia, pancytopenia) and HMs (acute myeloid leukemia, myelodysplastic syndrome, acute lymphoblastic leukemia) with onset before 40 years. Twenty ERG variants (19 missense, 1 truncating) including 3 missense population variants were functionally characterized. Thirteen potentially pathogenic ETS domain missense variants displayed loss-of-function characteristics disrupting transcriptional transactivation, DNA-binding and/or nuclear localization. Selected variants overexpressed in mouse fetal liver cells failed to drive myeloid differentiation and cytokine-independent growth in culture, and to promote acute erythroleukemia when transplanted into mice, concordant with these variants being loss-of-function. Four individuals displayed somatic genetic rescue by copy neutral loss of heterozygosity. Identification of predisposing germline ERG variants has clinical implications for patient/family diagnosis, counselling, surveillance, and treatment strategies including selection of bone marrow donors or cell/gene therapy.

Superficial erythematous cutaneous vascular malformations are assumed to be blood vascular in origin, but cutaneous lymphatic malformations can contain blood and appear red. Management may be different and so an accurate diagnosis is important. Cutaneous malformations were investigated through 2D histology and 3D whole-mount histology. Two lesions were clinically considered as port-wine birthmarks and another 3 lesions as erythematous telangiectasias. The aims were (i) to demonstrate that cutaneous erythematous malformations including telangiectasia can represent a lymphatic phenotype, (ii) to determine if lesions represent expanded but otherwise normal or malformed lymphatics, and (iii) to determine if the presence of erythrocytes explained the red color. Microscopy revealed all lesions as lymphatic structures. Port-wine birthmarks proved to be cystic lesions, with nonuniform lymphatic marker expression and a disconnected lymphatic network suggesting a lymphatic malformation. Erythematous telangiectasias represented expanded but nonmalformed lymphatics. Blood within lymphatics appeared to explain the color. Blood-lymphatic shunts could be detected in the erythematous telangiectasia. In conclusion, erythematous cutaneous capillary lesions may be lymphatic in origin but clinically indistinguishable from blood vascular malformations. Biopsy is advised for correct phenotyping and management. Erythrocytes are the likely explanation for color accessing lymphatics through lympho-venous shunts.