Exploring disease interrelationships in patients with lymphatic disorders: A single center retrospective experience

Abstract

Background:The lymphatic contribution to the circulation is of paramount importance in regulating fluid homeostasis, immune cell trafficking/activation and lipid metabolism. In comparison to the blood vasculature, the impact of the lymphatics has been underappreciated, both in health and disease, likely due to a less well-delineated anatomy and function. Emerging data suggest that lymphatic dysfunction can be pivotal in the initiation and development of a variety of diseases across broad organ systems. Understanding the clinical associations between lymphatic dysfunction and non-lymphatic morbidity provides valuable evidence for future investigations and may foster the discovery of novel biomarkers and therapies. Methods:We retrospectively analysed the electronic medical records of 724 patients referred to the Stanford Center for Lymphatic and Venous Disorders.Patients with an established lymphatic diagnosis were assigned to groups of secondary lymphoedema, lipoedema or primary lymphovascular disease. Individuals found to have no lymphatic disorder were served as the non-lymphatic controls. The prevalence of comorbid conditions was enumerated. Pairwise cooccurrence pattern analyses, validated by Jaccard similarity tests, was utilised to investigate disease-disease interrelationships. Results: Comorbidity analyses underscored the expected relationship between the presence of secondary lymphoedema and those diseases that damage the lymphatics. Cardiovascular conditions were common in all lymphatic subgroups. Additionally, statistically significant alteration of disease-disease interrelationships was noted in all three lymphatic categories when compared to the control population.

Genetic causes of lymphatic disorders: recent updates on the clinical and molecular aspects of lymphatic disease

“…Future research should focus upon elucidating the pathogenesis of these disorders in an attempt to improve diagnostic rates in this widely under-recognized population. The analysis of disease-disease interrelationships is a statistical approach that has been newly applied in the realm of lymphatic disorders to identify common diseases in which lymphatic dysfunction may act as a disease mediator [37 ▪▪ ]. The opportunity exists to shift the focus of this approach to the genetic level or toward the analysis of complex syndromes in order to identify new phenotypic patterns of lymphatic disorders and potential genetic causes of disease.…”

Functioning of People with Lipoedema According to All Domains of the International Classification of Functioning, Disability and Health: A Scoping Review

“…In total, twenty-seven cross-sectional studies [15,16,, ten cohorts [61][62][63][64][65][66][67][68][69][70], three randomized controlled trials [71][72][73], four controlled clinical trials [74][75][76][77], one clinical trial [78], five case report studies [6,[79][80][81][82], and one qualitative study [83] were included. Two studies used a cross-sectional and a cohort design to answer the research questions [84,85].…”

“…All but three studies [69,72,76] evaluated with the EPHPP had a global "weak" rating (Cohen's kappa = 0.71, substantial agreement) (Supplementary Table S4: Methodological quality assessment using the Effective Public Health Practice Project (EPHPP) instrument). The vast majority of studies introduced potential selection bias by recruiting participants from specialized clinics without specifying what percentage of the selected individuals participated.…”

“…Twenty-seven of the studies reported at least one outcome that fit within the domain personal factors [6,15,36,[39][40][41]43,53,57,[59][60][61][62][63][64][65][66]68,69,71,72,76,78,79,82,85,86] (Table 2). The majority of outcomes in this domain were coded with "comorbidities" as it was mentioned in 32% of the studies.…”

Lymphedema and lipedema: More than a swollen limb?

“…7 A single-center study demonstrated increased disease inter-relationship and a higher rate of comorbidities in patients with both lipedema and lymphedema compared to controls. 8 In their article, Aday and colleagues offer a unique perspective of the clinical features of lipedema via a patient survey. 1 Responses from over 700 women with selfreported lipedema were compared to 216 controls.…”