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

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 co-occurrence 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. CONCLUSIONS: The presence or absence of a lymphatic disease significantly influences disease interrelationships in the study cohorts. As a physiologic substrate, the lymphatic circulation may be an underappreciated participant in disease pathogenesis. These relationships warrant further, prospective scrutiny and study.