VII. Lymphoedema session
VII. Lymphoedema session
Optimal lymphoedema diagnosis and management in 2019
Peter Mortimer (London, UK)
Genomic medicine is the future for the diagnosis and management of primary lymphedema and vascular anomalies. Genomic medicine is the use of the genomic information of an individual to guide their clinical care. Genomic information is the sequencing and analysis of an organism’s entire DNA. Milroy disease is caused by a germ-line mutation in vascular endothelial growth factor receptor 3 (VEGRF3) that is associated with venous reflux and hydroceles in boys. Lymphedema distichiasis is caused by germ-line mutation in Forkhead Box C2 (FOXC2) that leads to a dominant hereditary lower limb lymphedema with onset at puberty and it is associated with varicose veins, cleft palate, ptosis, and congenital heart disease. Klippel-Trenaunay syndrome is caused by mosaic somatic mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and AKT serine/threonine kinase 1 (AKT1) gene (RAS/ MAPK pathway). A molecular (genomic) diagnosis can be made in 25% of primary lymphedema cases. Finding the gene permits an acquisition of knowledge concerning associated features (eg, venous or heart disease), allowing us to understand the gene function in the mechanism of disease, such as lymphatic valve failure, which provides information on the natural history of the disease (eg, FOXC2 can present at puberty [praecox] or later in life [tarda]). Germ-line mutations in VEGFR3, FOXC2, and gap junction protein gamma 2 (GJC2) cause hereditary human primary lymphedema and venous disease. FOXC2 causes deep venous reflux. Somatic mutations (eg, PIK3CA mutations), which is confined to the affected tissue, cause both venous and lymphatic malformations. In Klippel-Trenaunay syndrome (often caused by a PIK3CA mutation), the lymphatic anomaly may be significant, meaning that endovenous ablation may not reduce edema. Genotyping of affected tissue, where accessible, should therefore be a key element for management. The resulting genetic stratification may have prognostic value and it may serve to guide therapy.
A pragmatic approach to the assessment of swollen legs
Sarah Thomis (Leuven, Belgium)
The pathophysiology of edema includes increased capillary hydrostatic pressure, hypoalbuminemia (hence decreased oncotic capillary pressure), increased capillary permeability, and lymphatic obstruction (hence increased interstitial oncotic pressure). Causes of edema include venous edema resulting from chronic venous insufficiency and deep vein thrombosis, lymphedema, lipedema, and other causes, such as dependency edema, heart failure, kidney failure, and drugs. Lymphedema, chronic venous insufficiency, venous compression syndromes, strangulation edema, and trauma can cause unilateral edema, while heart failure, nephrotic syndrome, lipedema, lymphedema, chronic venous disease, dependency edema, idiopathic edema, and medications can cause bilateral edema. Anamnesis must contain time of onset and course, medical history for trauma, oncology, infection, medication, family history, immobility, cardiac or nephrotic problems, and associated symptoms, such as heaviness, tingling, and bruising. The clinical examination should investigate signs of venous insufficiency, such as varicose veins, lipodermatosclerosis, and ulcers, arterial pulsations and capillary refill, skinfold thickness (Stemmer sign), and pitting sign. An ultrasound is used to rule out deep vein thrombosis, venous valve incompetence, and metastasis in the lymph nodes as well as to visualize skin thickness. Ultra-high frequency ultrasound is used to visualize lymph vessels. CT and MRI are used to visualize swollen lymph nodes, visualize lymphedema, lymph vessels without functional information, and as MR lymphangiography.
MR lymphoscintography is used to quantify extraction from the injection point, arrival of the product in the lymph nodes at the groin/axilla, number of lymph nodes in the groin, dermal backflow, visualization of lymph nodes in the knee pit, and asymmetry. Lymphofluroscopy is used to image the superficial lymphatic system (with a maximum depth of 2 cm) and it shows the architecture of lymphatics as well as the lymphatic system. Indications for lymphofluroscopy are certain difficult-to-treat areas, deterioration of edema, and aid for surgical interventions and optimization of compression devices and lymph drainage.