Pathogenesis (development of disease)
In lymphedema, damage to the lymphatic system, which may be congenital or acquired, results in an increase in interstitial (from Latin interstitium = “interstitial space”) tissue fluid. As the disease progresses, tissue senescence (tissue alteration) occurs, with an increase in connective and adipose tissue, as well as changes in the extracellular matrix/structural components of a tissue (extracellular matrix, intercellular substance, EZM, ECM: glycosaminoglycans, hyaluronic acid, collagen).
Primary lymphedema can be distinguished from secondary lymphedema.
Etiology (causes) of primary lymphedema
Biographic causes
- Genetic burden from parents, grandparents
- Genetic diseases
- Nonne-Milroy syndrome (primary congenital lymphedema (PCL) type I) – genetic disorder with autosomal dominant inheritance with mutations in the FLT4 gene on chromosome 5q35.3; chronic, painless lymphedema of the lower and, in rare cases, upper extremities; edema (water retention) usually exists at birth or manifests in the first months of life
- Genetic diseases
Disease-related causes
Congenital malformations, deformities and chromosomal abnormalities (Q00-Q99).
- Atresia/aplasia (maldevelopment/non-development) of the lymphatic system.
- Meige’s syndrome (lymphoedema praecox) – characteristic is the combination of blepharospasm (unilateral or bilateral eyelid spasm resulting from a permanent contraction of the orbicularis oculi muscle) and oromandibular dystonia (generic term for dystonic movements of the masticatory muscles and the muscles of the lower (caudal) half of the face); Edema (water retention) does not develop until after puberty In individual Milroy and Meige patients, however, swelling does not develop until after age 35. Year of life (lymphoedema tarda).
Cardiovascular system (I00-I99).
- Aplasia/atresia of the lymphatic system
- Hyperplasia of the lymphatic system – abnormal proliferation of lymphatic system-specific cells.
- Hypoplasia of the lymphatic system – underdevelopment of the lymphatic system.
- Lymph node fibrosis – hardening of the lymph nodes.
- Lymph node agenesis
Etiology (causes) of secondary lymphedema
Disease-related causes
Cardiovascular (I00-I99).
- Chronic venous insufficiency (CVI) – chronic venous weakness of the lower extremities.
- Capillaropathies – changes in the vascular end distances that occur in various diseases.
- Lymph node fibrosis – hardening of the lymph nodes.
Infectious and parasitic diseases (A00-B99).
- Parasitoses – infections with parasites; lead to elephantiasis.
- Condition following infections (post-infectious), such as erysipelas or recurrent thrombophlebitides – inflammation of superficial veins.
Mouth, esophagus (food pipe), stomach, and intestines (K00-K67; K90-K93).
- Crohn’s disease – chronic inflammatory bowel disease (IBD); usually progresses in episodes and can affect the entire digestive tract; characterized by segmental involvement of the intestinal mucosa (intestinal mucosa), which means that several sections of the intestine may be affected, separated by healthy sections.
Neoplasms – tumor diseases (C00-D48).
- Malignant (malignant) neoplasms, often in breast carcinoma (breast cancer).
Injuries, poisonings, and other sequelae of external causes (S00-T98).
- Condition following major surgical procedures
- Condition following injury (post-traumatic), unspecified
Other causes
- Artificial (artificially added)
- Condition after lymphadenectomy (lymph node removal).
- Condition after radiatio (radiotherapy).
- Condition after vein harvesting for bypass surgery
