Focus on Primary Lymphoedema

Lymphoedema is the chronic swelling of one or more body parts, most commonly an arm or leg . If there is some sort of damage, blockage or defect of the lymphatic system, it fails to drain away the lymph fluid from the tissues effectively. So this fluid collects in the tissues of the affected body part and this build up of fluid is seen as swelling. This swelling is lymphoedema, which may be categorised as either primary or secondary.

The majority of cases of lymphoedema occur as a result of another problem i.e. secondary to some known cause. This "secondary" lymphoedema occurs from damage and interruption to the lymphatic vessels - from causes such as surgery to remove lymph nodes, radiotherapy, or trauma, for example.

In some cases of lymphoedema, there is no obvious cause. This lymphoedema of unknown cause is called "primary" lymphoedema. It is estimated to occur in about one in six thousand people, more often in females than males, and the age that the primary lymphoedema appears tends to be alike within families. However, it should be stressed that primary lymphoedema is often sporadic, meaning that there is no family history (the condition is not inherited) or that no other family members will develop the condition of lymphoedema.

PRIMARY LYMPHOEDEMA can be classed into three main groups according to the age it appears:

1. Congenital Lymphoedema
   • Was first described in 1892 by Milroy
   • Lymphoedema is present at birth or soon after
   • Accounts for ~ 5 - 10% of all primary lymphoedema cases
   • Swelling tends to show in the legs most commonly, but can occur in multiple limbs, or even affect the face.
   • Females are affected twice as often as males
   • 2% of primary lymphoedema cases have a familial (i.e. genetically caused) pattern of inheritance, termed Milroy's Disease. In other words, 2% of cases are hereditary.
   • It is thought that many genes carry the codes responsible for the development of the lymphatic system.
     Mutations (changes) to these genes may be a cause of the primary lymphoedema.
     Researchers from the University of Pittsburgh have in fact identified lymphoedema-causing mutations in a particular gene, known as the VEGFR-3 gene, in some families with Milroy's disease. The mutation of this gene causes underdevelopment of lymphatic vessels (hypoplasia). However, there were over 100 families in the study for which a mutation to the VEGFR gene was NOT identified. So, it is possible that there may be other primary lymphoedema genes yet to be identified. Also, not all people who do carry the gene will actually develop any symptoms. A genetic test for lymphoedema is not yet available. A lot is still unknown and there is still much research work to be completed.
2. Lymphoedema Praecox
   • Appears at puberty/adolescence.
   • Most common form of primary lymphoedema
   • Accounts for ~75-80% of all primary cases
   • Affects females four times as often as males
   • Majority of cases involve one leg only and often limited to the foot, ankle and calf.
3. Lymphoedema Tarda
   • Appears after the age of 35
   • Accounts for ~10% of cases
   • Similar characteristics to lymphoedema praecox.

All 3 groups of primary lymphoedema have inadequate lymphatic drainage. Although the cause is not well understood, it is likely due to genetic faults or from abnormalities that occur in the formation of the lymphatic system during the developmental phase of a baby.

The types of abnormalities of the lymphatic system leading to poor drainage are:

• Aplasia - the lymphatic channels have not been developed at all and are absent. This is usual in Milroy's Disease.
• Hypoplasia - underdeveloped lymphatics with the vessels and lymph nodes being few in number and/or with a smaller diameter than normal. Hypoplasia is the more common type of abnormality of the lymphatics in primary lymphoedema.
• Hyperplasia - there is an excessive number of lymphatics with impaired function due to them often being enlarged or distorted (similar to varicose veins) so that normal lymph flow is hampered.

Research continues in order to gain more understanding of the underlying causes and the genetic basis of primary lymphoedema. Perhaps then advances can be made in the recognition, diagnosis and treatment of this condition v

© Lymphomation, Winter 2003