The pathogenesis of lipedema is not completely understood but is believed to be multifactorial. Microvascular dysfunction and increased angiogenesis resulting from hypoxia secondary to excessive expansion of fatty tissue are also thought to play a role in abnormal tissue development. This microangiopathy in affected tissues is thought to lead to capillary fragility and subsequent leakage of protein and fluid. Abnormal distribution of alpha and beta estrogen receptors has been reported in fatty tissue of affected areas, and estrogen is believed to contribute to disease development. Familial aggregation of lipedema is commonly observed, and heritability of the condition is likely. Possible inheritance patterns include X-linked dominant or autosomal dominant pattern with sex limitation.
Lipedema is staged based on severity:
- Stage 1 – flat skin with enlarged subcutis
- Stage 2 – induration of overlying skin with irregular appearance
- Stage 3 – larger indurations and deforming fat deposits
The course of lipedema is chronic and can be progressive. Many women have stable disease, some have disease that progresses slowly over decades, and others experience a rapid progression. Secondary lymphedema (lipolymphedema) may develop at any time during the disease course and can occur gradually or suddenly.