Lymphedema Dermal Ultrasonography: Evaluation of Dermal and Sub-dermal Dimensions, Subcomponents, and Echogenicity

Introduction, Objectives, and/or Purpose: Lymphedema is a chronic disease in which impaired lymphatic vascular function leads to regional edema and inflammation. Early diagnosis and accurate assessment of lymphedema is crucial for the effective management of the condition. The advent of newer therapeutic strategies intensifies the need for accurate quantitative measures.

Dermal ultrasound, through its ability to discriminate the structure of the skin and underlying tissues has found early support in the diagnosis and assessment of lymphedema.

We have previously documented increased cellularity and thickening of the dermis in untreated preclinical and human lymphedema. However, quantitative dermal ultrasound has not been fully explored. The HEAL (Human Upper Extremity Acebilustat Lymphedema) trial (NCT05203835) is investigating the ability of leukotriene B4 (LTB4) antagonism to heal the structural damage caused by chronic lymphedema. The current investigation is devoted to characterizing the quantifiable pathological characteristics of untreated lymphedema as defined by dermal ultrasound. The objective of this study is to assess these quantifiable variables in the setting of upper limb lymphedema.

Methods: Twenty-five subjects were included in this investigation. Each participant provided written informed consent prior to enrollment. Ultrasound images of the upper forearm of the lymphedema arm and the normal arm were acquired. The sonographic appearance of the dermis can be qualitatively divided into three components ultrasonographically: the epidermis, the hypoechoic papillary dermis, and the hyperechoic reticular dermis (Figure 1). Dermal thickness, epidermal thickness, papillary dermal thickness, reticular dermal thickness, papillary dermal echogenicity, reticular dermal echogenicity, and subcutaneous echogenicity were measured for each image in random order by a radiologist blinded to participant identity. A dermal-to-subcutaneous echogenicity ratio was calculated by dividing the dermal echogenicity by the subcutaneous echogenicity. Paired samples two-sided t tests were performed for each variable, comparing the lymphedema arm with its paired normal extremity. P values < 0.05 were considered significant.

Results: All measured variables, with the exception of epidermal echogenicity, demonstrated statistically significant differences between the lymphedema arm and the normal arm (Table 1). As expected, the dermal thickness of the lymphedema arm was increased compared to the normal arm (p < 0.001). These subcomponents of the dermis were each individually increased compared to the normal limb. In addition, the echogenicity of papillary dermis and reticular dermis were both significantly decreased compared to normal dermis. As expected, the subcutaneous thickness as also significantly increased in the lymphedema limb (p < 0.001). In addition, the subcutaneous echogenicity of the subcutaneous tissues was also increased in the lymphedema arm compared to the normal arm (p < 0.001).

Conclusion(s): In summary, our study highlights the significant potential of dermal ultrasound to provide quantifiable variables that characterize the pathological responses of the skin in lymphedema. This non-invasive, readily repeated diagnostic intervention has the capacity to detect therapeutic responses in the damaged end organ in lymphedema, thereby providing valuable insight into treatment efficacy as newer therapeutic strategies continue to emerge.