Indocyanine green lymphography findings in older patients with lower limb lymphedema

Shuhei Yoshida, MD, PhD,a Isao Koshima, MD, PhD,a Hirofumi Imai, MD,a Ayano Sasaki, MD,b Yumio Fujioka, MD,b Shogo Nagamatsu, MD, PhD,b Kazunori Yokota, MD, PhD,b Mitsunobu Harima, MD,c Shuji Yamashita, MD, PhD,c and Kensuke Tashiro, MD,d. Journal of Vascular Surgery: Venous and Lymphatic Disorders July 2019

Abstract

Objective: Lymphedema is classified as primary or secondary according to the underlying cause. Primary lymphedema is hereditary and is considered a consequence of an inherited abnormality of the lymphatic system. Secondary lymphedema, however, is a consequence of lymphatic failure resulting from trauma, parasitic infection, or iatrogenic obstruction. Primary lymphedema is divided into three broad groups, namely, lymphedema congenita, lymphedema praecox, and lymphedema tarda. With the exception of lymphedema tarda, it is thought that age-related deterioration in lymphatic pump function is caused by oxidative stress. The aim of this study was to evaluate and to classify indocyanine green (ICG) lymphography findings in patients with lower limb lymphedema to ascertain whether there is a pattern to age-related deterioration.

Methods: There were 56 patients (104 edematous lower limbs) who had undergone ICG lymphography and for whom the lower extremity lymphedema (LEL) index had been calculated enrolled in this study. Specific inclusion criteria were used to exclude other causes of edema. ICG lymphography images were recorded in the plateau phase (12-18 hours after injection), when no further changes of images would be expected. The LEL index was calculated by summation of the squares of the circumference for five areas in each lower extremity divided by the body mass index.

Results: The clinical lymphedema pattern was determined as bilateral in 48 patients and unilateral in 8 patients. Patients with bilateral lymphedema were significantly older than those with unilateral lymphedema (76.40 6 8.03 years vs 53.13 6 14.12 years; P< .01). The ICG lymphography pattern was categorized as linear, low enhancement (LE), distal dermal backflow (DB), or extended DB in bilateral lymphedema. ICG lymphography showed the DB pattern on both the thigh and lower leg regions in all eight legs with unilateral lymphedema. There were also significant between-group differences in the LEL index (linear vs distal DB, P< .05; linear vs extended DB, P< .01; linear vs unilateral, P< .01; LE vs extended DB, P< .01; LE vs unilateral, P< .01; distal DB vs extended DB, P< .05; and distal DB vs unilateral, P< .01).

Conclusions: In this study, unilateral lymphedema, with its younger age at onset, severity, and unilateral dominance, corresponded to lymphedema tarda. In contrast, bilateral lymphedema corresponded to senile lymphedema, which is distinct from primary lymphedema in general and lymphedema tarda in particular. Age-related deterioration in lymphatic pump function rather than iatrogenic obstruction or genetic abnormality is likely to account for the characteristic older age at onset of lymphedema and its progression from the distal region. (J Vasc Surg: Venous and Lym Dis 2019;-:1-8.)

Main findings

  • In 104 edematous lower limbs of 56 patients, indocyanine green lymphography patterns were categorized as linear, low enhancement, distal dermal backflow, and extended dermal backflow. The lower extremity lymphedema index was calculated by summation of the squares of the circumference for five areas in each limb divided by the body mass index. The group with bilateral lymphedema showed progression of lymphedema from the distal to the proximal region.
  • Take-Home Message: The studies suggest age-related deterioration of lymphatic function.
  • Animal studies have shown that ageing lymphatic collecting ducts have decreased contraction frequency, systolic lymph flow velocity and pumping activity, and lymphatic vessel density and complexity.
  • Clinical studies using lymphoscintigraphy and ICG lymphography have demonstrated a reduction of lymph drainage with increasing age.
  • In secondary lymphedema with an iatrogenic aetiology, lymphatic function is initially retained.
  • Thereafter, accumulation of lymph starts at the proximal region close to the obstructed area and eventually extends to the distal region, with progressive deterioration of lymphatic function. However, in senile lymphedema, we suggest that deteriorating lymphatic function caused by ageing occurs in the entire area and that accumulation of lymph starts in the distal region because of the impact of gravity.
  • It is difficult to determine whether lymphedema tarda is congenital or acquired.
  • This study found that age-related lymphedema was less severe, it could be as severe as lymphedema tarda. This suggests that senile lymphedema should be treated regardless of age, given that the recent focus in treating lymphedema has shifted to risk reduction and prevention.
  • The older patients with bilateral lymphedema may be better regarded as having senile lymphedema rather than primary lymphedema.