Chantalle B van de Pas1,2,3, Robert Sm Boonen2, Shaula Stevens2, Sten Willemsen4, Roelf Valkema5, Martino Neumann1. 1. Department of Dermatology, Erasmus MC, Rotterdam, The Netherlands. 2. Polikliniek de Blaak, Rotterdam, The Netherlands. 3. Kliniek De Medici, Blaricum, The Netherlands. 4. Department of Biostatistics, Erasmus MC, Rotterdam, The Netherlands. 5. Department of Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
Lipoedema is a chronic, incurable disease that is often progressive and may be
associated with considerable morbidity. It was first described by Allen and Hines[1] in 1940 as a disease characterized by bilateral enlargement, mainly of the
legs, caused by abnormal depositions of subcutaneous fat that are often associated
with mild oedema.[2] While the arms are much less affected, the hands and feet are never involved.
It occurs almost exclusively in women. Although the abundance of synonyms indicates
how little is known of this syndrome,[3] it is more common than most physicians realize. Initially, patients
experience discomfort, easy bruising and tenderness of the disproportionately
enlarged legs, which may progress to severe pain and limited mobility.As well as physical problems, lipoedema may be associated with psychosocial
complaints. These complaints arise because the majority has a history of dieting and
exercising without any considerable benefit on the contours and complaints of the
lower extremities.The fact that it is normally first noticed at puberty, pregnancy or menopause
suggests a causative hormonal component, and the fact that it often affects several
members of the same family suggests a genetic component. However, the exact
pathogenesis is unknown. Diagnosis is based on patient history and physical
examination. The course of lipoedema is variable and partly depending on the
possible concomitant obesity.In lipoedema, the anatomy of the lymphatic vessel system has been found to be normal,
as far as the large lymph vessels are concerned. However, the increased
intercellular pressure due to expanding fat tissue (because of disproportionate
enlargement of the adipocytes) may cause slight mechanical obstruction of the small
lymphatic vessels in the septa, which result in mild lymphostasis and oedema of the
subcutaneous tissue.[4],[5]However, some publications suggest that a micro-angiopathy of the lymph capillaries
located in the connective tissue septa between fat lobes[6] causes increased permeability due to a fragile vessel wall. Similarly, the
easy bruising might be explained by a capillary fragility. This might also explain
an increased tendency to the formation of oedema.The increased permeability of the lymph capillaries leads to an increased lymphatic
volume that exceeds the existing drainage capacity and results in dilatation of the
prelymphatic vasculature. The stasis of extravasation of proteins causes first
inflammation followed by fibrosis, leading to pathological changes in lymphatic
capillaries typical in lipoedema. In long-standing lipoedema, these small
alterations of the lymphatic tissue can be visualized by indirect lymphography. The
injection depots look flame-like, unlike the usually visualized round deposits. The
‘tongues of flame’ are likely to represent distended pre-lymphatic spaces.[7-13] Some investigators found
enlarged and obliterated lymphatic microvessels,[11] lymphatic collectors following a tortuous course through the fatty
subcutaneous tissue[8],[11] and multiple microlymphatic aneurysms of lymphatic capillaries in patients
with lipoedema,[12] of which the pathophysiological role remains to be established.The chronic stasis of lymphoedema also ensues adipocyte hypertrophy. This adds to the
lymphatic load of an already overloaded lymphatic system (vicious cycle).The relationship between lymphatics and adipose tissue remains controversial.The mechanism of lipoedema might be a continuing deterioration in which the growing
adipocytes keep slowing the lymphatic drainage, while it is still unclear whether
the primary factor is the growing adipocyte or an intrinsic problem in the
interstitial space or microlymphatic pathway.Limb lymphatic function in lipoedemapatients can be assessed using quantitative
lymphoscintigraphy.[8,14-17] This is a reliable,
reproducible, minimally invasive research method for assessing/measuring lymph flow
and detecting and quantifying lymph stasis and dysfunction.Photoplethysmography and quantitative lymphoscintigraphic studies showed that
insufficiency may be present, as compared with healthy controls. However, the degree
of insufficiency never reached the level of true lymphoedema, and large lymph
vessels were normal and sufficient.[6],[8,14,15],[18-21]Because the pathogenesis of lipoedema is not exactly known, a curative treatment is
not available. However, the introduction of tumescent local anaesthesia in the 1980s
has greatly changed the therapeutic options for lipoedema.[22]In tumescent local anaesthesia, large amounts of fluid and low concentration of the
anaestheticum (containing saline, lidocaine, sodium bicarbonate and adrenaline) are
infiltrated in the subcutaneous tissues. Tumescent liposuction is at least as
effective as the conventional (‘dry’) liposuction and the so-called wet liposuction
in removing adipose aspirates, but has the advantage that it is significantly less
likely to damage the lymphatic vessels.[4],[6],[23],[24] However, there is not much scientific research done on this topic.To establish whether the lipoedemapatients initially had a dysfunction in lymph flow
or whether this was normal, we quantified the lymph flow of lipoedemapatients using
lymphoscintigraphy. To investigate whether the function of the lymphatic system has
changed after tumescent liposuction – and thus to establish whether tumescent
liposuction can be regarded as a safe technique – we compared lymphoscintigraphies
of lipoedemapatients before and after tumescent liposuction.
Methods
Study population
One hundred and seventeen women with lipoedema of the legs were included in our
study. All participants provided informed consent. The mean age, when the
lymphoscintigraphy in 2010 was performed, was 40.9 years (range 21.0–64.1
years). The diagnosis of lipoedema of the legs was established by clinical
history and physical examination.[4] We used standardized lymphoscintigraphy to quantify the lymph flow in all
lipoedemapatients. The lymphatic function in lipoedemapatients was compared
with those obtained from normal volunteers.1Normal values of clearance (disappearance from the depot) and inguinal uptake
after 2 h post injection have previously been established through evaluation of
a series of normal healthy volunteers without leg swelling or other clinical
evidence of venous or lymphatic disease.[6,25-27]Fifty lymphoscintigraphies out of the former 117 before and six months after
tumescent liposuction were compared. The mean age was 42.2 years (range
24.1–57.9 years).
Lymphoscintigraphy
Quantitative lymphoscintigraphy is an established technique for assessment of
limb lymphatic function. Briefly, this involves subcutaneous injection of 99mTc
in the first web space. A large-field-of-view gamma camera with on-line computer
facilities is positioned with the collimator facing close to the skin surface.
Images are obtained sequentially over feet, knees and inguinal regions at
minutes post injection.We used mean clearance percentages of radioactive protein loaded after 1 min with
respect to the total injected dose and corrected for decay of the
radiopharmaceutical in the subcutaneous lymphatics as functional quantitative
parameters as well as the clearance percentages and inguinal uptake percentages
2 h post injection.Clearance was disturbed 2 h post injection if <30% (abnormal <20% plus
questionable 20–30%). Inguinal uptake was disturbed 2 h post injection if
<10% (abnormal < 5% plus questionable 5–10%).
Tumescent liposuction
Tumescent liposuction in our study was performed according to the standard
treatment as described by Klein22 and executed by an experienced
professional who has treated lipoedemapatients with this treatment over the
last 15 years.
Statistics
To describe our sample we calculated the mean and range of the age at the time
the lymphoscintigraphy was performed. We also calculated the mean clearance and
inguinal uptake on the right and left side and categorized these values as
either normal (> 30% for the clearance and > 10% for the inguinal uptake)
or abnormal.We looked at the correspondence of these measurements on the left and the right
using the Pearson’s correlation.To evaluate the results of the tumescent liposuction, we compared the left, right
and average clearance and inguinal uptake using a paired t-test. We looked at
the differences (before–after) and provided a 95% confidence interval.All analyses were performed using R 3.2 (R Foundation for Statistical Computing,
Vienna, Austria). We considered results to be statistically significant whenever
their p-value was below 0.05. No multiplicity correction was applied.
Results
Lymphoscintigraphy results of 117 lipoedema patients
The mean age of 117 lipoedemapatients at the time the lymphoscintigraphy was
performed was 40.9 years (range 21.0–64.1 years). Clearance in the right and
left foot was disturbed ( = abnormal + questionable) in 79.5 and 87.2%
respectively and normal in 20.5 and 12.8% respectively compared to normal
volunteers (Table 1). The inguinal uptake after 2 h in the right and left groin
was disturbed in 60.3 and 64.7% respectively and normal in 39.7 and 35.3%
respectively compared to normal volunteers (Table 2).
Table 2.
Inguinal uptake groin 2 h post injection.
Frequency (in numbers)
Per cent (in %)
Inguinal uptake right leg 2 h post
injection
Disturbed (≤10%)
70
60.3
Normal (>10%)
46
39.7
Total
116 (1 missing)
100
Inguinal uptake left leg 2 h post injection
Abnormal (≤10%)
75
64.7
Normal (>10%)
41
35.3
Total
116 (1 missing)
100
Clearance foot 2 h post injection.Inguinal uptake groin 2 h post injection.The clearance and inguinal uptake correlation coefficient 2 h post injection of
radioactive protein between right and left after 2 h were both 0.39.
Lymphoscintigraphy results of 50 lipoedema patients before and after
tumescent liposuction
All lipoedemapatients were female. The mean age of the 50 lipoedemapatients at
which the first lymphoscintigraphy was performed before tumescent liposuction
was 42.2 years (range 24.1–57.9 years).Mean clearance before minus after tumescent liposuction of both right and left
foot (or of both feet) was slightly improved, 0.01 (p = 0.37). However, this was
not statistically significant.Mean inguinal uptake before minus after tumescent liposuction of the groin was
also slightly improved, 0.02 (p = 0.02). This is statistically significant
(Table 3).
Table 3.
Mean clearance feet and inguinal uptake groin before and minus after
tumescent liposuction.
Mean clearance feet and inguinal uptake groin before and minus after
tumescent liposuction.The clearance and inguinal uptake correlation coefficient 2 h post injection of
radioactive protein between right and left after tumescent liposuction were 0.51
versus 0.47.
Discussion
Lipoedema is a very common disease and a burden for the patient and the medical
profession. Weight reduction is not of great value due to the disturbed metabolism
of the lipocytes at the specific regions (legs, buttocks and arms but never the abdomen[6]) where lipoedema is present. Nevertheless, it is true that a significant part
of the lipoedemapatients also has obesity. As weight and by this BMI are not
realistic parameters to determine obesity, only abdominal circumference can diagnose
the obesity factor in lipoedemapatients. A good treatment for lipoedema is
therefore a combination of obtaining a normal abdominal circumference
(women < 90 cm), exercising and specific treatment for the areas of
lipoedema.Tumescent liposuction is the only available treatment for lipoedema with good and
long lasting results.[28] However, this technique could theoretically destruct the lymphatic vessels,
which will lead to lymph transport stasis and thus to lymphoedema. Although in
lipoedema stasis of lymph in the adipose tissue septa plays a role, this is
uncorrelated to the function of the major transporting lymph vessels of the
extremities. This means that lipoedema is not a complication with lymfoedema. This
is clearly visible in the patients because in lymphoedema the feet are first and
always swollen but in lipoedema the feet are never touched by the pathological
process. To investigate the potential risk of lymphoedema due to tumescent
liposuction for lipoedema, we started this protective study.Lymphoscintigraphy, a well established objective instrument to measure the lymph
drainage of extremities, has been performed since the 1950s and is still currently
the recommended technique for the examination of lymphoedema.[29-33]We examined the lymphatic outflow of a group of 117 lipoedemapatients. This study
showed that most of our lipoedemapatients had a delayed leg lymph transport as both
clearance (disappearance from the depot) and inguinal uptake were disturbed 2 h post
injection of radioactive protein. Whether the primary factor is the growing
adipocyte or an intrinsic problem in the interstitial space or microlymphatic
pathway is still under discussion. However, the major lymph vessels were normal in
function. This corresponds with the observation of Stutz[34] and Schmeller et al.[35]Also the clearance and inguinal correlation coefficient (n = 117) 2 h post injection
of radioactive protein between right and left were both 0.39. This means that there
is a moderate correlation of lymphatic function in lipoedemapatients between both
legs according to Dancey and Reidy's correlation. In conclusion this means that
lymphatic function was rather symmetrical.We also investigated whether the function of the lymphatic system in 50 lipoedemapatients was different after tumescent liposuction by comparing the values of
clearance and inguinal uptake 2 h post injection. This study shows clearly that
tumescent liposuction did not damage the lymphatic function as both mean clearance
and mean inguinal uptake before minus after tumescent liposuction were slightly
improved.The clearance and inguinal uptake correlation coefficient 2 h post injection of
radioactive protein between right and left after tumescent liposuction (n = 50) were
0.51 versus 0.47. This means a moderate correlation of lymphatic function in both
legs in lipoedemapatients according to Dancey and Reidy's correlation. Also here
lymphatic function was rather symmetrical.Tumescent liposuction gave minimal improvement in the lymphatic system but this was
only statistically significant for the inguinal uptake. Most important is that our
study proved that tumescent liposuction will not damage the lymph vessels in
lipoedemapatients. The outflow of lymph even increased after liposuction. Also
lipoedemapatients have less lymph transport capacity than healthy volunteers but
this does not lead to lymphoedema. We definitely need a bigger study to have our
data confirmed.
Conclusion
Lymphatic insufficiency plays a significant role in the pathophysiology of
lipoedema.Tumescent liposuction does not diminish the lymphatic function in lipoedemapatients.
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