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Abstract and Figures

Background: Lipedema is often unrecognized or misdiagnosed; despite an estimated prevalence of 10% in the overall female population, its cause is still unknown. There is increasing awareness of this condition, but its differential diagnosis can still be challenging. In this article, we summarize current hypotheses on its pathogenesis and the recommendations of current guidelines for its diagnosis and treatment. Methods: This review is based on publications about lipedema that were retrieved by a selective search in the MEDLINE, Web of Science, and Cochrane Library data- bases. Results: The pathophysiology of lipedema remains unclear. The putative causes that have been proposed include altered adipogenesis, microangiopathy, and disturbed lymphatic microcirculation. No specific biomarker has yet been found, and the diag- nosis is currently made on clinical grounds alone. Ancillary tests are used only to rule out competing diagnoses. The state of the evidence on treatment is poor. Treatment generally consists of complex decongestive therapy. In observational studies, liposuction for the permanent reduction of adipose tissue has been found to relieve symptoms to a significant extent, with only rare complications. The statutory health- insurance carriers in Germany do not yet regularly cover the cost of the procedure; studies of high methodological quality will be needed before this is the case. Conclusion: The diagnosis of lipedema remains a challenge because of the hetero- geneous presentation of the condition and the current lack of objective measuring instru- ments to characterize it. This review provides a guide to its diagnosis and treatment in an interdisciplinary setting. Research in this area should focus on the elucidation of the pathophysiology of lipedema and the development of a specific biomarker for it.
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MEDICINE
Review Article
Lipedema—Pathogenesis, Diagnosis, and
Treatment Options
Philipp Kruppa, Iakovos Georgiou, Niklas Biermann, Lukas Prantl, Peter Klein-Weigel, and Mojtaba Ghods
L
ipedema is a chronic condition that is currently
thought to be progressive as well. It mainly affects
women, male sufferers having been described in
only a few case reports (1) (e1, e2). Its progressive
nature, though not yet unequivocally demonstrated, is
assumed on the basis of clinical experience. Epidemi-
ologic estimates from the sparse available data suggest
an approximately 10% prevalence in the overall female
population (2, 3, e3–e6).
The initial manifestations of lipedema often arise in
phases of hormonal change (puberty, pregnancy,
menopause). Its hallmark is a disproportionate dis-
tribution of body fat on the extremities, while the
trunk remains slim. Hands and feet are not involved.
(4)
(Figure).
Aside from the circumscribed, bilaterally sym-
metrical, localized increase of the subcutaneous fatty
tissue of the limbs, lipedema has the typical clinical
manifestations listed in the
Box
(5). Three clinical
stages have been described through which the disease
progresses
(Figure 1)
(6).
Although Allan und Hines (7) described lipedema
as early as 1940, the condition attracted little attention
for many years. Even now that awareness of it has
been heightened by frequent discussion in the news
media (e7), there remains a great deal of uncertainty
as to how it can be correctly diagnosed. The diagnosis
is only rarely made on the patient’s first contact with a
physician (e8), and there is often a delay of several
years before specific treatment is initiated (8).
Current research focuses on the pathophysiology of
lipedema and on the development of tools to facilitate
its correct diagnosis and the exclusion of competing
diagnoses. In this review, we present the current state
of knowledge of, and hypotheses about, the etiology
and pathogenesis of lipedema. We also hope to in-
crease physicians’ awareness of the urgency of early
diagnosis and promptly initiated treatment.
Method
We selectively searched for publications about lipede-
ma in the MEDLINE (via PubMed), Web of Science,
and Cochrane Library databases using the key words
“Lipödem,” “lipedema,” “lipoedema,” and “multiple
symmetric lipomatosis,” and we carried out a
supplementary search among the references of these
publications. We included articles that were published
in English or German up to February 2020.
Summary
Background: Lipedema is often unrecognized or misdiagnosed; despite an estimated
prevalence of 10% in the overall female population, its cause is still unknown. There
is increasing awareness of this condition, but its differential diagnosis can still be
challenging. In this article, we summarize current hypotheses on its pathogenesis and
the recommendations of current guidelines for its diagnosis and treatment.
Methods: This review is based on publications about lipedema that were retrieved by
a selective search in the MEDLINE, Web of Science, and Cochrane Library data-
bases.
Results: The pathophysiology of lipedema remains unclear. The putative causes that
have been proposed include altered adipogenesis, microangiopathy, and disturbed
lymphatic microcirculation. No specific biomarker has yet been found, and the diag-
nosis is currently made on clinical grounds alone. Ancillary tests are used only to rule
out competing diagnoses. The state of the evidence on treatment is poor. Treatment
generally consists of
complex decongestive therapy
. In observational studies,
liposuction for the permanent reduction of adipose tissue has been found to relieve
symptoms to a significant extent, with only rare complications. The statutory health-
insurance carriers in Germany do not yet regularly cover the cost of the procedure;
studies of high methodological quality will be needed before this is the case.
Conclusion: The diagnosis of lipedema remains a challenge because of the hetero -
geneous presentation of the condition and the current lack of objective measuring instru-
ments to characterize it. This review provides a guide to its diagnosis and treatment in
an interdisciplinary setting. Research in this area should focus on the elucidation of the
pathophysiology of lipedema and the development of a specific biomarker for it.
Cite this as:
Kruppa P, Georgiou I, Biermann N, Prantl L, Klein-Weigel P, Ghods M:
Lipedema—pathogenesis, diagnosis and treatment options.
Dtsch Arztebl Int 2020; 117: 396–403. DOI: 10.3238/arztebl.2020.0396
Department of Plastic, Aesthetic, Hand and Reconstructive Micro Surgery,
Klinikum Ernst von Bergmann, Potsdam: Philipp Kruppa, Iakovos Georgiou, Dr. med. Mojtaba Ghods
Department of Plastic, Hand and Reconstructive Surgery, University Hospital Regensburg: Dr. med.
Niklas Biermann, Prof. Dr. Dr. med. Lukas Prantl
Department of Angiology, Klinikum Ernst von Bergmann, Potsdam: Dr. med. Peter Klein-Weigel
This article has been certified by the North Rhine Academy of Continuing
Medical Education. The test questions for this article can be found at http://da
ebl.de/RY95. This unit can be processed for CME credit until 31 May 2021.
Participation is possible only via the Internet at cme.aerztebatt.de.
cme plus
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Pathophysiology
The cause of lipedema is still unexplained. There are
various hypotheses about its pathophysiology (Figure
2).
As the condition has repeatedly been described in
familial clusters, a genetic predisposition is assumed
(9, e1, e9). As many as 60% of patients have an af-
fected first-degree relative (3, 10, e9, e10). Analyses
of familial clusters suggest an autosomal dominant in-
heritance pattern with incomplete penetrance (11, 12,
e11).
As lipedema usually first manifests itself in
periods of hormonal change, it is generally thought to
be estrogen-mediated (13). Despite the autosomal
dominant inheritance pattern suggested by pedigree
analyses, it has been proposed that the disorder results
from a polygenically mediated change in the pattern of
distribution of alpha- and beta-estrogen receptors (ER)
in the white fatty tissue of affected areas (ER-α
expression ↓, ER-β expression ↑) (13, 14, e12).
It is not yet entirely clear whether, in lipedema, the
subcutaneous fat cells become more numerous (hy-
perplasia) (15–17, e13, e14) or merely larger in size
(hypertrophy) (15, e15).
Cytobiological and protein-expression studies on
lipo-aspirates taken from lipedema patients suggest
that the disorder mainly arises through changes in the
initial steps of cell differentiation in adipogenesis (15,
16, 18–20).
Another pathophysiological hypothesis involves
primary microvascular dysfunction in the lymphatic
and blood capillaries (21, 22). This, in turn, is thought
to be due to a hypoxic stimulus brought about by
excessive expansion of adipose tissue, leading to en-
dothelial dysfunction, and thereby to increased angio-
genesis; alternatively, it may be due to a mechanical
disturbance of lymph drainage (13, 17, 23, e16, e17).
Capillary damage is also a proposed cause of the ob-
served increased tendency to form hematomas and
petechiae (21, 24).
Increased capillary permeability leads to shifting of
protein into the extracellular compartment (“capillary
leak”) and thereby to tissue edema. At first, the
additional fluid entering the interstitial space can be
compensated for by increased lymph drainage. As the
disorder progresses, however, the capacity of the
draining lymphatic vessels is exceeded, and high-
volume insufficiency (e18) results, while the larger
Figure 1:
the staging and typological classification of lipedema
Stages of lipedemaTypes of lipedema
123
IIIIIIVV
Classification by stage
1) thickened subcutis, soft, with small, palpable
nodules, skin surface still smooth
2) thickened subcutis, soft, some larger nodules,
skin surface uneven
3) thickened subcutis, hardened, with large
nodules, disfiguring fat deposition
Classification by morphology
II) thigh III) entire lower limb IV) arm* V) legI) buttock
* Type IV is often associated with type II or III.
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lymphatic vessels remain intact (e9, e19, e20).
Quantitative lymphatic scintigraphy has revealed
early and, in part, stage-dependent disturbances of
lymphatic transport capacity (e21, e22), as well as in-
itially increased lymphatic transport (e23).
The effect of capillary hyperpermability is in-
creased by pathological abnormalities in large blood
vessels. Stiffness of the aorta, which has been de-
scribed in patients with lymphedema, might promote
premature vascular remodeling and local hyperten-
sion (13, e16). Moreover, there is also dysregulation
of the veno-arterial reflex (VAR), which protects the
capillary bed from locally elevated hydrostatic
pressure by constriction of the arterioles (17). This,
combined with the capillary leak due to micro -
angiopathy, promotes the formation of edema and
hematoma.
The increased perception of pain that typifies
lipedema has been attributed to dysregulation of
locoregional sensory nerve fibers through an inflam-
matory mechanism. This hypothesis is based on
single case reports; there are no valid data showing a
significant increase of pro-inflammatory markers in
patients with lipedema (15, e24–25). Disordered pain
perception seems unlikely to be due to mechanical
compression of nerve fibers by the expanding mass of
fatty tissue and tissue edema, as there is no such dis-
turbance in other types of lipohypertrophy or lymphede-
ma (10).
The advanced stages of lipedema are associated with
various sequelae. A fluid load exceeding the capacity of
the lymphatic system can cause secondary lymphedema
(“lipo-lymphedema”) in any stage of the disease (12).
Mechanical irritation from large fatty deposits near the
joints can macerate the skin; such deposits on the thighs
and around the knee joints can also interfere with
normal gait and cause secondary arthritis (5). Further
secondary effects include the emotional disturbance and
lessened self-esteem that result from an appearance that
falls short of the contemporary ideal of beauty (e7, e26).
Diagnostic evaluation
The diagnosis is generally made on clinical grounds
after the exclusion of competing diagnoses. As the
presenting manifestations of lipedema are hetero -
geneous, the diagnosis should be confirmed by an ex-
perienced lymphologist in doubtful cases. The basic
diagnostic evaluation consists of history-taking, inspec-
tion, and palpation, with particular attention to the
manifestations listed in the Box. The clinical constel-
lation of the major manifestations of the disorder
appearing together—tissue tenderness, a feeling of
tightness, and an excessive tendency toward hematoma
formation, with worsening symptoms over the course
of the day, in a patient with a bilaterally symmetrical,
disproportionate proliferation of fatty tissue on the
limbs but not on the hands/feet—points toward the di-
agnosis of lipedema. Thus, the history obtained from
the patient is a major factor in the establishment of the
correct diagnosis.
Persons suffering from lipedema often have a
positive family history of the disorder. The physician
taking the history of the present illness must also ask,
in particular, about the time of onset of the initial
manifestations and progression in the intervening
time.
The onset of lipedema is typically triggered by
hormonal changes (puberty, pregnancy, menopause);
this helps in the differentiation of lipedema from
simple obesity. The distinction can be difficult to
draw, as these entities often appear together and the
clinical picture can vary
(Table
) (25). Even in an
obese person, however, the characteristic symptoms
of pain, a feeling of tightness, and a tendency toward
bruising (hematoma formation) indicate that lipedema
is present as well
(Box)
. Sometimes lipedema is un-
masked only after successful bariatric surgery for
obesity, when, after marked weight loss, a persistent
abnormal pattern of fat distribution reveals itself that
is typical of lipedema (26, e27).
The physician taking the history must also
routinely inquire about the commonly associated
psychiatric comorbidities, so that early treatment of
these can be initiated where necessary (e28).
Clinical examination
The three stages of the disease are characterized by pro-
gressive changes in the structure of the skin surface
(stage I, smooth; stage II, uneven or corrugated; stage
BOX
Clinical criteria for the diagnosis of
lipedema
bilateral, symmetrical, disproportionate fatty tissue
hypertrophy on the limbs
sparing of the hands and feet (cuff phenomenon)
approximately 30% involvement of the arms
negative Stemmer sign*
a feeling of heaviness and tension in the affected limbs
pain on pressure and touch
marked tendency to form hematomas
stable limb circumference with weight reduction or
caloric restriction
worsening of symptoms over the course of the day
telangiectases and visible vascular markings around fat
deposits
hypothermia of the skin
*positive Stemmer sign (in case of secondary lymphedema): the skin fold
between the second and third toe is thickened and cannot be lifted
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3, markedl
y
thickened and indurated) and in the find-
i
n
g
s on pa
l
pat
i
on:
sta
g
e I: small nodules, reversible edem
a
sta
g
e II: wa
l
nut-s
i
ze
d
no
d
u
l
es, revers
ibl
e o
r
irr
eve
r
s
i
b
l
e
ede
m
a
sta
g
e III:
di
sf
ig
ur
i
n
g
fat
d
epos
i
ts, macrono
d
u
l
a
r
c
h
an
g
es, w
i
t
h
accompan
yi
n
g
ly
mp
h
e
d
ema, poten
-
t
i
a
lly
Stemmer s
ig
n pos
i
t
i
ve
(
e29
)
.
e s
mptoms an
su
ect
ve
e
ree of suffer
n
are
not necessar
ily
corre
l
ate
d
w
i
t
h
t
h
e
di
sease sta
g
e
(
5
).
Stan
d
ar
di
ze
d
ant
h
ro
p
ometr
i
c measurements s
h
ou
ld
b
e a
p
art of rout
i
ne c
li
n
i
ca
l
fo
ll
ow-u
p
,
b
ot
h
to assess
t
h
e s
p
ontaneous course of t
h
e
di
sor
d
er an
d
to mon
i
to
r
i
ts res
p
onse to treatmen
t
:
b
o
dy
we
igh
t,
b
o
dy
-mass
i
n
d
ex
(
BMI
)
, wa
i
st-to-
hi
p rat
i
o
(
WHR
)
, wa
i
st-to-
h
e
igh
t rat
i
o
(
WHtR
)
, an
d
t
h
e c
i
rcumference an
d
vo
l
ume of t
h
e
li
m
b
s. T
h
e BMI
i
s of
li
m
i
te
d
ut
ili
t
y
i
n
di
st
i
n
g
u
i
s
hi
n
g
li
pe
d
ema from o
b
es
i
t
y
(
11, 25, e24
)
.
Moreover,
p
a
i
n
p
erce
p
t
i
on s
h
ou
ld
b
e assesse
d
a
t
re
g
u
l
ar
i
nterva
l
s, w
i
t
h
, e.
g
., t
h
e V
i
sua
l
Ana
l
o
g
Sca
l
e
(
VA S
)
an
d
t
h
e Sc
h
me
ll
er
q
uest
i
onna
i
re
(
e30
)
. An
n
ex of
a
act
v
t
s
ou
a
so
e
ocumente
,
e.
g
., b
y
the step-countin
g
app of the patient’s mobile
te
l
e
ph
one
(
5
).
T
h
e t
i
ssue ten
d
erness t
h
at
i
s c
h
aracter
i
st
i
c of
lip
e
d
ema
can
b
e c
h
ec
k
e
d
w
i
t
h
t
h
e
pi
nc
h
test, w
hi
c
h
i
s often fe
l
t as
very unp
l
easant
i
n t
h
e affecte
d
areas
b
ut causes no pa
i
n
e
l
sew
h
ere. Increase
d
cap
ill
ar
y
fra
gili
t
y
man
i
fests
i
tse
l
f
i
n
s
p
ontaneous
h
ematoma format
i
on. T
h
ere
i
s no nee
d
,
i
n
routine clinical practice, to document this further with an
y
s
pec
i
a
l
measur
i
n
g
i
nstruments or stress tests
(
e31–e33
).
L
a
b
orator
y
tests
Renal and hepatic d
y
sfunction
, h
y
poth
y
roidism (possibl
y
su
b
c
li
n
i
ca
l)
, pat
h
o
l
o
gi
ca
l
li
p
id
prof
il
es, an
d
i
nsu
li
n
res
i
stance s
h
ou
ld
b
e ru
l
e
d
out
by
l
a
b
orator
y
test
i
n
g
. An
y
h
ormona
l
or e
d
ema-promot
i
n
g
di
stur
b
ances t
h
at are foun
d
s
h
ou
ld
b
e treate
d
, a
l
t
h
ou
gh
no ev
id
ence
y
et
i
n
di
cates
a
b
enef
i
t of suc
h
treatment w
i
t
h
respect to t
h
e sever
i
t
y
o
r
course of
lip
e
d
em
a
(
1
)
.
A
nc
ill
ar
y
di
a
g
nost
i
c test
i
n
g
D
i
a
g
nost
i
c proce
d
ures t
h
at requ
i
re spec
i
a
l
equ
i
pment
are use
d
on
ly
to ru
l
e out compet
i
n
g
e
l
ements of t
h
e
di
f-
ferent
i
a
l
di
a
g
nos
i
s; t
h
e
y
p
l
a
y
no esta
bli
s
h
e
d
ro
l
e
i
n t
h
e
rout
i
ne eva
l
uat
i
on of
lip
e
d
ema
(
3, 12, 27, e34, e35
).
T
he
ski
n an
d
subcu
tan
eous
t
issue
c
an
be
s
t
udied
qua
li
tat
i
ve
ly
an
d
quant
i
tat
i
ve
ly
w
i
t
h
u
l
trasono
g
rap
hy
(
e36–e38
)
, compute
d
tomo
g
rap
hy
(
e39, e40
)
, or
ma
g
net
i
c resonance
i
ma
gi
n
g
(
e41, e42
).
Structura
l
an
d
funct
i
ona
l
eva
l
uat
i
on of t
h
e
l
y
mphatic s
y
stem with tests such as indirect
ly
mp
h
o
g
rap
hy
(
22, e43, e44
)
, f
l
uorescence m
i
cro
-
l
ymp
h
ograp
h
y
(
21, e45
)
, funct
i
ona
l
l
ymp
h
at
i
c
sc
i
nt
i
grap
h
y
(
22, e9, e19, e21, e23, e46
)
, an
d
magnet
i
c resonance
l
ymp
h
ang
i
ograp
h
y
(
e47
)
d
oes
not revea
l
an
y
spec
i
f
i
c or pat
h
o
g
nomon
i
c f
i
n
di
n
g
s of
lip
e
d
ema
.
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FIGURE 2
Hy
pot
h
eses a
b
out
p
at
h
o
g
enes
is
Note: the etiolo
gy
of li
p
edema has
not
y
et
b
een
conc
l
us
i
ve
ly
de
t
e
rm
i
n
ed.
The fi
g
ure depicts a
n
umber o
f
p
ossible
hy
pot
h
eses a
b
out
i
ts pat
h
o
g
enes
i
s.
hy
pox
ia
hypoxia
hi
neurogenic
inflammation
compression?
c
c
p
hematoma/
petechiae tissue fibrosis reduced mobility pain


h
o
rm
o
n
a
l
fac
t
o
r
s
g
enetic
f
actor
s
pro-in
f
lammatory
y
cytokines
al
tere
d
estrogen
pp
receptor pattern?
o
t
he
r
causes
hyperplasia/
hypertrophy of
adipocytes
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Other diagnostic methods, such as dual-energy
X-ray absorptiometry (DEXA) (e48) or bio-
impedance analysis (e49), are used only to answer
certain specific questions that may arise.
Treatment
Conservative management
Ever since lipedema was first described, the consen-
sus medical recommendation has been that patients
should be advised to accept the condition and modify
their mode of living accordingly. This remains true
today, despite the availability of treatments that can
bring relief (7). To prevent frustration, the physician
must inform the patient that the main goal of conser-
vative treatment is to relieve symptoms, not to
improve the appearance of the extremities
(17). No
causally directed treatment for lipedema has yet been
described.
The initiation, extent, and duration of treatment
should be agreed on with the patient, in consideration
of the individual degree of suffering caused by the
disease. The classic components of conservative man-
agement are the following:
manual lymph drainage, on a regular basis if
necessary
appropriate compression therapy with custom-
made, flat-knitted compressive clothing (compres-
sion classes II–III)
physiotherapy and exercise therapy
psychosocial therapy
dietary counseling and weight management
patient education on self-management.
Although conservative management brings about
only a small reduction in tissue volume—5–10% in
various studies, including one randomized, controlled
trial—it does lessen tenderness (pain on pressure) and
feelings of tightness in the limbs (10, 24, 28, 29, e17,
e50). A further goal of treatment is to prevent second-
ary complications, such as skin lesions in advanced
disease (11).
Reports that several weeks of inpatient treatment
can be beneficial (24, 28, 29, e17) do not imply any
long-term benefit from outpatient treatment. In fact,
there is hardly any evidence for the efficacy of con-
servative outpatient treatment “under the conditions
of normal, everyday life,” and the authors therefore
do not think conservative management can be
considered the gold standard of treatment. Nor does
any convincing evidence suggest that classic conser-
vative management prevents the progression of the
disease.
Patient education
Patients should be comprehensively informed about the
nature of the disease and the fact that it is chronic. They
should be told in a “non-ideological” way about all of the
treatment options and about the ways they themselves can
actively influence the disease. They should also be of-
fered the option of professional help in coping emotion-
ally with the disease. The pros and cons of confronting
the patient with the diagnosis are discussed in detail by
De la Torre et al. (25). As lipedema is a chronic, progres -
sive condition, the patient should be given adequate in-
formational material as soon as the diagnosis is made,
along with contact data for the relevant self-help organi -
zations. If necessary, the patient should also be educated
about
complex decongestive
therapy (30).
Weight control
Patients with lipedema are at increased risk of develop-
ing morbid obesity (25); conversely, overweight worsens
the manifestations of lipedema (11). The pathological
subcutaneous fat in lipedema is considered to be
diet-resistant (e51), but weight normalization can
TABLE
The differential diagnosis of lipedema (modified from [5])
+ to +++ present, (+) possible, Ø absent
Sex
Family history
Symmetry
Swollen feet
Increased fatty tissue
Disproportion
Edema
Tenderness
Hematoma tendency
Influence of diet
Lipedema
female
++
+++
Ø
+++
+++
depending on stage
Ø/+++
+++
+++
(+)
Lipohypertrophy
female/male
(+)
(+)
(+)
+++
+++
Ø
Ø
(+)
Ø
Obesity
female/male
+++
+++
(+)
+++
(+)
(+)
Ø
Ø
+++
Lymphedema
female/male
primary ++
secondary Ø
(+)
+++
(+)
+
+++
Ø
Ø
Ø
400
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prescription and referral as necessary:
dietary counseling
pain therapy
physiotherapy
psychotherapy
dermatology
The lymphologist/phlebologist/angiologist confirms the diagnosis
further (ancillary) diagnostic testing for differential diagnoses:
obesity
lymphedema
chronic venous insufficiency
comprehensive physical examination
objective description of morphology/Stemmer sign
body weight/height/BMI/waist-to-hip ratio/waist-to-height ratio
assessment of pain/general mobility/psychological manifestations
Stage I
smooth skin surface
evenly thickened, homogeneous
subcutis with small nodules
reversible edema (raising the limb)
circadian rhythmicity
Stages I–II
reimbursement must generally be decided upon by the
insurance carrier on an individual, case-by-case basis
submission of an application for reimbursement
Stage II
uneven, corrugated skin surface
nodular structures in thickened subcutis
reversible or irreversible edema
moderate to severe fibrosis
circadian rhythmicity
Complex decongestive therapy
sport and exercise therapy
skin care
regular manual lymph drainage (MLD)
provision of custom-made, flat-knitted compression wear of class II–III
i
n stage III: initial treatment with multilayered compression dressings before fitting of
compression wear
Stage III
BMI <35 kg/m²: reimbursable
BMI >35 kg/m²: accompanying guideline-based treatment of
obesity is required
BMI >40 kg/m²: the procedure should not be performed, the
treatment of obesity has priority
The patient presents with painful, disproportionate increase of limb size
FIGURE 3
Treatment
algorithm
interdisciplinary
treatment of pa-
tients with lipedema
in Germany
Staging
Basic measures
acceptance of the disease sport and exercise therapy skin care
patient education opportunity to take part in self-help groups weight management
lifestyle adaptation obesity treatment (interdisciplinary) as needed diet modification
Regular follow-up of the patient by the therapist, with the following goals:
alleviation of pain increased mobility and activity acceptance of the disease
reduction of edema weight control improved disease management
reduction of hematoma-forming tendency adequate skin care reduction of psychosocial symptoms
At least 6 months of ineffective conservative treatment
critical reevaluation of treatments and compliance to date by the lymphologist/phlebologist/angiologist
recommendation of and referral for surgery by the treating lymphologist/phlebologist/angiologist
preoperative psychological evaluation as indicated
Specialized center for lipedema surgery
(plastic surgery board certification or demonstration of qualification according to G-BA criteria)
determination of indication for lymph-vessel-sparing liposuction with wet technique
operation under tumescence local anesthesia (TLA) or general anesthesia
– use of power-assisted, i.e., vibration-assisted systems (PAL) or water-jet-assisted systems (WAL)
– if the amount of aspirated fat exceeds 3 L, postoperative observation for at least 12 hours
initiation of basic treatment measures
initiation of complex decongestive
therapy
differential diagnosis
Stage III
marked increase in size of extremities
disfiguring fat deposits
thickened, indurated subcutis with
macronodular changes
marked sclerosis and fibrosis
often, concomitant lymphedema
Additive measures
use of intermittent pneumatic
compression devices as needed
kinesiotaping as needed
The primary care physician makes a provisional diagnosis of lipedema
routine laboratory tests (creatinine, electrolytes, TSH, FBS, ASAT)
personal and family history, comprehensive physical examination
if lipedema is still suspected, refer to a specialized lymphologist, phlebologist, or
angiologist who is experienced in the treatment of lipedema
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nevertheless improve symptoms (e52). Obesity should be
treated if necessary, as recommended in current guide-
lines.
Dietary modification
There is no specific, evidence-based diet for patients
with lipedema, as no randomized and controlled trials
on this topic have been published. Current dietary
approaches generally rely on empirical data and are
designed to lower body weight through hypocaloric nu-
trition (e52), inhibition of systemic inflammation with
anti-oxidative and anti-inflammatory components
(e53–e55), and fluid removal (e54). Because many pa-
tients with lipedema also suffer from eating disorders
(12, 25), dietary modification should be carried out
under the care of a psychologist wherever possible (5).
Complex decongestive therapy
Manual lymph drainage (MLD), compression therapy,
exercise therapy, and skin care are the pillars of
complex
decongestive therapy
(1, 24, 28, e17).
As for the use of intermittent pneumatic compression
devices (IPC), 30 minutes of intermittent compression in
addition to 30 minutes of MLD was not found to have
any convincing, synergistic, beneficial effect on the
symptoms of lipedema in a randomized trial carried out
in the inpatient setting (28). When used in ambulatory
care, however, intermittent compression may lessen the
frequency of MLD and lessen both tissue tension and the
patient’s symptoms. Only mild pressure should be ap-
plied in the supplementary use of IPC to treat lipedema,
in order not to bring about the collapse of the superficial
lymphatic vessels, with ensuing tissue damage (28).
Exercise therapy should be tailored to the patient’s
individual needs and disease stage. In general, the
beneficial types of sport are those typified by
controlled, cyclical walking or running movements that
activate the calf-muscle pump but do not cause any
excessive tissue trauma (e32, e56). As the pressure
gradient under water helps lessen edema, swimming,
aqua-jogging, and aqua-gymnastics are recommended;
exercise under water also puts less stress on the joints
in overweight patients.
Patients who do not benefit from outpatient treat-
ment can be hospitalized in specialized lymphological
units for further care.
Surgery
If the symptoms persist and impair the patient’s quality
of life despite appropriate conservative management,
the potential indication for liposuction should be
evaluated (5). Its therapeutic benefit has not yet been
evaluated in any randomized, controlled trials.
Lymph-sparing liposuction
In five observational studies of liposuction for the lasting
reduction of fatty tissue, with follow-up for up to eight
years, significant relief of symptoms was found (31–35,
e57, e58). Surgery brought about improvement both in
subjective criteria (pain perception, feeling of tight-
ness, tendency to form hematomas, quality of life) and
in objectively measured variables, such as leg circum-
ference and the frequency and extent of conservative
treatment. Complication rates were low and
corresponded to the reported rates after liposuction in
larger cohorts of patients who did not have lipedema (1%
hemorrhage, 4% erysipelas, 4.5 % wound infection).
The available evidence in favor of liposuction for
lipedema still does not document its efficacy clearly
enough to justify its inclusion in the German health in-
surers’ catalog of regularly reimbursable procedures;
whether it can be reimbursed must be decided in each in-
dividual case (36). Its long-term therapeutic benefit is
now being investigated in a prospective, randomized
multicenter trial sponsored by the German Joint Federal
Committee (Gemeinsamer Bundesausschuss, G-BA)
(e59). For the time being, this treatment is only
selectively reimbursed by the statutory health-insurance
carriers after individual case assessment, and it is thus
mainly available to patients who have adequate financial
resources to pay for it themselves.
Liposuction is, however, reimbursable as of January
2020 and until 31 December 2024 for patients with stage
III lipedema who meet certain further conditions. Six
months of prior conservative treatment are a prerequisite,
and reimbursement further depends, to a great extent, on
the patient’s BMI (Figure 3) (e60). Yet the BMI is of only
limited utility for deciding on the indication for surgery,
particularly in stage III patients who may have advanced
fibrotic tissue changes in the involved areas of sub -
cutaneous fat (e61). The patient self-help organizations
have complained that these patients are receiving inad-
equate care (e62).
Key messages
It is not yet clear whether lipedema should be best defined as a primary lipodys-
trophy (pathological adipogenesis) or as a primary microangiopathy of small blood
and lymphatic vessels. No specific biomarker is yet available.
Its estimated prevalence in the overall female population is 10%. The costs engen-
dered by the treatment of lipedema are difficult to calculate, as it remains unclear
what percentage of the affected persons need to be treated.
The diseases is diagnosed on clinical grounds, on the basis of its main manifes-
tations: pain, a feeling of tension, and increased tendency to form hematomas in the
affected areas. Ancillary diagnostic testing is recommended mainly to rule out com-
peting diagnoses.
Treatment is symptomatically oriented and based on complex decongestive therapy.
Conservative treatment can lessen the painful feeling of tension and pressure, the
tendency to form hematomas, and the sequelae of the disease.
If conservative treatment is unsuccessful, lymph-sparing liposuction can be
considered as a means of permanently reducing fatty tissue mass. Only low-level
evidence supports this procedure to date; the long-term outcome of treatment is to
be studied in a prospective interventional trial commissioned by the German Joint
Federal Committee (Gemeinsamer Bundesausschuss, G-BA).
402
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Patients in any stage of the disease whose weight exceeds 120 kg
or whose BMI exceeds 32 kg/m² should be treated for obesity in
conformity with current guidelines before the potential indication
for liposuction is considered (5, 37). Liposuction should be per-
formed with wet technique to spare the lymphatic vessels (33,
38–40, e63–e65). Patients from whom more than 3 L of pure adi-
pose tissue have been aspirated should remain under qualified post-
operative care for at least 12 hours after the procedure. The surgical
techniques described in the literature differ from one another in
many ways, but it is generally recommended that liposuction should
be performed in multiple sittings, rather than a single sitting (40).
Surgical debulking
In highly advanced stages of the disease, with accompanying
lymphedema, the involved tissue is so fibrotic that liposuction
cannot adequately reduce its volume. In such cases, open surgical
debulking (dermato-fibro-lipectomy) may be indicated (e66).
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Corresponding author
Dr. med. Mojtaba Ghods
Klinik für Plastische, Ästhetische und Rekonstruktive Mikrochirurgie/Handchirurgie
Klinikum Ernst von Bergmann, Charlottenstr. 72, D-14467 Potsdam, Germany
mghods@klinikumevb.de
Cite this as:
Kruppa P, Georgiou I, Biermann N, Prantl L, Klein-Weigel P, Ghods M:
Lipedema—pathogenesis, diagnosis and treatment options.
Dtsch Arztebl Int 2020; 117: 396–403. DOI: 10.3238/arztebl.2020.0396
Supplementary material
For eReferences please refer to:
www.aerzteblatt-international.de/ref2220
Conflict of interest statement
Dr. Klein-Weigel has served as a paid medicolegal expert for the Berlin Social Court
(Sozialgericht Berlin) in cases related to the topic of this article.
The other authors state that they have no conflict of interest.
Manuscript submitted on 4 December 2019, revised version accepted on 26 March
2020.
Translated from the original German by Ethan Taub, M.D.
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Supplementary material
Supplementary material to:
Lipedema—Pathogenesis, Diagnosis, and Treatment Options
by Philipp Kruppa, Iakovos Georgiou, Niklas Biermann, Lukas Prantl, Peter Klein-Weigel, and Mojtaba Ghods
Dtsch Arztebl Int 2020; 117: 396–403. DOI: 10.3238/arztebl.2020.0396
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Supplementary material
Questions for the article in issue 22–23/2020:
Lipedema – Pathogenesis, Diagnosis and Treatment Options
CME credit for this unit can be obtained via cme.aerzteblatt.de until 31. 5. 2021.
Only one answer is possible per question. Please select the answer that is most appropriate.
Question 1
What is the estimated prevalence of lipedema
in the female population?
a) 3%
b) 6%
c) 10%
d) 12%
e) 15%
Question 2
Which of the following is a risk factor associ-
ated with the development of lipedema?
a) a carbohydrate-rich diet
b) smoking
c) lack of exercise
d) prolonged standing
e) positive family history
Question 3
Which of the following is a typical manifes-
tation of lipedema?
a) a feeling of tension in the affected limb
b) hypertension
c) body-mass index >28
d) ankle-to-arm index <0.75
e) ecessively warm skin
Question 4
Which of the following features is character-
istic of lipedema?
a) improvement of symptoms over the course of
the day
b) sparing of the hands and feet
c) insensitivity to pressure
d) knee arthritis
e) mild redness of the skin
Question 5
Which of the following is a feature of stage I
lipedema?
a) positive Stemmer sign
b) irreversible edema
c) subcuticular induration
d) a smooth skin surface
e) concomitant lymphedema
Question 6
What disease should be ruled out by laboratory testing in the
differential diagnosis of lipedema?
a) PCO syndrome
b) gout
c) hypothyroidism
d) lysosoma storage disease
e) celiac disease
Question 7
Which of the following is a central element of conservative
treatment?
a) Kneipp baths
b) manual lymph drainage
c) hypercaloric diet
d) restricted fluid intake
e) vibration training
Question 8
Which of the following is a typical finding in stage III
lymphedema?
a) small subuticular nodules
b) moderate increase in size
c) skin eruption on the calves
d) moderate fibrosis
e) disfiguring fat deposits/tissue overhangs
Question 9
What type of sport is especially recommended for persons with li-
pedema?
a) aqua-gymnastics
b) power sports
c) badminton
d) rock climbing
e) beach volleyball
Question 10
What surgical procedure is used to treat severe lipedema?
a) lymphovenous anastomosis
b) Roux-en-Y gastric bypass
c) liposuction
d) femoropopliteal bypass
e) debridement
cme plus
... Consequently, available data on its prevalence are sparse and divergent. However, previous studies have revealed that lipoedema may affect approximately 10% of the female population [4][5][6]. ...
... Moreover, lipoedema fat differs from typical fat in its structure and metabolism [9], with the loose connective tissue involved in lipoedema being characterized by hypertrophic adipocytes, fibrosis, and inflammatory angiogenesis [10]. Currently, no specific biomarkers for diagnosing lipoedema are available, with it being confirmed solely through the use of a thorough medical history-taking and a comprehensive physical examination that includes both inspection and palpation [6]. ...
... Present treatment focus on symptom relief, with management options including patient education, psychosocial support, promoting self-care, and the encouraging of a healthy lifestyle. More conservative treatment includes manual lymphatic drainage and compression therapy to lessen any pain and swelling [6]. Liposuction is one surgical option that has been shown to reduce bruising, immobility, and pain in a way that then improves quality of life. ...
Article
Full-text available
Background Lipoedema is a chronic disease in adipose tissue that almost exclusively affects women during periods of hormonal alterations. Its main symptoms include an abnormal accumulation of subcutaneous fat in the buttock, hips, and legs, which is associated with pain, swelling, and easy bruising. Herein, a grading in three stages is used to determine disease progression. Problematically, lipoedema manifestations are often confused with lifestyle-induced obesity, which is why the various health problems among affected women often remain unrecognized. Overall, research on lipoedema is scarce. As such, this study examined the health, health-related quality of life (HRQOL), and sense of coherence (SOC) among women with lipoedema. Methods We conducted a national cross-sectional study using an online survey assessing sociodemographic data, lipoedema characteristics, symptom severity, comorbidities, HRQOL (RAND-36), and SOC (SOC-13). In total, 245 women with lipoedema, recruited from all Lipoedema Association groups in Sweden, participated. Data were compiled with descriptive statistics, and mean differences between groups were analysed by using parametric and non-parametric tests. Results Moderate and severe leg heaviness, pain, numbness, cold skin, feeling cold, easy bruising, and sleep problems were found to occur in all lipoedema stages. Moreover, almost all participants reported having comorbidities. Worse physical health and most substantial limitations in daily life were reported among women with the most progressive lipoedema (i.e., stage 3). Social and emotional functioning and SOC were found to be, on the other hand, primarily related to respondents’ sociodemographic data and their ages at lipoedema onset. Even though approximately 70% of the women had experienced lipoedema onset before age 30, only three (1.6%) had been diagnosed by a healthcare professional before that age. Conclusion Having lipoedema is associated with several health problems and a lower HRQOL. In addition, the extent of delay in diagnosis within this sample indicates that many women with lipoedema are often underdiagnosed and are left without support from healthcare. These findings call for the need for greater attention on lipoedema. Moreover, further studies on how women with lipoedema manage their health and symptoms, as well as on their experiences of healthcare services and lipoedema treatments, are needed.
... Das klinische Erscheinungsbild ist sehr facettenreich. Trotz zunehmender Forschungstätigkeit liegen bislang nur wenige objektivierbare Befunde und gesicherte Erkenntnisse zur Pathophysiologie vor [2, 16,17,20]. Die Dermatologie 1 Abb. 1 8 Exemplarische Darstellung von Oberflächenvergrößerungen durch Kanal-und Hohlraumbildung am Beispiel eines zur Lappenplastik nach Avelar vorbereiteten leer gesaugten, "entfetteten" Gewebes.Das bindegewebige Gerüst mit residualemFettgewebeanderHaut ist gut erkennbar.Solche Einblicke in den subkutanen Raum sind bei der als Saugung durchgeführten Resektion "Lymphologische Liposculptur" bei LiDo natürlich nicht möglich Die Magnetresonanz-Lymphangiographie (MRL) bestätigt bei LiDo in der Regel ein orthologes Lymphgefäßsystem. Quantitative Messungen der indirekten Funktionslymphszintigraphie des Lymphflusses konnten jedoch eine alterskorrelierte Hochvolumentransportinsuffizienz nachweisen [4-7, 21, 22, 24]. ...
... Kruppa et al. report that the liposuction procedure including fat removal for esthetic reasons has a complication rate of 9.5%. Wound infections with 4.5% and the formation of erysipelas with 4% are clearly in the foreground [20]. ...
... Kenntnisse und Schulungen über die Durchführung des Tumeszenzverfahrens seien von entscheidender Bedeutung, um optimale Sicherheit zu gewährleisten[25,26].Kruppa et al. geben 2020 in ihrer Übersichtsarbeit im Deutschen Ärzteblatt eine Komplikationsrate von ca. 9,5 % für alle -sowohl kosmetisch oder medizinischindizierten Liposuktionen an[20]. Dabei entfallen auf Blutungskomplikation 1 %, auf Wundinfektionen 4,5 % und weiter 4 % auf die Entwicklung eines Erysipels.Kanapathy et al. berichten 2021 in ihrer Metaanalyse über 3583 Patienten. ...
Article
Full-text available
Background There are both conservative and surgical treatment options for lipohyperplasia dolorosa (LiDo). A procedure that has been established since 1997 is the surgical treatment through lymphological liposculpture according to Cornely™.AimAfter extensive suctioning of the extremities, an extensive subcutaneous wound cavity with a trabecular connective tissue scaffold remains. Nevertheless, surgery-related complications are rare. Postoperative management and administration of antibiotics and antithrombotics are reviewed. The therapies for complications are presented in detail.Materials and methodsRetrospectively, the frequencies of adverse events in 1400 LiDo surgeries in 2020 were evaluated. The mean age of the patients was 47.81 years (range 16–78 years). Symmetrically, 504 outer legs (outer half of the limb [BA]), 504 inner legs (inner half of the limb [BI]), and 392 arms [A] were surgically treated.ResultsRelevant adverse events rarely occurred: infections (1.79%), seromas (0.79%), erysipelas (0.28%), necrosis (0.14%) and deep vein thrombosis (0.07).DiscussionWe were able to reduce the rate of postoperative complications to 3.07% in the Lymphological Liposculpture™ regime for the surgical treatment of LiDo. In their meta-analysis on liposuction, Kanapathy et al. reported an overall incidence of major surgical complications of 3.48%. The overall incidence of minor surgical complications was 11.62%, with seroma (5.51%) being the most common minor complication [26]. Kruppa et al. report that the liposuction procedure including fat removal for esthetic reasons has a complication rate of 9.5%. Wound infections with 4.5% and the formation of erysipelas with 4% are clearly in the foreground [20].
... A chronic increase in leg circumference-either uni-or bilateral-can be caused by a range of pathological conditions: apart from venous disease and obesity, lymphedema and lipedema are recognized as major causes of increased extremity circumference [1,2]. Lymphedema is characterized by soft tissue swelling caused by impaired lymphatic drainage leading to an accumulation of interstitial fluid. ...
... Additionally, lymphedema may develop in the affected patients [3,4]. The pathophysiology of lipedema is so far poorly understood [1,4,5]. In patients suffering from either lipedema or lymphedema, both mechanic impairments-that can cause secondary arthritis or interfere with normal walking-and emotional disorders-resulting from an appearance that does not conform to today's ideal of beautycan result in impaired quality of life [1]. ...
... The pathophysiology of lipedema is so far poorly understood [1,4,5]. In patients suffering from either lipedema or lymphedema, both mechanic impairments-that can cause secondary arthritis or interfere with normal walking-and emotional disorders-resulting from an appearance that does not conform to today's ideal of beautycan result in impaired quality of life [1]. ...
Article
Full-text available
Objectives To contribute to a more in-depth assessment of shape, volume, and asymmetry of the lower extremities in patients with lipedema or lymphedema utilizing volume information from MR imaging. Methods A deep learning (DL) pipeline was developed including (i) localization of anatomical landmarks (femoral heads, symphysis, knees, ankles) and (ii) quality-assured tissue segmentation to enable standardized quantification of subcutaneous (SCT) and subfascial tissue (SFT) volumes. The retrospectively derived dataset for method development consisted of 45 patients (42 female, 44.2 ± 14.8 years) who underwent clinical 3D DIXON MR-lymphangiography examinations of the lower extremities. Five-fold cross-validated training was performed on 16,573 axial slices from 40 patients and testing on 2187 axial slices from 5 patients. For landmark detection, two EfficientNet-B1 convolutional neural networks (CNNs) were applied in an ensemble. One determines the relative foot-head position of each axial slice with respect to the landmarks by regression, the other identifies all landmarks in coronal reconstructed slices using keypoint detection. After landmark detection, segmentation of SCT and SFT was performed on axial slices employing a U-Net architecture with EfficientNet-B1 as encoder. Finally, the determined landmarks were used for standardized analysis and visualization of tissue volume, distribution, and symmetry, independent of leg length, slice thickness, and patient position. Results Excellent test results were observed for landmark detection (z-deviation = 4.5 ± 3.1 mm) and segmentation (Dice score: SCT = 0.989 ± 0.004, SFT = 0.994 ± 0.002). Conclusions The proposed DL pipeline allows for standardized analysis of tissue volume and distribution and may assist in diagnosis of lipedema and lymphedema or monitoring of conservative and surgical treatments. Key Points • Efficient use of volume information that MRI inherently provides can be extracted automatically by deep learning and enables in-depth assessment of tissue volumes in lipedema and lymphedema . • The deep learning pipeline consisting of body part regression, keypoint detection, and quality-assured tissue segmentation provides detailed information about the volume, distribution, and asymmetry of lower extremity tissues, independent of leg length, slice thickness, and patient position .
... However, conservative treatment using weight reduction and compression bandaging is effective in early stages and surgical interventions by liposuction is effective in advanced stages. 1,2 In the report at hand, we report a rare presentation of lipedema in a male patient. ...
... Furthermore, lipedema is classified into four stages by its severity; Stage 1: the skin surface is normal, and the subcutaneous fatty tissue has a soft consistency but multiple small nodules can be palpated; stage 2: the skin surface becomes uneven and harder due to the increasing nodular structure (big nodules) of the subcutaneous fatty tissue (liposclerosis); stage 3: hardening and thickening of the subcutaneous with lobular deformation; stage 4: lipedema with lymphedema, called lipolymphedema. 1,4,5 Lymphedema is accumulation of protein-rich fluid in interstitial tissue due to lymph drainage failure. On the contrary of lipedema, lymphedema may be asymmetrical, unaccompanied by easy bruising or pain or tenderness. ...
Article
Full-text available
Lipedema is a disorder of abnormal subcutaneous fat deposition which almost exclusively occured in women. It is an unusual case that happens in male patients. Lipedema is often misdiagnosed to obesity and lymphedema. In case at hand, a 39-year-old obese male (body mass index of 54.3 kg/m2) presented bilateral non-pitting edema from buttocks to knees, palpable fat tissue nodules, pain at pressure, positive cuff sign, negative Stemmer-Kaposi sign, hyperpigmentation and thickened skin along the calves, and minimal responds to compression therapy. Average blood pressure was 145/90 mmHg. Laboratory studies were unremarkable, except leukocytosis and increased erythrocyte sedimentation rate which might be related to obesity-associated leukocytosis. Diagnosis of type III lipedema subsequent with lymphedema, grade III obesity, and mild hypertension was made. The patient subsequently reported an improvement of the complaints after receiving nonsteroidal anti-inflammatory drug, proton pump inhibitors, and antihypertensive. Weight loss was encouraged as initial steps to reduce aggravating risks of obesity. This case underlines that lipedema needs to be considered as a differential diagnosis in male patients.
... The cause of lipoedema remains elusive. It has been hypothesized that it is a form of obesity, a form of lipodystrophy/fat disorder, a hormonal disorder, a form of connective tissue disorder given the association with hypermobility and finally a lymphatic disorder given the frequent progression to lymphoedema [15,39,40]. Here we report the first comprehensive collection of lipoedema cases recruited from a white British population, with the aim of conducting a GWAS to explore a possible polygenic architecture. ...
Article
Full-text available
Lipoedema is a chronic adipose tissue disorder mainly affecting women, causing excess subcutaneous fat deposition on the lower limbs with pain and tenderness. There is often a family history of lipoedema, suggesting a genetic origin, but the contribution of genetics is currently unclear. A tightly phenotyped cohort of 200 lipoedema patients was recruited from two UK specialist clinics. Objective clinical characteristics and measures of quality of life data were obtained. In an attempt to understand the genetic architecture of the disease better, genome-wide single nucleotide polymorphism (SNP) genotype data were obtained, and a genome wide association study (GWAS) was performed on 130 of the recruits. The analysis revealed genetic loci suggestively associated with the lipoedema phenotype, with further support provided by an independent cohort taken from the 100,000 Genomes Project. The top SNP rs1409440 (ORmeta ≈ 2.01, Pmeta ≈ 4 x 10-6) is located upstream of LHFPL6, which is thought to be involved with lipoma formation. Exactly how this relates to lipoedema is not yet understood. This first GWAS of a UK lipoedema cohort has identified genetic regions of suggestive association with the disease. Further replication of these findings in different populations is warranted.
... 22 Polygenic alteration in the distribution of alpha-and beta-estrogen receptors (ER) (decreased ER-alpha expression and increased ER-beta expression) in white adipose tissue from areas involved in lipedema may also play a role in pathogenesis of this disease. 23 However, to date, the importance of estrogen in the pathogenesis of lipedema has not been fully elucidated. ...
Article
Full-text available
Introduction: Lipedema is a disorder characterized by an excessive accumulation of subcutaneous body fat, mainly bilateral and symmetrical accumulation of fat deposits, particularly in the lower extremities excluding feet. Pain (spontaneous or with palpation) and increased capillary fragility with bruising are also part of clinical presentation. It is estimated to occur in approximately 11.0% of women worldwide. Management of obesity among patients with lipedema is a key component in its treatment. Purpose: The aim of this study was to compare effectiveness of two diets: low-carbohydrate-high-fat diet (LCHF) and medium-fat-medium-carbohydrate diet (MFMC) in body weight, body fat and limb circumference reduction in patients with lipedema. Material and methods: The studied women (n = 91) were divided into 2 groups and submitted to 1 of the 2 diets for 16 weeks. Anthropometric measurements such as body height [cm], body weight [kg], body fat percentage [%], body fat [kg], lean body mass [kg], and visceral fat level were collected at the beginning and end of the study. Results: We have not found any significant differences in anthropometric measurements at the baseline between groups. Body weight and all anthropometric parameters decreased significantly in both groups after 16 weeks of diets, excluding the circumference above the right ankle for the MFMC diet which did not change. The LCHF diet contributed to reduction of body weight (-8.2 ± 4.1 kg vs -2.1 ± 1.0 kg; p < 0.0001), body fat (-6.4 ± 3.2 kg vs 1.6 ± 0.8 kg; p < 0.0001), waist (-7.8 ± 3.9 cm vs -2.3 ± 1.1 cm; p < 0.0001), hips (-7.4 ± 3.7 cm vs -2.5 ± 1.3 cm; p < 0.0001), thighs and calves' circumferences compared with the MFMC diet. We observed reduction of pain in the extremities and mobility improvement in LCHF group (data not shown). Conclusion: The LCHF diet was more effective than MFMC in body weight, body fat and lower limb circumferences reduction.
... Since the knowledge of lipoedema pathophysiology is not complete, the treatment remains a challenge [3,25,32]. Moreover, an additional difficulty is the late diagnosis and delayed introduction of the therapy. ...
Article
Full-text available
(1) Background: Due to insufficient knowledge of lipoedema, the treatment of this disease is undoubtedly challenging. However, more and more researchers attempt to incorporate the most effective lipoedema treatment methods. When assessing a new therapeutic method, choosing correct, objective tools to measure the therapeutic outcome is very important. This article aims to present possible instruments that may be used in the evaluation of therapeutic effects in patients with lipoedema. (2) Methods: The data on therapeutic outcome measurements in lipoedema were selected in February 2022, using the Medical University of Gdansk Main Library multi-search engine. (3) Results: In total, 10 papers on this topic have been identified according to inclusion criteria. The tools evaluating the therapeutic outcomes used in the selected studies were: volume and circumference measurement, body mass index, waist-to-hip ratio, ultrasonography and various scales measuring the quality of life, the level of experiencing pain, the severity of symptoms, functional lower extremity scales, and a 6 min walk test. (4) Conclusion: The tools currently used in evaluating the effectiveness of conservative treatment in women with lipoedema are: volume and circumference measurement, waist-to-hip ratio, body fat percentage, ultrasonography, VAS scale, quality of life scales (SF-36, RAND-36), symptom severity questionnaire (QuASiL), Lower Extremity Functional Scale and 6 min walk. Choosing a proper tool to measure the treatment outcome is essential to objectively rate the effectiveness of therapeutic method.
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Objective: Lipedema is an inflammatory subcutaneous adipose tissue disease that develops in women and may progress to lipolymphedema, a condition similar to lymphedema, in which lymphatic dysfunction results in irresolvable edema. Because it has been shown that dilated lymphatic vessels, impaired pumping, and dermal backflow are associated with presymptomatic, cancer-acquired lymphedema, this study sought to understand whether these abnormal lymphatic characteristics also characterize early stages of lipedema prior to lipolymphedema development. Methods: In a pilot study of 20 individuals with Stage I or II lipedema who had not progressed to lipolymphedema, lymphatic vessel anatomy and function in upper and lower extremities were assessed by near-infrared fluorescence lymphatic imaging and compared with that of a control population of similar age and BMI. Results: These studies showed that, although lower extremity lymphatic vessels were dilated and showed intravascular pooling, the propulsion rates significantly exceeded those of control individuals. Upper extremity lymphatics of individuals with lipedema were unremarkable. In contrast to individuals with lymphedema, individuals with Stage I and II lipedema did not exhibit dermal backflow. Conclusions: These results suggest that, despite the confusion in the diagnoses between lymphedema and lipedema, their etiologies differ, with lipedema associated with lymphatic vessel dilation but not lymphatic dysfunction.
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Lipedema is a painful loose connective tissue disorder characterized by a bilaterally symmetrical fat deposition in the lower extremities. The goal of this study was to characterize the adipose-derived stem cells (ASCs) of healthy and lipedema patients by the expression of stemness markers and the adipogenic and osteogenic differentiation potential. Forty patients, 20 healthy and 20 with lipedema, participated in this study. The stromal vascular fraction (SVF) was obtained from subcutaneous thigh (SVF-T) and abdomen (SVF-A) fat and plated for ASCs characterization. The data show a similar expression of mesenchymal markers, a significant increase in colonies (p < 0.05) and no change in the proliferation rate in ASCs isolated from the SVF-T or SVF-A of lipedema patients compared with healthy patients. The leptin gene expression was significantly increased in lipedema adipocytes differentiated from ASCs-T (p = 0.04) and the PPAR-γ expression was significantly increased in lipedema adipocytes differentiated from ASCs-A (p = 0.03) compared to the corresponding cells from healthy patients. No significant changes in the expression of genes associated with inflammation were detected in lipedema ASCs or differentiated adipocytes. These results suggest that lipedema ASCs isolated from SVF-T and SVF-A have a higher adipogenic differentiation potential compared to healthy ASCs.
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Background and aim: Lipedema is a common painful SAT disorder characterized by enlargement of fat primarily in the legs of women. Case reports of lipedema tissue samples demonstrate fluid and fibrosis in the interstitial matrix, increased macrophages, and adipocyte hypertrophy. The aims of this project are to investigate blood vasculature, immune cells, and structure of lipedema tissue in a cohort of women. Methods: Forty-nine participants, 19 controls and 30 with lipedema, were divided into groups based on body mass index (BMI): Non-Obese (BMI 20 to <30 kg/m2) and Obese (BMI 30 to <40 kg/m2). Histological sections from thigh skin and fat were stained with H&E. Adipocyte area and blood vessel size and number were quantified using ImageJ software. Markers for macrophages (CD68), mast cells (CD117), T cells (CD3), endothelial cells (CD31), blood (SMA), and lymphatic (D2-40 and Lyve-1) vessels were investigated by IHC and IF. Results: Non-Obese Lipedema adipocyte area was larger than Non-Obese Controls (p=0.005) and similar to Obese Lipedema and Obese Controls. Macrophage numbers were significantly increased in Non-Obese (p < 0.005) and Obese (p < 0.05) Lipedema skin and fat compared to Control groups. No differences in T lymphocytes or mast cells were observed when comparing Lipedema to Control in both groups. SMA staining revealed increased dermal vessels in Non-Obese Lipedema patients (p < 0.001) compared to Non-Obese Controls. Lyve-1 and D2-40 staining showed a significant increase in lymphatic vessel area but not in number or perimeter in Obese Lipedema participants (p < 0.05) compared to Controls (Obese and Non-Obese). Areas of angiogenesis were found in the fat in 30% of lipedema participants but not controls. Conclusion: Hypertrophic adipocytes, increased numbers of macrophages and blood vessels, and dilation of capillaries in thigh tissue of non-obese women with lipedema suggest inflammation, and angiogenesis occurs independent of obesity and demonstrates a role of altered vasculature in the manifestation of the disease.
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Background Although lipedema is often clinically distinguished from lymphedema, there is considerable overlap between the two entities. The purpose of this study was to evaluate lymphoscintigraphic findings in patients with lipedema to better characterize lymphatic flow in this patient population. Methods Patients with lipedema receiving lymphoscintigraphy between January 2015 and October 2017 were included. Patient demographics, clinical characteristics, and lymphoscintigraphic findings were extracted. Klienhan's transport index (TI) was utilized to assess lymphatic flow in patient's lower extremities (LEs).Scores ranged from 0 to 45, with values > 10 denoting pathologic lymphatic transport. Results A total of 19 total patients with lipedema underwent lymphoscintigraphic evaluation. Mean age was 54.8 years and mean body mass index was 35.9 kg/m2. Severity of lipedema was classified as stage 1 in five patients (26.3%), stage 2 in four patients (21.1%), stage 3 in four patients (21.1%), and stage 4 in six patients (31.6%). The mean TI for all extremities was 12.5; 24 (63.2%) LEs had a pathologic TI, including 7 LEs with stage 1 (29.2%), 3 LEs with stage 2 (12.5%), 6 LEs with stage 3 (25.0%), and 8 LEs with stage 4 lipedema (33.3%). The mean TI was significantly greater for extremities with severe (stage 3/4) lipedema than those with mild or moderate (stage 1/2) lipedema (15.1 vs. 9.7, p = 0.049). Mean difference in TI scores between each LE for individual patients was 6.43 (standard deviation +7.96). Conclusion Our results suggest that patients with lipedema have impaired lymphatic transport, and more severe lipedema may be associated with greater lymphatic transport abnormalities.
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Background: Lipedema and Dercum's disease (DD) are incompletely characterized adipose tissue diseases, and objective measures of disease profiles are needed to aid in differential diagnosis. We hypothesized that fluid properties, quantified as tissue water bioimpedance in the upper and lower extremities, differ regionally between these conditions. Methods and Results: Women (cumulative n = 156) with lipedema (n = 110), DD (n = 25), or without an adipose disease matched for age and body mass index to early stage lipedema patients (i.e., controls n = 21) were enrolled. Bioimpedance spectroscopy (BIS) was applied to measure impedance values in the arms and legs, indicative of extracellular water levels. Impedance values were recorded for each limb, as well as the leg-to-arm impedance ratio. Regression models were applied to evaluate hypothesized relationships between impedance and clinical indicators of disease (significance criteria: two-sided p < 0.05). Higher extracellular water was indicated (i) in the legs of patients with higher compared with lower stages of lipedema (p = 0.03), (ii) in the leg-to-arm impedance ratio in patients with lipedema compared with patients with DD (p ≤ 0.001), and (iii) in the leg-to-arm impedance ratio in patients with stage 1 lipedema compared with controls (p ≤ 0.01). Conclusion: BIS is a noninvasive portable modality to assess tissue water, and this device is available in both specialized and nonspecialized centers. These findings support that regional bioimpedance measures may help to distinguish lipedema from DD, as well as to identify early stages of lipedema.
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Background: Lipedema is characterized by localized accumulation of fat in the extremities, which is typically unresponsive to dietary regimes or physical activity. Although the disease is well described and has a high incidence, little is known regarding the molecular and cellular mechanisms underlying its pathogenesis. The aim of this study was to investigate the pathophysiology of lipedema adipose cells in vitro. Methods: Adipose stem cells (ADSCs) were isolated from lipoaspirates derived from lipedema and non-lipedema patients undergoing tumescent liposuction. In vitro differentiation studies were performed for up to 14 days using adipogenic or regular culture medium. Supernatants and cell lysates were tested for adiponectin, leptin, insulin-like growth factor-1 (IGF-1), aromatase (CYP19A1), and interleukin-8 (IL-8) contents at days 7 and 14, using enzyme-linked immunosorbent assays (ELISAs). Adipogenesis was evaluated by visualizing and measuring cytoplasmic lipid accumulation. Results: Lipedema ADSCs showed impeded adipogenesis already at early stages of in vitro differentiation. Concomitantly with a strongly reduced cytoplasmic lipid accumulation, significantly lower amounts of adiponectin and leptin were detectable in supernatants from lipedema ADSCs and adipocytes compared to control cells. Additionally, lipedema and non-lipedema cells differed in their expression of IGF-1, aromatase (CYP19A1), IL-8 and in their proliferative activity. Conclusion: Our findings indicate that in vitro adipogenesis of lipedema ADSCs is severely hampered in comparison to non-lipedema ADSCs. Lipedema adipose cells not only differ in their lipid storage capacity but also in their adipokine expression pattern. This might serve as a valuable marker for diagnosis of lipedema, probably from an early stage on.
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Purpose: Lipedema is a common and painful fat disorder affecting the limbs of women leading to obesity; the fat cannot be lost by diet or exercise, called persistent fat. Lipedema is classified by stage. Stage 1: normal skin surface with enlarged hypodermis. Stage 2: uneven skin with indentations in fat and larger hypodermal masses. Stage 3: large extrusions of tissue drastically inhibit mobility. Lymphedema occurs at any stage, especially Stage 3, called lipo-lymphedema. Reduction of lipedema fat is achieved effectively only by removal of fat by lymph-sparing liposuction. Liposuction reduction of fat on the lower body improves mobility. Data from Europe demonstrate quality of life improves for women with lipedema after liposuction. There are no data on liposuction and lipedema in the United States (US). The purpose of this study is to determine how women with lipedema in the United States benefit or not from liposuction. Materials and Methods: Non-validated 183-item online questionnaire answered by women after undergoing liposuction for lipedema in the US. Results: One-hundred and eighty-nine women with lipedema consented and answered the questionnaire; the majority (51%) Stage 2. Women with Stage 1 and 2 had on average two procedures; women with Stage 3 or lipo-lymphedema had, on average, one additional procedure. Improvement in ambulation after liposuction was highest in patients with lipedema Stage 3 at 90.9% and lowest in Stage 1 at 71%, where ambulation pre-surgery tends to be less affected. Weight loss occurred in all groups 2-4 months after liposuction. Women from all stages reported growth of fat post-procedure outside areas of liposuction, highest in Stage 1 (62%) and lipo-lymphedema (70%). Growth of fat in liposuction areas occurred in ~1/2 of participants across all groups, most often in women in lipedema Stage 4 (71%). The complication of lymphedema after liposuction was not reported in Stage 1 but in two women with Stage 2, five with Stage 3, and three with lipo-lipedema. Improved quality of life after liposuction was significant in Stages 1-3 ranging from 81% improvement for Stage 1 to 86% for Stage 3, but only 70% for women with lipo-lymphedema. The perceived success of the procedure decreased with stage. Conclusion: Women with lipedema noticed improved ambulation after liposuction, likely due to removal of excess adipose tissue from the legs. Fat growth after liposuction was reported consistent with published data. Improvement in quality of life after liposuction agrees with European data, and greater perceived benefit in earlier stages emphasizes the importance of early detection of lipedema and earlier intervention with liposuction. Prospective studies are needed to assess quality of life, fat growth, weight loss and ambulation after liposuction in women with lipedema in the US.
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Zusammenfassung Das Lipödem war bis vor einigen Jahren ein eher unbekanntes Erkrankungsbild. In den letzten 5 Jahren gewann die Lipödemerkrankung immer mehr Bekanntheit, insbesondere durch die mediale Aufmerksamkeit. Neben der konservativen Behandlung durch eine komplex-konservative Entstauungstherapie gibt es immer mehr Studien, die das Potenzial eines Liposuktionsverfahrens zur erfolgreichen Therapie des Lipödems nahelegen. Infolgedessen werden Betroffene dieser Erkrankung zunehmend bei Plastischen Chirurgen vorstellig mit dem Wunsch nach Korrektur und Schmerzlinderung. Da die Liposuktion in Deutschland allerdings seitens des gemeinsamen Bundesausschusses (G-BA) noch nicht als Behandlungsalternative zur Therapie von Lipödemerkrankten positiv bewertet worden ist, ist eine Leistungserbringung zu Lasten der GKV immer noch eine Einzelfallentscheidung, welche gesondert von den Patientinnen in Zusammenarbeit mit dem behandelnden Plastischen Chirurgen beantragt werden muss. Im vorliegenden Übersichtsartikel legen wir die aktuelle Rechtslage dar und geben Hilfestellung bei der Beantragung von Kostenübernahmen.
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