Lipedema-Pathogenesis, Diagnosis, and Treatment Options

Abstract

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.

Full text

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
396
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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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MEDICINE
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
)
.
Th
e s
y
mptoms an
d
su
bj
ect
i
ve
d
e
g
ree of suffer
i
n
g
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
i
n
d
ex of
d
a
ily
act
i
v
i
t
y
s
h
ou
ld
a
l
so
b
e
d
ocumente
d
,
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
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MEDICINE
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).
18.
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tients with lymphedema and lipedema. Hautarzt 2018; 69: 471–7.
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Baumgartner A, Hueppe M, Schmeller W: Long-term benefit of liposuction in patients with
lipoedema: a follow-up study after an average of 4 and 8 years. Br J Dermatol 2016; 174:
1061–7.
32.
Schmeller W, Hüppe M, Meier-Vollrath I: Tumescent liposuction in lipoedema yields good
long-term results. Br J Dermatol 2012; 166: 161–8.
33.
Dadras M, Mallinger P, Corterier C, Theodosiadi S, Ghods M: Liposuction in the treatment
of lipedema: alongitudinal study. Arch Plast Surg 2017; 44: 324–31.
34.
Rapprich S, Dingler A, Podda M: Liposuction is an effective treatment for lipedema-results
of a study with 25 patients. J Dtsch Dermatol Ges 2011; 9: 33–40.
35.
Wollina U, Heinig B: Treatment of lipedema by low-volume micro-cannular liposuction in
tumescent anesthesia: results in 111 patients. Dermatol Ther 2019: e12820.
36.
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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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I
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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