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Cellulite: Etiology and Treatment

Chapter · October 2023

DOI: 10.1007/978-3-030-43840-1_41

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 Cellulite: Etiology and Treatment
41
Miriam Vicente-Ruiz

Take-Home Points Cellulite refers to the orange peel-type, mat-

• Cellulite purportedly affects up to 95% of post tress-like, or cottage cheese-like dimpling of the
pubertal women of all races. skin that appears on the thighs and buttocks of
• Cellulite is a multifactorial entity with skin post-adolescent women and is considered a com-
architecture and connective tissue, inflamma- plex, multifactorial, cosmetic disorder of the
tory, vascular, endocrine, and genetic factors subcutaneous fat layer and the overlying superfi-
playing a major role. cial skin [3]. Although the precise definition of
• The appearance of cellulite worsens during cellulite is not clear and many different, and
high estrogen states, including pregnancy, even conflicting, definitions for this entity have
nursing, and chronic use of oral been proposed, it can be described as an estheti-
contraceptives. cally disturbing, localized distortion of the skin
• Although no cure for cellulite exists, multiple architecture accompanied by a higher subcutane-
treatments have been developed over the years ous adipose tissue thickness in lower body fat
to try to improve its appearance. depots like the buttocks and thighs, as shown in
• It is not clear whether lifestyle modifications Fig. 41.1 [4].
such as weight loss or exercise can improve Although its exact prevalence is unknown, it is
the condition, but they may have some posi- reckoned to affect up to 80–90% of post pubertal
tive effects. females of all races [5]. It is known to accelerate
during adolescence, pregnancy, and around
menopausal age, and its incidence and severity
41.1 Introduction are influenced by sex, being more common in
women than men; race, being more common in
Cellulite remains one of the most common dis- Caucasians; and biological type, being found on
satisfactions among women after puberty [1]. It the hips and thighs of Latin American women but
has been estimated that up to 98% of females are not on the abdomen of European women [6].
concerned about their skin changes due to cellu- Cellulite has been given many names includ-
lite with a decrease in their self-esteem [2]. ing gynoid lipodystrophy, nodular liposclerosis,
edematofibrosclerotic panniculopathy, pannicu-
losis, adiposis edematosa, dermopanniculosis
M. Vicente-Ruiz (*) deformans, and status protrusus cutis [7, 8]. The
Clínica Universidad de Navarra, term “cellulite” should not be confused with
Pamplona, Navarra, Spain
“cellulitis,” a term used in scientific English to
e-mail: [email protected]

© Springer Nature Switzerland AG 2023 733

M. Gomes-Ferreira, J. Olivas-Menayo (eds.), Post-maternity Body Changes,
https://doi.org/10.1007/978-3-030-43840-1_41
734 M. Vicente-Ruiz

Additionally, while cellulite is generally asymp-

tomatic, the more severe stages can present with
painful nodules and increased local temperature,
which argues against the physiological nature of
this condition [4].
Many studies have suggested the association
of cellulite with age, smoking, estrogen use, poor
physical activity, body mass index (BMI), and
indexes of cardiac risk [4]. In relation to age, sig-
nificantly higher cellulite scores have been
described in older patients, with flaccidity play-
ing an important role as it worsens with aging
[12]. With respect to BMI, cellulite can affect
individuals regardless of their body mass index,
although it has been described that obese patients
have a higher percentage of fat inclusion in the
dermis in areas with cellulite, which correlated
Fig. 41.1 Dimpled appearance of cellulite on the but-
with higher cellulite scores [12–14]. Other
tocks and posterior thigh of a 24-year-old female authors suggest that cellulite is not a result of
(Reprinted from MacGregor JL, LaTowsky B, Arndt KA, increased body mass, but rather that the waist-to-­
Dover JS. Cellulite. In: Evidence-Based Procedural hip ratio may influence its appearance [15].
Dermatology [Internet]. New York, NY: Springer
New York; 2012) [54]
cc Important Cellulite is almost omnipresent in
indicate an infection of the subcutaneous cellular post pubertal women.
tissue [9]. It should also be differentiated from It appears as an orange peel-type,
obesity, which is characterized by hypertrophy mattress-like, or cottage cheese-like dimpling
and hyperplasia of adipose tissue that is not nec- of the skin on the thighs and buttocks.
essarily limited to the gluteal, femoral, or abdom- Cellulite should not be confused with
inal areas, as opposed to cellulite, which is most cellulitis or obesity.
commonly found in these areas [8]. Moreover, It is not clear whether we can consider
cellulite can also be found in slim and active per- cellulite a disease or a physiological feature
sons [10]. in women.
Whether cellulite is a real disease or only a Although cellulite scores are generally
disturbing aesthetic issue is still a matter of higher in older and more obese patients,
controversy [4]. There is no consensus about young and slim persons can present cellulite
whether or not we can consider it a disease, or it too.
is merely a physiological feature in women.
Some experts argue that there is no mortality or
morbidity associated with this condition, which 41.2 Etiology
makes it difficult to define as “pathologic.” Also,
given its ubiquitous nature, it is more appropri- Many studies have tried to clarify the origin of
ately thought of as a secondary sex characteristic cellulite; however, its precise etiology is still
rather than a disease [8, 11]. Others, however, unclear, and most authors consider it a multifac-
state that cellulite is more and more often treated torial entity with skin architecture and connective
as an illness since it more and more often nega- tissue, inflammatory, vascular, endocrine, and
tively influences the mental state of women [10]. genetic factors playing a major role [6, 7, 16, 17].
41 Cellulite: Etiology and Treatment 735

41.2.1 Skin Architecture thighs, ultrasonography, and MRI [13, 19–21].

and Connective Tissue Some studies have observed the correlation
between the range of these extrusions and cellu-
Nürnberger and Müller published the first scien- lite grading, while others found no correlation
tific paper on cellulite in 1978. They were the between their extent and the clinical severity of
first to describe the sex-typical differences of the cellulite [13, 21]. The extrusion of these papillae
skin and subcutaneous tissue. According to their adiposae into the dermis forced by external com-
findings, the subcutaneous tissue of the thighs is pression (pinch test) causes the overlying skin to
composed of three layers of fat with two planes protrude, creating the mattress phenomenon,
of connective tissue, being the uppermost layer which is a major sign of cellulite [21].
made up of “fat-cell chambers” separated by While three principal orientations of connec-
septa of connective tissue. In women, these septa tive tissue septa exist (perpendicular, parallel,
run perpendicular to the skin creating large, and angulated at about 45°), women with cellu-
standing fat-cell chambers. From these fat-cell lite have a higher percentage of perpendicular
chambers, “papillae adiposae” protrude into the septa than unaffected women or men, which
thin dermis creating the external appearance of allow the underlying fat to protrude [8, 20]. These
cellulite. They also observed these findings in gender-related differences in septal orientation
men with androgen deficiency, which suggests a have been found in affected and unaffected
major role of sex hormones in the development of women. This could explain the observation that
cellulite. In men, however, these septa run in a the areas where dimpling is evident are highly
crisscrossing pattern creating small polygonal variable depending on the position of the indi-
fat-cell chambers, and papillae adiposae are vidual lower extremity and positions that tend to
scarcer with a thicker dermis, which hinders the compress the adipose tissue in a specific area will
mattress phenomenon, as shown in Fig. 41.2. enhance the dimpling in that same area [19].
They therefore concluded that cellulite is not a Differences in connective tissue morphology
disease, but it is rather the result of the sex-typi- have also been described. In patients with cellu-
cal structure of the skin of women and the natural lite, connective tissue of the dermal-adipose tis-
consequence of aging [18]. sue border of the thigh has been described as
This extrusion of underlying adipose tissue irregular and discontinuous, as opposed to
into the reticular dermis has been confirmed by smooth and continuous in unaffected patients,
histological examination of wedge biopsy of the but this pattern was found to be diffuse, that is,

Fig. 41.2 The structure of cellulite (Reprinted from MacGregor JL, LaTowsky B, Arndt KA, Dover JS. Cellulite. In:
Evidence-Based Procedural Dermatology [Internet]. New York, NY: Springer New York; 2012)
736 M. Vicente-Ruiz

not localized to affected areas of the thigh [19]. Women with cellulite have a higher percent-
One study that compared subcutaneous tissue in age of perpendicularly running connective tissue
areas with and without cellulite showed that cel- septa.
lulite depressions on the buttocks were signifi- Differences in the morphology and density of
cantly associated with underlying thicker fibrous the connective tissue have been linked to
septa [22]. However, other studies have found no cellulite.
differences in the septa between raised lesions Cellulite is associated with the presence of a
and control areas [12]. Another study found that thin dermal layer, bad skin quality, and abnormal
women with cellulite and high BMI presented mechanical properties of the skin.
weaker and less dense connective tissue, thus
linking connective tissue density with the degree
of cellulite [13]. 41.2.2 Inflammatory and Vascular
Other studies have linked cellulite with the Factors
characteristics and quality of the dermis and the
biomechanical properties of the skin of women It is controversial whether localized tissue vascu-
affected. One study found that the presence of larity or inflammation plays a major role in the
cellulite corresponds to a thinning of the dermal etiology of cellulite [8]. Some studies have found
layer, a greater length of the dermis–hypoder- the presence of inflammatory cells in the fibrous
mis interface, a decrease of dermal density, and septa of cellulite biopsies, which might be the
the deterioration of biomechanical parameters cause of low-grade inflammation [7]. However,
of skin elasticity and extensibility, which are other studies found no evidence of inflammation
skin characteristics typical of older ages. The [8, 18, 21].
author therefore argues that the presence of cel- Adiponectin is an adipocyte-derived hormone
lulite is a cause of premature skin aging [23]. with anti-inflammatory, antifibrotic, and vasodi-
Another study observed that, women without latory functions. In areas with cellulite, signifi-
cellulite had a better-quality skin—firmer, with cant decreases in the subcutaneous expression of
less compliance, laxity, and capacity for defor- adiponectin mRNA have been found, with unal-
mation. By contrast, women with cellulite, pre- tered plasma levels, which suggests that it may
sented greater laxity and weakness of the dermis act as a local paracrine factor that influences the
and connective tissue. Adding to increased appearance of the skin, through a microcircula-
interstitial pressure and the negative effects of tory dysfunction, inflammation, and disrupted
aging, this favors connective tissue weakening, extracellular matrix homeostasis [3, 7].
making it more likely that fatty tissue may her- Glycosaminoglycans (GAGs) are polysac-
niate into the dermis [17]. charide chains found in the extracellular matrix.
Lastly, the mechanical cause of the skin dim- Through their water-attracting properties, they
pling in cellulite has been linked to that of dermal can create a swelling pressure to allow for the dif-
stretch marks. While dermal stretch marks result fusion of water. Some authors have found
from excessive tension applied in parallel with increased concentrations of GAGs in the ground
the skin surface, cellulite likely results from con- substance of dermis in cellulite skin, which could
tinuous and progressive tension vertically ori- determine a rise for water retained in the skin and
ented [24]. thus explain the edematous appearance of cellu-
lite skin [25]. Other studies have failed to demon-
Key Points strate increased water content in the adipose
Cellulite is based on a sexual dimorphic skin tissue of women with cellulite [20].
architecture. It has also been suggested that the process of
The external appearance of cellulite is caused cellulite originates with deterioration of the der-
by fat herniation into the dermis. mal vasculature, particularly in response to
41 Cellulite: Etiology and Treatment 737

altered precapillary arteriolar sphincters in in the course of the hormone replacement therapy
affected areas, which would add to the deposition [10].
of GAGs and lead to elevated excessive fluid Although there is no clear explanation for the
retention in the tissue. This edema can also lead topographic distribution of cellulite, it has been
to vascular compression, hypoxia, and capillary noted that the adipocytes in the gluteofemoral
neoformation, resulting in microhemorrages. region are larger than in other areas and are
These findings have been supported by some greatly influenced by female sex hormones. In
studies but refuted by others [8, 19]. addition, they are metabolically more stable and
resistant to lipolysis, which could partly explain
Key Points the gynoid fat distribution in women, with a
It is controversial whether localized tissue vascu- greater accumulation of fat in areas where cellu-
larity or inflammation plays a major role in the lite is present [8].
etiology of cellulite.
A decrease of adiponectin expression in the Key Points
subcutaneous tissue has been found in areas with Female sex hormones play a major role in cellu-
cellulite. lite development.
Increased concentrations of GAGs have been Cellulite appears only in women and men with
described in the dermis of cellulite skin. androgen deficiency.
An alteration in dermal vasculature of cellu- The first symptoms appear in puberty with the
lite areas has been suggested. rise in female sex hormones.
The skin lesions show progression during
hyperestrogenic states.
41.2.3 Endocrine Factors Hormonal imbalances, rather than isolated
hormonal peaks, are regarded as the crucial
The first scientific paper on cellulite, conducted cause of the cellulite.
by Nürnberger and Müller in the 1970s, described
cellulite as being present only in women or in
men with androgen deficiency, introducing the 41.2.4 Genetic Factors
relationship between female sex hormones and
cellulite [18]. Posterior findings have confirmed The distribution of two polymorphisms has
the major role of female sex hormones, notably recently been associated with cellulite [7, 26].
estrogens, in the development of cellulite. Hypoxia-inducible factor 1 (HIF-1) regulates
The first symptoms of cellulite appear in gene expression in response to hypoxia. During
women during puberty, with the rise in sex hor- hypoxia, it stimulates the production of the
mones. In addition, progression of the skin GLUT1 protein, erythropoietin, transferrin, and
lesions has been observed during high estrogen vascular endothelial growth factor (VEGF). In
states, including pregnancy, nursing, and chronic fat tissue, HIF-1 expression has been found to
use of oral contraceptives [6, 7]. activate fibrosis and local inflammation. T-allele
Hormonal imbalances, rather than isolated polymorphism 11549465 for HIF1A reduces the
hormonal peaks, are regarded as the crucial cause activity of this HIF-1A factor, and one study
of the cellulite. More precisely, an excess in found that women presenting this polymorphism
estrogen concentration in relation to progester- did not develop cellulite, or if they did, it was at
one causes a relative hyperestrogenism. These a low level [6, 26]. The same study found that
occur physiologically in the period of pregnancy, women who carry the D allele of the angiotensin
maturation, and menopause, or pharmacologi- I-converting enzyme (ACE) increase the risk of
cally through systemic hormone contraceptive or developing cellulite, which is related to the rise
of production of angiotensin II in the subcutane-
738 M. Vicente-Ruiz

ous adipose tissue. This growth provokes blood blood stasis, resulting in swelling, ischemia, and
flow dysregulation and facilitates adipocyte hypoxia in the subcutaneous tissue, as well as
hypertrophy, increased deposition at the extra- increased wall permeability and swelling of sur-
cellular matrix, and the formation of a complex rounding tissues, which places pressure on small
mesh of subcutaneous fibrous tissue [26]. veins and arterioles, leading to abnormal blood
Another study found a significant synergism flow within the skin and fatty tissue. This pro-
between this polymorphism and smoking for the cess exacerbates the fibrosis and formation of
risk of cellulite, suggesting for the first time that nodules in the subcutaneous tissue [6]. Pregnancy
smoking might be a risk factor in the develop- is also associated with an increase in certain hor-
ment of cellulite [27]. mones, such as prolactin and insulin, with an
increase in overall fluid volume. Both of these
Key Points factors promote cellulite by lipogenesis and fluid
T-allele polymorphism 11549465 for HIF1A is retention [8].
protective against cellulite development. During menopause, a low estrogen concen-
ACE rs1799752 increases the risk of develop- tration is responsible for increased vascular per-
ing cellulite. meability and decreased vascular tone, which
Smoking might be a risk factor in the develop- lead to microcirculation impairment and are
ment of cellulite. important factors predisposing to the develop-
ment of cellulite. The effects of estrogen defi-
ciency on the skin connective tissue include a
41.2.5 Other Factors decreased production and topical content of both
type I and III collagen and elastin fibers, which
Various authors have suggested that limitation of also contributes to cellulite [10].
fluid movement and impairment in lymphatic
drainage may contribute and aggravate cellulite.
However, studies have refuted the presence of 41.4 Pretreatment Evaluation
enlarged lymph vessels in the dermis [21]. One
study group described improvement in cellulite Clinical examination with a focus on a palpable
appearance after lymphatic drainage therapy and visual medical examination is at the center of
[28–30], whereas another group found no signifi- cellulite diagnosis and evaluation. However,
cant improvement, concluding that manual lym- some authors propose the use of complementary
phatic drainage is not effective as an isolated clinical and image tools.
treatment of cellulite [31]. The examiner should look for cellulite
mainly in the outer thighs, posterior thighs,
and buttocks. However, it can also be found in
41.3 Cellulite and Maternity hips, periumbilical abdomen, breasts, posterior
arms, and posterior neck [7]. Cellulite must
As previously mentioned, it is known that cellu- always be evaluated with patients standing in
lite may worsen during high estrogen states, anatomic position. Pinching the affected areas
including pregnancy, nursing, and chronic use of with the thumb and index finger (pinch test) as
oral contraceptives [7]. However, the underlying shown in Fig. 41.3, having the patient contract
cause appears to be a relative hyperestrogenism the underlying muscle group, and the use of
rather than an isolated increase of estrogens, tangential hard light can all help accentuate
which occurs physiologically in the period of and visualize contour irregularities in affected
pregnancy and menopause [10]. areas [7].
During pregnancy, the excess in estrogens Other clinical tools that may be useful in the
causes excessive relaxation of the veins, causing office include anthropometry, perimetry, scale of
41 Cellulite: Etiology and Treatment 739

a b

Fig. 41.3 Clinical examination of a healthy volunteer at rest (a), after applying the pinch test (b)

severity of cellulite (CSS), and quality of life by [7, 10]. Recently, a study has shown the efficacy
Celluqol questionnaire, which evaluates the of thermal imaging using infrared thermography
impact of cellulite on the choice of clothing, lei- in the diagnosis of cellulite stage by analyzing
sure, physical activities, relationship with part- the superficial temperature distribution, as shown
ner, feelings, and changes in daily habits [1, 11, in Fig. 41.4 [33].
32].
Some image tools that have been proposed as
pretreatment evaluation methods include 41.4.1 Cellulite Classification
Cutometer to assess skin elasticity, ultrasound and Grading
for thickness of hypodermis, macrography, tran-
sepidermal water loss (TEWL) determination, Cellulite may be divided according to clinical
videocapillaroscopy, or electric bioimpedance. type (fatty, lymphatic, or alleged) or character of
CAT and MRI have also proven to be useful skin changes (tough type, slender form, or
tools, but they ought to be employed responsibly hydropic form) [10]. But most commonly, cellu-
in account of their costs and radiation exposure lite is characterized by the use of clinical scales.
740 M. Vicente-Ruiz

a b

c d

Fig. 41.4 Typical thermal images of thighs of a healthy from Bauer, J., Grabarek, M., Migasiewicz, A. et al. Non-­
volunteer (a), a volunteer with high occurrences of contact thermal imaging as potential tool for personalized
cellulite (b) and volunteers with cellulite of first stage (c), diagnosis and prevention of cellulite. J Therm Anal
second stage (d), and third stage (e). Suspect areas were Calorim 133, 571–578 (2018))
marked using ThermaCAM software (c, d). (Reproduced
41 Cellulite: Etiology and Treatment 741

The first was described by Nürnberger and Table 41.2 Scoring system of the Cellulite Severity
Müller [18] and included three grades: Scale and Cellulite Classification [34]
Cellulite Severy Scale Classification
–– Grade I: Skin is smooth at rest. 1–5 Mild
–– Grade II: Skin demonstrates a mattress or 6–10 Moderate
orange peel appearance at rest. 11–15 Severe
–– Grade III: Skin has grade II features and nod-
ules intermixed with raised and depressed
areas at rest. used, which has shown an excellent reliability
and internal consistency when used to evaluate
More recently, other scales have been pro- cellulite of the buttocks and posterior thighs [16].
posed, being the Cellulite Severity Scale (CSS)
(Tables 41.1 and 41.2) [34] the most commonly
41.5 Treatment
Table 41.1 Photonumeric Cellulite Severity Scale [34]
Photonumeric severity Although no cure for cellulite exists, multiple
scale Score treatments have been developed over the years to
Number of evident 0 = None/no depressions try to improve its appearance [1, 2, 11] (see
depressions 1 = A small amount: 1–4 Table 41.3). These treatments should have a mul-
depressions are visible
tidirectional action, and patients should be
2 = A moderate amount:
5–9 depressions are informed that they will not eliminate the problem
visible but rather offer a temporary improvement [10].
3 = A large amount: 10 or In light of its etiology, two criteria have
more depressions are
been proposed to consider a treatment effec-
visible
Depth of depressions 0 = No depressions tive: it must both expel the fat protrusions back
1 = Superficial beneath the dermis and strengthen the dermis
depressions to prevent further protrusions [35]. The treat-
2 = Medium depth ments available display these criteria in differ-
depressions
3 = Deep depressions ent degrees.
Morphological 0 = No raised areas From the multiple studies that have aimed to
appearance of skin 1 = “Orange peel” analyze the effectiveness of different treatment
surface alterations appearance modalities, most authors agree that the best
2 = “Cottage cheese”
effects are obtained by combined therapy [5, 10,
appearance
3 = “Mattress” 35–37].
appearance
Grade of laxity, flaccidity, 0 = Absence of laxity,
or sagging skin flaccidity, or sagging skin 41.5.1 Noninvasive Treatments
1 = Slight draped
appearance
2 = Moderate draped 41.5.1.1 Topical and Oral Treatments
appearance Numerous topical cosmeceutical ingredients
3 = Severe draped have been reported to improve the appearance of
appearance
cellulite, including caffeine, retinoids, and botan-
Classification Scale by 0 = Zero grade
Nürnberger and Müller 1 = First grade ical extracts. Although it has been hypothesized
2 = Second grade that these ingredients cause the lipolysis of the
3 =Third grade adipose tissue, the stimulation of the peripheral
742 M. Vicente-Ruiz

Table 41.3 Some devices available in the market with their proposed modes of action and advantages
Device Mode of action Advantages
THORK Shock Way® Electromagnetic shock wave therapy Energy is applied on target zones, avoiding
damage to surrounding tissue
Utrashape® High intensity-­focused ultrasound Energy is concentrated in selected
subcutaneous areas, preventing excessive
damage to surrounding tissue
Velasmooth® Bipolar radiofrequency, infrared light, Increase of deeper skin temperature without
suction, and mechanical massage damage to the skin surface
Alma Accent® Unipolar and bipolar radiofrequency Increase of deeper skin temperature without
damage to the skin surface
TriActive® Low-dose laser, contact cooling, Combination of energy-­based and mechanical
massage and suction stimulation techniques
SmoothShapes® Laser, biostimulating light, massage, Combination of energy-­based and mechanical
and suction stimulation techniques
VaserSmooth® Ultrasound-­assisted liposuction with a Decreased bleeding compared to traditional
cutting cannula liposuction, combines cellulite correction and
fat removal
Smartlipo® Liposuction with Nd:YAG (1064-nm) Less invasive than traditional liposuction,
laser combines liposuction with skin tightening
Cellfina® Tissue-stabilized guided subcision Precise control of anesthesia infiltration and
system treatment depth and area
Endermologie® Machine-assisted massage system that Greater potency than manual massage
combines positive and negative
pressure to the skin
3DEEP® Multisource radiofrequency system Exact energy delivery customized in real time
to individual patient’s skin impedance

microcirculation to facilitate lymphatic drainage, grapes (Vitis vinifera), Cynara Scolymus, Ivy,
and the reduction of edema, there is little evi- Melilotus officinalis
dence that topical treatments have a potential –– Reduce lipogenesis and promote lipolysis:
positive effect on the appearance of cellulite [7, Methylxanthines, B-adrenergic agonists,
11, 38, 39]. Furthermore, given that cellulite is a A-adrenergic antagonists
condition that develops over years, several –– Restore the normal structure of dermis and
months may be necessary before the effect of any subcutaneous tissue: Retinol (vitamin A).
treatment may come apparent [5]. –– Prevent free radical formation or scavenge
Topical treatments are most often used to treat free radicals: Alpha-tocopherol (vitamin E),
mild-to-moderate cellulite and as an adjuvant ascorbic acid (vitamin C), Ginkgo biloba, red
treatment for severe cellulite. These substances grapes (Vitis vinifera).
can be divided into four groups according to their
proposed mechanism of action [38]: Special attention should be given to three
agents that appear to be giving some benefit:
–– Increase microcirculation flow: Ginkgo
biloba, Pentoxifylline, Centella asiatica, –– Aminophylline is believed to help in the
Ruscus aculeatus, Silicium, papaya (Carica breakdown of fat and cellulite by activating
papaya), pineapple (Ananas sativus), red enzymes, which cause the release of fat stores
and ultimately lead to a smoothing effect on
the skin [35].
–– Retinoids have a known effect of increasing
dermal collagen fibers, thus strengthening the
41 Cellulite: Etiology and Treatment 743

dermis and improving the strength of the modalities, such as Endermologie, deliver posi-
hypodermal septa [35, 39]. Retinol (vitamin tive pressure to the skin and subcutaneous tissue
A) can also act as an antiadipogenic agent by via rhythmic folding and unfolding as well as
inhibiting the differentiation of human adipo- negative pressure through aspiration. It has
cyte precursor cells [38]. shown improvement in cellulite grading and a
–– Methylxanthines, such as caffeine, amino- reduction in thigh circumference in some stud-
phylline, theophylline, and theobromine, are ies, although its long-term efficacy and the lon-
B-agonists and are the main category with gevity of these effects is still questionable [5, 7,
documented action in the treatment cellulite. 11, 35, 39].
The most useful and safest is caffeine, which
acts directly on adipose cells, promoting lipol- 41.5.1.3 Noninvasive Body
ysis. Caffeine also has a stimulating effect on Contouring Devices
the cutaneous microcirculation [38]. In the recent years, noninvasive body contouring
–– Peroxisome Proliferator-Activated Receptors devices have become one of the most widespread
(PPAR) and their agonists, including petroselinic procedures and are growing fast in areas of
acid and conjugated linoleic acid (CLA), are a esthetic medicine. Some have shown statistically
recently discovered family of nuclear transcrip- significant effects on body contouring, removing
tion factors that have shown to enhance skin unwanted fat and cellulite. However, the effect of
tightening and reduce adipose invagination into such devices have been reported to be mild to
the dermis [5]. moderate [2]. Plus, no long-term clinical studies
have ever been carried out with these devices in
Many of the agents used in topical treatments the treatment of cellulite; therefore, maintenance
are also used in oral supplements for the treat- therapy will be required for continued improve-
ment of cellulite, such as PPAR agonists (notably ment in most patients [40].
CLA) or Centella asiatica extracts, which can
also be found in combined formulations, such as –– Electromagnetic Shock Wave Therapy
Cellasene, which contains Ginko biloba, sweet (ESWT). Although its full mechanism is not
clover, sea weed, grape seed oil, and evening clear yet, it seems to be based on the conver-
primrose oil. Although their efficacy has not been sion of electrical energy to mechanical energy
proven, they appear to provide some relief from on target zones, avoiding damage in the sur-
the symptoms of cellulite [5]. rounding tissue, which can improve local
blood circulation, mechanoreduction, induce
41.5.1.2 Mechanical Stimulation lipolysis, and/or apoptosis of the adipose cell.
Massage will reduce edema, there is also some Studies show improvement of degrees of cel-
evidence for increased collagen synthesis and lulite severity as seen in Fig. 41.5, gross elas-
stimulation of fibroblast (and keratinocyte) activ- ticity, and skin deformation ability, with
ity while decreasing adipocyte activity [5]. improvement in the quality of life. Devices
Mechanical stimulation of the skin is supposed to include THORK Shock Wave [1, 2, 7, 11,
stimulate microcirculation as well as lymphatic 41–43].
drainage to improve lymphedema, which may –– High Intensity-Focused Ultrasound
improve the appearance of cellulite. Presumably, (HIFU). Ultrasound waves can induce adipo-
it causes damage to the subcutaneous fat cells cyte destruction by various mechanisms such
that subsequently rebuild with an improved dis- as cavitation and thermal damage. Devices
tribution that evens skin contour. It also enhances include LipoSonix, Proslimelt, Medcontour,
the presence of longitudinal collagen bands Ultracontour, Novashape, Accent Ultra, and
through the tensional stimulation of fibroblasts. Ultrashape. Although the Federal Drug
However, its efficacy is not clear [11]. Administration (FDA) has not approved them
Mechanical stimulation can be carried out for cellulite treatment, Ultrashape has shown
manually or through a device. Device-based
744 M. Vicente-Ruiz

Fig. 41.5 Improvement of the Cellulite Severity Score in Joest, B., Krämer, R. et al. Cellulite and Focused
a female patient suffering from cellulite before and Extracorporeal Shockwave Therapy for Non-Invasive
3 months after six sessions of focused Extracorporeal Body Contouring: a Randomized Trial. Dermatol Ther
Shock Wave Therapy (Reproduced from Knobloch, K., (Heidelb) 3, 143–155 (2013)) [55]

to decrease subcutaneous fat tissue thickness sumed to be absorbed by adipocytes inducing

[2, 35, 39, 44]. their apoptosis. Several RF devices are avail-
–– Cryolipolysis is based on the sensitivity of able, including VelaSmooth and VelaShape,
adipocytes to cold in comparison with other Thermage, Alma Accent and Accent XL,
water-rich cells. Therefore, the application of 3DEEP, Exilis, ThermaCool, TriPollar, Venus
cooling panels on the target zone provokes the Freeze, Viora Reaction, and TiteFX. Some of
apoptosis of fat cells without damaging the these devices combine RF with other modali-
circumambient tissue. It is usually carried out ties of treatment, such as Velasmooth that
through cup-shaped applicators with two combines bipolar RF with infrared light, suc-
cooling panels, where a vacuum pulls the tis- tion, and mechanical massage, or Alma
sue and draws the target zone between cooling Accent that combines unipolar with bipolar
panels. It has been proved effective for patients modalities. Some have been approved by the
with separate fat bulges. It presents the advan- FDA for their use in cellulite treatment and
tage of being operator-independent but the have shown to be useful in the treatment of
disadvantage of long-treatment sessions [2]. cellulite (Fig. 41.6), although more studies are
–– Radiofrequency (RF) generates heat in dif- needed [2, 7, 10, 11, 35, 39, 40, 45].
ferent tissues by transforming energy from an –– Laser and light-based devices. Different laser
electromagnetic field to the target tissue, in a devices using various wavelengths have been
monopolar, unipolar, bipolar, or multipolar studied for the treatment of cellulite.
modality. This results in an increase of deeper Noninvasive long-pulsed 1064 nm neodym-
skin temperature without epidermal or dermal ium-doped yttrium aluminum garnet (Nd:YAG)
ablation, which leads to collagen denaturation lasers would deliver thermal energy into the
and tissue tightening. In addition, the heat that deep dermis and the hypodermis to generate a
is delivered to the subcutaneous layer is pre- wound-healing response that promotes the for-
41 Cellulite: Etiology and Treatment 745

Fig. 41.6 Before and after five sessions of Alma Accent (Reprinted from ravo BSF, Torrado CM, Issa MCA. Non-­
(RF–Accent – Alma Lasers). Improvement of the skin ablative Radiofrequency for Cellulite (Gynoid
depressions in number and depth on the buttocks Lipodystrophy) and Laxity. In 2018. p. 375–88) [56]

mation of new collagen. Minimally invasive –– TriActive combines low-dose laser, contact
pulsed 1440 nm Nd:YAG laser would smooth cooling, suction, and massage and has shown
the uneven dermal-­ hypodermal interface by results comparable to other available
selectively melting the hypodermal adipocytes treatments.
that protrude into the dermis. In addition, it –– SmoothShapes combines laser, biostimulat-
would sever the hypodermal septa that connect ing light, massage, and suction and has also
the dermal and muscle layers by thermal subci- shown improvement in the appearance of cel-
sion and heat the dermis from the inside out to lulite although its results are short-lived [2, 10,
increase dermal thickness and skin elasticity by 11, 35].
stimulating neocollagenesis and collagen
remodeling. While there is very little evidence
that the noninvasive use of 1064 nm Nd:YAG 41.5.2 Invasive Procedures
lasers is effective, the minimally invasive
1440 nm lasers seem to significantly improve 41.5.2.1 Subcutaneous Injections
the clinical appearance of cellulite, decrease Mesotherapy involves the subcutaneous injec-
dimple depth, the number of dimples, and tion of compounds with the intention of inducing
smoothen the contour of the skin. Low-Level lipolysis and improving the appearance of cellu-
Laser Therapy (LLLT), which works at a lite. They usually contain a mixture of herbs,
645 nm wavelength, is thought to stimulate col- vasodilators, anti-inflammatory medications, or
lagen synthesis [2, 11]. hormones, such as methylxanthines (caffeine),
One study showed that the subdermal aminophylline, and theophylline, which cause
application of the Nd:YAG laser combined lipolysis. The one ingredient most consistently
with autologous fat transplantation is a safe used is phosphatidylcholine, which has proven to
and effective treatment for cellulite [46]. cause panniculitis with necrosis and lipoatrophy
–– Infrared light (IR) and Intense Pulsed Light in the site of injection. However, the substances
(IPL) also have a role in the treatment of cellu- currently in use have not been thoroughly evalu-
lite. They are supposed to promote microcircula- ated for safety or efficacy [35, 39, 47].
tion, lymphatic drainage, and collagen synthesis Carboxy therapy is a treatment in which car-
through the heating of the skin [35]. bon dioxide is injected into the subcutaneous tis-
sue. This would create a hypercapnic environment,
Devices that combine laser and light-based causing a rise in capillary blood flow, a drop in
radiation with mechanical stimulation are fre- cutaneous oxygen consumption, or a right shift of
quently used. the oxygen-dissociation curve (Bohr Effect),
746 M. Vicente-Ruiz

which would facilitate the physiologic oxidative Recently, a new surgical technique has been
lipolytic process [5]. proposed that combines liposuction, including
Collagenase injections can also be used to wide areas of undermining and release of fibrous
break the connective tissue septa that cause the septa, with autologous fat grafting for smooth
dimpling [11]. structural support of the subcutaneous tissue.
Although more studies are needed, this tech-
41.5.2.2 Liposuction nique appears to be a safe and effective treat-
Liposuction is not a unanimously accepted treat- ment, with high level of patient satisfaction,
ment for cellulite. Some authors argue that con- sustained results after long-term follow-up, and
ventional liposuction reduces fat tissue content a low incidence of surgical revision and post-
but does not directly act on the factors that cause treatment complications [49].
cellulite and can increase skin irregularities.
However, superficial liposuction exists, which is 41.5.2.3 Subcision
executed close to the dermis and can release sub- Subcision is an invasive procedure in which, fol-
cutaneous fibrous septa. Its use on cellulite near lowing local anesthesia, a 16 or 18 gauge needle
the skin surface with only a thin layer of dermis or a blade is inserted parallel to the epidermis
dividing it from the epidermis often leads to into the subcutaneous fat to shear the septa sepa-
increased dimpling of the skin and can cause skin rating the fat lobules, interrupting the architec-
necrosis from devascularization after extensive ture of the protruding fat cells. Subcision is
undermining, which constitutes an important recommended for cellulite depressions present at
limitation [35, 39]. However, some studies have rest, not for depressions visible only with muscle
showed some improvement in cellulite appear- contraction. Depressions are marked immedi-
ance after surgical treatment using liposuction ately preprocedure with the patient standing in a
and the release of the fibrous tissue bridges with relaxed position. The procedure may be carried
blunt, thin cannulas [48]. out manually, combined with upward traction, or
vacuum-assisted (Cellfina system), which pro-
Laser-Assisted Liposuction vides a precise control of anesthesia infiltration,
Laser-assisted liposuction is often a preferred treatment depth, and area and has demonstrated
option for the treatment of localized adiposities long-term efficacy and safety. Post treatment rec-
and is a frequent treatment for cellulite. The ommendations should include avoidance of
Nd:YAG (1064-nm) laser such as Smartlipo tar- strenuous physical activity for 1–2 weeks and use
gets selected areas of fat for destruction in addi- of a compressive garment for 2–4 weeks. Post
tion to simultaneously tightening the skin. This treatment adverse events include painful bruising
technology is less invasive compared to conven- and hemosiderin pigmentation in almost all
tional liposuction, as it employs a smaller can- patients. Therefore, repeat manual subcision
nula, and the application of laser pulses selectively should be avoided for at least 2 months from ini-
damages adipocyte membranes while coagulat- tial therapy or until all bruising or hemosiderin
ing, promoting collagen tightening and hemosta- pigmentation from that first session has resolved.
sis [39, 49]. Subcision can temporarily improve the skin dim-
Ultrasound-assisted liposuction (Vaser) has pling seen in cellulite-prone areas. However, its
demonstrated increased skin retraction and, when long-term efficacy remains controversial [7, 35,
utilized with a cutting cannula (VaserSmooth), 39, 49–53].
may be an effective treatment for areas of cellu- No systematic tool exists to measure the out-
lite, with decreased blood loss compared to tradi- comes after cellulite treatment, which makes it
tional liposuction [49]. difficult to compare studies on the efficacy of dif-
41 Cellulite: Etiology and Treatment 747

ferent treatment modalities. Real-time scanning 41.6.2 Exercise

ultrasound image, three-dimensional optical skin
surface measurement, clinical photographing, A sedentary lifestyle or the lack of physical activ-
historical findings, or personal questionnaires are ity increases the severity of cellulite by weaken-
often used for this purpose [2]. ing the muscle layers of blood vessels and causing
local hemostasis, which leads to secondary
Pearls and Pitfalls hypoxia and ischemia of the adipose tissue [6].

–– Vacuum-assisted subcision, and more pre-

cisely the Cellfina device, has recently proven 41.6.3 Weight Loss
to be a long-term effective and safe treatment
for cellulite. Weight loss has proven to have dual effects on
–– A new technique that combines liposuction cellulite appearance. Studies show that in the
with autologous fat grafting of the subcutane- majority of subjects, cellulite severity decreases
ous tissue has recently been proposed with following weight loss, especially in those with
promising results. higher body mass index. However, in some cases,
–– No systematic tool exists to measure the out- it may have the opposite effect. This may be
comes after cellulite treatment, which makes it caused by septa acting as a tethering system, thus
difficult to compare studies on the efficacy of worsening the typical dimpling pattern or skin
different treatment modalities. laxity with major weight loss, or an increase in
skin looseness, which can adversely affect skin
dimpling [11, 16, 39].
41.6 Lifestyle

Lifestyle has been associated with the aggrava- 41.6.4 Smoking

tion of cellulite appearance through different
mechanisms [6, 10]. Therefore, all treatments Smoking provokes a greater amount of free
should be accompanied by the control of aggra- radicals and contraction of small blood vessels
vating factors, with a focus on a well-­balanced responsible for local micro-circulatory impair-
diet and exercise. ments [6]. Also, as reported previously, smok-
ing has been linked to the ACE gene
polymorphism and an increased risk of devel-
41.6.1 Diet oping cellulite.

An imbalanced diet, with excessive food intake

and alcohol consumption, can exacerbate cellulite 41.7 Conclusion
development and appearance in various ways.
Excessive intake of food causes metabolic disor- Cellulite affects the majority of post pubertal
ders including hyperinsulinemia, which can women and remains a major cosmetic concern.
increase lipodystrophy. Alcohol consumption Although its precise etiology is still not clear, it is
stimulates lipogenesis and causes body dehydra- considered multifactorial with sex-related differ-
tion, resulting in the excessive and improper stor- ences in skin architecture, connective tissue,
age of fat. In addition, an overall excess in body inflammatory factors, hormones, and genes play-
fat causes adipocytes to become hypertrophic ing a major role. Cellulite is known to worsen
with a progressive reduction of microcirculation during high estrogen states, including pregnancy,
locally as individual cells constrict each other [6]. nursing, and chronic use of oral contraceptives.
No cure for cellulite exists; however, some treat-
ments have shown to be effective for improving
748 M. Vicente-Ruiz

its appearance with combined therapies having 14. Smalls LK, Lee CY, Whitestone J, Kitzmiller WJ,
the best results. It is not clear whether weight loss Wickett RR, Visscher MO. Quantitative model of
cellulite: three-dimensional skin surface topog-
or exercise can improve the condition, but they raphy, biophysical characterization, and relation-
may have some positive effects. ship to human perception. J Cosmet Sci [Internet].
2006;56(2):105–120. http://www.ncbi.nlm.nih.gov/
pubmed/15868063.
15. Pierard GE. Commentary on cellulite: skin mechano-
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