Cellulite: Patient Selection and Combination Treatments

for Optimal Results—A Review and Our Experience

DiAnne S. Davis, MD, MS,* Monica Boen, MD, FAAD,† and Sabrina G. Fabi, MD, FAAD, FAACS†

BACKGROUND More than 90% of women have reported concerns of cellulite on their skin. Both commer-
cially advertised creams and topical pharmacological agents have shown limited improvement. Thus far, there
has been a paucity of thorough review articles on how to address and treat this condition.

OBJECTIVE To investigate how the etiology and pathogenesis of cellulite can help guide treatment combinations
and provide a more algorithmic approach to comprehensively address a condition that affects so many women.

MATERIALS AND METHODS A review of the literature surrounding treatment options for cellulite and the
authors’ experience in this area are provided.
Downloaded from http://journals.lww.com/dermatologicsurgery by BhDMf5ePHKbH4TTImqenVE17rCHCwnx1f4asCc5eZziiZ5LGsx2Gphq7b4KYI+9w on 12/15/2019

CONCLUSION This review summarizes available treatment options for cellulite, including topical agents,
controlled subcision, energy-based devices, dermal fillers, and new injectable medications. Furthermore, the
various ways that these treatments can be combined in an algorithmic and sequential approach based on the
degree of volume loss, skin laxity, and excess adiposity associated with cellulite are addressed. These com-
bination therapies for cellulite are supported both in the published literature and the authors’ experience to
help clinicians tailor a comprehensive treatment plan for the multiple factors that contribute to cellulite. Further
clinical trials are needed to compare various devices and techniques for cellulite as well as combination
treatments.

The authors have indicated no significant interest with commercial supporters in regards to this article.

M ore than 90% of women have reported concerns

of cellulite on their skin, especially their proximal
lower extremities. In addition to home remedies or
commercially advertised “magic creams,” patients will
often turn to their dermatologists for minimally invasive
treatment options for the appearance of their skin.
Although the exact etiology is unknown, it can be a
psychologically burdening disease to those who suffer
from it. We present this review article to further
investigate how the etiology and pathogenesis of cellulite
can help guide treatment combinations and provide a
more algorithmic approach to more comprehensively
address a condition that affects so many women.1
bumpy or uneven texture of the skin. The dimpling
appearance that can appear on the buttocks, thighs, or
hips characterizes the clinical appearance of cellulite,
often coined “cottage cheese” or “orange peel” given
the resemblance. Women of all races are plagued by
this condition, and approximately, 2% of men are
affected as well.1,2 The common emergence around 20
to 30 years of age has led to the theory of a possible
hormonal etiology. Goldman described cellulite as a
normal physiologic state in postpubescent females
that enhances adipose retention to guarantee
sufficient caloric availability for pregnancy and
lactation.3,4

There are several predisposing factors that lead to the

Definition
development of cellulite, most of which are unable to
Medically termed liposclerosis or edematofibro- be changed or altered (Table 1).4,5 Female sex,
sclerosis, cellulite is often characterized as either a increasing age, higher amounts of subcutaneous fat,

*Department of Dermatology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma;
†
Cosmetic Laser Dermatology, San Diego, California

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· ·
ISSN: 1076-0512 Dermatol Surg 2019;45:1171–1184 DOI: 10.1097/DSS.0000000000001776

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 CELLULITE PATIENT SELECTION AND COMBINATION TREATMENTS

TABLE 1. Predisposing Factors for Cellulite

Gender Because of the perpendicular orientation of the thick fibrous septae previously described,
women are more likely to develop cellulite
Age Normal anatomical and physiological changes occurring during the postpubertal period result in
women developing cellulite
With increased age, atrophy of the epidermis results in increased severity of cellulite
Genetic Women often have a similar body habitus as other women in their family, which theoretically
predisposition supports the degree and presence of cellulite
Race Caucasian women commonly present with cellulite more than Asian or African American women
Increased The appearance of cellulite is enhanced on the surface of the skin as a result of increased adipose
subcutaneous fat tissue in the subcutaneous layer
Diet Diets rich in high carbohydrates can result in hyperinsulinemia and stimulate lipogenesis, which
may result in an overall increase of body fat content thus increasing the development of
cellulite
Sedentary lifestyle Sustained periods of sitting and/or standing may hinder blood circulation, resulting in stasis and
changes of the microcirculation in cellulite prone areas
Pregnancy A surge in certain hormones, such as prolactin and insulin, and increase in overall fluid volume
can stimulate cellulite by lipogenesis and fluid retention

Adapted from Rao and colleagues. J Cosmet Dermatol 2005;4:93–1024 and Khan and colleagues. J Am Acad Dermatol 2010; 62:361–70.5

and Caucasian rather than Asian ethnicity are all risk
factors for cellulite.
Pathophysiology
Cellulite can be viewed as an architectural disorder as a
result of genetic predisposition, and metabolic and bio-
chemical disturbances. Based on magnetic resonance
imaging (MRI) and gross ex vivo and in vivo examina-
tion, cellulite is believed to be the result of the herniation
of fat through perpendicularly oriented collagen fibrous
septae. The collagenous septae course through the sub-
cutaneous tissue, from the deep fascia and attach to the
level just under the skin. These septations have an uneven
thickness and distribution in patients with cellulite.6
When a patient is standing, the fat that encircles the
fibrous bands protrudes outward, illustrating the “dim-
pling” appearance of cellulite.7 Given that cellulite is
attributed to irregular components of the skin structure,
both obese patients and patients with a normal body
mass index can be affected, although being overweight
can exacerbate its appearance.
Tissue vascularity and inflammation have also been
hypothesized to play a role in cellulite development. It
is hypothesized that adipocytes in cellulite prone areas
have unique biochemical properties and are more
resistant to lipolysis.8 De Godoy and colleagues9
hypothesized that an accumulation of fluids in the
interstitial space, of both the lymphatic and venous
systems, creates the changes that lead to the develop-
ment of cellulite. More importantly, the accumulation
of certain macromolecules results in local inflamma-
tion impeding the exchange of particles between both
systems, and it is this interference that leads to stasis in
the lymphatic system that results in cellulite.9 As a
result of stasis, increased microedema results in further
stress on the subcutaneous fat layer and surrounding
connective tissue and collagen. In response, the num-
ber and thickness of reticular fibers increases, which
leads to accentuation of skin irregularities and ulti-
mately the appearance of cellulite.3,4 The above theory
was supported by de Godoy and colleagues7 who
demonstrated that both mechanical and manual lym-
phatic drainage techniques with relocation and redis-
tribution of the macromolecules interferes in the
pathophysiology of cellulite. In this particular study,
the authors looked at 150 subjects with cellulite (with
no evidence of lipedema or edema) that underwent
daily manual lymph drainage sessions for 10 days that
resulted in a mean perimetric reduction of 3.81 6
2.76 g (p-value <.0001), and thus the overall
enhancement in the aesthetic look of cellulite.7 How-
ever, in clinical practice, manual lymphatic massage is
rarely used.
Hormones are another contributing factor to cellulite
as cellulite coincides with the start of puberty. It is also

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 DAVIS ET AL

more common in females and is exacerbated by high-quality photography, or 3D photography, with

pregnancy, nursing, or menstruation. Adipose hyper- appropriate overhead lighting and patient position is
trophy results from estrogen-driven lipogenesis paramount to assess the results of therapy. Patients
(through stimulation of lipoprotein lipase) and should be evaluated in a relaxed standing position,
impeding lipolysis.10 In male counterparts, the com- without muscle activation, with legs hip length apart
paratively lower level of estrogen explains the lower as the dimples may disappear in a prone position.13,14
incidence of cellulite.4 Also, although not proven, Marking the patient in similar lightening, where
circulating androgens may have an inhibitory effect on shadows allow all the dimples to be captured, while
cellulite.4 In addition, the connective tissue in men is having photographs of the areas to be treated of the
oriented in a criss-crossing pattern, around the thighs patient in hand, has also been helpful at our practice to
and buttocks, that minimizes thick bands of fibrous ensure every dimple is treated (S.G.F.). Handheld
septa organizing into a configuration that would allow lights may add an additional benefit of assessing the
for the protrusion of subcutaneous fat into the dermal patient in different dimensions, both above and below
layers resulting in the appearance of cellulite.6 Once in the areas of concern. Finally, it is important to use the
menopause, an increase in lipoprotein lipase activity in
female abdominal fat correlates with greater central
obesity and cellulite as opposed to gynoid feminine-
TABLE 2. Cellulite Severity Scale
type obesity and cellulite.
No. of Depressions 0 = No depressions
1 = 1–4 visible
Patient Assessment depressions
2 = 5–9 visible
When assessing a patient for cellulite, it is important depressions
for both the patient and physician to cohesively discuss 3 = 10+ visible
depressions
and examine the areas of concern given the many eti-
Depth of depressions 0 = No depressions
ologies that can lead to contour irregularities in the
1 = Superficial
skin. Although, for many patients, any irregularity of depressions
the skin might be seen as cellulite, it is important for 2 = Medium depth
depressions
dermatologists to educate patients on additional tex-
3 = Deep depressions
tural discrepancies that might otherwise be treated by
Morphology of skin surface 0 = No raised areas
different modalities based on its pathogenesis, such as alterations
skin laxity as well as superficial skin crepiness from 1 = Orange peel
appearance
both epidermal and dermal atrophy. True cellulite
2 = Cottage cheese
dimples are most commonly located on the posterior appearance
and lateral thighs, buttocks, and sometimes the hips.1 3 = Mattress
There are several validated cellulite scales to evaluate appearance
Skin laxity 0 = Absence of laxity
patients before and after treatment, and 2 of the most
1 = Slight draped
frequently used scales in clinical trials are the appearance
Nurnberger–Muller Scale and the Cellulite Severity 2 = Moderate draped
Scale (CSS),11 Tables 2 and 3, respectively. The appearance
3 = Severe draped
Nurnberger–Muller Scale is a 4-point scale that has a
appearance
visual assessment of dimple severity and also uses a Classification scale by 0 = Zero grade
pinch test of the skin or muscle contraction to deter- Nurnberger and Muller
mine the extent of the cellulite. On the other hand, the 1 = First grade
2 = Second grade
CSS uses 5 clinical features of cellulite, including the
3 = Third grade
number of depressions, depth of depressions, mor-
phology of skin surface alterations, skin laxity, and the Adapted from Hexel and colleagues. J Eur Acad Dermatol
Venereol 2009;23:523–8.11
original Nurnberger–Muller Scale.2,12 In addition,

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 CELLULITE PATIENT SELECTION AND COMBINATION TREATMENTS

TABLE 3. Nurnberger–Muller Scale for Cellulite

Grade Clinical Appearance

I Smooth skin without any dimpling upon standing or lying down. However, an orange peel–like configuration
upon pinching the skin (which forces the fat into the reticular and papillary dermis)
II Mattress-like appearance of skin present upon standing but disappearing upon lying down in the supine
position
III Skin dimpling upon standing and while in the supine position
Appearance of cellulite exacerbated by pinching of the skin

Adapted from de Godoy, JM and de Godoy Mde F. Int J Med Sci 2011;8:453–5.12

same lighting and positioning before and after treat-
ment to evaluate the effects of treatment.
There are several mimickers of cellulite that are
important to keep in mind when evaluating patients.
Lipoatrophy may clinically appear as depressions in
the skin and may be the result of trauma, a history of
steroid injections, post-traumatic fat necrosis, or even
the removal of excess subcutaneous tissue during
liposuction. Infragluteal bulges, folds, or protrusions,
often referred to as a “banana roll,” are the result of
infragluteal fascial bands present at the base of the
gluteal folds that may accentuate adipose tissue infe-
rior to the buttocks.13 Generalized edema or lymphe-
dema and generalized obesity can also lead to
alternating depressions and protrusions of the skin,
prominently on the lower extremities, as a result of
impaired lymphatic flow or impaired microcircula-
tion, both which need to be addressed with dietary and
lifestyle changes, diuretics, and maybe even compres-
sion therapy. Taking all these entities into consider-
ation is important during the evaluation and
treatment, given that treatment modalities reserved for
cellulite may lead to exacerbations in the above men-
tioned conditions.13
Review of Treatment Options
In recent years, many new topical agents and devices
have been developed to help treat or minimize the
appearance of cellulite. Initially, many of the therapies
were aimed at the pathophysiologic phenomenon of
lymphatic drainage deficiencies and impaired micro-
circulation; however, later devices targeted the ana-
tomical abnormalities of cellulite, such as the thin and
perpendicular fibrous septae. Based on the etiologies
reviewed in the literature thus far, the major therapeutic
categories of cellulite treatment include both topical
and injectable pharmacological agents, mechanical
methods, radiofrequency (RF) devices, laser therapy,
microfocused ultrasound, and controlled subcision. We
present this comprehensive review of the different
therapeutic modalities to aid in an algorithmic
approach to treat the various factors that contribute to
the appearance of cellulite and discuss how combina-
tion treatments can provide optimal results.
Topical Pharmacological Agents
Aims of topical therapy for cellulite include increasing
microcirculatory flow, reestablishing the normal
configuration of the dermis and subcutaneous tissues,
reducing inflammation and therefore the production
of free radicals, and decreasing lipogenesis.1 However,
very little data has supported the use of topicals, such
as vitamins A, C, E, or Gingko biloba.1 Caffeine,
commercially available in 3% formulations, has the
capability to prevent excess accumulation of fat inside
cells.15 One example is a cream (ZONE-5 Slimming
Zone Smart Silhouette Cream; Skin & Tech, Seong-
nam, Korea) composed of 3.5% water-soluble caffeine
and xanthenes, which was shown to significantly
improve in the appearance of cellulite based on a 9-
point visual cellulite scale after twice daily application
for 6 weeks.16 Caffeine’s alkaloid properties inhibit
phosphodiesterase activity, thereby enhancing the
breakdown of adipose tissue during lipolytic proce-
dures and can improve microcirculatory blood flow.15
Retinols have also been studied for cellulite reduction,
and Dupont and colleagues conducted a double-blind,
randomized, placebo-controlled study in which they
demonstrated that a patent-pending retinol topical gel

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(manufactured by Immanence Integral Dermal Cor-
rection Inc., Québec, QC, Canada) statistically
improved the appearance of cellulite after twice daily
application for 3 months. Although the topical agent
contained retinol, which helps to stimulate collagen
and overall increased thickness in the skin, the topical
gel also contained caffeine, retinol, forskolin, and
sacred lotus.1,17 In conclusion, it is debatable to the
extent topical treatments can improve cellulite, and
further studies are needed to clarify this uncertainty.
Injectable Pharmacological Agents
Collagenase, produced by Clostridium histolyticum,
is a new treatment that selectively hydrolyzes the triple
helical region of collagen and can thus target the
fibrous collagen septae in cellulite.18 It is currently
being investigated in Phase 2 and 3 clinical trials and is
showing promising results. In this therapy, the colla-
genase is injected by a trained physician into the
dimpled areas of cellulite on the buttocks or poste-
riolateral thighs to directly target the septae in a non-
invasive manner.19,20 Injections are very tolerable, but
as with other treatments targeting the fibrous septae,
patients do have a significant amount of bruising after
the injection, which can last several weeks.
A phase 2a, randomized, double-blind, placebo-
controlled study was performed involving 150 women
randomized to low (0.06 mg), mid (0.48 mg), high
dose (0.84 mg), or placebo. The patients received up to
3 subcutaneous injections to cellulite in the posterior
thigh or buttocks approximately 21 days apart.19 The
mid- to high-dose groups had statistically significant
improvement in their mean global aesthetic improve-
ment score (mean response of improved or better), and
post hoc analysis showed that 56% to 65% of patients
in the mid- to high-dose groups were responders versus
25% for placebo. Adverse events included injection
site bruising and pain in approximately 25% of
patients. Further data from ongoing clinical trials will
elucidate optimal dosing and treatment regimens.
Bipolar Radiofrequency
One of the first technologies approved by the FDA for
the treatment of cellulite uses a combination of bipolar
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DAVIS ET AL
RF energy, infrared light, and mechanical manipula-
tion of the skin and fat to target cellulite (VelaSmooth
system; Syneron Medical Ltd., Yokneam, Israel).
Radiofrequency produces an electric current that
transforms into thermal energy based on the imped-
ance of the skin tissue.21 RF has the advantage of using
an electric current to produce energy instead of light,
which decreases melanocyte and tissue damage. RF is
often combined with other energy devices to bypass
the limited thermal penetration of bipolar RF tech-
nology. The original system simultaneously used both
bipolar RF energy (at a depth of 5–10 mm) and
infrared light (emitted at a wavelength of 700–
1500 nm) to synergistically target cellulite.22–24 With
each treatment, repeated manipulation of the skin
through vacuum suction and between rollers (40 · 40-
mm applicator head), the device breaks down adipose
tissue, enhances lymphatic drainage, and stretches the
vertical septa and connective tissue, thus overall
improving the dimpled appearance of the skin.22
In a preliminary study regarding safety and efficacy,
Mulholland and colleagues looked at 35 women who
received either 8 or 16 twice-weekly treatments with
increasingly higher energy levels of the combined RF
energy, infrared light, and mechanical manipulation
system.24 Although a reduction in thigh circumference
was seen in all patients after 8 weeks of treatment, the
decrease was only 0.8 inches. There was also some
level of improvement in skin texture and the overall
appearance of cellulite in 100% of the patients, but no
standard cellulite scales were used. Magro and col-
leagues demonstrated that 71.87% of patients had a
decrease in thigh circumference along with improve-
ment in the overall skin texture and appearance of
cellulite after 6 twice-weekly treatment sessions with
the combined system, but once again, the mean
decrease in thigh circumference was small with a mean
decrease of 0.44 cm of the lower thigh and 0.53 cm of
the upper thigh, and no standardized cellulite scales
were used.23 Goldman and colleagues compared the
combined RF energy, infrared light, and mechanical
manipulation system and a low energy 810-nm diode
laser with contact cooling, suction, and massage
(TriActive; Cynosure, Westford, MA) to reduce the
appearance of cellulite on the lower extremity.25 Both
devices showed a mild improvement in the appearance
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 CELLULITE PATIENT SELECTION AND COMBINATION TREATMENTS
of cellulite and decrease in thigh circumference meas-
urements, without a significant difference between the
devices (75% improvement with the combined RF
energy, infrared light, and mechanical manipulation
system vs 55% with low-energy diode modality).25
These findings were comparable with another study by
Alster and Tanzi26 using the same device, in which 18
women experienced improvement in the appearance
of cellulite on the treated area, with a mean improve-
ment of 50% at 1 month, and investigators saw an
average circumferential thigh reduction size of 0.8 cm
after 8 biweekly treatments.
By combining RF energy with infrared energy, the
required amount of optical energy is reduced, and the
synergistic action is believed to favorably support
reducing the appearance of cellulite. The combined RF
energy, infrared light, and mechanical manipulation
is a safe option for many skin types given the reduced
energy required for treatments. Each treatment session
is approximately 20 to 30 minutes per side of the body,
and it is recommended that treatments occur once
every 4 to 6 weeks. The targeted end points are ery-
thema and warmth for each treatment area. Adverse
events include erythema, pain, edema, bullae forma-
tion, scabbing, ecchymosis, postinflammatory hyper-
pigmentation, and scarring.24,26,27
There have been several updates to the combined RF
energy, infrared light, and mechanical manipulation
system, including increased power, efficacy, and faster
treatment time (VelaShape, VelaShape II, VelaShape
III; Syneron Medical Ltd., Yokneam Illit, Israel).28,29
Adatto and colleagues30 performed a prospective
study with 35 patients with skin laxity and cellulite
treated with this new treatment modality once a week
for 6 weeks. There was a decrease in the circumference
of the abdomen, buttocks, and thighs of 1.4, 0.5, and
1.2 cm, respectively, at the 3-month follow-up and a
29% reduction in the thickness of the fat layer as
assessed by ultrasound 1 month after the final treat-
ment. Skin laxity and cellulite showed 1% to 49%
improvement in 87% of patients. Most recently, the
third version of this system received FDA clearance for
treating cellulite not only on the thigh and buttock
regions, but also on the abdomen. This system
encompasses increased bipolar RF energy (at 150 W),
1176 DERMATOLOGIC SURGERY
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and studies report an overall mean reduction in
abdominal circumference to be 5.4 + 0.7 cm.31 With
enhanced capability, decreased downtimes, and fewer
sessions, the newer treatment devices with increased
wattage show promise for body contouring.32,33
In clinical practice, the results of these devices for the
treatment of cellulite can be variable, but they are safe
procedures with minimal downtime.
Monopolar Radiofrequency
Monopolar radiofrequency (MRF) devices differ from
bipolar RF devices in that the return electrode, or
grounding pad, is located at a further distance from the
handpiece, and thus, the energy can be delivered at a
greater depth into the skin.34 One of these devices
(Accent XL platform; Alma Lasers Ltd., Caesarea,
Israel) uses both a unipolar RF and a bipolar treatment
head.35 Treatments can be safely performed every
week over the course of 3 to 4 months. Although
transient erythema is a targeted end point, blistering,
scarring, changes in pigment, and bruising are poten-
tial adverse events.34,36 Histological studies have
demonstrated fibroplasia in the dermis 6 months after
the last treatment, which could be the cause of sus-
tained improved appearance of cellulite.34
Another MRF device (Thermage; Solta Medical,
Inc., Hayward, CA) creates thermal damage, thus
reorganizing dermal collagen and the irregular con-
tours of the skin. MRF helps to improve skin laxity
on the buttocks or thighs and ameliorate cellulite in
this area. The original device consists of a generator,
cryogen unit, and a handpiece with unique
treatment tips that deliver simultaneous vibration.37,38
Usually only one treatment is needed, but yearly
maintenance treatments are recommended. As with
other treatments, contour irregularities, blistering,
scarring, and the development of nodules have been
reported. Based on AccuREP technology, RF energy is
automatically quantified and accurately tuned to
deliver the right amount to the patient and treatment
area. Treatment time is reduced by up to 25% given
the newer device has a vibrating handpiece that
covers larger treatment areas with enhanced patient
comfort.39

Microfocused Ultrasound With Visualization
Although not cleared for these indications, micro-
focused ultrasound with visualization (MFU-V) has
been used to noninvasively lift and tighten lax skin on
various parts of the body, including the upper arms,4,40
elbows,41 thighs,4,40 knees,4,40,42 and buttocks.4,43
Microfocused ultrasound with visualization delivers
discrete and focused columns (<1 mm3) of trans-
cutaneous ultrasound energy to heat the target tissue
to at least 65C at a depth of 1.5 to 4.5 mm. At this
temperature, collagen within the dermal and sub-
cutaneous tissue denatures and contracts to produce
skin tightening, all while sparing surrounding tis-
sue.44,45 The visualization component (MFU-V) helps
to determine where the energy will be applied and
ensures proper acoustic coupling between the trans-
ducer and the skin before energy is delivered.44
Sasaki and Tevez40 demonstrated that MFU-V produced
moderate improvement in the inner brachium, peri-
umbilicus, and knee regions. In a pilot study, Rokshar
and colleagues showed that MFU-V is a nonsurgical
option for increased skin laxity above the elbow.41 Nine
of the 16 patients (56%) showed an aesthetic improve-
ment and as per the Physician Global Aesthetic
Improvement Scale, 94% of patients achieved aesthetic
improvement at both 90 and 180 days. Patient satisfac-
tion surveys showed that 83% saw visual improvements
in their elbow 90 days after treatment and 81% dem-
onstrated improvement in 180 days after treatment.41
Goldberg and colleagues43 demonstrated a 89.5%
improvement in skin laxity in the buttocks with MFU-V
at Day 180 by both investigator and subject global
improvement scores. The authors did not comment on
improvement in cellulite; however, they noted that this
treatment is most effective in nonobese patients. We have
performed hundreds of MFU-V procedures on the knees,
inner thighs, posterior thighs, buttocks, abdomen, and
inner arms and have seen significant improvement in
tightening lax skin, which contributes to the overall
improvement in the appearance of cellulite.
Subsurface Technologies
With advanced technology, minimally invasive pro-
cedures that directly target the fibrotic tethered bands
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DAVIS ET AL
in cellulite are becoming more ideal treatment
modalities. One laser device, in particular (Cellulaze;
Cynosure), uses 1,440-nm neodymium-doped yttrium
aluminum garnet (Nd:YAG) laser therapy that is
absorbed by both adipose tissue and water. After
affected areas on the skin are marked and tumescent
anesthesia is administered, the laser is angled in 3
different directions to target different structural
defects in cellulite. The laser is first angled down
toward the skin, at a depth up to 2 cm, to target the
adipose tissue. The second direction is parallel to the
skin, which allows for the release of the fibrous sep-
tations that tether down the skin. The third direction
of angulation is upward toward the underside of the
skin, which results in remodeling of the dermal colla-
gen and elastin.1,46 With the addition of a handheld
temperature-sensitive cannula, real-time feedback of
the skin surface temperature can be continuously
monitored by the operator for precise energy that will
yield optimal results. In addition, a side-firing fiber
aids in a more targeted delivery of thermal energy that
releases the dermal septae and overall stimulates
neocollagenesis resulting in thicker and tighter skin.37
Targeting all 3 components, including the adipose
tissue, fibrous septae, and remodeling of dermal col-
lagen and elastin, has led to decreased depth of skin
dimples, improvement in the contour of the skin, and
improved patient satisfaction, all which were demon-
strated by Katz and colleagues. In this particular study,
15 women received one subsurface 1,440-nm laser
treatment followed by 1 week of compression therapy.
Six months after treatment 3D imaging demonstrated
a mean 49% decrease in dimple depth, 66%
improvement in skin contour, and overall enhance-
ment in the patient’s quality of life.1,46 In another study
with 10 healthy women with moderate to severe cel-
lulite, patients underwent a single treatment to one
thigh while the contralateral thigh served as a control.
At 1-, 3-, 6-, and 12-month follow-up timeframes, the
mean skin thickness (as shown by ultrasound) and skin
elasticity were shown by objective measurements to
increase significantly. Also the subjective physician
and subject evaluations on cellulite reduction, skin
texture, and satisfaction at 1 year were roughly equal
to those, if not greater, than at 3 and 6 months.37
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 CELLULITE PATIENT SELECTION AND COMBINATION TREATMENTS
Controlled subdermal MRF is another tool to address
skin laxity on the body, especially the neck, but also on
the thighs. This device (ThermiTight, Thermi, Irving,
TX) contains a temperature-controlled probe that
precisely heats the target subdermal area to a set
temperature of 50 to 65C, with epidermal tempera-
ture monitoring through an infrared camera, to pro-
mote neocollagenesis. Although there have been no
formal studies evaluating the efficacy of this device for
cellulite, it offers the potential to treat skin laxity to
approve the appearance of cellulite.47,48
A subsurface bipolar RF device (BodyTite; Invasix,
Inc., Yokneam, Israel) uses 1 electrode on the skin
and 1 RF electrode placed subdermally, in the sub-
cutaneous plane. The RF energy coagulates the adi-
pose, connective, and vascular tissues in the vicinity
of the internal cannula tip and gently heats the dermis
below the external electrode. As with other devices,
target internal temperatures are set at 38 to 42C and
maintained for 1 to 3 minutes49,50 An applicator has
been specifically designed to address cellulite by tar-
geting the immediate hypodermal space, which
results in an enhanced collagen barrier in the deep
hypodermis.51 The device uniformly heats large vol-
umes of tissue, with controlled temperature moni-
toring, allowing for the breakdown of adipose tissue
with coagulation of surrounding blood vessels
to minimize bruising and bleeding.
Subcision Treatments
Traditionally, subcision has been performed manu-
ally, using a tribeveled 16- or 18-gauge needle (BD
Nokor 18-G Needle; Bectron, Dickinson and Com-
pany, Franklin Lakes, NJ) inserted in the deep dermal
layer to release the fibrous septations under local
anesthesia.52,53 The subcision treatment most effec-
tively addresses the “dimples” seen in cellulite, and
similar to the 1,440-nm subsurface laser device, cel-
lulite dimples are marked before the procedure. In
addition to dimples, it also has been shown to
effectively minimize depressed lines that can lead to
irregular contours on the thighs and buttocks,13 but
not the infragluteal horizontal bands (“banana roll”).
However, it is important to note that to accurately
identify the affected areas, the patient must be standing
1178 DERMATOLOGIC SURGERY
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in the appropriate position with overhead, tangential,
and even possible handheld lighting to highlight the
contours of the skin of the thighs, buttocks, and even
lower back. Preoperative marked photographs are an
additional tool that can be used for accurately identi-
fying skin irregularities.13 Affected areas are individ-
ually marked before administering tumescent
anesthesia to ensure accurate identification of fibrous
septations during the nominally invasive procedure.
Manual subcision of cellulite was first performed by
Hexsel who performed the subcisions parallel to the
skin surface in the deep layer of the subcutaneous tis-
sue approximately 10 to 20 mm below the depressed
areas. The release of the fibrous septations alleviates
the traction exerted on the skin and promotes the
formation of new connective tissue through “autolo-
gous filling” from the bruises that are produced.
Redistribution of tension between the fat lobules into
the new spaces is created to produce a smoother
appearance to the skin. Subcision results were
shown to be persistent in a study by Hexsel and
Mazzuco who treated 232 female subjects with
either grade II or III cellulite, given 23 of the subjects
continued to have visible results more than 2 years
after one procedure. In this study, 83/232 of subjects
were satisfied with their improvement after just one
treatment session (considered successful treatment),
47/232 had reasonable results (considered partially
successful), and 2/232 subjects were dissatisfied
with their results.52 Recently, Hexsel and col-
leagues53 were able to further support the efficacy of
subcision treatments, both clinically and through
imaging results. Two patients with severe cellulite
according to the CSS underwent MRI imaging for
one dimpled lesion on each buttock both before and
1, 3, and 7 months after subcision. The post-
procedure images demonstrated visible loss of the
subdermal septations suggesting long-term accept-
able outcomes through this treatment modality.53
With time, the manual subcision technique has lost
some favor given its inability to produce consistent
results and the pain, bruising, and seromas associ-
ated with the procedure.1,13
A new device (Cellfina; Ulthera/Merz, Meza, AZ)14
produces a controlled subcision treatment using a

vacuum-assisted chamber with a microblade that can
either extend to precisely 6 mm or 10 mm in depth to
mechanically release the fibrous septae through a
forward and backward motion (Figure 1). Kaminer
and colleagues conducted the pivotal trial of 55
patients with limited with moderate to severe cellulite
using the controlled vacuum-assisted subcision system
in a single treatment. Three months after the pro-
cedure, the CSS score improved by 2.1 points from 3.4
to 1.2, on a 5-point scale, and 93% of patients showed
improvement in lesions per independent assessment by
blinded physicians.14 This improvement was seen even
after 1 year where there was a mean improvement of 2
points on the 5-point cellulite scale, with a 100% of
patients showing noticeable improvement. Adverse
events during this clinical trial included 4.5/10 dis-
comfort during administration of anesthesia, 3/10
discomfort during septation tissue release, and bruis-
ing was noted in 37/54 subjects at the 2-week follow-
up.14 Although no formal compression therapy is
necessary, yoga pants, shapewear, or bike shorts are
recommended for the first 2 weeks postoperatively
to minimize leakage of fluid and bruising. This pivotal
trial had a 3-year extension to evaluate the long-term
efficacy of the device, and 47/55 subjects completed
this extension where the authors found that 41/45
subjects demonstrated at least a 1-point improvement
on the 5-point cellulite scale, and all subjects showed
improvement (56% were much improved or better).
The lack of sustained results over 3 years in some of the
subjects may be due to the fact that some patients had
weight gain (47% of patients had a weight gain of 19.9
pounds).54 Further long-term results of subcision are
Figure 1. (A and B) Patient is a 44-year-old woman with moderate to severe cellulite dimples before (left) and 4 months after
one treatment (right) with vacuum-assisted controlled subcision.
© 2019 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
DAVIS ET AL
still to be elucidated. In summary, controlled, vacuum-
assisted subcision is an attractive option for many
patients given its initial results and reports of its long-
lasting results beyond the US Food and Drug Admin-
istration’s clearance of 2 years.1
Dermal Fillers
Biostimulatory injectable fillers, poly-L-lactic acid
(PLLA) and calcium hydroxylapatite (CaHA),55 are
commonly used for skin tightening and lifting and
have been used to treat upper-arm skin laxity and
buttocks.56 Recently, CaHA combined with MFU-V
has been shown to be effective for improving the
appearance of cellulite dimpling and skin laxity on the
buttocks and upper thighs in 20 patients after a single
same-day treatment.57 The authors’ frequently use
CaHA in a 1:1 or 1:2 dilution with normal saline to
improve skin laxity in the dorsal hands and upper
chest, respectively, without complications. When
combining these procedures on the same day, the
energy device is used first, such as MRF or MFU-V,
immediately followed by the injectable biostimulatory
agent.58,59 If the dermal filler is performed first, MRF
or MFU-V is performed at least 1 week, preferably
1 month later.60,61
Coleman and Pozner described various ways to com-
bine treatments from their clinical experience to treat
cellulite. They noted that in patients with cellulite and
volume loss, they recommend combining subcision or
subdermal technologies with PLLA or a hyaluronic
acid filler.59 Combination treatments work
45:9:SEPTEMBER 2019 1179
 CELLULITE PATIENT SELECTION AND COMBINATION TREATMENTS

synergistically to produce more optimal results, and is exacerbated by the following: volume loss that
many can be performed on the same day. exacerbates the visibility of the fibrous septae,
increased adipose tissue, skin atrophy, and skin lax-
There has been anecdotal evidence from the literature ity.65 There are other mechanisms involved in cellulite
and the authors’ personal experience using PLLA to formation, such as molecular and hormonal influen-
improve the dimpled appearance of cellulite, by ces, but they will not be addressed in this review as
addressing the dermal depressions and skin laxity these pathways are still to be elucidated. In each
components of cellulite. Sadick and colleagues62 patient, these additional 3 architectural aspects of
demonstrated improvement in skin laxity and volume cellulite should be evaluated, and Figure 2 lists some
loss in the gluteal region in a 2-patient case series of the therapies presently available to address each
after a series of 2 to 3 monthly PLLA injections.63 They issue.
used 3 to 4 vials of PLLA per injection session, and
each vial was diluted with 10 mL of sterile water and Safety
2 mL 1% lidocaine 24 hours in advance of the injec-
In daily practice, many cosmetic dermatologic pro-
tion. The filler was injected in the upper and middle
cedures are performed in combination to achieve
part of the buttocks for maximum lift. Although cel-
optimal results and also to reduce the number of
lulite improvement was not assessed in this case series,
clinic visits for patients. However, scarcity in the lit-
Sadick and colleagues noted PLLA injections could
erature exists on the use of these combination ther-
reduce the appearance of cellulite.
apies for cellulite, and many of our proposed
combinations are from personal experience of hun-
The authors use larger dilutions of PLLA off the face,
dreds of cases. In the authors’ experience, combina-
15 mL of bacteriostatic water and 1 mL of 1% lido-
tion therapies that target different planes of tissue can
caine per vial, and have not encountered nodule for-
be safely performed on the same day.59 We advise
mation with this larger dilution. Although these
caution on therapies that deliver too much heat to a
cosmetic injectables have shown great promise for the
given area on the same day, or if performing the
treatment of cellulite, further well-designed clinical
procedures on the same day increases the risk to the
trials are necessary to determine their efficacy and
patient, they should be scheduled on separate days,
safety.
such as fat transfer and MFU-V. The order of the
Of note, before the advent of dermal fillers, fat transfer combination therapies matters as well. For instance,
has been used to fill depressions and atrophy in the we usually perform MFU-V or RF before injection of
skin, and this can also be a viable option for cellulite. PLLA or CaHA to avoid contaminating the energy
Tumescent liposuction can be combined with fat device transducers.
transfer to decrease the appearance of cellulite on the
buttocks and thighs. Uebel and colleagues described
this surgical approach in which the combination of
tumescent liposuction, subcision release of the fibrous
septa, and fat grafting led to sustained improvement in
cellulite. This is in part hypothesized to be as a result of
the scaffold that the transferred fat provides that
allows for the subcutaneous tissues to rearrange
themselves in a more uniform fashion.64

Cellulite Algorithm
Figure 2. Cellulite components and treatment options.
Cellulite is a complex disorder that is due to an Any of the treatments in each column can be combined to
inherent structural alteration of the fibrous septae and address the multifactorial etiology of cellulite.

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 DAVIS ET AL

Optimizing Combination Treatments

We have summarized the various combination therapies
available for cellulite, noted the order in which they
should be performed, and the time interval of the pro-
cedures (Table 4). Most of the combination treatments
can be performed safely on the same day. Three options
are given in Table 4, with option 1 being the least inva-
sive treatment combination and option 3 showing more
invasive options, many times needing more than one
clinic visit for optimal results. Although combination
treatments for cellulite are still in their infancy, the
authors believe they will be more common as they
address the various physical etiologies of cellulite.
(1) Volume loss and cellulite dimples: Noninvasive
options for patients with both cellulite dimples
and volume loss involve starting with controlled
subcision, followed by biostimulators as early as
1 to 2 months after nodules or swelling from
controlled subcision has subsided using a series
of 3 treatments with PLLA (16-cc reconstitution)
or CaHA (1:1) spaced 1 month apart. If there is
significant volume loss, patients can undergo fat
transfer instead of biostimulatory agents.
(2) Excess fat and cellulite dimples: Excess adiposity
can contribute to the dimpling effect of cellulite,

TABLE 4. Potential Combination Therapies for Cellulite

Potential Combination Therapies for Cellulite

Option 1 Option 2 Option 3

Volume loss and cellulite 1. MFU-V or RF 1. Controlled subcision 1. Controlled
subcision
2. PLLA or CaHA 2. MFU-V or RF 2. Fat transfer
3. PLLA or CaHA
Excess fat and cellulite 1. Detergent lipolysis or 1. Liposuction or field 1. Controlled
cryolipolysis radiofrequency subcision
1 month later: 1 month later: 1 month later
Controlled subcision Controlled subcision 2. Liposuction or
cryolipolysis
Skin laxity and cellulite 1. MFU-V or RF 1. Controlled subcision 1. Controlled
subcision
2. Controlled subcision 2. PLLA or CaHA 1 month later
2. MFU-V or MRF
3. PLLA or CaHA
Volume loss/skin laxity and cellulite 1. MFU-V or RF 1. Fat transfer 1. Fat transfer
2. PLLA or CaHA 1 month later 2. Controlled
MFU-V or RF subcision
1 month later
MFU-V or RF
Volume loss/excess fat (separate 1. Cryolipolysis or 1. Liposuction 1. Liposuction
locations) and cellulite detergent lipolysis
2. Controlled subcision 2. Subdermal RF 2. Controlled
subcision
3. PLLA or CaHA 1 month later 1 month later
PLLA or CaHA PLLA or CaHA
Skin laxity/excess fat and cellulite 1. Cryolipolysis or 1. Liposuction 1. Liposuction
detergent lipolysis
2. Controlled subcision 2. Subdermal RF 2. Controlled
subcision
3. MFU-V or RF 1 month later
4. PLLA or CaHA PLLA or CaHA

CaHA, calcium hydroxylapatite; MFU-V, microfocused ultrasound with visualization; PLLA, poly-L-lactic acid; RF, radiofrequency.

45:9:SEPTEMBER 2019 1181

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 CELLULITE PATIENT SELECTION AND COMBINATION TREATMENTS
Figure 3. (A and B) Patient is a 70-year-old woman with a combination of hip dell volume loss, skin laxity of buttock, lateral
and posterior thighs, and cellulite dimples on buttock. Before (left) and after treatment (right) with MFU-V of buttock,
posterior and lateral thighs immediately followed by 1 treatment using vacuum-assisted controlled subcision, followed by
a series of 2 sessions of 4 vials/session of PLLA starting 1 month later. MFU-V, microfocused ultrasound with visualization;
PLLA, poly-L-lactic acid.
which can be addressed with tumescent lipos-
culpture, or noninvasively with cryolipolysis or
detergent lipolysis, immediately followed by
controlled subcision if cryolipolysis is performed,
but 1 month later if liposculpture or detergent
lipolysis is used. Liposuction and subcision
performed on the same day increases the risk of
hematoma and seroma formation.
(3) Skin laxity and cellulite dimples: Lax skin can
exacerbate the rippling appearance of cellulite,
especially in older patients and in patients who
have recently lost a significant amount of weight.
These patients can benefit from a skin-tightening
treatment, such as MFU-V or RF (surface or
subsurface), or PLLA/CaHA combined with
controlled subcision. It is important to perform
the energy-based device treatment before subci-
sion because the infiltration of local anesthetic
for the subcision treatment can alter the intended
tissue plane of energy delivery. This could be
followed on the same day with controlled sub-
cision and/or biostimulators (Figure 3).
(4) Volume loss, skin laxity, and cellulite dimples:
Patients with a mixture of volume loss, skin laxity,
and cellulite dimples would benefit from MFU-V
or RF, which could be followed on the same day
with controlled subcision and/or biostimulators. If
controlled subcision is performed, biostimulators
would be used as early as 1 to 2 months after
nodules or swelling from controlled subcision has
subsided. Typically, a series of 3 monthly treat-
ments with PLLA or CaHA is needed. If there is
significant volume loss, the patients can undergo
fat transfer instead of biostimulatory agents.
1182 DERMATOLOGIC SURGERY
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(5) Volume loss, excess fat, and cellulite dimples:
Some patients have a mixed picture of volume
loss and adiposity in cellulite-prone areas.
Minimally invasive ways to address all these
issues involve decreasing the areas of adiposity
with tumescent liposculpture, cryolipolysis, or
detergent lipolysis first, immediately followed
by controlled subcision if cryolipolysis is per-
formed but 1 month later if liposculpture or
detergent lipolysis is used. A biostimulatory
dermal filler is used as early as 1 to 2 months
after nodules or swelling from controlled sub-
cision has subsided.
(6) Excess fat, skin laxity, and cellulite dimples: In
patients with cellulite dimples, along with areas
of skin laxity and excess fat, several procedures
are needed. Minimal downtime procedures
involve starting with targeting excess fat using
tumescent liposculpture, detergent lipolysis, or
cryolipolysis, followed 1 month later by micro-
focused ultrasound or RF treatments, which
could be followed on the same day with con-
trolled subcision and/or biostimulators. If con-
trolled subcision is performed, biostimulators
would be used as early as 1 to 2 months after
nodules or swelling from controlled subcision
has subsided. Patients may need touch-up treat-
ments with biostimulatory fillers as well.
Conclusion
In the past decade, we have witnessed a large growth in
the available technologies to treat cellulite, and they have
been increasingly effective in treating this challenging
condition. We present a treatment strategy to help guide
physicians in tailoring a plan for the multiple factors that

contribute to cellulite to more comprehensively meet
patient demands. Further clinical trials are needed to
compare various devices and techniques for cellulite as
well as combination treatments.
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Address correspondence and reprint requests to: DiAnne
S. Davis, MD, MS, Gateway Aesthetic Institute and Laser
Center, 440 West 200 South, Suite 250, Salt Lake City, UT
84102, or e-mail: sdavis3957@aol.com