ISSN 2421-7115

Aesthetic Medicine / Volume 4 / Nº 3 / July/September 2018

Official Journal of the

International Union of Aesthetic Medicine UIME

Official UIME English Language Journal of:

Aesthetic and Anti-Aging Medicine Society of South Africa
Aesthetics Medical Society of Uruguay
Aesthetic Medicine Society of Venezuela
Algerian Society of Aesthetic Medicine
American Academy of Aesthetic Medicine
Argentine Society of Aesthetic Medicine
Association of Aesthetic and Antiaging Medicine of Guatemala
Belgian Society of Aesthetic Medicine
Canadian Association of Aesthetic Medicine
Colombian Association of Aesthetic Medicine
Croatian Society of Aesthetic Medicine
Ecuadorian Society of Aesthetic Medicine
French Society of Aesthetic Medicine
Georgian Society of Aesthetic Medicine
Indian Society of Aesthetic Medicine
Italian Society of Aesthetic Medicine
Kazakhstan Association of Aesthetic Medicine and Plastic Surgery
Korean Academy of Aesthetic Medicine
Mexican Scientific Society of Aesthetic Medicine
Moroccan Society of Aesthetic Medicine
Polish Society of Aesthetic and Anti-Aging Medicine of Polish Medical Society
Portuguese Society of Aesthetic and Anti-Aging Medicine
Scientific Association of Aesthetic Medicine of Peru
Society of Aesthetic Medicine in Turkey
Spanish Society of Aesthetic Medicine
Swiss Society of Aesthetic Medicine
Ukrainian Society of Aesthetic Medicine

www.aestheticmedicinejournal.org
Editor-in-chief
Francesco Romanelli
Rome, Italy

Editors Executive Editors Managing Editor Main Handling Editor

Emanuele Bartoletti, Italy Emanuele Bartoletti, Italy Emanuele Bartoletti, Italy Hernán Pinto, Spain
Alfonso Carvajal Gomez, Colombia Annarosa Catizzone, Italy
Annarosa Catizzone, Italy Loredana Cavalieri, Italy
Loredana Cavalieri, Italy Nadia Fraone, Italy
Nadia Fraone, Italy Giovanni Messina, Italy
Fernando García Manforte, Spain Hernán Pinto, Spain
Mohamed Oughanem, Algeria Raffaele Rauso, Italy
Raul Pinto, Argentina
Sandra Ramirez Naranjo, Colombia
Dorota Wydro, Poland
Wooha Han, Korea

Associate Editors
Diana Aguilar, Peru - Kulwant S. Bhangoo, India - Luis Bravo, Peru - Patricia Frisari, Argentina - Tulegenova Gulnur, Kazakhstan - An-
drzej Ignaciuk, Poland - Monica Kapoor, India - John Kim, California (USA) - Alexander Kutubidze, Georgia - Omnia Latif, New Jersey
(USA) - Leonor Lemmo, Venezuela - Alp Mamak, Turkey - Xavier Martin, Swiss - Gilda Marzullo, Chile - David Melamed, California
(USA) - Farid-Salim Oughanem, Algeria - Olga Panova, Russia - Asja Perovic, Croatia - Susan Roberts, Canada - Pilar Rodrigo Anoro,
Spain - Ismael Terzano, Uruguay - Viveka Tinoco Kirby, Ecuador - Sonia Lamari, Algeria.

Statistical Editor
Patrizio Pasqualetti, Italy

Editorial Board
Gladys Arroyave Estrada, Colombia - Angelo Bellido, Peru - Ahmed Bourra, Morocco - Elma Bunar, Croatia - José Cabo Soler, Spain -
Julia Carroll, Canada - Alfonso Carvajal Gómez, Colombia - Andrés Eliú Castell Rodriguez, Mexico - Eduardo Civila, Uruguay - Michel
Delune, California (USA) - Fernando Echeverria, Chile - Alberto Elbaum, Uruguay - Victor Garcia-Guevara, Venezuela - Han Woo-ha,
Korea - Jean Hebrant, Belgium - Daniel H. Hurtado Terrazas, Bolivia - Andrzej Ignaciuk, Poland - Alexander Katsitadze, Georgia - Serge
Lê Huu, Switzerland - Jean-Jacques Legrand, France - Li Shirong, China - Xavier Martin, Switzerland - Joao Pedro Vale, Portugal - Gilda
Marzullo, Chile - Alena Mayorova, Russia - Irina Medvedeva, Ukraine - Hans Robert Metelmann, India - Blanca Miller Kobisher, Mexico
- Issa Ogata, Peru -Mohamed Oughanem, Algeria - Olga Panova, Russia - Iván Pinto, Venezuela - Raul Pinto, Argentina - Catalin Mihai
Popescu, Romania - Ajay Rana, India - Carlos A. Rosales Gonzales, Guatemala - Aicha Salhi, Algeria - Hasan Subasi, Turkey - Vladimir
Tsepkolenko, Ukraine - Viveka Tinoco Kirby, Ecuador - Ekaterina Ugrekhelidze, Georgia - Joao P. Vale, Portogallo - Renier Van Aardt,
Canada - Cobus Van Niekerk, South Africa - Petra Vega, Spain - Jerzy Woy-Wojciechowski, Poland - J. Yun, Korea - Gulnar Zhumatova,
Kazakhstan.

Aesthetic Medicine (registered by the Court of Rome on 28/4/2015 under the number 63/2015) is published 4 times a year (March, June, September,
December) by Salus Internazionale ECM Srl, via Monte Zebio, 28 - 00195 Roma, tel. +39 06 36003462 - fax +39 06 37519315,
E-mail: [email protected]; www.lamedicinaestetica.it.
Subscription Information: All subscriptions inquiries, orders, back issues, claims, and renewals should be addressed to Salus Internazionale ECM Srl.
Free subscription (Four issues: March, June, September, December).
Copyright Permission: Permission requests to photocopy or otherwise reproduce material published in this journal should be submitted by
sending and e-mail to [email protected].
Advertising: Current advertising rates and specifications may be obtained by sending and e-mail to [email protected].
EPub [15/10/2018]

II
 Aesthetic Medicine / Volume 4 / Nº 3 / July/September 2018

Editorial
Francesco Romanelli X

Contents
Original article

AFLAX MLT®: a new medical treatment, effective and powerful to treat skin flaccidity
Graciela Melamed pag 14

Original Article

Results of practical application of fibroblasts in treating age-related skin changes. An open,

prospective, non-randomized study
Anna Tsepkolenko, Aleksandr Litus, Vladimir Tsepkolenko pag 19

Original article

Cryolipolysis with active vacuum technology and simultaneous stimulation of the microcirculation
in body reharmonization: comparative study on 40 patients divided into 2 cohorts
Fabrizio Melfa, Daniela Gaetana Caruso, Michela Maggi pag 25

Review

Dercum’s disease or Adiposis Dolorosa: a complex condition still awaiting full definition
Paola Palumbo, Benedetta Cinque, Francesca Lombardi, Lucia Romano, Corinna Genovesi, Gino Orsini, Pietro Leocata, Maria Grazia Cifone,
Maurizio Giuliani pag 31

Case Report

Clinical and aesthetic results after medical treatment of subeyelid nodular basal cell carcinoma
Vincenzo Di Blasio, Angelo Forgione, Antonio Di Lucrezia, Dario Dorato pag 39

Courses and Congress pag 44

 Guidelines for Authors
Aesthetic Medicine is a multidisciplinary Journal with the aim of informing readers about the most important developments in the
field of Aesthetic Medicine.

Submission of manuscripts
All articles in their final version - completed with name, surname, affiliation, address, phone number and e- mail address of the
author (s) - must be sent in word format to the Editorial Committee at the following e-mail address:
[email protected]. Manuscripts must be written in English, and authors are urged to aim for clarity, brevity, and
accuracy of information and language. All manuscripts must include a structured abstract. Authors whose first language is not
English should have their manuscripts checked for grammar and stylistic accuracy by a native English speaker.

Manuscript specifications
Title page
The title page should include:
• The name(s) of the author(s)
• A concise and informative title
• The affiliation(s) and address(es) of the author(s)
• The e-mail address, telephone and fax numbers of the corresponding author
• Include a short title (not to exceed 30 characters in length, including spaces between words) for use as a running head
• The authors must disclose any commercial interest that they may have in the subject of study and the source of any
financial or material support

Abstract
The length of the abstract should be no more than 250 words and should include the following hea- dings: Background, Aim,
Methods, Results, Conclusions

Keywords
Up to six keywords should be listed and separated by a comma (please, verify keywords on MeSH).

Manuscript categories
Original article
The manuscript should be organised in the following sections:
• Structured Abstract. The length of the abstract should be no more than 250 words and should include the following
headings: Background, Aim, Methods, Results, Conclusions
• Introduction
• Materials and Methods
• Results
• Discussion and Conclusions
• Acknowledgments
• Conflict of interest
• Reference list
• Legends (max 10)

The manuscript must not exceed 4000 words and 50 references.

Review
This type of article uses Unstructured Abstract. It must not exceed 4000 words and includes figures and tables (max 15), legends,
and up to 200 references.

Mini-review
This type of article uses Unstructured Abstract. It must not exceed 2000 words and includes figures and tables (max 12), legends,
and up to 100 references.

Case Report
This type of article uses Unstructured Abstract. It must not exceed 1500 words and includes figures and tables (max 6), legends, and
up to 30 references.

Style
• Use a normal, plain font (e.g., 12-point Times Roman) for text
• Double-space the text
• Use italics for emphasis
• Use the automatic page numbering function to number the pages
• Do not use field functions
• Use tab stops or other commands for indents, not the space bar
• Use the table function, not spreadsheets, to make tables

Acknowledgments
The authors declare that they have no conflict of interest.
If potential conflicts of interest do exist, the authors should provide details (see below) for each affected author in a note in a
separate DISCLOSURE section of the manuscript document text, before the list of references.

Conflict of interest disclosure

Conflicts of Interest need to be explicitly defined before any manuscript can be considered for publication.

References
References must be cited consecutively in the text as superscript numerals and listed on a separate sheet in numerical order at the
end of the text. The references must be cited according to the AMERICAN MEDICAL AS- SOCIATION (AMA) CITATION STYLE.
For this reason, they must contain author’s surname and name initial, the original title of the article, the title of the journal
(abbreviated and in italic), the year of publication, the number of the volume, the number of the first and last page.

IV
AMERICAN MEDICAL ASSOCIATION (AMA) CITATION STYLE
Rev. 11/1/2012

General rules from the 10th edition

• Items are listed numerically in the order they are cited in the text
• Include up to 6 authors
• For more than six, provide the names of the first three authors and then add et al
• If there is no author, start with the title
• Periodicals (journals, magazines, and newspapers) should have abbreviated titles; to check for the proper abbreviation,
search for the Journal Title through LocatorPlus at the National Library of Medicine website

Citation Type Example

Journal article - in print - one author Spencer J. Physician, heal thyself - but not on your own please.
Med Educ. 2005; 89: 548-549.

Journal article - in print - 2-6 authors Salwachter AR, Freischlag JA, Sawyer RG, Sanfey HA. The
training needs and priorities of male and female surgeons and
their trainees. J Am Coll Surg. 2005; 201: 199-205.

Journal article – in print - more than 6 authors Fukushima H, Cureoglu S, Schachern P, et al. Cochlear changes
in patients with type 1 diabetes mellitus. Otolaryngol Head Neck
Surg. 2005; 133: 100-6.

Journal article - online* Coppinger T, Jeanes YM, Hardwick J, Reeves S. Body mass,
*if there is no DOI, provide the URL for the specific frequency of eating and breakfast consumption in 9-13- year-
article olds. J Hum Nutr Diet. 2012; 25(1): 43-49. doi: 10.1111/j.1365-
277X.2011.01184.x

Journal article - online from a library database* Calhoun D, Trimarco T, Meek R, Locasto D. Distinguishing
*there is no specific way to cite articles found in diabetes: Differentiate between type 1 & type 2 DM. JEMS [serial
library databases according to the AMA so double online]. November 2011; 36(11):32-48. Available from: CINAHL
check with your professor Plus with Full Text, Ipswich, MA. Accessed February 2, 2012.

Newspaper article - in print* Wolf W. State’s mail-order drug plan launched. Minneapolis
*if the city name is not part of the newspaper name, Star Tribune. May 14, 2004:1B.
it may be added to the official name for clarity
* if an article jumps from one page to a later page
write the page numbers like D1, D5

Newspaper article - online Pollack A. FDA approves new cystic fibrosis drug. New York
Times. January 31, 2012. http://www.nytimes.com/2012/02/01/
business/fda-approves-cystic-fibrosis-drug.html?ref=health
Accessed February 1, 2012.

Websites Outbreak notice: Cholera in Haiti. Centers for Disease Control

and Prevention Web site. https://www.cdc.gov
Published October 22, 2010. Updated January 9, 2012. Accessed
February 1, 2012.

Entire book - in print Modlin J, Jenkins P. Decision Analysis in Planning for a Polio
Outbreak in the United States. San Francisco, CA: Pediatric
Academic Societies; 2004.

Book chapter - in print Solensky R. Drug allergy: desensitization and treatment of

reactions to antibiotics and aspirin. In: Lockey P, ed. Allergens
rd
and Allergen Immunotherapy. 3 ed. New York, NY: Marcel
Dekker; 2004:585-606.

To find more AMA style citations, go checkout the

AMA Manual of Style: A Guide for Authors and Editors. 10th ed. Oxford: Oxford UP.

V
AMERICAN MEDICAL ASSOCIATION (AMA) CITATION STYLE
Rev. 11/1/2012

Citing sources within your paper

Unlike APA or MLA, you will not use the author’s last name for the in-text citations. Instead, you will number each
instance when you are referencing an article. The order of numbering will be contingent on the order in which you
use that reference within your paper. In the example below, the first article referenced is given the number one in
superscript. In the References section, you will find the matching article listed as number 1.

Example Article
1. Zoellner J, Krzeski E, Harden S, Cook E, Allen K, Estabrooks PA. Qualitative application of the theory of planned
behavior to understand beverage consumption behaviors among adults. J Acad Nutr Diet. 2012;112(11):1774-1784.
doi: 10.1016/j.jand.2012.06.368.

L
In-Text Citation Example ARGE INCREASES IN AMERICANS’ CONSUMPTION
OF sugar-sweetened beverages (SSB) have been
a topic of concern. Between 1977 and 2002, the
intake of “caloric” beverages doubled in the United
States, with most recent data showing that children and
adults in the United States consume about 172 and 175
1
kcal daily, respectively, from SSB, lt is estimated that SSB
2,3
account for about 10% of total energy intake in adults .
High intake of SSB has....

References
References Section Example 1. Duffey KJ. Popkin BM. Shifts in patterns and consumptions of
beverages between 1965 and 2002. Obesity. 2007:15(11):2739-2747.

2. Nielsen SJ. Popkin BM. Changes in beverage intake between 1977 and
2001. Am J Prev Med. 2004;27(3):205-210.

3. Drewnowski A. Bellisle F. Liquid calories, sugar, and body weight. Am

J Clin Nutr. 2007;85(3):651-661.

Use commas to separate multiple citation numbers in text, like you see between references 2 and 3. Unpublished works
and personal communications should be cited in the text (and not on the reference list).1 Superscript numbers are
placed outside periods and commas, and inside colons and semicolons. When citing the same source more than once,
give the number of the original reference, then include the page number (in parentheses) where the information was
found. See pages 41-44 of the AMA Manual of Style for more information.

References
Citing AMA guide website http://libguides.stkate.edu/c.php?g=101857&p. Updated April 2011. Accessed October 24,
2012.

To find more AMA style citations, go checkout the

AMA Manual of Style: A Guide for Authors and Editors. 10th ed. Oxford: Oxford UP.

VI
Images and Tables
All images within the word file must be numbered progressively and accompanied by the corresponding cap- tions,
with precise references in the text. Moreover, the images should be sent separately and in HD (at least 300 Dpi, in TIFF
or JPEG format).
Graphs and charts are progressively numbered and accompanied by the corresponding captions, with precise
references in the text. They must be sent separately, preferably in Excel format.
It is necessary to give the authorization to reproduce already published materials or to use people portraits, in case
they are recognizable. The Authors has full, exclusive and personal responsibility and respect for the rules protecting
privacy, originality and content (text, images) of the articles.

Artwork instructions
Permission
Photographs in which a person is identifiable must either have the face masked out, or be accompanied by written
permission for publication from the individual in the photograph. Authors wishing to include figures, tables, or text
passages that have already been published elsewhere are required to obtain permission from the copyright owner(s)
for both the print and the online format and to include evidence that such permission has been granted when
submitting their papers. Any material received without such evidence will be assumed to originate from the authors.
Please be informed that we will not be able to refund any costs that may have occurred in order to receive these
permissions from other publishers. Please be aware that some publishers do not grant electronic rights for free (an
example is Thieme Publishers). In these cases we kindly ask you to use figures from other sources.

Editorial Office

Via Monte Zebio, 28 - 00195 Rome

Phone + 39 06 37353333 - Fax +39 06 37519315
www.aestheticmedicinejournal.org

Submit your manuscripts at

[email protected]

VII
Publication Ethics and Publication Malpractice Statement
Aesthetic Medicine undertakes to defend the rules of ethical behavior in every stage of the process by adopting and promoting the
standards set by Code of Conduct and Best Practice Guidelines for Journal Editors.

Duties of Editors
Publication decisions
The editor of a peer-reviewed journal is responsible for deciding which of the articles submitted to the journal should be published.
The editor will evaluate manuscripts without regard to the authors’ race, gender, sexual orientation, reli- gious belief, ethnic origin,
citizenship, or political philosophy. The editor may be guided by the policies of the journal’s editorial board and constrained by such
legal requirements as shall then be in force regarding libel, copyright infringement and plagiarism.

Confidentiality
The editor and any editorial staff must not disclose any information about a submitted manuscript to anyone other than the
corresponding author, reviewers, potential reviewers, other editorial advisers or the publisher, as appropriate.

Disclosure and conflicts of interest

Unpublished materials disclosed in a submitted manuscript must not be used in an editor’s own research without the express
written consent of the author. Privileged information or ideas obtained through peer re- view must be kept confidential and not
used for personal advantage. When the editorial board is notified or discovers a significant problem regarding errors/ inaccuracy,
undisclosed conflict of interest, plagiarism, in a published article, the editorial board will promptly notify the corresponding author
and the publisher and will undertake the necessary actions to clarify the issue and in case of need to retract the paper or publish an
Erratum, following the COPE Guidelines.

Involvement and cooperation in investigations

An editor should take reasonably responsive measures when ethical complaints have been presented concer- ning a submitted
manuscript or published paper, in conjunction with the publisher (or society). Such measures will generally include contacting the
author of the manuscript or paper and giving due consideration of the respective complaint or claims made, but may also include
further communications to the relevant institutions and research bodies, and if the complaint is upheld, the publication of a
correction, retraction, expression of concern, or other note, as may be relevant. Every reported act of unethical publishing behaviour
must be looked into, even if it is discovered years after publication.

Duties of Reviewers
Contribution to editorial decisions
Peer review assists the editor in making editorial decisions and through the editorial communications with the author may also
assist the author in improving the paper. Peer review is an essential component of formal scho- larly communication, and lies at the
heart of the scientific endeavour. Aesthetic Medicine shares the view of many that all scholars who wish to contribute to publications
have an obligation to do a fair share of reviewing.

Promptness
Any selected referee who feels unqualified to review the research reported in a manuscript or knows that its prompt review will be
impossible should notify the editor and excuse him/herself from the review process.

Confidentiality
Any manuscripts received for review must be treated as confidential documents. They must not be shown to or discussed with
others except as authorised by the editor.

Standards of objectivity
Reviews should be conducted objectively. Personal criticism of the author is inappropriate. Referees should express their views
clearly with supporting arguments.
Acknowledgement of sources
Reviewers should identify relevant published work that has not been cited by the authors. Any statement that an observation,
derivation, or argument had been previously reported should be accompanied by the relevant citation. A reviewer should also call
to the editor’s attention any substantial similarity or overlap between the manuscript under consideration and any other published
paper of which they have personal knowledge.

Disclosure and conflict of interest

Unpublished materials disclosed in a submitted manuscript must not be used in a reviewer’s own research wi- thout the express
written consent of the author. Privileged information or ideas obtained through peer review must be kept confidential and not
used for personal advantage. Reviewers should not consider manuscripts in which they have conflicts of interest resulting from
competitive, collaborative, or other relationships or con- nections with any of the authors, companies or institutions connected to
the papers.

Duties of Authors
Reporting standards
Authors of reports of original research should present an accurate account of the work performed as well as an objective discussion
of its significance. Underlying data should be represented accurately in the paper. A paper should contain sufficient detail and
references to permit others to replicate the work. Fraudulent or knowingly inaccurate statements constitute unethical behaviour and
are unacceptable. Review and professional publica- tion articles should also be accurate and objective, and editorial ‘opinion’ works
should be clearly identified as such.

Data access and retention

Authors may be asked to provide the raw data in connection with a paper for editorial review, and should in any event be prepared
to retain such data for a reasonable time after publication.

VIII
Originality and plagiarism
The authors should ensure that they have written entirely original works, and if the authors have used the work and/or words of
others, that these have been appropriately cited or quoted. Plagiarism takes many forms, from “passing off” another’s paper as the
author’s own paper, to copying or paraphrasing substantial parts of another’s paper (without attribution), to claiming results from
research conducted by others. Plagiarism in all its forms constitutes unethical publishing behaviour and is unacceptable.

Multiple, redundant or concurrent publication

An author should not in general publish manuscripts describing essentially the same research in more than one journal or primary
publication. Submitting the same manuscript to more than one journal concurrently consti- tutes unethical publishing behaviour
and is unacceptable. In general, an author should not submit a previously published paper for consideration in another journal.

Acknowledgement of sources
Proper acknowledgment of the work of others must always be given. Authors should cite publications that have been influential
in determining the nature of the reported work. Information obtained privately, for example in conversation, correspondence, or
discussion with third parties, must not be used or reported without expli- cit, written permission from the source. Information
obtained in the course of confidential services, such as refereeing manuscripts or grant applications, must not be used without the
explicit written permission of the author of the work involved in these services.

Authorship of the paper

Authorship should be limited to those who have made a significant contribution to the conception, design, execution or interpretation
of the reported study. All those who have made significant contributions should be listed as co-authors.
Where there are others who have participated in certain substantive aspects of the research project, they should be acknowledged or
listed as contributors. The corresponding author should ensure that all co-authors have seen and approved the final version of the
paper and have agreed to its submission for publication.

Hazards and human or animal subjects

If the work involves chemicals, procedures or equipment that have any unusual hazards inherent in their use, the author must
clearly identify these in the manuscript. If the work involves the use of animal or human subjects, the author should ensure
that the manuscript contains a statement that all procedures were perfor- med in compliance with relevant laws and institutional
guidelines and that they have been approved by the appropriate institutional committee(s). Authors should include a statement in
the manuscript that informed consent was obtained for experimentation with human subjects. The privacy rights of human subjects
must always be observed.

Disclosure and conflicts of interest

All authors should disclose in their manuscript any financial or other substantive conflict of interest that might be construed to
influence the results or interpretation of their manuscript. All sources of financial sup- port for the project should be disclosed.
Examples of potential conflicts of interest which should be disclosed include employment, consultancies, stock ownership, honoraria,
paid expert testimony, patent applications/ registrations, and grants or other funding. Potential conflicts of interest should be
disclosed at the earliest stage possible.

Fundamental errors in published works

When an author discovers a significant error or inaccuracy in his/her own published work, it is the author’s obligation to promptly
notify the journal editor or publisher and cooperate with the editor to retract or correct the paper. If the editor or the publisher
learns from a third party that a published work contains a significant error, it is the obligation of the author to promptly retract or
correct the paper or provide evidence to the editor of the correctness of the original paper.

IX
Editorial
In modern years, aesthetics has become quite important in every aspect of everyday life: following the hundreds of
journals, magazines, blogs and websites pointing their attention towards this interesting and fascinating topic, the
request for aesthetic medicine has increased manifolds.
Aesthetic Medicine is a new field of medicine, in which different specialists share the aim of constructing and
reconstructing the physical equilibrium of the individual. Treatment of physical aesthetic alterations and unaesthetic
sequel of illnesses or injuries, together with the prevention of aging, are perhaps two of the most iconic areas of
intervention for Aesthetic Medicine.
However, in order to prevent frailty in the elderly, a program of education is similarly important.
Furthermore, the line between health and beauty is extremely thin: psychosomatic disorders resulting from low self-
esteem due to aesthetic reasons are frequent and can- not be ignored by a clinician.
It is therefore clear that there is no figure in the field of medicine which is not involved in Aesthetic Medicine:
endocrinologists, gynecologists, angiologists, psychologists and psychiatrists, plastic surgeons, dermatologists,
dieticians, physiotherapists, orthopedists, physical education instructors, massophysiotherapists, podologists, and
rehabilitation therapists are just some of the specialists who are sooner or later going to have to answer their patients’
needs for aesthetic interventions.
The involvement of all these specialists fits the description of health as defined by the WHO: “a state of complete
physical, mental and social well-being and not merely the absence of disease or infirmity” for which, undeniably, a team
of different physicians is required.
The number of patients requiring medical consultation for esthetic reasons is rapidly increasing: in order to be able to
provide adequate feedback, medical and paramedical specialists should be trained and, more importantly, should be
taught how to work together. Existing Societies of Aesthetic Medicine from different countries share the aim of creating
such teams and provide constant updates to the literature: the creation of an international network of specialists from
all around the world under the flag of Aesthetic Medicine represents a challenge, but at the same time it is the proof of
the widespread interest in this topic.
The first issue of this Journal represents the results of the efforts of the many national Societies and of the Union
Internationale de Medecine Esthetique, now together as one; it is our hope that in years to come this Journal might
improve our knowledge in this field, and provide adequate scientific advancement in the field of Aesthetic Medicine.

Francesco Romanelli
MD Editor-in-chief
Associate Professor at “Sapienza” University of Rome

X
Editors’ notes
Aesthetic Medicine, the booming medical activity
Aesthetic Medicine was born in France 40 years ago.
The French Society of Aesthetic Medicine was the first of its kind in the world, followed by Italy, Belgium and Spain.
Starts were rather difficult as aesthetic procedures in those early years were only surgical.
At that time aesthetic doctors and cosmetic dermatologists had very few real medical procedures to offer to their patients
for treating aesthetic problems on face and body.
At the beginning of the ‘80s, viable medical procedures started to emerge in Europe for aesthetic and cosmetic purposes.
Mostly, at that time, they were imported from the United States: those included collagen injections for wrinkles (Zyderm
by Dr. Stegman), and chemical peels (phenol by Dr. Baker, TCA by Dr. Oba- gi). But, subsequently, European research on
Aesthetic Medicine gained momentum. Hyaluronic acid appeared on the market, as it was discovered that it could be used
as a dermal filler for wrinkles. During the ‘90s, the use of lasers offered aesthetic doctors and cosmetic dermatologists
new possibilities.
The “beam revolution” started with CO2 laser for facial resurfacing.
Today, CO2 resurfacing is not used as much anymore, because of the long and difficult postop. CO2 laser was replaced
with the gentler Nd-YAG and Erbium lasers and more recently with non invasive photonic devices for facial rejuvenation,
including IPL, US and radiofrequency. These new technologies allow today’s aesthetic doctors and cosmetic dermatologists
to offer their patients procedures with low risk of post- op complications. Then, Botulinum Toxin has “invaded” both
sides of the Atlantic Ocean.
Today, Botox injections are the most popular treatment for facial expressive wrinkles.
Botox injections are now so common everywhere that many cosmetic surgeons have given up their bistouries for
syringes. Last but not least, development in Aesthetic Medicine is shown by mesotherapy and adipolipolysis.
About lipolysis, new data and recent publications have explained that radiofrequency, ultrasounds and cryolyse could
have positive action to dissolve fat and to improve some unaesthetic disorders like cellulite.
These non invasive procedures intend to replace the surgical liposculpture with success.
Nowadays, Aesthetic Medicine has the necessary tools to address all major disorders within the aesthetic field. After 40
years, Aesthetic Medicine is now active in 32 countries in the world (France, Italy, Spain, Belgium, Morocco, Poland, Russia,
Switzerland, Kazakhstan, Algeria, Brazil, Argentina, Uruguay, Venezuela, Colombia, Chile, Mexico, U.S.A, Canada, South
Korea, Ecuador, China, South Africa, Turkey, Ukraine, Georgia and recently Croatia, Portugal, India, Guatemala, Peru and
Bolivia). All 32 national Societies are members of the Union Internationale de Médecine Esth tique (U.I.M.E.). Aesthetic
Medicine is taught in 7 countries (France, Italy, Spain, Argentina, Mexico, Venezuela, Kazakhstan) in universities that
deliver UIME’s diplomas after 3 to 4 years of studies.

What is the future of Aesthetic Medicine?

In the last few decades, patients’ desires to look and feel younge, have fueled Aesthetic Medicine and Cosmetic
Dermatology: many different procedures have been developed to satisfy the demands.
As life-span have increased, patients today are not only asking about aesthetic procedures, they are also asking for a
way to stay in good physical conditions in the last decades of their lives. As a direct result, Anti-Aging Medicine, which
covers skin aging and general aging, has recently emerged and expanded very quickly. Anti-Aging Medicine can offer
senior patients better nutrition, dietary supplementation with vitamins, minerals, antioxidants, and eventually hormone
replacement therapy, but only when needed.
Today, and in the near future, both Aesthetic Medicine and Anti-Aging Medicine will offer to our patients, who now live
longer, better wellness with aesthetic treatments for skin aging and anti-aging treatments for general aging. Aesthetic
Medicine is booming, but all medical practitioners should be correctly trained, so its future will be bright.

Jean-Jacques Legrand
Former General Secretary and Honorary President of UIME

XI
Aesthetic Medicine: a bioethic act
When in 1977 the Italian Society of Aesthetic Medicine published the first issue of the magazine “La Medicina Estetica”
Carlo Alberto Bartoletti, the Founder, wrote an editorial in which traced the pathway of the discipline and of the Scientific
Society, still valid and projected into the future.
Today from that Editorial Board arise an International Journal, which wants to be indexed, in order to give to the doctors
practicing Aestehetic Medicine all around the world a solid basis of shared knowledge.
In the late ‘60s, what was called in Italy Aesthetic Medicine, moved its first steps thanks to “remise en forme and anti
aging projects” imported from the experience the “Institutul de geriatrie Bucuresti”, directed by Dr. Ana Aslan.
For this reason,there is the bioethical imperative that the Discipline should be first prevention, then return to physiology
and finally correction.
The worldwide diffusion and the efforts of Industries born on the wave of the phenomenon have often led to choose
the fastest route to achieve and maintain the physical aspect in the myth of beauty at all costs, without considering that
aesthetic is not synonymous of beauty, but it is a balance between body and mind, and the role of the doctor is to take
care of the Person globally and not only focusing on the correction of “a badly accepted blemish”.
Faithful to the teaching of my Master had almost 50 years ago, this new journal will have the task of elevating the human
resources, aligning and validating methodologies, but above all affirming the humanitas of the medical art in its purest
sense to pursue the good and the graceful for the person who relies on it.

Fulvio Tomaselli, MD
Honorary President of the Italian Society of Aesthetic Medicine

Aesthetic Medicine needs science. All over the world

All Aesthetic Doctors know that science is the basis for safety. Safety is the most important issue in our discipline.
Unfortunately, Aesthetic Medicine is more often surrounded by marketing than by science, despite the hard work done by
Scientific Societies all over the World. And, too often doctors working in this field are dealing with sellers that promote
products with insufficient scientific studies.
However, they sell it anyway. I think that doctors must learn that the first thing to ask about a medical device is
the scientific background regarding that product: patients treated, follow up period, adverse events and, most of all,
publications.
With this new International Journal completely dedicated to Aesthetic Medicine, proposed by the Italian Society of
Aesthetic Medicine, endorsed by UIME and shared by all the National Societies of Aesthetic Medicine belonging to UIME,
World Aesthetic Medicine wants to stimulate scientific production in this discipline to increase safety and quality in
aesthetic medical procedures.
Another important goal of the Journal is to catalyze the proposal of new protocols and guidelines in Aesthetic Medicine,
with the consensus of the entire Aesthetic Medicine Scientific Community.
What this Journal should achieve in the near future is to improve the number and quality of scientific production in
Aesthetic Medicine, in order to allow this discipline to grow in the field of evidence based medicine, not only in the
rationale field.
I hope this can be the start of a new era for Aesthetic Medicine, with the commitment of all Scientific Societies all over
the world.

Emanuele Bartoletti, MD
Managing Editor
President of the Italian Society of Aesthetic Medicine

XII
 INTERNATIONAL SOCIETIES
and NATIONAL SOCIETIES OF AESTHETIC MEDICINE

INTERNATIONAL SOCIETY OF AESTHETIC MEDICINE ITALIAN SOCIETY OF AESTHETIC MEDICINE

154, rue Armand Silvestre - 92400 Courbevoie Via Monte Zebio 28 - 00195 Rome - Italy
France Honorary Presidents: C.A. BARTOLETTI † (Italy), A. BOURRA (Morocco), M. [email protected] - www.lamedicinaestetica.it
DELUNE (USA), A. FARIA DE SOUZA (Brazil), J. FONT-RIERA† (Spain), G. MARZULLO President: E. BARTOLETTI
(Chile), R. PINTO (Argentine), J. HEBRANT (Belgium), A. ELBAUM (Uruguay), J.J.
LEGRAND (France), M. OUGHANEM (Algeria) KAZAKHSTAN ASSOCIATION OF AESTHETIC MEDICINE AND PLASTIC SURGERY
139, Tulebaeva Str. – 480091 Almati, Medeouski
President: V. GARCIA GUEVARA (Venezuela) [email protected]
Vicepresident: A. IGNACIUK (Poland) President: G. ZHUMATOVA
General Secretary: E. BARTOLETTI (Italy)
General Secretary in charge KOREAN ACADEMY OF AESTHETIC MEDICINE
of the American Continent: R. PINTO (Argentina) Han-Song B.D. 801, Myeong-dong, Jung-gu, Seoul - Korea
of Africa and Middle East: A. BOURRA (Morocco) [email protected]
President: WOOHA HAN
ALGERIAN SOCIETY OF AESTHETIC MEDICINE
Bt.T1, N°2, Diar Es Saada, El Madania, Algiers - Algeria MEXICAN SCIENTIFIC SOCIETY OF AESTHETIC MEDICINE
[email protected] Cincinnati 81-307 - Col. Noche Buena - Mexico D.F. 03720
President: M. OUGHANEM [email protected] - www.facebook.com/Sociedad.Mexicana.Cientifica.
Medicina.Estetica
ARGENTINE SOCIETY OF AESTHETIC MEDICINE President: J-B. MILLER KOBISHER
Avenida Santa Fé 3288, 4°A - 1425 Buenos Aires - Argentina
[email protected] - www.soarme.com MOROCCAN SOCIETY OF AESTHETIC MEDICINE
President: R. PINTO 19, place du 16 Novembre - 20250 Casablanca - Morocco
[email protected] - www.dermastic.asso.ma
BELGIAN SOCIETY OF AESTHETIC MEDICINE President: A. BOURRA
Chaussée de Marche 390 - 5100 Jambes - Belgium
[email protected] - www.aesthetic-medicine.be SCIENTIFIC ASSOCIATION OF AESTHETIC MEDICINE OF PERU
President: J. HEBRANT Av. Jose Pardo 1801, Miraflores Lima - Peru
[email protected] - www.asocime.com.pe
BOLIVIAN ASSOCIATION OF AESTHETIC MEDICINE President : I. OGATA
[email protected]
President : D. H. HURTADO TERRAZAS POLISH SOCIETY OF AESTHETIC AND ANTI-AGING MEDICINE
OF POLISH MEDICAL SOCIETY
BRASILIAN ASSOCIATION OF AESTHETIC MEDICINE SCIENCES Ujazdowskie 22, 00-478 Warszawa - Poland
Avenida Vereador José Diniz - 2480 - Brooklin - Sao Paulo CEP 04604-004 [email protected] - www.ptmeiaa.pl
[email protected] President: A. IGNACIUK
President: C. SANTOS
PORTUGUESE SOCIETY OF AESTHETIC AND ANTI-AGING MEDICINE
CANADIAN ASSOCIATION OF AESTHETIC MEDICINE Rua Maria Vitoria Bourbon Bobone, Lote 21, N°41, Apto. 201 P-3030-502 Coimbra
1087 Roosevelt Crescent, North Vancouver, BC Canada V7P 1M4. [email protected] - www.spme.pt
[email protected] - www.caam.ca President: J.P. VALE
President: R. Van AARDT
RUSSIAN NATIONAL AESTHETIC MEDICINE SOCIETY
CHILEAN ASSOCIATION OF AESTHETIC MEDICINE 12/3 Fotievoi Street, Pol. n.3 - of.512 - 119333 Mosca - Russia
Avda President Riesco 2955, apto 1102, Las Condes Santiago - Chile [email protected]
[email protected] - www.sochme.cl President: O. PANOVA
President: G. MARZULLO
AESTHETIC AND ANTI AGING MEDICINE SOCIETY OF SOUTH AFRICA
CHINA ACADEMY OF AESTHETIC MEDICINE PO Box 26716, Monumentpark, Pretoria, Gauteng, South Africa, 0105
Department of Stomatology, General Hospital of PLA 28 Fuxing road, BEIJING [email protected] - www.aestheticdoctors.co.za - [email protected]
100853 - China President : J. VAN NIEKERK
[email protected]
President: LI SHIRONG SPANISH SOCIETY OF AESTHETIC MEDICINE
Ronda General Mitre, 210
COLOMBIAN ASSOCIATION OF AESTHETIC MEDICINE 08006 Barcelona - Spain
Calle 4 Sur, n. 43 a 195 - Oficina 141 - Bloque B - Medellin - Colombia [email protected] - www.seme.org
[email protected] - www.acicme.com.co President: P. VEGA
President: G. ARROYAVE ESTRADA
SWISS SOCIETY OF AESTHETIC MEDICINE
CROATIAN SOCIETY OF AESTHETIC MEDICINE La Clinique - avenue de Collonge, 43 - CH - 1820 Territet - Montreux
51414 Opatija, Croatia - Phone: 0038 5921707322 [email protected] - www.ssme.ch
[email protected] - www.huem.eu President: S. LE-HUU
President: E. BUNAR
SOCIETY OF AESTHETIC MEDICINE IN TURKEY
ECUADORIAN SOCIETY OF AESTHETIC MEDICINE Rumeli Caddesi Durak Apt N° 2, D.7 - Nisantasi, Istanbul
Ave de los Shyris 344 y Eloy Alfaro, Edificio Parque Central, Oficina 609 - Quito - Ecuador [email protected] - www.estetiktipdernegi.org.tr
[email protected] - www.seem.com.ec President: H. SUBASI
President: V. TINOCO KIRBY
UKRAINIAN SOCIETY OF AESTHETIC MEDICINE
FRENCH SOCIETY OF AESTHETIC MEDICINE Bunina Street, 10 Odessa 65026 - Ukraine
154, rue Armand Silvestre - 92400 Courbevoie - France [email protected] - usam.org.ua
[email protected] - www.sfme.info President: V. TSEPKOLENKO
President: J.J. LEGRAND
AESTHETIC MEDICINE SOCIETY OF URUGUAY
GEORGIAN SOCIETY OF AESTHETIC MEDICINE Ave. Sarmiento, 2470 - 11300 Montevideo - Uruguay
Irakli Abashidze str. 77, Tbilisi 0162 - Georgia [email protected] - www.sume.com.uy
[email protected] President: A. ELBAUM
President: E. UGREKHELIDZE
AMERICAN ACADEMY OF AESTHETIC MEDICINE
ASSOCIATION OF AESTHETIC AND ANTIAGING MEDICINE OF GUATEMALA 24671 La Vida Drive - Laguna Niguel, Ca 92677 - USA
6a Av. 9-18 Zona 10 Edif. Sixtino 2, Of. 405 ala 2, Guatemala Cd. [email protected] - www.aaamed.org
[email protected] President: M. DELUNE
President: C. A. ROSALES GONZÁLEZ
AESTHETIC MEDICINE SOCIETY OF VENEZUELA
INDIAN SOCIETY OF AESTHETIC MEDICINE Av. Sucre de Los Dos Caminos, entre 4ta y 5ta transversal,
E-52/Basement/ Greater Kailash-Il, New Delhi-110048 Res. Centro Parque Boyacà, Edificio Centro, Piso 20, Off. 201 1070 Caracas - Venezuela
[email protected] [email protected] - www.fuceme.org - www.sociveme.org
President: A. RANA President: V. GARCIA GUEVARA

XIII
Original Article

AFLAX MLT®: a new medical treatment,

effective and powerful to treat skin
flaccidity
Graciela Melamed
MD, GMC Clinic, Buenos Aires - Argentina

Abstract
Introduction: cutaneous flaccidity is a complex problem that involves intrinsic and extrinsic factors. Many treatments
and procedures have been developed to improve it, but the results obtained so far have not been truly satisfactory, thus,
the development of new minimally invasive products that can recover the mechanical properties of the skin and offer
natural results continues. The objective of this study was to evaluate the efficacy and safety of a new treatment, AFLAX
MLT®, minimally invasive that acts at different levels of the skin.
Methods: prospective, study was carried out in women between 29 and 62 years old with abdominal flaccidness, who
received three AFLAX MLT® treatment sessions. Each session consisted in the administration of two injectable vials
(one at superficial subcutaneous level and another one intradermal) and a cream that was applied topically, in the last
place. All treatments were performed by the same researcher. The firmness and flexibility of the skin were evaluated by
cutometry, and pain as well as patient/physician satisfaction were evaluated by self-assessment scales.
Results: 39 patients with a mean age of 45.80 (10.09) were treated. The differences between pre- and post-treatment
measurements were statistically significant for all the variables, achieving an improvement of skin flaccidity at 30 days
after the third session of 22.91% for R0, 16.82% for R2, 14.40% for R5 and 20.73 for R7.
Conclusion: the results obtained with the new AFLAX MLT® multilevel therapy were well tolerated and rated very
satisfactorily by patients. It showed an improvement of the mechanical properties of the skin, with a significant increase
in the firmness as well as the elasticity of the treated area.

Keywords
Flaccidity, abdomen, aging

Received for publication June 18, 2018; accepted September 6, 2018 - © Salus Internazionale ECM srl - Provider ECM nº 763

Correspondence

Graciela Melamed, MD
GMC Clinic, Buenos Aires – Argentina
E-mail: [email protected]

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 14

 AFLAX MLT®: a new medical treatment, effective and powerful to treat skin flaccidity

Introduction product specifications. A follow-up visit was made 30

Flaccidity is closely related to age. Currently, the fight days after the third treatment. The treatment consisted
against the passage of time and its impact on the of the administration of three products, two of them
body results in a continuous i+d race for products injectable and a third topical:
and procedures aimed at mitigating the visible signs • Vial 1: injectable for subcutaneous action. Assets
of aging. Cutaneous flaccidity is a complex problem specially designed to act in depth, nourish and
that involves intrinsic and extrinsic factors. The loss protect the tissues that offer trophic support and
of volume, excess of skin pigmentation and the low or provide structural basis for the upper layers. Active
irregular reflectance of light are among the intrinsic principles: glycine, proline, lysine, leucine, alanin,
factors1. On the other hand, the most relevant extrinsic hialuronic acid, decapeptide-4, oligopeptide-24, lipoic
factor is sun exposure, also known as photo-aging. acid, thiamin, cyanocobalamin, adenine.
• Vial 2: intradermal injectable product specifically
One of the first events in skin aging is flaccidity. For designed to act where proteins such as collagen, fibrin
example in the face, a descent of the middle and lower or elastin are synthesized. Improves skin mechanical
thirds occur. Flaccidity can also be seen in other areas of properties. Active principles: centroxifenoxine,
the body, such as the abdomen or brachial area. In this ascorbic acid, sodium lactate, copper gluconate, zinc
dynamic process, aging, as well as soft tissue and bone gluconate, condroitin sulphate, tripeptide-6.
structures are involved1. Not only is there a decrease in • Vial 3: cosmetic topical product. This cream on
collagen, skin thinning and fat loss lead to flaccidity2,3. the most superficial layers of the skin (epidermis)
In addition, there is a subtle interaction between bone producing a tensor effect, immediate and lasting.
resorption, fat atrophy, the thinning of collagen and Active principles: glutapeptide, cafesilane C2, celutrat,
elastic fibers1, and an evident decrease in cell turnover. raffermine, sesaflash, lecithin.
All these factors together added to the effect of gravity Aflax MLT® protocol must be administered by a
on the loose tissue, ultimately conduct to the formation physician.
of folds, wrinkles and the fine lines4.
Very frequently, the correction of these aging signs has Procedures prior to treatment
been approached with surgical techniques and other Before starting the treatment, skin mechanical
invasive rejuvenation procedures, such as sutures5, properties were evaluated with a cutometer /MPA
or other suspension systems, like threads. But these 580, Courage + Khazaka Electronic GmbH, Cologne,
invasive procedures are not the desired choice for many Germany). The Cutometer® measures the elasticity of
patients. the skin by means of pressure (suction) that deforms the
Skin rejuvenation therapies should be oriented towards skin. The resistance of the skin to the negative pressure
the mitigation of the damage and the restoration of the is related to the firmness and its ability to return to the
original structure of the tissues, in order to recover initial position. All parameters are shown as curves in
their mechanical properties. Procedures should be as real time during the measurement. This device allows
minimally invasive, safe and effective as possible, and the obtainment of information about the elastic and
deliver natural and more lasting, focusing on the needs mechanical properties of the skin and to quantify
of each patient individually4. objectively its efficiency6-7. Measurements were taken
The objective of this study was to evaluate the safety at a pressure of 450 mbar, through a 2 mm probe hole.
and efficacy of AFLAX MLT®, a new multilevel, Cutometry parameters were: suction 2 seconds (on), 10
minimally invasive treatment to recover the elasticity repetitions and 2 seconds between suction (off).
and firmness of the skin.
Treatment protocol
The treatment protocol included 3 sessions of AFLAX
MLT® multilevel therapy in the abdomen, in a period
Materials and methods of 1 month. Each session lasted approximately 20
Study design minutes and was performed by the same physician
Prospective, non-randomized, single-center study, and in the same facilities. Every session, included the
carried out on women, at the GMC Clinic center in application of the 3 AFLAX MLT® products (vial 1, vial 2
Buenos Aires (Argentina), during February 2018. and cream): i) vial 1 was injected at a depth of 5-6 mm
The study was conducted in accordance with the through a slow, retrograde, fan technique, with a 27G
principles established in the current revised version of / 40mm needle; ii) vial 2 was injected intradermally (3
the Declaration of Helsinki, with Good Clinical Practice mm), with a 30G1/2 needle: iii) and vial 3 was applied
(BPC). topically in the consultation. The patient was given the
Inclusion criteria: Women from 29 to 62 years old, with tube of cream for a home-based application during the
signs of abdominal flaccidity. following 10 days, in the same area and once a day, until
Exclusion criteria: i) systemic pathologies, ii) under the next session.
daily medication, and iii) have received any aesthetic
treatment one month before or less of the first session. Post treatment evaluation
After each treatment, pain was assessed with a visual
Study protocol analog scale (VAS), classifying it from 0 to 10 (0: no
Patients were consecutively recruited. pain and 10: maximum pain that the patient was able to
Patients received 3 treatment sessions with AFLAX imagine).
MLT® in the abdomen, over a month, according to the 30 days after the third therapeutic session, patient and

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 15

 AFLAX MLT®: a new medical treatment, effective and powerful to treat skin flaccidity

physician satisfaction was evaluated, using a subjective Results

1 to 5 scale (1: not satisfied, 2: I am not sure, 3: a little bit The study included 39 female patients, with an average
satisfied, 4: satisfied and 5: very satisfied). age of 45.80 (10.09).
30 days after the third therapeutic session cutometry
was performed again. R0, R2, R5 and R7 variables were Skin characteristics
re-evaluated with the Cutometer®MPA 580. Before treatment, the mean results of skin cutometry
At each treatment and follow-up visit, any adverse were: R0 = 0.28 (0.05) mm, R2 = 0.65 (0.09) mm, R5 =
effects and its characteristics were recorded. 0.42 (0.07) mm and R7 = 0.33 (0.04) mm. After 30 days
of the third treatment, the results were: R0 = 0.34 (0.05)
Evaluation of the data mm, R2 = 0.76 (0.07) mm, R5 = 0.48 (0.07) mm and R7
Analyzed variables were: age, patient and researcher = 0.33 (0.04) mm. The differences between the pre- and
satisfaction (outcome), pain and cutometry variables post-treatment values were statistically significant for
(R0, R2, R5 and R7): all variables R0 p <0.0001, R2 p <0.0001, R5 p = 0.0003
• R0: Parameter that shows the maximum amplitude of and R7 p <0.0001 (Figure 1).
the curve and represents the passive response of the The percentages of improvement of the characteristics
skin to force (firmness). of the skin at 30 days after the third treatment were:
• R2: represents the gross elasticity, which is the 22.91% for R0, 16.82% for R2, 14.40% for R5 and 20.73%
resistance versus return capacity for R7.
• R5: represents the net elasticity: elastic portion of the R0: Parameter that shows the maximum amplitude
curve of the curve and represents the passive response of
• R7: Assesses the portion of the elastic curve compared the skin to force (firmness). R2: represents the gross
to the complete curve. The closer is to 1 (100%), the elasticity, which is the resistance versus return capacity.
more elastic the curve. R5: represents the net elasticity: elastic portion of the
Side effects were recorded at every visit. curve. R7: Assesses the portion of the elastic curve
compared to the complete curve. The closer is to 1
Statistical analysis (100%), the more elastic the curve.
Unless otherwise indicated, quantitative variables
are described as the mean followed by the standard Subjective evaluation
deviation (SD) between brackets, while categorical The subjective evaluation of the treatment by the
variables are described as a percentage. Statistical patients, 30 days after the third treatment with AFLAX
analysis included appropriate measures for statistical MLT® was: 35.90% 5 points “very satisfied”, 53.85% 4
significance (Student’s paired two-sample t test) using points “satisfied”, 10.26% 3 points “a little satisfied”, 0%
the standard cutoff for significance of P<0.05 via 2 “I’m not sure”, 0% 1 “not satisfied”.
Microsoft Excel. The subjective evaluation of the treatment by the
researcher, 30 days after the third treatment with
AFLAX MLT® was: 28.21% 5 “very satisfied”, 53.85% 4
“satisfied”, 12.82% 3 “a little satisfied”, 5.13% 2 “I’m not
sure”, 0% 1 “not satisfied”.

Figure 1 - Mean result of cutometry parameters obtained before treatment and 30 days after the third session.

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 16

 AFLAX MLT®: a new medical treatment, effective and powerful to treat skin flaccidity

The average of the subjective assessment by the the visible signs of flaccidity and restore the damage.
patients included in the study was 4.26 ± 0.64 and 4.05 These statements can be made after reviewing the
± 0.79 by the researcher. The differences between the results of the cutometry, a validated technique that
two assessments were not statistically significant (p = analyzes the mechanical behavior of the skin and thus,
0.2010). the repercussion of age-related changes and photo-
aging. R parameters recorded an important increment
Pain assessment in skin firmness compared to the basal values. Other
The average value of pain assessment by the patients treatments, such as injected conditioned autologous
after the application of each product of AFLAX MLT® serum, have also reported an improvement in skin
treatment, by a VAS scale: was: 2.33 ± 1.44 for vial 1; characteristics, but the results have not been as good
2.77 ± 1.51 for vial 2 and 0.03 ± 0.16 for cream. The as the ones reported in this study, with AFLAX MLT®.
differences between vial 1 and vial 2, both administered Increments of 10.38% in R0, 16.59% in R2, 11.21% in R5
by injection with 27G and 30G1/2 needle respectively, and 16.16% in R7 were reported8. Other techniques such
were not statistically significant (Table 1) as non-invasive treatment with ultrasound, have also
reported the amelioration of the mechanical properties
Safety data of the skin. A study assessed the improvement of normal
The only adverse effects observed were the usual mild skin after the application of ultrasound, obtaining an
inflammatory signs after a puncture. All resolved improvement in firmness (R = 0) of 15.95%, and 5.52% in
within few days. the elastic component (R2)9.

Discussion Conclusions
The results of the study show that AFLAX MLT® The multi-level treatment AFLAX MLT® offers a
multilevel therapy improves the mechanical properties minimally invasive option, with no important side
of the skin, significantly increasing firmness and effects and with significant results that improve the
elasticity. Both the patients and the researcher evaluated mechanical characteristics of the skin in a natural way.
positively the results. The treatment was well tolerated However, more studies would be needed with a greater
by the patients, without observing adverse effects. number of patients, in which men were included and
AFLAX MLT® multi-level treatment is designed for each with longer follow-up. Likewise, the duration of the
product to act at the proper level and help replenish the treatment effect should be evaluated and assessed to see
original structure of the tissue that has deteriorated if it is possible to improve the result by administering
over time. Each product contains different actives and a greater number of sessions and analyze whether it
its action targets a specific depth of the skin. offers the same benefits in other areas of the body.
This approach is based on the multi-factorial
physiopathology of flaccidity. The results obtained
are good and patients´ appearance is natural. This
treatment is indicated when the first symptoms of Conflict of interests
skin aging appear, so that it could delay the onset of None.

Table 1 - Patients’ pain assessment after the application of each product.

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 17

 AFLAX MLT®: a new medical treatment, effective and powerful to treat skin flaccidity

REFERENCES

1. Beer K, Beer J. Overview of Facial Aging. Facial Plast Surg. 2009;

25(5):281-4.

2. Kahn D, Shaw RB. Overview of current thoughts on facial volume and

aging. Facial Plast Surg. 2010; 26(5):350-5.

3. Farage MA, Miller KW, Elsner P, Maibach HI. Structural characteristics

of the aging skin: a review. Cutan Ocul Toxicol. 2007; 26(4):343-57.

4. Goldman A, Wollina U. Facial rejuvenation for middle-aged women: a

combined approach with minimally invasive procedures. Clin Interv
Aging. 2010; 5:293-9.

5. Kalra R. Use of barbed threads in facial rejuvenation. Indian J Plast

Surg. 2008; 41(Suppl):S93-100.

6. Dobrev H. Application of Cutometer area parameters for the study of

human skin fatigue. Ski Res Technol. 2005; 11(2):120-2.

7. Ohshima H, Kinoshita S, Oyobikawa M, et al. Use of Cutometer area

parameters in evaluating age-related changes in the skin elasticity of
the cheek. Ski Res Technol. 2013; 19(1):1-5.

8. Pinto H, Garrido-Gorgojo L. Study to Evaluate the Aesthetic Clinical

Impact of an Autologous Antiaging Serum. Jour Drugs Dermatol.
2013; 12(3):322-6.

9. Brancalion Catapani L, da Costa Gonçalves A, Morano Candeloro

N, Rossi LA, Caldeira de Oliveira Guirro E. Influence of therapeutic
ultrasound on the biomechanical characteristics of the skin. J Ther
Ultrasound. 2016; 4(1):21.

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 18

Original Article

Results of practical application of fibroblasts

in treating age-related skin changes. An
open, prospective, non-randomized study
Anna Tsepkolenko1, Aleksandr Litus2, Vladimir Tsepkolenko3
1Dermatologist at Institute Virtus, postgraduate student of the dermatovenerology department at P.L. Shupik National Academy of Postgraduate Education

2MD, PhD., Professor, head of the dermatovenerology department at P.L. Shupik National Academy of Postgraduate Education

3MD PhD., Professor, director of Institute Virtus, professor of the dermatovenerology department at P.L. Shupik National Academy of Postgraduate Education

Abstract
Growth factors and inflammatory cytokines of platelet origin effectively stimulate proliferative and synthetic ability of
fibroblasts thus justifying their use for increasing the efficiency of cell therapy in correcting aging skin involutionary
changes.
Objective: present the results of practical application of neofibrolifting method based on the ability of growth factors
and cytokines to stimulate the functional activity of connective tissue and immune cells with the following autologous
dermal fibroblasts transplantation.
Methods: the research work included 60 women of different age who turned to the Institute of Plastic Surgery and
Cosmetology “Virtus.” Platelet-rich plasma was processed using automatic centrifuge Harvest Smart PReP2 (USA). The
material for achieving and culturing dermal fibroblasts was harvested using punch-bioptate from the postauricular area.
The research employed the method of ultrasound dermoscanning using «DUB - Digital Ultraschall Bildsystem-tpm»
device and DUB- SkinScan ver. 3.2 software (Germany). Multi Skin Test Center® MC 1000 (Courage+Khazaka electronic
GmbH, Germany) system was applied for moisture tests and its evaporation. The blood flow was determined by Doppler
scanning (“Minimax-Doppler-K” device St. Petersburg, Russia).
Results: involutionary skin changes development with ageing is defined by progressively decreased epidermal, dermal
thickness, acoustic skin density, its hydration, increased transepidermal loss of water and slow blood flow rate.
As a result of the application of the developed neofibrolifting approach with transplantation of dermal autofibroblasts
into skin, conditioned by administration of platelet-rich plasma in all age groups of female patients we observed obvious
correction of involutionary facial skin changes in the course of the twelve months of the conducted research.
Conclusion: anti-ageing neofibrolifting is based on the administration of selectively chosen young fibroblasts taken from
the culture and implanted into the area enriched with growth factors and inflammatory PRP-cytokines. This method
represents an effective way of correcting aging skin involutionary changes.

Keywords
Skin, aging changes, rejuvenation, autologous dermal fibroblasts, PRP, neofibrolifting

Received for publication June 21, 2018; accepted July 19, 2018 - © Salus Internazionale ECM srl - Provider ECM nº 763

Correspondence

Vladimir Tsepkolenko, MD PhD.

Institute Virtus: Sudostroitelnaya 1, Odessa, Ukraine.
Phone: +380503164088

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 19

 Results of practical application of fibroblasts in treating age-related skin changes.
An open, prospective, non-randomized study

Introduction transplanted following the platelets, and therefore,

As it is known the leading and prompting role of we can expect an increased number of young skin
involutionary skin changes genesis is caused by fibroblasts because of their high remodeling activity.
abnormal microcirculation based on endothelial and In the view of the above said and considering the main
immune dysfunction as well as structural and functional function of fibroblasts, at the heart of the method of
alterations in intercellular matrix (ICM), represented by involutionary changes correction development called
the consequences of mainly quantitative and functional neofibrolifting lies the idea of autotransplantation of
interruptions in systemic interaction of connective exactly these cells. Based on the information regarding
tissue and immune cells 1-4. the fibroblasts properties in ex vivo cultures as well
Along with that, objective characteristics of involutionary as currently known powerful stimulatory action, we
skin changes with well-known clinical signs can be designed the method which implies prearrangement of
achieved using instrumental skin assessment to make moderate and positive inflammation using the platelet-
it more specific. based product. As a result we influence fibroblasts and
Nowadays, autofibroblasts have proven their efficiency inflammatory immune system cells with the following
in correcting facial contour, various folds, wrinkles, transplantation of autofibroblasts in the initially
and atrophic scarring. Satisfactory clinical effect prepared area.
was observed after three transplantation procedures
and lasted for some months5-6. It is convenient that
the biopsy can be repeated many times, cells can be
obtained at early passages with the possibility of Objective
cryobanking until the next time application. Safety and Throughout this article we would like to present the
efficiency of dermal fibroblasts autotransplantation results of practical use of neofibroblifting method,
have been proven by the results of many multi-central which is based on stimulation of connective tissue and
randomized placebo-controlled double-blind clinical immune cells by means of growth factors and cytokines
studies7. Until now, the most well-known and officially followed by administration of autologous dermal
recognized technology of dermal autofibroblasts fibroblasts.
application was developed in the USA, LAVIV (azficel-T)
by Fibrocell Science company. In 2011, FDA (Food and
Drug Administration) authorized Fibrocell Science with
the right to use LAVIV (azficel-T) for nasolabial folds Materials and methods
correction7. Characteristics of the study: open, prospective, non-
However, despite the quite convincing results of randomized study
fibroblasts autotransplantation, the obtained effect is
not always satisfactory neither regarding the clinical Study population
manifestations nor the duration of action. Therefore, The study involved female patients who turned to the
currently, new approaches are being developed to the Institute of Plastic Surgery “Virtus” for cosmetological
method, sometimes combining it with transplantation assistance, with concerns regarding the process of
of cells with different tissue origin. involutionary skin changes. They were divided into 4
A new way of using platelets properties in the course age groups: 25-35 y.o. (n=13), 36-45 y.o. (n=16), 46-55 y.o.
of their co-transplantation with fibroblasts is currently (n=18), 56 and older (n=13).
being developed. However, there has yet to be presented
convincing evidence of such an approach’s effectiveness Inclusion criteria
in cosmetology at this point. Nowadays platelet Prior to participation in the research program all
functions have demonstrated a fundamentally new, patients were examined by a dermatologist, physician,
unexpected side. As it turned out, the platelets actively surgeon, endocrinologist and clinical immunologist.
participate in inducing inflammation, necessary to
prompt the immune reflex, renewal, and formation Exclusion criteria
of immunological response via the cells of native and In cases of existing pathology that required treatment,
adaptive immunity (containing TLR-2, TLR-4, TLR-7 і patients received necessary recommendations and
TLR-9)8. They produce lots of growth factors as well as were excluded from the program of involutionary skin
other biologically active substances. According to the changes correction.
available data, platelet granules contain 827 proteins9
and their secretion provides cross-coupling of platelets, Protocol used
immune and stromal cells. The material for obtaining and culturing dermal
It has been shown that fibroblasts stimulated by fibroblasts was obtained from the postauricular area
cytokines respond with the synthesis of collagen and punch-bioptate using the 3.5 mm punch-needles.
non-collagen proteins10. Administration of platelets Following the mechanical morcellization, the achieved
or their products prior to dermal fibroblasts leads to tissue fragments were transferred to the Petri dish into
the limited, moderate inflammation. It may create the the warm (37,0±0,5°С) growth medium DMEM/F12 with
conditions for adequate influence upon the transplanted L-glutamin (CTS™ GlutaMAX™-I Supplement, Gibco), 1%
fibroblasts of inflammatory cytokines which in their non-essential aminoacids (MEM Non-Essential Amino
turn, provide a positive selection of young cells and Acids Solution, 100×, Gibco), 9 nmol main fibroblasts
stimulate their activity. In this way an increase of growth factor (FGF-Basic (AA 1-155) Recombinant
cellular efficiency of autofibroblasts can be achieved, Human Protein, Gibco), 15% fetal bovine serum (Fetal

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 20

 Results of practical application of fibroblasts in treating age-related skin changes.
An open, prospective, non-randomized study

Bovine Serum, Gibco) and 0.5% antibiotics (Penicillin- Table 3, shows the acoustic skin density also increases
Streptomycin, Gibco). Then the dishes with the material as a result of neofibrolifting. In two young groups this
were placed into CO2-incubator. The culture medium result took place after six and twelve months following
was changed every 3-4 days. the fibroblasts administration, while in other older
Plasma rich platelets (PRP) were extracted out of 20 ml groups the skin acoustic density increased already after
of the patients’ whole venous blood. For that purpose, the PRP administration and remained increased up to
a Harvest Smart PReP2 centrifuge (USA) was used. For the end of the studies and even grew thicker in the 2nd
structural skin changes evaluation an Ultrasound dermal and 3rd groups after twelve months.
scanning method by means of mobile high-frequency
US device «DUB - Digital Ultraschall Bildsystem-tpm»
with Software DUB-SkinScan ver.3.2 (Germany) was
used. Epidermal hydration level was evaluated using
corneometry, based on the measurement of electric
capacity of dielectric medium. Examination of the
epidermal barrier function was carried out by measuring
skin surface moisture evaporation, transepidermal
water loss (TEWL).
The studies employed the diagnostic system Multi Skin
Test Center® MC 1000 (Courage+Khazaka electronic
GmbH, Germany). For blood flow testing an ultrasound
Doppler scanning (device “Minnimax-Dopler-K”, St.Pete,
Russia) was used. Blood flow rate in microcirculatory
bloodstream was measured using the sensor with
emission frequency of 25 mHz. Additionally, volumetric
blood flow rate skin control, forehead and mental area
was performed (Qas in ml/sec/cm). Table 1 - Epidermis thickness in patients of different age groups in
For the interpretation of the results the critical value of treatment dynamics.
significance level was considered 0.05.
The obtained results were processed using the
variational statistics methods and Excell (MS Office
XP). As a means of descriptive statistics for quantitative
measure, the mean (M) value with standard deviation
(±SD) was used as well as the Student parametric
statistics (t).

Treatment method
Neofibrolifting technique was performed the following
way: PRP was administered intradermally at the amount
of 14 ml. After 2 weeks, the same area was treated with
intradermal transplantation of 60 mln autofibroblasts.
Bioptates harvesting for the research was performed
prior to the treatment, 2 weeks after PRP administration
and then 2 weeks afterwards, on the 6th and 12 months
after the fibroblasts autotransplantation.
On certain dates, clinical lab and instrumental exams Table 2 - Dermal thickness in female patients from different age groups
were performed. in treatment dynamics.

Results
As shown in tables 1-7, neofibrolifting resulted in the
essential improvement of structural and functional
skin parameters (Table 1).
Table 2 shows that the dermal thickness essentially
increased in the youngest group as a result of PRP
action and remained thick up to six months after the
administration of fibroblasts, having normalized
after twelve months. Such an easy enhancement
might be the evidence of the so-called reserve of
regeneration mechanisms at a relatively young age.
In three other older groups, a considerable increase
of dermal thickness took place just six months after
autotransplantation and continued increasing up to the Table 3 - Acoustic skin density in female patients in different age groups
twelfth month following the treatment. in treatment dynamics.

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 21

 Results of practical application of fibroblasts in treating age-related skin changes.
An open, prospective, non-randomized study

Analyzing the changes of corneometric and vaparometric

values in female patients’ skin of different age groups
in the dynamics of fibrolifting treatment (Tables 4 and
5), it was discovered that the level of skin hydration in
all studied groups increased following the treatment,
while TEWL gradually decreased.
We can observe pronounced tendency of increasing
corneometric indicators after PRP administration in all
the studied groups, while considerable increase was
shown only in group 3. After fibroblasts administration
skin hydration became considerably high in all groups,
however the high and level in 12 months was recorded
only in the 2nd and 3rd groups. Table 7 - Volumetric blood flow rate in the cheek area dermis in patients
of different age groups in treatment dynamics.
TEWL indicators influenced by neofibrolifting dropped
considerably after 6-12 months following autofibroblasts
implantation, except for the older group of patients, where
the changes after 12 months period seemed uncertain
(Tables 6 and 7). In patients of 56 years of age and older, Discussion
the increased VBF in the forehead area was observed just Involutionary skin changes process was determined by
after PRP administration; proved stimulation in the cheek progressively decreased epidermal, dermal thickness,
area was registered after fibroblasts autotransplantation. acoustic skin density, its hydration, increased
transepidermal loss of water (TWEL) and slow blood
flow rate, in the forehead and cheek area that possibly
is a proving evidence of the influence of microcirculation
disorder that leads to structural and functional
skin disorganization. Our studies proved that after
the administration of the fibroblasts the epidermal
thickness clearly increased in all age groups, while in
group 46-55 y.o., it had a demonstratively positive and
considerable reaction to the PRP administration (Table
1). In the 1st, 2nd and 4th groups the effect was achieved
following autofibroblast administration. Positive effect
of the procedure related to the epidermal thickness was
observed after six and twelve months only in the 46-
Table 4 - Corneometry indicators in female patients of different age 55 y.o. age group. Increased skin acoustic density as a
groups in treatment dynamics.
result of neofibrolifting influence can be explained by the
enhanced synthesis of collagen fibers, which represents
the key elements, that reflect ultrasound waves in the
organized state [Jasaitiene D et al, 2011]. Therefore,
according to the structural and functional indicators
skin conditions were substantially improved based on
such indicators as epidermal and dermal thickness,
acoustic density, corneometric and evaporimetric data
practically in all age groups, most frequently following
the fibroblast administration. The achieved effect lasted
for 6-12 months in most cases after autotransplantation
It can be assumed that positive skin changes in the
process of neofibrolifting treatment can basically be
Table 5 - TEWL indicators in patients of different age groups in treatment explained by the considerable stimulating therapeutic
dynamics. effect on the volumetric blood flow rate (Tables 6
and 7). As it is demonstrated in the presented tables,
the volumetric blood flow (VBF) in the course of
neofibrolifting increased in the forehead and cheek
area. However, in the 1st and the youngest group of
patients (25-35 y.o.) the increase in the forehead area was
observed only in terms of pronounced tendency and it
was only in the cheek area that the increased blood flow
was real at the end of observation period. In the group of
patients of 36-45 y.o., VBF increased considerably in the
forehead area for six months following the fibroblasts
treatment and lasted for twelve months. Increased VBF
in the cheek area in this group took place immediately
after fibroblasts administration and as well lasted until
Table 6 - Dermal volumetric blood flow rate in the forehead area in
patients of different age groups in treatment dynamics. the end of observation. In the group of 46-55 y.o., the

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 22

 Results of practical application of fibroblasts in treating age-related skin changes.
An open, prospective, non-randomized study

real increase of VBF in both areas took place immediately Conclusion

after autotransplantation and lasted for twelve months 1. As a result of neofibrolifting, VBF rate essentially
of observation, however in the forehead area the increases under the influence of fibroblast
increased indicators during the observation period had autotransplantation. PRP administration can strongly
only pronounced tendency nature. influence indicators mainly in the forehead area and
It is important to note that VBF stimulation at the level only in the group of patients at the age of 56 and older.
of pronounced tendency in both areas in all groups of However, in all cases, obvious regenerative tendency can
patients was registered just after PRP administration. be observed.
Such an obvious consistency even despite the large 2. All structural and functional aging skin indicators
range of measured values, allows one to assume that can be largely normalized by using neofibrolifting. PRP
PRP administration practically always promotes those administration in some cases could lead to positive
necessary fundamental changes that provide further results, however, the “complete” neofibrolifting, that is
development of transplanted autofibroblasts effect. PRP combined with autofibroblasts led to the promotion
Therefore, as a result of the neofibrolifting treatment of regeneration and normalization of functional and
we can observe pronounced stimulation of age-related structural indicators. Most studies which demonstrated
structural and functional skin indicators such as: a regeneration of aging skin were observed over the
epidermal and dermal thickness, acoustic density, whole period following the treatment of twelve months.
hydration of epidermis and TEWL, as well as VBF in
forehead and cheek areas.
The obtained results indicate that aging skin goes
through serious structural and functional changes that Acknowledgments
involve both epidermis and dermis. They have complex We would like to thank Dmytro Pykhtieiev (biotechnology
and complicated nature and result in the abnormalities company “SmartCell”) for their help in growing and
of different levels of regulatory mechanisms. That is preparing of fibroblasts and PRP, professor Nikolsky
why dermal fibroblasts stop receiving enough metabolic for fruitful discussions, Roman Vlasov and Natalia
microcirculatory support, and are negatively influenced Karavatskaya for the art work and English revision.
by endothelial dysfunction, which is largely developed by
immunologic mechanisms. Apparently, understanding
the immunopathology process of skin aging mechanism
and its influence over the development of involutionary Conflict of interests
changes has become the key issue in the aging skin The Authors declare no conflict of interests or funding.
regeneration approaches.

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 23

 Results of practical application of fibroblasts in treating age-related skin changes.
An open, prospective, non-randomized study

REFERENCES

1. Smith SR, Munavalli G, Weiss R, Maslowski JM, Hennegan KP,

Novak JM. A multicenter, double-blind, placebo-controlled trial of
autologous fibroblast therapy for the treatment of nasolabial fold
wrinkles. Dermatol Surg. 2012; 38(7 Pt 2):1234-43.

2. Midttun M. Blood flow rate in arteriovenous anastomoses: from the

cradle to the grave. Clin Physiol. 2000; 20(5):360-365.

3. Gao Z, Wilson TE, Drew RC, Ettinger J, Monahan KD. Altered coronary
vascular control during cold stress in healthy older adults. Am J
Physiol Heart Circ Physiol. 2012; 302(1):H312-318.

4. Fisher GJ, Quan T, Purohit T, et al. Collagen fragmentation promotes

oxidative stress and elevates matrix metalloproteinase – 1 in
fibroblasts in aged human skin. Am J Pathol. 2009; 174(1):101-114.

5. Keller G, Sebastian Dzh, Lakombe Iu, Toft K, Lask G, Revazova E.

Preservation of injected autologous human fibroblasts. Bulletin of
Experimental Biology and Medicine. 2000; 130(8):203-6 [in Russian].

6. Weiss RA, Weiss MA, Beasley KL, Munavalli G. Autologous cultured

fibroblast injection for facial contour deformities: a prospective,
placebo-controlled, Phase III clinical trial. Dermatol Surg. 2007;
33(3):263-8.

7. Schmidt C. FDA approves first cell therapy for wrinkle-free visage.

Nat Biotechnol. 2011; 29(8):674–75.

8. Koupenova M, Vitseva O, MacKay CR, et al. Platelet-TLR7 mediates

host survival and platelet count during viral infection in the absence
of platelet-dependent thrombosis. Blood. 2014; 124(5):791-802.

9. Zufferey A, Schvartz D, Nolli S, Reny JL, Sanchez JC, Fontana P.

Characterization of the platelet granule proteome: evidence of the
presence of MHC1 in alpha-granules. J Proteomics. 2014; 101:130-40.

10. Freedland M, Karmiol S, Rodriguez J, Normolle D, Smith D Jr, Garner

W. Fibroblast responses to cytokines are maintained during aging.
Ann Plast Surg. 1995; 35(3):290-6.

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 24

Original Article

Cryolipolysis with active vacuum

technology and simultaneous stimulation
of the microcirculation in body
reharmonization: comparative study on 40
patients divided into 2 cohorts
Fabrizio Melfa1, Daniela Gaetana Caruso2, Michela Maggi3
1MD, MSc, Lecturer at the University of Pavia, Pavia, Italy, and Founder of the Mediaging Program, Palermo/Milano/Catania, Italy

2MD, Aesthetic physician in private practice, Mediaging program, Catania, Italy

3Medical engineer, laser and technical equipment expert

ORCID: https://orcid.org/0000-0002-1009-0527

Abstract
Background: cellulite is a common syndrome. Many studies have examined whether cellulitis should even be considered
a disease. The nature of cellulite is linked to different physical and hormonal factors as well as to lifestyle and is
characterized by the presence of localized adiposity and weight increase.
Aim: we aimed to measure the clinical and scientific value of cryolipolysis treatment combined with bioactive currents.
We studied both the effectiveness of cryogenesis on adipose tissue and the action of 50-Hz current pulses on tonicity.
Methods: enrolled patients were evaluated with an anthropo-plicometric examination, ultrasonography, blood tests,
and photographs and divided into two groups: one group maintained a low-calorie balanced diet and the other group
combined the same diet with cryolipolysis treatment. The cryolipolysis device used in the study had an active no-inertial
vacuum technology for the maintenance and integrity of the vascular system, suffering if subjected to cryogenesis and
aspiration. Bioactive currents preserved the functionality of the cells and tissue oxygenation. Results were obtained at
baseline and at 8 weeks after treatment delivery. We call this specific device cryoliposculpt.
Results: we enrolled 40 patients (mean age, 43 years), 20 patients in each group. Average decreases in treated adiposity
and cellulite with accompanying improvement in dermoepidermal tissues were greater in the group treated with a low-
calorie balanced diet plus cryolipolysis than in the diet only group.
Conclusions: cryolipolysis combined with bioactive currents produced measurable improvements at 8-week follow-up,
even after only one treatment session. The ability to manage the controlled food program, by patients submitted to
cryoliposculpt than others was better.

Keywords
Cryoliposculpt, cryolipolysis, cellulite, adipose tissue

Received for publication July 9, 2018; accepted July 25, 2018 - © Salus Internazionale ECM srl - Provider ECM nº 763

Correspondence

Fabrizio Melfa, MD, MSc

Mediaging Program
Address: Via M. D’Azeglio, 27/c - 90141 Palermo, Italy
E-mail: [email protected]

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 25

 Cryolipolysis with active vacuum technology and simultaneous stimulation of the microcirculation in body
reharmonization: comparative study on 40 patients divided into 2 cohorts

Introduction collateral risks10 and ineffective outcomes. In this

Cellulite is a very common syndrome, universally study, we combined the destruction of adipose cells
characterized by the accumulation of localized with the simultaneous emission of modulated currents
adiposity and increased body weight1,2. The condition (50-Hz pulses) to sculpt the dermal-epidermal profile
is so prevalent (especially in women) that many studies (cutaneous), while improving the elasticity of the skin
have sought to determine whether it is a pathologic and preserving uninvolved tissues. The use of cold
occurrence or should even be considered a chronic temperatures combined with a vacuum exploits the
disease precisely because it is so common. Although principles of cryogenesis and cryocyanogenesis, which
it is very difficult to define a condition that is not act on areas with excess fat, facilitating its disposal. As
considered pathologic, if a condition affects quality of stated previously, after treatment, an apoptotic process
life, it becomes pathologic. Scientific research tells us is triggered in the adipocytes, which leads to a natural,
that although the genesis of so-called cellulitis is linked physiological death. The cells of the immune system
to causal, hormonal, genetic, circulatory, and lymphatic determine the natural disposal of damaged adipocytes1.
factors, it also depends on the subject’s lifestyle. Our approach to this retrospective study was to
In the last few years, different modalities have become demonstrate the irrefutable and certain validity of
available for the noninvasive reduction of adipose cryoliposculpt treatment through the analysis of data
tissue, including radiofrequency and low-energy laser and presentation of the results.
procedures, high intensity focused ultrasonography,
and cryolipolysis3.
In March 2018, an American Society of Plastic Surgeons
Report showed a rise in body shaping and non-invasive Materials and Methods
procedures; the statistics also reveal Americans are A total of 40 patients were involved in our retrospective
turning to new and innovative ways to shape their study, divided into two cohorts. Inclusion criteria
bodies, as minimally invasive cosmetic procedures included an age between 20 and 66 years, presence
have increased nearly 200% since 2000. More people of localized adiposity and so-called Cellulite (PEFS
are choosing to shape different parts of their bodies - Edematofibrosclerotic Panniculopathy), in diet
using ultrasound, radio frequency, infrared light, treatment by weight loss with personalized diet.
vacuum massage and injectable medication to reduce Exclusion criteria: patients in pregnancy / lactation,
fat cells. Non-invasive procedures to eliminate fat and renal / hepatic insufficiency, previous cardiac
tighten the skin are gaining popularity, with the fastest pathologies and / or in pharmacological treatment.
growing procedure - cellulite treatments - up nearly 20% For this study, recruitment of patients was ultimately
over last year 20174. based on choice of anatomic area and thickness of
The term cryolipolysis refers to the gradual and the fat layer and recognition that cryolipolysis is
noninvasive cooling of adipose tissue to induce a not recommended for everyone (ie, it is indicated for
process called lipolysis, or the breakdown of lipids. localized adiposity rather than for obese patients and
Among these technologies, cryolipolysis has been is most suitable for “body sculpture”). All subjects were
studied most often, both in in vitro animal models and evaluated after undergoing a medical examination, an
in randomized controlled trials involving humans5,6. anthropoplicometric examination, ultrasonography of
Scientific studies have shown that under conditions of the panniculus adiposus, and blood tests. Patients were
prolonged exposure to temperatures close to freezing, assigned to one of two groups: patients who followed a
fat cells are more vulnerable to the effects of cold than balanced low-calorie diet only or patients who followed
surrounding tissues are7. a balanced low-calorie diet and underwent a body
Other scientific articles have demonstrated that rehabilitation protocol with cryolipolysis combined with
exposure to cold induces the apoptosis of fat cells bioactive currents in different areas (Cryoliposculpt).
and the production of cytokines and other mediators Every 15 days the weight was checked and the measures
of inflammation that gradually eliminate the cells of waist, hip, abdominal line, buttocks circumference,
involved8. In the weeks after treatment, macrophages thigh root and thigh median were evaluated.
steadily digest the fat cells exposed to cooling, thus Photographs were taken before and after the evaluation
reducing the thickness of the treated adipose layer. The period because it has been shown that cryoliposculpt
lipids derived from the cells are slowly released and also induces action on fibroblasts over time11. The
transported by the lymphatic system for processing and evaluations of our retrospective and observational
elimination, as happens with fats derived from food. study were conducted at T0 (baseline) and at T1 (ie at 8
Although inflammatory reactions and the in situ recall weeks from the beginning of the therapeutic program)
of cells responsible for the elimination of particles are as inspected by other studies in the literature7. All the
triggered by cryolipolysis, the therapy does not alter raw data collected, of the anthropometric measurements
blood chemistry values. This finding indicates that already specified, have been elaborated and produced
the technology is noninvasive compared with other using statistically relevant graphs.
techniques9. The cryolipolysis device used in this study is called
The low rate of adverse effects associated with Cryoliposculpt. It has unique technical characteristics
cryolipolysis is, in fact, the main reason doctorsand that guarantee the efficacy and safety of the treatment
patients prefer this technology over others7. while preserving cellular structures and their
The first target of a body remodeling treatment is functionality. The applicator generates aspiration
certainly to guarantee the best result, one that is through an active vacuum, which sucks the treated area
tangible, lasting, and maximally safe in terms of inside a cavity, where it comes into contact with two

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 26

 Cryolipolysis with active vacuum technology and simultaneous stimulation of the microcirculation in body
reharmonization: comparative study on 40 patients divided into 2 cohorts

cooling elements. These cooling elements reduce the

temperature by 8°C to 10°C. A contact sensor constantly
monitors the surface temperature of the skin to ensure
safety and efficacy throughout the treatment (Figure 1).
The active non-inertial vacuum, which is continuous and
customizable (with respect to the mechanical resistance
of the tissues), preserves local microcirculation.
In addition to an inertial vacuum, the device allows
delivery of a cycle of modulated microcurrents emitted
in succession (spikes of current at 50 Hz) in a random
way that does not induce adaptation in the cells. The
microcurrents act on the extracellular interstitium, the
microcirculation, and the remodeling and orientation
of the collagen fibers without inducing a joule heating
in contact with the tissues12.
During treatment, the applicators were positioned
on the area of the body where the patient hoped to
reduce fat. An inverse thermal shock was applied to the
underlying adipose tissue, cooling it to freezing, while
avoiding other tissues. Although the tissues were under
a negative pressure of about 30 mm Hg for 50 minutes
during standard treatment, the constant mobilization
of the tissue ensured there was no vascular damage or
atrophy of the microcirculation; thus, no post-treatment
massage was necessary13 (Figure 2).
The other Cryolipolysis machines on the market cause
the formation of the “stick of butter” and, therefore, to
avoid problems are matched as a result of the treatment
or manual massages14 or shock waves to accelerate
the process of ‘restitutio ad integrum’ of the treated
Figure 1 - Cryoliposculpt treatment with 4 hand pieces.
tissues15.

Results
We enrolled a total of 40 patients with localized fat and
cellulite (average age, 43 years). Of these, 20 patients
were treated with a personalized balanced low-calorie
diet and cryoliposculpt and 20 patients followed only
a personalized balanced diet. After measuring the
previously indicated areas (waist, hips, abdominal line,
buttocks, thigh root and thigh median) at T0 and T1, in
this retrospective study we observed in the cohort that
performed both the diet and the cryoliposculpt, better
results compared to the cohort that only performed the
diet. All 40 patients performed a similar personalized
diet. We observed that the cohort patients who did both
the diet and the cryoliposculpt, were much more adherent Figure 2 - Patient abdomen immediately after treatment with cryoliposculpt.
and precise in following the dietary indications achieving
better weight loss results. From the measurements
measured at T0 and T1, in the areas already specified,
we observed a quantitative improvement in localized
fat deposits and treated cellulite (Figure 3). In patients
treated with cryoliposculpt, we observed a marked
improvement in the dermoepidermal tonicity of the
treated areas. We verified with these patients the
results, using a verbal questionnaire concerning the
result obtained on a scale from 0 to 3 (0 = null result, 1
= discrete, 2 = good, 3 = excellent), which confirmed our
observation. These observations were also confirmed
by the photographic documentation carried out at T0
and T1, with frontal, rear, right lateral and left lateral
views, using a standardized grid for the position of
the feet. The evaluation of the photos was made by us

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 27

 Cryolipolysis with active vacuum technology and simultaneous stimulation of the microcirculation in body
reharmonization: comparative study on 40 patients divided into 2 cohorts

doctors and by the patients themselves. Figure 3 shows

the average measurements reported between T0 and
T1 (ie, 8 weeks from the beginning of the therapeutic
path), the period necessary to determine real results of
the treatment7. We managed to reduce the average waist
circumference by 3.65 cm with combined cryolipolysis
and diet versus a 1.65-cm reduction with diet alone, a
greater than twofold difference between the groups.
The most striking and significant result was evident in
the side area, with an average reduction of 4.55 cm in
the combined cryolipolysis and diet group compared
with 0.275 cm with diet alone, an approximately 16-
fold difference between the groups. In the abdominal
area, average reductions were approximately 6 cm and
Figure 3 - Average reductions (in centimeters) of different anatomic areas
1.7 cm, respectively. In the buttocks, average reductions between patients who were treated with a low-calorie diet alone and
were 7.9 cm and 1.4 cm, respectively. In the thighs, patients who were treated with cryoliposculpt in addition to the diet.
reductions of 3.35 and 2.625 cm were observed in the
cryoliposculpt and diet group compared with reductions
of 1.05 cm and 1.275 cm in the diet only group (Figure
4 and Figure 5). We therefore deduce that a therapeutic
treatment program that includes cryoliposculpt and a
balanced and controlled diet facilitated reductions in
circumference in different areas of the body that were
approximately 4 times greater than those produced by
diet alone.

Figure 4 - Raw data and statistical evaluations of the cohort of patients treated only with the diet.

Figure 5 - Raw data and statistical evaluations of the cohort of patients treated with diet and cryolipolysis.

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 28

 Cryolipolysis with active vacuum technology and simultaneous stimulation of the microcirculation in body
reharmonization: comparative study on 40 patients divided into 2 cohorts

Discussion and Conclusions

The results of the present study suggest an important
role of cryoliposculpt in the so-called cellulite, as
association of cryolipolysis and active microcurrents
for the improvement of the tone and texture of the
treated tissue.
This new technique was shown to be a good and safe
alternative to invasive treatments of adipose tissue16,
even if it remains the gold standard.
Overall, the study demonstrated a reduction in different
anatomic areas that was approximately four times
greater than that obtained with diet alone.
The safety of all results obtained and efficacy of
treatments, in a protocol tested worldwide, lets convalited
non-invasive alternatives to body remodeling.
No adverse collateral effects were shown. Damage to
and destruction of adipose cells was achieved without
adverse effects to nearby tissues and vascular vessels Figure 6 - (A, B, C, D) – Pre and Post two months after treatment with
Crioliposculpt and diet.
while preserving all cellular functions of the treated
tissues that were under mechanical stress and thermal
shock inverted. Nerves and bones were also unaffected,
and no changes were observed in the main organs of
the body17.
Gradual improvements over time in the thickness of
adipose tissues, illustrating the concept of systemic body
remodeling, induced physiological - but nontraumatic -
reactions in the body.
Overall, we observed greater improvements in areas
with a large quantity of adipose tissue; in addition, the
biological inflammatory process removed adipocytes
over time and reduced the adipose layer.
Thus, adipose tissue freezing offers a potential new
option for many people by remodeling the body without
any invasive side effects18.

Figure 7 - (E, F, G, H) – Pre and Post two months after treatment with
Crioliposculpt and diet.

Acknowledgments
Financial Support and Sponsorship None.

Conflict of Interest
The authors declare that they have no conflict of interest.

Disclosures
Michela Maggi, she is Biotec scientific consultant and was
responsible for training in southern Europe Lumenis

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 29

 Cryolipolysis with active vacuum technology and simultaneous stimulation of the microcirculation in body
reharmonization: comparative study on 40 patients divided into 2 cohorts

REFERENCES

1. Avram MM, Harry RS. Cryolipolysis for subcutaneous fat layer

reduction. Lasers Surg Med. 2009; 41(10):703-8.

2. Garibyan L, Sipprell WH 3rd, Jalian HR, Sakamoto FH, Avram M,

Anderson RR. Three-dimensional volumetric quantification of fat
loss following cryolipolysis. Lasers Surg Med. 2014; 46(2):75-80.

3. Jewell ML, Solish NJ, Desilets CS. Noninvasive body sculpting

technologies with an emphasis on high-intensity focused ultrasound.
Aesth Plasr Surg. 2011; 35(5):901-912.

4. Adam Ross
https://globenewswire.com/news-release/2018/03/01/1402022/0/
en/New-Statistics-Reveal-the-Shape-of-Plastic-Surgery.html
https://www.plasticsurgery.org/documents/news/statistics/2017/
plastic-surgery-statistics-report-2017.pdf

5. Pinto H, Ricart-Janè D, Pardina E, Melamed G. Lipocryolysis: cooling

speed affects adipocyte survival. J Surg. 2015; 3(1-1):11-13.

6. Gavénis K, Andereya S, Schmidt-Rohlfing B, Mueller-Rath R,

Silny J, Schneider U. Millicurrent stimulation of human articular
chondrocytes cultivated in a collagen type-I gel and of human
osteochondral explants. BMC Compl & Altern Medicine. 2010; 10:43.

7. Meyer PF, da Silva RM, Oliveira G, et al. Effects of cryolipolysis on

abdominal adiposity. Case Rep Dermatol Med. 2016; 2016:6052194.

8. Manstein D, Laubach H, Watanabe K, Farinelli W, Zurakowski D,

Anderson RR. Selective cryolysis: a novel method of non-invasive fat
removal. Lasers Surg Med. 2008; 40(9):595-604.

9. Klein KB, Zelickson B, Riopelle JG, et al. Non-invasive cryolipolysis for

subcutaneous fat reduction does not affect serum lipid levels or liver
function tests. Lasers Surg Med. 2009; 41(10):758-790.

10. Kim J, Kim DH, Ryu HJ. Clinical effectiveness of non-invasive selective
cryolipolysis. J Cosmet Laser Ther. 2014; 16(5):209-213.

11. Carruthers J, Stevens WG, Carruthers A, Humphrey S. Cryolipolysis

and skin tightening. Dermatol Surg. 2014; 40 Suppl 12:S184-S189.

12. Zhao M, Bai H, Wang E, Forrester JV, McCaig CD. Electrical stimulation
directly induces preangiogenic responses in vascular endothelial
cells by signaling through VEGF receptors. J Cell Sci. 2004; 117(Pt
3):397-405.

13. Krueger N, Mai SV, Luebberding S, Sadick NS. Cryolipolysis

for noninvasive body contouring: clinical efficacy and patient
satisfaction. Clin Cosmet Investig Dermatol. 2014; 7:201-205.

14. Boey GE, Wasilenchuk JL. Enhanced clinical outcome with manual
massage following cryolipolysis treatment: a 4-month study of safety
and efficacy. Lasers Surg Med. 2014; 46(1):20-26.

15. Ferraro GA, De Francesco F, Cataldo C, Rossano F, Nicoletti G,

D’Andrea F. Synergistic effects of cryolipolysis and shock waves for
noninvasive body contouring. Aesthetic Plast Surg. 2012; 36(3):666-
679.

16. Stevens WG. Response to “Cryolipolysis: the importance of scientific

evaluation of a new technique”. Aesthet Surg J. 2015; 35(5):NP120-
NP122.

17. Klein KB, Bachelor EP, Becker EV, Bowes LE. Multiple same day
cryolipolysis treatments for the reduction of subcutaneous fat are
safe and do not affect serum lipid levels or liver function tests. Lasers
Surg Med. 2017; 49(7):640-644.

18. Bernstein EF, Bloom JD, Basilavecchio LD, Plugis JM. Non-invasive
fat reduction of the flanks using a new cryolipolysis applicator
and overlapping, two-cycle treatments. Lasers Surg Med. 2014;
46(10):731-735.

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 30

Review

Dercum’s disease or Adiposis Dolorosa:

a complex condition still awaiting full
definition
Paola Palumbo1, Benedetta Cinque2, Francesca Lombardi3,
Lucia Romano4, Corinna Genovesi5, Gino Orsini6, Pietro Leocata7,
Maria Grazia Cifone8, Maurizio Giuliani9
1PhD, Department of Life, Health and Environmental Sciences, University of L’Aquila - Building Delta 6, Coppito - 67100 L’Aquila, Italy.

E-mail: [email protected]
2PhD, Department of Life, Health and Environmental Sciences, University of L’Aquila - Building Delta 6, Coppito - 67100 L’Aquila, Italy.

E-mail: [email protected]
3PhD, Department of Life, Health and Environmental Sciences, University of L’Aquila - Building Delta 6, Coppito - 67100 L’Aquila, Italy.

E-mail: [email protected]
4 MD, Plastic and Reconstructive Surgery Unit, Casa di Cura Di Lorenzo, 67051 Avezzano, L’Aquila - Italy.

E-mail: [email protected]
5MD, Plastic and Reconstructive Surgery Unit, Casa di Cura Di Lorenzo, 67051 Avezzano, L’Aquila - Italy.

E-mail: [email protected]
6MD, Plastic and Reconstructive Surgery Unit, Casa di Cura Di Lorenzo, 67051 Avezzano, L’Aquila - Italy.

E-mail: [email protected]
7MD, Department of Life, Health and Environmental Sciences, University of L’Aquila - Building Delta 6, Coppito - 67100 L’Aquila, Italy.

E-mail: [email protected]
8MD, Department of Life, Health and Environmental Sciences, University of L’Aquila - Building Delta 6, Coppito - 67100 L’Aquila, Italy.

E-mail: [email protected]
9MD, Department of Life, Health and Environmental Sciences, University of L’Aquila - Building Delta 6, Coppito - 67100 L’Aquila, Italy; Plastic and

Reconstructive Surgery Unit, Casa di Cura Di Lorenzo, 67051 Avezzano, L’Aquila - Italy. E-mail: [email protected]

Short title: Dercum’s Disease or Adiposis Dolorosa

Abstract
Dercum’s disease (DD), also called adiposis dolorosa (AD), is known as a rare, chronic and progressive disorder
characterized by multiple, subcutaneous painful adipose tissue masses. DD mainly occurs in overweight or obese
adults, mostly post-menopausal women. Pain, which can be severe and often debilitating, is frequently, but not always,
associated with generalized weakness and mental disturbances. Other associated symptoms are also recorded but are
not common in all cases diagnosed as DD. To date, the etiology remains indefinite and the basis of the pain is not yet
clear. Thus, DD is mainly described for its symptoms rather than for the pathophysiological process. In sporadic cases,
the condition has been reported to be inherited as an autosomal dominant trait. To date, treatment is still symptomatic
and includes liposuction or surgery for the most painful fatty masses and analgesics to control pain. Nonetheless,
the symptoms are often uninfluenced by conventional pain therapy. In the present review, we have retraced the most
significant historical steps of research and study on DD, mostly highlighting the difficulties in defining pathophysiology,
diagnosis and treatment which are mainly due to the wide variability of the findings and clinical signs in the cases
described in the literature. The extremely complex picture that emerges should strongly stimulate to develop scientific
studies aimed at identifying the etiologic factors of this devastating pathology that, with high probability, is not always
recognized and, too often, neglected.

Keywords
Dercum’s disease, adiposis dolorosa

Received for publication July 10, 2018; accepted July 25, 2018 - © Salus Internazionale ECM srl - Provider ECM nº 763

Correspondence
Maurizio Giuliani, MD
Department of Life, Health and Environmental Sciences, University of L’Aquila - Building Delta 6, Coppito. L’Aquila, Italy
Phone: +390862434934
E-mail: [email protected]

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 31

 Dercum’s disease or Adiposis Dolorosa: a complex condition still awaiting full definition

Historical notes What was reported by Burr in 190018, was then confirmed
Adiposis dolorosa (AD) was first described in 1892 in 1902 by Dercum19 who described two other cases of
by the physician, philosopher, neurologist, scientist, AD and considered the most interesting histological
Francis Xavier Dercum1-4, from a case in the Philadelphia finding to be interstitial inflammation of the nerves in
Hospital5. In this original paper, Dercum described the adipose tissue of the painful sites. In the same year,
3 cases of the disease with the gross pathological Dercum and MacCarthy20 published a case of AD with
findings of 2 cases, both of which showed abnormal complete autopsy findings, the main pathological lesion
thyroid glands, thus leading the neurologist to believe being an “adenocarcinoma” of the pituitary body, while
that the disease was a clinical entity on the basis of the thyroid appeared regular. Next, several cases were
a “disthiroydia”. This article was preceded by a case described, many of which showed abnormalities of the
report by Dercum himself in 18886, as a 51 year-old pituitary gland21-24. DD was also defined as a disorder
woman of Irish heritage with severe pain and enlarged of the “haemolymph” system by Dercum and McCarthy
subcutaneous adipose tissue on her arms and back. themselves20 and “a general disease of the lymphatic
He wrote: “Evidently the disease is not simple obesity. If system” by Mills25, suggesting that dysfunction in the
so, how are we to dispose of the nervous elements present? hemovascular and/or lymphatic systems may contribute
Equally plain is it that we have not myxoedema to deal to the development of lipomas. As early as 1910, Stern26
with. All of these cases lack the peculiar physiognomy, the noted that neuropsychiatric disturbances and asthenia
spade-like hands, the infiltrated skin, the peculiar slowing did not accompany every case. Cushing in 191227 first
of speech, and the host of other symptoms found in questioned the rationale of calling the disease a clinical
myxoedema. It would seem then, that we have here to deal entity, stating that, in his opinion, many cases reported
with a connective tissue dystrophy, a fatty metamorphosis as AD, “are actually examples of disturbed metabolism
of various stages of completeness, occurring in separate secondary to disease of the ductless glands”. In his later
regions, or at best unevenly distributed and associated articles, Dercum appeared to be of the same opinion.
with symptoms suggestive of an irregular and fugitive In sections from DD adipose tissue increased levels of
irritation of nerve-trunks - possibly a neuritis... Inasmuch connective tissue were described by Myers in 192328. In
as fatty swelling and pain are the most prominent 1924 Purves-Stewart29 classified the disease among the
features of the disease, I propose for it the name Adiposis thropho-neuroses, probably due to disturbed activity
Dolorosa”. of the thyroid and the posterior lobe of the pituitary
Dercum regarded the disease as a clinical entity and body. Winkelman and Eckel in 192530 reported that
named it adiposis dolorosa (AD) because of its most the disease could be considered as a polyglandular
characteristic symptom, painful fat. disorder with a consequent altered fat metabolism. In
In 1899 White7 described an interesting case of AD as the first decades of the 1900s several further cases of
follows: “My patient shrieks when she is gripped...my AD were described31-39. Moreover, Foot et al in 192623
patient can hardly walk,...My patient goes out of her mind described a case of AD with necropsy: “The body is that
temporarily. Headache is a common symptom. of an extraordinarily adipose negress. …The necropsy
Herpes, hematemesis, epistaxis, early menopause, slight findings coincide very accurately with those in undoubted
pigmentation of the skin, atrophy of the muscles of the cases of AD. The very definite lesions in practically all
hand, and reaction of degeneration of them have all been the endocrine glands are striking: pituitary sclerosis
described as occasional symptoms. and hyperplasia, with a tumor; sclerosis and changes
...In my case administration of thyroid did no good....She in the colloid content of the thyroid; persistent and well
has been in several hospitals but all with no benefit”. preserved thymic rests; adenoma of both suprarenals,
The first clinical classification system for AD (also with hyperplasia; ovarian sclerosis and atrophy; and
named Dercum’s Disease, DD) was developed in 1900 definite, though slight, changes in the pancreas. Besides
by Giudiceandrea8 as follows: these, we see changes in the cranial bones, with exostoses
I. Nodular type. and definite cerebral atrophy, with some generalized
A form with painful lipomas, most commonly on the thickening of the dura. …. It is justifiable, however, to
arms or the legs or on the back or thorax. Sometimes the ascribe the pathologic findings in this case to a profound
lipomas occur on multiple locations and occasionally the disturbance in the endocrine system, probably arising
lipomas form a confluent mass. as a result of one of the lesions found in the hypophysis
The nodules are variable in size and painful on palpation. cerebri”. At the same time, Labbé and Boulin40 reported
II. Diffuse type. a case of AD with psychic and nervous disorders which
A form with diffusely painful adipose tissue. The pain is they could not attribute to any one thing which could at
symmetric. the same time cause obesity. These Authors questioned
III. Mixed type. whether the weakness and susceptibility to fatigue
A form with diffusely painful adipose tissue and with and psychiatric manifestations should be classified as
painful nodular masses. cardinal symptoms.
This classification was then revised in 1901 by Roux They argued that obesity per se can induce asthenia,
and Vitaut9 which proposed four cardinal symptoms of and that it is unclear whether mental disturbances
DD, used as diagnostic criteria for several years10-17: should be included as cardinal symptoms. Gram in
1. Multiple, painful, fatty masses 193041 described a high incidence of obesity with tender
2. Generalised obesity subcutaneous infiltrations, “deforming arthritis” of the
3. Weakness and susceptibility to fatigue (asthenia) knee, and arterial hypertension in women around and
4. Psychiatric manifestations, including emotional after the climacteric age. Newburgh in 193142 pointed
instability, depression, epilepsy, confusion, and dementia. out that painful areas of fat could disappear just by

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 32

 Dercum’s disease or Adiposis Dolorosa: a complex condition still awaiting full definition

regulating diet. According to Wilson43 the disease could if some patients were also affected by an autoimmune
be considered as “really a syndrome of symptoms in obese disease58,75,77. Commonly, markers for autoimmune
people” and “AD could not be a clinical entity since there disease, such as autoantibodies, are negative in DD77-79. A
have been no findings consistent in all the cases reported review of the histopathologic findings of DD showed no
in literature”. He considered more reasonable to assume consistent histologic abnormality in the adipose tissue
that the condition is one of either simple obesity or that might distinguish these tumors from common
lipomatosis associated with neurosis or neurasthenia, sporadic lipomas80. The involvement of hormones
and that the pathological conditions that had been and neuropeptides as well as a low level chronic
found in these cases that have come to autopsy were inflammation and vascular factors was discussed by
incidental. A report by Boller in 193444 showed that Hansson et al in 201181. In theory, the sudden appearance
intralesional injections of procaine relieved pain in six of the disease together with the incidence of a slight
cases. Kling in 193745 reported on 112 cases of juxta- increase in the number of inflammatory cells in the fat
articular AD, their significance and relation to DD and pointed toward the disease being, in part, an immune
osteoarthritis. Since then, four cases of juxta-articular defense reaction76,82. Herbst et al in 200983 reported
DD in association with seropositive rheumatoid that inflammation and excess collagen may contribute
arthritis were reported46,47. Furthermore, Kling45 came to lower relative resting energy expenditure in patients
up with the theory that adipose tissue deposits around with AD. The authors observed significantly higher IL-6
the knees might interfere by pressure on the joint with as well as mononuclear giant cell levels in AD compared
the blood supply and resulted in the development of with control adipose tissue. The study on adipokines
painful osteoarthritis. In 1952 Steiger et al48 expressed indicated that there was no difference in the levels
their doubts on the pluriglandular involvement in DD. of tumor necrosis factor (TNF)-α , leptin, adiponectin,
Hovesen in 195311 reported the inflammatory signs in plasminogen activator inhibitor-1, interleukin (IL)-1β,
the DD adipose tissue, i.e. infiltration of leukocytes and IL-8, IL-10, macrophage inflammatory protein (MIP)-1α ,
plasma cells. The painful lipomas could appear in any and monocyte chemotactic protein (MCP) compared
location and, even if several adipose tissue diseases to controls83. Nonetheless, significantly lower MIP-
may present similarly, the pain of DD is specifically 1β expression and a trend toward higher levels of IL-
associated with fatty nodules49-52. The absence of pain of 13 (interleukin-13) were reported. In addition, lower
the adipose masses should indeed distinguish DD from levels of fractalkine, also known as chemokine (C-X3-C
Cushing syndrome, multiple symmetric lipomatosis, motif) ligand 1, were seen. The authors concluded that
familiar multiple lipomatosis and lipedema as well as the lowered fractalkine levels were logical, since with
cutaneous malignant metastases53-56. prolonged release of fractalkine as seen in neuropathic
In 2005 DD was unrelated with malignancy by Wortham pain, the receptors to which fractalkine binds are
and Tomlinson52. Gastrointestinal symptoms were also upregulated. This suggests that there is shift from
found to be associated in some DD patients57,58 as well fractalkine release to receptor-bound fractalkine.
as metabolic complications including obesity, diabetes, The lower levels of fractalkine found in DD could
hypertension, dyslipidemia, and nonalcoholic fatty liver thus suggest that the substance is receptor-bound.
disease58,59. When receptors are occupied by fractalkine, pain and
Hereditary factors in DD have been reported by resistance to opioid analgesia are promoted.
some Authors53,60,61; however, most reported cases of Rasmusssen et al84 discovered an abnormal lymphatic
familiar occurrence of the condition was considered phenotype in three patients with the disease compared
to be sporadic62. DD has been suggested to be an with four female controls using near-infrared
expression of familial multiple lipomas, which is an fluorescence (NIRF) lymphatic imaging. The lymphatics
autosomal dominant disease characterized by multiple in the participants with DD were intact and dilated
asymptomatic lipomas63. This observation was derived but could not readily clear lymph when compared
by studying the family patterns of 2 siblings with DD; with lymphatics in four control patients. Further NIRF
findings suggested that the disease segregates in an imaging revealed masses of fluorescent tissue within
autosomal dominant fashion with variable phenotypic the painful nodules, suggesting a lymphovascular
expressivity, ranging from totally asymptomatic etiology. Kawale et al85 presented a DD patient with
to extremely painful lipomas. Mutational analysis painful thickening of the scalp in bilateral parieto-
excluded the 8344A→G mitochondrial mutation occipital areas and vertex for more than a year. The pain
seen in other patients with multiple lipomas62,63. The in the scalp caused headaches and disturbed sleep and
A→G transition at position 8344 in the tRNAlys gene daily activities. CT and MRI revealed diffuse thickening
of mitochondrial DNA has been described in the of the scalp tissue, but no evidence for other anomalies.
syndrome myoclonic epilepsy and ragged-red fibers Tsang et al86 noted a case of DD that caused weight loss
(MERRF). The presence of multiple lipomas resembling failure after Roux-en-Y gastric bypass. Eighteen months
those of multiple symmetrical lipomatosis had been after the operation the patient was unable to lose weight,
described in some members of pedigrees with MERRF despite adherence to behavioral and dietary guidance.
harboring the 8344 tRNA mutation64. An inflammatory Endoscopy performed 15 months after the operation
etiology has been proposed for DD65-67. However, excluded that any complications had occurred. Dercum
laboratory markers for inflammation markers, such patients often report that their obesity is refractory to
as erythrocyte sedimentation rate (ESR) and C-reactive diet and exercise intervention. Nonetheless, this has
protein (CRP), were reported by some authors as normal never been studied.
in most patients12,47,57-59,67-76. On the other hand, a few Hao et al (2018)87 have recently described an interesting
studies revealed elevated levels of CRP and ESR, even case of a 39-year old man with trauma induced DD. The

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 33

 Dercum’s disease or Adiposis Dolorosa: a complex condition still awaiting full definition

authors in their report highlighted the rare nature of factor, interleukin–1, and leptin104,105. The pilot study
painful adipose deposits and the diagnostic challenges. of Herbst and Rutledge105 suggested that rapid cycling
On histopathology, the fat deposition in DD was notable hypobaric pressure might reduce pain in patients with
for mature adult fatty tissue and sometimes, a number DD. Nonpharmacological approaches for DD may be
of blood vessels suggesting an angiolipoma. used as adjuncts to pharmacologic treatments. Some
According to some reports, ultrasonography and of these include acupuncture, cognitive behavioral
magnetic resonance imaging (MRI) may aid in the therapy, hypnosis, and biofeedback68,106. Several
diagnosis of DD74,88,89. In the study by Tins et al88 on 13 liposuction treated patients were reported by Hansson
patients with DD, lesions of the condition were found et al in 2011107. According to Dalziel the mechanism
to be markedly hyperechoic on ultrasound, superficial behind pain relief following liposuction was nerve
in location, and distinct from characteristic lipomas. plexus destruction within the adipose tissue94.
Further, when validated on more than 6000 MRIs, However, Hansson et al retained unlikely that direct
they appeared as ill-defined, nodular, “blush-like” nerve destruction alone explained the pain reduction
subcutaneous fat on unenhanced MRI with a decreased seen following liposuction107,108. Liposuction is regarded
T1-weighted signal. No case of DD was without these as a supportive treatment for DD. Any skeletal pain is
features in the study, and the authors concluded that not affected. A significant initial reduction of pain and
these findings, along with multiple subcutaneous fatty an improved quality of life is seen but these effects
lesions, is “very suggestive and possibly pathognomonic” decrease over time109.
for the condition. In regards to the pain treatment in
DD, some improvement was reported after systemic
or intralesional treatment with corticosteroids47,80,90,91,
whereas others experienced worsening of the pain92. Dercum’s disease still looking for clear and definitive
According to Taniguchi et al93, the alterations of fat answers
metabolism induced by corticosteroid excess could In an extensive review published in 2012 based on literature
play a role in the development of this syndrome. An data and studies concerning 111 DD patients81,107,108,
earlier study suggested that a defect in the synthesis Hansson et al56 described the classification, symptoms
of monounsaturated fatty acids may play a role in its and diagnosis, as well as, the epidemiology, etiology,
development12. Further studies are needed to support genetic counselling, treatment and prognosis of the
this hypothesis and to identify a specific biochemical disease. They discussed which symptoms were cardinal
defect. Dalziel94 suggested that the autonomous nervous and which were associated and promoted a “minimal
system mediates pain in DD. Vasoconstrictor response definition” of AD which including the following signs:
could be normalized by lidocaine infusion that is • Most often generalized overweight or obesity
thought to decrease the local or central sympathetic • Chronically painful adipose tissue (>3 months)
vasoconstrictor tone. Nonetheless, any substantial These authors also suggested the following classification
evidence of nervous system dysfunction has never been system:
found in DD and is hence merely a theory. • Type I: Generalized diffuse form; generalized, widespread
Gonciarz et al95 reported in 1997 that interferon (INF)- painful adipose tissue in the absence of discreet lipomas
alfa-2b induced long-term relief of pain in 2 patients Type II: Generalized nodular form; widespread painful
with AD and chronic hepatitis C. The analgesic effect • adipose tissue with concomitant intense pain in and
of IFN therapy occurred 3 weeks after treatment for around multiple discreet lipomas
6 months. Whether the mechanism of pain relief with Type III: Localized nodular form; pain in and around
IFN is related to its antiviral effect, to the production • multiple discreet lipomas
of endogenous substances, or to the interference of INF Type IV: Juxta-articular form; discreet deposits of excess
with cytokines involved in cutaneous hyperalgesias, • fat in specific locations, including the medial aspect of
i.e. interleukin 1 and tumor necrosis factor-alpha, the knee, the hips, and, rarely, the upper arm.
remains still undefined. Two DD case reports have Hanssen et al56, by retracing many cases described in
described pain relief with daily intake of mexiletine, the literature, analyzed the consistency between the
an antiarrhythmic70,96. Traditional analgesics, such as clinical signs reported and the minimum criteria for the
nonsteroidal anti-inflammatory drugs (NSAIDs), had diagnosis of DD. With the exception of a few cases110,
been thought to have a poor effect, with the pain in DD according to the authors most of the analyzed literature
often refractory to analgesics and to non-steroidal anti- cases67,72,85,104,111-114, were not fully consistent with the
inflammatory drugs (NSAIDs)44,46,68,77-79,91-100. However, minimal diagnostic criteria.
in their extensive article published in 2007, Herbst and Since the original description of DD, in addition to
Asare-Bediako concluded that 89% achieved relief when the painful nodular fatty deposits (which are often
treated with an NSAID, as did 97% when treated with unaffected by weight loss), the clinical spectrum has
an opiate58. In the same year, Singal et al101 reported changed to include to various degrees other components
improvement of a DD patient on infliximab, with and of DD58 i.e. general obesity, easy fatigability and
without methotrexate. In 2008, Desai et al102 reported weakness (asthenia), and a wide variety of unexplained
on successful treatment with a lidocaine (5%) patch, emotional disturbances, such as depression, confusion,
and Lange et al69 on one with pregabalin associated to and dementia. This observation is why DD has been
manual lymphatic drainage. Metformin was used with proposed to be relabeled as “Dercum syndrome”80. DD
success for AD associated pain by Labuzek et al103. It has been classified by the World Health Organization
was hypothesized that the drug could favorably alter (WHO) as a distinct entity and listed as a rare disease
the cytokine profile, impacting on tumor necrosis by the Orphanet115 and by the National Organization

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 34

 Dercum’s disease or Adiposis Dolorosa: a complex condition still awaiting full definition

for Rare Disorders (NORD)116. According to the latter

“Dercum Disease is a rare disorder in which there
are fatty deposits which apply pressure to the nerves,
resulting in weakness and pain. Various areas of the body
may swell for no apparent reason. The swelling may
disappear without treatment, leaving hardened tissue
or pendulous skin folds”. Steiner et al70 referred to DD
as a frequently overlooked disease and considered its
assignment to the neuropathic pain syndromes to be
justified. Traditional management of DD relying on
weight reduction and surgical excision of particularly
troublesome lesions has been largely unsatisfactory.
Even at the present time, no known drug can change
the course of the disease, and available treatments are
only symptomatic. Originally, Dercum5 attributed the
disease to an endocrine dysfunction, as he found atrophy
of the thyroid gland. Similarly, Waldorp proposed that
the disease is caused by hypophyseal dysfunction 24.
However, endocrine involvement was ruled out as early
as in 195248. In addition, more actual approaches have
not revealed any endocrine abnormalities12,16,59,80,117.
So, an endocrine dysfunction as the etiology of DD has
little support in the modern literature.
Moreover, there are no uniform findings pointing to an
inflammatory etiology in DD.
In conclusion, the findings on DD pathophysiology are
still inconclusive and the clinical significance of some
reports is unclear.
Based on literature data and personal experience,
the perception is that this complex condition, which
often takes on the contours of a real syndrome, is
much more frequent than one might think. Specific
research aimed at defining its pathophysiological
aspects could undoubtedly allow better clinical
results and therefore a strong effort by the scientific
community is warranted to make the diagnosis more
accurate and develop targeted therapies against such
complex pathological condition which, despite being
devastating for patients, is not always recognized and,
too often, either underestimated or even neglected.

Conflict of interest disclosure

The authors declare no conflicts of interest.

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 35

 Dercum’s disease or Adiposis Dolorosa: a complex condition still awaiting full definition

REFERENCES

1. Goodcharles FA. Dercum, Francis Xavier M.D., M.A., Ph.D.: physician, 27. Cushing HC. The Pituitary Body and its Disorders. Philadelphia, J.B.
philosopher, scientist. In: Goodcharles FA, ed. Encyclopedia of Lippincott, 1912, 8°, X.
Pennsylvania biography. Vol. 20 New York, NY: Lewis Historical
Publishing Company, Inc. 1932; 114-116. 28. Myers B. Case of Adiposis Dolorosa. Proc R Soc Med. 1923; 16(Clin
Sect):11-12.
2. Brubaker AP. Francis X. Dercum. Proc Am Philos Soc. 1932; 71:39-48.
29. Purves-Stewart Sir J. The Diagnosis of Nervous Diseases. Ed 6, 238,
3. Throchmorton TB. Francis X Dercum: physician teacher and New York, E.B. Treat & Co., 1924.
philosopher. J New Ment Dis. 1942; 96:529-541.
30. Winkelman NW, and Eckel JL. Adiposis dolorosa (Dercum’s disease):
4. Patel DA, Kenneth GS. Francis Xavier Dercum: a man for all seasons. CIinicopathological study. JAMA. 1925; 85:1935-1939.
Ann Clin Transl Neurol. 2015; 1(3):233-237.
31. Hammond JA. An instance of adiposis dolorosa in two sisters. Br Med
5. Dercum F X. Three cases of hitherto unclassified affection resembling J. 1904; 121:5.
in its grosser aspects obesity, but associated with special nervous
systems, adiposis dolorosa. Am J Med Sci. 1892; 104:521-535. 32. Hall JH, Walbrack CE. Adiposis dolorosa with report of three cases.
Am J Med Sci. 1904; 128:218-322.
6. Dercum FX. A subcutaneous connective-tissue dystrophy of the
arms and back, associated with symptoms resembling myxoedema. 33. McMullam G. Case of Adiposis Dolorosa (Dercum’s Disease). Proc.
University Medical Magazine Philadelphia 1888; 140-150. Royal Soc Med. 1910; 3:55-61.

7. White WH. A case of Adiposis Dolorosa. Br Med J. 1889; 1533-1534. 34. Carless A. Adiposis Dolorosa. Proc Royal Soc Med. 1911; 4:3-4.

8. Giudiceandrea V. L’adiposis dolorosa (malattia di Dercum). Riv Patol 35. Gossage AM. Proc Royal Soc Med. 1911; 4:4-8.
Nerv Ment. 1900; V:289-304.
36. Graham Little EG. Case of Dercum’s Disease. Proc R Soc Med. 1919;
9. Roux J, Vitaut M. Maladie de Dercum (Adiposis dolorosa). Revue 12:35-36.
Neurol (Paris). 1901; 9:881-888.
37. Myers B. Case of Adiposis Dolorosa. Proc R Soc Med. 1922; 15(Clin
10. Spaeth W. Adiposis dolorosa with report of a case. N C Med J. 1949; Sect):6-8.
10(5):269-273.
38. Stolkind E. Cases of Adiposis Dolorosa (Dercum’s Disease). Proc
11. Hovesen E. Adiposis doloross (Dercum’s syndrome). Nord Med. 1953; Royal Soc Med. 1923; 16(Clin Sect):45-47.
50(28):971-973.
39. Asana DJ. Dercum’s disease or Adiposis Dolorosa. Indian Medical
12. Blomstrand R, Juhlin L, Nordenstam H, Ohlsson R, Werner B, Engström Gazette. 1927; 636-637.
J. Adiposis dolorosa associated with defects of lipid metabolism.
Acta Derm Venereol. 1971; 51(4):243-250. 40. Labbe M and Boulin R. Dercum’s disease, not a clinical entity. Bull. et
mem. Soc. med. d. bop. de Paris. 1927; 5 I:687-695.
13. Iwane T, Maruyama M, Matsuki M, Ito Y, Shimoji K. Management
of intractable pain in adiposis dolorosa with intravenous 41. Gram HC. A symptom triad of the post-climatic period (adipositas
administration of lidocaine. Anesth Analg. 1976; 55(2):257-259. dolorosa-arthritis genuum-hypertensio arterialis). Acta Med Scand.
1930; 73:139.
14. Lemont H, Picciotti J, Pruzansky J: Dercum’s disease. J Am Podiatry
Assoc. 1979; 69(6):389-391. 42. Newburgh LH. Cause of obesity. JAMA. 1931; 97:1659-1661.

15. Pouliquen A, Baize P, Lebosse J, Fellion G. What remains of Dercum’s 43. Wilson CL. Adiposis dolorosa. Am J Surg. 1933; XIX(3):485-488.
disease? Ann Med Psychol (Paris). 1984; 142(5):730-737.
44. Boller R. Die Novocainbehandling des morbus Dercum. Klinische
16. Jensen JJ, Kiilerich S. A case of adiposis dolorosa-Dercum’s disease. Wochenschrift. 1934; 13:1786-1789.
Ugeskr Laeger 1991; 153(50):3564.
45. King D. Juxta-articular adiposis dolorosa, its significance and relation
17. Sierro Ch, Suter PM, Vetter W. Painful lipoma? Schweiz Rundsch Med to Dercum’s disease and osteoarthritis. Arch Surg. 1937; 34(4):599-
Prax. 2002; 91(4):129-132. 630.

18. Burr CW. A case of adiposis dolorosa with necropsy. J Nerv Ment Dis. 46. Eisman J, Swezey RL. Juxta-articular adiposis dolorosa: what is it?
1900; XXVII 519-525. Report of 2 cases. Ann Rheum Dis. 1979; 38(5):479-482.

19. Dercum FX. Two cases of adiposis dolorosa: One in a man complicated 47. Weinberger A, Wysenbeec AJ, Pinkhas J. Juxta-articular adiposis
by epilepsy; another in a woman presenting also circinate retinitis. dolorosa associated with rheumatoid arthritis. Report of 2 cases
Philadelphia Med J. 1902; 392-399. with good response to local corticosteroid injection. Clin Rheumatol.
1987; 6:446-448.
20. Dercum FX, McCarthy DJ. Autopsy in a Case of Adiposis Dolorosa.
Am J Med Sci. 1902; 124(6):994-1005. 48. Steiger WA, Litvin H, Lasché EM, Durant TM. Adiposis dolorosa
(Dercum’s disease). New Eng J Med. 1952; 247:393-396.
21. Price GE. Adiposis dolorosa: a cIinical and pathological study, with
the report of two cases with necropsy. Am J Med Sci. 1909; 137:705- 49. Stallworth JM, Hennigar GR, Jonsson HT Jr, Rodriguez O. The
715. chronically swollen painful extremity. A detailed study for possible
etiological factors. JAMA. 1974; 228(13):1656-1659.
22. Price GE, Bird JT. Adiposis dolorosa: report of a case with increased
sugar tolerance and epileptiform convulsions. JAMA. 1925; 84:247- 50. Mella BA. Adiposis dolorosa. Univ Mich Med Cent J. 1967; 33(2):79-81.
248.
51. Lemont H, Picciotti J, Pruzansky J. Dercum’s disease. J Am Podiatry
23. Foot NC, Good RW, Mènarq MC. Case of adiposis dolorosa with Assoc. 1979; 69(6):389-391.
necropsy. Am J Path. 1926; 2(3):251-262.
52. Wortham NC, Tomlinson IP. Dercum’s disease. Skinmed. 2005;
24. Waldorp NW. An original clinical interpretation of Dercum’s disease 4(3):157-162.
(adiposis dolorosa). Endocrinology. 1924; 8:51-60.
53. Gologorsky Y, Gologorsky D, Yarygina AS, Surti U, Zirwas MJ. Familiar
25. Mills CK. A Case of Adeno Lipomatosis: With Some Remarks on the multiple lipomatosis: report of a nwew family. Cutis. 2007; 79(3):227-
Differential Diagnosis of the Affection from Adiposis Dolorosa and 232.
Other Diseases. J Nerv Ment Dis. 1909; 36(2):106-108.
54. Nierman LK, Biller BM, Finding JW, et al. The diagnosis of Cushing’s
26. Stern H. Adiposis dolorosa with myxoedematous manifestations. Am syndrome: an Endocrine Society Clinical Practice Guideline. J Clin
J Med Sci. 1910; 139:359-363. Endocrinol Metab. 2008; 93(5):1526-1540.

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 36

 Dercum’s disease or Adiposis Dolorosa: a complex condition still awaiting full definition

55. Shin BW, Sim YJ, Jeong HJ, Kim GC. Lipedema, a rare disease. Ann 79. De Silva M, Earley MJ. Liposuction in the treatment of juxta-articular
Rehabil Med. 2011; 35(6):922-927. adiposis dolorosa. Ann Rheum Dis. 1990; 49(6):403-404.

56. Hansson E, Svensson H, Brorson H. Review of Dercum’s disease and 80. Palmer ED. Dercum’s disease: adiposis dolorosa. Am Fam Physician.
proposal of diagnostic criteria, diagnostic methods, classification 1981; 24(5):155-157.
and management. Orphanet J Rare Dis. 2012; 7:23.
81. Hansson E, Svensson H, Stenram U, Brorson H. Histology of adipose
57. Stormorken H, Brosstad F, Sommerschild H. The fibromyalgia tissue inflammation in Dercum’s disease, obesity and normal weight
syndrome: a member of the painful lipomatosis family? In: Pederson controls: a case control study. J Inflamm (Lond). 2011; 8(1):24.
JA, ed. New Research on Fibromyalgia. NewYork: Nova Science
Publishers, Inc.; 2006:157-185. 82. Leites SM, Davtian NK, Emanuel’ VIa. Pathophysiological
characteristics of adipose tissue in Dercum’s syndrome. Patol Fiziol
58. Herbst KL, Asare-Bediako S. Adiposis Dolorosa is more than painful Eksp Ter. 1972; 16(1):47-51.
fat. Endocrinologist. 2007; 17(6):326-344.
83. Herbst KL, Coviello AD, Chang A, Boyle DL. Lipomatosis-associated
59. Tiesmeier J, Warnecke H, Schuppert F. An uncommon cause of inflammation and excess collagen may contribute to lower relative
recurrent abdominal pain in a 63-year-old obese woman. Dtsch Med resting energy expenditure in women with adiposis dolorosa. Int J
Wochenschr. 2006; 131(9):434-437. Obes (Lond) 2009; 33(9):1031-1038.

60. Lynch HT, Harlan WL. Hereditary Factors in Adiposis Dolorosa 84. Rasmussen JC, Herbst KL, Aldrich MB, et al. An abnormal lymphatic
(Dercum’s Disease). Am J Hum Genet. 1963; 15(2):184-190. phenotype is associated with subcutaneous adipose tissue deposits
in Dercum’s disease. Obesity (Silver Spring). 2014; 22(10):2186-2192.
61. Cantu JM, Ruiz-Barquin E, Jimenez M, Castillo L, Macotela-Ruiz E.
Autosomal dominant inheritance in adiposis dolorosa (Dercum’s 85. Kawale J, Mahore A, Dange N, Bhoyar K. Adiposis dolorosa of scalp
disease). Humangenetik. 1973; 18(1):89-91. presenting with severe headache: an unusual case. J Headache Pain.
2010; 11(6):539-541.
62. Campen R, Mankin H, Louis DN, Hirano M, Maccollin M. Familial
occurrence of adiposis dolorosa. J Am Acad Dermatol. 2001; 86. Tsang C, Aggarwal R, Bonanomi G. Dercum’s disease as a cause of
44(1):132-136. weight loss failure after gastric bypass surgery. Surg Obes Relat Dis.
2011, 7:243-245.
63. Gamez J, Playan A, Andreu AL, et al. Familial multiple symmetric
lipomatosis associated with the A8344G mutation of mitochondrial 87. Hao D, Olugbodi A, Udechukwu N, Donato AA. Trauma-induced
DNA. Neurology. 1998; 51(1):258-260. adiposis dolorosa (Dercum’s disease). BMJ Case Reports. 2018;
doi:10.1136/bcr-2017-223869.
64. Silvestri G, Ciafaloni E, Santorelli FM, et al. Clinical features associated
with the A-->G transition at nucleotide 8344 of mtDNA (“MERRF 88. Tins BJ, Matthews C, Haddaway M, et al. Adiposis dolorosa (Dercum’s
mutation”). Neurology. 1993; 43(6):1200-1206. disease): MRI and ultrasound appearances. Clin Radiol. 2013;
68(10):1047-1053.
65. Kirpila J, Ripatti N. Adiposis dolorosa juxta-articularis: Dercum’s
disease & its therapy. Nord Med. 1958; 59(10):358-360. 89. Petscavage-Thomas JM, Walker EA, Bernard SA, Bennett J. Imaging
findings of adiposis dolorosa vs. massive localized lymphedema.
66. Brorson H, Fagher B. Dercum’s disease. Fatty tissue rheumatism Skeletal Radiol. 2015; 44(6):839-847.
caused by immune defense reaction?. Läkartidningen. 1996;
93(15):1433-1436. 90. Spota BB, Brage D. Cortisone therapy of Dercum’s disease. Dia Med.
1952; 24(73):1930-1932.
67. Szypula I, Kotulska A, Szopa M, Pieczyrak R, Kucharz E. Adiposis
dolorosa with hypercholesterolemia and premature severe 91. Brodovsky S, Westreich M, Leibowitz A, Schwartz Y. Adiposis
generalized atherosclerosis. Wiad Lek. 2009; 62(1):64-65. dolorosa (Dercum’s disease): 10-year follow-up. Ann Plast Surg. 1994;
33(6):664-668.
68. Campen RB, Sang CN, Duncan LM. Case records of the Massachusetts
General Hospital. Case 25-2006. A 41-year-old woman with painful 92. Greenbaum SS, Varga J. Corticosteroid-induced juxta-articular
subcutaneous nodules. N Engl J Med. 2006; 355(7):714-722. adiposis dolorosa. Arch Dermatol. 1991; 127(2):231-233.

69. Lange U, Oelzner P, Uhlemann C. Dercum’s disease (Lipomatosis 93. Taniguchi A, Okuda H, Mishima Y, et al. A case of adiposis dolorosa: lipid
dolorosa): successful therapy with pregabalin and manual lymphatic metabolism and hormone secretion. Int J Obes. 1986; 10(4):277-281.
drainage and a current overview. Rheumatol Int. 2008; 29(1):17-22.
94. Dalziel K. The nervous system and adipose tissue. Clin Dermatol.
70. Steiner J, Schiltz K, Heidenreich F, Weissenborn K. Lipomatosis 1989; 7(4):62-77.
dolorosa–a frequently overlooked disease picture. Nervenarzt. 2002;
73(2):183-187. 95. Gonciarz Z, Mazur W, Hartleb J, et al. Interferon alfa-2b induced long-
term relief of pain in two patients with adiposis dolorosa and chronic
71. Kosseifi S, Anaya E, Dronovalli G, Leicht S. Dercum’s Disease: An hepatitis C. J Hepatol. 1997; 27(6):1141.
Unusual Presentation. Pain Med. 2010; 11(9):1430-1434.
96. Petersen P, Kastrup J. Dercum’s disease (adiposis dolorosa).
72. Margherita G. Considerations on a case of post-traumatic adiposis Treatment of the severe pain with intravenous lidocaine. Pain. 1987;
dolorosa associated with a pathologic fracture. Rass Neuropsichiatr. 28(1):77-80.
1964; 18:211-218.
97. Atkinson RL: Intravenous lidocaine for the treatment of intractable
73. Bonatus TJ, Alexander AH. Dercum’s disease (adiposis dolorosa). A pain of adiposis dolorosa. Int J Obes. 1982; 6(4):351-357.
case report and review of the literature. Clin Orthop Relat Res. 1986;
(205):251-253. 98. George R, Poonnoose P, Isaiah R. Dercum’s disease (Adiposis
dolorosa): delayed diagnosis in a patient with cervical cancer. J Palliat
74. Amine B, Leguilchard F, Benhamou CL. Dercum’s disease (adiposis Care. 2004; 20(4):324-325.
dolorosa): a new case-report. Joint Bone Spine. 2004; 71(2):147-149.
99. Juhlin L. Long-standing pain relief of adiposis dolorosa (Dercum’s
75. Kling DH. Juxta-articular adiposis dolorosa. Its significance and disease) after intravenous infusion of lidocaine. J Am Acad Dermatol.
relation to Dercum’s disease and osteo-arthritis. Arch Surg. 1937; 1986; 15(2 Pt 2):383-385.
34:599-630.
100. Scheinberg MA, Diniz R, Diamant J. Improvement of juxtaarticular adiposis
76. Skagen K, Petersen P, Kastrup J, Norgaard T. The regulation of dolorosa by fat suction. Arthritis Rheum. 1987; 30(12):1436-1437.
subcutaneous blood flow in patient with Dercum’s disease. Acta
Derm Venereol. 1986; 66(4):337-339. 101. Singal A, Janiga JJ, Bossenbroek NM, Lim HW. Dercum’s disease
(adiposis dolorosa): a report of improvement with infliximab and
77. Nahir AM, Schapira D, Scharf Y. Juxta-articular adiposis dolorosa–a methotrexate. J Eur Acad Dermatol Venereol. 2007; 21(5):717.
neglected disease. Isr J Med Sci. 1983; 19(9):858-859.
102. Desai MJ, Siriki R, Wang D. Treatment of pain in Dercum’s disease
78. Chopra A, Walia P, Chopra D, Jassal JS. Adiposis dolorosa. Indian J with Lidoderm (lidocaine 5% patch): a case report. Pain Med. 2008;
Dermatol Venerol Leprol. 2000; 66(2):101-102. 9(8):1224-1226.

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 37

 Dercum’s disease or Adiposis Dolorosa: a complex condition still awaiting full definition

103. Labuzek K, Liber S, Suchy D, Okopieå BA. A successful case of pain

management using metformin in a patient with adiposis dolorosa. Int
J Clin Pharmacol Ther. 2013; 51(6):517-524.

104. Schaffer PR, Hale CS, Meehan SA, Shupack JL, Ramachandran S.
Adiposis dolorosa. Dermatol Online J. 2014; 20(12).

105. Herbst KL, Rutledge T. Pilot study: rapidly cycling hypobaric pressure
improves pain after 5 days in adiposis dolorosa. J Pain Res. 2010;
3:147-153.

106. Martinenghi S, Caretto A, Losio C, Scavini M, Bosi E. Successful

Treatment of Dercum’s Disease by Transcutaneous Electrical
Stimulation: A Case Report. Medicine (Baltimore). 2015; 94(24):e950.

107. Hansson E, Svensson H, Brorson H. Liposuction may reduce pain in

Dercum’s disease (adiposis dolorosa). Pain Med. 2011; 12(6):942-952.

108. Hansson E, Svensson H, Rosen I, Brorson H. Thermal and vibratory

thresholds after liposuction in patients with Dercum’s disease. J Plast
Surg Hand Surg. 2011; 45(2):72-76.

109. Wollina U, Heinig B, Langner D, Nowak A. Juxta-articular adiposis

dolorosa (Dercum’s disease type IV): report of four cases and
treatment by dermolipectomy. Wien Med Wochenschr. 2015; 165(17-
18):374-377.

110. Haddad D, Athmani B, Costa A, Cartier S. Dercum’s disease: a severe

complication in a rare disease. A case report. Ann Chir Plast Esthet.
2005; 50(3):247-250.

111. Kyllerman M, Brandberg G, Wiklund LM, Mansson JE. Dysarthria,

progressive parkinsonian features and symmetric necrosis of
putamen in a family with painful lipomas (Dercum disease variant).
Neuropediatrics. 2002; 33(2):69-72.

112. Rosenberg B, Hurwitz A, Hermann H: Decum’s disease with unusual

retroperitoneal and paravesical fatty infiltration. Surgery. 1963;
54:451-455.

113. Trentin C, Di Nubila B, Cassano E, Bellomi M. A rare cause of mastalgia:

Dercum’s disease (adiposis dolorosa). Tumori. 2008; 94(5):762-764.

114. Reece PH, Wyatt M, O’Flynn P. Dercum’s disease (adiposis dolorosa). J

Laryngol Otol. 1999; 113(2):174-176.

115. Adiposis dolorosa.

http://www.orpha.net/consor/cgi-bin/OC_Exp.
php?lng=EN&Expert=36397

116. Dercum’s Disease.

http://www.rarediseases.org/rare-disease-information/rare-
diseases/byID/490/viewAbstract

117. Pimenta WP, Paula FJ, Dick-de-Paula I, et al. Hormonal and metabolic
study of a case of adiposis dolorosa (Dercum’s disease). Braz J Med
Biol Res. 1992; 25(9):889-893.

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 38

Case Report

Clinical and aesthetic results after medical

treatment of subeyelid nodular basal cell
carcinoma
Vincenzo Di Blasio¹, Angelo Forgione¹, Antonio Di Lucrezia¹, Dario Dorato²
1MD, Emergency Service - PSAUT Maria delle Grazie - ASL BN1- Benevento

²MD, General Secretariat - Italian Society of Aesthetic Medicine - Rome

Abstract
Basal Cell Carcinoma is the most common skin cancer worldwide. Currently, the best treatment method is surgical
removal, but there are cases in which surgery is not feasible and alternative methods must be used. Imiquimod, a potent
immune-modulator recently introduced, was effective in the topical treatment of several skin diseases of viral and
neoplastic origin, with promising results.
This study aims, firstly, to evaluate Imiquimod’s effectiveness in the treatment of subeyelid Nodular Basal Cell Carcinoma;
secondly, to evaluate the aesthetic and functional results, in an area of the face where surgery is not always indicated.
A 95 year old women, who for two years had a Nodular-BCC, was treated with topical application of 5% Imiquimod cream,
with the following protocol: 3 applications a week for a duration of 7 weeks. After the end of treatment, a monthly
follow-up was performed for the first six months, then quarterly, in the next six months; subsequent monitoring was
done every six months.
The method we used, was fully effective, leading to complete disappearance of the tumor, with no evidence of recurrence
at 36 months. There were good functional results, without any static or dynamic alteration of the eyelid function.
Aesthetic results appeared excellent, without scar, discoloration or atrophy, and without other types of damage.
This method appears fully effective and easily achievable, with excellent aesthetic and functional results. The method
could become the first choice for this particular site and it could also find broad indication in other delicate areas of
the face.

Keywords
Basal Cell Carcinoma, nodular basal cell carcinoma, imiquimod

Received for publication July 3, 2018; accepted September 6, 2018 - © Salus Internazionale ECM srl - Provider ECM nº 763

Correspondence

Vincenzo Di Blasio, MD
Emergency Service - PSUT Maria delle Grazie - ASL BN1 - Benevento
Phone: + 39 0824 812203 - Fax: +39 0824 812233
E-mail: [email protected]

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 39

 Clinical and aesthetic results after medical treatment of subeyelid nodular basal cell carcinoma

Introduction of therapy, a monthly follow-up was performed for the

Basal Cell Carcinoma (BCC) is the most common skin first six months; then quarterly, in the next six months;
cancer worldwide, with an incidence of 146-422 cases/ subsequent monitoring was done every six months.
year/100,000 persons in the US, depending on latitude1.
It is more frequent in men and in elderly, but its
__________________________________________________________
incidence amongst people younger than 40 is increasing,
particularly in women1. The main cause is the exposure
to UV rays of the sun (intermittent intense, rather than Subtypes Incidence
cumulative)1,2,3, which is why it is more common in
equatorial regions, in the most sun-exposed areas of ____________________________________________________________________________________________________________________

skin and in fair skin types (tendency to burn, rather

than tan)1,3. The sites most affected are the photo-
exposed areas and in 90% of cases it is localized to the Three main clinical subtypes:
head, preferring cheeks, nasolabial folds, forehead and
eyelids1. The periocular region is interested in 20% of Nodular Basal Cell Carcinoma 50-79%
cases4. Regarding the clinical features of BCC, six overall
subtypes have been identified, of which three are more
Superficial Basal Cell Carcinoma 10-15%
frequent and three are quite rare, but more aggressive
(high risk). Nodular Basal Cell Carcinoma is the most
common subtype (50-79%) of all basal cell carcinomas1
Morpheaform (Sclerosing) BCC 5-10%
(Table 1). Basal Cell Carcinoma may be treated with
different therapeutic procedures, even with high rates of
healing1, but the surgical removal of the tumor remains
Other rare subtypes:
the preferred method, due to its greater therapeutic
efficacy1,5. Despite surgical treatment being the best
method, there are cases in which surgery is not feasible Infiltrative BCC
and alternative methods must be used6,7. Over time,
several alternative topical therapies have been utilized, Micronodular BCC
some of which are now obsolete, others are rarely used,
and others, more recent, appear promising1,2,5,7,8 (Table Basosquamous Carcinoma (Metatypical)
2). Imiquimod (IMQ), an immune-modulator recently
introduced, was effective in the medical treatment of __________________________________________________________
certain skin diseases of viral and neoplastic origin7. Table 1 - Basal Cell Carcinoma: Clinical features.
Currently, many studies are underway in order to
evaluate its effectiveness in several skin diseases and
neoplasms, while the preliminary results are already
very promising1,7,8. Objectives of this study are: first,
to evaluate Imiquimod effectiveness in the treatment
of subeyelid Nodular Basal Cell Carcinoma; second, to
evaluate its ease and safety in delicate areas of the face; _________________________________________________________
third, to evaluate the aesthetic and functional results,
in an area of the face where surgery is not always
Method Notes
indicated, because of possible permanent sequelae.
__________________________________________________________________________________________________________________

Case Report Intralesional Injections obsolete and painful

A 95 year old woman, with fair skin, light brown
hair and blue eyes (Fitzpatrick skin-type 3), for two
Cryosurgery discolored scar, recurrence
years had a Nodular Basal Cell Carcinoma in the left
subeyelid region. From six months the lesion ulcerated
(rodent ulcer), with a crater-like appearance and Radiation Therapy dermatitis, atrophy, fibrosis
hardened edges (Figure 1). The patient was treated
with topical application of 5% Imiquimod cream with 5-Fluorouracil, topic approved, but rarely used
the following protocol: 3 applications a week (Mon-
Wed-Fri) for a duration of 7 weeks. The cream was Laser Therapy controversial, but promising
applied in the morning, by covering with a thin layer
across the neoplasm, including an annular area of Photodynamic Therapy not approved, but promising
healthy skin around the lesion, for a width of 2 mm.
The cream was left to act for 8 hours, and then it was
Imiquimod, 5% topic recent, approved, promising
washed with warm water and mild detergent. Care was
taken to anamnestic and clinical evaluation, also with
_________________________________________________________
photographic documentation, at the start of each week,
before applying the cream. After finishing the course Table 2 - BCC: Alternative topical therapies.

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 40

 Clinical and aesthetic results after medical treatment of subeyelid nodular basal cell carcinoma

Results
In the first two weeks, the treatment produced a
progressive erythema, which affected the tumor, the
upper portion of the cheek and the lower eyelid. In
the next week, it established a growing edema, with
a mild serous oozing and some crusts. Meanwhile,
in the upper cheek, growing itching appeared, and
sometimes burning with desquamation. From the
fourth week a progressive regression of the tumor was
observed, while intense erythema persisted associated
with edema. At the end of treatment the tumor had
disappeared; the residual edema resolved within two
weeks, while the erythema showed a progressive
reduction and disappeared altogether during the third
month (Figure 2). In the following controls we never
observed redness or swelling, discolored or atrophic
outcomes, and we did not find any other sign of Figure 1 - Nodular-BCC in the left subeyelid region.
aesthetic damage. At 36 months, there was no evidence
of tumor recurrence and no functional impairment of
the involved eyelid; cheeks and eyelids were perfectly
symmetrical, with excellent aesthetic results and high
satisfaction of the patient (Figure 3).

Discussion
Surgical removal is the best treatment method for all
Basal Cell Carcinoma, due to its greater therapeutic
efficacy1. Currently, three main surgical techniques may
be used, all of which are effective in high percentage of
cases1,2,9 (Table 3). Electrodesiccation and Curettage is
effective in 95.1% of cases, but it may exit in discolored
scar1; Standard Surgical Excision is effective in 95.2%
of cases, but it may give unacceptable aesthetic and
functional outcomes1,3,10. Mohs Micrographic Surgery,
a tissue sparing method, gives the best results, with
efficacy in 98.6% of cases1,3,4; however, this technique
is not always feasible, for the frequent lack of specific
infrastructures3. Despite surgical removal remaining
Figure 2 - Result after the end of treatment.
the best therapeutic method for Basal Cell Carcinoma,
there are cases in which surgery is not possible2,4. There
is no indication for surgery in cases of large or multiple
lesions, in difficult anatomical sites, and in high surgical
risk patients (elderly, comorbidity, anticoagulants); in
other cases there is a consistent risk of unacceptable
aesthetic and functional outcome or the patient refuses
surgery4,5,8. Moreover, as in the case we observed, the
tumor also may involve a part of the lower eyelid,
exposing to the risk of functional damage in case of
surgical removal, with possible ectropion, as well as
unpredictable cosmetic damage4. When surgery is not
feasible, there are several alternative topical therapies1,2
(Table 2), of which Imiquimod 5% topic cream, is
the most recent and the most promising, because it
was effective in the medical treatment of several skin
diseases of viral and neoplastic origin7.
At present, Imiquimod is approved by the FDA only for
the treatment of Anogenital Warts, Actinic Keratosis
and Superficial-BCC3,7,11. Consequently, the use of IMQ
in the Nodular subtype of BCC, currently, must be
considered off label. However, as some recent studies
show, it may also be effective in the Nodular-BCC4,5,9, as
in other skin tumors1,6,8,10. Figure 3 - 36 months follow-up: no tumor recurrence.

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 41

 Clinical and aesthetic results after medical treatment of subeyelid nodular basal cell carcinoma

___________________________________________________
Conclusions
Effectiveness: Imiquimod shows full effectiveness also
Technique Efficacy in the Nodular-BCC, with complete disappearance of the
tumor and no recurrence at 36 months.
__________________________________________________________________________________________________________________
Easy and safe: home treatment may be done, without
need for hospitalization; IMQ use is easy and safe in
difficult sites and in certain patients, without need for
Electrodesiccation and Curettage 95.1% anesthesia, tissue removal, sutures or reconstruction.
Aesthetic results: IMQ gives excellent aesthetic results,
Standard Surgical Excision 95.2% as well as functional, without scar, discoloration or
atrophy, and without functional damage.
Mohs Micrographic Surgery 98.6% This recent therapeutic method appears fully effective
and easily achievable. The procedure could become the
_________________________________________________________
first choice for this particular site and could also find
broad indication in other delicate areas of the face.
Table 3 - Basal Cell Carcinoma: Surgical options.

Imiquimod acts as a potent immune response modifier: Conflict of interest

it has, firstly, a direct action, with induction of apoptosis The authors declare that they have no conflicts of
in tumor cell lines, by up-regulating pro-apoptotic interest, and have not received any contribution for this
proteins8; secondly, an indirect action, by release of publication.
modulatory cytokines (ILs, IFNa-g) which increase the
cytotoxic T-cells and natural Killer-cells7,8,11. The main
advantages are: high effectiveness with low costs, easy
home use, and useful alternative for subjects who Legends
cannot be treated surgically7,10. The local side effects of BCC Basal Cell Carcinoma
IMQ are, generally, modest and tolerable, consisting of: N-BCC Nodular Basal Cell Carcinoma
erythema, edema, itching, burning, erosion, scabbing, IMQ Imiquimod
crusting1,2,3. The systemic adverse effects are very rare FDA Food and Drug Administration
and may consist of: flu-like symptoms, nausea, headache,
myalgia, fatigue and fever5. For the use of Imiquimod,
a standardized protocol does not exist3. The most used
application is provided 5 times a week, for 6 weeks3,5,8,9;
but there are other protocols with application 2-7 times
a week, for 4-12 weeks2,4,5,10,11,12. The effectiveness of
the treatment varies from 78,4 to 93,4%, in relation to
different variables, and in some works success rates
up to 100% have been reported4,5,10,11. The method we
used, with topical application of 5% Imiquimod cream,
3 times a week for 7 weeks, was fully effective, leading
to the complete disappearance of the tumor, with no
evidence of recurrence at 36 months (Figure 3). Also
from a functional point of view, there were good
results, as no static or dynamic alteration of the eyelid
function was observed, which can happen with surgical
treatment4. Technically, the method was easy to play;
the procedure was done at home, without the need for
hospitalization. The treatment was well tolerated, with
erythema, edema, crusting, and only a mild itching
or, sometimes, a burning sensation. In addition, the
method did not require anesthesia, removal of tissue,
suture, reconstruction or other surgical traumatism.
With regard to aesthetic aspects, there was no scar,
no discoloration, no atrophy or fibrosis, and no other
type of cosmetic damage. Cheeks and eyelids appeared
perfectly symmetrical, without any anatomical
alteration to the lower left eyelid. The hypo-pigmented
area, under the medial canthus, appearing in figure 3,
was not caused by this treatment, because it was pre-
existing, as seen in figure 1, and was due to photo-
chrono-aging, like other discolorations of the face.

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 42

 Clinical and aesthetic results after medical treatment of subeyelid nodular basal cell carcinoma

REFERENCES

1. Marzuka AG, Book SE. Basal cell carcinoma: pathogenesis,

epidemiology, clinical features, diagnosis, histopathology, and
management. Yale J Biol Med. 2015; 88(2):167-179.

2. Totonkchy M, Leffell D. Emerging concepts and recent advances in

basal cell carcinoma. F1000Res. 2017; 6:2085.

3. Singal A, Daulatabad D, Pandhi D, Arora VK. Facial basal cell carcinoma

treated with topical 5% Imiquimod cream with dermoscopic
evaluation. J Cutan Aesthet Surg. 2016; 9(2):122-125.

4. de Macedo EM, Carneiro RC, de Lima PP, Silva BG, Matayoshi S.

Imiquimod cream efficacy in the treatment of periocular nodular
basal cell carcinoma: a non-randomized trial. BMC Ophthalmol. 2015;
15:35-41.

5. Karabulut GO, Kaynak P, Ozturker C, Fazil K, Ocak OB, Taskapili M.

Imiquimod 5% cream for the treatment of large nodular basal cell
carcinoma at the medial canthal area. Indian J Ophthalmol. 2017;
65(1):48-51.

6. Fahradyan A, Howell AC, Wolfswinkel EM, Tsuha M, Sheth P, Wong

AK. Updates on the management of Non-Melanoma Skin Cancer
(NMSC). Healthcare (Basel). 2017; 5(4):82-95.

7. Lanoue J, Goldenberg G. Basal cell carcinoma. A comprehensive

review of existing and emerging nonsurgical therapies. J Clin Aesthet
Dermatol. 2016; 9(5):26-36.

8. Bubna AK. Imiquimod - Its role in the treatment of cutaneous

malignancies. Indian J Pharmacol. 2015; 47(4):354-359.

9. Ozolins M, Williams HC, Armstrong SJ, Bath-Hextall FJ. The SINS trial:
A randomized controlled trial of excisional surgery versus Imiquimod
5% cream for nodular and superficial basal cell carcinoma. Trials.
2010; 11:42-50.

10. Alessi SS, Sanches JA, de Oliveira WR, Messina MC, Pimentel ER, Festa
Neto C. Treatment of cutaneous tumors with topical 5% imiquimod
cream. Clinics (Sao Paulo). 2009; 64(10):961-966.

11. Lewin JM, Carucci JA. Advances in the management of basal cell
carcinoma. F1000Prime Rep. 2015; 7:53-65.

12. Cannon PS, O’Donnell B, Huilgol SC, Selva D. The ophthalmic side-
effects of Imiquimod therapy in the management of periocular skin
lesions. Br J Ophthalmol. 2011; 95(12):1682-1685.

Aesthetic Medicine / Volume 4 / Nº3 / July - September 2018 43

Courses and Congresses
2018 2019

7 - 8 September - Paris (France) 21-23 February - Malaga (Spain)

39th National Congress SFME 34th National Congress SEME
French Society of Aesthetic Medicine Spanish Society of Aesthetic Medicine
Palais des Congrès de Paris Palacio de Ferias y Congresos
President: J.J. Legrand President: P. Vega
Email: [email protected] Email: [email protected]
Web: www.sfme.info Web: www.seme2019.org

27 - 30 September - Warsaw (Poland) 9 - 10 March - Seoul (Korea)

XVIII International Congress of Aesthetic and Anti- 22th World Congress of Aesthetic Medicine - UIME
Aging Medicine Organised by: Korean Academy of Aesthetic Medicine
Poland Society of Aesthetic and Anti-Aging Medicine - Coex, Seoul
PTMEiAA President: Wooha Han
Hilton Warsaw Hotel and Convention Center - Warsaw E-mail: [email protected]
President: A. Ignaciuk Web: http://ons.thewithin.kr/register/2019_24/intro.html
Web: www.icaam.pl
26 - 27 April - Brussels (Belgium)
26 - 27 October - Toronto (Canada) Congress SBME - BVEG 2019
CAAM 15th Annual Conference Belgian Society of Aesthetic Medicine
Canadian Association of Aesthetic Medicine Radisson Blu Royal Hotel
Hilton Toronto / Markham Suites Conference Centre President: J. Hebrant
President: R. Van Aardt Web: www.radissonblu.com
Web: www.caam.ca/annual-conference
17 - 19 May - Rome (Italy)
9 - 10 November - Santiago (Chile) 40th SIME Congress
XII Chilean Congress of Aesthetic Medicine Italian Society of Aesthetic Medicine
Chilean Association of Aesthetic Medicine Rome Cavalieri Congress Center
Hotel International - Las Condes, Santiago - Chile President: E. Bartoletti
President: G. Marzullo E-mail: [email protected]
Email: [email protected] Web: www.lamedicinaestetica.it
Web: www.sochme.cl/congesomedicinaestetica
14 - 15 June - Basel (switzerland)
9 - 11 November - Miami (Florida - USA) 16th Congress of the Swiss Society of Aesthetic Medicine
15th Annual AAAM Congress 7th Congress of the Swiss Society of Aesthetic Surgery
American Academy of Aesthetic Medecine Safran Zunft, Basel
JW Marriott, Miami President: S. Le Huu
President: M. Delune Email: [email protected]
Email: [email protected] Web: www.ssme.ch
Web: www.aaamed.org
13 - 14 September - Paris (France)
7 - 9 December - Cascais, Lisbona (Portugal) 40th National Congress SFME
3rd National Congress of Aesthetic Medicine French Society of Aesthetic Medicine
Portuguese Society of Aesthetic Medicine Palais des Congrès de Paris
Hotel The Otaivos, Cascais President: J.J. Legrand
Presidente: J.P. Vale Email: [email protected]
Email: [email protected] Website: www.sfme.info
Web: www.spme2018.com

2020

15 - 17 October - Quito (Ecuador)

XIII Pan American Congress of Aesthetic Medicine - UIME
Organised by: Ecuatorian Society of Aesthetic Medicine
President: V. Tinoco Kirby
Email: [email protected]
Web: www.seem.com.ec

Aesthetic Medicine / Volume 4 / Nº 2 / April - June 2018 44