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Received: 18 December 2018    Revised: 20 June 2019    Accepted: 1 August 2019

DOI: 10.1111/jocd.13115

REVIEW ARTICLE

Mesotherapy: Safety profile and management of complications

Kerasia‐Maria Plachouri MD, PhD  | Sophia Georgiou MD, PhD

Dermatology Department, University of
Patras, Patras, Greece
Correspondence
Kerasia‐Maria Plachouri, University General
Hospital of Patras, Rio 265 04, Patras,
Greece.
Email: kerasia.plachouri@hotmail.com
Abstract
Background: Mesotherapy is a procedure that involves the injection of active sub‐
stances into the dermis and subcutaneous tissue in order to treat several local medi‐
cal and cosmetic conditions. Despite being considered as a relatively safe method, a
series of adverse reactions can occur due to its wide application and lack of stand‐
ardization processes.
Objectives: The aim of this paper is to summarize all the mesotherapy‐related compli‐
cations published so far, and to provide an insight into their management.
Patient/Methods: Articles derived from the databases, PubMed, EMBASE, and
SCOPUS, and published between 1992 and 2018, were analyzed for this review. The
study was conducted according to the PRISMA guidelines.
Results: In this literature, there is a number of case series and isolated case reports
describing various side effects of different severities. The therapeutic management
of these complications is—in most cases—individualized.
Conclusions: Larger systematic studies are needed in order to adequately evaluate
the safety profile of mesotherapy, and in order to determine standardized therapy
parameters, so as to minimize the risk of potential adverse reactions.

KEYWORDS
complications, management, mesotherapy

1 |  I NTRO D U C TI O N The development of various mesotherapeutic protocols for numer‐

Mesotherapy is a modern treatment with various cosmetic and non‐
cosmetic indications, first introduced in 1952 by French physician
Pistor.1 The aim of this procedure is the direct transepidermal trans‐
port of various active substances in the dermis or deeper skin lay‐
ers, so as to stimulate the fibroblast activity and collagenogenesis,
as well as to reverse the degeneration of elastin and the continu‐
ous transepidermal water loss, all of which occur during the aging
process. 2 The external application of these active substances could
not lead to the same results, either due to the impairment of their
penetration through the lipid barrier and the stratum corneum, or
due to their chemical decomposition on the epidermis surface. 2,3
Mesotherapy has gained massive popularity over the last years, due
to the fact that it offers an inexpensive direct drug delivery in the
area of interest and it requires minimal training for the physicians.4
ous indications makes the cumulative safety evaluation difficult and
no larger cohort studies for risk assessment on mesotherapy have
been conducted up to this point.5 This report aims to present all the
mesotherapy‐associated complications reported in the literature
so far and to provide an insight into as far as their management is
concerned.
2 | M ATE R I A L S A N D M E TH O DS
This study was conducted according to the PRISMA guidelines
(Preferred Reporting Items for Systematic Reviews) for system‐
atic reviews. The databases of MEDLINE (PubMed), EMBASE, and
SCOPUS were screened using the following Mesh key terms: “meso‐
therapy,” “microneedling,” “subcutaneous injection,” “side effects,”

J Cosmet Dermatol. 2019;00:1–5. © 2019 Wiley Periodicals, Inc. |  1

wileyonlinelibrary.com/journal/jocd  
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2       PLACHOURI and GEORGIOU
“complications,” and “adverse reactions.” Further papers were also
identified from the reference lists of the above‐retrieved papers and
citations, as identified by Web of Science. Our search included articles
in the English, Spanish, German, and French language, published be‐
tween 1992 and 2018. The selection process included first screening
of titles and abstracts, and then evaluation of full‐text articles.
3 |   R E S U LT S
3.1 | Infectious complications
Among the main adverse events during mesotherapy are the ones
related to sterility issues and infection risk.6 Orjuela et al present a
case series of six patients who developed cutaneous tuberculosis
with Mycobacterium tuberculosis after the injection of unknown mes‐
6
otherapy cocktails for the cellulite treatment. Despite the efficacy of
the standard antibiotic treatment, eventually permanent scarring was
not always avoidable.6 Spontaneous healing after several months was
also observed in one of the patients who refused the antibiotic treat‐
ment.6 While infection with M tuberculosis is only rarely described
in the literature, there are numerous reports on injection‐site infec‐
tions with opportunistic nontuberculous mycobacteria, even in the
forms of outbreaks related to specific treatment centers.7-17 Most
of the isolated mycobacteria in the reported cases include M ab‐
scessus,7-10 M chelonae,11-13 and M fortuitum,14-16 while less frequent
reports include not so common species, like M cosmeticum or M im‐
17 18
munogenum, as well as M bovis in rare cases. The treatment of a
mycobacterial infection can be very challenging, due to its resistance
in multiple antibiotics.8 The therapy should be individualized after an
antibiogram has been obtained and it should consist of at least two
antibiotic agents, in order to reduce the risk of induced resistance.8,9
15
In difficult cases, even triple regimens have been described. Most
of the mycobacteria are susceptible to antibiotics such as clarithro‐
mycin, erythromycin, amikacin, doxycycline, ciprofloxacin, tobramy‐
cin, tigecycline, and cefoxitin.8,9,13 In the majority of the cases, the
duration of therapy can vary from 2 to 6 months, depending on the
immunocompetence status of the patient and the severity of the in‐
8,14
fection. In many cases, residual lesions have been described to
persist, despite long‐term antibiotic treatment.8 Another approach
for these resistant cases of mycobacterial infections is the surgical
excision of isolated lesions, with or without accompanying antibiotic
therapy.13,14 It should be noted that, even in cases of successful treat‐
ment of the infection, permanent scarring can still remain.16
Apart from mycobacteria, other organisms have been described
less frequently as mesotherapy‐associated infectious agents.19,20
Rodriguez‐Gutierez et al describe a case of Nocardia brasiliensis in‐
fection emerging 1 week after mesotherapy with silica, triiodoacetic
acid, and artichoke oil in the abdomen of a 30‐year‐old female pa‐
tient.19 After a 3‐month treatment with 800/160 mg of trimetho‐
prim/sulfamethoxazole for every 12 hours and 100 mg of dapsone
daily, the patient showed a complete remission.19 Mesotherapy‐as‐
sociated sporotrichosis has also been described by Gamo et al in a
case report of two patients: In these cases, the treatment of choice
was 300 mg of potassium iodide, three times a day, for 8 months
and 100 mg of itraconazole, daily, for 6 months, respectively, until
complete resolution of the lesions was achieved. 21
In order to minimize the infection risk, it is important that such
mini‐invasive procedures are conducted by licensed physicians, who
comply with sterility regulations, since the epidermis can serve as a
temporary carrier for several nontuberculous mycobacteria species,
like M fortuitum.7,14 Proper hygienic conditions in the treatment clinic
and the use of contamination‐free instruments and tools, such as
cotton swabs or anesthetic creams, should also be guaranteed.7,8,14
Since reports on contaminated homeopathic products with ques‐
tionable processes of manufacturing, handling, and packaging have
also been reported,8 it is advisable to use officially approved inject‐
able products that are prepared according to standard sterility‐en‐
suring guidelines.7
3.2 | Noninfectious complications
When it comes to noninfectious complications, several types of ad‐
verse reactions have been described, mostly as isolated case reports
of individual patients.
Granulomatous foreign body reactions have been reported to
occur after the mesotherapy application of agents such as phospha‐
tidylcholine, deoxycholate, buflomedil, silica, or carnitine, as well as
a large number of several other different substances, in some cases
even oil‐based, which are widely used for lipolytic purposes. 22-25
The management in these cases can include the application of in‐
tralesional steroids, such as triamcinolone acetonide, in several
sessions. 22 Approaches with the administration of systemic corti‐
costeroids have also been described, however, without significant
benefits, 22,25 while the administration of 100 mg of dapsone daily
for several weeks has been reported by Gokdemir et al lead to a sub‐
stantial improvement of the granulomatous lesions. 24 Ramos‐e‐Silva
et al describe a case of an oleoma, a severe granulomatous reaction
after injection of an oil‐based mesotherapeutic cocktail for the cel‐
lulite treatment. 25 The lesions remained unresponsive to systemic
steroids but seemed to respond to treatment with 0.5 mg/day of
colchicine for three more months, leaving, however, an atrophic
scarring. 25 A case of mesotherapy‐associated granuloma annulare
has also been reported by Strahan et al; however, no information
on a successful therapeutic management is provided in this work. 26
Apart from the formation of granulomas, another commonly
seen side effect is a prominent inflammatory reaction due to the in‐
jection of the mesotherapeutic agent, resulting in the formation of
microabscesses in the dermis, septal, or lobular panniculitis, or even,
in severe cases, extensive fat necrosis with microcalcification and
cyst formation subcutaneously, as well as ulcer formation. 27 This is
especially observed with phosphatidylcholine‐containing mesother‐
apy cocktails, serving as cellulite treatment. 27 Cases of histologically
confirmed mesotherapy‐associated factitial panniculitis are present
in the literature. 27-29 As far as their management is concerned, dap‐
sone has been used successfully in isolated occasions. 28,29 Tan et
al report a complete clinical resolution under 100 mg of dapsone
PLACHOURI and GEORGIOU
daily, over a period of three months. 29 Davis et al also report the im‐
provement of steroid‐refractory granulomatous panniculitis under
the same regimen.30 Lee et al describe a case of a histologically con‐
firmed panniculitis due to subcutaneous injections of 5% dextrose
combined with lidocaine that aggravated to the point of fat tissue
31
necrosis and liquefaction with ulcer formation. A therapy with
minocycline (100 mg/d for 2 weeks) and prednisolone (20 mg/d for
2 weeks) proved to be unsuccessful; therefore, the authors opted for
a conservative local treatment with wound‐dressings and mupirocin
31
application. Other regimens for mesotherapy‐associated cutane‐
ous ulcers include the use of 100 mg of doxycycline daily, in addition
to the local treatment with 2% fusidic acid as well as 1% hydrocorti‐
sone acetate, as described by Al‐Khenaizan.32
Among the uses of mesotherapy is the treatment of androgenetic
alopecia.4 However, scarring or nonscarring alopecia can occur as a
result of the treatment itself, mostly due to mesotherapy‐induced fat
necrosis and abscess formation.33 In such a case presented by Kadry
et al, the conservative treatment seemed to show no effect; so the
surgical removal of the inflamed tissues was selected as the treatment
of choice.33 El‐Komy et al describe a series of three patients, where
the prominent histologic feature was not an inflammation of the fat tis‐
sue, but rather an inflammatory scarring process with perivascular and
perifollicular lymphohistiocytic infiltration and sebaceous gland hyper‐
plasia, as well as a hypertrophy of the perifollicular collagen fibers.34
The mesotherapy cocktail used in two out of the three cases included
dutasteride 0.005% (Mesologica®), insulin‐like growth factor‐1 (IGF‐1),
basic fibroblast growth factor (bfGf), vascular endothelial growth factor
(VEGF), copper tripeptide‐1, multi‐vitamins, amino acids, and minerals
® 34
(Mesologica MRS Hair ). The management of this adverse reaction
included the prescription of topical minoxidil or the application of in‐
tralesional saline injections twice daily at the affected area, combined
with a topical melatonin solution.34 Cases of noncicatrical alopecia, as
an acute side‐effect of mesotherapy, have also been described.35,36
The main histopathologic features here are absent terminal anagen hair
follicles, and increased numbers of telogen and catagen follicular units,
as observed in the cases of anagen effluvium.35,36 Evidently, the thera‐
peutic management, in this case, consists of a wait‐and‐see approach;
however, a biopsy is necessary in order to be able to distinguish such
a patient from a patient who develops scarring alopecia and therefore
35,36
needs an appropriate anti‐inflammatory treatment.
Several other dermatologic complications in the form of intoler‐
ance reactions have been reported in isolated cases, as a result of
various mesotherapeutic treatments. When it comes to acute urti‐
caria following mesotherapy, the suggested approach is the discon‐
tinuation of treatment and the administration of antihistamines.37,38
Of the few cases described in the literature, the initial urticarial rash
37,38
was interestingly limited only to the treated area. Other reported
intolerance reactions include the appearance of lichenoid drug erup‐
tions; therefore, requiring both the discontinuation of treatment and
39,40
the use of systemic steroids.
Interestingly, mesotherapy has often been incriminated as the
stimulating factor that can lead to the aggravation of preexisting
41-43
dermatological conditions through the Koebner phenomenon.
|
      3
Rosina et al describe the case of a 67‐year‐old female patient who
developed generalized plaque psoriasis after the mesotherapeutic
treatment with a cocktail containing aminophylline, xantinol nico‐
tinate, and lidocaine. A therapy with systemic cyclosporine A was
initiated, initially with a dose of 4 mg/kg/day and then tapering over
14 weeks.42 In a similar pattern, mesotherapy‐associated localized
urticaria pigmentosa in a patient with previously occult mastocytosis
has been reported by Bessis et al Here, the treatment of choice was
the application of a medium‐potency topical corticosteroid cream for
a few weeks, resulting in a partial improvement of the lesions.43 A
rare case of induction of erythema‐nodosum‐like lesions after me‐
sotherapy in a patient with Behcet's disease is described in the lit‐
erature.41 The lesions showed only partial response to the initiated
regimen of colchicine, prednisolone (32 mg/day and then slow taper‐
ing), and azathioprine (2.5 mg/kg/day).41 Although this case cannot
be characterized as a koebnerization, but rather as a positive path‐
ergy test––which is the hyperreactivity reaction seen in Behcet's
disease as a response to cutaneous trauma––it is still an indication
that mesotherapy can trigger the eruption of various dermatologic
and systemic conditions with several pathogenetic mechanisms, that
are not always fully understood.41 As such, is a reported induction
of severe systemic lupus erythematosus in a 31‐year‐old patient
after mesotherapy with acetyl‐l‐carnitine, an agent with known im‐
munomodulating effects, which is frequently used for fat reduction
purposes.44 In this dramatic case described by Colon‐Soto et al, an
aggressive immunosuppressive regimen with a methylprednisolone
pulse therapy, oral prednisone daily, as well as a pulse therapy with
intravenous cyclophosphamide, was necessary for disease control.44
Less frequently seen are mechanical complications due to the mi‐
gration of the injected substances during mesotherapy.45,46 Calonge
et al describe the case of a 43‐year‐old woman who developed mas‐
sive subcutaneous edema on the right flank and anterior abdominal
wall up to the submammary fold, following subcutaneous injections
of carbon dioxide on both thighs in the previous days. The gas was
absorbed within 10 days and apart from antibiotic coverage no other
specific intervention was necessary.45 An accidental injection of the
used material into an arteriole can result in vessel obliteration with
livedoid dermatitis and cutaneous necrosis, a condition known as
embolia cutis medicamentosa or Nicolau syndrome.46 The manage‐
ment in such cases includes, apart from a local treatment with ulcers
dressing, also a systemic administration of anticoagulative agents in
a therapeutic dose, and the administration of systemic vasodilata‐
tors.46 Zaragoza et al report a complete resolution of mesotherapy‐
associated Nicolau‐syndrome lesions in a 53‐year‐old patient, under
a treatment with enoxaparin in a doses of 175 UI/kg per day, as well
as amlodipine orally over a period of 4 months.46
Another category of mesotherapy adverse reactions involves the
effects of the injected substances when absorbed systemically.47
A rare case of caffeine poisoning in a 51‐year‐old patient, who re‐
ceived subcutaneous injections of a caffeine‐containing cocktail, has
been presented by Vulkevic et al.47 The selected therapy here was a
symptomatic and supportive treatment.47 A rare case of mesother‐
apy‐related factitious thyrotoxicosis is also present in the literature:
 |
4       PLACHOURI and GEORGIOU
In this case, the patient developed a symptomatic thyrotoxicosis
as a result of injections with a mesotherapeutic cocktail contain‐
ing triiodothyroacetic acid, as well as vasoactive compounds that
enhanced triiodothyroacetic acid absorption. The thyroid function
was normalized after the cessation of mesotherapy treatment, and
no other specific measures were necessary.48 A possible vasoactive
effect after mesotherapy is also described by Kim et al, who report
the case of ischemic colitis after mesotherapy combined with anti‐
obesity medication.49 The used cocktail contained aminophylline,
epinephrine, and lidocaine, and the administered oral medication
included fluoxetine, ephedrine hydrochloride, anhydrous caffeine,
and green tea powder. The authors assume that the ischemic colitis
occurred as a result of the direct and indirect vasoconstrictive ac‐
tions of the used substances, and the management here included
supportive therapy with intravenous fluids, electrolytes, and antibi‐
otics.49 Tor et al describe the case of a 40‐year‐old female patient,
who presented with an isolated episode of delirium with psychotic
features, approximately 12 hours after a mesotherapy session with
unknown substances.50 The authors of this work hypothesize that
the injected substances could have affected the brain parenchyma
after having crossed the blood‐brain barrier.50 However, the lack of
more information on the mixture used, as well as the lack of relevant
published data, create a difficulty in establishing a definite causative
50
relation between the mesotherapy and this isolated episode.
Less grave complications of mesotherapy include procedure‐
associated pain, bruising, and edema due to the inflammation pro‐
voked by the injected substances. These tend to be rather localized
and transient, and their management includes the application of
local anesthetics as well as larger time intervals between visits.4,51
Mild symptoms of self‐limiting headache and pruritus have also been
described in scalp‐mesotherapy treatment.51 Although mild bleed‐
ing or easily reabsorbed hematomas can be expected as a result of
the punctures, the formation of larger organized hematomas has also
been described in extremely rare occasions.52
Finally, a potentially life‐threatening complication was recently
reported by Arenbergerova et al, who described the development
of a nodular melanoma on a congenital naevus on the scalp of a 49‐
year‐old patient, after treatment of a mild telogen effluvium, with
a mesotherapeutic cocktail containing IGF‐1, bFGF, VEGF, copper
tripeptide‐1, as well as adipose‐derived stem cell extract.5 Although
the authors do not exclude the possibility of a coincidental event, a
potential acceleration of the melanoma development due to the ef‐
fect of all the injected growth factors must be definitely taken into
consideration.5 More studies on the safety profile of such substances
on the aspect of oncogenesis should be conducted in order to draw
clear conclusions.5 Furthermore, it is advisable to examine carefully
the area to be treated, with an emphasis on melanocytic nevi.5
4 |  CO N C LU S I O N S
Mesotherapy is becoming such an increasingly common proce‐
dure, that is now widely applied not only by physicians but also by
nonmedical personnel in aesthetic institutions.1,4,53 Most patients,
and in some cases even physicians, tend to underestimate the nu‐
merous potential side effects that can occur by such methods. 53 In
order to minimize the risk of adverse reactions, a standardization
of this procedure for each indication is necessary. 53 Professional
training, adequate scientific background, as well as an abiding to
basic hygiene standards must be guaranteed so as to optimize the
treatment conditions. Furthermore, it is rather important to in‐
clude an informed consent before therapy initiation, not only in
order to protect the physicians from possible legal complications,
but also in order to educate the patient into a better understand‐
ing of the benefits and risks of this procedure overall. 53
F U N D I N G S TAT E M E N T
This research received no funding support.
C O N FL I C T O F I N T E R E S T
The authors report no conflicts of interest.
ORCID
Kerasia‐Maria Plachouri  https://orcid.
org/0000-0002-4116-6344
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How to cite this article: Plachouri K‐M, Georgiou S.
Mesotherapy: Safety profile and management of
complications. J Cosmet Dermatol. 2019;00:1–5. https​://doi.
org/10.1111/jocd.13115​