Intradermal Therapy (mesotherapy) in Dermatology

Flora Canzona1, Mammucari Massimo2*, Arianna Tuzi3, Enrica Maggiori2, Maria Gabriella Grosso4, Luciano Antonaci2, Stefania Santini3, Anna Rosa Catizzone3, Fiammetta Troili3, Alessandra Gallo3, Teresa Paolucci3, Piergiovanni Rocchi3, Costanza Guglielmo3, Domenico Russo5, Chiara Giorgio6, Dario Dorato3, Raffaele Di Marzo3, Giovanna Viglione3, Anna G Fiorentini3, Manuela Giardini3, Silvia Natoli7

1Istituto Dermopatico dell'Immacolata, IRCCS Foundation, Rome, Italy

2Primary Care Unit ASL RM 1, Rome, Italy

3Member of the Italian Society of Mesotherapy, Rome, Italy

4Ospedale Israelitico, Rome Italy

5San Marco Hospice and Palliative Care, Latina, Italy

6Rehabilitation Unit, F Pirinei Hospital, Altamura (BA), Italy

7Department of Clinical Science and Translational Medicine, Tor Vergata University, Rome, Italy


Mesotherapy consists of a series of micro injections in the superficial layer of the skin of active ingredients that slowly diffuse into the underlying tissues. This technique is applied in different clinical conditions and also in dermatology it could play a useful role in the treatment path of many patients. However, further clinical studies are needed to standardize its application in various dermatological pathologies. The recommendations of the Italian Mesotherapy Society aim at personalized therapy based on evidence, efficacy and safety.


Intradermal therapy, also known as mesotherapy, is an injection technique which, if well applied alone or in combination with other therapies, is useful in various clinical conditions1. It has rapidly spread in the field of pain medicine for the management of painful syndromes2, in chronic veno-lymphatic insufficiency3,4. It is also used in the cosmetic field but little scientific evidence supports this application5. The scientific rationale for this technique is based on the fact that a drug injected in small doses into the surface layer of the skin slowly spreads to the underlying tissues and remains longer than systemic administration, as confirmed in preclinical studies1. In fact, higher concentrations of intradermally injected drug have been detected in the skin, muscles and joints underlying the infiltration site compared to intramuscular administration. Furthermore, a higher immune response, both primary and secondary, has been reported after intradermal injection compared to intramuscular administration1,6. Furthermore, it has also been hypothesized that the micro trauma induced by the needle and the chemical-physical reactions induced by the liquid infiltrated into the dermis could induce dermal reactions capable of increasing the effect of the drug injected into the dermis7. The set of these intradermal mechanisms, called meso-dermal modulation, constitute hypotheses that must be experimentally verified8.

Many advantages of this technique have been described: minimally invasive, lower dose of drug compared to systemic treatment, lower risk of systemic adverse events, simple application1,6,8. Mesotherapy consists of one or more micro intradermal injections in the area to be treated or along the edges of the dermatological lesion. 13 mm needles (30 or 32 gauge) or 4 mm needles (27 gauge) are used1. Infiltration should be performed after adequate disinfection of the skin to be treated. The needle should be introduced quickly and the drug should be injected gently to avoid pain. To date, the clinical data available do not allow to standardize the technique in dermatological indications. However, the various authors agree on the depth of infiltration and recommend tilting the needle between 30° and 45° to deposit the drug in the dermis to a depth of about 2 millimeters1,6,8. The number of treatment sessions and the frequency (weekly or with greater or lesser frequency) depend on the pathology treated, but there are no standard dermatological protocols and therefore the response of the individual patient represents the driver for the treatment1,6,8,9.

In the dermatological field, mesotherapy has been applied in many skin conditions10-23 (Table 1) and several drugs have been used10-32 (Table 2). However, in addition to pain medicine and dermatology, mesotherapy has also been applied in the field of aesthetics.

Table 1: Dermatological pathologies that have been treated with intradermal drugs

Alopecia10

Cystic acne11

Keloid12

Suppurative hydrosadenitis13

Psoriasis14

Warts15

Cutaneous leishmaniasis16

Vitiligo17

Melasma18

Pretibial myxedema19

Necrobiososis lipoidica20

Cutaneous neoplasms21,22,23

 

Table 2: Drugs used intradermally for the treatment of certain dermatological diseases

triamcinolone acetonide 10-15, 18,24,26

bleomycin15

meglumine antimoniate16

5-fluorouracil17

glucocorticoid19,20

interferon alpha-2b21

interleukin-223

lincomycin24

botulinium toxin25

methotrexate26

cyclosporine26

platelet rich plasma27

minoxidil27

tranexamic acid28

ixekizumab29

secukinumab30

brodalumab31

verapamil32

For over a century pharmacologically active substances have been injected intradermally, for example in 1910 Mantoux33 wondered about the clinical interpretation of intradermal reaction to tuberculin.

Since 1952 Michel Pistor popularized this technique suggesting its usefulness in various clinical conditions34 but, following the French suggestions, the trend spread of applying mesotherapy with products (or mixtures of substances) without scientific support in favor of efficacy and tolerability in the pathology treated5,35. For this reason the Italian Society of Mesotherapy has conducted national and international consensus to limit indications, suggesting that the choice of the drug must be based on clinical tolerability and efficacy data and that mesotherapy should only be conducted by qualified doctors1,6 (general recommendations are shown in Table 3). For example, even if some authors report a consolidated efficacy of steroids both in monotherapy and in combination10-14 we have doubts about the use of corticosteroid intradermally for erythema, pain, sterile abscess, hypopigmentation and skin atrophy caused by this drug and we suggest diluting the dose and injecting minimum quantities only if necessary. In fact, one of the main advantages of mesotherapy is the drug sparing effect with respect to the deeper route of administration. Moreover, the dose-saving effect is also well reported in the field of immunoprophylaxis practiced with the intradermal routes36-37. These studies show that the dermis has a microcirculation capable of interacting with the immune system and the intradermal inoculation of vaccines offers numerous advantages over the intramuscular route of administration, including a reduction in the necessary dose of antigen, a reduced need for adjuvant, a greater immune response and a simpler method of administration. Furthermore, the intradermal route could have enormous potential in anticancer therapy, as demonstrated by dendritic cell vaccines38-39. Even some biological drugs are now injected intradermally in the treatment of psoriasis and obtain prolonged clinical remission and a reduction in the severity index of the psoriasis area40,41.

Table 3: General recommendations for correct application of mesotherapy in dermatology1,6

Mesotherapy is a technique based on the administration of pharmaceutical substances

in the upper layers of the skin

Mesotherapy should be applied by skilled doctors

If it is used for indications without evidence of efficacy and tolerability, it should be conducted

in accordance with the rules of good clinical practice

Mesotherapy must be integrated with standard treatments according to the needs of the individual patient

Before applying mesotherapy, a diagnosis must be made

When the intradermal route is useful, mesotherapy can be considered to reduce the systemic impact of drugs

Collect all clinical data in the patient's medical record

Doctors should report the pros and cons of this technique to allow the patient to make a valid decision (informed consent)

A single drug is recommended in the syringe (the use of mixtures is allowed only if there is data to support efficacy tolerability and chemical stability)

The doctor must avoid any contamination to avoid the risk of infections. Disposable gloves and materials are mandatory

The drugs are used according to the authorized indications. When used off label are the current rules must be respected in individual countries

Although the intradermal route has many applications in clinical practice, we do not know how the drugs spread through the various thicknesses of the skin and how it affects the pressure with which the substances are injected42 or what role the cytochromes play on the metabolism of the drugs injected locally43.

In conclusion, mesotherapy applied in dermatology needs more clinical confirmation. Studies are needed to identify the ideal drug concentration, the short depth of infiltration and the patients who benefit most from this technique. The dermis appears to be a target organ for many pathologies and clinical dermatologists will play a crucial role in the development of mesotherapy. Preclinical and clinical dermatological research could help other professionals to understand the mechanism of action of mesotherapy. While ad hoc studies are being conducted, mesotherapy must be considered a medical act and must be applied by qualified doctors45. Evidence-based recommendations are needed to standardize this technique also for the management of dermatological conditions. Pending new guidelines, we recommend following the recommendations available today1,6.

The Authors declare that no conflicts of interest exist in relation to the contents of this article. Compliance with ethics guidelines. This article in based on previously conducted studies. The Authors does not involve any new studies (on human or animal subjects).

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Article Info

  • Journal of Dermatology and Skin Science
  • Article Type : Mini Review Article
  • View/Download pdf

Article Notes

  • Published on: March 17, 2020

Keywords

  • Mesotherapy

  • Intradermal therapy

*Correspondence:

Dr.Mammucari Massimo
Primary Care Unit ASL RM 1, Rome, Italy
Email: massimo.mammucari@libero.it.

©2020 Mammucari M. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License.