Systematic review of mesotherapy: a novel avenue for the treatment of hair loss.

Mesotherapy is a technique by which lower doses of therapeutic agents and bioactive substances are administered by intradermal injections to the skin. Through intradermal injections, mesotherapy can increase the residence time of therapeutic agents in the affected area, thus allowing for the use of lower doses and longer intervals between sessions which may in turn improve the treatment outcome and patient compliance. This systematic review aims to summarize the current literature that evaluates the efficacy of this technique for the treatment of hair loss and provides an overview of the results observed. Of the 416 records identified, 27 articles met the inclusion criteria. To date, mesotherapy using 6 classes of agents and their combinations have been studied; this includes dutasteride, minoxidil, growth factors or autologous suspension, botulinum toxin A, stem cells, and mesh solutions/multivitamins. While several studies report statistically significant improvements in hair growth after treatment, there is currently a lack of standardized regimens. The emergence of adverse effects after mesotherapy has been reported. Further large-scale and controlled clinical trials are warranted to evaluate the utility of mesotherapy for hair loss disorders.

Effect of topical local anaesthesia on injection pain associated with administration of sterile water injections - a randomized controlled trial.

BACKGROUND: Sterile water injections can provide effective pain relief during childbirth, particularly for low back pain related to childbirth. However, the pain associated administering the injections can negatively impact women's impressions of the procedure. It may discourage women from considering repeat doses despite the quality of analgesia experienced. Determining strategies to reduce the pain related to the administration of sterile water injections would improve the acceptability of the technique. Therefore, the aim of this study was to evaluate the effect of topical local anesthesia on the pain associated with administration of sterile water injections. METHODS: The study was designed as a multi-arm single-blind, randomized, controlled trial and 120 female healthy students were randomly divided according to one of four groups. The Intervention group received sterile water injections with topical local anesthesia. Control group 1 received sterile water injections without topical local anesthesia, control group 2 received injections of isotonic saline 0.9% with topical local anesthesia and control group 3 received injections of isotonic saline 0.9% without topical local anesthesia. Pain Immediately after the injections and subsidence in pain were recorded using a visual analogue scale. Sensations in the injection area were reported 15 min and the day after the injections. RESULTS: The main finding of this study was that local anesthesia with EMLA® reduces the pain associated with the administration of intracutaneous sterile water injections. There was a significant difference in the self-assessed pain score immediately following the injections between the control (73.3 mm) and intervention groups (50.0 mm), p = 0.001. No adverse side effects were reported. CONCLUSION: Local anesthesia with EMLA® reduces the pain associated with intracutaneous administration of sterile water injections. TRIAL REGISTRATION: The study was registered 08/07/2014 at ClinicalTrials.gov Identifier: NCT02213185 .

Intradermal therapy (mesotherapy): the lower the better.

BACKGROUND: Intradermal therapy (mesotherapy) is a technique used to inject drugs into the surface layer of the skin. The intradermal micro deposit allows to modulate the kinetics of drugs, slowing down its absorption and prolonging the local mechanism of action. This technique is applied in the treatment of some forms of localized pain when a systemic drug-saving effect is useful, when it is necessary to synergize with other pharmacological or non-pharmacological thera-pies, when other therapies have failed or cannot be used. AIM: The purpose of our study was to evaluate the effect of a mixture with respect to its lower concentration. We also wanted to evaluate the number of sessions needed to reach the therapeutic goal (50% reduction in pain from baseline) in patients with acute or chronic neck pain. METHOD: We analyzed retrospectively data from 62 patients with cervicobrachial pain treated with intradermal drugs. Group A received a mixture of drugs; group B received half the dose of drugs. RESULTS: Patients who received a lower concentration of drugs achieved similar results to those who received a higher dose. The therapeutic goal was achieved on average with 3.5 + 1.7 sessions on a weekly basis (min 1; max 9). Subjects in group A required 4+1.7 treatments (min 1; max 9), while subjects in group B required 3+1.5 treatments (min 1; max 7). CONCLUSIONS: Our study confirms that even a lower dose of drugs can induce a clinically useful result. This study confirms that the useful effect of mesotherapy is only partly due to the pharmacological action. Further randomized prospective studies are needed to standardize the technique in the various pain syndromes, but it is recommended to follow the guidelines of the Italian Society of Mesotherapy to ensure patients receive appropriate treatment.

Intradermal injection of lidocaine with a microneedle device to provide rapid local anaesthesia for peripheral intravenous cannulation: A randomised open-label placebo-controlled clinical trial.

BACKGROUND: Peripheral venous cannulation is one of the most common procedures in medicine. It is associated with noticeable pain and apprehension, although in most cases it is performed without any anesthesia due to lack of a painless, cost-effective option, which would provide rapid local anesthesia with subsequent significant reduction in the experienced pain. We conducted an open-label placebo-controlled clinical trial to evaluate the efficacy and safety of a 2% lidocaine injection using the commercially available microneedle device MinronJet600 (NanoPass Technologies Ltd, Israel) to achieve rapid local anesthesia prior to peripheral venous cannulation. METHODS: One hundred and two subjects were randomly allocated into two groups. In the first group, 100µL of lidocaine hydrochloride (2%) was injected intradermally to subjects using the MicronJet600 device in the left arm (MJ-Lido) and 100µL of saline was injected intradermally using the device in the right arm (MJ-Saline). In the second group, 100µL of lidocaine hydrochloride (2%) was injected using the MicronJet600 device into the left arm (MJ-Lido), with no injection into the right arm of subjects (No pretreatment). In both groups the intradermal injection was performed at the cannulation site prior to insertion of a 18G cannula into a median cubital vein in both arms. As a primary variable, a score of cannulation-induced pain was indicated by subjects using a 100-point visual analog scale immediately after cannulation. As a secondary variable, subjects in Group 2 also indicated their preference to receive the anaesthetic injection with MicronJet600 in the future by using the 5-point Likert scale. Also, as a secondary variable, the duration of skin numbness after lidocaine injection was indicated by performing a superficial pin-prick with a 27G needle at 15, 30 and 45 minutes, at distances of 1, 2 and 3 centimeters from the injection site. RESULTS: A significant pain reduction (11.0-fold) was achieved due to the lidocaine injection compared to the cannulation without any pretreatment (p< 0.005). After the lidocaine injection the anesthesia was effective up to 2 centimeters from the injection site and remained for up to 30 minutes. Eighty percent of subjects from the second group preferred cannulation after the lidocaine injection over cannulation without any pretreatment. No significant side effects were identified. CONCLUSION: Intradermal injection of anaesthetic with Micronjet600 was found to be a safe and effective option for providing rapid local anesthesia for peripheral intravenous cannulation. TRIAL REGIATRATION: The clinical trial was registered, before the patient enrollment began, in the Research Registry publicly accessible database (registration identifier: researchregistry4662). Also, the trial was registered in ClinicalTrials.gov (registration identifier: NCT05108714) after its completion.

Extended Injection Intervals of Gonadotropins by Intradermal Administration in IVF Treatment.

CONTEXT: Gonadotropins can be administered every 5 days under intradermal injection in in vitro fertilization (IVF) treatment. OBJECTIVE: To explore the effectiveness of intradermal injection of recombinant human FSH (rhFSH) for women undergoing IVF. METHODS: Women who received their first IVF treatment enrolled in this prospective intervention in 2018. All women received a bolus of 900 IU rhFSH intradermally at day 2 of the treatment cycle followed by additional dosage of rhFSH at day 7 and/or day 10. The main outcome measures included the total dose of rhFSH and number of injections required, sequential serum FSH level detected, and number of mature oocytes retrieved. RESULTS: Seventy women completed the study. On average, 2.31 ±â€…0.73 injections and 1662 ±â€…397 IU of rhFSH were administered. While the baseline FSH level was 5.6 ±â€…2.2 IU/L, the serum concentrations of FSH after rhFSH administration were 35.3 ±â€…7.0 on the first day (24 hours) and 10.7 ±â€…3.7 IU/L on the fifth day (120 hours). A total of 10.5 ±â€…6.6 mature oocytes were retrieved, resulting in 7.3 ±â€…5.1 pronuclear embryos; 1.8 ±â€…0.6 embryos were transferred to the uterus. Our findings resulted in 72% fertilization, 91% cleavage, 31% implantation, and 36% live birth rates. Although fewer larger follicles were found, noninferiority results were noted in the mature oocytes retrieved, good embryos available, and clinical pregnancy rate compared with those received conventional daily subcutaneous rhFSH administration. CONCLUSION: Intradermal administration of rhFSH, with a smaller dose of rhFSH and fewer injections, may achieve the goal of a cost-effective and more patient-friendly regimen.

A Call to Action by the Italian Mesotherapy Society on Scientific Research.

Mesotherapy (local intradermal therapy, LIT) is a technique used to slowly spread drugs in tissues underlying the site of injection to prolong the pharmacological effect with respect to intramuscular injection. Recommendations for proper medical use of this technique have been made for pain medicine and rehabilitation, chronic venous disease, sport medicine, musculoskeletal disorders, several dermatological conditions, skin ageing, and immune-prophylaxis. Although mesotherapy is considered a valid technique, unresolved questions remain, which should be answered to standardize methodology and dosing regimen as well as to define the right indications in clinical practice. New randomized controlled trials are needed to test single products (dose, frequency of administration, efficacy and safety). Even infiltration of substances for dermo-cosmetic purposes must be guided by safety and efficacy tests before being proposed by mesotherapy. In this article, we put forth a preclinical and clinical research plan and a health technology assessment as a call to action by doctors, researchers and scientific societies to aid national health authorities in considering mesotherapy for prevention, treatment and rehabilitation paths.

Active Tumoral/Tumor Environmental Dual-Targeting by Non-Covalently Arming with Trispecific Antibodies or Dual-Bispecific Antibodies on Docetaxel-Loaded mPEGylated Nanocarriers to Enhance Chemotherapeutic Efficacy and Minimize Systemic Toxicity.

PURPOSE: This study was aimed at developing the trispecific antibodies (anti-EGFR/anti-FAP/anti-mPEG, TsAb) or dual bispecific antibodies (anti-EGFR/anti-mPEG and anti-FAP/anti-mPEG) docetaxel (DTX)-loaded mPEGylated lecithin-stabilized micelles (mPEG-lsbPMs) for improving the targeting efficiency and therapeutic efficacy. METHODS: mPEG-lsbPMs were simply prepared via thin film method. The trispecific antibodies or bispecific antibodies bound the mPEG-lsbPMs by anti-mPEG Fab fragment. The formulations were characterized by DLS and TEM; in vitro and in vivo studies were also conducted to evaluate the cellular uptake, cell cytotoxicity and therapeutic efficacy. RESULTS: The particle sizes of mPEG-lsbPMs with or without the antibodies were around 100 nm; the formulations showed high encapsulation efficiencies of 97.12%. The TsAb and dual bispecific antibodies were fabricated and demonstrated their targeting ability. Two EGFR-overexpressed cell lines (HT-29 and MIA PaCa-2) were co-cultured with FAP-overexpressed WS1 cells (HT-29/WS1; MIA PaCa-2/WS1) to mimic a tumor coexisting in the tumor microenvironment. Cellular binding study revealed that the binding of anti-FAP micelles to three co-culture ratios (4:1, 1:1, and 1:4) of HT-29/EGFR to WS1/FAP was significantly higher than that for TsAb micelles and dual (1:1) micelles, and the binding of those targeting antibodies to WS1/FAP and MIA PaCa-2/EGFR was equally efficacious resulting in a similar binding amount of the TsAb and dual BsAbs (1:1) with the co-culture of MIA PaCa-2/EGFR and WS1/FAP at a 1:1 ratio. Antitumor efficacy study showed that treatment with DTX-loaded mPEG-lsbPMs modified with or without BsAbs, dual BsAbs (1:1), and TsAbs was enhanced in inhibiting tumor growth compared with that for Tynen® while showing fewer signs of adverse effects. CONCLUSION: Active targeting of both tumors and TAF-specific antigens was able to increase the affinity of DTX-loaded mPEG-lsbPMs toward tumor cells and TAFs leading to successive uptake by tumor cells or TAFs which enhanced their chemotherapeutic efficacy against antigen-positive cancer cells.

Aqueous intradermal low-dose house dust mite immunotherapy in tropical settings: a valid cost-effective approach for developing nations?

INTRODUCTION: Aqueous allergen injections, an effective and century-old technique, is considered a second-line approach in daily clinical practice. Inconveniences still surround conventional subcutaneous immunotherapy (SCIT) administration, such as a need for frequent injections, prolonged up-dosing schedules, elevated costs, and the unlikely possibility of a systemic reaction. The intradermal immunotherapy route (IDR) might favorably impact many of the aforementioned issues (Table 1). House dust mite (HDM) allergens are the main perennial sensitizers in the tropics, and as such, are solely employed in immunotherapy treatments. METHODS: We carried out a year-long real-life study in 25 perennial allergic rhinitis children, symptomatic on exposure to house dust, employing an intradermal low-dose allergen mix consisting of 50 ng of Dermatophagoides pteronyssinus/Dermatophagoides farinae and 120 ng of Blomia tropicalis, under a unique cost-wise protocol. Basal symptoms/signs and face Visual Analog Scale (fVAS) scores were recorded for 2 weeks and later compared with those registered throughout the 1-year treatment. Serum-specific IgG4 and IL-10 levels were employed in the assessment of the immune responses. RESULTS: Symptoms/signs and fVAS scores were significantly reduced from days 42 and 49, respectively, and remained so until treatment completion. Increases in specific IgG4's and IL-10 levels reflected significant immune responses. Injections were well tolerated and families reported improved health status (quality of life, QoL). CONCLUSIONS: A unique cost-effective immunotherapy alternative for deprived allergic communities in tropical settings is depicted; further research is needed.

The effect of lyophilized platelet rich-plasma on skin aging: a non-randomized, controlled, pilot trial.

Platelet-rich plasma (PRP) showed positive results in the improvement of skin aging. Lyophilized PRP can be interesting in clinical practice due to the facility to obtain many samples in a single blood collection and can be used in multiple injections. To evaluate the effect of lyophilized PRP in the treatment of skin aging, through a Phase II pilot study. Nineteen women (54 years ± 7 years) with Glogau photoaging II and III types were select for this non-randomized, split-face controlled study. They received monthly intradermal injections of lyophilized PRP and saline solution (as control) into the facial skin, during a period of 2 months. The evaluation was performed by imaging method, histological techniques, and multiphoton microscopy. Although lyophilized PRP presented 10 times the platelet baseline value (P < .0001) and growth factors in adequate levels, only saline solution showed an increase of dermis thickness (p = .0009). Collagen pre and post-application remained the same for both types of treatments. The use of lyophilized PRP by mesotherapy showed no improvement on skin aging. TRIAL REGISTRATION APPROVAL: RBR-3n9wxw, UTN U1111-1226-6093-retrospectively registered.

Novel insights on the encapsulation mechanism of PLGA terminal groups on ropivacaine.

Currently, the influences of free terminal groups (hydroxyl, carboxyl and ester) of PLGA on encapsulating active pharmaceutical ingredient are relatively ambiguous even though PLGA types were defined as critical quality attributes in vast majority of design of experiment process. In this study, emulsion method combined with premix membrane emulsification technique has been used to encapsulate ropivacaine (RVC), a small molecule local anesthetic in clinical. Based on the narrow particle size distribution, the influences and mechanisms of the terminal groups on properties of ropivacaine loaded microspheres have been investigated in detail. It was found that microspheres prepared by PLGA with hydroxyl or ester groups exhibited lower encapsulation efficiency but faster in vitro release rate than that of carboxyl groups. In the meanwhile, on microcosmic level analysis by quartz crystal microbalance with dissipation, atomic force microscope and confocal laser scanning microscopy, we attributed this distinction to the specific interaction between ropivacaine and different terminal groups. Subsequently, the reaction activation centers were verified by density functional simulation calculation and frontier molecular orbital theory at molecular level. Additionally, pharmacokinetics and pharmacodynamic research of infiltration anesthesia model were performed to compare sustained release ability, duration and intensity of the anesthetic effect in vivo. Finally, potential safety and toxicity were evaluated by the biochemical analysis. This study not only provides a novel mechanism of drug encapsulation process but also potential flexible selections in terms of various anesthesia indications in clinical.

Rejuvenating the periorbital area using platelet-rich plasma: a systematic review and meta-analysis.

Intradermal injection of autologous platelet-rich plasma (PRP) is a non-surgical cosmetic therapy to rejuvenate the periorbital area pathologies of wrinkles, periorbital hyperpigmentation (POH), and photoaging. The past decade has seen the adoption of this novel therapy around the world. This is the first systematic review and meta-analysis evaluating PRP treatment of periorbital pathologies. This is a PRISMA compliant review that includes a comprehensive search of the databases Cochrane Library, Ovid Medline, Ovid Embase, and clinicaltrials.gov. The search was performed in June 2019 to obtain all peer-reviewed articles published in English that describe the application of PRP to periorbital pathologies. A meta-analysis of patient satisfaction was performed for randomized controlled trials. Nineteen studies treating 455 patients (95% female, age range 28-60) were included. Studies were categorized based on reported outcomes: wrinkles (11 studies), POH (7 studies), and photoaging (6 studies). Patients were treated a mean of 3 times (range 1-8) in mean intervals of 23 days (range 14-56 days). Follow-up averaged 3 months (range 1-6 months). Meta-analysis of 3 randomized controlled clinical trials (RCTs) shows that patients treated with PRP have increased satisfaction above controls of saline, platelet-poor plasma, mesotherapy, and as an adjunct to laser therapy (overall effect p = 0.001, heterogeneity I2 = 64%). PRP treatment of periorbital area pathologies results in histologic improvements of photoaging, subjective satisfaction score increases, and blind evaluator assessments of rejuvenated skin appearance. Future studies are needed to address limitations of the current literature and should include long-term follow-up, delineation of the POH etiology that is treated, RCTs with low risk of bias, and be absent conflicts of interest or industry sponsors.Trial registration: Prospero Systematic Review Registration ID: CRD42019135968.

The effectiveness of intradermal sterile water injection for low back pain in the emergency department: A prospective, randomized controlled study.

AIM: Low back pain (LBP) is a common musculoskeletal complaint among emergency department (ED) admissions. In this study, it was aimed to compare the effectiveness of systemic treatment with intradermal sterile water injection (ISWI) treatment protocol combined with systemic therapy in patients with LBP of unclear chronicity. METHODS: A prospective randomized, unblinded, controlled clinical study was conducted on patients admitted to the ED for LBP of unclear chronicity. One hundred twelve patients were randomly assigned to two groups; Group ISWI (n = 56) administered ISWI in the LBP region of patients along with systemic intravenous dexketoprofen therapy, while the other group (n = 56) received only systemic intravenous dexketoprofen therapy. The treatment methods' effectiveness was compared by measuring the pain intensity with the Visual Analog Scale (VAS) at admission, 10th minutes, 20th minutes, 30th minutes, and 24 h later. Also, opioid and analgesic consumptions in 24 h after treatment and patient satisfactions were compared. RESULTS: In the treatment of LBP, ISWI treatment was found to be more effective in relieving pain than systemic therapy alone (p < 0.001). Also, it was observed that opioid consumption in the ED and analgesic consumption within 24 h after treatments were decreased in the ISWI group (p < 0.001). The patient satisfaction in the ED was statistically increased (p < 0.001). DISCUSSION: In this unblinded study, ISWI with systemic therapy improved pain outcomes more than systemic therapy alone. Further research is needed to determine whether this was due entirely to placebo effect.

A Novel Apilic Antivenom to Treat Massive, Africanized Honeybee Attacks: A Preclinical Study from the Lethality to Some Biochemical and Pharmacological Activities Neutralization.

Massive, Africanized honeybee attacks have increased in Brazil over the years. Humans and animals present local and systemic effects after envenomation, and there is no specific treatment for this potentially lethal event. This study evaluated the ability of a new Apilic antivenom, which is composed of F(ab')2 fraction of specific immunoglobulins in heterologous and hyperimmune equine serum, to neutralize A. mellifera venom and melittin, in vitro and in vivo, in mice. Animal experiments were performed in according with local ethics committee license (UFRJ protocol no. DFBCICB072-04/16). Venom dose-dependent lethality was diminished with 0.25-0.5 µL of intravenous Apilic antivenom/µg honeybee venom. In vivo injection of 0.1-1 µg/g bee venom induced myotoxicity, hemoconcentration, paw edema, and increase of vascular permeability which were antagonized by Apilic antivenom. Cytotoxicity, assessed in renal LLC-PK1 cells and challenged with 10 µg/mL honeybee venom or melittin, was neutralized by preincubation with Apilic antivenom, as well the hemolytic activity. Apilic antivenom inhibited phospholipase and hyaluronidase enzymatic activities. In flow cytometry experiments, Apilic antivenom neutralized reduction of cell viability due to necrosis by honeybee venom or melittin. These results showed that this antivenom is effective inhibitor of honeybee venom actions. Thus, this next generation of Apilic antivenom emerges as a new promising immunobiological product for the treatment of massive, Africanized honeybee attacks.

Intradermal injections with 0.5% minoxidil for the treatment of female androgenetic alopecia: A randomized, placebo-controlled trial.

Female androgenetic alopecia is one cause of alopecia in women, although the ideal treatment for this condition remains far from defined. The objective of this study was to evaluate the efficacy and safety of intradermal injections with 0.5% minoxidil for the management of female androgenetic alopecia in a randomized, placebo-controlled trial. A total of 54 women diagnosed with female androgenetic alopecia were divided into two groups: one group received intradermal injections of 0.5% minoxidil, and the other received 0.9% saline. Biopsy, trichogram, Trichoscan (Tricholog GmbH, Freiburg, Germany), and self-assessment findings were used to evaluate the outcomes of treatment with minoxidil. In the treated group, there was a significant increase in the terminal-to-vellus hair ratio (P < .001) and in the percentage of anagen hairs (P = .048) and an improvement in hair loss and volume (P = .021 and P = .028, respectively). These results show that intradermal injections with minoxidil were more effective than placebo (P < .001) in the treatment of female androgenetic alopecia with a good safety profile.

Evaluation of platelet-rich plasma on hair regrowth and lesional T-cell cytokine expression in alopecia areata: A randomized observer-blinded, placebo-controlled, split-head pilot study.

BACKGROUND: Platelet-rich plasma has shown some promise in the treatment of alopecia areata. OBJECTIVE: To evaluate the effect of platelet-rich plasma on hair regrowth and lesional T-cell cytokine expression in alopecia areata. METHODS: This was a randomized, placebo-controlled, split-head study involving 27 patients with alopecia areata (Severity of Alopecia Tool score ≥25%). Alopecia patches on either side of the scalp were randomized to receive 3 intradermal injections of platelet-rich plasma or normal saline at monthly intervals and evaluated 3 months after the last session. Lesional T-cell cytokine messenger RNA expression was compared pre- and posttreatment in the platelet-rich plasma-treated sites. RESULTS: The mean Severity of Alopecia Tool score did not change significantly compared with baseline with either platelet-rich plasma or placebo injections at any visit; however, the mean percentage reduction in the score in the platelet-rich plasma arm was more than in the placebo arm (9.05% ± 36.48% vs 4.99% ± 33.88%; P = .049) at final assessment. The mean interferon gamma (P = .001) and interleukin 17 cytokine (P = .009) messenger RNA expression decreased, whereas the mean interleukin 10 (P = .049) and FOXP3 (P = .011) messenger RNA expression increased significantly after platelet-rich plasma treatment. LIMITATIONS: Small sample size and a relatively short follow-up. CONCLUSION: Platelet-rich plasma was found to have limited efficacy in alopecia areata. However, it may play a role in restoring immune balance in the alopecic patches.

Intradermal Phleum pratense allergoid immunotherapy. Double-blind, randomized, placebo-controlled trial.

BACKGROUND: In allergology, the intradermal approach is generally used to establish an aetiological diagnosis, with limited experience in specific allergen immunotherapy. OBJECTIVE: To evaluate the efficacy and safety of immunotherapy with an allergen extract of glutaraldehyde-polymerized Phleum pratense, administered intradermally, in patients with rhinoconjunctivitis sensitized to grass pollen. METHODS: Multicentre, randomized, double-blind, placebo-controlled clinical trial in patients from 12 to 65 years of age with rhinitis or rhinoconjunctivitis, with or without asthma, due to grass pollen allergy. Patients were divided into three groups and received a total of six doses in a weekly interval, of either placebo; 0.03 or 0.06 µg of protein per dose of P pratense allergoid. The primary objective was to evaluate the combined symptoms and medication consumption score (CSMS). The secondary objectives were symptoms and medication, tolerance to the conjunctival provocation test, specific IgE and IgG4 antibodies and the safety profile according to the WAO scale. RESULTS: The dose of 0.06 µg of protein proved to be effective versus the placebo by significantly reducing CSMS and increasing tolerance to the allergenic extract in the conjunctival provocation test, after the first pollen season. This group showed a significant reduction in specific IgE after the second pollen season relative to the baseline. There were no variations in IgG4 levels. Only one grade 2 systemic reaction was recorded. CONCLUSION & CLINICAL RELEVANCE: Intradermal immunotherapy with P pratense allergoid has been shown to be effective and safe, reducing CSMS, increasing tolerance to the conjunctival provocation test and reducing IgE levels.

Tranexamic Acid for Melasma Treatment: A Split-Face Study.

BACKGROUND: Melasma is an acquired hyperpigmented skin disorder. Tranexamic acid (TXA) prevents ultraviolet radiation induced pigmentation in melasma through interfering with the plasminogen-plasmin pathway. OBJECTIVE: This study was conducted to evaluate the therapeutic effect and safety of TXA by intradermal injection versus TXA with microneedling for melasma treatment. METHODS: Fifty-six female patients with bilateral symmetrical melasma were recruited in a split-face study. All patients received an intradermal injection of TXA on one side of the face, and the other side received TXA with microneedling for 6 sessions at 2 weeks intervals. Clinical efficacy was assessed using a modified Melasma Area Severity Index (mMASI) score at the baseline and after treatment. Global photographs underwent blinded review by 2 dermatologists. Patient self-assessment and satisfaction were recorded. RESULTS: After the treatment, the mMASI score was significantly reduced compared with the baseline in both treated sides (p < .001). No significant difference between both treated sides (p > .05). Patient satisfaction was higher in the microneedling-treated side than the intradermal-injected side (p < .001). No significant adverse effects were observed in both treated sides. CONCLUSION: Intradermal injection and microneedling of TXA could be safe and effective in melasma treatment. Microneedling of TXA was significantly more satisfying to the patients.

Mesotherapy: From Historical Notes to Scientific Evidence and Future Prospects.

Intradermal therapy, known as mesotherapy, is a technique used to inject a drug into the surface layer of the skin. In particular, it involves the use of a short needle to deposit the drug in the dermis. The intradermal microdeposit modulates the drug's kinetics, slowing absorption and prolonging the local mechanism of action. It is successfully applied in the treatment of some forms of localized pain syndromes and other local clinical conditions. It could be suggested when a systemic drug-sparing effect is useful, when other therapies have failed (or cannot be used), and when it can synergize with other pharmacological or nonpharmacological therapies. Despite the lack of randomized clinical trials in some fields of application, a general consensus is also reached in nonpharmacological mechanism of action, the technique execution modalities, the scientific rationale to apply it in some indications, and the usefulness of the informed consent. The Italian Mesotherapy Society proposes this position paper to apply intradermal therapy based on scientific evidence and no longer on personal bias.

Diphtheria toxoid dissolving microneedle vaccination: Adjuvant screening and effect of repeated-fractional dose administration.

In this study the effect of repeated-fractional intradermal administration of diphtheria toxoid (DT) compared to a single administration in the presence or absence of adjuvants formulated in dissolving microneedles (dMNs) was investigated. Based on an adjuvant screening with a hollow microneedle (hMN) system, poly(I:C) and gibbsite, a nanoparticulate aluminum salt, were selected for further studies: they were co-encapsulated with DT in dMNs with either a full or fractional DT-adjuvant dose. Sharp dMNs were prepared regardless the composition and were capable to penetrate the skin, dissolve within 20 min and deposit the intended antigen-adjuvant dose, which remained in the skin for at least 5 h. Dermal immunization with hMN in repeated-fractional dosing (RFrD) resulted in a higher immune response than a single-full dose (SFD) administration. Vaccination by dMNs led overall to higher responses than hMN but did not show an enhanced response after RFrD compared to a SFD administration. Co-encapsulation of the adjuvant in dMNs did not increase the immune response further. Immunization by dMNs without adjuvant gave a comparable response to subcutaneously injected DT-AlPO4 in a 15 times higher dose of DT, as well as subcutaneous injected DT-poly(I:C) in a similar DT dose. Summarizing, adjuvant-free dMNs showed to be a promising delivery tool for vaccination performed in SFD administration.