Article

Facial Allergic Granulomatous Reaction and Systemic Hypersensitivity Associated With Microneedle Therapy for Skin Rejuvenation

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Abstract

Importance: Microneedle therapy includes skin puncture with multiple micro-sized needles to promote skin rejuvenation or increase transdermal delivery of topical medications. In cosmetic practices, various cosmeceuticals are applied before microneedling to enhance the therapeutic effects. This results in intradermal tattooing of the topical product. Despite rapid increase in the use of microneedles in dermatology, there are few data about their safety. Observations: We describe 3 women, aged 40s to 60s, who developed open [corrected] facial granulomas following microneedle therapy for skin rejuvenation. Two patients had undergone microinjection of the same branded topical moisturizer (Vita C Serum; Sanítas Skincare) during microneedle therapy. Biopsy in all cases showed foreign body-type granulomas. Results of tissue cultures were negative. Chest radiography and serum angiotensin-converting enzyme findings were normal. The first 2 patients had a positive patch test reaction to Vita C Serum. Initial treatment with topical and oral corticosteroids was ineffective. Therapy with doxycycline hydrochloride and minocycline hydrochloride led to partial improvement in one case and resolution in another. Conclusions and relevance: Application of topical products prior to microneedling can introduce immunogenic particles into the dermis and potentiate local or systemic hypersensitivity reactions. Because the microneedle therapy system is accessible for home use, health care providers need to be aware of its potential consequences.

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... This is a rare complication, with only 10 previous cases found upon review of the literature. [4][5][6][7][8][9][10][11] Soltani-Arabshahi et al. originally described three similar cases of women who developed facial granulomas following microneedling, with evidence of foreign body-type granulomas on biopsy and a positive patch test reaction to vitamin C serum in two cases. They hypothesized that these cases represented true delayed-type hypersensitivity granulomas secondary to an immunologic response after intradermal tattooing of an antigenic topical product. ...
... They hypothesized that these cases represented true delayed-type hypersensitivity granulomas secondary to an immunologic response after intradermal tattooing of an antigenic topical product. 4 In other cases, the needles themselves have been the antigenic source for post-microneedling cutaneous reactions, with patients demonstrating an allergy to nickel on patch testing. 5, 6 We suspect a similar mechanism underlying our patient's presentation, with either the vitamin C topical or the nickel in the needle acting as the antigen source. ...
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Background Microneedling is a common non-invasive procedure used for a variety of dermatologic conditions. It is associated with a low rate of adverse events which are typically temporary. Hypersensitivity reactions, including granuloma formation, are a rare adverse event, with only 10 cases previously reported. Case Summary We report a case of a 49-year-old female who presented with asymptomatic edematous erythematous annular plaques on her left cheek following a microneedling procedure in which a Vitamin C cosmeceutical was applied to the skin beforehand. Skin biopsy confirmed non-necrotizing granulomatous dermatitis with negative tissue cultures. Systemic workup for sarcoidosis was negative. Conclusion Delayed facial granulomatous reaction is an uncommon adverse event following microneedling. Increased risk may be related to peri-procedure use of cosmeceuticals such as Vitamin C. Given the popularity of microneedling, and that it is an unregulated procedure, it is important for dermatologists to be aware of this possible sequela in order to counsel patients appropriately and understand management options.
... Two of the three cases were considered to be due to pretreatment with vitamin C serum. 28 In another report, a woman received RMN with hyaluronic acid on the dorsal hands and inadvertently applied an arnica-based cream on the treatment areas at home; subsequently, the involved areas evolved into a dermatitis-like reaction with erythema and yellow papules. 29 The topicals being used, however, were not necessarily intended for use in conjunction with MN or for delivery into the dermis. ...
... It is important to note for clinical application and extrapolation of these data that most studies use topical lidocaine prior to MN, thus mitigating associated pain. 2,6,7,9,10,18,20,22,26,28,32,33,[43][44][45][46][47]50 While pinpoint bleeding is often a desired endpoint, the risk of bruising and bleeding may be lower in those patients who have not been on blood thinners. Overall, this review did not discover excessive bleeding to be a side e ect of MN. ...
Article
BACKGROUND: Microneedling is a relatively safe therapeutic procedure used to treat many dermatological conditions, including acne vulgaris, alopecia, melasma and other pigmentary disorders, as well as to promote skin rejuvenation, rhytide reduction, and scar remodeling. Given its popularity among patients and increasing use in the clinic and at home, we aim to explain the adverse effects associated with microneedling procedures. OBJECTIVE: We reviewed the current literature describing microneedling and the complications that may accompany this therapeutic procedure. PubMed was searched to identify studies that involved microneedling procedures using the standard roller microneedling, stamp microneedling, pen-type microneedling, and/or fractional radiofrequency microneedling devices. The resulting publications included clinical trials, retrospective studies, and case reports, which were then thoroughly reviewed for description of potential or observed complications that arose secondary to the microneedling procedure. RESULTS: In this systematic review, a total of 51 articles were reviewed, which included 1,029 patients who received microneedling procedures for a variety of different skin conditions. Overall, this review found that microneedling, regardless of the specific device used, is a relatively safe procedure with minimal adverse effects, including, but not limited to, expected erythema, pain, edema, and temporary skin irritation. CONCLUSIONS: Microneedling has become an attractive treatment option for many patients with dermatological conditions. We advise that clinicians and patients be informed about the adverse side effects associated with microneedling so that the risk of preventable complications can be reduced or avoided.
... Topical vitamin C in rare cases can cause granuloma formation with use during microneedle therapy. 8 Microneedles creates tiny holes in the skin's surface like ablative lasers. However, there is less evidence to show one-time use of topical vitamin C immediately after ablative laser leads to complications 9 but there is a theoretical risk. ...
Article
Background: Hypermobile Ehlers-Danlos Syndrome (hEDS) is a connective tissue disorder with cutaneous manifestations including poor wound healing and atrophic scar formation. There is evidence supporting the use of topical vitamin C and laser for scar revisions, but limited reports of using topical vitamin C in scar revisions in patients with hEDS. Objective: To present a case where topical vitamin C applied post-laser treatment resulted in improved healing and aesthetic outcomes in a patient with a connective tissue disorder. Methods: We present a case of treatment of atrophic and hypertrophic scars in a patient with hEDS with ablative fractional laser, pulsed dye laser, and post-procedural topical vitamin C. We discuss the patient’s treatments, outcomes, and previous literature on the matter. Results: This patient had markedly improved wound healing after topical application of vitamin C post-laser treatment with no complications. Additionally, the patient had improved aesthetic outcomes with topical vitamin C and laser treatment just after one session. Conclusion: This case suggests that hEDS scars may be safely treated with lasers when combined with post-procedural topical vitamin C.
... The safety of MNs is gained evidenced by Zosano Pharma, the comprehensive phase II clinical trial study (Search-Zosano web), and Corium (MicroCor web). In this research, the frequent administration of coated (titanium) and dissolving (polymeric) MNs in post-menopausal women with parathyroid hormone analog showed no adverse reactions, indicating the safety of microneedle technology [148]. ...
Article
The skin serves as the major organ in the targeted transdermal drug delivery system for many compounds. The microneedle acts as a novel technique to deliver drugs across the different layers of the skin, including the major barrier stratum corneum, in an effective manner. A microneedle array patch comprises dozens to hundreds of micron-sized needles with numerous structures and advantages resulting from their special and smart designs. Microneedle approach is much more advanced than conventional transdermal delivery pathways due to several benefits like minimally invasive, painless, self-administrable, and enhanced patient compliance. The microneedles are classified into hollow, solid, coated, dissolving, and hydrogel. Several polymers are used to fabricate microneedle, such as natural, semi-synthetic, synthetic, biodegradable, and swellable polymers. Researchers in the preparation of microneedles also explored the combinations of polymers. The safety of the polymer used in microneedle is a crucial aspect to prevent toxicity in vivo. Thus, this review aims to provide a detailed review of microneedles and mainly focus on the various polymers used in the fabrication of microneedles.
... In light of the course of Appreciation and Analysis of Cosmetic, it probes into some professional knowledge with cosmeticassociated dermatology and enhances a person's self-cultivation for the general public. Cosmetic products are closely associated with a series of dermatoses, such as sensitive skin, contact dermatitis, atopic dermatitis and rosacea (9,10). While we all refrain from going outdoors, people have reduced the use of make-up during the pandemic. ...
Article
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Objectives: During the pandemic, quarantine has led to the lockdown of many physical educational institutions. Thus, massive open online courses (MOOCs) have become a more common choice for participants. MOOCs are often flagged as supplemental methods to educational disparities caused by regional socioeconomic distribution. However, dissenters argue that MOOCs can exacerbate the digital divide. This study aimed to compare the participants' performance before and after the outbreak of COVID-19, analyze the impact of the epidemic on online education of cosmetic dermatology from the view of the regional socioeconomic distribution, and investigate whether MOOCs exacerbate the digital divide in the COVID-19 epidemic. Methods: The study was conducted in participants of the MOOC course Appreciation and Analysis of Cosmetics from January 2018 to December 2020. Based on the platform data and official socioeconomic statistics, correlation of multivariate analysis was used to determine the factors related to the number of total participants. A panel regression model and stepwise least squares regression analysis (STEPLS) were employed to further analyze the relationship between GDP, population, number of college students and number of total participants in different years in the eastern, central and western regions of China. Results: The number of total participants in 2020 surged 82.02% compared with that in 2019. Completion rates were generally stable in 2018 and 2019 before the COVID-19 pandemic and significantly decreased in 2020 after the outbreak of the pandemic. GDP was the most important socioeconomic factor that determined the total number of participants and it was positively related to the total number of participants before and after the outbreak of the pandemic. The number of college students was unrelated to the total number of participants before the epidemic, and after the outbreak of COVID-19 in 2020, the number became positively related in all regions of China. Conclusions: This study shows that the epidemic pushes more people to choose MOOCs to study cosmetic dermatology, and online education could exacerbate rather than reduce disparities that are related to regional and socioeconomic status in the cosmetic field in the COVID-19 pandemic.
... 48 A 2014 paper recommended caution regarding the simultaneous application of antioxidants because of the risk of granuloma formation. 74 Compared to their individual application, the simultaneous use of tretinoin and microneedling accelerated the proliferation, thickened the epidermis, and increased the density of collagen fibers. 75 Simultaneous use of mesomicroneedling and stem cell therapy was also found effective in skin rejuvenation. ...
Article
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Microneedling can accelerate skin repair through numerous complex processes triggered by micro-injuries it produces on the skin surface with very thin needles. The current growth in the application of microneedling in the treatment of cutaneous diseases can be explained by its numerous effects on the skin as reported in the literature. Despite the numerous studies conducted on the application of microneedling in the treatment of skin lesions, its effects on pigmented skin lesions have remained relatively unexplored. The present review comprises an examination of the evidence for the application of microneedling in skin diseases in general and a comprehensive review of the applications of microneedling in pigmentation disorders. The review involved a search of all clinical studies, including trials, case reports, and case series, in the databases MEDLINE/PubMed and Google Scholar using the following keywords: “microneedling”, “dermal needling”, “percutaneous collagen induction”, “skin needling”, “dermaroller”, and “dermatology disorder”. Pertinent data were extracted from all relevant articles published from 1990 to April 2021, and focused on the application of microneedling in the treatment of pigmented skin lesions. Despite the limited number of available studies, evidence suggests the effectiveness and safety of microneedling in treating vitiligo, melasma, and periorbitalhypermelanosis. It is noteworthy that the combination of any type of non-aggressive needing technique with other effective therapies (especially topical agents and mesotherapy) yields more promising therapeutic results than single therapy for melasma, dark cycles and vitiligo as the prototype of pigmentary disorders. However, single needling therapy is significantly effective, too. This article is protected by copyright. All rights reserved.
... Literatürde mikroiğneleme sırasında uygulanan topikal C vitamini sonrası biyopsi ile kanıtlanmış yabancı cisim tipi granülom geliştiği bildirilmiştir. 44 Bununla birlikte, topikal anesteziklere ve enfeksiyonlara bağlı olası yan etkiler göz önünde bulundurulmalıdır. Elektrikli kalemlerin tek kullanımlık iğne uçları enfeksiyon riskini sınırlar. ...
Chapter
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Mezoterapi, medikal ve kozmetik tedavi amacıyla çeşitli bileşenlerin mikroen-jeksiyon yoluyla dermise iletildiği minimal invaziv bir tekniktir. 1 İlk defa 1952 yılında Fransız hekim Michel Pistor tarafından tanımlanmıştır. Günümüzde, minimal invaziv ve görece ağrısız bir yöntem olması nedeni ile kozmetik dermatolojide selülit tedavisi, vücut şekillendirme, kırışıklıkların giderilmesi, pigmentasyon tedavisi ve saç dökülmesi gibi çeşitli endikasyonlarda sıklıkla tercih edilmektedir. 2,3 Mezoterapinin en önemli avantajları kullanılan bileşenlerin oral/intravenöz ilaç yo-lunun sistemik etkilerini atlaması ve basit bir topikal tedaviye kıyasla daha derine etki etmesidir. Vücudun dolaşım, lenfatik ve bağışıklık sistemini uyararak biyolojik bir ya-nıta sebep olur. Ayrıca, mezoterapi ile yüzeysel olarak verilen ilaçlar genel dolaşım ta-rafından daha yavaş temizlenir. Böylece, ilaçlar dermise kademeli olarak nüfuz eder, daha az doz ile daha uzun bir etki süresi ve daha hızlı sonuçlar elde edilir. 4 Saç dökülmesi hastaların yaşam kalitesini etkileyen önemli bir faktördür. Saç dö-külmesi tedavisinde mezoterapinin saç kalitesini ve nemini iyileştirdiği, anajen fazı uzat-tığı, mikrosirkülasyonu ve besin kaynağını iyileştirdiği ve 5-alfa redüktazı engellediği düşünülmektedir. Mezoterapinin kullanıldığı başlıca alopesi formları androgenetik alo-pesi (AGA), telogen effluvium ve alopesi areatadır. Mezoterapi, sikatrisyel alopesiler için önerilmemektedir, ancak kortikosteroidlerin deri içine uygulandığı intralezyonel 63 Saç Dökülmelerinde Mezoterapi ve Mikroiğneleme Mesotherapy and Microneedling in Hair Loss ÖZET Saç dökülmesi hastaların yaşam kalitesini etkileyen önemli bir faktördür. Son yıllarda saç dö-külmesi tedavisinde mezoterapi ve mikroiğneleme yöntemlerinin kullanımı oldukça yaygınlaşmıştır. Ancak, her iki yöntem için de uygulayıcılar tarafından kullanılan standart bir protokol yoktur. Ayrıca, bu yöntemlerin etkinliklerini ve güvenilirliklerini değerlendiren klinik çalışmalar az sayıda ve yetersiz-dir. Bu derlemede, saç dökülmesi tedavisinde kullanılan mezoterapi ve mikroiğneleme yöntemleri lite-ratür ışığında gözden geçirilmiştir. Anah tar Ke li me ler: Alopesi; mezoterapi; mikroiğneleme; saç dökülmesi ABS TRACT Hair loss has a significant burden on the quality of life of patients. Recently, the use of mesotherapy and microneedling in the treatment of hair loss has become a common practice. However, there is no standard protocols used by clinicians for both methods. In addition, clinical studies evaluating the efficacy and safety of these methods are scarse and inadequate. In this review, mesotherapy and microneedling methods used in hair loss treatment are reviewed in the light of the literature.
... sessions induced granulomas. 27 Only approved injectable mesotherapy products should be used with microneedling to do mesoneedling. No side effects were encountered in this study. ...
Article
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Background Melasma is a common, multifactorial and recurring disease which is not easy to treat. Aims The purpose of this study is to evaluate the efficacy of microneedling in combination with Q‐switched neodymium‐doped yttrium aluminum garnet laser (QsNd‐YAG laser) for treatment of melasma. Patients/Methods Fifteen female patients with epidermal or mixed‐type melasma on the face were included in the study. Patients were first treated with QsNd‐YAG laser, and then with microneedling containing mesotherapy products of biomimetic peptides, at the same session. Modified Melasma Area Severity Index (mMASI) scores were calculated before the first session and again 2 weeks after the last session. The same treatment protocol was repeated every two weeks for five sessions within period of three months of therapy. The evaluation was performed according to the before and after photos taken from three angles including 90‐degree front and 45 degrees from left and right with the VISIA device. Results Of the 15 patients included in the study the mean mMASI scores before and after treatment were 9.2±5.7 (3.8‐23.1) and 3.6±4.0 (0.6‐16.8), respectively. mMASI scores were significantly reduced after completion of the protocol. Six (40%) patients had ‘very good response’, 4 (26.7%) patients had ‘good response’, and 5 (33.3%) patients were ‘unresponsive’. Six (40%) patients were followed‐up for 1 year and only 1 patient had a recurrence (6.7%). Conclusions In addition to the use of photoprotective measures, multimodality treatment including QsNd‐YAG laser and microneedling with mesotherapy products containing biomimetic peptides is effective to treat melasma and they work synergistically.
... Furthermore, concentrations of systemic inflammation biomarkers were all found to be within the normal range (133). It appears as though MNs may cause adverse events (such as skin irritation and intradermal granulomas) only when used inappropriately, i.e., when used in combination with cosmetic products that were not intended for application to MNpunctured skin (134,135). ...
Article
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The success of protein, peptide and antibody based therapies is evident - the biopharmaceuticals market is predicted to reach $388 billion by 2024 [1], and more than half of the current top 20 blockbuster drugs are biopharmaceuticals. However, the intrinsic properties of biopharmaceuticals has restricted the routes available for successful drug delivery. While providing 100% bioavailability, the intravenous route is often associated with pain and needle phobia from a patient perspective, which may translate as a reluctance to receive necessary treatment. Several non-invasive strategies have since emerged to overcome these limitations. One such strategy involves the use of microneedles (MNs), which are able to painlessly penetrate the stratum corneum barrier to dramatically increase transdermal drug delivery of numerous drugs. This review reports the wealth of studies that aim to enhance transdermal delivery of biopharmaceutics using MNs. The true potential of MNs as a drug delivery device for biopharmaceuticals will not only rely on acceptance from prescribers, patients and the regulatory authorities, but the ability to upscale MN manufacture in a cost-effective manner and the long term safety of MN application. Thus, the current barriers to clinical translation of MNs, and how these barriers may be overcome are also discussed.
... From the few reports, hypersensitivity induced by micro-needling shall be a type IV hypersensitivity. The application of topical products during the micro-needling procedure can introduce immunogenic particles into the dermis and potentiate local or systemic hypersensitivity reactions [13]. ...
Article
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Objective Botulinum toxin injection, micro-needling injection, and filler injection are the most widely used non-surgical facial cosmetic treatments. Hypersensitivity reactions associated with injections have not received sufficient attention due to their low incidence rates. The authors tried to summarize the characteristics of the hypersensitivity caused by cosmetic injections and helped to improve the diagnosis and treatment.MethodsA comprehensive search of the PubMed database to September 2019 was performed. Articles were screened using predetermined inclusion and exclusion criteria. Data collected included patient characteristics, injection information (injected material, trade name, location of injection, symptoms of allergy, time of onset), diagnostic examination, treatment, and prognosis.ResultsA total of 14 articles (57 patients) were included. There were 3 patients receiving botulinum toxin injection, 3 patients receiving micro-needling injection, and 46 patients receiving hyaluronic acid injection. Five patients were injected with collagen, polyacrylamide, paraffin, alkyl-imide or hyaluronidase, separately. The symptoms were redness, swelling, itching or induration at the injection site. The diagnosis and treatment methods vary greatly depending on the injection fillers. Removing the injected filler is the primary treatment.Conclusion Although hypersensitivity reaction is a relatively uncommon adverse event, more practice guidelines and research on diagnosis and treatment are demanded to help improve the outcomes.Level of Evidence IIIThis journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the table of contents or the online instructions to authors www.springer.com/00266.
... Several cases of granulomatous reactions from topical application before and after microneedling have been reported in the literature. [16][17][18] The topical agents reported to cause the granulomatous reactions include vitamin C and arnica-based creams. Therefore, particular caution should be taken regarding the safety of ingredients in topical agents. ...
Article
Background: Microneedling- and laser-assisted drug delivery are emerging techniques used to treat various conditions. However, key parameters affecting drug penetration remain unknown. Objective: This study aims to investigate the importance of timing of topical application, needle length, and device type for drug delivery. Materials and methods: Skin harvested from cosmetic surgeries was treated with black ink applied before or after treatment with a microneedling pen (MP), roller, or fractional ablative CO2 laser, and incubated for different time intervals. Ink penetration was additionally tested using different needle lengths. Sandwich estimator was used for statistical analysis. Results: Ink applied before MP penetrated deeper compared to ink applied afterward at 1 and 3 hours, and roller microneedling in both the ink-before and -after scenarios at 1, 3, and 6 hours (p < .05). Microneedling demonstrated lateral extension of ink beyond microchannels with increased ink penetration over time. CO2 laser demonstrated ink localization within microthermal zones without time-dependent increases in depth after 30 minutes. Ink penetration increases by 0.06 mm per 1 mm increase in needle length. Conclusion: Ink applied before MP results in the deepest penetration of ink. Microneedling offers unique advantages in transdermal delivery as its channels exhibit increasing penetration over time and lateral extension of product.
... The risk of infections and blood-borne pathogen exposures through the microchannels and possible breakage of stainless-steel arrays are the main disadvantages of using solid MNs [28]. Granulomas and skin inflammation have also been evaluated as possible risks [29]. However, MNs are effective in delivering drugs through the skin. ...
Article
Objective In vitro diffusion experiments were performed to assess the permeation of magnesium sulfate across pig skin. Method The mean thickness of the dermatomed porcine skin was 648 ± 12 µm. Magnesium concentration was measured using inductively coupled plasma-optical emission spectroscopy. Transdermal flux of magnesium sulfate across MN-treated and untreated porcine skin was obtained from the slope of the steady-state linear portion of cumulative amount versus time curve. Results Statistical analysis of the results was done with Student’s t-test. The transdermal flux of magnesium sulfate across microneedle-treated porcine skin was 134.19 ± 2.4 µg/cm2/h, and transdermal flux across untreated porcine skin was 4.64 ± 0.05 µg/cm2/h. Confocal microscopy was used to visualize the microchannels created by a solid microneedle roller (500 µm). Conclusion From our confocal microscopy studies, it was evident that the 500 µm long microneedles disrupted the stratum corneum and created microchannels measuring 191 ± 37 µm. The increase in transdermal flux across the microneedle-treated skin was statistically significant compared to that of controls, i.e., without the application of microneedles. With the application of microneedles, the transdermal flux of magnesium permeated over 12 h was approximately 33-fold higher in comparison to passive diffusion across an intact stratum corneum.
... The biocompatibility of the patient-contacting components of microneedling devices was evaluated by assessing their cytotoxicity, irritation, sensitization, acute systemic toxicity, and material-mediated pyrogenicity. Facial allergic granulomatous reactions and systemic hypersensitivity have been reported with microneedle therapy for skin rejuvenation (Soltani-Arabshahi et al., 2014). Biocompatibility was also extensively researched by Donnelly et al. (Donnelly et al., 2012). ...
... Other untoward events can result from the use of bio-incompatible procedural and aftercare cosmeceutical and pharmaceutical topical products or from the invasion of bacteria, fungi, and viruses. [17][18][19][20][21] The FDA has drafted recently a nonbinding regulatory consideration for microneedling devices, based on currently available information on "risks with MN to include infection, nerve and blood vessel damage, disease transmission between users, scar formation, hyperpigmentation, skin inflammation, allergic reactions, and skin irritation." 22 As practitioners continue to use MN and MN-RF devices and apply cosmeceuticals and sunscreens after treatments, adverse events can be expected to increase. ...
Article
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Background Microneedling (MN) and microneedling-radiofrequency (MN-RF) result in skin rejuvenation and skin exposure to pathogens. Objectives The aim was to determine histopathological changes of needle-depth injuries in preauricular skin and measure time-dependent repair of transepidermal water loss (TEWL) in subjects. Methods MN and MN-RF procedures were performed at 0.5- and 1.5-mm needle depths on preauricular skin strips from a facelift patient. In 10 subjects, MN and MN-RF procedures were performed at 0.5-mm needle lengths on 6 marked opposing face and body sites. MN and MN-RF at 1.5-mm needle lengths were also carried out on each subject’s midface skin lateral to the nasolabial fold. TEWL measurements were recorded with a calibrated DermaLab Cortex device (Hadsund, Denmark). Results Histological examination confirmed that the penetration depths of microchannels closely approximated the 0.5- or 1.5-mm needle lengths. In addition, MN-RF exhibited zones of coagulation injury at the distal end of the channel. After MN or MN-RF at 0.5-mm needle length, TEWL values were greatest immediately after needling to scalp, midface, neck, chest, arm, and thigh sites and remained slightly higher than baseline throughout the 48-h evaluation period. TEWL measurements after MN or MN-RF at 1.5-mm needle length resulted in the highest- and longest-lasting values throughout the 2-day observation period. Conclusions MN and MN-RF devices are novel devices that require further investigation into optimal treatment parameters and protocols, patient selection, and protection against intrusion of external pathogens and reactive cosmeceutical ingredients with barrier repair. Level of Evidence: 2
... 2 A técnica de drug delivery consiste em utilizar técnicas para otimizar a penetração de fármacos por meio de métodos químicos, mecânicos ou físicos. 2 O uso de formulações não específicas para drug delivery pode causar efeitos indesejáveis, tais como dermatite irritativa e alérgica, granulomas de corpo estranho e infecção cutânea. 3 Muitas formulações cosméticas disponíveis no mercado contêm conservantes e aditivos químicos em sua formulação, o que as torna inadequadas para uso em drug delivery; além disso, pode ocorrer contaminação das formulações por micro-organismos, tornando-as não ideais para esse fim. 4 ...
Article
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Introdução: A entrega tópica de medicamentos é essencial na Dermatologia. Devido à dificuldade de permeação do estrato córneo, as técnicas de drug delivery vêm recebendo destaque. O uso de formulações não específicas para este fim nos faz atentar para possíveis efeitos adversos e para a segurança microbiológica destas formulações. Objetivo: Avaliar crescimento bacteriano e fúngico no sérum anidro fluido por meio do teste de esterilidade simples. Materiais e métodos: O teste de esterilidade simples foi realizado em um sérum anidro contendo ativos lipofílicos e hidrofílicos. Este teste foi realizado três meses após a manufatura do produto. Resultados: A formulação estudada foi aprovada no teste de esterilidade simples realizado três meses após a manufatura do produto, mesmo sem uso de conservantes na formulação. A formulação em estudo foi aprovada no teste de esterilidade possivelmente devido ao fato de o veículo sérum ser de origem mineral e anidra, características que não favorecem a proliferação de micro-organismos. Conclusões: Embora somente o veículo contando ativos específicos tenha sido testado, os resultados deste estudo são promissores e demonstram a necessidade de estudos futuros que englobem de forma mais ampla o assunto.
... The safety of microneedles with respect to repeated skin application is further supported by results of the extensive phase II clinical trial conducted by Zosano Pharma [87] and Corium [88]. In these studies, the repeated application of coated titanium and dissolving polymeric microneedle for delivery of parathyroid hormone analogues in postmenopausal women resulted in no adverse reaction, illustrating the safety of such drug delivery technology [89]. ...
Article
Since the first patent for microneedles was filed in the 1970s, research on utilising microneedles as a drug delivery system has progressed significantly. In addition to the extensive research on microneedles for improving transdermal drug delivery, there is a growing interest in using these devices to manage dermatological conditions. This review aims to provide the background on microneedles, the clinical benefits, and challenges of the device along with the potential dermatological conditions that may benefit from the application of such a drug delivery system. The first part of the review provides an outline on benefits and challenges of translating microneedle-based drug delivery systems into clinical practice. The second part of the review covers the application of microneedles in treating dermatological conditions. The efficacy of microneedles along with the limitations of such a strategy to treat diseased skin shall be addressed.
... Additionally, oil granulomas have been described in the literature after lip and face augmentation with a paraffin-containing oil (Friedrich and Zustin, 2014;Uchida et al., 2007). Granulomatous reactions have also been reported after facial injections of silicone (Ficarra et al., 2002), microneedle therapy for skin rejuvenation (Soltani-Arabshahi et al., 2014), and injection of a foreign material such as Vaseline into the penis and scrotum (Hohaus et al., 2003). ...
Article
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Lipogranulomas represent foreign body reactions to exogenous lipid or oil-like substances introduced into the skin. These lesions characteristically have round-to-ovoid, vacuole-like cavities of varying sizes in the dermis, which results in a Swiss cheese-like appearance. We present the case of a 51-year-old Hispanic woman with an onset of painful, swollen, subcutaneous nodules on the face, most prominently on the right lower lip and both cheeks, after multiple self-injections of vitamin A oil. Histopathology test results of the lower lip showed a superficial-to-deep, nodular and interstitial, polymorphous inflammatory infiltrate of predominantly histiocytes with necrobiotic-type granulomatous changes, lymphocytes, and plasma cells. The cheek revealed deep dermal and subcutaneous small collections of foamy/vacuolated histiocytes, without significant numbers of other inflammatory cells. Given the patient's history of injecting oil extracted from vitamin A capsules into her skin, the light microscopic features are consistent with lipogranulomatous changes that are secondary to a local injection of foreign material. Clinicians and pathologists should be aware of the granulomatous immune reaction generated by the injection of unregulated products into the face and other areas of the body.
Article
Physicians advocating the frequent use of microneedling for skin care are advocating for a potentially dangerous procedure, especially when coupled with the topical application of bone marrow stem cell derived cytokines. Not only are the physicians who advocate for frequent microneedling as a skin care procedure not Board Certified in Dermatology (FAAD or FAOCD), they are not dermatologist; rather they are family practitioners. Further, they don't have M.D. or D.O. medical doctorate degrees, rather they have truncated bachelor in medicine degrees with limited education and training. Unlike board certified dermatologists, these physicians simply have neither a deep knowledge of dermatology, nor knowledge of the immunology of the skin. These physicians have developed and promulgated books, blogs, and training classes for these procedures that are offered to non-physicians, often to estheticians. Advocating the frequent use of microneedling for skin care, especially when coupled with the topical application of bone marrow stem cell derived cytokines induces a damaging chronic inflammatory state in the skin, and likely systemic inflammation too. Microneedling of the skin, even under sterile conditions, elicits a sterile inflammatory response, including early recruitment of neutrophils, throughout the layers of the skin, and even systemically. Given the non-sterile nature of the skin, a rich microbiome, including bacteria, viruses, and fungi, at the skin's surface, these procedures may allow microneedling to cause these microorganisms to gain entry into the epidermis and dermis, furthering an inflammatory response already induced by the wound and associated inflammatogenic self-molecules. The use of bone marrow stem cell cytokines can amplify the inflammatory response induced by injury, instead of resolving the inflammation such as that by the pro-resolving effects induced by adipose derived mesenchymal stem cells and fibroblasts acquired from skin tissue.
Article
Microneedling, also referred to as percutaneous collagen induction therapy, uses small needles to create mechanical injury to the skin, stimulating the wound-healing cascade and new collagen formation. Compared with other skin resurfacing techniques, microneedling preserves the epidermis and is nonablative, therefore reducing inflammation, downtime, and risk of dyspigmentation. In addition to increasing collagen production in fibroblasts, microneedling also helps normalize cell function of keratinocytes and melanocytes and can be used to increase absorption of topical medications, growth factors, or deliver radiofrequency directly to the dermis. The benefits of microneedling, associated procedures, indications for use, technical considerations, and potential complications are discussed.
Article
Objectives: The topical application of a combination Vitamin C, Vitamin E, and Ferulic acid serum following ablative fractional resurfacing has been reported to shorten post-procedure downtime and improve wound healing. However, transcutaneous drug delivery of cosmeceuticals initially meant for topical application have also been shown to have unintended side effects. The objective of our study was to report safety data from our single academic center experience consisting of patients treated with topical application of a vitamin C-containing cosmeceutical immediately following fractional ablative CO2 laser treatment with a focus on reportable side effects. Methods: A retrospective chart review of all patients at the University of Minnesota M Health Cosmetic Center who had fractional ablative CO2 (10,600 nm) laser procedure for any diagnosis followed by immediate one-time application of a combination serum containing 15% Vitamin C, 1% Vitamin E, and 0.5% Ferulic acid (C E Ferulic®, SkinCeuticals Inc., New York, NY) from Jan 1, 2015 to Dec 31, 2018 was performed. Pediatric and research opt-out patients were excluded. The medical records of these patients were manually reviewed for the following: age, sex, diagnosis, location, after-care instructions, antiviral and/or antibacterial prophylaxis use, and documentation of post-procedure side effects. Results: Thirty-three patients, encompassing a total of 45 treatment encounters, met inclusion criteria. There were ten cases of expected side effects: erythema (6), erythema with tenderness (1), erythema with mild bumpiness (1), skin peeling with pattern marking (1), and pain with slight bleeding (1). These were attributed to the normal post-procedure course and resolved without complications. There were no reported side effects related to the topical application of Vitamin C, Vitamin E, and Ferulic acid serum. Conclusions: The topical application of a Vitamin C, Vitamin E, and Ferulic acid serum immediately following fractional ablative CO2 laser therapy did not result in associated complications. However, these results may not be generalizable to longer application courses beyond the immediate post-procedure time period, nor to other cosmeceutical formulations. More studies examining the safety profile of topical cosmeceutical serums in laser-assisted drug delivery are needed.
Chapter
Microneedling, a minimally invasive technique utilized to induce neocollagenesis, is frequently combined with platelet-rich plasma (PRP) to enhance results for a variety of medical and cosmetic dermatological conditions. It is generally well-tolerated and effective with preliminary data demonstrating improved outcomes for the treatment of acne scarring, striae distensae, melasma, and photoaging.
Chapter
The structure and composition of the stratum corneum limits the free permeation of most substances applied to intact skin. To enhance the permeation, the use of methods or equipment, to make micropores or to increase the spaces between cells in the stratum corneum, has being increasing in order to enhance the treatment results – drug delivery. However, the inappropriate use of active ingredients and formulations can cause complications, increase recovery time, and decrease the result of the treatment. Knowing the physicochemical characteristics of the assets and formulations suitable for drug delivery, together with the application protocols, enhances the results and practically reduces the risk of complications.
Chapter
Drug delivery assisted by microneedling allows increasing the permeation of drugs with the use of a minimally invasive technique. Microneedling produces micropunctures that can be used as transportation routes of substances through biologic membranes, such as the stratum corneum. For this purpose, needles should penetrate at least until the viable epidermis or to the superficial dermis. Needles can be solid or hollows, they can also be coated, covered by a thin external layer containing the substance of choice, or be made with degradable polymers or carbohydrates, allowing the delivery of the substance at the time of the micropuncture. The time these microchannels remain open varies, and some procedures can retard the time of closure, such as occlusion. Medicines used in dermatology already studied include substances of different molecular weights. In this chapter we will discuss some drugs used in dermatology that have evidence to support microneedling-assisted drug delivery.
Article
Background: Microneedling is a minimally invasive procedure that stimulates collagen and elastin proliferation. It is used in the treatment of various skin pathologies, that is, scarring, photodamage, and hair loss; however, its safety profile has yet to be comprehensively reviewed. Objective: This review will discuss the reported side effects of microneedling in the current literature and delineate factors that increase the risk of complications. Materials and methods: A literature search in August 2019 was conducted using the PubMed database to identify studies reporting adverse events (AEs) after microneedling therapy. Results: Eighty-five articles were included in this systematic review. The most common reported AEs are transient procedural events that are expected postprocedure lasting up to 7 days, such as transient erythema/edema and pain, postinflammatory hyperpigmentation (PIH), dry skin/exfoliation, lymphadenopathy, and irritant contact dermatitis. Persistent serious adverse effects included PIH, tram-track scarring, and granulomatous reactions. Factors that increase the risk of events are active infections, darker skin, and metal allergies. Conclusion: Microneedling is a relatively safe therapy. Most reported AEs are minimal, resolving quickly and spontaneously. Caution should be taken in patients with active infection, darker skin types, metal allergies, and when used in conjunction with products not approved for intradermal use.
Article
The fast-advancing progress in the research of nanomedicine and microneedle applications in the past two decades has suggested that the combination of the two concepts could help to overcome some of the challenges we are facing in healthcare. They include poor patient compliance with medication and the lack of appropriate administration forms that enable the optimal dose to reach the target site. Nanoparticles as drug vesicles can protect their cargo and deliver it to the target site, while evading the body's defence mechanisms. Unfortunately, despite intense research on nanomedicine in the past 20 years, we still haven't answered some crucial questions, e.g. about their colloidal stability in solution and their optimal formulation, which makes the translation of this exciting technology from the lab bench to a viable product difficult. Dissolvable microneedles could be an effective way to maintain and stabilise nano-sized formulations, whilst enhancing the ability of nanoparticles to penetrate the stratum corneum barrier. Both concepts have been individually investigated fairly well and many analytical techniques for tracking the fate of nanomaterials with their precious cargo, both in vitro and in vivo, have been established. Yet, to the best of our knowledge, a comprehensive overview of the analytical tools encompassing the concepts of microneedles and nanoparticles with specific and successful examples is missing. In this review, we have attempted to briefly analyse the challenges associated with nanomedicine itself, but crucially we provide an easy-to-navigate scheme of methods, suitable for characterisation and imaging the physico-chemical properties of the material matrix.
Poster
Introduction: Warts are the viral infection of the skin caused by Human Papilloma Virus occurring in form of verrucous growth over the surface of the skin. Incomplete removal or local recurrence of the infection is the disadvantage with the currently available local tissue destructive therapies. Newer therapy i.e. intralesional immunotherapy with purified protein derivative offers the advantage of taking care of viral infection not only at treatment site but also at the remote site, and also offers lifelong immunity. Materials and methods: The study was conducted on 40 patients of warts of all ages. After clinical examination, patients were given 0.1 ml of 5 TU of PPD intralesionally in the largest wart at an interval of one week for four weeks. Patient’s assessment in follow -up visits were done with clinical photographs and by filling proforma for effects and side effects. Results: Complete clearance was seen in 26(65%) patients, partial clearance in 8(20%) patients, and no clearance in 6 (15%) patients. The variation in response in a different morphologic type of warts was as follows: Periungual and palmar wart 100% clearance, plantar wart showed 70% clearance, verruca plana 40% clearance, and verruca vulgaris 40% clearance. Conclusion: PPD immunostimulation is worth in all types of warts; it can be used as a valuable first line treatment in difficult to treat sites like palmoplantar wart and periungual wart.
Chapter
Aging of the skin is undesirable and occurs with time due to both natural (intrinsic) and environmental (extrinsic) factors. Microneedling is a cosmetic procedure gaining popularity as it has been clinically shown to address both intrinsic and extrinsic skin aging. This cosmetic procedure is minimally invasive and utilizes fine needles to puncture the skin, creating microwounds, which induces the release of growth factors and induction of collagen and elastin production. The combination of the antiaging facial moisturizer and radiofrequency (RF) microneedling was comfortable for the patients and patients were satisfied. Another study was done to assess the safety and efficacy of two topical tri‐ and hexapeptide‐containing products pre‐ and posttreatment with RF microneedling of the photoaged neck with respect to healing and aesthetic outcomes. Skin needling provides a clear channel for topical agents to be absorbed more effectively through the top layer of the skin, such as the platelet‐rich plasma.
Chapter
Microneedling (MN), also known as percutaneous collagen induction therapy, is a relatively new minimally invasive procedure involving superficial skin puncture by rolling multiple miniature fine needles into the skin. This chapter focuses on microneedling of hyperpigmentation problems through different mechanisms. Melasma is one of the most common acquired symmetrical hypermelanotic disorders, mostly affecting females with darker skin types. It has a considerable negative psychological impact on the patient's quality of life. There is no evidence‐based guideline presently established for the use and efficacy of MN on melasma patients. Periorbital melanosis presents with dark circles under both eyes occurring after puberty or in early childhood. It is commonly found in dark‐skinned patients, especially Asians. Microneedling therapy has shown success in treatment of periorbital melanosis. Platelet‐rich plasma (PRP) is developed by enriching plasma with an autologous high concentration of platelets derived from whole blood. PRP has multiple uses in dermatology.
Chapter
During treatment, needles pierce the stratum corneum and create the microchannels without damaging the epidermis, making it possible to create an accessible means of transporting macromolecules and other hydrophilic substances to the skin. The microchannels facilitate drug delivery efficiently and can increase the absorption of larger molecules by up to 80%. The application of drugs by the transdermal drug delivery system has been used as an alternative to the oral or parenteral administration of various substances. Transdermal patches can, for example, be useful for the application of vaccines and medications that require slow and controlled release into the skin. However, the transdermal route of drug absorption faces a major challenge, which is the barrier function of the skin, mainly exercised by the stratum corneum, which limits the absorption of many actives. PCI is a simple, safe method with low incidence of side effects. The association with drug delivery has the advantage of being a safe, low cost, and effective procedure that enhances the results of dermatological treatments.
Article
Background Melasma is a chronic pigmentary condition that can have significant negative effects on quality of life. Vitamin C can be effective in the treatment melasma, but its delivery often proves to be challenging due to instability of the drug and subsequent cutaneous irritation at higher concentrations. Aim In this prospective, open‐label, evaluator‐blinded study, we aimed to assess the efficacy and tolerability of twice‐daily application of a novel, highly potent, non‐irritating 30% tetrahexyldecyl (THD) ascorbate serum in combination with 100% mineral‐based sunscreen in the treatment of melasma during the summer months. Patients/Methods Ten female subjects of ages ranging from 18 to 60 years underwent twice‐daily application of 30% THD ascorbate serum in combination with an anti‐aging 100% mineral tinted broad‐spectrum protection SPF 45 sunscreen moisturizer for 12 weeks during the summer months (July to September). Two blinded evaluators scored baseline and post‐treatment photographs using the Griffiths’ 10‐point scale and global aesthetic improvement scale. Results All subjects showed an improvement in hyperpigmentation with an average improvement of 33.7%. Seventy percent of subjects showed an improvement in skin tone evenness (redness), and among those subjects, the average improvement was 33.3%. The median global aesthetic improvement score was 2.0 (very much improved). Conclusion Our study demonstrated efficacy and safety in treating the pigmentary as well as vascular components of melasma with a novel 30% THD ascorbate serum and a purely mineral‐based tinted moisturizing sunscreen.
Article
Full-text available
Derma roller, a device rolled onto the skin to form micropores, is extensively used for cosmetic purposes. The pores thus created are utilized to either result in the induction of collagen production, leading to glowing and wrinkle-free skin or for permeating the applied formulations to the site of action within the skin. Recent studies have shown the benefits of using derma rollers for transdermal delivery of drugs. In the nascent stage, this approach paves a way to successfully breach the stratum corneum and aid in the movement of medications directed towards the dermis and the hair follicles. The review essentially summarizes the evidence of the use of derma rollers in cosmetic setup, their designing, and the preclinical and clinical reports of efficacy, safety, and concerns when translated for pharmaceutical purposes and transdermal drug delivery.
Article
Background: Melasma is an acquired disorder of hyperpigmentation that is often recalcitrant to current therapies. Microneedling is used to treat scars, striae, and rhytides and has a relatively low risk of post-treatment dyspigmentation. Several studies have examined its use in melasma. Objective: To review the published evidence on the efficacy and safety of microneedling in the treatment of melasma. Methods: A systematic review was performed. A meta-analysis could not be performed because of methodological differences across studies and data heterogeneity. Results: Eight studies were included for analysis. Most studies assessed the utility of microneedling in combination with other topical therapies and detected some success. However, microneedling-mediated transdermal delivery of medications is not superior to microinjections of medications. There is less evidence supporting the use of microneedling as monotherapy. Microneedling, when used with a 1064-nm Q-switched Nd:YAG laser, may provide additional benefit, although with a risk of post-treatment dyspigmentation. Conclusion: Based on low-quality evidence, microneedling may play a role in the treatment of melasma, with the mechanism of action likely being the facilitation of delivery of topical therapies to the epidermis and dermis, and one ancillary benefit of this approach being the very low risk of postinflammatory hyperpigmentation.
Article
Full-text available
Skin infections caused by bacteria, viruses and fungi are difficult to be treated by conventional topical administration because of poor drug penetration across the stratum corneum. This results in low bioavailability of drugs to the infection site, as well as the lack of prolonged release. Emerging antimicrobial transdermal and ocular microneedle patches have become promising medical devices for the delivery of various antibacterial, antifungal and antiviral therapeutics. In the present review, skin anatomy and its barriers along with skin infection are discussed. Potential strategies for designing antimicrobial microneedles and their targeted therapy are outlined. Finally, biosensing microneedle patches associated with personalized drug therapy and selective toxicity toward specific microbial species are discussed.
Chapter
Since it has been developed and improved over the last two decades, microneedling is one of the few examples that combine technology and simplicity. It is an effective, safe, and minimally invasive technique involving puncturing of the skin by rolling a handheld device with fine needles. The success of the technique is precisely to provide regeneration rather than cicatrization. As opposed to ablative procedures, microneedling preserves the epidermis and promotes normal collagen formation in place of scar collagen [1]. In addition to acne scars, it is also used for skin rejuvenation, other etiologies scars, stretch marks, alopecia, acne, hyperhidrosis and as a transdermal delivery system for therapeutic drugs and vaccines (drug delivery) [2].
Article
Background: Cutaneous warts are an extremely common problem, whose eradication can be challenging. Topical PDT involves applying a porphyrin precursor, 5-aminolevulinic acid (ALA) or methyl aminolevulinate (MAL) to the affected area. ALA-PDT has been well documented to be successful in the treatment of recalcitrant warts. PDT has a limited role in the treatment of thicker lesions because the photosensitizer does not penetrate keratotic lesions well, though this is vehicle dependent. Objective: The aim of this study was to evaluate the efficacy and safety of curettage + microneedling + ALA-PDT for the treatment of resistant acral warts. We hypothesized that microneedling may increase the efficacy of PDT, providing a channel to deliver the ALA to deeper areas of warts. Methods: Our study was carried out between November 2017 and July 2018. Eligible participants had one or more resistant plantar or palmar warts. Thirteen patients were recruited. They underwent a thorough curettage, followed by the application of 5-ALA 10% cream on the wart, and by microneedling. Later, the pricked skin was covered for three hours by an occlusive polyurethane dressing, and finally irradiated with a red-light source. Patients performed one session every three weeks for a total of three cycles. Results: After 3 treatments of curettage + microneedling + ALA-PDT, 11 patients (84.6%) showed complete remission (defined as complete disappearance of their warts). One patient (7.7%) showed partial remission (defined as greater than 50% decrease in the wart area) after 3 sessions; this patient needed other 2 sessions to achieve complete remission. The mean follow-up period after healing was 4.3 months. Adverse effects were recorded. Conclusion: We have demonstrated, for the first time to our knowledge, that the combination of curettage + microneedling + topical ALA-PDT may offer an effective and safe alternative for the treatment of acral resistant warts, even when PDT alone has already been insufficient.
Article
This article presents the authors' experience with the use of fat grafting via the Coleman technique, for the adjuvant treatment of facial burn wounds and their sequelae. It demonstrates the regenerative effects of fat injected under the wound and/or the scar as well as of fat delivered to the debrided surface of the wound and to the surface of the scar after laser treatment or microneedling.
Article
Microneedling is a procedure that uses fine, sterile needles to puncture the skin to different depths. Inducing the wound-healing cascade in this way helps stimulate collagen, elastin and glycosaminoglycan production and thus improve the quality and appearance of the skin. Microneedling has been shown to be a safe and efficacious treatment for a number of medical and aesthetic concerns. This article reviews the physiology, protocols and applications of microneedling in the aesthetic medical arena, as well as the reported side effects and adverse reactions.
Article
Full-text available
Developed within the last few decades, microneedles (MNs) have only recently seen wide-scale use among the general population, especially in the area of cosmetics. With the FDA only starting to regulate microneedling devices and the many new microneedling products that enter the modern global market, it is of utmost importance to establish the safety profile and reasonable expectations of the microneedling practice and its products. In our review of current literature, the authors searched the keyword “microneedle” with the following terms: “safety”, “side effect”, “toxicology”, “adverse effect”, “adverse event”, “infection”, “dermatitis”, “granuloma”, “scarring”, and “hyperpigmentation”. Despite wide-scale implementation of MNs, we are likely only beginning to understand the potential of MNs as a medical and consumer product, and we should, therefore, be aware of any potential adverse events associated with the product.
Article
Radiofrequency (RF) skin rejuvenation is improved using RF microneedling (RFM) devices. More aggressive treatments are performed safely with minimal downtime than previous RF devices. Optimizing treatment parameters is essential for safety and efficacy. Multiple RFM studies support minimal risks even in dark skin types. RFM has been used to treat acne scarring successfully as well as skin laxity and hyperhidrosis.
Chapter
Over the past decade, there has been a surge in demand for minimally invasive treatments for aging skin. Patients seek non-surgical treatments due to reduced procedure-associated risks and faster recovery time compared to traditional surgical methods. One component of aging skin is the appearance of laxity, which is due to thinning of the epidermis, loss of dermal connective tissue and atrophy and/or redistribution of subcutaneous fat, or all of the above. Innovation in energy-based devices has created multiple avenues to address the various factors leading to skin laxity. This chapter will discuss the mechanism of action, efficacy and safety of ablative and non-ablative lasers, infrared light, ultrasound, and microneedling in treatment of skin laxity.
Article
Background Even though dermatologists often perform drug delivery procedures, it is necessary to assess their safety. Objective Quantify the amount of medication delivered using the MMP drug delivery technique and outline other safety parameters. Methods Using a simple and novel technique, we attempted to quantify the amount of medication delivered by weighing human skin samples before and after delivery. Results In drug delivery done on human skin using a liquid with a density of 1,271,460 μg/ml (the values expressed in this manuscript are in µg), a needling density of 570 perforations/cm², and a needling depth of 300 microns, we estimate that 1,175 μg/cm² were delivered (standard deviation 601 μg/cm², standard error 190 μg/cm²). Limitations This result is only applicable to the protocol proposed in this study for the MMP drug delivery technique. Conclusion The MMP drug delivery technique injects small amounts of medication (1,175 μg/cm²) homogeneously into the dermis.
Article
Absorption of topical products through the epidermis is limited by the skin's barrier function. Numerous techniques and agents such as microneedling, dermabrasion, radiofrequency, and lasers have been used to increase penetration within an approach known as transdermal drug delivery. One of these techniques is laser-assisted drug delivery (LADD), which often uses ablative fractional lasers (CO2 or erbium:YAG lasers) because of their capacity to produce microscopic ablated channels. The parameters in LADD need to be adjusted to the patient, the skin condition and its location, and the drug. LADD has been used with various topical products, such as corticosteroids, photosensitizers, and immunotherapy agents (imiquimod or 5-fluorouracil) to treat numerous conditions, including scars, nonmelanoma skin cancer, and photodamage. LADD is a promising technique that enhances the absorption of topical molecules while adding the synergic effect of the laser.
Article
Full-text available
Melasma is a common hypermelanotic disorder affecting the facial area which has a considerable psychological impact on the patient. Managing melasma is a difficult challenge that requires long-term treatment with a number of topical agents, such as rucinol and sophora-alpha. Aims. We aim to compare the combined treatment of skin needling and depigmenting serum with that using depigmenting serum alone in the treatment of melasma, in order to evaluate the use of microneedles as a means to enhance the drug's transdermal penetration. Methods. Twenty patients were treated with combined skin needling and depigmenting serum on one side of the face and with depigmenting serum alone on the other side. The outcome was evaluated periodically for up to two months using the Melasma Area Severity Index score and the Spectrocolorimeter X-Rite 968. Results. The side with combined treatment (skin needling + depigmenting serum) presented a statistically significant reduction in MASI score and luminosity index (L) levels compared to the side treated with depigmenting serum alone, and clinical symptoms were significantly improved. Conclusions. Our study suggests the potential use of combining skin needling with rucinol and sophora-alpha compounds to achieve better results in melasma treatment compared to rucinol and sophora-alpha alone.
Article
Guinea pigs were injected intradermally with 5 mg, 0.5 mg, and 0.05 mg of the following compounds: zirconium carbonate (ZrCO3), aluminum chlorhydrate (ACH), and zirconium aluminum glycine complex (ZAGS), or 6.5 mg, 0.65 mg, and 0.065 mg of aluminum hydroxide (Al(OH)3), in 0.1 ml of saline. Al(OH)3 produced measurable granulomas with the 6.5-mg and 0.65-mg doses; those produced by the 6.5-mg dose persisted for over 28 days. No increase in skin thickness was detected with ZrCO3. Histologic examination of the Al(OH)3 granulomas revealed large undifferentiated macrophages and occasional giant cells surrounding the area containing the injected material. There was little evidence of infiltration with other inflammatory cells and no evidence of fibrosis, although there was always some degree of central necrosis. While ZrCO3 induced no measurable granulomas, the injection site usually contained a small collection of macrophages that had ingested crystalline material. Both ACH and ZAGS produced increases in skin thickness even at the 0.05-mg dos. This began 14 days after injection, and reached a maximum at 21 days. Histologically, the lesions showed granulomas which consisted of shredded bundles of intensely basophilic collagen,, which also stained with Weigert's elastic stain. This area contained many giant cells and histiocytes, which were markedly pleomorphic, strongly hyperchromatic, and occasionally phagocytic. This process was succeeded by intense fibrosis. The changes in collagen could be the same as those seen in senile elastosis.
Article
The Journal of Investigative Dermatology publishes basic and clinical research in cutaneous biology and skin disease.
Article
Eighteen patients who developed cutaneous reactions to red tattoos were studied to identify the chemicals responsible for the reactions to modern red tattoo pigments. Biopsies from the tattoos were examined histologically and the chemical composition of the red pigments was analysed by X-ray microanalysis. A variety of metallic elements including aluminium, iron, calcium, titanium, silicon, mercury and cadmium were detected. Patch tests were performed to the relevant chemicals in nine cases, and only one patient reacted to mercury. This study demonstrates that although reactions to mercury still occur, other red dyes containing a variety of inorganic pigments may provoke a cutaneous inflammatory response.
Article
Subcutaneous or submucosal infiltration of cosmetic materials is a very common practice, because of the ease with which such materials can be deposited, and their presumed innocuousness. However, in recent years there have been reports of foreign body granulomatous reactions occurring many years after infiltration. Data were collected on the clinical manifestations, histopathological findings, treatment, and course of the lesions of 15 patients. One male and 14 females presented orofacial swelling an average of 7 years after the infiltration of silicone (n = 9), hyaluronic acid (n = 2), collagen (n = 2), methacrylate (n = 1), and polyalkylimide (n = 1). The patients were treated mainly with systemic corticosteroids, and were followed for an average of 17 months. Systemic corticosteroids are able to control granulomatous reactions, which manifest in the form of outbreaks and tend to undergo spontaneous remission over the years.
Article
Guinea pigs were sensitized to potassium dichromate, nickel sulfate and sodium zirconium lactate by three methods of immunization in Freund's complete adjuvant: Polak, split adjuvant, and maximization (modified Magnusson and Kligman). These were followed after 2 weeks by weekly intradermal injections of 25 microng of the metal salt. Delayed hypersensitivity-like reactions developed 3 to 12 weeks after initial injection. Reactivity, although strong with an increase in thickness of over 0.7 mm and/or diameter of erythema of over 8 X 8 mm, was frequently transient, the animal losing reactivity on subsequent skin test or after 2 or 3 skin tests. In two-thirds of the experiments using sodium zirconium lactate, delayed hypersensitivity-like reactions at 24 hr developed into nodular lesions which reached peak intensity at 8 days and histologically contained histiocytes with an epithelioid cell appearance and giant cells. In some experiments, sodium zirconium lactate-sensitive animals showed cross reactivity with potassium dichromate, but not with nickel sulfate.
Article
Eighteen patients who developed cutaneous reactions to red tattoos were studied to identify the chemicals responsible for the reactions to modern red tattoo pigments. Biopsies from the tattoos were examined histologically and the chemical composition of the red pigments was analysed by X-ray microanalysis. A variety of metallic elements including aluminium, iron, calcium, titanium, silicon, mercury and cadmium were detected. Patch tests were performed to the relevant chemicals in nine cases, and only one patient reacted to mercury. This study demonstrates that although reactions to mercury still occur, other red dyes containing a variety of inorganic pigments may provoke a cutaneous inflammatory response.
Article
In this article we describe a technique of needle dermabrasion (tattoo without pigment) used to improve achromic, hypertrophic, and unsightly scars. It is simple, safe (no complications), and it gives us consistently good results.
Article
The authors review the case of a 30-year old female hair-dresser, into the breasts of whom silicone-gel implants have been implanted for cosmetic reasons. Ten months after the operation Löfgren-syndrome evolved, which improved only temporarily after the removal of the implants. The present symptom-free state, existing for 6 months now, required a 17-month corticoid therapy. The authors share the view that in rare cases silicon-gel implants might induce an autoimmune reaction, which is unforeseeable. When it is rightly presumed that human adjuvant disease or some other specified systemic disease is evolving, it is advisable that the implants should be removed and the patient should be treated with immunological therapy.
Article
Hyaluronic acid (HA) fillers have been proposed as alternatives to other temporary skin fillers, such as bovine collagen, for treating facial skin lines and for providing lip augmentation. Several types of commercial HA fillers are now available in many countries. They include Restylane, which is produced by microbiologic engineering techniques, and Hylaform, which is HA extract derived from rooster combs. They have been approved for use in several countries, but not currently in the United States. There are no recommendations to perform pretreatment skin testing by the manufacturers. Our purpose is to describe and comment on our experiences with Hylaform and Restylane fillers. Observation of any side effects and skin testing results were documented. Between September 1996 and September 2000, 709 patients were treated with Hylaform and Restylane and were followed up clinically for at least 1 year. Three of these patients (0.42%) developed delayed skin reactions. Three other patients were referred for evaluation of their skin reactions from other practitioners. Five of these 6 patients agreed to skin testing of their forearms. In the 5 patients tested, challenge intradermal skin testing was positive in 4 patients; the reactions started approximately 8 weeks after injection. There was a slight incidence of delayed inflammatory skin reactions to two HA fillers. Both of these reactions occurred after the first and repeat injections. Challenge skin testing was positive in 4 of 5 tested patients.
Article
The development of granulomatous lesions within tattoos is a well-recognized occurrence in individuals with sarcoidosis. The characteristic histopathological finding of sarcoidosis is the presence of noncaseating granulomas; however, similar histopathogical findings may be seen in foreign body granulomas. Several reports have challenged the assertion that the presence of foreign material within sarcoidal granulomas is incompatible with a diagnosis of sarcoidosis. We describe a patient who had multiple linearly arranged papules along her eyebrows and the vermillion border of her upper lip. She had had cosmetic tattooing performed on these areas 3 year prior to presentation. Histopathologic examination revealed sarcoidal granulomas, polarizable foreign material, and pigment granules. Hilar adenopathy was noted on a chest radiograph. After 4 months of treatment with a midpotency topical steroid and doxycycline, she experienced complete clearance of her cutaneous lesions and normalization of chest x-ray film findings. This case demonstrates a unique adverse result after cosmetic tattooing and highlights the concept that granulomatous histopathologic findings containing foreign material should not be an exclusionary criterion for the diagnosis of sarcoidosis. In this setting, further investigation for the presence of systemic disease is indicated.
Article
Artecoll is a recently developed permanent synthetic cosmetic filler substance, composed of 80% bovine collagen and 20% polymethylacrylate (PMMA) microspheres of 32-40 mum in diameter. It is used for the augmentation of deep wrinkles and is to be injected subdermally. We report the development of granulomas at the site of Artecoll injections in the face in a 48-year-old woman who had pulmonary sarcoidosis. There were features consistent of both sarcoid and foreign-body granuloma, typical of those reported previously with Artecoll. We postulate that the PMMA foreign material contained within Artecoll acted as a stimulus for the development of the cutaneous sarcoid granulomas.
Article
Skin laxity, rhytides, and photoaging are generally treated by ablative procedures that injure or destroy the epidermis and its basement membrane, at least in the beginning, and subsequently lead to fibrosis of the papillary dermis. The ideal treatment would be to preserve the epidermis and promote normal collagen and elastin formation in the dermis. Percutaneous collagen induction takes us closer to this ideal. The authors performed a retrospective analysis of 480 patients in South Africa and Germany with fine wrinkles, lax skin, scarring, and stretch marks treated with percutaneous collagen induction using the Medical Roll-CIT to produce tighter, smoother skin. Most patients had only one treatment, but some have had as many as four treatments. Patients were prepared with topical vitamin A and C cosmetic creams for a minimum of 4 weeks preoperatively. On average, patients in Germany rated their improvement between 60 and 80 percent better than before the treatment. Histologic examination was carried out in 20 patients and showed a considerable increase in collagen and elastin deposition at 6 months postoperatively. The epidermis demonstrated 40 percent thickening of stratum spinosum and normal rete ridges at 1 year postoperatively. Percutaneous collagen induction was started in 1997 and has proved to be a simple and fast method for safely treating wrinkles and scars. As opposed to ablative laser treatments, the epidermis remains intact and is not damaged. For this reason, the procedure can be repeated safely and is also suited to regions where laser treatments and deep peels cannot be performed.
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Tattooing has become quite popular in Western countries. With the increasing prevalence, there is also an increased risk of adverse effects. We describe a 17-year-old female patient with a black and red-colored tattoo, who developed immediately after red tattooing general malaise with fever, nausea, and vomiting. A bullous reaction was temporarily seen within the red part of her tattoo. The reaction later shifted to a subacute dermatitis with bacterial superinfection. Two months later, she felt ill again. She developed painful tender nodules on the anterior aspect of both lower legs identified as erythema nodosum without sarcoidosis. Is this is a unique case of adverse reaction to tattoo pigments with a type I and a type IV reaction, or is this a coincidence? The treatment was initiated with systemic and topical corticosteroids and topical antibiotics combined with compression bandages for the legs. After 3 weeks of treatment, the erythema nodosum completely resolved and did not reappear during a 1-year follow-up. The treatment of the local reactions, however, was unsatisfactory without complete response. There is an indispensable need for regulation of tattoo pigments and tattooing to improve consumer safety.
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The success of transdermal drug delivery has been severely limited by the inability of most drugs to enter the skin at therapeutically useful rates. Recently, the use of micron-scale needles in increasing skin permeability has been proposed and shown to dramatically increase transdermal delivery, especially for macromolecules. Using the tools of the microelectronics industry, microneedles have been fabricated with a range of sizes, shapes and materials. Most drug delivery studies have emphasized solid microneedles, which have been shown to increase skin permeability to a broad range of molecules and nanoparticles in vitro. In vivo studies have demonstrated delivery of oligonucleotides, reduction of blood glucose level by insulin, and induction of immune responses from protein and DNA vaccines. For these studies, needle arrays have been used to pierce holes into skin to increase transport by diffusion or iontophoresis or as drug carriers that release drug into the skin from a microneedle surface coating. Hollow microneedles have also been developed and shown to microinject insulin to diabetic rats. To address practical applications of microneedles, the ratio of microneedle fracture force to skin insertion force (i.e. margin of safety) was found to be optimal for needles with small tip radius and large wall thickness. Microneedles inserted into the skin of human subjects were reported as painless. Together, these results suggest that microneedles represent a promising technology to deliver therapeutic compounds into the skin for a range of possible applications.