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Treatment of Dystrophic Epidermolysis Bullosa with Transforming Powder Dressing

Abstract

Dystrophic epidermolysis bullosa is a disabling blistering disorder, characterized by significant pain, extensive nursing care, and difficult wound healing. The following case presents a transforming powder dressing which provided pain reduction, atraumatic and reduced dressing changes, as well as improved healing in one patient.

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Induced Auto-Regeneration with Adipose Tissue in Humans – Beyond Frontiers of Healing

Opinion

The search for regeneration of the face and other structures of the human body has undergone several attempts, based on complex surgical techniques with the use of transplantation of fragments or limbs removed from donors, followed by the administration of immunosuppressive drugs for the rest of the patient’s life. The results of these face transplants are far from ideal and the degree of dissatisfaction in these patients is very high, leading to cases of severe depression, treatment abandonment and even suicide. In addition to technical problems such as recovery of facial mobility, transplantation of an external anatomical unit differs greatly from transplantation of an internal organ, as its immune behavior is very different. The skin represents the interface between the internal environment of our body and the external environment, therefore it has a rich defense system specialized in responding to all sorts of invaders, which makes it extremely antigenic. For this reason, the doses of immunosuppressive drugs need to be higher and constantly adjusted. We know that immunosuppressants have several side effects such as the possibility of bacterial, viral or fungal infections, with the risk of sepsis, kidney failure and even an increased incidence of malignant tumors, which adds an additional risk to a previously healthy patient [1-5].

The expectation of the patient with severe facial deformity is resocialization, the recovery of self-esteem, in short, psychosocial well-being. In practice, none of these factors materialize. The transplant has little facial mimicry, chronic edema, and the patient still needs to take several medications daily, living with the perennial prospect of rejection or the possibility of manifesting some side effect to the use of immunosuppressants For all these reasons, I believe that this search has not yet ended and that the path of transplantation should be replaced by that of biomimetic regeneration, through three-dimensional self-regeneration triggered or induced by some biomolecular mediator. If we take into account that there are other vertebrate organisms that have this capacity, such as some fish or amphibians, in particular the Salamander, that manage to perform the complete and perfect self-regeneration of a lost limb and remember that in the fertilization of the human egg, only one cell will give rise to the entire complex structure of our body, we can conclude that there is a way to activate this function in human tissues, we just haven’t mastered this knowledge yet. In my way of thinking, as long as we continue on the path of transplants + immunosuppressants, the more we will move away from the chance of achieving this cellular unlocking that will start the self-regenerating process [5-10].

Human cells have 3 differentiation blocking moments. In the formation of the zygote, cells are totipotent, that is, they can differentiate into any human cell. After that, the first block occurs, when the cells become pluripotent and differentiate by leaflets: ectoderm, mesoderm and endoderm, then the second block will occur, when the cells become multipotent, differing only in cells of a specific leaflet, and the third block occurs when the cell becomes differentiated, that is to say unipotent, just reproducing itself. But human cells have the capacity to transdifferentiate and reprogram themselves, as occurs in the female breast, where adipose tissue is transdifferentiated in the mammary gland at puberty and pregnancy, and vice versa after breastfeeding. In the Salamander, the regenerative process begins with the formation of a conglomerate of pluripotent cells called blastema that, controlled by the sympathetic nervous system, are differentiating and walking towards the member that will be newly formed [10- 19].

It is important to note that the current concepts of adipose derived stem cells (ADSCs) are rudimentary and in many publications do not consider the intercellular crosstalk and the importance of the cellular niche as a micro anatomical metabolic unit, where several cells of the same tissue (including stem cells) complement their cellular and molecular capabilities to achieve a single goal, whether revascularization, regeneration or other. Another consideration to be made is how to control the regenerative mechanism: what form to take and when to stop. These messages are certainly memorized in the nuclear DNA of all our cells, like a map or three-dimensional (holographic?) architectural project. Still far from being a regeneration like that of Salamander, we have been able to obtain very surprising results using the adipose tissue as an inducer of cell trans differentiation in complex wounds, obtaining a regeneration of the lesion with revascularization, epithelial growth, absence of fibrosis and mimicking the aspect prior to injury, which I called “Salamander effect”, as you will see in the following examples (Figures 1-3).

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Do Normal Human Epidermal Keratinocytes Require a Priming Step to Activate the NLRP3 Inflammasomes to Exogenous Threats?

Opinion

In recent work examining the expression of inflammasome-induced release of active Caspase-1 on Normal Human Epidermal Keratinocytes (NHEK), it was noted that two exogenous threats, UVB radiation and ATP were effective at activating the NLRP inflammasomes and inducing the release of significant quantities of active Caspase-1 [1]. It is generally thought that activation of the NLRP inflammasomes is a two-step process requiring: 1) activation of the NLRP inflammasome by signaling from the Toll-Like Receptors (TLR), and 2) creation of the inflammasome proteins after transcription via NF-ƙβ nuclear signaling, assembly of the inflammasome complex and subsequent activation of Caspase-1 upon binding to the ASC binding domain of the inflammasome [2]. Active Caspase-1 then begins to cleave inert cytokines such as IL-1β and IL-18 and causes the activation of gasdermin D, a transmembrane pore-forming protein, that initiates a form of cell death called pyroptosis that commences the downstream processes of inflammation. In the recent work examining the impact of various exogenous threats on Normal Human Epidermal Keratinocytes, employing the Promega Caspase Glo1 Assay, the original data indicated that after the cells were exposed to both UVB radiation and ATP, within the first 3 hours after exposure there was no appreciable increase in the expression of active Caspase-1 [1].

However, after 20 hours, the two exogenous influencers caused a statistically significant, dose-dependent increase in active Caspase-1 release indicating that somewhere between 3 and 20 hours, the exogenously treated cells began to express active Caspase-1 without an apparent initial priming step. It appears that the NHEKs were self-priming the release of active Caspase-1 without the initial anticipated priming requirement of messaging from the Toll-Like Receptors. Recently, Gritsenko et al., published work suggesting that human monocytes could be self-primed to express active Caspase-1 when exposed to the LPS nigericin [3]. This work was one of the first papers to suggest that human cells might be able to form canonical inflammasomes without the need for a priming step. Such findings are fundamentally important as they suggest these critical defense mechanisms may develop through yet not completely understood processes that do not require an initial priming step through the Toll-Like Receptors to initiate the innate immune inflammation response. It suggests, instead, that the inflammasomes themselves may be the primary initiators of the cellular release of active Caspase-1 under certain circumstances. Certainly, when considering the role of various cells that face external threats such as epidermal keratinocytes or lung epithelial cells, which are now known to respond to the SARS-CoV-2 virus by inflammasome activation, whether the cells need a priming step or not is important to understanding not only the role of inflammation in the body, but more importantly, how various cell lines may operate differently depending on their needs [4].

It may be that cells that are in direct contact with exogenous threats like epidermal keratinocytes, and eye, throat and lung epithelial cells may respond more directly to threats by direct induction of the innate immune response while other more downstream immune cells may require some type of priming step to activate. This makes some sense as the body would not want to have its adaptive immune response “turned on” all the time without some element of feedback control like a priming step. One the other hand, cells prone to contact with external threats like energy (UV), chemicals (ozone or PM2.5 particles), or microbial or viral threats, all of which have been shown to initiate inflammasome activation in NHEKs, might need to respond more directly to the threats. All of this may sound a little like how many angles can dance on the head of a pin, but it may also be critical in life threatening diseases such as COVID where treatments are being developed that can help suppress the NLRP inflammasome response that can lead to sepsis while not completely shutting down the inflammation response needed to clear the viral threat. In skin, it is known that most cells associated with the epidermis and dermis can express NLRP inflammasome proteins and they can likely act as initiators of the innate immune response. When discussing topical treatments that may impact inflammasome induced effects, particularly the processes that can lead to prolong inflammation and the aging process called inflammaging, better understanding of the mechanisms by which the cells respond can make topical therapeutics and cosmetics more effective treatments.

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A Novel Methodology for Correction of Cosmetic Problems via Secondary Eyebrow Transplantation - Juniper Publishers

A Novel Methodology for Correction of Cosmetic Problems via Secondary Eyebrow Transplantation - Juniper Publishers

Authored by Yi Jung Lin

Abstract

Eyebrows create a very imperative and noticeable feature of the face. With increasing information, eyebrow transplant has become a prevalent technique. Though it is a small area still requires a lot of precision, knowledge and aesthetic skill regarding anatomy, designing of brows, extraction and implantation technique. In this paper, we performed many cases of eyebrow reconstuction including revision by our own implanter. The cases analyzed in this paper were corrected only by transplantation of occipical donor hair without laser hair removal nor tattoos. This article gives a comprehensive view regarding how to correct previously unsatisfactory eyebrow transplant with special emphasis on several points as hair follicle density, eyebrow shape, entire or partially reconstruction, which has become the most skillful technique.

Keywords: Eyebrow Transplantation; Implanter; Hair Follicle Density; Hypothyroidism

Introduction

Eyebrows are the most communicative feature and form a masterline of the face. It is the orientation fact concerning which all other perspectives and outlines of the face are established. Repairing eyebrows have become a reworthing procedure of hair transplant because of the increasing information and exceptional results. However, eyebrow transplant requires a high degree of skill and experience, not to mention the reconstruction transplant under the condition of previously unsatisfactory eyebrow transplant. With the extensive experience of the author in the field of follicular unit extraction (FUE) and follicular unit transplant (FUT)/strip, especially in aesthetic facial hair restoration, it is feasible to perform high-quality surgical techniques creating satisfactory results and a happy outcomes to patients after previously eyebrow transplant under comprehensive communication.

Procedure evaluation before the transplant

Cosmetic is the most common signs of eyebrow transplant such as inherited absence or insufficient coverage, of a normal appearing eyebrow requiring darker colour or an uneven eyebrow with lack of lateral third or medial portion. The other uncommon indications are trichotillomania, scar due to trauma, burn or tumours, stable alopecia areata, madarosis due to hypothyroidism, leprosy, etc. [1]. Although a correct candidate is one who has accurate expectations, understands limits in density achieved, has a pronounced defect than purely cosmetic purposes and stable or treated disease, the patient still expects a near-perfect surgical result. Even well awaring the difficulties of the reconstruction of eyebrow transplant, after seeing the patients undergoing previous surgery, showing an extremely depressed and anxious state, the authors had to try to deal with the cosmetic problem secondary to previous eyebrow transplant.

Methods

The outline of the eyebrows comes from the arrangement and display of each hair follicle. The qulity and survival rate of the follicles implanted decide the appearance of the eyebrow. FUT/ strip with long hair has long been used using single or small hair grafts for brow transplant [2,3]. Persuing grafts of high quality, Graft quality index (GQI) of grade 1, can present the shape of the eyebrow more accurately. We prefer FUT with long hair to control the qulity of grafts, especially a grade 1 of GQI [4], and only a high surviral rate of hair follicle could show a beautiful outline of eyebrows. We use DIMIS-T 100A of high solution of digital Microscope and Samsung LED monitor for follicle dividing. Despite preparing graft using a dissecting microscope gives the dividing a little slower, however, it is worth the effort and much more perfect.

Case Analysis

Entire reconstruction

The patient received eyebrow transplantation by body hair (leg hair) one year before visiting the clinic. Occasionally, the implanted body hair was too thin and too sparse to connect the original eyebrow hair to present an intact curve. This time, we used the occipital donor hair to make an entire reconstruction. And the result gets more complete than the body hair (Figures 1 & 2).

Partially modified

The patient received eyebrow tattoo before eyebrow transplantion resulting in eyebrow hair lost and fibrosis under eyebrow area noted afterwards. She requested eyebrow implantation and liked it to go unnoticed. After the first implantation, partial eyebrow tail didn’t grow well. We checked the direction and quality of the eyebrow head and made a consecutive curve of the eyebrow. The result of integral contour presented after secondary remodification (Figures 3 & 4).

Shape adjustment

Some patients intend to change their eyebrow shape after transplantation. The stretching points of the eyebrow contour are mostly affected by the spots of brow’s peak. If the peaks’ position beyond the lateral canthus, the patient will appear angry and old look. Trying to enhance both brow heads and closer to the middle nose, it will lower down the arch of the eyebrow’s contour. After adjustment and strengthening the heads of the eyebrows, it would make the face appearing kinder, gentler, and more pleasant (Figures 5 & 6).

Density problem

The contour and shape of the eyebrow are built by several hundred hairs. To implant several hundred hairs onto this limited area is really an arduous and skillful technique. However, the patients often desire the evenly displayed eyebrow hairs without any interspace for the better homogeneous presentation. We used single hair and small 2- hair grafts interspersing in the original hairs, making it look more pleasing and homogeneous (Figures 7 & 8).

Curl direction

Generally, most common problems are related to direction and curl, colour and texture mismatch or lack of regrowth [5]. Despite of the shape design and point location, the curl direction is an important factor to make up the image of the eyebrow. Reverse or crooked direction would damage the smooth curve of the eyebrow. To remedy the interference of the bad curl, we implant more and thicker hairs inside and beside them to ease off the visual effects of the undesired curl directions as much as possible (Figures 9 & 10).

Shaft diameter

Compatible hair qualities are necessary in eyebrow revision, even though it is unreasonable in some case. Selection of shaft diameter is related to the eyebrow even face image before surgery. Thus, selecting compatible shaft diameter is important factor in eyebrow revision. It is more important to check the eyebrow shaft of previous implant by trichoscopy before eyebrow transplant, it could find a better reference for revision [6] (Figures 11 & 12).

Low survival rate

FUE is popular in recent years. Howeveer, unskilled physicians may have undesirable consequences. The patient received FUE eyebrow transplant one year before coming to our clinic. Unfortunately, the implanted follicles from FUE presented extremely low survival rate. And owing to the short shaft of follicle is difficult to orient the hair flow, the hairs growed in odd directions. Because of poor survival rate and different hair flow, it will not present a smooth curve of the eyebrow at all. The affected area is too large for the patient to distinguish between old and new hairs. So, the author has to implant the eyebrows with very high density to facilitate the patient trimming (Figures 13 & 14).

Post-operativecare

The patients are instructed not to wash the face and doing make-up on the periorbital area from the next post-operative day until all crusts have fallen off, about ten days after. After ten days, the implanted hair will start to fall off and nearly all brow transplanted hair fall due to anagen effluvium [7] until two months. Hair regrowth begins at 3-5 months. In next 6-8 months, number increases with more density.

Conclusion

The revision of eyebrow restoration is even more challenging than the virgin eyebrow implantation. The details include low follicle density, peculiar hair curl directions, unnatural looks, unsatisfied shapes, hair qulity and so on after implantation. Inspite of the above, sometimes it still varies regarding the personalities of the patients. To keep careful and conservative communication with the anxious patients is a main determinant before making decision. Overall, with the use of highest standards of techniques and with increasing experience, we provide excellent and beautiful results with patient’s accurate anticipations.

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REGENERAGE® Cream Anti-aging Effect in Women

Summary

Introduction: The skin aging, in addition to the general guideline of the whole organism, is negatively influenced by various internal and external factors that can accelerate and modify it. There are several anti-aging therapies, including those for topical use with greater acceptance among users. Bioquantine® is an innovative product with regenerative properties that has been added to REGENERAGE® cream.

Objective: To evaluate the REGENERAGE® cream anti-aging effect in 12 women.

Material and Methods: Exploratory clinical trial, randomized, double-blind, placebo-controlled parallel group. Ten healthy volunteers with a diagnosis of facial photo-aging were included. They were randomly assigned to the REGENERAGE® cream in half of the face and placebo cream in the other; The study products were applied every day in the morning and evening, for 12 weeks. Baseline evaluations were carried out in week 6 and 12 of: the surface of the living skin (SELS, Surface Evaluation of Living Skin) with the VISIA equipment, clinical scales, as well as irritation and safety parameters (Figure 1).

Results: The patients had an average age of 44 ± 3.9 years. The surface parameters of living skin: superficial spots, wrinkles, texture, pores, deep spots, redness and porphyrins, showed no statistically significant differences at 12 weeks with respect to the baseline; in addition, no differences were observed between groups. The UV spots parameter had an average improvement after 12 weeks of 17% in the REGENERAGE® group and 24% in the placebo group, p<0.05; No differences were observed between the groups. In irritation symptoms: 1 patient reported redness, other pimples and in 2 cases of skin burning when the study product is applied; all of mild intensity. The overall satisfaction of the sub-researcher was: “regular” 50% (n=5), “good” 40% (n=4) and “bad” 10% (n=1). The overall satisfaction of the study products by the patients was: “good” 50% (n=5), “very good” 40% (n=4) and “excelent” 10% (n=1). There were no adverse events.

Introduction

The decrease in mortality and the consequent increase in life expectancy, contributes to more people surviving to advanced ages, which increases the size of the cohorts that move along the successive steps of the age pyramid [1]. Unlike the chronological aging that can be studied by intrinsic biological processes, the skin is influenced by external factors such as sun exposure and environmental pollution that affect it negatively [2]. Over the

years, physical attractiveness and social status are strongly correlated, since in our society a youth aspect confers economic and social advantages [3]. Anti-aging medicine is as old as the history of mankind. From the first civilizations there is evidence of a constant search to find a “potion” so as not to grow old. In ancient Egypt, olive leaves were used to increase beauty and extend life, while Ayurvedic medicine in India developed diets, lifestyle changes and specific herbs for the same purpose [4]. It is clear that topical treatment with cosmetics can help improve facial aging problems, in particular, by improving pigmentation, general skin tone, surface roughness, fine and deep wrinkles, diffuse redness and stains [5]. Based on what was previously described, the present study was carried out to evaluate the anti- aging effect and safety of the REGENERAGE® cream, which contains Bioquantine® as the active substance.

Participants

Mexican women over 18, residents of Jalisco, were invited to participate in the study with diagnoses of facial aging. Patients were included who voluntarily agreed to participate in the study by granting the signature of informed consent, clinically healthy, with a Fitzpatrick ́s I-IV phototype and at least 2 points deep in the surface wrinkles on the Griffiths scale. Likewise, they should be outpatients, with a negative pregnancy test and because of the nature of the study, they should be able to read, write and complete questionnaires. Pregnant or lactating women were not included, those who had no contraceptive method; were in treatment with other products or anti-aging therapies 6 months prior to the start of the study (antioxidants, botulinum toxin fillers, laser therapies, firming or facial therapies and/or neck with energy-based equipment). Nor those with use of Cosmetics with anti-aging products at least 2 weeks prior to the start of treatment (antioxidants, retinol, retinoids, alpha hydroxy acid, peptides, growth factors) Administration of hormonal contraceptives, autoimmune diseases, history of chronic skin allergies, skin cancer, or rosacea, as well as active lesions at the site of application, hypersensitivity to the study products, atopic dermatitis and chronic degenerative diseases such as type 2 diabetes mellitus, systemic arterial hypertension, renal insufficiency or a history of smoking [6].

Visits and procedures: In general, the study was divided into 4 visits, in which the clinical and photographic evaluations of the patients were carried out.

Informed consent: All procedures and study requirements were explained to the patients before any intervention. The signature of the participants and two witnesses was obtained. A copy was delivered to the participants

Internal code: All patients were assigned an internal personal identification number to guarantee confidentiality throughout the study, for logistic aspects, as well as for the analysis of the information. Eg PEC-19.001.

Clinic history: A medical history was developed based on NOM-004-SSA3-20126. Likewise, we inquired about previous diagnoses, treatments, allergies and hypersensitivity to the products in the study.

Vital signs: Seating blood pressure, heart rate, respiratory rate and body temperature were evaluated.

Pregnancy test: Patients were asked to grant a urine sample in a plastic container and the presence of chorionic gonadrotropin was determined by a rapid test [7].

Review of inclusion and exclusion criteria: With the activities carried out during the visit, the decision was made to invite the patients to participate in the research protocol.

Dermatological clinical history: A detailed dermatological medical history was developed that included physical examination of the skin with emphasis on the region of the face and neck.

Clinical scales of photoaging: The clinical signs of facial skin photo-aging were evaluated according to the scales (Table 1).

Digital photographic record: Digital photographs of the face were taken with the VISIA equipment (VISIA Complexion Analysis (Canfield Scientific, Fairfield, NJ, USA) in three projections: right, left and frontal oblique (Figure 2).

Review inclusion and exclusion criteria: With the activities carried out in this visit, the decision was made to randomize the patients.

Assignment study code: A unique study code was awarded to each patient with which all the information generated during their participation in the study was identified. Example: REG-001. Likewise, this code corresponded to the randomization of the treatment received.

Deliver study products: According to the unique identification code, 2 packages were delivered: one marked with the legend “1Right” and another with “2-Left”, which by the randomization process could contain either of the two study treatments (Table 2) (Figure 3).

First dose application of medication: The correct way of applying the study products was explained and doubts were resolved. The first dose was applied in the office (Figure 4).

Daily Patient Delivery: A diary was delivered where they should record every day: date, time of application, symptoms or signs of irritation, adverse events, as well as medications or concomitant therapies.

Schedule the appointment week 6: After carrying out the activities of this visit the next one, corresponding to week 6, was schedule. Follow-up activities. Vital signs were taken, inquired about the presence of adverse events, concomitant medications, study deviations and accounting of the study products.

Survey of irritation: Patients were questioned about symptoms of irritation with the study products.

Daily Patient Delivery: When no elimination criteria were presented, the patient’s second diary was delivered and the appointment was scheduled for week 12.

Overall satisfaction survey for patients: Additionally, the patients answered the satisfaction survey of the study products.

Global satisfaction survey for sub-researcher: After the clinical and photographic evaluation of the patients, the subresearcher answered the satisfaction survey of the study products. Patients were graded for their participation in the study, an original sample of the REGENERAGE® cream was delivered and it was recommended to continue with the sun protection measures [8] (Figure 5).

Ethical Considerations

i. This protocol was reviewed and evaluated in the methodological, scientific and ethical aspects, by the Research Ethics Committee and the Research Committee of the Jalisco Institute of Clinical Research S.A. of C.V.; which, granted the approval opinion, on July 9, 2019, with Folio number 1068, which was valid throughout the trial.

ii. The study was submitted to the Jalisco Ministry of Health and was verbally notified that by modification in the internal processes, folios of the State Research Registry are no longer granted to protocols that are not from a federal entity.

iii. In accordance with the Regulations of the General Law of Health in the Area of Health Research, Second Title, Chapter I, Article 17, was considered with a greater risk than the minimum [9].

iv. This protocol was conducted according to the regulations established in the Declaration of Helsinki (59th General Assembly, Seoul, Korea, October 2008). It also adhered to the guidelines of Good Clinical Practices and the International Harmonization Conference on Technical Requirements for the Registration of Medicinal Products for Human Use.

v. The patients received standard medical care and in accordance with the Mexican Official Standard of Pharmacovigilance (NOM-220-SSA1-2012) there were no serious adverse events [6].

Overall objective: To evaluate the anti-aging effect of REGENERAGE® cream in Mexican women.

Specific objectives

a. Determine on the face surface parameters of living skin (SELS, Surface Evaluation of Living Skin): superficial spots, wrinkles, texture, pore, UV spot, deep spot, red area and porphyrins with the use of REGENERAGE® cream in Mexican women.

b. Evaluate the aging parameters on the face with the Glogau and Griffiths scales with the use of REGENERAGE®cream in Mexican women.

c. Evaluate the signs and symptoms of irritation with the use of REGENERAGE® cream in Mexican women.

d. Evaluate the overall therapy satisfaction with the use of REGENERAGE® cream in Mexican women.

e. Evaluate the safety by spontaneously reporting adverse events with the use of REGENERAGE® cream in Mexican women .

Hypothesis: H1= REGENERAGE® cream has an anti-aging effect in Mexican women.

Independent variables: Administration of REGENERAGE® cream or placebo.

Dependent Variables: Surface stains, wrinkles, texture, pore, UV spot, deep stain, red area, porphyrins, Glogau and Griffiths scales, irritation scale, adverse events, Global Satisfaction Therapy Scale (Researcher / Patient), adverse events.

Efficacy analysis: Efficacy was determined in the complete analysis set (per-protocol) of women, which is defined as all randomized patients. All results were analyzed according to the allocation of randomized study products.

Security analysis: Safety analysis was performed in all randomized patients who received ≥ 1 dose of the researched product. For the safety analysis, patients were grouped according to the allocation of randomized study products.

Sample size: Because it is an exploratory study, no sample size calculation was performed. Randomization. The assignment of treatments was carried out by generating a random number table in Excel, specifying the number 1 as a lower rank, and the 12 as the top rank, group A and group B. Thus, each generated number was assigned one of the two treatments: 12 REGENERAGE® and the following 12 to placebo. For each treatment, according to its random number, the code REG-n and legend “1-Right” “2-Left” was assigned.

Blinding: The study was conceived as double blind, in which neither the sub-investigator / clinical coordinator nor the patient knew which study product was being administered. The study products delivered had the same characteristics in any of the study groups and were labeled with the following information: Protocol identification number, Research Center, Identification code and sequential number, Date of Expiry.

Terms of use: The following legends: “External use on skin”, “Sale is prohibited”, “Exclusive use of clinical protocol patients”, “Do not use in children or pregnant women”, language in Spanish and Alert symbols or pictograms.

Effectiveness evaluation. Quantitative variables were expressed in average, median, standard deviation and ranges. Vital signs and anthropometric parameters were evaluated using parametric statistics with the T- Studen test to find differences between visits and groups. On the other hand, the response data were evaluated with non-parametric statistical tests. Analysis was performed with the Wilcoxon test to evaluate the differences between treatments over time. The Mann-Whitney U test was used as post-hoc to evaluate the differences between the study groups. For qualitative variables, these were expressed in% and were compared by means of the Chi2 test. It was considered that there were significant differences when p <0.05.

Safety assessment: The safety criteria that were evaluated to establish intra and/or differences between treatments are described below. Safety was evaluated by the clinical review of all relevant parameters, including adverse events, irritation parameters and vital signs. The number of cases that presented adverse events, the number of cases directly related to the study drugs, and the percentage of cases that resulted from these incidents were calculated. These frequencies were compared between treatments using the Chi test [2]. It was considered that there were significant differences when p <0.05.

Results

Flow of participants: Fifteen women were invited to participate in the study. 5 were not included, because they did not comply whit the criteria. For the assignment of the study treatments, 10 women who comply whit the criteria were randomized and signed their informed consent. In this way, 10 treatments were applied in one side face and another 10 treatments in the opposite side face. There were no follow-up losses in any patient and the groups for the final analysis were distributed as follows: 10 REGENERAGE® treatments and 10 treatments to the placebo group.

Recruitment: First patient inclusion date: August 9, 2019. Last patient closing date: November 23, 2019.

Demographic characteristics: 100% (n=10) of the patients were women. The average age was 44 ± 3.9 years. The level of education was mostly bachelor’s degree in 90% (n=9), followed by 10% high school (n=1). 90% (n=10) of the patients were active workers with administrative activities and 10% (n=1) trader.

Effectiveness

Surface parameters of living skin: In the efficacy analysis performed for the face surface evaluation parameters for each of the study groups, the percentages of the baseline measurements were compared against the percentages of the final measurements and statistically significant differences were observed for both groups in the percentage of UV spots. On the other hand, when the percentages of the differences in the evaluations between the two groups were analyzed, no statistically significant differences were found between the study groups.

Glogau scale: Regarding the classification of facial aging with the Glogau scale, it was observed that at the beginning of the study, the majority of patients 70% (n=7) were classified as type III and the 30% (n=3) type II, keeping the same percentages at the end of the intervention.

Griffiths scale: In the clinical evaluations carried out with the Griffths scale, it was observed that the patients started with an overall score of 13.1 ± 2.2 and at the end of the intervention with 13.4 ± 2.5, p = NS. The average scores for each of the parameters are broken down.

Irritation: In the phone calls of weeks 2 and 4, none of the patients reported manifesting any symptoms of irritation. For the visit of week 6, in 4 patients the presence of irritation symptoms was reported. In all cases the symptom was mild and did not merit the suspension of the study products.

Overall patient satisfaction: 50% (n=5) of the patients

referred to the study products they received during the intervention as “good”, 40% (n=4) as “very good” and a patient 10% described it as “excellent” (Figure 6).

Adverse events: There were no adverse events in the entire study. Likewise, the administration of concomitant therapy was not reported.

Adhesion to treatment: No deviation was presented with the study products. All patients complied. > 80% of the applications of the study products were made in 12 weeks.

Conclusion

a. Differences were observed at the end of the intervention with respect to baseline in both study groups, in the UV spot parameter; probably by the joint administration whit sunscreen.

b. In the parameters of the live skin surface, scales of Glogau, Griffiths and irritation, no statistically significant differences were observed between the groups.

c. The study patients and the sub-researcher felt satisfied with the study products.

The administration of REGENERAGE® cream on the face for 12 weeks proved to be a safe topical treatment in the anti-aging management of Mexican women. 

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A Young Woman with Coomb's Positive Severe Haemolytic Anaemia and Hodgkin Lymphoma that Responded Completely to Rituximab: A Case Report

Abstract

Introduction

Lymphoma has been historically divided into a Hodgkin and Non-Hodgkin variety. There are reported cases of Hemolytic Anemia in Non- Hodgkin Lymphoma but Hodgkin Lymphoma very rarely also present with Hemolytic Anemias.

Case presentation

A 27-year-old African woman presented with chronic fatigue, dyspnoea, jaundice and Splenomegalie. Her blood work revealed severe anaemia (haemoglobin, 4.9 g/dl) with biochemical evidence of haemolysis. A direct Coomb's test was reported positive. A biopsy of the lymph nodes in the neck confirmed Hodgkin Lymphoma. Initial therapy consisted of intravenous methyl prednisolone and switched over to Oral Prednisolone. However, the patient came back with raised sugar levels and there was no clinically response. The patient continued to have lower hemoglobin levels and was transfused blood repeatedly. She was started on chemotherapy with ABVD regimen and after literature review, on Intravenous Rituximab 375 mg/m2/week. The patient's hemoglobin started to rise after two doses of Rituximab therapy and completely stabilized.

Conclusion

This is the one of the rare reported case of autoimmune haemolytic anaemia that went into complete remission with rituximab after no clinical or biochemical response to Steroid Therapy. We demonstrate here that severe haemolysis associated with autoimmune haemolytic anaemia in Hodgkin Lymphoma can achieve complete clinical and biochemical response with Rituximab therapy when not amenable to steroid therapy.

Keywords: Rituximab, Haemolytic anaemia, Hodgkin lymphoma

Abbreviations: AIHA: Auto-Immune Hemolytic Anemia; HL: Hodgkin Lymphoma; LDH: Lactate Dehydrogenate; IgG: Immunoglobulin G; CT: Computed Tomography

Introduction

Though autoimmune hemolytic anemia (AIHA) is seen in Chronic Lymphoid Leukemia and Non-Hodgkin Lymphoma, it is rarely seen in Hodgkin lymphoma (HL) patients [1].‘The presence of a positive direct Coombs test in the patient with Hodgkin’s disease suggests active and advanced disease”[2]. Autoimmune haemolytic anaemia (AIHA) is one of the most common causes of acquired haemolytic anaemia [3]. Treatment options for AHIA patients include treating the underlying lymph proliferative disorder with cytotoxic drugs, radiotherapy and corticosteroids. Treatment with Rituximab has emerged as a new alternative with good response [4].our case report demonstrates the effectiveness of this therapy.

Case Presentation

A 27-yr old pre-menopausal lady with a history of chronic alcohol abuse presented to the outpatient clinic with complaints of 'Feeling Weak', fever, blurred vision of 10 days duration. The patient had sinus tachycardia of 120 beats/min with a blood pressure of 100/60 mmHg and a respiratory rate of 22/min. She was a febrile. She complained of loss of weight and loss of appetite. She also complained of fever and night sweats. She is married with two young children and had stopped breast feeding her young three months back. The patient had good social and spiritual support but did feel drained physically and emotionally.

She had irregular menses with reduced flow and lasting only two days. She was seen by the physician three months earlier with similar complaints and a severe anaemia of 4.9 g/dl. She was started on steroid therapy after a combs test came positive for IgG. She was referred to the oncologist as an examination revealed multiple lymph nodes in the axilla on the right side. Her physical examination was remarkable for severe pallor, shifting dullness, Splenomegalie and bilateral lower-extremity pitting oedema. There were multiple lymph nodes in the right axilla the largest of which measured 6cms.

The complete blood count revealed anaemia with a haemoglobin level of 7.1 g/dl, a normal reticulocyte count, Red blood cell count of 2.04 x 106/|il and normal white cell and platelet counts. Lactate dehydrogenate (LDH) was elevated with a value of 410 U/L. Peripheral smear reported Red blood cell agglutination, microcytic and anisocytosis with Leucopoenia. The direct Coombs test was positive for immunoglobulin G (IgG) antibody. The Renal Function tests were normal. Liver function tests were significant for an elevated total bilirubin level of 36 μmol/L, a direct bilirubin level of 13.9 μmol/L.

Tests for Hepatitis, Human Immunodeficiency Virus, AntiNuclear antibody and Anti-Smooth Muscle antibody were negative. Ultrasound of the abdomen and pelvis revealed a large spleen measuring 13.28cms. Computed tomography (CT) of the chest, abdomen and pelvis confirmed Splenomegalie with multiple lymph nodes in the Right Axilla. The biopsy of the lymph nodes revealed Reed Sternberg Cell diagnostic of Hodgkin Lymphoma which was Lymphocyte Depleted Reticular Subtype (Table 1).

Results

The patient had undergone transfusions with several units of packed cells and was on twice daily doses of oral prednisolone 10mg. After corticosteroid therapy, the patient's haemoglobin improved only marginally, and she continued to require blood transfusions. Consequent to the initiation of steroid, her sugars started to raise with Fasting Blood sugars reaching 18.1 μmol/L. She was started on Subcutaneous Insulin twice daily After reviewing the Literature that has demonstrated benefit of rituximab treatment in haemolytic anaemia's, steroid was tapered and the patient was started on rituximab therapy at a dose of 375 mg/m2 every week.

A total of four doses were administered over a period of four weeks. The patient showed marked clinical improvement after two weeks of therapy and had the haemoglobin rise to 13.7 g/dL at the end of the four weeks. Subsequently, steroids and insulin were stopped completely as her Fasting Blood sugars normalised. She continued with her monthly chemotherapy cycles and had complete resolution of all the disease. After four months of Rituximab Therapy, her haemoglobin remained at 13.3 g/dl. On follow up after six months of therapy, her haemoglobin remains at 13.8 g/dl and she is completely symptom free.

Discussion

Haemolytic Anaemias with an underlying proliferative disorder have been treated with various drugs and radiotherapy [5,6]. Literature review suggested that the first line of treatment has always almost been a corticosteroid [7,8]. Rituximab is a monoclonal antibody which is active against CD20 and has been used in the treatment of CD20 positive Non-Hodgkin lymphoma and Lymphocyte dominant Hodgkin Lymphoma. Rituximab has been used to treat Haemolytic anaemia who did not respond to conventional steroid therapy or had a relapse [9,10]. To the best of our knowledge, our case is a rare presentation of autoimmune haemolytic anaemia in a Lymphocyte Depleted Hodgkin Lymphoma that did not respond to steroids but showed a complete and sustained response to Rituximab.

Conclusion

It is clear from this case report that Rituximab caused complete resolution of the Hemolytic Anemia in Hodgkin lymphoma patient resistant to corticosteroid therapy and can be considered as a line of treatment in similar cases.

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Pretibial Myxedema, Nodular Variant: Unique Presentation and Clinical Course

Abstract

Literature has shown morphological diversity in the presentation and occurrence of pretibial myxedema following I-131 treatment. We present a case of a 47 y.o African American male with post I-131 hypothyroidism for Graves disease that presented with enlarging bilateral lower extremity and ankle lesions. Examination revealed firm, tender, hemispherical, large, hyperpigmented nodules. Ultrasound demonstrated nonspecific hypovascular nodular thickening of the skin. Excisional biopsy showed reactive dermal and subcutaneous fibrosis with dermal mucinosis. Alcian blue stain confirmed the diagnosis. Graves’ dermopathy is generally rare, with the nodular variant accounting for 10% of cases. Our case reflects a variable appearance of post-I-131 treatment dermopathy partially resistant to the multimodal treatment.

Keywords:Myxedema; Nodular Variant; Hypothyroidism; Dermopathy

Abbreviations: Radioactive iodine (I-131)

Introduction

Graves dermopathy is a rare entity (approximately 4%), with the nodular variant accounting for 10% of all reported cases [1]. Many patients with Graves’ disease receive radioactive iodine (I- 131) as a treatment. Literature has shown morphological diversity in the presentation and occurrence of pretibial myxedema following I-131 for Graves’ disease [2].

Case Report

A 47 year-old African American male presented with complaints of bilateral lower extremity and ankle lesions that developed after receiving radioactive ablation 20 years ago for his Graves’ disease. The lesions were causing constant discomfort and preventing him from wearing shoes. Examination revealed bilateral large firm, tender, hemispherical and hyperpigmented nodules at the distal portion of his lower extremities and ankles (Figure 1). Other findings include mild edema and Graves’ opthalmopathy. His lab tests revealed elevated thyrotropin-stimulating hormone levels at 15.94 mIU/mL and suppressed free thyroxine (T4) levels at 0.69 ng/dL consistent with his history of noncompliance. A previous ultrasound on the lesions showed nonspecific findings of hypovascular areas of diffuse nodular dermal soft tissue thickening involving both ankles. A decision to preform an extensive excisional biopsy of his left ankle lesions with skin grafting was made. Microscopically, the lesion showed reactive dermal and subcutaneous fibrosis with dermal mucinosis (Figure 2). A positive Alcian blue stain confirmed the diagnosis of pretibial myxedema (Figure 3). The excision measured 17x 7 cm.

Discussion

Pretibial myxedema, or thyroid dermopathy, is an infiltrative dermopathy occurring as a result of excess glycosaminoglycan deposition in the dermis and subcutis. This process is stimulated by thyrotropin receptor antibody-mediated cytokine release and activated Th1 cells [3]. Classical clinical manifestation includes peau d’orange appearance and non-pitting edema. These lesions are usually confined to the pretibial area but can occur at any other sites. The differential diagnosis includes erythema nodosum, keloid, and stasis dermatitis. Nodular variant of pretibial myxedema is generally considered self-limited. However, our case presents the variable appearance of post-radioactive iodine treatment dermopathy that was partially resistant to multimodal treatment approach.

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Propranolol for the Treatment of Hemangiomatosis with Hepatic Lesions: Case Report with Great Response

Abstract

We present a case of a 2 months-old male nursling with neonatal hemangiomatosis with skin and hepatic, showing great response with systemic propranolol, with good acceptance, without side effects, after a 9 months follow-up.

Keywords:Hemangiomatosis, Disseminated; Hemangioma/drug therapy; Liver Neoplasms/drug therapy; Propranolol/therapeutic use

Abbreviations: IH: Infantile Hemangioma; ISSVA: International Society for the Study of Vascular Anomalies; NH: Neonatal Hemangiomatosis; BNH: Benign Neonatal Hemangiomatosis; VEGF: Vascular Growth Endothelial Factor; DNH: Diffuse Neonatal Hemangiomathosis; FGF: Fibroblast Growth Factor

Introduction

Vascular tumors are vasculature neoplasms that present endothelial cell proliferation. Infantile hemangioma (IH) is a proliferation of endothelial cells, that develop during the first 12-18 months of life, and then involute1. The lesions may be present at birth as a precursor lesion, but practically all lesions are noticeable at the end of the first month of life [1]. Based on the latest classification by the International Society for the Study of Vascular Anomalies (ISSVA), IH are classified (according to its pattern) as local, multifocal, segmental or indeterminate [2]. The term “neonatal hemangiomatosis (NH) is used to describe the condition of multiple HI (multifocal pattern) and it is cathegorized as “benign neonatal hemangiomatosis” (BNH) and “diffuse neonatal hemangiomathosis”(DNH) [3].

BNH stands for multiple cutaneous hemangiomas without the involvement of internal organs [3]. Its growth phase occurs in the first weeks of life, later passing to the stationary phase and, finally, involution [4]. HND is defined by the identification of hemangiomas in 3 or more organ systems, it must be observed in the neonatal period, in addition to there being no evidence of malignancy [3]. Its development probably begins in the intrauterine phase and progresses along with the fetus growth. The current trend is to adopt a spectral concept and the use of the terms HN with and without visceral involvement [1].

Case Report

Two month old male nursling, born by cesarean section with 39 weeks and 6 days of gestational age, uneventful, exclusive breastfeeding up to 2 months, later supplemented with milk formula, showing adequate weight-stature gain and neuro-psychomotor development, immunizations according to schedule; comes in consultation due to reddish skin lesions, which appeared in the first month of life. Upon examination, multiple erythematous-violaceous, fibroelastic nodules, reducible to digital pressure, measuring between 0.2 and a maximum of 1.5 cm, with diffuse distribution throughout the entire integument. None of them ulcerated or with phlogosis. Apparently painless on palpation.

With the clinical diagnosis of neonatal Hemangiomatosis, ultrasound (USG) transfontanellar and total abdomen was requested, in addition to a referral to the pediatric Cardiologist for evaluation for the use of oral propranolol. Normal cardiological examination and electrocardiogram, authorizing systemic treatment. Central nervous system USG was normal, meanwhile abdominal image showed two nodules of up to 1.0 cm in the liver parenchyma, suggestive of hemangiomas. Treatment with manipulated Propranolol, 10mg / ml in suspension, at a dose of 2mg / kg / day, was started at 3 months and 5 days of age, divided into two doses, after the morning and late afternoon feedings.

Comparative photographs record the evolution of the lesions in the pre-treatment period and after 9 months (Figure 1). The patient presented involution of all skin lesions, mostly maintaining residual hyperchromia. There were no side effects related to medication. Abdominal control USG with the same radiologist considered as normal (therefore it is not possible to identify the lesions previously seen, after 6 months of medication).

Discussion

The natural history of hemangiomas is divided into 3 phases. The first phase, also called a precursor lesion, appears in the first days of life (most of which is very evident at the end of the first month of life) and can present as an anemic, erythematous and/or ecchyotic spot, grouping of red-live or telangiectasias surrounded or not by an anemic halo. The rapid growth of this phase is usually greater in the first 3 to 6 months of life, but can reach up to one year of age [5,6]. The second phase is the involutive one, which is characterized by a regression of approximately 10% of the injury per year. Ultimately, the last phase is the one that represents the involuted injury. It is expected that in approximately half of the patients it will be complete and in the other half it will present some type of residual lesion [5,6]. As it is more rare, HN does not have a well-defined natural history. Forms restricted to the skin have a good prognosis. However, it is difficult to establish who are the patients who evolved with complete bleaching of the lesions [3,7,8]. The diagnosis is clinical, and can be supported by histopathological examination when dubious or even to support indication of systemic treatment [1,5,6]. In the present case, we consider the clinical aspect and classic evolution sufficient, taking into account the cost/benefit of performing biopsy in an infant patient. The treatment of HN, especially with lesions restricted to the skin, can be expectant, individualizing according to the number and topography of the lesions [3,4,7,8]. In the present case, considering the number of lesions, the potential esthetic impairment if there was no involution, in addition to liver injury, systemic treatment was chosen.

Propranolol is the first-line treatment of HI, especially in complicated, segmental or unfavorable lesions [1,5,6]. It is used at a dose of 2 - 3 mg / kg / day, divided into two or three doses, via oral. It is effective in the first two phases of the disease as it stimulates vasoconstriction of capillaries, decreases the angiogenesis of endothelial cells, by reducing the expression of vascular growth endothelial factor (VEGF) and fibroblast growth factor (FGFb) genes, in addition to inducing apoptosis of endothelial cells6. The experience of its use in NH is small, still restricted to small reports published in the literature, being off-label. However, it finds support in its logic of use and disease mechanism, taking advantage of publications involving its use of HI [7,8].

Conclusion

We present an illustrative case of HN with skin lesions and liver damage, treated with Propranolol orally, with good acceptance, without side effects, in addition to a positive outcome in follow-up after 9 months of continuous use.

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Single Plaque-Type Chromoblastomycosis: Great and Sustained Response with Itraconazole Plus Cryosurgery

Abstract

We present a 72-years-old male patient, resident in a urban area, with a chronic cutaneous ulcer on the left forearm, diagnosed with chromoblastomycosis, treated with a combination therapy of oral itraconazole and cryocirurgery, with 6-months follow up after treatment.

Keywords:Black Fungi; Chromoblastomycosis; Chromomycosis; Melanized Fungi; Muriform (Sclerotic) Cells

Introduction

The Chromoblastomycosis (CBM) is a chronic fungal infection caused by the traumatic implantation of demeaceous fungi of the Herpotrichiellaceae family on the skin and subcutaneous cellular tissue [1-3]. These fungi are more common in tropical and subtropical areas, and can be found in the soil, in vegetation and decomposing wood [1,2]. It is more common in male rural workers, lumbermen or sellers of agricultural products [4]. Brazil is the second country in number of cases, being found throughout its entire territory [2,5].

History and Clinical Manifestations

Male pacient, 72 years, urban dweller, retired (former bricklayer), sought medical attention due to injury to the left forearm. It started 6 months earlier as a papulo-pustular lesion, wich progressed slowly and progressively to an erythematous plaque, with a rough surface; asymptomatic. Upon examination, an infiltrated, erythetous-keratotic plaque was indentified, with well-defined edges and an irregular, slightly verrucous surface, measuring about 5.0cm in the largest diameter (Figure 1). Dermoscopy indentified black dots (Figure 2). When questioned, he associated the injury with a sharp puncture trauma during the repair of the house fence. With the hypothesis of subcutaneous mycosis (chromomycosis and sporotrichosis), tuberculosis, in addition to neoplasia (squamous cell carcinoma), an incisional biopsy was performed.

Histopathological examination showed chronic granulomatous dermatitis associated with pseudoepitheliomatous hyperplasia of the epidermis. In the dermis, the presence of sclerotic cells (Figure 3), confirming the diagnosis of Chromoblastomycosis. Fungal culture isolated the demeaceous fungus Fonsecaea Pedrosoi. Treatment with Itraconazole 200mg/day for 6 months, associated with 4 sessions of Cryosurgery (local infiltrative anesthesia, tip B, intermittent jets, 2 cycles, thawing time 2 times that of freezing) at 1-month intervals. Apparent clinical cure 6 months after the end of treatment (Figure 4).

Discussion

CBM begins with a primary lesion at the traumatic fungus inoculation site, usually oligosymptomatic, delaying the demand for care [2,4]. A papule is noted, usually in areas of exposed skin, wich grows in a centrifugal manner. There may be progression of the condition due to contiguity, in addition to lymphatic and/ or hematogenic dissemination [1,2,6]. It is classified clinically in 5 types: nodular, verrucous or verruciform, plaque, tumor and scar or atrophic. Possible complications are secondary bacterial infection, elephantiasis and carcinomatous degeneration [2,6]. The differential diagnosis is made with paracoccidioidomycosis, sporotrichosis, lacaziosis, leishmaniasis, mycetomas, leprosy, tuberculosis, atypical mycobacteriosis, prototecosis, in addition to squamous cell carcinoma [2].

Epidemiology assists in diagnosis, especially in endemic areas.4 This can be confirmed by visualization of the fungus in direct examination, in tissues with histopathological examination, in addition to culture isolation.5 The sclerotic (muriform) cells are pathognomonic for CBM, regardless of the causative species [2]. The treatment is difficult, with recurrence and chronic lesions being common.6 There is no gold standard of treatment. Some options are cryosurgery, carbon, dioxide laser, itraconazole, flucytosine, terbinafine, amphotericin B, fluconazole, posaconazole, imiquimod, super-satured potassium iodide and thermotherapy, used alone or in combination. The choice depends on the age and comorbidities of the pacient, as well as the location of the lesions [5]. Cryosurgery with liquid nitrogen and thermotherapy are suitable options for isolated and limites lesions [2]. Already the antifungals that have shown greater effectiveness are itraconazole and terbinafine for 6 to 12 months, preferably in higher doses, if tolerated [2].

Conclusion

We present an illustrative case of CBM, plaque shape, in an elderly man from an urban area, with a report after questioning trauma involving a wooden and wire fence, seeking to draw attention to this entity in the day-to-day of the dermatologist even if outside endemic area and without typical epidemiology. In parallel, a good therapeutic result is demonstrated with the association of surgical and medication techniques, which are accessible and well tolerated.

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Importance of Psychiatric Evaluation and Patient Selection in the Field of Cosmetic Dermatology

Introduction

Cosmetics is an ever-increasing component of every-day practice for dermatologists. However, as elective procedures such as neuromodulator injections, dermal fillers, and body contouring have pushed their way into most dermatology practices, little objective research has been done to identify ideal patients to undergo these procedures. It is the opinion of these authors that objective studies to evaluate the pre and post procedural psychologic well-being are essential to identify patients who may have an underlying and undisclosed psychiatric illness that is contributing to their decision-making process. This issue is further complicated by the plethora of cosmetic day-spas that offer these services without physician oversite or ethical obligation to responsibly select candidates. One example regarding the importance of patient selection is exemplified by patients with body-dysmorphic disorder (BDD) - a condition in which the subject has a fixation with one or more perceived flaws in their appearance.

Some studies have reported as high as 12% of patients seen in a dermatology clinic are afflicted with this disorder, and it is our opinion that part of the solution in managing patients such as this is through proper identification and preventing unnecessary procedures that may serve to reinforce their delusion [1]. Furthermore, the rapid growth of sensitive cosmetic procedures such as non-surgical penoplasy is a relatively new field in which previously developed procedures are being creatively applied in ways that are wholly unstudied with regards to the appropriate patient populations. We feel that in order to responsibly select patients, a simple screening tool used for pre and post procedure evaluation of their happiness and/or psychologic well-being would serve as a simple way for clinicians to help monitor their patient’s satisfaction while preventing procedures on patients who may never be satisfied. There are very few studies which use such tools, most of which only assess post-procedure scores. Of the limited studies available, some scoring systems that have been used include the Happiness Measures Scale, FACE-Q, and Derriford Appearance Scale (Litner). [2-4] Of course, without any reports of studies that evaluate the patient’s perception of their problem both before and after a cosmetic procedure, clinicians will not have a baseline in which to compare their patient’s results.

Conclusion

In summary, the field of cosmetic dermatology is growing rapidly and can be expected to continue this trend for years to come. It is the responsibility of the physician to understand what is driving their patient’s decisions and interpret if there is a psychiatric illness contributing. In order to do this, we feel there must be an objective means to measure dissatisfaction and satisfaction before and after any cosmetic procedure is pursued with emphasis on pre-procedure evaluation.

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Visual Properties of Striae Distensae of Chinese Women

Abstract

Background: Striae Distensae (SD) or stretch marks are manifestations of epidermal atrophy that would arise from a combination of hormonal factors and mechanical stretching and that are characterized by distinct microstructural features. The objective of this in vivo study was to investigate the biophysical properties of recent versus old SD in a Chinese population.

Methods: A cohort of 110 Chinese women, aged between 21 and 45 years old, were recruited. Fifty-five presented recent and inflamed SD while the other 55 volunteers suffered old and scarred SD. Morphological characteristics and anatomical distribution of the SD were evaluated by a trained expert. Contrast, entropy and anisotropy of SD were obtained from cross-polarized images and skin glossiness was computed from parallel and cross-polarised images. Spectrocolorimetric data were used to calculate colour and estimate chromophores concentration in SD and in adjacent normal skin.

Results: 98.2% of the volunteers claimed their SD are due to pregnancy. They were mainly located on the abdomen (93.6% of women), the thighs (72.7%) and the hips (83.6%). The recent SD are significantly darker (L*) and redder (a*) than old ones. These colour differences correlate to a higher concentration of skin chromophores in recent SD. Texture contrast is also more important in recent SD but old SD are brighter while there in no differences in skin texture complexity nor in the directional properties between recent and old SD.

Conclusion: The visual contrast of SD can be related to chromophore distribution (recent) or light scattering (old).

Keywords: Striae Distensae Visual Properties Colour Chromophore Texture

Introduction

Striae distensae (SD) or stretch marks are common linear skin scars accompanied by epidermal atrophy [1]. They appear during pregnancy, adolescence, obesity, weight loss, bodybuilding, cachexia or in conditions associated with extensive corticosteroid use [1-4] Areas most commonly affected are the abdomen, breasts, buttocks, hips and thighs [1,5]. Despite being of no medical importance, they are an important cosmetic concern: their occurrence can be as high as 88% of pregnant women [6] and they cause significant psychological burden to many patients [4].

At the onset, the lesions appear as erythematous and inflammatory streaks (striae rubrae), oriented perpendicular to the direction of skin tension which, over months to year, mature into striae alba: atrophic, wrinkled, hypopigmented and permanent scars [7-9]. Even if the exact cause remains unclear, they would arise from a combination of hormonal factors and mechanical stretching due to rapid tissue expansion [10]. This expansion results in the reduction, thinning and disorganisation of the elastic fibre network due to elastolysis mediated by infiltrating mast cells and macrophages [11-13]. At early stages, SD formation also involve oedema in the dermis whilst striae albae are less vascularised [14].

Despite the advances made in the characterization of SD at the molecular level, their objective clinical grading by an easy to use, reproducible, and non-invasive methods is still a challenge [15]. Therefore, the objective of this study is to better characterize the biophysical properties of recent versus old SD using objective non-invasive methods. We also decided to focus our study on Chinese women, a population for which only few data are available

Material and Methods

Population

A cohort of 110 Chinese women from the city of Wuhan and its surrounding (Hubei province, Central China) was recruited after signing a written informed consent. The age of the volunteers wasranging between 21 and 45 years old. Fifty-five of them (mean age = 28.5 years old) suffered recent (less than a year in 95% of the cases) and inflamed SD while the other 55 volunteers (mean age = 35.9 years old) presented old (more than a year-old in 85% of the cases) and scarred SD.

Clinical scoring of SD

Morphological characteristics and anatomical distribution of the SD were evaluated by a trained expert. The study focused on the abdomen, the breasts, the thighs, the hips and the arms where the number, the length and the width of SD were determined. A 109 items questionnaire was also used to identify the origin of the SD and their influence on self-appreciation of the volunteers’ body.

Visual and spectrocolorimetric analysis of SD

The visual properties were investigated with a digital camera system using controlled polarised light conditions (Nomad, Newtone Technologies, France). Texture of SD was evaluated in term of roughness, regularity and isotropy. Roughness and regularity are quantified using, respectively, the contrast and entropy parameters described by Haralick [16]. These parameters are obtained by the computation of co-occurrence matrix. This statistical tool measures the distribution of grey levels in the image, or in a given region of interest, and highlights the frequency and regularity of a colour to detect a possible pattern. The contrast, which measures local variations of grey levels is defined according to the following formula:

Where, Pi,j is the co-occuring value of a pair of pixels withspecific values (i and j) and in a specified spatial relationship occur in an image; and where N the number of rows (i) and columns (j) of the co-occurrence matrix. With this formula, contrast decreases when the texture becomes smoother. It is equal to 0 when all image intensities are identical.

Entropy reflects the complexity of texture. It decreases when the texture becomes more regular and is defined as follow:

Skin texture anisotropy was measured to determine the homogeneity in the orientation of the skin texture at the level of SD. For this purpose, a tensor image is computed from the cross-polarized image. This image allows visualization of skin lines orientation from a 2D image. The anisotropic coefficient is quantified according to Zahouani et al. [17]:

To calculate specular glossiness, a gloss map was generated by compensating parallel and cross polarized images exposition and computing the difference between them. Glossy pixels were extracted from the gloss map using an automatic threshold method [18] (Figure 1). Their value was averaged to obtain the specular glossiness value, value that increases when the skin is glossier. Finally, reflexion spectra of SD and adjacent normal skin were acquired using a CM 700d spectrocolorimeter (Konica Minolta Sensing, Japan). Spectra were used to calculate the L*, a*, b* colour parameters [19 and the ΔE colour difference parameter [19]. They were also used to calculate oxy , deoxy hemoglobin and melanin concentrations [20] in SD and to compare to those of adjacent skin.

Statistical analysis

Data are expressed as mean ± standard deviation. Statistical comparisons were performed using paired or unpaired Student’s t-test (significance level at a = 0.05) following confirmation of normality of the data distribution using the Anderson–Darling test

Results

The cohort recruited shows “normal” clinical scoring of SD

The SD of the 110 Chinese women volunteers were mainly located on the abdomen (93.6% of the women), the hips (83.6%)and the thighs (72.7%). Only 6.4% of the women presented SD on the breasts and 3.6% on the arms. For 98.2% of the volunteers, SD were due to pregnancy. Only one woman claimed they were due to body development and another one to weight gain.

Clinical grading (Table 1) reveals no differences between women harbouring recent or old SD: the average number of SD on each zone is similar as well as the length or the width of SD. Finally, self-assessment of the impact of SD on appreciation of the volunteers’ body confirms their negative influence: 58% of the volunteers claimed having a rather negative image of their body, SD bother 68% of them for the image they have of themselves and 81% of them for the image they present to others. Finally, SD influences the way 65% of the volunteers dress.

While old SD have similar colour than adjacent normal skin, recent SD are darker and redder

Initial comparison of the skin’s L*, a*, b* parameters obtained by spectrocolorimetric analysis show that the two groups of women have normal skin with significantly different colour L*, a* and b* parameters (Figure 2 - ΔE = 2.65). Therefore, our analysis focused on the colour difference between SD and adjacent normal skin within each group. This analysis shows that while there is no significant difference in the L*, a*, b* parameters between old SD and adjacent normal skin, there are differences between recent SD and adjacent normal skin (Figure 2). Recent SD are 5.4% darker (p < 0.0001) and 35.3% redder (p < 0.0001) while there is no significant difference in the yellow-blue b* parameter (p = 0,099).

Oxy-, deoxy-hemoglobin and melanin concentrations are higher in SD than in normal skin, but the difference is more important and more significant in recent SD

To gain possible insight in the underlying colour differences between recent and old SD we used the spectral data acquired with the spectrocolorimeter to compute the concentration of oxy-, deoxy-hemoglobin and melanin. Again, to avoid effect due to normal skin colour variation between the two groups, the analysis focused on the comparison between SD and adjacent normal skin. Results show (Figure 3) that the amount of oxy-, deoxyhemoglobin and melanin is respectively 12.1% (p = 0.0018), 5.7% (p = 0.0005) and 8.6% (p = 0.029) higher in old SD than in adjacent normal skin. For recent SD, the differences are more pronounced and show higher significance with 61.2% (p < 0.0001) more oxyhemoglobin in SD than in adjacent normal skin, 16.0% (p < 0.0001) more deoxy-hemoglobin and 34.3% (p < 0.0001) more melanin.

We also studied the texture differences that exist between recent and old SD using pictures taken under polarised light. Results (Figure 4) show that the specular glossiness is higher in old SD than in recent SD (+5.8%, p < 0.0001) while the texture contrast is more important in recent SD compared to old ones (+33.2%, p < 0.0001). In other words, if old SD reflect more light than recent SD, the skin micro-relief of SD is more important when they are recent. In addition, texture entropy and anisotropy are similar in both recent and old SD, namely there is no significant difference in skin texture complexity nor in the directional properties between recent and old SD.

Discussion

Since their first histological description [21], SD have been described in many ethnic groups and where shown to have similar clinical appearance. Still, their colour can vary [14,22]. On white colour skin, recent SD are generally erythematous (striae rubrae) and then turn white (striae albae). They can also be blackish in dark-pigmented populations (striae nigrae) or bluish in case of prolonged corticotherapy (striae caeruleae). Therefore, we were interested in better characterising the appearance of SD in the Chinese population for which little is known.

To circumvent the fact that the volunteers with recent and old SD where presenting normal skin with different complexion, we focused our analysis on the comparison of SD to adjacent normal skin within each group. Results show that recent SD are slightly darker and much redder than adjacent normal skin while the colour of old SD does not differ to that of adjacent skin. The colour data of recent SD are in agreement with the increased concentration of oxy-, deoxy-hemoglobin and melanin we quantified in recent SD. This increase in skin chromophore is also detected in old SD but to a lower and less significant extend which probably explains why it is not detected as a colour difference.

The results we obtained for the colour and chromophore content of recent SD in the Chinese population we studied are in agreement with previous studies performed on other ethnic groups which relates the initial red and erythematous appearance of recent SD to changes in microvasculature and melanocyte activity [14,22,23]. We also show that, similarly to a Caucasian population, old SD from Chinese women still present a slight accumulation of melanin [24]. Conversely, the increase of oxy-, deoxy-haemoglobin we show in old SD differs from what has been obtained in a Caucasian population where such an increase was not detected [24]. Indeed, old SD are generally described as being lighter than surrounding skin [14] which most probably relates to differences in methodology and the higher specular glossiness of old SD.

This high specular glossiness of old SD indicates a higher skin glossiness, due to less variation in skin micro-relief, than in recent SD. It also correlates to the lower texture contrast we found in old SD compared to recent SD. Both results clearly relate to changesin skin structure. Indeed, SD are also known to be accompanied by several microstructural changes. They are characterized by gradual atrophy of the epidermis, including loss of rete ridges [25]. The mid-dermis undergoes elastolysis as evidenced by mast cell degranulation and stimulation of macrophages [12]. The elastic fibre network breaks down, collagen fibres thicken, become more densely packed and arranged in a parallel pattern [13,15]. The fact that we do not observed any difference in texture entropy or anisotropy suggest that, at the macroscopic level, underlying changes in skin structure occurring in recent SD remains in old SD. Still these differences are more visible, producing more microrelief to skin texture, in recent SD.

Conclusion

If some differences might exist in populations with different skin complexion, especially when darker, we show that, similarly to the Caucasian population, the visual characteristics of recent SD in Chinese women relates to colour. Darker and redder than adjacent normal skin, the colour difference relates to an increased concentration of oxy-, deoxy-hemoglobin and melanin. If old SD also show higher concentration of chromophores than normal skin, they show no colour difference and are characterised by their glossiness that relates to changes in skin structure.

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Dead or Alive? A New Dilemma of Probiotic Skin Care for Healthier Skin

Abstract

Our microbiota, a collection of micro-organisms is a living ecosystem inside (gut) and outside (skin) of our body. As a part of the inner and outer barrier of the body, it plays an important role in maintaining health. One attractive approach to enhance health and combat certain gut and skin inflammatory diseases is to modulate our microbiome using probiotics (live bacteria). Probiotics benefits on gut health is widely accepted, but we just started to understand health benefits of their use in skin care formulations. The formats already adopted in topical applications are live bacteria (probiotic) and dead bacteria, either inactivated or homogenized or ferments (postbiotics, or also called lysates or ferments). It is still a dilemma which format is the most suitable for skin care inventions but considering challenges in formulation design, development, manufacturing, and life cycle management of live bacteria in topical formulation, the focus is now shifted more toward postbiotic research to obtain similar claims as their alive counter partners. But still, the question remains, what are these additional benefits of having live bacteria in skin health care and if this is something worth the extra effort? Our first comparative study on both dead and live L. reuteri DSM 17938 indicated that probiotic in both formats could be used in management of skin inflammation related to photoaging and skin barrier claims like dry/sensitive skin. Additionally, the live format could be suitable for the management of pathogenic bacterial overgrowth such as in acne/sensitive skin conditions.

Keywords: Skin Microbiome Probiotics Postbiotic Ferment UV Inflammation Skin Barrie Lysate Health Aging Bacteria

Abbrevations: S.A: Staphylococcus Aureus; C.A: Cutibacterium Acnes; L Reuteri: Lactobacillus Reuteri; UV: Ultraviolet; UVB: Ultraviolet B

Introduction

Our microbiota, a collection of micro-organisms such as bacteria, viruses and fungi are a living ecosystem inside (gut) and outside (skin) of our body. As a part of the inner and outer barrier of the body, it plays an important role in maintaining health [1,2]. Microbiota impact in gut health and disease is widely accepted, but we are just starting to understand the role of cutaneous microbiota and its influence on skin health and aging. Clearly, there is a strong tête-à-tête between our gut and the skin, where healthy gut contributes to beautiful skin appearance too [3]. A recent study showed interesting inverse relation, where skin exposure to external stressor, such as Narrow Band Ultraviolet B (NB-UVB) light impacted the human intestinal microbiome [4]. This novel study opens a new vision between two barrier organ bidirectional interactions. How does the microbiota influence our skin health? As an outermost layer of the skin barrier, our microbiota is involved in regulating host inflammation, skin barrier, wound healing and premature skin aging process [5-8]. There are many skin concerns associated with dysbiotic (imbalanced) microbiota such as psoriasis, rosacea, atopic dermatitis, acne [9,7]. Thus, keeping the microbiota diverse and in a good balance is crucial for maintaining healthy skin. One attractive approach to enhance health and combat certain gut and skin inflammatory diseases is the use of probiotics [10], defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host” [11].

Probiotics, when taken orally, can transiently colonize the human gut mucosa, influence the intestinal microbiota and exert their effects not only in the gut [12], but also impact on overall skin health [13]. Based on recent in vivo studies, oral probiotics could be considered for the management of acne, rosacea, and as a protection against photodamage/premature skin aging [10, 14,15]. Due to these effects, it was reasonable to consider that the same/similar probiotics could also benefit skin when administered topically. The formats already adopted in topical applications are live bacteria (probiotic) and dead bacteria either inactivated or homogenized or ferments of probiotics (postbiotic, or also called lysates or ferments). It is still a dilemma which format is the mostsuitable for skin care inventions, but considering challenges in formulation design, development, manufacturing, and life cycle management of live bacteria in topical formulation, the focus is now shifted more toward postbiotic research to obtain similar claims as their live counter partners. To date, many skincare brands have started to incorporate lysates and ferments in their formulations with skin health claims such as strengthening skin barrier, boosting skin´s natural defense, support healthy microbiome growth, photo/ pollution protection, soothe the skin and etc. But still, the question remains, what are these additional benefits of having live bacteria in skin care and if this is something worth extra effort? To tackle the dilemma, we have performed the first comparative study of dead and live bacterias´ of L. reuteri DSM 17938 using skin equivalent ex vivo models [16]. This specific strain of L. reuteri is widely studied for gut health improvement [17-19], but there are limited studies in topical applications for cutaneous health. Interestingly, our results showed that live both forms of L. reuteri, dead and live, possessed anti-inflammatory effects toward UV induced inflammatory cytokines (IL-6 and IL-8) at protein level and a positive impact on skin barrier. Additionally, and differently from lysate, live L. reuteri had an inhibitory action against pathogenic skin bacteria such as Staphylococcus aureus (S.A) and Cutibacterium acnes (C.A) [16]. In conclusion, both dead and live formats of L. reuteri DSM 17938 could be used in management of skin inflammation related to photoaging and skin barrier claims like dry/sensitive skin. Additionally, the live format or probiotic ferments could be suitable for the management of pathogenic bacterial overgrowth such as in acne/sensitive skin conditions due to the anti-microbial activity of such formats [16].

Conclusion

Based on consumer’s growing interest in having natural, probiotic derived active ingredients in skin care formulation, we performed the first comparative study on a dead and alive bacterial strain of L. reuteri DSM 17938 and propose the use of dead (lysate, postbiotics) bacteria of L. reuteri in topical applications when UVB protection and skin barrier improvements are desired. However, live bacteria, probiotics, exert additional anti-microbial effect toward pathogenic/opportunistic bacterias´ on the skin, compared to postbiotics. Our findings open for more exploration to consider probiotics for enhanced skin health to mitigate or treat diverse skin inflammatory conditions and/or dysbiosis.

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Rhinoplasty in Thick Skinned Patients, is there a Role for the Dermatologist?

Abstract

Rhinoplasty in thick Skinned patients can be very challenging. This is of great importance for surgeons whom practice involves patients from the Middle east, South America, Africa and Asia as a good percentage of the population has thick skin. In dealing with nasal surgery for patients with thick skin, many challenges arise; the relatively inelastic skin-soft tissue envelope, small weak nasal cartilages leading to weak structural support, the tendency for scar formation and prolonged post-operative edema are all culprits to less than ideal results. In this review, I would like to highlight the importance of proper skin management in dealing with such cases. This includes pre-operative skin preparation and post-operative care.

Keywords: Rhinoplasty; Thick Skinned; Skin-soft; Epidermis; Surface Oiliness; Exfoliation; Ingredients; Skin Inflammation

Introduction

Pre-Operative Skin Preparation

All Patients benefit from a perioperative skin care program. However, this is crucial in thick skinned patients. The main objectives are to re-establish healthy skin conditions (as much as possible) and to diminish the skin’s inflammatory response [1,2]. This can be achieved by addressing all skin layer; epidermis, dermis and subcutaneous tissue. Regarding epidermal layer, products that control surface oiliness, promote exfoliation, unclog pores, and decrease trapped sebum can be used. A simple daily regimen can be developed and tailored to each individual patient need, preferably in collaboration with a dermatologist. Suggested products include:

a. A cleanser: According to patient skin type, a gentle cleanser or one that include active ingredients can be used. These include gentle exfoliants to unclog pores such as glycolic acid or salicylic acid and topical antibacterial such as benzoyl peroxide to control skin inflammation [3-5].

b. Topical retinoids: Topical retinoids have been shown to modulate epidermal keratinization and differentiation and alter various transcription factors involved in cascades of skin inflammation [6].

c. Sunblock and minimizing sun exposure in order to stabilize the epidermis against UV light injury [4].

d. Additional treatments: These include moisturizers topicalantioxidant, topical antibiotics, micro dermabrasion, and in-office peels, depending on individual skin issues [7-9].

To achieve best results, a skin care regimen should be started 4-6 weeks before surgery. If this is not possible, they can be started at the initial consultation and followed until the patient is operated upon. To avoid hypersensitivity reactions from topical disinfectants and adhesive materials placed over the nose during surgery, products containing active ingredients should be stopped stop 5 days before surgery, to be resumed 10 days afterwards [2]. Regarding deeper skin layers, the rational of topical and systemic treatments is to control sebum production, this will diminish size of sebaceous glands and will eventually decrease inflammation and swelling. This can be achieved predominantly by topical or oral retinoids [6,10]. Adjuvant therapeutic modalities include trichloroacetic acid TCA peels, photodynamic therapy, and intradermal botulinum toxin [11-13]. It is important to highlight that in severe cases where oral isotretinoin is used, no evidence supports delaying skin surgery. It can be stopped one week before surgery and restarted 2 to 3 weeks after surgery. If the patient wants surgery first, it can be started two weeks after surgery [2,14,15].

Post-Operative Care

The rationale behind post-operative care is to decrease edema, minimize inflammation, and eliminate dead space. Simple measures such as head elevation, cold compresses, avoiding excessive sun exposure and strenuous exercise shouldn’t be overlooked

a. Medications such as non-steroidal anti-inflammatory drugs can be used to control both pain and soft tissue swelling, oral antihistamines and nasal steroids for allergic rhinitis control, and judicious use of oral steroid can greatly reduce the extent and duration of post-operative edema [16,17].

b. In regard to the above-mentioned skin care regimes, they should be followed postoperatively for at least 6-12 months after surgery to achieve best results.

c. Taping: in patients with thick nasal skin, postoperative taping is essential. It helps to compress the skin envelope to the underlying framework, therefore eliminating dead space. The effects of nasal taping have been demonstrated recently by Ozucer et al. who showed that 4 weeks of post-rhinoplasty taping significantly decreased postoperative edema in the thick skin patient population. It is recommended to use hypoallergenic porous tape to minimize skin reaction from taping [18].

d. Massage: Many surgeons advise thick skin patients to perform nasal massage three times a day for several months after tapes are removed. The patient should stand in front of a mirror and place extended index fingers on each side of the lateral nasal sidewall. Skin should be stretched, and fingers should exert pressure on the bones pushing everything slightly to the midline. This will help eliminate edema and dead space formation. Despite the popularity of this practice by many surgeons, compelling evidence is currently lacking to support this practice.

e. Injectable steroids and 5-Flurouracil: If supra-tip fullness develop postoperatively, different protocols are proposed; 0.1- 0.2 ml of triamcinolone 10-40 mg/ml can be administered every 4-6 weeks until the intended definition is achieved. The injection should be placed between the dorsal frame and the soft tissue and not into the dermis [19-21]. In resistant cases, 5-fluorouracil, hyaluronidase or a combination of these agents can be used [22,23].

Conclusion

In conclusion, dealing with thick skin patients undergoing rhinoplasty can be a daunting task. It is important for both the surgeon and the patient to understand the importance of pre and post-operative skin care as its contribution to a satisfactory result is as important as the surgical technique. The importance of having experienced dermatologist on board couldn’t be overemphasized.

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Periorbital Vitiligo Caused by Wrinkle-Removing Eye Cream: A Case Report

Abstract

The prospect of slowing and/or reversing the aging process of one’s skin by applying topical over-the-counter commercial products is becoming increasingly attractive. In particular, facial wrinkle removers are generating significant consumer attention, but the potential for these products to cause permanent skin damage has not been previously addressed. This report investigates the ingredients found in a single product and correlates their presence with an adverse clinical outcome.

Keywords: Periorbital Vitiligo Commerical Products Wrinkle Removers Detergents Adhesives Motor Oils Skin Pigmentation Eye Cream

Introduction

Chemical induced vitiligo usually occurs following skin exposure to phenol containing compounds that may be unknowingly present in worksite industrial materials, hair dyes, skin lightening creams, household cleaning products, deodorants, detergents, adhesives, rubber gloves and sandals, motor oils, and laboratory reagents [1,2]. It is clinically indistinguishable from spontaneous loss of skin pigmentation related to genetic risks and autoimmune phenomena. We report a case of periorbital vitiligo caused by a routine commercially available eye cream advertised to remove unwanted wrinkles. None of the risk factors mentioned above are relevant to this case.

Case Report

A 51-year-old Caucasian female applied Lancome Renergie Lift Multi-Action Eye Cream twice a day for one week in the following locations: below her eyebrows, underneath her lower eyelids, and the lateral corners of her eyes. There was no previous history utilizing similar products, and there was no history of burning, itching, nor skin rash in the application contact areas. On the eighth day she ceased usage after noticing progressive loss of pigmentation in the areas of application (Figures 1-3). Over the next three years her periorbital vitiligo remained unimproved despite a variety of therapeutic dermatologic interventions, including laser treatments. No other areas of skin depigmentation have developed. Her only other ongoing medical problem was a four-year history of mild, non-progressive, untreated multiple sclerosis characterized by intermittent fatigue, self-limited lower extremity myalgias, occasional lack of coordination, and occasional memory lapses

Discussion

There exists an exhaustive list of ingredients in the topical product used by this patient, namely: water, dimethicone, glycerin, isohexadecane, alcohol, squalene, cetyl alcohol, stearic acid, mineral oil, palmitic acid, PEG-100 stearate, glycerol stearate, PEG-20 stearate, beeswax, octyldodecanol, Ci77891, titanium dioxide, Ci16035 (red 40), Ci19140 (yellow 5), C13-14 isoparaffin, mica, saccharomyces (yeast), hydrolyzed linseed extract, sodium hydroxide, soy protein, hyalauronic acid, sodium benzoate, phenoxyethanol, adenosine, acetyl tetrapeptide, caffeine, silica, polyacrylamide, chlorphenasin, chlorhexidine digluconate, polyethylene dimethiconol, limonene, benzyl alcohol, linalool, capryloyl, salicylic acid, microcrystalline wax, paraffin, shea butter, laureth-7, coumarin, and parfum. Dimethicone and dimethiconol are polydimethylsiloxanes (silicones), which chemically are the same artificial organosiloxane materials present in silicone gel-filled breast implants. These two items, in concert with octyldodecanol (an emulsifier), readily penetrate the skin and adhere to the subcutaneous fat, as silicones are lipophilic. Fat cells (adipocytes and lipocytes) contain a number of mediators of inflammation, and fat cells are also capable of converting the amino acid tyrosine into catecholamines (epinephrine and norepinephrine). Tyrosine is an essential ingredient used by melanocytes to produce normal skin pigmentation (melanogenesis). Vitiligo and tachyarrythmias are two items in a long list of proven toxic clinical phenomena manifested by recipients of silicone gel-filled breast implants [3-5].

It is therefore hypothesized that one of the mechanisms of vitiligo production in this patient is the localized preferential shunting of tyrosine usage to activated adipocytes, thereby depriving melanocytes of their substrate. A second mechanism is silicone-induced stimulation of adipocytes to produce localized inflammation, as panniculitis (subcutaneous fat necrosis) is another well-known ailment occurring in implant recipients [3-5]. Localized inflammation has been shown to be lethal to melanocytes [1,2]. Five other ingredients in this topical product are also of critical importance in the development of vitiligo in this patient. Two of these include salicylic acid and sodium benzoate. Salicylic acid by itself acts as an exfoliant to reduce dry patches, and sodium benzoate by itself is designed to kill bacteria on the skin. The other three key ingredients are sodium hydroxide, calcium hydroxide (present in mica), and water. When all five are mixed togethera chemical reaction ensues between salicylic acid and sodium benzoate, whereby phenols are produced. Phenols are directly toxic to melanocytes because they act as tyrosine analogues, thereby inhibiting the process of melanogenesis [1,2].

All of the other ingredients in this product have varied actions. For example, isohexadecane in an emollient and a solvent designed to soften and smooth the skin in concert with enabling other substances to easily dissolve into a homogeneous entity. Ci16035 (red 40) is known to cause allergic reactions, and Ci19140 (yellow 5) is known to cause purple spots on the skin. Squalene is utilized for adding moisture but is known to clog pores in the skin. Phenoxyethanol is a preservative known to cause skin irritation. Silica has a long and sordid history of toxicity to the body. Polyacrylamide absorbs water and is used as a thickener. Chlorphenesin is utilized as a preservative and is known to cause contact dermatitis. Chlorhexidine digluconate is an antiseptic utilized to kill bacteria. Limonene is an antioxidant and also is known to cause skin senisitivity. Laureth-7 is a surfactant that contains 1,4-dioxane (a solvent that is a known toxin). Essentially, Lancome Renergie Lift Multi-Action Eye Cream is a soup mixture of ingredients with the clear-cut potential to damage the skin via many adverse mechanisms. Over the past ten years the proliferation of over-the-counter anti-aging materials are legion, and the same is true for multiple other multi-purpose topical products such as moisturizers, softeners, rejuvenators, make-up, lotions, shampoos, and soaps. One can only speculate how many other consumers may have developed permanent vitiligo upon exposure to similar compounds encountered in this case, since many or all of these compounds are not necessarily restricted to just wrinkle removers.

With regard to cosmetics, using a make-up remover at the end of the day may paradoxically enhance an adverse skin reaction, because many removers contain an emulsifier known as TEA (triethanolamine). TEA temporarily changes the pH of the skin to alkaline, thereby transiently loosening the tight bonds between skin cells. Thus, a certain proportion of what is on the skin may actually wind up being impacted below it. The induction of wrinkle remover induced vitiligo may be more likely to occur if the user does not experience skin burning, itching, and or rashes on initial contact. Under these circumstances (as noted in this case) a consumer is more likely to continue further applications beyond the first day or two of usage. Once subclinical inflammation and melanocyte damage become obvious, it is probably too late to reverse the unsightly cosmetic outcome.

Conclusion

Consumers need to be aware of the complexity of topical skin products they are purchasing, as these products may contain potentially harmful ingredients capable of causing unwanted and permanently altered dermatologic appearances.

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A New Strategy Increases Hair Growth – Combination of Topical Adenosine and Caffeine Hair Tonic

Abstract

Male pattern hair loss (MPHL) and female pattern hair loss (FMPL) are important issues in cosmetic dermatology. The efficacy of hair tonic product containing 0.75% adenosine and 1.5% caffeine was assessed in male and female subjects with MPHL and FMPL. A single-blind, randomized, half-split study was conducted. Effectiveness of the hair tonic was assessed in the improvement of hair density by 6 weeks. In addition, satisfaction on product characteristics and hair shedding reduction were also evaluated. The results showed that the hair density was significantly increased by 40% and 55% at week 6 and week 8, respectively. Subjects scored high level on product characteristics and efficacy. No serious side effect was observed after the application. The results showed that 0.75% adenosine and 1.5% caffeine hair tonic were effective in MPHL and FMPL subjects with a high level of overall satisfaction.

Keywords: Hair Growth Adenosine Caffeine Hair Tonic Alopecia

Introduction

Male pattern hair loss (MPHL) and female pattern hair loss (FPHL) are common situations that generate negative impact in patient self-esteem. MPHL, also known as androgenic alopecia, often showed moderately miniaturization of hair follicles and hair shedding. The cause of MPHL is considered as an androgen-dependent. The major causes of MPHL may include hormonal dysfunction, extracellular matrix proteins in the follicular bed reduction, and local inflammation [1]. In case of FPHL, hair density reduction is often recognized. The miniaturization of hair follicles in FPHL is typically localized in the central-, frontal-, and parietal-scalp area [2]. FPHL is relevant to multiple genes, factors, and environmental influences [3]. Previous study showed that the development of FPHL may be involved with androgen [4]. Another study suggested that FPHL may be associated with metabolic syndrome [5]. The prevalence of MPHL and FPHL has been widely studied. Topical administration of hair tonic containing some active ingredients such as caffeine and adenosine has been reported for their effectiveness in hair loss [6,7]. It is known that androgen is an important regulators of hair loss and 5α-reductase enzyme is a critical factor. Testosterone is metabolized by 5α-reductase enzyme to 5α-dihydrotestosterone (DHT). The high level of DHT could suppress hair growth, which was found in bald scalp. Caffeine could inhibit 5α-reductase enzyme activity leading a reduc tion of DHT in the scalp and improving hair follicle growth stimulation [1]. In the case of adenosine, an activation of adenosine receptor in the scalp could increase the production of fibroblast growth factor [8]. These mechanisms could have effects on hair growth enhancement. Therefore, a combination of both caffeine and adenosine, may provide an effectiveness to male and female with early MPHL and FPHL. The aim of this study was to assess the efficacy of topical adenosine and caffeine hair tonic in comparison with a placebo (vehicle only) in male and female with early MPHL and FPHL. Product attributes satisfaction and hair shedding reduction of subjects were also evaluated and discussed.

Materials and Methods

Subjects and Treatment

A single-blind, randomized, half-split study was conducted. Eight subjects aged 30-51 years with early MPHL and FPHL, who experienced an increase in hair shedding participated in the study. One point five milliliter of 0.75% adenosine and 1.5% caffeine hair tonic was applied to the fixed area on one side of the subject’s frontal scalp, designated as the Treatment area. On another side of the scalp was treated with the same volume of vehicle to serve as the Control area. The subjects were blinded to the treatment, both adenosine-caffeine solution and vehicle were applied twice a dayfor eight weeks. The study protocol was conformed to the declaration of Helsinki and the written informed consent were obtained before the recruitment.

Efficacy and satisfactory evaluation

During the studying periods, the scalp was examined for the sign of skin irritation every day. Fixed area ultra-close image of the hairs and scalp was photographed by IBS-01Pro Intelligent Beauty Scope (Kowa Optics Corp., Taiwan) every week. The total number of hairs was counted using J Micro Vision (version 1.2.7), and the hair density was determined as the total number of hairs per 1 mm2 area in a blind manner by the investigator. Nominal Paired t-test was used for statistical analysis (Excel 2013, Microsoft, USA). The significance of the results was considered at a p-value < 0.05. Secondary evaluation for subject’s satisfactory on product characteristics and hair shedding was assessed using questionnaire. Perceptiveness scores were analyzed using Pareto chart (Excel 2013, Microsoft, USA). In addition, allergic reaction on the scalp was assessed.

Results

Effect of treatment on hair density and overall appearance

All subjects completed 8-week study. None of the participants showed the sign of skin irritation. At week 0, the hair density of the control area was 1.19 ± 0.23 hair/mm2, which was not difference to the treatment area, 1.21 ± 0.25 hair/mm2. No significant differences in hair density or overall appearance in the control area was observed (p-value > 0.2) (Figure 1). In contrast, combination of adenosine and caffeine hair tonic showed a significant improvement in hair density (Figure 1). At week 6, hair density of treated scalp was 1.7 ± 0.27 hair/mm2, significantly higher than that of the control area, 1.24 ± 0.34 hair/mm2 (p-value < 0.05). Similarly, hair density of treated area in week 8 was significantly higher than that observed in the control area (p-value < 0.05). At the end of the study, about 55 percent increment of hair density was observed in the treatment area, indicated the favorable effects of the combination of topical adenosine and caffeine treatment on hair growth. The ultra-close image examples of subject’s scalp were shown in (Figure 2). The images showed dramatic improvement of hair density in comparison to the untreated area, as a similar manner with the result in (Figure 1). The hair density at a hair tonic treated area of subjects at week 6 and week 8 were significantly denser

Product satisfactory assessment

No adverse reactions or allergic reactions due to the application of 0.75% adenosine and 1.5% caffeine hair tonic or placebo hair tonic were observed in any subjects in this study. (Figure 3) showed product satisfactory attribute score, add which were evaluated by all subjects after using the hair tonic. The average scores of product attributes such as texture and smell were 4.88 ± 0.35 and 5.00 ± 0.00, respectively. More than 80% of subjects indicated high level of satisfaction on product’s texture and smell. The level of hair shedding was considered as high (4.44 ± 0.9). More than 100% of the subjects recognized the hair shedding reduction afterapplying the hair tonic. In total, 75% of subjects revealed very high satisfaction on the hair tonic and the overall satisfaction score was 4.46 ±0.43.

Discussion

A combination of adenosine and caffeine in hair tonic significantly enhanced the hair density compared to baseline. Previous study revealed that an application of 0.2% caffeine-based topical liquid on scalp could improve anagen hair in androgenetic alopecia males [6]. An increase in anagen hair may be due to the anagen phase prolongation by caffeine. Caffeine, as a phosphodiesterase inhibitor, could enhance cyclic adenosine monophosphate levels in cells and then increases cell proliferation via stimulation of cell metabolism [9]. The testosterone/dihydrotestosterone-induced miniaturization of hair follicle may be counteracted by caffeine [10]. This mechanism of caffeine may increase the hair density of subjects after hair tonic application. Adenosine also showed effects on hair density improvement as reported in previous studies [7,11]. Adenosine has an effect on the upregulation of fibroblast growth factor production by adenosine receptor A2b activation [8]. In addition, a stimulation of adenosine receptor could decrease inhibitory factor transforming growth factor [12]. The modulation of genes encoding growth factors including fibroblast growth factor and transforming growth factor by adenosine resulted in hair growth enhancement by adenosine. In a similar manner, our hair tonic containing adenosine could improve hair density of subjects. The product attributes such as texture and smell, hair shedding reduction and overall satisfaction scores were considered as high. The high scores confirmed that 0.75% adenosine and 1.5% caffeine hair tonic provided a high level of subject satisfaction and promote an adherence to long-term application.

Conclusion

The hair tonic containing 0.75% adenosine and 1.5% caffeine showed the efficacy in hair density enhancement by 6 weeks compared to baseline. Subjects scored high level on product characteristics and efficacy. No serious side effect was observed after the application. The results showed a high level of subject satisfaction.

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