Intense Pulsed Light: A Methodical Approach to Understanding Clinical Endpoints.

BACKGROUND: Intense Pulsed Light (IPL) is a non-coherent polychromatic broadband filtered flashlamp that emits light in the spectrum of approximately 400–1200 nm. Its effects on photorejuvenation are well documented. The goal of this study is to help practitioners better conceptualize and fine tune IPL device settings in order to produce the most effective and safest clinical outcome. MATERIALS/METHODS: This was a prospective study testing several filters (515 nm; 560 nm; 590 nm and 530–650; 900–1200 nm vascular filter), fluences, pulse durations, and pulse numbers (ie, multiple sequence pulsing or MSP) with a new IPL system. RESULTS: Post-procedure erythema response was more pronounced with increasing fluence, decreasing wavelength, fewer pulses and shorter pulse duration. The exception was the 515 nm filter with regard to pulse duration, which was observed to have a more pronounced response with longer pulse durations. The overall clinical outcome at the 4-week follow-up visit demonstrated greatest improvement in erythema and pigmentation using the 515 nm filter on a Fitzpatrick Skin Type III individual. CONCLUSION: Greatest clinical endpoint response at 4-week follow-up was observed with more robust initial responses. This was most apparent at higher fluence levels and fewer pulse counts. However, when the IPL is pushed to aggressive parameters, there is risk of hypopigmentation and hair loss as seen in this case study. Skin type is an important consideration when using IPL and MSP adds to its safety profile. J Drugs Dermatol. 2021;20(2):203-207. doi:10.36849/JDD.5638.

Minimizing injury to the donor area in follicular unit extraction (FUE) harvesting.

BACKGROUND: Follicular Unit Extraction (FUE) is considered to be a minimally invasive procedure, and the injury to the donor area caused by a sharp punch may result in dermal fibrosis and clinically observed hypopigmentation. OBJECTIVE: To evaluate with advanced image processing the efficacy of using 0.9% normal saline in minimizing the injury to the donor area in FUE donor harvesting. PATIENTS AND METHODS: The term acute extraction (AE) is used to describe the donor harvesting technique, whereby a follicular unit (FU) is removed with a punch that is aligned parallel with the exit angle of the hair follicle. The term vertical extraction (VE) describes the technique where a FU is removed in like manner, but normal saline is injected intradermally prior to harvesting so the punch being perpendicular to the skin. Thirty-five patients were selected for this study to apply both harvesting techniques and then to compare the differences in wound surface size and skin mass removed by the punch. RESULTS: A significant reduction in the mean values of wound surface and skin mass was recorded in vertical extraction compared to those in acute extraction. CONCLUSION: The injection of normal saline prior to harvesting proved to be very efficient in minimizing skin injury in FUE harvesting.

Utilización de plasma rico en plaquetas en la profilaxis del daño cutáneo inducido por radioterapia: modelo experimental / Use of platelet rich plasma as prophylactic method for skin damage after radiotherapy: experimental study

Introducción y Objetivos. La radioterapia conlleva la aparición de complicaciones cutáneas que afectan a la calidad de vida del paciente y en algunos casos condicionan la reconstrucción. El plasma rico en plaquetas (PRP) es una terapia emergente; se trata de una sustancia autóloga, biocompatible, segura y económica. Está descrito su uso en disminución de la inflamación local, de los tiempos de curación de las heridas, en el tratamiento de lesiones por radioterapia y últimamente en el campo de la Medicina Estética mejorando la calidad de la piel. Nuestro estudio analiza el uso del PRP en la profilaxis de las lesiones cutáneas inducidas por radioterapia evaluando un modelo experimental. Material y Métodos. Realizamos un ensayo clínico controlado, doble ciego, en animales: 12 ratas Wistar, 2 para la obtención del PRP y 10 para el análisis clínico e histológico. Resultados. Del análisis clínico destacamos que de los sectores sin PRP previo a la radioterapia: 8 ratas presentaron alopecia y 7 hipopigmentación. La alopecia fue total en un 60%, parcial en 20% y un 20% no presentó alopecia. En los sectores con PRP: 4 presentaron alopecia y 3 hipopigmentación. La alopecia fue parcial en un 40%, un 60% no presentó alopecia y no hubo casos de alopecia total. Los resultados del análisis histológico demostraron un 100% de atrofia leve-moderada para los sectores con PRP. Por contrapartida, los sectores sin PRP presentaron 80% de atrofia moderada-severa y un 20% de atrofia leve-moderada. Conclusiones. Existe un beneficio en el uso del PRP como profilaxis de la alopecia (p<0.05) e hipopigmentación (p<0.1) inducido por radioterapia en un modelo experimental (AU)

Background and Objectives. Radiotherapy is usually associated with skin complications that affect the quality of life of patients and in some cases can also affect the timing of the reconstruction. The plateletrich plasma (PRP) is an emerging therapy; is autologous, safe and economic. Current use of PRP includes: efficacy in decreasing local inflammation, enhance wound healing, treatment of skin ulcers caused by radiotherapy and its use extends to the field of aesthetic plastic surgery improving the quality of the skin. The authors made an experimental trial to analyze the use of PRP as a prophylaxis method for skin damage after radiotherapy. We analyze the benefits of PRP as a prophylaxis method for skin damage after radiotherapy using an experimental model. Methods. We conduct a double blind trial with rats. Twelve Wistar rats were used, 2 for obtaining the PRP and 10 for clinical and histological analysis. Results. Data collected from the clinical analysis showed that those areas without PRP: 8 rats presented alopecia and 7 hypopigmentation. Total alopecia was present in 60%, partial alopecia in 20%, and 20% did not present alopecia. In those areas with PRP before radiotherapy: 4 presented alopecia and 3 hypopigmentation. There were no cases of total alopecia, 60% did not present alopecia and 40% presented partial alopecia. Data collected from the histological analysis showed 100% of mild-moderate atrophy in those areas with PRP. On the other hand, 80% of moderate-severe atrophy and 20% of mildmoderate atrophy was present on those areas without PRP. Conclusions. The authors showed the benefit of PRP as a prophylaxis method for alopecia (p<0.05) and hypopigmentation (p<0,1) produced after radiotherapy in this experimental model (AU)

Glutathione maintenance is crucial for survival of melanocytes after exposure to rhododendrol.

Rhododendrol is a phenolic compound that shows a tyrosinase-dependent toxicity for melanocytes and occasionally induces a vitiligo-like skin depigmentation. The post-tyrosinase mechanisms determining melanocyte death or survival, however, are far from clear. Here, we find that rhododendrol treatment leads to a reduction in the levels of cellular glutathione but also induces a cellular antioxidant response that eventually increases glutathione levels. We further find that rhododendrol toxicity is enhanced when glutathione levels are experimentally reduced and alleviated when glutathione levels are increased. Hence, it appears that the size of the preexisting glutathione pool along with the capacity to supply glutathione via the antioxidant response determines whether melanocytes survive or die after rhododendrol exposure. It is conceivable, therefore, that rhododendrol-induced leukoderma depends on the capacity to maintain appropriate glutathione levels and that enhancement of glutathione levels may preserve a patient's melanocytes and potentially help in repigmentation.

A bioassay for the detection of neutralizing antibodies against the α-melanocyte stimulating hormone analog afamelanotide in patients with erythropoietic protoporphyria.

The tridecapeptide afamelanotide (Scenesse®) is a congener of α-melanocyte stimulating hormone (α-MSH). Upon binding to the melanocortin 1 receptor (MC1R) on the surface of pigment cells of the skin, the melanocytes, α-MSH or afamelanotide trigger the synthesis of cAMP, which stimulates the synthesis of melanin and therefore induces skin tanning. In a recent trial, afamelanotide administered as controlled release implants protected erythropoietic protoporphyria (EPP) patients from sunlight induced phototoxic skin reactions. Administration of biological therapeutic peptides may elicit unwanted immunogenic responses in recipients of these products. Although in a previous study using ELISA technique we excluded any newly developed immunogenicity during prolonged exposure to afamelanotide, we confirmed the previously published existence of low titers of antibodies against α-MSH in drug-naïve individuals that cross-reacted with afamelanotide. In order to investigate whether such antibodies are neutralizing, i.e. could block the biological effect of afamelanotide, we developed a cell culture-based bioassay. The basis of our assay was the measurement of afamelanotide-induced cAMP formation in a strain of the B16 mouse melanoma cell line, G4F-7, expressing the transfected human MC1R. Average half-effective concentrations of the natural hormone α-MSH and its congener afamelanotide were 38.8 ± 10.6 and 10.9 ± 7.17 nM (n=5), respectively. Neutralizing antibodies would reduce the cAMP formation. Two neutralizing anti-α-MSH antibodies served as positive controls. cAMP formation in the G4F-7 cells after addition of sera of drug-naïve (n=6) and of drug-exposed EPP patients (n=17) was significantly lower than after that from healthy volunteers (n=13). There was no difference between drug-naïve and drug-exposed patients. Using forskolin as a hormone-independent stimulator of cAMP formation, we excluded an unspecific interference of EPP sera with cAMP formation. We conclude that afamelanotide even after prolonged application to EPP patients did not elicit neutralizing antibodies. Further, the low titer immunoreactivity observed in sera of some drug-naïve individuals had no effect on the biological activity of afamelanotide.

Premature hair graying.

Hair pigmentation and graying are important topics for the understanding of the physiology of aging; the differentiation of stem cells; and the mechanisms underlying disease processes such as progeroid syndromes, vitiligo, and hypothyroidism. Although hair graying, or canities, is a common process occurring in people as they age, an unknown percentage of individuals experience premature graying from familial inheritance or pathologic conditions. We review the physiology of hair pigmentation and the mechanism underlying physiologic graying, and we explore the etiology of pathologic causes of premature graying, pathologies associated with premature graying, and the limited available treatment options for hair graying.

[Vitiligo as an aesthetic problem. Noninvasive therapeutic methods in vitiligo]. / Bielactwo nabyte jako problem estetyczny. Nieinwazyjne metody leczenia bielactwa.

Vitiligo is an idiopathic chronic skin disease that is notable for depigmented macules forming by destruction of melanocytes mediated by cells of the immune system. Vitiligo occurs in 1-2% of the population irrespective of race and without predilection to gender or age. The dynamics and extent of the disease vary widely, ranging from stable cases with isolated minor foci to states showing rapid progression and occupying large areas of the skin. For many patients, the disease represents a serious cosmetic defect which limits their activities in various spheres of life. There are many noninvasive methods of treatment but none of them offers a guarantee of complete therapeutic success. PUVA- and UVB-therapy are recognized as the most effective and most commonly used methods. The management of vitiligo should also include education, cosmetic correction options, and psychotherapy in some cases.

Patients with early relapse of primary hemophagocytic syndromes or with persistent CNS involvement may benefit from immediate hematopoietic stem cell transplantation.

Primary hemophagocytic syndromes represent a group of rare immunodeficiencies, which are characterized by development of life-threatening systemic inflammatory manifestations, so-called accelerated phases. Immunosuppressive therapies are only temporarily effective to control this complication and the prognosis is dismal unless treated by hematopoietic SCT (HSCT). At present, optimal modalities of this potentially curative approach remain incompletely defined. In this study, we analyzed our experience in 18 patients with primary hemophagocytic syndromes treated since 1984 in our center by HSCT. Ten of these patients had previously developed accelerated phases and were in remission at the time of HSCT, whereas five patients had findings of active disease, with two cases in early phases of recurrences of less than 2 weeks duration and three cases with persistent central nervous system disease, whereas three patients had never experienced accelerated phases. In the group with active disease, four of five patients are long-term survivors and are well, whereas one patient died of CMV pneumonia. This outcome compares favorably with results in patients transplanted in remission, where 6 of 10 are long-term survivors. Our findings indicate that HSCT can have a favorable prognosis even in patients with active disease of primary hemophagocytic syndrome.

Postburn sequelae in the pediatric patient: clinical presentations and treatment options.

Each year, more and more children acquire burns that require serious medical attention. A vast number of these burns lead to permanent disfigurement and long-term disability. As health care providers, focus should not only be on the immediate treatment, but also on the long-term outcome of these burns and the required rehabilitation that these burn patients must go through. During the rehabilitation phase of the burn, focus should be placed on how to prevent and treat several sequelae that include hypertrophic scarring, keloids, contractures, heterotopic ossification, leukoderma, and pruritus. One must also use a multidisciplinary team approach to help reintegrate the patient back into their environment.

Effect of skin surface temperature on skin pigmentation during contact and intralesional cryosurgery of keloids.

BACKGROUND: This 15-month study was designed to compare the effect of skin surface temperature on skin pigmentation following a single intralesional or contact cryosurgical treatment of keloids. PATIENTS/METHODS: Thirty Caucasian patients with 45 keloids present for more than 6 months were included in this study. Twenty-one keloids were treated by the contact method while the remaining 24 scars were managed using an intralesional cryosurgery technique. The skin surface temperature at the keloids was measured and recorded using a Ni/Cd thermocouple. Four variables of the thermal history were evaluated with the contact and the intralesional methods, namely cooling rate, hold time, end temperature and thawing rate. Assessment of the local hypopigmentation was performed 6 months after the treatment using a pigmentation scale. RESULTS: Significantly slower cooling (6.09 +/- 4.56 degrees C/min) and thawing rates (54.52 +/- 32.17 degrees C/min) were recorded with the intralesional cryosurgery method when compared with the cooling rates (13.47 +/- 9.04 degrees C/min) and thawing rates (89.00 +/- 86.42 degrees C/min) of the contact method (P < 0.000001). The end temperature of the contact technique was significantly cooler (-46.77 +/- 14.74 degrees C) when compared with that of the intralesional method (-15.55 +/- 6.77 degrees C) (P < 0.000001). There was a trend for the hold time of intralesional cryosurgery to be longer (82.67 +/- 138.03 s) than that of the contact method (16.86 +/- 23.49 s) (P < 0.059). A significant difference in skin pigmentation was demonstrated between the two cryosurgical methods. In 91.7% of the keloids treated by the contact technique a significant hypopigmentation was noticed, while no marked hypopigmentation was detected in the skin surface of the keloids treated by the intralesional method (P < 0.0001). CONCLUSION: We hypothesize that the thermal history of the skin surface during the intralesional cryosurgery technique provides a better survival environment for the melanocytes than the contact method, thus producing a lower rate of permanent hypopigmentation and disfiguring.

Laser resurfacing-induced hypopigmentation: histologic alterations and repigmentation with topical photochemotherapy.

BACKGROUND: Hypopigmentation is a relatively common side effect of CO2 laser resurfacing. Little is known regarding the histologic features of the areas of pigmentation loss. To date, hypopigmentation is considered a permanent complication of this procedure. OBJECTIVE: To assess the histologic features of hypopigmentation caused by laser resurfacing and to evaluate the efficacy and safety of topical psoralen photochemotherapy. METHODS: Ten patients were included in this pilot study. Four had baseline biopsies performed. Histologic parameters assessed included epidermal melanin, dermal melanophages, perivascular inflammation, Mel-5 immunostaining for melanocytes, and dermal fibrosis. Seven patients were treated twice a week with topical photochemotherapy utilizing 0.001% 8-methoxypsoralen. RESULTS: All of the biopsy specimens demonstrated varying quantities of epidermal melanin and residual epidermal melanocytes. Mild perivascular inflammation was evident in two specimens. Superficial dermal fibrosis was noted in all biopsy specimens. Topical photochemotherapy induced moderate to excellent repigmentation in 71% of the treated patients. Adverse effects were minimal. CONCLUSION: The results of this investigation suggest that hypopigmentation induced by laser resurfacing may result from a suppression of melanogenesis rather than destruction of area melanocytes. The preliminary data further suggest that hypopigmentation caused by laser resurfacing can be effectively treated by topical photochemotherapy.

Melanocyte repopulation in full-thickness wounds using a cell spray apparatus.

Melanocyte restoration is critical in reconstituting skin color. We developed a spotted (piebald) pig wound model to study methods of restoring melanocytes to the epidermis. Paired, full-thickness, porcine wounds were covered with nonpigmented, fully expanded, 3:1 meshed, split-thickness skin grafts and were sprayed with an epidermal cell suspension. The suspensions were highly pigmented skin (HPS) cell isolates for half of the wounds (n = 16) and nonpigmented skin (NPS) cell isolates for the remaining wounds (n = 16). Histologic sections showed 6.0 +/- 3.0 and 15 +/- 4.0 pigmented melanocytes per high-power field on days 8 and 20 in HPS-treated wounds and no pigmented melanocytes in NPS-treated wounds. Melanin pigment was dispersed in all layers of the epithelium for the HPS group on day 20 compared with a lack of melanin pigment observed in the NPS group. Cell spraying may provide a clinical method to restore color to skin; further work is needed to control the expression of melanin.

An intense light source. The photoderm VL-flashlamp as a new treatment possibility for vascular skin lesions.

BACKGROUND: Up to now, vascular diseases were treated with various lasers, such as argon, pulsed dye, and copper vapor lasers, which can lead to side effects like hypopigmentations, hyperpigmentations, and scarring. We treated patients with vascular lesions with an incoherent intense light source, the PhotoDerm VL-flashlamp. OBJECTIVE: The aim of the study was to test the effectiveness and safety of the PhotoDerm VL for vascular skin lesions. METHODS: One hundred and twenty patients with facial or leg telangiectasias, spider nevi, erythrosis interfollicularis, and senile angiomas were treated with the PhotoDerm VL. RESULTS: In 73.6% of patients there was an immediate clearing, and in 84.3% a clearing after 1 month was found of leg telangiectasias up to 1 mm in diameter. Facial telangiectasias and erythrosis interfollicularis colli showed clearance up to 90%. Spider nevi and senile angiomas often only needed to be treated once. CONCLUSION: From our experience we conclude that the PhotoDerm VL is an excellent device to treat vascular lesions as there were hardly any side effects seen, however, the user needs a sufficient experience to get good results.

Effect of dynamic cooling on 585-nm pulsed dye laser treatment of port-wine stain birthmarks.

BACKGROUND AND OBJECTIVE: The objective of this study was to determine the effectiveness of a dynamic cooling device (DCD), spraying the skin with a brief spurt of cryogen prior to the laser pulse, in reducing transient pain associated with 585-nm pulsed dye laser (PDL) treatment of port-wine stains (PWS), and reducing epidermal damage (hypo/hyperpigmentation) caused by this laser during PWS treatment. MATERIALS AND METHODS: Matched treatment sites were compared with and without the use of the cryogen spray in 47 patients at two investigational sites. Pain ratings, clearance of the PWS, and pigmentation changes were assessed. The results were analyzed by skin type and patient age. RESULTS: A statistically significant reduction in pain ratings was found in all patient groups using the DCD without changing the efficacy of PWS clearance. Pain reduction was most remarkable in patients with darker skin types. Dynamic cooling prevented the occurrence of epidermal damage or pigmentation change in most cases. CONCLUSIONS: This study suggests that dynamic cooling can dramatically diminish pain during PWS treatment with the 585-nm PDL without reducing treatment efficacy. The absence of epidermal damage in most patients suggests that precooling with the DCD may allow the use of higher laser fluences to expedite clearance without inducing epidermal change. Dynamic cooling has potential use with other lasers and different lesions where discomfort and epidermal effects limit therapy.

Treatment of capillary vascular malformation (port-wine stains) with photochemotherapy.

One-hundred and thirty patients (85 female, 45 male) with port-wine stains were treated with photodynamic therapy, also called photochemotherapy, which recently has become acknowledged as effective for a variety of malignant tumors. Probably based on the photochemical reaction with the generation of toxic species, photochemotherapy results in endothelial cell injury and death of abnormal capillaries under overlying epidermis. A retrospective review of 118 available patients with port-wine stains reveals that 98.3 percent responded to photochemotherapy with varying degrees of success after one-time treatment. Results were reported under a simple classification system ranging from ordinary to dilated to posttreatment type. In the ordinary group, the results evaluated as excellent, good, fair, and poor were 37.8, 53.7, 8.5, and 0 percent, respectively, before a second treatment; the treated area was an average of 9.8 (range 7 to 13) cm in diameter. In addition, hypertrophic scars, permanent hyperpigmentation, and hypopigmentation were not seen based on proper parameters. Photochemotherapy offers a potentially efficient and promising choice based on a completely different mechanism from that of selected photothermal therapy with the pulsed-dye laser.