Topical antibiotics limit depigmentation in a mouse model of vitiligo.

Oral neomycin administration impacts the gut microbiome and delays vitiligo development in mice, and topical antibiotics may likewise allow the microbiome to preserve skin health and delay depigmentation. Here, we examined the effects of 6-week topical antibiotic treatment on vitiligo-prone pmel-1 mice. Bacitracin, Neosporin, or Vaseline were applied to one denuded flank, while the contralateral flank was treated with Vaseline in all mice. Ventral depigmentation was quantified weekly. We found that topical Neosporin treatment significantly reduced depigmentation and exhibited effects beyond the treated area, while Bacitracin ointment had no effect. Stool samples collected from four representative mice/group during treatment revealed that Neosporin treatment aligned with reduced abundance of the Alistipes genus in the gut, while relevant changes to the skin microbiome at end point were less apparent. Either antibiotic treatment led to reduced expression of MR1, potentially limiting mucosal-associated invariant T-cell activation, while Neosporin-treated skin selectively revealed significantly reduced CD8+ T-cell abundance. The latter finding aligned with reduced expression of multiple inflammatory markers and markedly increased regulatory T-cell density. Our studies on favorable skin and oral antibiotic treatment share the neomycin compound, and in either case, microbial changes were most apparent in stool samples. Taken together, neomycin-containing antibiotic applications can mediate skin Treg infiltration to limit vitiligo development. Our study highlights the therapeutic potential of short-term antibiotic applications to limit depigmentation vitiligo.

Towards Formulation of Highly Acidic Active Ingredients: Development of Clinically Effective Concentrated Trichloroacetic Acid Gel for Wart Management.

Common warts are benign skin lesions caused by the human papillomavirus. Although they are usually not harmful, they can cause pain, depending on their location. While many modalities are available for treatment of warts, none is a gold standard, and many are not affordable and/or have suboptimal outcomes. Trichloroacetic acid (TCA) is a chemical tissue-destroying agent used as a highly concentrated solution for wart management. While available and efficient, it is difficult to handle as the solution spreads to tissue surrounding the wart causing pain and burning. Hence, we developed a new polymer-based gel of high TCA content (100% w/v). Gels were formed successfully as hydroxyethyl cellulose (HEC) and chitosan were used to impart viscosity and bioadhesion. Formulae of different concentrations were tested for their physical properties, and the optimal formulation was selected for clinical evaluation. A combination of 3% HEC and 2% chitosan provided optimal viscosity and limited water content and have acceptable stability. The efficacy and safety of the biweekly application of TCA gel were evaluated in 30 patients. The clinical study revealed gel's efficacy and tolerability; half of the patients showed a complete cure, and 90% showed improvement within 6 weeks. Only 10-12% of the patients reported side effects. In summary, transforming TCA solution into a gel enabled its application and handling in a practical manner by physicians and patients alike, while maintaining its efficacy as a tissue-destroying agent. Moreover, it is economic and easy to apply, rendering it a promising formulation for similar conditions requiring controlled tissue ablation.

Clinical characteristics of pediatric hidradenitis suppurativa: a cross-sectional multicenter study of 140 patients.

Hidradenitis suppurativa (HS) rarely affects pediatric patients. The literature on pediatric HS patients is scarce. This is a cross-sectional study based on case note review or interviews and clinical examination of 140 pediatric patients undergoing secondary or tertiary level care. Patients were predominantly female (75.5%, n = 105) with a median age of 16. 39% reported 1st-degree relative with HS. Median BMI percentile was 88, and 11% were smokers (n = 15). Median modified Sartorius score was 8.5. Notable comorbidities found were acne (32.8%, n = 45), hirsutism (19.3%, n = 27), and pilonidal cysts (16.4%, n = 23). Resorcinol (n = 27) and clindamycin (n = 25) were the most frequently used topical treatments. Patients were treated with tetracycline (n = 32), or oral clindamycin and rifampicin in combination (n = 29). Surgical excision was performed in 18 patients, deroofing in five and incision in seven patients. Obesity seemed to be prominent in the pediatric population and correlated to parent BMI, suggesting a potential for preventive measures for the family. Disease management appeared to be similar to that of adult HS, bearing in mind that the younger the patient, the milder the disease in majority of cases.

Microneedling combined with platelet-rich plasma or trichloroacetic acid peeling for management of acne scarring: A split-face clinical and histologic comparison.

BACKGROUND: Minimally invasive procedures provide effective, safe, relatively long-lasting, and natural results without large damage to the skin. A combination treatment is considered an approach that includes at least 2 different and unrelated modalities. OBJECTIVES: This study aims to evaluate the use and effectiveness of some combined minimally invasive procedures for management of acne scarring. PATIENTS/METHODS: Twenty-four volunteers with postacne atrophic scars were randomly divided into 3 equal groups according to performed procedure on each side of the face (microneedling by dermaroller alone or combined with platelet-rich plasma [PRP] or trichloroacetic acid [TCA] 15% peeling) and received 6 bi-weekly sessions of treatment. Photography and punch biopsies were taken before and after 3 months of treatment for clinical, histological, and histometrical evaluation. RESULTS: Combined treatment of dermaroller and PRP or dermaroller and TCA 15% showed significant improvement when compared with dermaroller alone (P = .015 and .011 respectively). Epidermal thickness showed statistically significant increase in studied groups, mainly after dermaroller and TCA 15%. Moreover, the 3 studied groups showed more organized collagen bundles and newly formed collagen formation and markedly decreased abnormal elastic fibers. CONCLUSIONS: Based on the clinical, histometrical, and histochemical assessment, inspite that most volunteers showed significant improvement after treatment, however, the combined use of dermaroller and TCA 15% was more effective in postacne atrophic scars than the use of dermaroller and PRP or dermaroller only.

Microdermabrasion: a clinical, histometric, and histopathologic study.

BACKGROUND: Microdermabrasion is a nonchemical superficial resurfacing procedure that removes the stratum corneum. Because it is a somewhat subtle procedure, it may be difficult to demonstrate its cosmetic benefit. OBJECTIVES: To assess the efficacy of microdermabrasion in treatment of melasma, postacne scarring, striae distensae, and photoaging by a series of microdermabrasion sittings through clinical, histometric, and histopathologic analysis. PATIENTS AND METHODS: The study was conducted on 38 patients constituting four groups (melasma, acne scars, striae destinsae, and photoaging), each patient was subjected to a series of 8 microdermabrasion treatments performed at 1-week interval. Punch biopsies, at base line, 1 week after the 4th and the 8th session, were obtained from each subject for histometric and histopathologic analysis. RESULTS: Clinically, the improvement in melasma, acne scars, and striae distensae groups was mainly mild to moderate, while in photoaging group was mainly mild. Histometric analysis of epidermal thickness showed insignificant changes in all groups. Histopathologically, decreased melanization and regular distribution of melanosomes in the epidermis were noted in melasma group while increased density of collagen fibers with more regular arrangement in collagen bundles was detected in all candidates of acne scars, striae distensae, and photoaging groups. Meanwhile, Orcein stain did not show any significant changes in elastic fibers. CONCLUSIONS: Microdermabrasion is an easy and safe technique. In this study, most cases showed mild to moderate improvement. Decreased melanization with regular distribution of melanosomes and increased collagen density with regular arrangement of collagen bundles were the most common observed histologic changes.

Forehead wrinkles: a histological and immunohistochemical evaluation.

BACKGROUND: Wrinkles are associated with cutaneous aging especially on sun-exposed skin. Despite they are considered a major topic in cosmetic dermatology, very few reports have studied the specific histological and immunohistochemical changes characteristic for wrinkles. AIM: The study aims to evaluate the histological and immunohistochemical changes of static forehead wrinkles in relation to surrounding photoaged skin. METHODS: Biopsy specimens were obtained from the forehead wrinkles of 20 volunteers of Glogau's class III-IV wrinkles. Using histological and immunostaining methods coupled with computerized morphometric analysis, measurement of epidermal thickness and quantitative evaluation of total elastin and tropoelastin as well as collagen types I, III, and VII were performed for skin biopsies. RESULTS: In the wrinkle site, there was statistically significant lower epidermal thickness (P = 0.001), elastin (P < 0.001), tropoelastin (P < 0.001), and collagen VII (P < 0.001) than the surrounding photoaged skin. Meanwhile, there was no significant difference between the wrinkle site and adjacent photoaged skin regarding collagen type I (P = 0.07) or III (P = 0.07). CONCLUSION: This study detected some histological and immunohistochemical differences in the wrinkle site when compared to adjacent photoaged skin. This may help in understanding the pathophysiology of facial wrinkling as well as its ideal way of management.

Multiple fractional erbium: yttrium-aluminum-garnet laser sessions for upper facial rejuvenation: clinical and histological implications and expectations.

BACKGROUND: Fractional photothermolysis is a modern resurfacing technique, in which microscopic zones of thermal injury are created, stimulating turnover of both epidermis and dermis. Fractional laser rejuvenation has been developed to overcome the drawbacks of traditional ablative laser. OBJECTIVES: To objectively evaluate the effectiveness of multiple sessions of fractional Er:YAG laser rejuvenation for aging upper face clinically, histologically and immunohistochemically. PATIENTS/METHODS: Ten volunteers asking for facial rejuvenation were subjected to multiple sessions (3-5) of fractional Er:YAG laser. Clinical evaluation with both histopathological and immunohistochemical assessment for skin biopsies was carried out before, after 1 month and 6 months of laser resurfacing. Histometry for epidermal thickness and quantitative assessment for neocollagen formation, collagen I, III, and VII, elastin and tropoelastin were carried out for all skin biopsies. RESULTS: Comparing before, after 1 month and 6 months of fractional Er:YAG laser resurfacing resulted in improved clinical appearance with increased epidermal thickness (P < 0.001). Dermal collagen showed increased neocollagen formation (P = 0.006), with increased concentration of collagen types I (P < 0.001), III (P < 0.001), and VII (P = 0.001). Dermal elastic tissue studies revealed decreased elastin, while tropoelastin concentration increased after laser resurfacing (P < 0.001). An increase in collagen (I and III) and tropoelastin level and decreased elastin content was encountered with increasing the number of sessions, yet it was not significant. CONCLUSIONS: Multiple sessions are effective in rejuvenation of the aging face with high safety, short downtime, and no adverse effects. They stimulated formation of new collagen (type I, III, and VII) up to 6 months after treatment with better improvement in skin texture and fine wrinkles. The variable number of fractional Er:YAG laser sessions (3-5) showed no significant difference as regards efficacy.

Evaluation of apoptosis regulatory proteins in response to PUVA therapy for psoriasis.

BACKGROUND: The histopathologic changes characteristic of psoriasis might be related to suppressed apoptosis. One of the actions of psoralen ultraviolet A (PUVA) in psoriasis could be exerted through induction of apoptosis of keratinocytes and lymphocytes; however, its exact molecular mechanism is still confusing. AIM: In this study, we evaluated the expression of pro-apoptotic (P53, Fas and Bax) and anti-apoptotic (Bcl-2) proteins correlating it with apoptotic index (AI) and epidermal thickness in psoriatic skin before and after PUVA therapy. METHODS: Lesional and non-lesional skin biopsy specimens were obtained from 10 patients with generalized plaque psoriasis before and after 8 weeks of PUVA therapy. Histometric measurements of epidermal thickness as well as P53, Fas, Bax and Bcl-2 expressions were evaluated using immunoperoxidase technique and apoptotic cells were detected by terminal deoxynucleotide transferase (TdT) mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. RESULTS: After PUVA therapy, the epidermal thickness of psoriatic skin was significantly decreased (P < 0.001) and keratinocytes of psoriatic skin showed significant increased expression of P53 (P < 0.001), Fas (P < 0.001) and Bcl-2 (P < 0.001) with no significant change in Bax expression (P > 0.05). Apart from significant decrease of Bcl-2 expression (P = 0.01), no significant difference in all previous markers were encountered in lymphocytes (P53, Fas and Bax; P > 0.05) after PUVA therapy. The AI was significantly increased (P = 0.008) after PUVA therapy especially in lymphocytes (P = 0.002). CONCLUSION: The present study suggests that one of the actions of PUVA therapy in psoriasis might be exerted through induction of apoptosis especially of lymphocytes by suppression of Bcl-2 expression and of keratinocytes through P53 and Fas pathways leading to healing of psoriasis.

Fractional versus ablative erbium:yttrium-aluminum-garnet laser resurfacing for facial rejuvenation: an objective evaluation.

BACKGROUND: Laser is one of the main tools for skin resurfacing. Erbium:yttrium-aluminum-garnet (Er:YAG) was the second ablative laser, after carbon dioxide, emitting wavelength of 2940 nm. Fractional laser resurfacing has been developed to overcome the drawbacks of ablative lasers. OBJECTIVE: We aimed to objectively evaluate the histopathological and immunohistochemical effects of Er:YAG 2940-nm laser for facial rejuvenation (multiple sessions of fractional vs single session of ablative Er:YAG laser). METHODS: Facial resurfacing with single-session ablative Er:YAG laser was performed on 6 volunteers. Another 6 were resurfaced using fractional Er:YAG laser (4 sessions). Histopathological (hematoxylin-eosin, orcein, Masson trichrome, and picrosirius red stains) and immunohistochemical assessment for skin biopsy specimens were done before laser resurfacing and after 1 and 6 months. Histometry for epidermal thickness and quantitative assessment for neocollagen formation; collagen I, III, and VII; elastin; and tropoelastin were done for all skin biopsy specimens. RESULTS: Both lasers resulted in increased epidermal thickness. Dermal collagen showed increased neocollagen formation with increased concentration of collagen types I, III, and VII. Dermal elastic tissue studies revealed decreased elastin whereas tropoelastin concentration increased after laser resurfacing. Neither laser showed significant difference between their effects clinically and on dermal collagen. Changes in epidermal thickness, elastin, and tropoelastin were significantly more marked after ablative laser. LIMITATIONS: The small number of patients is a limitation, yet the results show significant improvement. CONCLUSION: Multiple sessions of fractional laser have comparable effects to a single session of ablative Er:YAG laser on dermal collagen but ablative laser has more effect on elastic tissue and epidermis.

Evaluation of apoptosis regulatory markers in androgenetic alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is a common androgen-induced progressive disorder; the pathways of which are regulated by local genetic codes and hormonal control. Meanwhile, it is unclear whether an altered proliferation or increased apoptosis could contribute to its pathogenesis. AIMS: To evaluate the role of some apoptosis regulatory markers and follicular proliferation in the pathogenesis of AGA. PATIENTS/METHODS: Thirty biopsies were taken from the frontal (bald) area and occipital (hair-bearing) area of 15 male patients with AGA, as well as five specimens from the frontal area of five age-matched controls. The biopsies were stained with apoptosis regulatory markers (Bcl-2, p53, Bax & Fas) and PCNA (proliferating cell nuclear antigen), as well as TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling) staining for the detection of DNA fragmentation in apoptotic cells. RESULTS: Bcl-2 expression was localized to epidermal basal layer and follicular dermal papilla with highly significant correlation with PCNA expression (P < 0.001). Perifollicular lymphocytic infiltrate of the bald area showed significant expression of Bcl-2. However, pro-apoptotic Bax and Fas were expressed in the epidermis and not in the hair follicles which does not show any apoptotic keratinocytes by TUNEL staining. CONCLUSION: The low proliferation rate in the bald area of patients, together with persistent perifollicular inflammatory infiltrate as evidenced by the anti-apoptotic Bcl-2 expression in dermal lymphocytes, would result in follicular miniaturization and fibrosis.

Androgenetic alopecia in males: a histopathological and ultrastructural study.

BACKGROUND: Androgenetic alopecia is a common cosmetic hair disorder, resulting from interplay of genetic, endocrine, and aging factors leading to a patterned follicular miniaturization. Microinflammation seems to be a potential active player in this process. AIMS: To study the histopathological and ultrastructural changes occurring in male androgenetic alopecia (AGA). Patients/methods Fifty-five subjects were included in this study (40 with AGA and 15 as normal age-matched controls). Skin biopsies from frontal bald area and occipital hairy area were subjected to histopathological examination, immunohistochemical staining for collagen I and ultrastructural study. RESULTS: The frontal bald area of patients showed highly significant increase in telogen hairs and decrease in anagen/telogen ratio and terminal/vellus hair ratio (P < 0.001). Perifollicular inflammation was almost a constant feature in early cases and showed a significant inverse correlation with perifollicular fibrosis (P = 0.048), which was more marked with thickening of the follicular sheath in advanced cases. CONCLUSION: Follicular microinflammation plays an integral role in the pathogenesis of AGA in early cases. Over time, thickening of perifollicular sheath takes place due to increased deposition of collagen, resulting in marked perifollicular fibrosis, and sometimes ends by complete destruction of the affected follicles in advanced cases.

Effect of laser resurfacing on p53 expression in photoaged facial skin.

BACKGROUND: p53 overexpression has been reported in photoaged skin. Meanwhile, p53 gene mutations have been implicated as an important factor in the pathogenesis of ultraviolet (UV) light-induced skin cancer. OBJECTIVE: The objective was to evaluate the effect of laser resurfacing on the epidermal thickness and expression of p53 in photoaged skin. METHODS: Specimens were obtained from the facial skin of 10 patients before and after 3 months and 1 year of treatment using CO(2) (five cases) and erbium (Er):YAG (five cases) lasers. Specimens were also obtained from six age-matched controls. These biopsies were used for routine histopathology, histometry, and p53 immunoperoxidase staining. RESULTS: Both CO(2) and Er:YAG lasers were found to induce a significant decrease in p53 expression in biopsies obtained after 3 months (p=.0004 and .002, respectively) followed by gradual increase (p=.01 in both groups). A significant increase (p<.01) in epidermal thickness was also observed after 1 year of resurfacing. This increase, however, is inversely correlated with the level of p53 expression in such patients. CONCLUSION: The decrease in epidermal p53 expression after CO(2) and Er:YAG lasers may account for some of the benefits of resurfacing on the epidermis, as well as prevention of actinic neoplasia by adjusting any disturbance in the proliferation/apoptosis balance observed in photoaged facial skin.