Faculty Bibliography

BACKGROUND:Hair transplant surgery creates consistently natural appearing transplanted hair for men. It is increasingly popular procedure to restore natural growing hair for men with hair loss. OBJECTIVE:To review some current controversies in hair transplant surgery. MATERIALS AND METHODS/METHODS:Review of the English PubMed literature and specialty literature in hair transplant surgery. RESULTS:Some of the controversies in hair transplant surgery include appropriate donor harvesting technique including elliptical donor harvesting versus follicular unit extraction whether manual versus robotic, the role of platelet-rich plasma and low-level light surgery in hair transplant surgery. CONCLUSION/CONCLUSIONS:Hair transplant surgery creates consistently natural appearing hair. As with all techniques, there are controversies regarding the optimal method for performing the procedure. Some of the current controversies in hair transplant surgery include optimal donor harvesting techniques, elliptical donor harvesting versus follicular unit extraction, the role of low-level light therapy and the platelet-rich plasma therapy in the procedure. Future studies will further clarify their role in the procedure.

Atopic dermatitis (AD) is the most common inflammatory skin disease, but treatment options for moderate-to-severe disease are limited. Ustekinumab is an IL-12/IL-23p40 antagonist that suppresses Th1, Th17 and Th22 activation, commonly used for psoriasis patients. We sought to assess efficacy and safety of ustekinumab in patients with moderate-to-severe AD. In this phase II, double-blind, placebo-controlled study, 33 patients with moderate-to-severe AD were randomly assigned to either ustekinumab (n=16) or placebo (n=17), with subsequent crossover at 16 weeks, and last dose at 32 weeks. Background therapy with mild topical steroids was allowed to promote retention. Study endpoints included clinical (SCORAD50) and biopsy-based measures of tissue structure and inflammation, using protein and gene expression studies. The ustekinumab group achieved higher SCORAD50 responses at 12, 16 (the primary endpoint) and 20 weeks compared to placebo, but the difference between groups was not significant. The AD molecular profile/transcriptome showed early robust gene modulation, with sustained further improvements until 32 weeks in the initial ustekinumab group. Distinct and more robust modulation of Th1, Th17 and Th22 but also Th2-related AD genes was seen after 4 weeks of ustekinumab treatment (i.e. MMP12, IL-22, IL-13, IFN-γ, elafin/PI3, CXCL1 and CCL17; P<.05). Epidermal responses (K16, terminal differentiation) showed faster (4 weeks) and long-term regulation (32 weeks) from baseline in the ustekinumab group. No severe adverse events were observed. Ustekinumab had clear clinical and molecular effects, but clinical outcomes might have been obscured by a profound "placebo" effect, most likely due to background topical glucocorticosteroids and possibly insufficient dosing for AD.

BACKGROUND:Topical glucocorticosteroids are considered an efficient treatment option for atopic dermatitis (AD), but a global assessment of glucocorticosteroid responses on key disease circuits upon weeks to months of treatment is currently lacking. OBJECTIVE:We sought to assess short (4 weeks) and long-term (16 weeks) application of topical glucocorticosteroids on AD skin and define response biomarkers. METHODS:The effects of triamcinolone acetonide cream 0.025% were assessed based on gene expression and immunohistochemistry studies at baseline, 4 weeks, and 16 weeks in biopsy specimens from 15 patients with moderate-to-severe AD. RESULTS:At 16 weeks, only 3 patients were clinical responders (by using SCORAD50 criteria), but 6 patients qualified as responders based on histologic criteria. Baseline characteristics indicated more severe disease in nonresponders. While 3 of 15 patients experienced only transient benefit after 4 weeks, others showed progressive improvements toward 16 weeks. Topical glucocorticosteroid use in patients with AD resulted in improvements of the AD genomic signature of 25.6% at 4 weeks and 71.8% at 16 weeks, respectively, and even 123.9% in the histologic responder group. Cytokines (IL-12p40, IL-13, IL-22, CCL17, CCL18, peptidase inhibitor 3 [PI3]/elafin, and S100As) showed consistent decreases from baseline toward 16 weeks with corresponding improvements in epidermal disease hallmarks (keratin 16 and loricrin) in lesional skin from responders (P < .05). Nonresponders largely showed lesser/nonsignificant reductions in key inflammatory and barrier markers (keratin 16, IL-13, IL-22, CCL17, CCL18, PI3/elafin, S100As, and loricrin). The combination of IL-21 and IFN-γ baseline expression closely predicted individual clinical glucocorticosteroid responses at 16 weeks of treatment. CONCLUSION:Our study indicates that even low-potency glucocorticosteroids can broadly affect immune and barrier responses in patients with moderate-to-severe AD, associating higher baseline severity with increased steroid resistance in patients with AD.

BACKGROUND:Petrolatum is a common moisturizer often used in the prevention of skin infections after ambulatory surgeries and as a maintenance therapy of atopic dermatitis (AD). However, the molecular responses induced by petrolatum in the skin have never been assessed. OBJECTIVE:We sought to define the cutaneous molecular and structural effects induced by petrolatum. METHODS:Thirty-six healthy subjects and 13 patients with moderate AD (mean SCORAD score, 39) were studied by using RT-PCR, gene arrays, immunohistochemistry, and immunofluorescence performed on control skin, petrolatum-occluded skin, and skin occluded with a Finn chamber only. RESULTS:Significant upregulations of antimicrobial peptides (S100A8/fold change [FCH], 13.04; S100A9/FCH, 11.28; CCL20/FCH, 8.36; PI3 [elafin]/FCH, 15.40; lipocalin 2/FCH, 6.94, human β-defensin 2 [DEFB4A]/FCH, 4.96; P < .001 for all) and innate immune genes (IL6, IL8, and IL1B; P < .01) were observed in petrolatum-occluded skin compared with expression in both control and occluded-only skin. Application of petrolatum also induced expression of key barrier differentiation markers (filaggrin and loricrin), increased stratum corneum thickness, and significantly reduced T-cell infiltrates in the setting of "normal-appearing" or nonlesional AD skin, which is known to harbor barrier and immune defects. CONCLUSIONS:Petrolatum robustly modulates antimicrobials and epidermal differentiation barrier measures. These data shed light on the beneficial molecular responses of petrolatum in barrier-defective states, such as AD and postoperative wound care.

BACKGROUND AND OBJECTIVES/OBJECTIVE:A 28-year-old female presented with extensive scarring after a traumatic injury to her right lower extremity. She had been hit by a vehicle one year prior to presentation and had several open fractures with extensive overlying cutaneous damage, which required multiple surgeries and skin grafts. She had limited range of motion of the affected limb secondary to scar contracture. STUDY DESIGN/MATERIALS AND METHODS/METHODS:The patient received 6 treatments with a non-ablative fractional resurfacing (NAFR) device with two wavelengths (Fraxel DUAL, Solta Medical, Hayward, CA) spaced 4-8 weeks apart. The patient received two treatments with the 1927 nm NAFR thulium laser (10 mJ, 30% density, 8 passes) and two treatments with the 1550 nm NAFR laser (40 mJ, 17-26% density, 8 passes). Before and after treatment photographs were taken, as well as range of motion measurements with respect to her right ankle. RESULTS:The patient had 50-75% improvement in the texture and discoloration. There was both subjective and objective improvement in the range of motion of her right lower extremity. The patient experienced mild erythema and edema, both of which resolved after 7-10 days. CONCLUSION/CONCLUSIONS:Recent studies have shown great functional improvement in scar contractures with ablative fractional laser treatments; however, these treatments are accompanied by significant downtime along with risk of further scarring and infection. NAFR is an accessible treatment with a low side effect profile and to our knowledge has not been reported as efficacious in the treatment of scar contracture. This case report is novel in its demonstration of the utility of a dual wavelength NAFR in the treatment of scar contracture and functional impairment.

BACKGROUND AND OBJECTIVE/OBJECTIVE:A port wine stain (PWS) is a type of capillary vascular malformation composed of malformed, dilated blood vessels within the papillary and reticular dermis. Currently, pulsed dye laser (PDL) is considered the therapeutic gold standard, although greater than 90% of lesions may be refractory to treatment. Studies have shown that a delay in treatment results in a higher proportion of patients who develop hypertrophy and nodularity within lesions that become more resistant to therapy. Therapeutic resistance is multifactorial, but is believed to be largely due to revascularization after laser treatment. Oral sirolimus and topical imiquimod have shown promise as adjunctive therapies to minimize post-laser revascularization, but both have significant side effects. We wish to demonstrate the utility of adjunct topical sirolimus to reduce revascularization after PDL treatment. STUDY DESIGN/PATIENTS AND METHODS/METHODS:This is a single patient case report of a 56-year-old male patient with an extensive PWS. After seeing initial improvement with PDL alone, he began to experience thickening and nodularity of his PWS necessitating surgical debulking. Since this procedure, topical sirolimus 0.5% ointment has been added to his treatment regimen as an adjunct to PDL. The patient is being treated with PDL (Vbeam Perfecta, Candela/Syneron, Wayland, MA) every 4-6 weeks at varied settings with the following laser parameters: fluence 9-11 J/cm(2), pulse duration 0.45-1.5 ms, focal spot size 7 mm, cooling 30/20. Sirolimus 0.5% ointment is applied to the area twice daily. RESULTS:The patient showed significant improvement in color and texture of his PWS. Compared to the initial therapy of PDL alone, topical sirolimus ointment in conjunction with PDL demonstrated greater improvement and maintenance of therapeutic results with fewer overall laser treatments. CONCLUSION/CONCLUSIONS:Topical sirolimus 0.5% ointment is a safe and effective adjunct to PDL in the treatment of PWS.

BACKGROUND: Atopic dermatitis (AD) is the most common inflammatory disease. The prevalence of allergic contact dermatitis to allergens (eg, fragrance) is higher in patients with AD, despite a trend toward weaker clinical allergic contact dermatitis reactions. The role of the AD skin phenotype in modulating allergic sensitization to common sensitizers has not been evaluated. OBJECTIVE: We sought to investigate whether patients with AD have altered tissue immune responses on allergen challenge. METHODS: Gene expression and immunohistochemistry studies were performed on biopsy specimens from 10 patients with AD and 14 patients without AD patch tested with common contact allergens (nickel, fragrance, and rubber). RESULTS: Although 1085 differentially expressed genes (DEGs) were commonly modulated in patch-tested skin from patients with AD and patients without AD versus control skin, 1185 DEGs were uniquely altered in skin from patients without AD, and only 246 DEGs were altered in skin from patients with AD. Although many inflammatory products (ie, matrix metalloproteinase 12/matrix metalloproteinase 1/S100A9) were upregulated in both groups, higher-magnitude changes and upregulation of interferon responses were evident only in the non-AD group. Stratification by allergen showed decreased expression of immune, TH1-subset, and TH2-subset genes in nickel-related AD responses, with increased TH17/IL-23 skewing. Rubber/fragrance showed similar trends of lesser magnitude. Negative regulators showed higher expression in patients with AD. CONCLUSIONS: Through contact sensitization, our study offers new insights into AD. Allergic immune reactions were globally attenuated and differentially polarized in patients with AD, with significant decreases in levels of TH1 products, some increases in levels of TH17 products, and inconsistent upregulation in levels of TH2 products. The overall hyporesponsiveness in skin from patients with background AD might be explained by baseline immune abnormalities, such as increased TH2, TH17, and negative regulator levels compared with those seen in non-AD skin.