Faculty Bibliography

BACKGROUND: Hyaluronidase is an enzyme capable of dissolution of hyaluronic acid (HA). There is a lack of evidence-based research defining time- and concentration-dependent reversal of HA filler using hyaluronidase. OBJECTIVE: To explore the efficacy of different concentrations of hyaluronidase in digesting commercially available HA-based reversible fillers-Belotero Balance (BEL), Juvederm Ultra XC (JUVXC), Juvederm Ultra Plus (JUVX+), Juvederm Voluma XC (JUVV), Restylane-L (RESL), Restylane Silk (RESS), and Perlane/Restylane Lyft (RESLYFT). MATERIALS AND METHODS: This was a blinded randomized study involving 15 participants. Participants received HA filler injection into their back, followed by no secondary injection, or injection with normal saline, 20 or 40 units of hyaluronidase. Using a 5-point palpation scale, the degradation of HA filler was monitored over 14 days. RESULTS: In the authors' study, there is a significant decrease in HA filler degradation using 20 and 40 units of hyaluronidase compared with no secondary injection or normal saline. There is no significant difference in HA filler dissolution when comparing 20 to 40 units of hyaluronidase. CONCLUSION: Lower concentrations of hyaluronidase may be just as effective as higher concentrations to degrade HA filler in situations where the reversal of cutaneous augmentation with HA filler arises.

"Fractionated photodynamic therapy (PDT)" is a new term being used by dermatologists to describe advances in PDT technology including fractionated light or the adjuvant use of fractional lasers. Although dermatologists have used PDT since the early 1990s for the treatment of photodamage and precancerous lesions, newer developments in technology have allowed for the treatment of non-melanoma skin cancers (NMSCs), in ammatory disorders, and even uses in the eld of anti-aging. Recent developments in fractionated light therapy have allowed for PDT with dark intervals and two-fold illumination schemes to increase cellular damage and apoptosis. Combining PDT with fractional laser technology has allowed for enhanced dermal penetration of topical photosensitizers including 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL), as well as increased ef cacy of treatment. These advances in PDT technology will allow for increased convenience, decreased treatment time, only one application of topical photosensitizer, and decreased cost to the patient and dermatologist. J Drugs Dermatol. 2016;15(11):1324-1328.

Purpose of the Review This article serves to review the newest combination approaches of fractionated resurfacing lasers with other treatment modalities and highlights our clinical pearls. Recent Findings Combination therapies with fractionated lasers include treatments with transdermal drug delivery, radio-frequency, light-based devices, photodynamic therapy, and transdermal acoustic pressure. Summary Fractional resurfacing lasers revolutionized the laser skin resurfacing surgery by offering similar clinical outcomes to ablative lasers with fewer side effects and less post-treatment downtime. Fractionated lasers are the pillar of skin resurfacing treatments for photodamaged skin such as rhytides, lentigines, and dermal elastosis, actinic damage, and other dermatologic conditions, including acne, rosacea, and scars.

BACKGROUND AND OBJECTIVES: Laser procedures in skin of color (SOC) patients are challenging due to the increased risk of dyspigmentation and scarring. A novel 755 nm alexandrite picosecond laser has demonstrated effectiveness for tattoo removal and treatment of acne scars. No studies to date have evaluated its applications in pigmentary disorders. The purpose of this retrospective study was to evaluate the safety profile and efficacy of the picosecond alexandrite laser compared to the current standard treatment, Q-switched ruby and neodynium (Nd):YAG nanosecond lasers, for pigmentary disorders in SOC patients. STUDY DESIGN/MATERIALS AND METHODS: A retrospective photographic and chart evaluation of seventy 755 nm alexandrite picosecond, ninety-two Q-switched frequency doubled 532 nm and 1,064 nm Nd:YAG nanosecond, and forty-seven Q-switched 694 nm ruby nanosecond laser treatments, in forty-two subjects of Fitzpatrick skin types III-VI was conducted in a single laser specialty center. The picosecond laser was a research prototype device. Treatment efficacy was assessed by two blinded physician evaluators, using a visual analog scale for percentage of pigmentary clearance in standard photographs. Subject assessment of efficacy, satisfaction, and adverse events was performed using a questionnaire survey. RESULTS: The most common pigmentary disorder treated was Nevus of Ota (38.1%), followed by solar lentigines (23.8%). Other pigmentary disorders included post-inflammatory hyperpigmentation, congenital nevus, cafe au lait macule, dermal melanocytosis, Nevus of Ito, and Becker's nevus. Clinical efficacy of the Q-switched nanosecond lasers and picosecond laser treatments were comparable for lesions treated on the face with a mean visual analog score of 2.57 and 2.44, respectively, corresponding to approximately 50% pigmentary clearance. Subject questionnaires were completed in 58.8% of the picosecond subjects and 52.0% of the Q-switched subjects. Eighty four percent of subjects receiving Q-switched nanosecond laser treatments and 50% of the subjects receiving alexandrite 755 nm picosecond laser treatments felt satisfied to completely satisfied. Side effects observed in subjects treated with the alexandrite 755 nm picosecond laser were similar to those commonly observed and reported with the nanosecond Q-switched technology. All side effects were temporary, resolving within one month, and no long-term complications were noted. All patients who were very satisfied with their picosecond laser treatment for Nevus of Ota noted a delayed improvement only after 3 months. CONCLUSION: The 755 nm alexandrite picosecond, 694 nm ruby, 532 nm, and 1064 nm neodynium:YAG nanosecond lasers appear to be safe and effective modalities for removal of pigmentary disorders in skin of color patients with no long-term complications if used appropriately. This study demonstrates the potential of the 755 nm alexandrite picosecond laser in further clinical applications beyond tattoo removal. While the Q-switched lasers were effective, promising results were also observed using an early version of the novel picosecond laser for the removal of pigmentary lesions in SOC patients. As we continue to improve our understanding of the 755 nm picosecond laser, this device may prove to be a safe and effective alternative to the Q-switched lasers for the treatment of facial pigmented lesions in patients with skin of color. Lasers Surg. Med. 48:181-187, 2016. (c) 2016 Wiley Periodicals, Inc.

We present a 53-year-old woman with diffuse macular amyloidosis. We discuss the clinical manifestations, pathophysiologic mechanisms, and associations of cutaneous macular amyloidosis.

We present a 67-year-old man with an ulcerated, indurated plaque on the right mid back with a presumed diagnosis of morphea that was complicated by an allergic contact dermatitis. Further clinical and histopathologic data elucidated the diagnosis of fluoroscopy-induced radiation dermatitis. We present a brief review of the common locations, clinical characteristics, pathophysiology, and management options for fluoroscopy-induced radiation dermatitis.

Antimicrobial effector mechanisms are central to the function of the innate immune response in host defense against microbial pathogens. In humans, activation of Toll-like receptor 2/1 (TLR2/1) on monocytes induces a vitamin D dependent antimicrobial activity against intracellular mycobacteria. Here, we report that TLR activation of monocytes triggers induction of the defensin beta 4 gene (DEFB4), requiring convergence of the IL-1beta and vitamin D receptor (VDR) pathways. TLR2/1 activation triggered IL-1beta activity, involving the upregulation of both IL-1beta and IL-1 receptor, and downregulation of the IL-1 receptor antagonist. TLR2/1L induction of IL-1beta was required for upregulation of DEFB4, but not cathelicidin, whereas VDR activation was required for expression of both antimicrobial genes. The differential requirements for induction of DEFB4 and cathelicidin were reflected by differences in their respective promoter regions; the DEFB4 promoter had one vitamin D response element (VDRE) and two NF-kappaB sites, whereas the cathelicidin promoter had three VDREs and no NF-kappaB sites. Transfection of NF-kappaB into primary monocytes synergized with 1,25D3 in the induction of DEFB4 expression. Knockdown of either DEFB4 or cathelicidin in primary monocytes resulted in the loss of TLR2/1-mediated antimicrobial activity against intracellular mycobacteria. Therefore, these data identify a novel mechanism of host defense requiring the induction of IL-1beta in synergy with vitamin D activation, for the TLR-induced antimicrobial pathway against an intracellular pathogen.

Propionibacterium acnes is a critical component in the pathogenesis of acne vulgaris, stimulating the production of various inflammatory mediators, such as cytokines and chemokines, important in the local inflammatory response found in acne. This study explored the role of P. acnes and its ability to induce matrix metalloproteinases (MMPs) in primary human monocytes and how this induction is regulated by retinoids. MMP-1- and MMP-9-expressing cells were present in perifollicular and dermal inflammatory infiltrates within acne lesions, suggesting their role in acne pathogenesis. In vitro, we found that P. acnes induced MMP-9 and MMP-1 mRNA, and the expression of MMP-9, but not of MMP-1, was found to be Toll-like receptor 2-dependent. P. acnes induced the mRNA expression of tissue inhibitors of metalloproteinase (TIMP)-1, the main regulator of MMP-9 and MMP-1. Treatment of monocytes with all-trans retinoic acid (ATRA) significantly decreased baseline MMP-9 expression. Furthermore, co-treatment of monocytes with ATRA and P. acnes inhibited MMP-9 and MMP-1 induction, while augmenting TIMP-1 expression. These data indicate that P. acnes-induced MMPs and TIMPs may be involved in acne pathogenesis and that retinoic acid modulates MMP and TIMP expression, shifting from a matrix-degradative phenotype to a matrix-preserving phenotype.

Propionibacterium acnes is a major etiological factor of acne, triggering an inflammatory response in part through the activation of TLR2. In this study, we demonstrate that activation of peripheral blood monocytes with P. acnes in vitro induced their differentiation into two distinct innate immune cell subsets, CD209(+) macrophages and CD1b(+) dendritic cells. Furthermore, P. acnes induced expression of mRNA for the cytokines IL-15 and GM-CSF, which differentiate CD209(+) and CD1b(+) cells, respectively. The CD209(+) cells were more effective in uptake of P. acnes, compared with the CD1b(+) cells, and demonstrated a 2-fold greater antimicrobial activity against the phagocytosed bacteria. Although CD1b(+) cells secreted inflammatory cytokines in response to both P. acnes and a TLR2 ligand control, the CD209(+) cells responded only to P. acnes. The addition of all-trans retinoic acid, a commonly used agent for the treatment of acne, directly induced differentiation of monocytes into CD209(+) macrophages and enhanced the P. acnes-mediated differentiation of the CD209(+) subset. Therefore, the differentiation of monocytes into CD209(+) macrophages and CD1b(+) dendritic cells distinctly mediate the innate immune response to P. acnes.