Sonia A. Lamel

Epidermal Grafting Using a Novel Suction Blister–Harvesting System for the Treatment of Pyoderma Gangrenosum

Patient 1 A woman in her 40s without other significant medical history presented in 2013with an 8-month history of an exquisitely painful ulcer on thedistal left lateral leg. Shenoted that the lesionbeganas “a small red bump” that she believedtobean insectbite.Aphysician at another institutionperformedan incision anddrainage to treat a suspected abscess andprescribedoral antibiotics, but the lesiondeteriorated. Abiopsyperformed in 2012hadnonspecific results and Gram, acid-fast, and Fite stains were negative for organisms. Venous and arterial insufficiencywere excludedby lower limb duplexultrasound.She receivedadiagnosisofpyodermagangrenosum(PG)andwasprescribedprednisone60mgdailyandtopical clobetasol propionate ointment, 0.05%, to the wound edges. On referral,physicalexaminationrevealedasharplydemarcatedulcerwith purple undermined borders, consistent with the PG diagnosis. The prednisonedosagewas taperedbecauseof adverse effects, and cyclosporine 400 mg daily and weekly leg compression were initiated. Although the inflamed undermined borders improved, the wound failed to reduce in size after 2months of therapy (Figure 1).

US-National Institutes of Health-funded research for cutaneous wounds in 2012.

Chronic cutaneous wounds are a major burden on patients, healthcare providers, and the US healthcare system. This study, carried out in part by the Wound Healing Societys Government Regulatory Committee, aimed to evaluate the current state of National Institutes of Health funding of cutaneous wound healing–related research projects. National Institutes of Health Research Portfolio Online Reporting Tools Expenditures & Results system was used to identify wound healing projects funded by the National Institutes of Health in the 2012 fiscal year. Research projects focusing on cutaneous wound prevention/education, mechanisms, complications, treatment, or imaging/monitoring were included in the analysis. Ninety‐one projects were identified, totaling a collective funding of

Isolated human and animal stratum corneum as a partial model for the 15 steps of percutaneous absorption: emphasizing decontamination, part II

29,798,991 and median funding of

Topical Timolol for Recalcitrant Wounds

308,941. Thirteen institutes/centers from the National Institutes of Health were responsible for awarding funds; three of which (National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases) accounted for 60.4% of the grant funding. The predominant funding mechanisms included R01 (48.3%), R43 (14.3%), and R21 (9.9%). New applications and pre‐existing applications accounted for 39.6 and 55.0% of the awarded grants, respectively. Grants awarded to investigators affiliated with universities accounted for 68.1% of grants and 25.3% were to investigators in the private sector. This analysis of current National Institutes of Health funding may facilitate more transparency of National Institutes of Health‐allocated research funds and serve as an impetus to procure additional support for the field of wound healing.

Postinflammatory hyperpigmentation secondary to external insult: an overview of the quantitative analysis of pigmentation

Cutaneously directed chemical warfare agents can elicit significant morbidity and mortality. The optimization of prophylactic and therapeutic interventions counteracting these agents is crucial, and the development of decontamination protocols and methodology of post dermal exposure risk assessments would be additionally applicable to common industrial and consumer dermatotoxicants. Percutaneous (PC) penetration is often considered a simple one‐step diffusion process but presently consists of at least 15 steps. The systemic exposure to an agent depends on multiple factors and the second part of this review covers absorption and excretion kinetics, wash and rub effects, skin substantivity and transfer, among others. Importantly, the partitioning behavior and diffusion through the stratum corneum (SC) of a wide physicochemical array of compounds shows that many compounds have approximately the same diffusion coefficient which determines their percutaneous absorption in vivo. After accounting for anatomical variation of the SC, the penetration flux value of a substance depends mainly on its SC/vehicle partition coefficient. Additionally, the SC acts as a ‘reservoir’ for topically applied molecules, and tape stripping methodology can quantify the remaining chemical in the SC which can predict the total molecular penetration in vivo. The determination of ideal decontamination protocols is of utmost importance to reduce morbidity and mortality. However, even expeditious standard washing procedures post dermal chemical exposure often fails to remove chemicals. The second part of this overview continues to review percutaneous penetration extending insights into the complexities of penetration, decontamination and potential newer assays that may be of practical importance. Copyright

Primary nonadherence (failure to obtain prescribed medicines) among dermatology patients

Patient 1 A woman in her 80s with a history of venous insufficiency based on clinical presentation and vascular studies presentedwithmultiplepainfululcerationsonthebilateral ankles. She developed wounds in 1972 with subsequent trauma that led to repetitive skin breakdown.Her currentwounds began 1 year ago. The patient was initially treated with multilayered elastic compression bandages (Profore; Smith & Nephew), which were changed weekly, and various foam dressings (Allevyn; Smith & Nephew; Mepilex Ag; Molnlycke Health Care).When herwound failed to heal, adjuvant therapies, including serial applications of porcine small intestine submucosa (Oasis;HealthpointBiotherapeutics), bilayered living skin equivalent (Apligraf; Organogenesis) and an autologous splitthickness graft from the thighwere used but did not result in complete closure. After 6months, thewoundwas 3.2 cm2 and a β2-adrenergic receptor (B2AR) antagonist, topical timolol, 0.5% (Timoptic;AtonPharma),was instilled, 1dropevery2 cm of wound edge weekly, then covered with silicone foam and 3-layer compression. All wounds, including her target ulcer, were fully epithelialized after 8 weeks of treatment, and the patient was prescribed a compression apparatus (JuxtaCure; CircAid Medical Products) to prevent recurrence.

Isolated human/animal stratum corneum as a partial model for 15 steps in percutaneous absorption: emphasizing decontamination, Part I: 15 steps in percutaneous absorption

Context: Despite new technologies, few studies have quantified changes in melanocyte numbers associated with postinflammatory hyperpigmentation (PIH) secondary to exogenous causes. Objective: This article aims to review what is known about the pathogenesis of PIH secondary to external insults and its relationship to the resultant degree of quantitative changes in melanocytes. Methods: We performed a review of articles exploring PIH resulting from external cutaneous insults retrieved through database searching. We reviewed relevant articles for the pathogenesis, histopathology, and quantitative changes in melanocytes related to specific etiologies of PIH. Methodologies to quantify pigmentation changes in dermatologic conditions with clinical hyperpigmentation were also explored. Results: Significant increases in melanocyte counts of irritant affected skin is seen compared with melanocyte counts of unaffected skin. An increase in melanocyte counts was also found for spontaneous inflammatory dermatoses, even in the absence of clinical hyperpigmentation. Furthermore, changes in melanocyte density and appearance are also seen secondary to inflammation. In addition, increases in epidermal melanocytes are seen with cutaneous exposure to certain agents, and melanocyte increases vary by exposure agent. Conclusions: The degree of hyperpigmentation related to the intensity and duration of exposure to the causative factors of PIH is essential to better understand the pathophysiology of the disease process. The application of new methodologies to determine quantitative changes in melanocytes elicited by specific causative inflammatory agents has implications to prevent PIH, add to knowledge about disease duration, to develop better treatments for PIH, and to aid our understanding of the biology of the melanocyte.

Dermal exposure to methamphetamine hydrochloride contaminated residential surfaces: surface pH values, volatility, and in vitro human skin.

intraepidermal neutrophilic dermatosis-type IgA pemphigus (IEN-type) and the remaining 8 had the subcorneal pustular dermatosis-type IgA pemphigus (SPD-type). The aim of this study focused the IgA pemphigus therapeutic approach, with a follow-up length from 1 to 12 years (mean 3.8 years). The following treatments were used: dapsone, colchicine, prednisone, acitretin, isotretinoin, tetracycline, sulfamethoxazole/trimethoprim, methotrexate, cyclosporine, adalimumab, sulfamethoxypyridazine, azathioprine, and PUVA. Dapsone was used as a first line therapy (25 to 125 mg/day) in 6 patients. One patient with IEN-type disease was in complete remission off therapy. Two patients with SPD-type disease had a partial response. Three of 9 patients had side effects (methemoglobinemia and hemolysis) of dapsone therapy, and withdrawal of medication was necessary. Another 2 of 9 patients showed no response to any of the proposed therapies. Five of 9 patients were treated with colchicine (0.5 to 2 g/day): 4 had no response and 1 was lost to follow-up. Four of 9 patients received prednisone (0.5 to 1.5 mg/kg/day): 3 had no response with medication withdrawal, and 1 patient stayed in partial remission on therapy. Two of 9 patients were treated with tetracycline (1 to 2 g/day): acute urticaria developed in 1 patient, and 1 showed no response to treatment. Two of 9 patients were unresponsive to treatment and so were treated with multiple drugs. The condition of 1 of these patients stabilized in partial remission with adalimumab 40 mg biweekly, and she is currently receiving 40 mg bimonthly, 1 year after treatment was initiated, without any side effect so far. This was the most recalcitrant IgA pemphigus case of our series, with the patient showing no response to 10 therapeutic options over 6 years. The other patient had a severe form of the disease and received acitretin 30 mg/day after undergoing a hysterectomy for postpartum hemorrhage. This patient had a very good response and no longer required frequent hospitalization. Although her case is classified as a partial remission on therapy, acitretin exerted a great impact on her quality of life. Five patients were in partial remission on therapy, 1 patient was lost to follow-up, and 2 patients died of unrelated causes. The only patient who had complete remission off therapy was the patient with IEN-type disease. A review of 49 patients of both subtypes of IgA pemphigus suggests that those with IEN-type showed a better response to treatment, in comparison to SPD-type. Our experience was limited to one IEN-type patient, and therefore we could not conclude that IENor SPD-type showed different responses to treatment. So far, there is no consensus on IgA pemphigus treatment. Our results confirmed the recalcitrant nature of IgA pemphigus in response to distinct therapies, indicating that further research focusing on therapeutic approaches for this group of IgA diseases is needed.

Onychopharmacokinetics of terbinafine hydrochloride penetration from a novel topical formulation into the human nail in vitro

Since the advent of World War II, governments and laboratories have made a concerted effort to improve prophylactic and therapeutic interventions counteracting cutaneously directed chemical warfare agents (CWA), and by inference, common industrial and consumer dermatotoxicants. In vitro percutaneous penetration assays, first utilized by Tregear in the 1940s and presently in various modifications, have been fundamental to this effort. Percutaneous penetration, often considered a simple one‐step diffusion process, consists of at least 15 steps. The first part of this review covers the initial steps related to absorption and excretion kinetics, vehicle characteristics, and tissue disposition. Importantly, the partitioning behavior and stratum corneum (SC) diffusion by a wide physicochemical array of compounds shows that many compounds have similar diffusion coefficients determining their percutaneous absorption in vivo. After accounting for anatomical SC variation, the penetration flux value of a substance depends mainly on its SC/vehicle partition coefficient. Additionally, the SC acts as a ‘reservoir’ for topically applied molecules and application of tape stripping has been found to quantify the chemical remaining in the SC which can predict total molecular penetration in vivo. Decontamination is of particular concern and even expediting standard washing procedures after dermal chemical exposure often fails to remove chemicals. This overview summarizes knowledge of percutaneous penetration extending insights into the complexities of penetration, decontamination and potential newer assays that may be of practical importance. Copyright

Randomized, vehicle-controlled trials of topical 5-fluorouracil therapy for actinic keratosis treatment: an overview

This study evaluated pH effects on [(14)C] d-methamphetamine hydrochloride ([(14)C]-meth HCl) percutaneous penetration in vitro and volatility and stability in aqueous solution, on solid surface, or human skin using the finite dose technique and flow through diffusion cells. Results show that when the pH level exceeds 4 or 5, the nonvolatile [(14)C]-meth HCl salt becomes unstable, likely converting to its volatile freebase form. Additionally, contaminated smooth, dense surfaces retain and transfer more [(14)C]-meth HCl than those with rough, loose surfaces, especially under acidic conditions. Skin surface pH is a critical factor affecting the rate and magnitude of dermal absorption. [(14)C]-Meth HCl penetrates into and through the human cadaver skin quickly following exposure. [(14)C]-Meth HCl retained in the skin layer is released into the receptor fluid even if the contact material has been removed. Future exploration of decontaminant and removal procedure efficacies and their effect on dermal penetration of [(14)C]-meth HCl is recommended.