Statins may be associated with six-week diabetic foot ulcer healing.

Diabetic foot ulcers (DFUs) affect 1.5 million Americans annually, of which only a minority heal with standard care, and they commonly lead to amputation. To improve care, investigations are underway to better understand DFU pathogenesis and develop more effective therapies. Some currently used medications may improve healing. One small, randomized clinical trial found statins improve DFU healing. In this secondary analysis of a large multisite prospective observational cohort of 139 patients with DFUs receiving standard care, we investigated whether there was an association between 6-week DFU wound size reduction and use of a variety of medications including alpha-blockers, beta-blockers, angiotensin converting enzyme inhibitors (ACEi) and statins. We found no significant (p < 0.05) association between six-week wound reduction and use of any of the evaluated drugs; however, statins did trend toward an association (p = 0.057). This suggests a potential benefit of statins on DFU healing, and larger, targeted studies are warranted.

Adalimumab treatment leads to reduction of tissue tumor necrosis factor-alpha correlated with venous leg ulcer improvement: a pilot study.

Venous leg ulcers (VLUs) have higher tumor necrosis factor-α (TNF-α) levels compared with normal skin. Refractory VLUs of long duration have higher TNF-α levels compared with VLUs of shorter duration. As up to 75% of VLUs fail to heal with standard care, we sought to evaluate the role of anti-TNF-α therapy for patients with refractory VLUs. Evaluable data were obtained in four of five subjects with recalcitrant VLUs treated with 80 mg of subcutaneous adalimumab at week 0 and with 40 mg at week 2 along with compression therapy and were followed-up for 6 weeks. Wound biopsies taken at weeks 0 and 4 were stained with anti-TNF-α antibodies. Average 4-week percent wound size reduction was 20.5% ± 6.4%. Two patients had wound size reduction more than 25%, and their percent wound size reduction correlated to percent TNF-α staining score reductions (P = 0.02, R(2) = 0.999). VLU TNF-α level decrease 4 weeks post-adalimumab treatment correlated with wound healing.

Ketoconazole-induced Sweet syndrome: a new association.

Sweet syndrome (SS) is an acute febrile neutrophilic dermatosis that can be associated with malignancy and medications. A 60-year-old man presented with erythematous, edematous, and ulcerated plaques in the extensor surface of the upper extremities, after a ketoconazole course due to pityrosporum folliculitis. Skin biopsy showed a dense dermal neutrophilic infiltrate, associated with marked papillary dermal edema. Blood count showed leukocytosis and neutrophilia. Skin lesions resolved spontaneously with discoloration after 2 weeks of discontinuation of ketoconazole. Although most cases of drug-induced SS are associated with granulocyte colony-stimulating factor, other medications need to be considered. This is the first reported case of ketoconazole-induced SS despite its widespread use.

Is Tumor of Follicular Infundibulum a Reaction to Dermal Scarring?

Tumor of follicular infundibulum (TFI) is currently believed to be a benign epithelial neoplasm with follicular differentiation. It has been suggested that TFI is associated with dermal scarring, but further investigation is needed to confirm this correlation. To approach this question, a retrospective study was presented, a total of 67 cases (64 lesions) were found in a search covering cases over a 10-year period. Overall, the presence of histological dermal scarring was noted in 34 of 64 (53.13%) cases. Of the cases where TFI was an incidental finding, the presence of dermal scarring was noted in 13 of 18 (72.22%) cases. Meanwhile, of the cases where TFI was the main diagnosis, the presence of dermal scarring was noted in 12 of 34 (35.29%) cases. This suggests that TFI may, in some cases, represent an epidermal reaction pattern to dermal scarring.

Cryo-Induced Thermal Wounds: A Human Acute Wound Model.

INTRODUCTION: Clinical models are invaluable in studying wound healing. Challenges in studying human wounds include heterogeneity of patients and wounds, as well as prolonged study time, resulting in high costs. Animal models are an efficient method to study wound healing, but often lack correlation with human acute wound healing. Human wound models can be created using sharp instruments, suction, acids, heat and cold. In this observational study, we propose a practical human acute wound model where partial thickness wounds are induced by cryosurgery to create wounds that could facilitate wound healing research and development. METHODS: On forearms of 8 healthy adult volunteers, freeze injuries were induced using liquid nitrogen spray delivered onto a target area of a 1 cm circular opening at a distance from the cryo-device to the skin of 0.5-1 cm. Several freeze-thaw time cycles were implemented by administering pulses ranging from 3 to 12 seconds. Clinical evaluation was performed at a 24-hour follow-up period. Blister roofs were histologically analyzed by a blinded dermatophathologist. Clinical assessment of time to heal was determined. RESULTS: Freeze-times greater than 5 seconds caused a majority of subjects to develop blisters, and freeze-times greater than 8 seconds resulted in uniform blister formation. Consistent histology of full thickness necrotic epidermis with intact detached basement membrane with minimal acute neutrophilic inflammatory infiltrate was observed in all blister specimens examined. The 8-second freeze-time group had a time to heal of 13-14 days, while the 12-second freeze-time group required 3 weeks to heal. After healing, an area of hypopigmented skin and slightly hypertrophic scarring remained. DISCUSSION: This novel cryo-induced wound model is a potential simple, efficient and reliable model for studying the dynamic processes involved in acute wound healing and to aid in the development of new wound healing therapies. Clinicaltrials.gov identifier: NCT01253135.

Wound research funding from alternative sources of federal funds in 2012.

Chronic wounds represent a major healthcare burden, costing $25 billion annually, and are associated with high mortality. We previously reported that cutaneous wound healing represented only 0.1% ($29.8 million) of the National Institutes of Health budget. This current study focuses on quantifying the contribution by federal agencies other than the National Institutes of Health for fiscal year 2012. Federal databases including USA Spending, Veterans Affairs, Tracking Accountability in Government Grants Systems, Health Services Research Projects in Progress, and Patient-Centered Outcomes Research Institute, were searched for individual projects addressing wound healing. Twenty-seven projects were identified, totaling funding of $16,588,623 (median: $349,856). Four sponsor institutions accounted for 74% of awarded funds: Department of the Army, National Science Foundation, Department of Veterans Affairs, and Agency for Healthcare Research & Quality. Research projects and cooperative agreements comprised 44% and 37% of awarded grants. New applications and continuing projects represented 52% and 37%. Wound healing represented 0.15% of total medical research funded by the non-National Institutes of Health federal sector. Compared with potential impact on US public health, federal investment in wound research is exiguous. This analysis will draw attention to a disproportionately low investment in wound research and its perils to American public health.

Probiotics and prebiotics in dermatology.

The rapid increase in the medical use of probiotics and prebiotics in recent years has confirmed their excellent safety profile. As immune modulators, they have been used in inflammatory skin conditions, such as atopic dermatitis. We review the literature regarding the use of probiotics and prebiotics in dermatology. Probiotics and prebiotics appear to be effective in reducing the incidence of atopic dermatitis in infants, but their role in atopic dermatitis treatment is controversial. Their role in acne, wound healing, and photoprotection is promising, but larger trials are needed before a final recommendation can be made.

Gluten and skin disease beyond dermatitis herpetiformis: a review.

Gluten, a protein found in wheat, rye, and barley, is known to cause an immune reaction in patients with celiac disease (CD) resulting in small bowel villous atrophy and impaired nutrient absorption and cutaneous manifestations in patients with dermatitis herpetiformis (DH). It is common that patients associate skin conditions with their diet, and the advantages of a gluten-free diet (GFD) are brought up frequently. Indeed, there is evidence that certain dermatologic conditions can respond to a GFD, especially for those with concomitant CD and DH. In the last decade, new data have become available on the significance of gluten in skin disease. Herein, we review the role of gluten and a GFD on various cutaneous diseases beyond DH.

Association between baseline abundance of Peptoniphilus, a Gram-positive anaerobic coccus, and wound healing outcomes of DFUs.

Diabetic foot ulcers (DFUs) lead to nearly 100,000 lower limb amputations annually in the United States. DFUs are colonized by complex microbial communities, and infection is one of the most common reasons for diabetes-related hospitalizations and amputations. In this study, we examined how DFU microbiomes respond to initial sharp debridement and offloading and how the initial composition associates with 4 week healing outcomes. We employed 16S rRNA next generation sequencing to perform microbial profiling on 50 samples collected from 10 patients with vascularized neuropathic DFUs. Debrided wound samples were obtained at initial visit and after one week from two DFU locations, wound bed and wound edge. Samples of the foot skin outside of the wounds were also collected for comparison. We showed that DFU wound beds are colonized by a greater number of distinct bacterial phylotypes compared to the wound edge or skin outside the wound. However, no significant microbiome diversity changes occurred at the wound sites after one week of standard care. Finally, increased initial abundance of Gram-positive anaerobic cocci (GPAC), especially Peptoniphilus (p < 0.05; n = 5 subjects), was associated with impaired healing; thus, GPAC's abundance could be a predictor of the wound-healing outcome.

Optimizing Skin Grafting Using Hair-derived Skin Grafts: The Healing Potential of Hair Follicle Pluripotent Stem Cells.

BACKGROUND: A man in his 60s with recurrent venous leg ulcers (VLUs) presented with an 18-month history of a VLU on his medial left leg measuring 59.3 cm(2). He had been treated with multi- component compression bandages without significant decrease in ulcer size. Given the ulcer's size, refractory nature, and history of recurrence, the authors sought to optimize the patient's healing. METHODS: Approximately 23% of the total wound was treated using punch grafts (PGs) harvested from different locations on the body based on hair density using the "stick and place" method. RESULTS: One month later, a 56% reduction in ulcer size was observed, especially in the area that received hair-bearing skin. CONCLUSION: Punch grafts from hair-bearing skin are a viable source of follicular stem cells and may be superior to PG from nonhair-bearing skin for the treatment of chronic wounds.

Patient Preference in Dermatologist Attire in the Medical, Surgical, and Wound Care Settings.

IMPORTANCE: Patients' perceptions of their physician can affect subjective and objective outcomes. Physician attire influences patients' perceptions of their physician and consequently may affect patient outcomes. OBJECTIVE: To determine patient preferences for different types of dermatologist attire in dermatology medical, surgical, and wound care clinics. We hypothesized that patients in the dermatology medical setting would prefer professional attire, while patients in the dermatology surgical and wound care setting would prefer surgical scrubs. DESIGN, SETTING, AND PARTICIPANTS: This study analyzed responses to a cross-sectional, anonymous survey by English-speaking dermatology patients (aged 18 years or older) at general, surgical, and wound care clinics in an academic center in Miami, Florida. Patients who could not read and understand the survey were excluded. Participants received pictures of a physician wearing business attire, professional attire, surgical attire, and casual attire, and responded by indicating which physician they preferred for each of 19 questions. Frequencies of responses were recorded, and χ2 and regression tests were performed. MAIN OUTCOMES AND MEASURES: Response frequencies. RESULTS: Surveys were administered to 261 persons, and 255 participated and completed enough of the questions to be included in the outcome analyses (118 men, 121 women, 22 unknown [did not answer sex question]), mean (SD) age, 56.3 (18.6) years; about 49% of those who reported their sex were men; 56% were Hispanic; and 85% were white. Approximately 72% of respondents held a college degree or higher. About 63%, 24%, and 13% of respondents were medical, surgical, and wound care dermatology patients, respectively. Roughly 73%, 19%, 6%, and 2% of cumulative responses were for professional, surgical, business, and casual attire, respectively. Respondents who received a picture of a black male or black female physician were more likely to exclusively prefer professional attire: unadjusted odds ratios (ORs) 3.21 (95% CI, 1.39-7.42) and 2.78 (95% CI, 1.18-6.51), respectively, compared with respondents who received a picture of a white male physician. Nonwhite and unemployed respondents were less likely to prefer professional attire exclusively: ORs, 0.28 (95% CI, 0.1-0.83) and 0.28 (95% CI, 0.08-0.99), respectively. Respondents preferred professional attire in all clinic settings, though respondents in the dermatology surgery clinic were less likely to prefer professional attire compared with respondents in the medical dermatology clinic: race-adjusted OR, 0.74 (95% CI, 0.56-0.98). Wound care and medical dermatology respondents preferred professional attire comparably. CONCLUSIONS AND RELEVANCE: In this study, most patients preferred professional attire for their dermatologists in most settings. It is possible that patients' perceptions of their physicians' knowledge and skill is influenced by the physicians' appearance, and these perceptions may affect outcomes.

Lichen Planopilaris in the Androgenetic Alopecia Area: A Pitfall for Hair Transplantation.

BACKGROUND: Classic lichen planopilaris (LPP) is a patchy form of primary lymphocytic cicatricial alopecia localized on the vertex of the scalp. It is important, however, to be aware of other, less recognized presentations that may be missed without dermatoscopy and pathology. METHODS AND RESULTS: We report 26 patients with LPP presenting with subtle erythema and scaling colocalized in the area of patterned thinning (androgenetic alopecia, AGA). All patients had been treated for seborrheic dermatitis in the past. Dermatoscopy showed the presence of 2-4 hairs emerging as a tuft from the same ostium surrounded by erythema, peripilar casts and interfollicular scaling associated with hair miniaturization. Histopathology obtained from those areas corresponded to LPP with concomitant follicular miniaturization. CONCLUSION: Subtle or focal cases of LPP may be missed for seborrheic dermatitis when overlapping with AGA. Dermatoscopy-guided biopsy from the affected scalp is the best approach to make a timely diagnosis. This is particularly important in patients with AGA evaluated to undergo hair transplantation, as active LPP is a contraindication for these patients.

Healing refractory venous ulcers: new treatments offer hope.

Non-healing wounds are associated with an inflammatory and proteolytic wound environment, and recent therapeutic strategies have been focused on reversing these changes. Connexins, as members of gap junctions, are important in intercellular signaling and wound repair. Connexin 43 (Cx43) downregulation is associated with normal wound healing, and it has been found to be upregulated in non-healing venous leg ulcers (VLUs). Ghatnekar et al. (2014) report findings of a small phase II trial performed in Indian patients with chronic VLUs, reporting that ACT1, a mimetic peptide of Cx43, accelerates healing in the treatment group. Despite standard care with compression therapy and adjuvant therapy for refractory wounds, at present in clinical practice a significant number of patients remain unhealed. The potential for ACT1 exists to help heal refractory VLUs, but it faces additional regulatory hurdles.

Contact dermatitis caused by preservatives.

Preservatives are biocidal chemicals added to food, cosmetics, and industrial products to prevent the growth of microorganisms. They are usually nontoxic and inexpensive and have a long shelf life. Unfortunately, they commonly cause contact dermatitis. This article reviews the most important classes of preservatives physicians are most likely to encounter in their daily practice, specifically isothiazolinones, formaldehyde and formaldehyde-releasers, iodopropynyl butylcarbamate, methyldibromoglutaronitrile, and parabens. For each preservative mentioned, the prevalence of sensitization, clinical presentation of contact dermatitis, patch testing concentrations, cross reactions, and related legislation will be discussed. Mandatory labeling of preservatives is required in some countries, but not required in others. Until policies are made, physicians and patients must be proactive in identifying potential sensitizers and removing their use. We hope that this article will serve as a guide for policy makers in creating legislation and future regulations on the use and concentration of certain preservatives in cosmetics and industrial products.