[Show abstract][Hide abstract] ABSTRACT: Hidradenitis suppurativa (HS) is a chronic, recurrent, debilitating disease predominantly involving apocrine gland-bearing skin. The folliculoinfundibular dysfunction and an aberrant cutaneous immune response to commensal bacteria are recognized as potential contributors. Topical antibiotics, such as clindamycin, and keratolytic agents have been used in the management of early stages of HS. Proper wound care is a key part of management, particularly in patients with advanced HS. The evidence for the optimal topical therapy or optimal local wound care is limited. As such, a multidisciplinary approach is necessary to address all aspects of HS, including topical therapy, systemic therapy, and proper wound care. The focus of this paper is to review the evidence for the topical management and local wound care strategies in patients with HS.
Journal of the American Academy of Dermatology 11/2015; 73(5):S55-S61. DOI:10.1016/j.jaad.2015.07.048 · 4.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
International Wound Journal 09/2015; DOI:10.1111/iwj.12497 · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Perforin-2 (MPEG1) is a pore-forming, antibacterial protein with broad-spectrum activity. Perforin-2 is expressed constitutively in phagocytes and inducibly in parenchymal, tissue-forming cells. In vitro, Perforin-2 prevents the intracellular replication and proliferation of bacterial pathogens in these cells. Perforin-2 knockout mice are unable to control the systemic dissemination of methicillin-resistant Staphylococcus aureus (MRSA) or Salmonella typhimurium and perish shortly after epicutaneous or orogastric infection respectively. In contrast, Perforin-2-sufficient littermates clear the infection. Perforin-2 is a transmembrane protein of cytosolic vesicles -derived from multiple organelles- that translocate to and fuse with bacterium containing vesicles. Subsequently, Perforin-2 polymerizes and forms large clusters of 100Å pores in the bacterial surface with Perforin-2 cleavage products present in bacteria. Perforin-2 is also required for the bactericidal activity of reactive oxygen and nitrogen species and hydrolytic enzymes. Perforin-2 constitutes a novel and apparently essential bactericidal effector molecule of the innate immune system.
[Show abstract][Hide abstract] ABSTRACT: Diabetes Mellitus (DM) is a chronic, severe disease rapidly increasing in incidence and prevalence and is associated with numerous complications. Patients with DM are at high risk of developing diabetic foot ulcers (DFU) that often lead to lower limb amputations, long term disability, and a shortened lifespan. Despite this, the effects of DM on human foot skin biology are largely unknown. Thus, the focus of this study was to determine whether DM changes foot skin biology predisposing it for healing impairment and development of DFU. Foot skin samples were collected from 20 patients receiving corrective foot surgery and, using a combination of multiple molecular and cellular approaches, we performed comparative analyses of non-ulcerated non-neuropathic diabetic foot skin (DFS) and healthy non-diabetic foot skin (NFS). MicroRNA (miR) profiling of laser captured epidermis and primary dermal fibroblasts from both DFS and NFS samples identified 5 miRs de-regulated in the epidermis of DFS though none reached statistical significance. MiR-31-5p and miR-31-3p were most profoundly induced. Although none were significantly regulated in diabetic fibroblasts, miR-29c-3p showed a trend of up-regulation, which was confirmed by qPCR in a prospective set of 20 skin samples. Gene expression profiling of full thickness biopsies identified 36 de-regulated genes in DFS (>2 fold-change, unadjusted p-value ≤ 0.05). Of this group, three out of seven tested genes were confirmed by qPCR: SERPINB3 was up-regulated whereas OR2A4 and LGR5 were down-regulated in DFS. However no morphological differences in histology, collagen deposition, and number of blood vessels or lymphocytes were found. No difference in proliferative capacity was observed by quantification of Ki67 positive cells in epidermis. These findings suggest DM causes only subtle changes to foot skin. Since morphology, mRNA and miR levels were not affected in a major way, additional factors, such as neuropathy, vascular complications, or duration of DM, may further compromise tissue's healing ability leading to development of DFUs.
PLoS ONE 08/2015; 10(8):e0137133. DOI:10.1371/journal.pone.0137133 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
J Drugs Dermatol . 2015;14(7):734-738.
Journal of drugs in dermatology: JDD 07/2015; 14(7):734-738. · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: As restoration of the integument is paramount to wound healing, dermatologists should be central to managing wounds; yet this is often not the case. If a training gap exists during residency training, this may account for the observed discrepancy.
OBJECTIVES: To identify United States (US) dermatology residents' impressions regarding their preparedness to care for wounds, and to assess the amount and type of training devoted to wound care during residency.
DESIGN, SETTING, AND PARTICIPANTS: An online survey among current US dermatology residents enrolled in a residency training program.
MAIN OUTCOMES AND MEASURES: The primary goal was to determine whether dermatology residents believe more wound care education is needed, evaluate preparedness to care for wounds, and identify future plans to manage wounds.
RESULTS: Responses were received from 175 of 517 (33.8%) US Dermatology residents contacted. The majority of residents did not feel prepared to manage acute (78.3%) and chronic (84.6%) wounds. Over three quarters (77.1%) felt that more education is needed. Fewer than half (49.1% and 35.4%) of residents planned to care for acute and chronic wounds, respectively, when in practice.
CONCLUSIONS AND RELEVANCE: There is a gap in wound care education in US dermatology residency training. This translates to a low percentage of dermatology residents planning to care for wounds in future practice. Dermatology residents need to receive focused wound care training in order to translate the underpinnings of wound healing biology and ultimately better serve patients.
J Drugs Dermatol. 2015;14(7):716-720.
Journal of drugs in dermatology: JDD 07/2015; 14(7):716-720. · 1.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: UV radiation is among the most prevalent stressors in humans and diurnal rodents, exerting direct and indirect DNA damage, free-radical production, and interaction with specific chromophores that affects numerous biological processes. In addition to its panoply of effects, UVB (290-320 nm) radiation can specifically affect various local neuroendocrine activities by stimulating the expression of corticotropin-releasing hormone (CRH), urocortin, proopiomelanocortin (POMC), and POMC-derived peptides. Although very little is known about the interplay between the central hypothalamic-pituitary-adrenal (HPA) axis and the skin HPA axis analog, in the current issue Skobowiat and Slominski propose a novel mechanism by which exposure to UVB activates a local HPA axis in skin, which in turn activates the central HPA axis, with the requirement of a functional pituitary gland. This is the first evidence of the local HPA axis in skin contributing to the central neuroendocrine response. This raises intriguing possibilities regarding how local production of cortisol and other HPA axis molecules in skin influence overall systemic levels of cortisol and help regulate local and central HPA axes in the context of homeostasis, skin injury, and inflammatory skin disorders.
[Show abstract][Hide abstract] ABSTRACT: Livedoid vasculopathy (LV) is a thrombo occlusive disorder presenting with recurrent painful ulcers of lower extremities. Association of LV with increased level of lipoprotein (a) (LP(a)), a risk factor for cardiovascular disease, has been reported. Danazol has been used with success in the management of LV, but none of the previous studies looked at the correlation between response to the treatment and level of LP(a). The aim of this study was to demonstrate the efficacy of low-dose danazol in the treatment of LV and its effects on LP(a). We present four cases with LV who were successfully treated with low-dose danazol, assessing the clinical characteristics and laboratory tests including the level of LP(a). The average age of the patients was 45 years and the mean duration of the disease was 19 years. The treatment regime of danazol 200 mg daily led to complete healing of ulcers and reduction in pain and a 70% (ranging from 52 to 87%) reduction in the level of LP(a). The limitation of this study is " small sample size. " In our patients with LV, low-dose danazol led to clinical improvement along with significant reduction in the level of LP(a).
[Show abstract][Hide abstract] ABSTRACT: Objective: This study compares two different negative pressure wound therapy (NPWT) modalities in the treatment of venous leg ulcers (VLUs), the ultraportable mechanically powered (MP) Smart Negative Pressure (SNaP(®)) Wound Care System to the electrically powered (EP) Vacuum-Assisted Closure (V.A.C.(®)) System. Approach: Patients with VLUs from 13 centers participated in this prospective randomized controlled trial. Each subject was randomly assigned to treatment with either MP NPWT or EP NPWT and evaluated for 16 weeks or complete wound closure. Results: Forty patients (n=19 MP NPWT and n=21 EP NPWT) completed the study. Primary endpoint analysis of wound size reduction found wounds in the MP NPWT group had significantly greater wound size reduction than those in the EP NPWT group at 4, 8, 12, and 16 weeks (p-value=0.0039, 0.0086, 0.0002, and 0.0005, respectively). Kaplan-Meier analyses showed greater acceleration in complete wound closure in the MP NPWT group. At 30 days, 50% wound closure was achieved in 52.6% (10/19) of patients treated with MP NPWT and 23.8% (5/21) of patients treated with EP NPWT. At 90 days, complete wound closure was achieved in 57.9% (11/19) of patients treated with MP NPWT and 38.15% (8/21) of patients treated with EP NPWT. Innovation: These data support the use of MP-NPWT for the treatment of VLUs. Conclusions: In this group of venous ulcers, wounds treated with MP NPWT demonstrated greater improvement and a higher likelihood of complete wound closure than those treated with EP NPWT.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Patients with venous leg ulcers (VLUs) have calf muscle pump dysfunction, which is associated with reduced ankle range of motion (ROM). Physical therapy or exercise that targets ankle joint mobility may lead to improvement in calf muscle pump function and subsequent healing. However, little is known regarding the effect of physical therapy or exercise on healing and quality of life (QOL), which is impaired in patients with VLUs.
To systematically review the current literature on the effect of physical therapy on healing and QOL outcomes in patients with VLUs and to identify research gaps that warrant further investigation.
PubMed (MEDLINE), CINHAHL, and Cochrane databases were searched in April 2014.
We found 10 articles, consisting of randomized clinical trials and single-arm cohort studies with small sample sizes, that used physical therapy or exercise for patients with open or healed VLUs. Although there is evidence that exercise strengthens the calf muscle pump and improves ankle ROM, few studies have investigated the effect of these interventions on QOL and healing, and few involved the supervision of a physical therapist.
The lack of evidence and randomized clinical trials suggests the need for further investigation on physical therapy-oriented exercise on wound healing and QOL. In addition, more studies are needed to investigate sustainability of the increased ankle ROM after physical therapy has ended or if VLU reoccurrences are prevented.