Atypical Pyoderma Gangrenosum in the Setting of Venous and Arterial Insufficiency.

Ulcers of mixed etiology are diagnostically elusive and challenging to treat, especially when rare conditions are superimposed. Pyoderma gangrenosum (PG) is an autoinflammatory, ulcerative skin disease that is difficult to diagnose. Diagnostic criteria exist but there are no specific clinical tests to identify it. We discuss a case of PG initially diagnosed as venous ulcer in the setting of peripheral artery disease, complicated by superinfection, refractory to standard wound care, multiple surgical debridements, revascularization, negative pressure therapy, and parenteral antibiotics. Findings differentiating PG from other wound etiologies are explored, with the aim of improving clinical recognition of this condition.

Iron Deficiency Anaemia and Atonic Postpartum Haemorrhage Following Labour.

The purpose of this retrospective cohort study is to determine if iron deficiency anaemia (IDA) is associated with increased atonic postpartum haemorrhage (PPH) following labour. Women with singleton pregnancy carried to 24 or more weeks gestation, who were delivered under our care from 1997 to 2019, constituted the study population. A diagnosis of IDA was based on the finding of haemoglobin <10 g/dL and serum ferritin <15 µg/L in the absence of haemoglobinopathies. Women with elective caesarean section were excluded. Maternal characteristics, use of oxytocin, labour outcome and occurrence of PPH were compared between women with and without a diagnosis of IDA. The 1032 women (0.86%) with IDA exhibited slightly but significantly different maternal characteristics and had significantly higher incidence of total (4.5% versus 3.2%, p = 0.024) and atonic PPH (3.1% versus 2.0%, p = 0.011) despite similar incidences of labour induction, augmentation, and instrumental and intrapartum caesarean delivery. Multivariate analysis with adjustment for the effects of age, body mass index, height, parity, abortion history, labour induction and augmentation, instrumental delivery and infant macrosomia demonstrated that IDA was independently associated with total PPH (adjusted relative risk, aRR: 1.455, 95% confidence ratio, CI: 1.040-2.034) and atonic PPH (aRR: 1.588, 95% CI: 1.067-2.364). Our results indicate that despite the low prevalence in our population, IDA was independently associated with atonic PPH, probably consequent to placental adaptive changes in the presence of IDA. The correction and prevention of IDA could be the most important measure in countering the rising global prevalence of atonic PPH.

The importance of caveolins and caveolae to dermatology: Lessons from the caves and beyond.

Caveolae are flask-shaped invaginations of the cell membrane rich in cholesterol and sphingomyelin, with caveolin proteins acting as their primary structural components that allow compartmentalization and orchestration of various signalling molecules. In this review, we discuss how pleiotropic functions of caveolin-1 (Cav1) and its intricate roles in numerous cellular functions including lipid trafficking, signalling, cell migration and proliferation, as well as cellular senescence, infection and inflammation, are integral for normal development and functioning of skin and its appendages. We then examine how disruption of the homeostatic levels of Cav1 can lead to development of various cutaneous pathophysiologies including skin cancers, cutaneous fibroses, psoriasis, alopecia, age-related changes in skin and aberrant wound healing and propose how levels of Cav1 may have theragnostic value in skin physiology/pathophysiology.

Pharmacological and Genetic Inhibition of Caveolin-1 Promotes Epithelialization and Wound Closure.

Chronic wounds-including diabetic foot ulcers, venous leg ulcers, and pressure ulcers-represent a major health problem that demands an urgent solution and new therapies. Despite major burden to patients, health care professionals, and health care systems worldwide, there are no efficacious therapies approved for treatment of chronic wounds. One of the major obstacles in achieving wound closure in patients is the lack of epithelial migration. Here, we used multiple pre-clinical wound models to show that Caveolin-1 (Cav1) impedes healing and that targeting Cav1 accelerates wound closure. We found that Cav1 expression is significantly upregulated in wound edge biopsies of patients with non-healing wounds, confirming its healing-inhibitory role. Conversely, Cav1 was absent from the migrating epithelium and is downregulated in acutely healing wounds. Specifically, Cav1 interacted with membranous glucocorticoid receptor (mbGR) and epidermal growth factor receptor (EGFR) in a glucocorticoid-dependent manner to inhibit cutaneous healing. However, pharmacological disruption of caveolae by MßCD or CRISPR/Cas9-mediated Cav1 knockdown resulted in disruption of Cav1-mbGR and Cav1-EGFR complexes and promoted epithelialization and wound healing. Our data reveal a novel mechanism of inhibition of epithelialization and wound closure, providing a rationale for pharmacological targeting of Cav1 as potential therapy for patients with non-healing chronic wounds.

Extracutaneous involvement of pyoderma gangrenosum.

Pyoderma Gangrenosum (PG) is an inflammatory neutrophilic dermatosis (ND) associated with underlying chronic inflammation and/or malignancy. Diagnosis remains to be challenging as a gold standard diagnostic test is lacking. Initial manifestations may include papules, vesicles, or pustules that subsequently develop into ulceration with features of undermining and violaceous borders. Timely recognition of pyoderma gangrenosum is impeded by clinical findings shared with other etiologies, such as granulomatosis with polyangiitis, polyarteritis nodosa, and antiphospholipid syndrome. As with any other ND, extracutaneous involvement may also occur preceding, during, or following the appearance of skin lesions. Sterile neutrophilic infiltrates have been found to affect internal organs supporting the concept of PG being a systemic disease, with lung being the most common extracutaneous manifestation followed by ocular and visceral compromise. Therefore, in this review, we describe the current knowledge of extracutaneous involvement of PG and its respective clinical manifestations to aid dermatologists in diagnosis, management, and determining prognosis.

Bioidentical hormone therapy in menopause: relevance in dermatology.

Hormone replacement therapy has been shown to be effective in alleviating menopausal symptoms. However, its use is controversial owing to potential health risks, such as thromboembolism and cancer. Bioidentical hormone therapy has recently become popular as an alternative to conventional hormone replacement therapy. These bioidentical hormones have a molecular structure identical to endogenous hormones found in a woman's body. A claimed advantage of bioidentical hormone therapy is the compounding practice in order to individualize therapy depending on patient's own hormone levels and symptoms. However, there is no scientific evidence to assess the validity of these claims. Bioidentical hormone therapy has also been used by dermatologists for its anti-aging effects on the skin, but little is known about efficacy and side effects of bioidentical hormones in this field. This review illustrates the main purpose of bioidentical hormone therapy for dermatological uses and its potential side effects, serving as a tool for dermatologists when facing these patients.

Single cell analyses reveal specific distribution of anti-bacterial molecule Perforin-2 in human skin and its modulation by wounding and Staphylococcus aureus infection.

Perforin-2 (P-2) is a recently described antimicrobial protein with unique properties to kill intracellular bacteria. We investigated P-2 expression pattern and cellular distribution in human skin and its importance in restoration of barrier function during wound healing process and infection with the common wound pathogen Staphylococcus aureus. We describe a novel approach for the measurement of P-2 mRNA within individual skin cells using an amplified fluorescence in situ hybridization (FISH) technique. The unique aspect of this approach is simultaneous detection of P-2 mRNA in combination with immune-phenotyping for cell surface proteins using fluorochrome-conjugated antibodies. We detected P-2 transcript in both hematopoietic (CD45+ ) and non-hematopoietic (CD45- ) cutaneous cell populations, confirming the P-2 expression in both professional and non-professional phagocytes. Furthermore, we found an induction of P-2 during wound healing. P-2 overexpression resulted in a reduction of intracellular S. aureus, while infection of human wounds by this pathogen resulted in P-2 suppression, revealing a novel mechanism by which S. aureus may escape cutaneous immunity to cause persistent wound infections.

The epithelialisation phase in wound healing: options to enhance wound closure.

This review highlights epithelialisation and therapeutic options to optimise and speed the epithelialisation process. To influence this process therapeutically, it is important for clinicians to understand the underlying principles of epithelialisation. The role of growth factors and the hostile local wound environment can explain why epithelial wound closure is so difficult to speed up in some chronic wounds. Clinicians should be aware of the different surgical techniques of skin grafting and more advanced technologies, such as skin substitutes, as options for wounds which fail to respond to standard protocols. Finally, novel dressing-based concepts are discussed, including macromolecular crowding, a concept which aims at boosting growth factor activities produced in the wound space once wound healing is normalised and underway.

Descriptive vs mechanistic scientific approach to study wound healing and its inhibition: Is there a value of translational research involving human subjects?

The clinical field of wound healing is challenged by numerous hurdles. Not only are wound-healing disorders complex and multifactorial, but the corresponding patient population is diverse, often elderly and burdened by multiple comorbidities such as diabetes and cardiovascular disease. The care of such patients requires a dedicated, multidisciplinary team of physicians, surgeons, nurses and scientists. In spite of the critical clinical need, it has been over 15 years since a treatment received approval for efficacy by the FDA in the United States. Among the reasons contributing to this lack of effective new treatment modalities is poor understanding of mechanisms that inhibit healing in patients. Additionally, preclinical models do not fully reflect the disease complexity of the human condition, which brings us to a paradox: if we are to use a "mechanistic" approach that favours animal models, we can dissect specific mechanisms using advanced genetic, molecular and cellular technologies, with the caveat that it may not be directly applicable to patients. Traditionally, scientific review panels, for either grant funding or manuscript publication purposes, favour such "mechanistic" approaches whereby human tissue analyses, deemed "descriptive" science, are characterized as a "fishing expedition" and are considered "fatally flawed." However, more emerging evidence supports the notion that the use of human samples provides significant new knowledge regarding the molecular and cellular mechanisms that control wound healing and contribute to inhibition of the process in patients. Here, we discuss the advances, benefits and challenges of translational research in wound healing focusing on human subject research.

Effectiveness of Platelet-Rich Plasma for Androgenetic Alopecia: A Review of the Literature.

Androgenetic alopecia (AGA) is a hair loss disorder affecting 80% of men and 50% of women throughout their lifetime. Therapies for AGA are limited and there is no cure. There is a high demand for hair restoration. Platelet-rich plasma (PRP), a treatment modality shown to promote wound healing, has also been explored as a treatment for AGA. This literature review was conducted to assess the effectiveness of PRP treatment for AGA. Twelve studies conducted from 2011 to 2017 were evaluated and summarized by study characteristics, mode of preparation, and treatment protocols. A total of 295 subjects were given PRP or control treatment in these studies, and evaluated for terminal hair density, hair quality, anagen/telogen hair ratio, keratinocyte proliferation, blood vessel density, etc. Some studies also provided subject self-assessment reports. Most of the studies reviewed showed effectiveness of PRP in increasing terminal hair density/diameter. Additional investigations are needed to determine the optimal treatment regimen for high efficacy of PRP in AGA.