Senotherapeutic Effect of Retinaldehyde and Hyaluronate Fragments in Dermatoporosis.

Cellular senescence is one of the important mechanisms of skin aging. In a recent study, we have shown that in patients with dermatoporosis, an extreme senescence condition of the skin, cells positive for p16Ink4a, a biomarker of senescence, were significantly increased in the epidermis. Senescent cells can develop a senescence-associated secretory phenotype (SASP) comprising pro-inflammatory cytokines, chemokines, and other soluble factors, leading to chronic inflammation and tissue dysfunction. These senescent cells and SASP pathways represent therapeutic targets for the development of senotherapeutics either by inducing selective cell death of senescent cells called senolytics, or suppressing markers of the SASP, called senomorphics. In this study where we conducted a retrospective immunohistochemical analysis of p16Ink4a expression in the skin samples of dermatoporosis patients included in a previous clinical study, we describe the senotherapeutic effect of retinaldehyde (RAL) and intermediate-size hyaluronate fragments (HAFi). Topical application of RAL and HAFi significantly reduced the number of p16Ink4a-positive cells in the epidermis and dermis in dermatoporosis patients which also showed a significant clinical improvement.

Clinical and Histopathological Features and Potential Pathological Mechanisms of Skin Lesions in COVID-19: Review of the Literature.

In recent weeks, several reports have emerged of skin lesions with different clinical presentations in COVID-19 cases. All dermatologists should be aware of these cutaneous lesions, which may be early clinical symptoms of infection. We reviewed the literature on cutaneous manifestations in the PubMed database from December 2019 and June 2020. From the cases described as case reports or series in 57 recent articles, it appears that skin lesions (i) are highly varied, (ii) may not be related to the severity of the condition and (iii) resolve spontaneously in a few days. The frequency of these lesions in COVID-19 patients varies between 1.8% and 20.4%. The major clinical forms described were maculopapular eruptions, acral areas of erythema with vesicles or pustules (pseudochilblain), urticarial lesions, other vesicular eruptions and livedo or necrosis. The lesions were mainly localized in the trunk and extremities. The majority of patients were male, aged between 4.5 and 89 years. A minority of the patients were children presenting with acral, chilblain-like lesions, papulo-vesicular eruptions or Kawasaki disease-like pediatric inflammatory multisystem syndrome. The mean duration of the lesions was a few days, but some lasting as little as 20 min and others as long as four weeks have been reported. The mean latency time in the majority of cases was between 1 and 14 days; however, in some patients, lesions appeared 2 to 5 days before the onset of COVID-19 symptoms. The histopathological features of these lesions also vary, corresponding to the diversity of clinical manifestations. These features underline the nature of epidermal and dermal vascular lesions-and in severe cases, microvascular injury and thrombosis-associated with COVID-19, and provide important clues to their pathological mechanisms.

Induction of Hyalurosome by Topical Hyaluronate Fragments Results in Superficial Filling of the Skin Complementary to Hyaluronate Filler Injections.

Hyaluronate (HA) plays a major role in the process of skin aging. The main use of HA has been for hydration and dermal fillers. Another approach, based on the discovery of the signaling effects of topically applied hyaluronate fragments (HAF), has subsequently been developed. It has been thoroughly demonstrated that topical applications of HAF of a very specific size induce HA filling of the epidermis and the upper dermis. These effects are particularly visible in dermatoporotic patients. Moreover, the combination of HA-based filler injections with topical applications of HAFs/retinoids showed an optimization of the effects of HA. Thus, a new classification of the different effects of HA is proposed here.

Dermatoporosis, a prevalent skin condition affecting the elderly: current situation and potential treatments.

The term "dermatoporosis" was introduced a decade ago to highlight the need to pay attention to the problems posed by premature skin aging beyond esthetic considerations. People with this condition have a thinner skin that becomes fragile, tends to tear, and may lead to deep dissecting hematomas-as a final stage-corresponding to a medical emergency. Various studies have demonstrated a high prevalence of dermatoporosis in the elderly, with women being more exposed than men. We have developed a scoring system for dermatoporosis, providing different strategies to treat and prevent this skin condition, as well as a followup of patients treated at the University Hospital of Geneva.

Injected Hyaluronidase Reduces the Volume of Exogenous Hyaluronate Fillers in Mice and Results in Clinical Improvement in a Patient with Pretibial Myxedema.

BACKGROUND: Hyaluronidases are essential for the breakdown of hyaluronate (HA) in tissues and may be used to prevent the adverse effects of HA fillers. OBJECTIVES: We explored the effect of hyaluronidase on exogenous and endogenous HA in vitro and in vivo. MATERIALS AND METHODS: HA fillers were incubated with different concentrations of hyaluronidase and visualized by electrophoresis. HA fillers were injected in the skin of hairless mice, and 4 h later hyaluronidase was injected in the papules of exogenous HA. Hyaluronidase was injected in the nodule of pretibial myxedema of a male patient with Graves' disease. Skin sections of mice and of the patient were performed, and a skin ultrasound system was used to monitor the evolution of skin lesions. RESULTS: Hyaluronidase showed a degrading effect on HA with increasing concentrations. Hyaluronidase injection significantly decreased the content of exogenous HA within 3 days. Intralesional injection of hyaluronidase resulted in dissolution of the nodule of pretibial myxedema with no recurrence during 3 months. CONCLUSION: These results show that the injection of hyaluronidase is capable of degrading exogenous HA in mouse skin and endogenous HA in human skin in vivo and may be a therapeutic option for skin diseases characterized by abnormal accumulation of HA.

Aryl Hydrocarbon Receptor Activation in Acne Vulgaris Skin: A Case Series from the Region of Naples, Italy.

BACKGROUND: Dioxins are persistent organic pollutants present in the environment. They exert their biological effects by binding to an intracellular receptor, the aryl hydrocarbon receptor (AhR). Activation of AhR leads to the induction of cytochrome p450 1A1 (CYP1A1). Expression of CYP1A1 in human skin is a key marker for AhR activation, and it may induce comedogenesis resulting in acne-like lesions known as chloracne/metabolising acquired dioxin-induced skin hamartomas (MADISH). The contribution of this pathway in patients seen in a busy acne clinic is unknown. MATERIALS AND METHODS: We explored the expression of CYP1A1 by immunohistochemistry in the acne lesions of 16 patients living in the region of Naples, Italy, where epidemiological studies have suggested a possibly increased exposure to environmental dioxins. A composite score to outline potential components of the chloracne/MADISH histological pattern was used. RESULTS: CYP1A1 expression was observed in 11 lesions (69%) and was distributed in sebaceous glands, follicular epithelium, cystic wall and endothelial cells. The histological score for chloracne/MADISH was 'likely' in 3 cases and 'possible' in 11 cases. Compared to current data on CYP1A1 expression in the skin of 67 patients with proven exposure to AhR agonists, these data indicate a high incidence of AhR activation in this series. CONCLUSION: This is the first study analysing AhR activation in skin in a series of patients from a hospital-based acne clinic. It provides information for future controlled prospective studies. The significance of CYP1A1 expression in terms of AhR ligand exposure is discussed.

Dobrava hantavirus infection complicated by panhypopituitarism, Istanbul, Turkey, 2010.

We identified Dobrava-Belgrade virus infection in Turkey (from a strain related to hantavirus strains from nearby countries) in a patient who had severe symptoms leading to panhypopituitarism, but no known risk for hantavirus. Our findings emphasize the need for increased awareness of hantaviruses in the region and assessment of symptomatic persons without known risk factors for infection.

Deep dissecting hematoma: an emerging severe complication of dermatoporosis.

OBJECTIVE: To outline the characteristics of deep dissecting hematoma (DDH). DESIGN: Retrospective medical record review. SETTING: Department of Dermatology, University Hospital of Geneva, Geneva, Switzerland. PATIENTS: Thirty-four patients with DDH. INTERVENTIONS: Deep incision or surgical debridement was performed in all the patients. Direct closure of the incision was possible in 6 patients, and split-thickness skin grafting was applied to 17 patients. MAIN OUTCOME MEASURES: Sex of the patient, the affected area, presence of dermatoporosis, presence of systemic treatment, initial and late symptoms, anatomic location of DDH, and the mean length of hospital stay. RESULTS: Most frequently, elderly women were affected (mean age, 81.7 years); women outnumbered men by a ratio of 5:1. In all the patients, the leg was the affected part of the body. All the patients, except for the 2 youngest ones, had advanced dermatoporosis, and the most severe form was seen in the older patients who were receiving long-term treatment with systemic corticosteroids. Half of the patients were receiving anticoagulation drugs. The initial symptoms in all the patients were pain and swelling of the leg. Erythema and edema without fever were observed. Skin necrosis developed as a late manifestation. Erysipelas was the initial diagnosis in up to 14 patients who had been treated with antibiotics before admission. The mean delay before hospital referral was 16.4 days. Magnetic resonance imaging and histopathological analysis confirmed deep anatomical location of DDH. Hospital treatment consisted mainly of deep incision and debridement followed by direct closure, skin grafting, or wound healing per secundam. The mean length of hospital stay was 3.5 weeks. CONCLUSIONS: Deep dissecting hematoma is an emerging clinical entity and a major complication of dermatoporosis. Prompt diagnosis and treatment is a major factor for the prognosis. Health care professionals, especially general practitioners, should be aware of the symptoms and signs of this condition as well as the risk factors involved. Given the high cost of treatment, in addition to the inconvenience it causes for the patient, preventive measures should be implemented early.