Background Coronavirus disease 2019 (COVID-19) is a systemic multi-organ viral illness. Previous studies have found that many patients had a procoagulant state and/or severe hypoxemia with relatively well-preserved lung mechanics. Mechanisms underlying the damage to vascular tissues are not well-elucidated yet. Histological data in COVID-19 patients are still limited and are mainly focused on post-mortem analysis. Given that the skin is affected by COVID-19 and the relative ease of its histological examination, we aimed to examine the histology of skin lesions in COVID-19 patients to better understand the disease's pathology. Methods Five skin lesions from COVID-19 adult patients were selected for a deep histological tissue examination. Results A strong vasculopathic reaction pattern based on prominent vascular endothelial and myointimal cell growth was identified. Endothelial cell distortion generated vascular lumen obliteration and striking erythrocyte and serum extravasation. Significant deposition of C4d and C3 throughout the vascular cell wall was also identified. A regenerative epidermal hyperplasia with tissue structure preservation was also observed. Conclusions COVID-19 could comprise an obliterative microangiopathy consisting on endothelial and myointimal growth with complement activation. This mechanism, together with the increased vascular permeability identified, could contribute to obliteration of the vascular lumen and hemorrhage in COVID-19. Thus, anticoagulation by itself could not completely reverse vascular lumen obliteration, with consequent increased risk of hemorrhage. Findings of this study could contribute to a better understanding of physiopathological mechanisms underlying COVID-19 on living patients and could help further studies find potential targets for specific therapeutic interventions in severe cases.
Hailey–Hailey disease (HHD) or chronic benign familial pemphigus is an autosomal dominant genodermatosis with complete penetrance characterized by painful vesicles, erosions, and macerated intertriginous skin. We present a 66‐year‐old woman with a personal 35‐year history of pruritic recurrent vesicles and erosions in both axillae and inguinal folds. HHD was confirmed by cutaneous biopsy. Past treatments had failed, including topical corticosteroids, antibiotics and oral doxycycline, minocycline, dapsone, and acitretin. Phototherapy and intralesional injection of toxin botulinum A was performed in the axillae. The patient was started on naltrexone 6.25 mg nightly. Six weeks later, complete clearing was observed. At typical doses, naltrexone blocks μ and δ opiod receptors, thereby blocking the union of β‐endorphins at those sites. Paradoxically, at low doses, the partial binding to those receptors leads to a homeostatic increase of opioid receptors and an upregulation of endogenous opioids. Low‐dose naltrexone (LDN) may also exert an anti‐inflammatory action through its antagonist effect on toll‐like receptor 4 found on macrophages. We consider that LDN is an effective and safe alternative for the HHD, representing an important progress in the management of this disease with limited therapeutic options.
Background: Severe coronavirus disease 2019 (Covid-19) is a systemic multi-organ viral invasion. Previous studies found that many patients had a procoagulant state and/or severe hypoxemia with relatively well-preserved lung mechanics. Mechanisms underlying the vascular and its surrounding tissue are not well known yet. Histological data in Covid-19 tissues´ patients are still limited and mainly focused on post-mortem analysis. Since SARS-CoV-2 largely affects cutaneous tissue, we aim to assess the pathophysiologic mechanisms in depth in living skin tissue related to Covid-19.Methods: Five skin lesions from caucasian Covid-19 adult patients were selected for cutaneous tissue histological examination including immunohistochemistry (IHC) and direct immunofluorescent (DIF) vast amount of data. Results: A common strong vasculopathic reaction pattern based on prominent vascular endothelial and myointimal cellgrowth was identified. Endothelial cell distortion generated vascular lumen obliteration and a strike erythrocyte and serum extravasation. Extensive significant vascular C4d and C3 deposition throughout vascular cell wall was also identified. A regenerative epidermal hyperplasia with tissue structure preservation was also found. Conclusions: Covid-19 could comprise an obliterative micro-angiopathy consisting on endothelial and myointimal intensive growth with complement activation. This mechanism, together with increased vascular permeability identified, could contribute to obliterative vascular lumen and hemorrhage in Covid-19 disease. Activation of the complement and angiogenic pathways could have an important role in inducing and maintaining this vasculopathic reaction pattern. Thus, anticoagulation by itself could not completely reverse vascular lumen obliteration, with consequent hemorrhagic increased risk associated. Skin is the largest organ in the body, the most accessible one and can mirror other organs of the body. Findings of this study could contribute to a better understanding of physio-pathological mechanisms underlying Covid-19 infection on living tissue and could help further studies find potential targets for specific therapeutic interventions in Covid-19 severe patients.
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