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      Platelet-Rich Plasma Injection and Cutaneous Sarcoidal Granulomas

      brief-report

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          Abstract

          Dear Editor: Sarcoidosis is a systemic granulomatous disease that affects multiple organs including the lung, eyes and skin1. Platelet-rich plasma (PRP) is an autologous concentration of human platelets and has been used for treatment of skin wrinkles2. Here, we report the first case of sarcoidosis diagnosed by lesions of the lung, eyes and skin which was manifested as multiple sarcoid granulomas on the face where PRP had been injected for the treatment of skin wrinkles. A 68-year-old Japanese woman who was suspected of ocular sarcoidosis was referred to us in January 2014 for evaluation of her skin lesions that had developed 5 months earlier. Physical examination showed multiple slightly reddish nodules up to 1 cm in diameter on the cheeks and forehead, around the eyes and mouth (Fig. 1). Her skin wrinkles on the nasolabial folds and outside the eyes had been treated by the injection of hyaluronic acid (12 times) and botulinum toxin (7 times) during 4 years from 2006. Thereafter skin wrinkles on her face had been treated by PRP injection (12 times) during 2 years beginning in 2010. In August 2013, multiple skin nodules had appeared on her face where PRP had been injected. Two months later, she had seen an ophthalmologist complaining of dim eyesight. She had been suspected of ocular sarcoidosis because of her uveitis with granulomatous keratic precipitates and vitreous opacity. She had no other symptoms such as cough. Laboratory finding disclosed an elevated level of angiotensin converting enzyme (37.1 U/ml, normal 7.0~25.0 U/ml) and chest computed tomography showed bilateral hilar adenopathy. Skin biopsy specimen revealed non-caseating granulomas in the mid to deep dermis and subcutis (Fig. 2A). Granulomas contained numerous epithelioid cells and giant cells including Langhans' type with a small number of lymphocytes, indicating the naked granuloma (Fig. 2B). From these findings, the diagnosis of sarcoidosis was made and her skin lesions were effectively treated by topical corticosteroid injection without other systemic treatments. PRP has been used for the treatment of skin wrinkles as it contains various growth factors such as platelet-derived growth factor and vascular endothelial growth factor (VEGF)3. The appearance of cutaneous sarcoid granulomas is well known to be related to the presence of foreign bodies such as silica, silicone and hyaluronic acid4. However, there has been no report of sarcoid granuloma appearing in the skin where PRP has been injected. We could not rule out completely the possibility that hyaluronic acid and botulinum toxin induced the formation of sarcoid granulomas. We speculate that PRP might be a trigger of cutaneous sarcoidal granulomas in an active sarcoidosis patient rather than that systemic sarcoidosis developed related with PRP injection. Although PRP does not contain foreign bodies, it contains various growth factors including VEGF, which is known to be an activating and chemotactic factor for monocytes and might be a triggering factor for cutaneous granuloma formation5. In addition, the possibility remains that cutaneous sarcoidosis developed incidentally at the PRP injection sites by the unknown factors other than PRP itself under the active sarcoidosis patient.

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          The vascular endothelial growth factor receptor Flt-1 mediates biological activities. Implications for a functional role of placenta growth factor in monocyte activation and chemotaxis.

          Two distinct receptors for vascular endothelial growth factor (VEGF), the tyrosine kinase receptors Flt-1 and Flk-1/KDR, have been described. In this study we show that monocytes, in contrast to endothelium, express only the VEGF receptor Flt-1, and that this receptor specifically binds also the VEGF homolog placenta growth factor (PlGF). Both VEGF and PlGF stimulate tissue factor production and chemotaxis in monocytes at equivalent doses. In contrast, endothelial cells expressing both the Flt-1 and the Flk-1/KDR receptors produce more tissue factor upon stimulation with VEGF than after stimulation with PlGF. Neutralizing antibodies to the KDR receptor reduce the VEGF-stimulated tissue factor induction in endothelial cells to levels obtained by stimulation with PlGF alone, but do not affect PlGF-induced tissue factor induction in endothelial cells nor the VEGF-dependent tissue factor production in monocytes. These findings strongly suggest Flt-1 as a functional receptor for VEGF and PlGF in monocytes and endothelial cells and identify this receptor as a mediator of monocyte recruitment and procoagulant activity.
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            Diagnostic criteria for sarcoidosis.

            Sarcoidosis is a multiorgan system disease that often presents insidiously. The diagnosis is often made fortuitously upon routine chest radiography or that done for other reasons. Blacks are more commonly affected than whites and age of onset is typically adolescents to young adults. Lung involvement is common and symptoms may include cough, dyspnea and chest pain. Extrapulmonary symptoms may include the skin, joint and eye findings. Bilateral hilar adenopathy is the classic finding on chest radiograph. Anemia or other cell line deficiencies, elevated liver enzymes, hypercalciuria, and EKG abnormalities may also be present. Angiotensin converting enzyme levels may be elevated but are not diagnostic. Histopathological confirmation of noncaseating granulomas is essential for diagnosis. It is generally performed through a biopsy of the most peripheral site possible, although transbronchial biopsy is commonly required. Finally, other possible etiologies must be evaluated and differentiated with a particular emphasis on tuberculosis due to the multiple overlapping symptoms and findings. Newer techniques such as proteomics and transcriptional gene signatures may contribute to the understanding of the pathophysiology of sarcoidosis, and may even serve as diagnostic tools in the future. Copyright © 2014 Elsevier B.V. All rights reserved.
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              Assessment of efficacy of platelet-rich plasma (PRP) on infraorbital dark circles and crow's feet wrinkles.

              Infraorbital skin hyperpigmentation, commonly called dark circles, and crow's feet wrinkles are common cosmetic concerns. Various methods of treatment have been evaluated with variable outcomes.
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                Author and article information

                Journal
                Ann Dermatol
                Ann Dermatol
                AD
                Annals of Dermatology
                The Korean Dermatological Association; The Korean Society for Investigative Dermatology
                1013-9087
                2005-3894
                April 2017
                24 March 2017
                : 29
                : 2
                : 239-241
                Affiliations
                Department of Dermatology, Nippon Medical School, Tokyo, Japan.
                [1 ]Department of Ophthalmology, Nippon Medical School, Tokyo, Japan.
                Author notes
                Corresponding author: Hidehisa Saeki, Department of Dermatology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan. Tel: 81-3-5814-6254, Fax: 81-3-3823-6731, h-saeki@ 123456nms.ac.jp
                Article
                10.5021/ad.2017.29.2.239
                5383757
                28392659
                4aa1860a-6f88-4d72-a394-1fe7f729c81e
                Copyright © 2017 The Korean Dermatological Association and The Korean Society for Investigative Dermatology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 05 February 2016
                : 06 April 2016
                : 07 April 2016
                Categories
                Brief Report

                Dermatology
                Dermatology

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