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      Management of hair loss after severe acute respiratory syndrome coronavirus 2 infection: Insight into the pathophysiology with implication for better management

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          Abstract

          Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was declared a pandemic by the World Health Organization, and COVID‐19 continues to have a major impact on society. Numerous studies have reported impaired health sequelae after COVID‐19 recovery, one of which is hair loss. Individuals with hair loss experience a substantial mental burden, which potentially hinders their social life. However, few studies have systematically analyzed the details including hair loss. Therefore, we conducted a narrative review using PubMed on the frequency, associated comorbidities, disease characteristics, and treatment of hair loss after SARS‐CoV‐2 infection (HLASCI). Two search strings were used to identify 28 articles. Of note, most of the literature identified on COVID‐19 sequelae reported an emergence/occurrence of hair loss. HLASCI is speculated to be composed of a heterogeneous population, with the onset or exacerbation of telogen effluvium (TE), anagen effluvium, androgenetic alopecia (AGA), and alopecia areata (AA) reported as possible underlying mechanisms. Among these, acute TE is thought to be the primary cause of HLASCI, with COVID‐19 treatment and TE improvement being considered crucial for HLASCI management. An association between COVID‐19 and AA exacerbation has also been implicated with still insufficient evidence. Spontaneous recovery of TE can be expected once infection reduces; however, faster improvement in symptoms is expected to reduce the mental and social burden of patients. An additional search string identified 11 articles about TE treatment which suggested that the use of minoxidil may be beneficial. Topical minoxidil has been widely used for AGA patients, who have been speculated to exhibit poor resistance to SARS‐CoV‐2. Topical minoxidil may provide relief from HLASCI, but future clinical research is warranted to confirm this observation.

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          Clinical sequelae of COVID-19 survivors in Wuhan, China: a single-centre longitudinal study

          Objectives To describe the prevalence, nature, and risk factors for the main clinical sequelae in COVID-19 survivors who have been discharged from the hospital for more than 3 months. Methods This longitudinal study was based on a telephone follow-up survey of COVID-19 patients hospitalized and discharged from Renmin Hospital of Wuhan University, Wuhan, China before March 1, 2020. Demographic and clinical characteristics and self-reported clinical sequelae of the survivors were described and analysed. A cohort of volunteers who were free of COVID-19 and lived in the urban area of Wuhan during the outbreak were also selected as the comparison group. Results Among 538 survivors (293[54.5%] female), the median age was 52.0 years (IQR 41.0–62.0), and the median time from discharge from hospital to first follow-up was 97.0 days (IQR 95.0–102.0). Clinical sequelae were common, including general symptoms (n=267, 49.6%), respiratory symptoms (n=210, 39%), cardiovascular-related symptoms (n=70, 13%), psychosocial symptoms (n=122, 22.7%) and alopecia (n=154, 28.6%). We found that physical decline/fatigue (P<0.01), post-activity polypnea (P=0.04) and alopecia (P<0.01) were more common in females than in males. Dyspnoea during hospitalization was associated with subsequent physical decline/fatigue, post-activity polypnea and resting heart rate increases, but not specifically with alopecia. A history of asthma during hospitalization was associated with subsequent post-activity polypnea sequela. A history of pulse ≥90 beats per min during hospitalization was associated with resting heart rate increase in convalescence. The duration of viral shedding after COVID-19 onset and hospital length of stay were longer in survivors with physical decline/fatigue or post-activity polypnea than in those without. Conclusion Clinical sequelae during early COVID-19 convalescence were common, and some of these sequelae might be related to gender, age and clinical characteristics during hospitalization.
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            Minoxidil: mechanisms of action on hair growth.

            We have known for over 30 years that minoxidil stimulates hair growth, yet our understanding of its mechanism of action on the hair follicle is very limited. In animal studies, topical minoxidil shortens telogen, causing premature entry of resting hair follicles into anagen, and it probably has a similar action in humans. Minoxidil may also cause prolongation of anagen and increases hair follicle size. Orally administered minoxidil lowers blood pressure by relaxing vascular smooth muscle through the action of its sulphated metabolite, minoxidil sulphate, as an opener of sarcolemmal KATP channels. There is some evidence that the stimulatory effect of minoxidil on hair growth is also due to the opening of potassium channels by minoxidil sulphate, but this idea has been difficult to prove and to date there has been no clear demonstration that KATP channels are expressed in the hair follicle. A number of in vitro effects of minoxidil have been described in monocultures of various skin and hair follicle cell types including stimulation of cell proliferation, inhibition of collagen synthesis, and stimulation of vascular endothelial growth factor and prostaglandin synthesis. Some or all of these effects may be relevant to hair growth, but the application of results obtained in cell culture studies to the complex biology of the hair follicle is uncertain. In this article we review the current state of knowledge on the mode of action of minoxidil on hair growth and indicate lines of future research.
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              Effect of minoxidil on proliferation and apoptosis in dermal papilla cells of human hair follicle.

              Minoxidil has been widely used to treat androgenetic alopecia, but little is known about its pharmacological activity or about the identity of its target cells in hair follicles. We hypothesized that minoxidil has direct effects on the proliferation and apoptosis of dermal papilla cells (DPCs) of human hair follicle. To elucidate the mechanism of topical minoxidil action in terms of stimulating hair growth. We evaluated cell proliferations in cultured DPCs by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and measured the expressions of extracellular signal-regulated kinase (ERK), Akt, Bcl-2, and Bax by Western blot. We also measured elongation of hair follicles in organ culture. Minoxidil significantly increased the proliferation of DPCs. The levels of ERK phosphorylation and of phosphorylated Akt increased significantly 1 h post-treatment; percentage increase of ERK phosphorylation was 287% at 0.1 microM and 351% at 1.0 microM of minoxidil, and that of Akt phosphorylation was 168% at 0.1 microM and 257% at 1.0 microM of minoxidil. 1.0 microM of minoxidil increased Bcl-2 expression over 150%, while 1.0 microM of minoxidil decreased Bax expression by more than 50%. Moreover, a significant elongation of individual hair follicles in organ culture was observed after adding minoxidil. Minoxidil promotes the survival of human DPCs by activating both ERK and Akt and by preventing cell death by increasing the ratio of Bcl-2/Bax. We suggest that minoxidil stimulates the growth of human hairs by prolonging anagen through these proliferative and anti-apoptotic effects on DPCs.
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                Author and article information

                Contributors
                manabuohy@ks.kyorin-u.ac.jp
                Journal
                J Dermatol
                J Dermatol
                10.1111/(ISSN)1346-8138
                JDE
                The Journal of Dermatology
                John Wiley and Sons Inc. (Hoboken )
                0385-2407
                1346-8138
                27 May 2022
                27 May 2022
                : 10.1111/1346-8138.16475
                Affiliations
                [ 1 ] Department of Dermatology Kyorin University Faculty of Medicine Tokyo Japan
                [ 2 ] Clinical Development, Research and Development Headquarters Self‐Medication Taisho Pharmaceutical Co.Ltd Tokyo Japan
                Author notes
                [*] [* ] Correspondence

                Manabu Ohyama, Department of Dermatology, Kyorin University Faculty of Medicine, 6‐20‐2 Shinkawa Mitaka‐shi Tokyo 181‐0004 Japan.

                Email: manabuohy@ 123456ks.kyorin-u.ac.jp

                Author information
                https://orcid.org/0000-0002-2662-5717
                https://orcid.org/0000-0002-3700-182X
                Article
                JDE16475 JDE-2022-0490.R1
                10.1111/1346-8138.16475
                9348110
                35633047
                45d5085b-918f-4dc7-a865-48dc3cb8c1e8
                © 2022 The Authors. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 April 2022
                : 08 April 2022
                : 12 May 2022
                Page count
                Figures: 3, Tables: 3, Pages: 9, Words: 4807
                Funding
                Funded by: Taisho Pharmaceutical Co.
                Categories
                Review
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                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:03.08.2022

                alopecia,covid‐19,minoxidil,pandemic,quarantine
                alopecia, covid‐19, minoxidil, pandemic, quarantine

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