Systemic Sarcoidosis with Psoriasiform Plaques and Patchy Nonscarring Alopecia.

ABSTRACT: Cutaneous sarcoidosis occurs in about one-quarter of patients with systemic disease and presents with either specific or nonspecific signs. Psoriasiform sarcoidosis is an uncommon presentation. Herein, study authors report a rare case of systemic sarcoidosis that presented with psoriasiform plaques and patchy alopecia. The main patient complaint was disfigurement from skin lesions over different areas of his body, followed by scalp alopecia and uveitis. These lesions were well-defined plaques, some oozing and others scaly. Dermoscopic examination revealed yellow-orange globular structure. A biopsy was taken; the eventual diagnosis was sarcoidosis, for which the patient received treatment with systemic steroids, resulting in improvement of all of his lesions. Physicians should suspect sarcoidosis in any patient presenting with psoriasiform skin lesions not responding to traditional psoriasis treatment.

Cell cycle regulation in human hair follicle dermal papilla cells using nonthermal atmospheric pressure plasma-activated medium.

ABSTRACT: Nonthermal atmospheric pressure (NAP) plasmas have recently been developed and have been used for wound healing, blood coagulation, and cancer therapy. NAP plasmas can induce either cell proliferation or cell death, depending on the dose. Due to their efficacy and application easily, plasma activated mediums (PAMs) have been used in human cells recently.In atmosphere, NAP plasmas react with molecular content of air such as N2, O2, H2O vapor, etc, and generate a variety of reactive oxygen and nitrogen species. High reactive oxygen species (ROS) levels promote damage of cellular DNA, proteins, and lipids. Such damage can lead to cell-cycle arrest, and cellular death. However, low levels of ROS have been caused an increase in cell cycle progression.Human skin is arranged in 3 layers, including (from top to bottom) the epidermis (and its appendages), the dermis, and the hypodermis. Human dermal papilla cells (DPCs) are located in the middle or even deep part of the dermis. DPCs play a key role in hair regeneration, and a lot of effort have been made to promote DPC hair formation ability. DPC is increased proliferation, delayed senescence, and enhanced hair by depending on the amount of ROS through the NAP-PAM treatment.In this study, we used NAP plasmas to the human hair follicle DPCs exposed from 0 to 20 minutes, so we were investigated the effects of PAM on cell proliferation and cell cycle progression. After NAP-PAM treatment for 24 hours, cell cycle was arrested in the G0/G1 phase. The NAP-PAM-treated human hair follicle DPCs recovered gradually after 48 hours of the treatment compared to the untreated cells.Therefore, this approach offers promising results for further application of NAP-PAM in clinical dermatology. In future, it can be applied clinically in the form of active water that can delay the progression of baldness and alopecia areata.

Severe primary hypothyroidism in an apparently asymptomatic 19-year-old woman: a case report.

BACKGROUND: Hypothyroidism is diagnosed on the basis of laboratory tests because of the lack of specificity of the typical clinical manifestations. There is conflicting evidence on screening for hypothyroidism. CASE PRESENTATION: We report a case of an apparently healthy 19-year-old Kuwaiti woman referred to our clinic with an incidental finding of extremely high thyroid-stimulating hormone (TSH), tested at the patient's insistence as she had a strong family history of hypothyroidism. Despite no stated complaints, the patient presented typical symptoms and signs of hypothyroidism on evaluation. Thyroid function testing was repeated by using different assays, with similar results; ultrasound imaging of the thyroid showed a typical picture of thyroiditis. Treatment with levothyroxine alleviated symptoms and the patient later became biochemically euthyroid on treatment. CONCLUSION: There is controversy regarding screening asymptomatic individuals for hypothyroidism; therefore, it is important to maintain a high index of suspicion when presented with mild signs and symptoms of hypothyroidism especially with certain ethnic groups, as they may be free of the classical symptoms of disease.

Dihydrotestosterone-induced hair regrowth inhibition by activating androgen receptor in C57BL6 mice simulates androgenetic alopecia.

Androgenic alopecia (AGA), also known as male pattern baldness, is one of the most common hair loss diseases worldwide. The main treatments of AGA include hair transplant surgery, oral medicines, and LDL laser irradiation, although no treatment to date can fully cure this disease. Animal models play important roles in the exploration of potential mechanisms of disease development and in assessing novel treatments. The present study describes androgen receptor (AR) in C57BL/6 mouse hair follicles that can be activated by dihydrotestosterone (DHT) and translocate to the nucleus. This led to the design of a mouse model of androgen-induced AGA in vivo and in vitro. DHT was found to induce early hair regression, hair miniaturization, hair density loss, and changes in hair morphology in male C57BL/6 mice. These effects of DHT could be partly reversed by the AR antagonist bicalutamide. DHT had similar effects in an ex vivo model of hair loss. Evaluation of histology, organ culture, and protein expression could explain the mechanism by which DHT delayed hair regrowth.

Anti-androgenetic alopecia effect of policosanol from Chinese wax by regulating abnormal hormone levels to suppress premature hair follicle entry into the regression phase.

Previously, we have demonstrated that policosanol from Chinese wax suppressed testosterone(T)-induced alopecia in mice. However, the underlying mechanism remained to be determined. Herein, we investigated the mechanism of policosanol against androgenetic alopecia (AGA). AGA was induced in Kunming mice by subcutaneous administration of testosterone propionate for 60 d. Policosanol (0.5 %, 1% or 2%) was applied topically on the back of mice. Finasteride (2%) was applied topically as a positive control. The serum T and estradiol (E2) concentrations were determined by ELISA after 28 and 60 days of treatment. The cutaneous expression or activity of key mediators of hair growth, such as alkaline phosphatase (ALP), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF), was measured. MTS assay was performed to evaluate cell proliferation in cultured human dermal papilla cells (DPCs) treated with dihydrotestosterone (DHT). Western blotting was performed to evaluate the protein expression of Bax, Bcl2, TGF-ß2, caspase-9, and caspase-3. We found lower T and T/E2 ratio in mice treated with policosanol than in the model group. Policosanol suppressed premature hair follicle entry into the regression phase, as shown by improving VEGF and EGF expression and ALP activity. The MTS assay showed that policosanol markedly inhibited the apoptosis of DHT-treated DPCs. Western blotting showed that policosanol significantly reduced the protein expression of TGF-ß2, cleaved caspese-9, cleaved caspase-3, and Bax, and increased that of Bcl2. The optimal effect was obtained with 12.50 g/mL policosanol. In conclusion, policosanol prevents androgenetic alopecia by regulating hormone levels and suppressing premature hair follicle entry into the regression phase.

Severe metabolic disorders coexisting with Werner syndrome: a case report.

Werner syndrome, also called adult progeria, is a heritable autosomal recessive human disorder characterized by the premature onset of numerous age-related diseases including juvenile cataracts, dyslipidemia, diabetes mellitus (DM), osteoporosis, atherosclerosis, and cancer. Werner syndrome is a segmental progeroid syndrome whose presentation resembles accelerated aging. The most common causes of death for WS patients are atherosclerosis and cancer. A 40-year-old female presented with short stature, bird-like facies, canities with alopecia, scleroderma-like skin changes, and non-healing foot ulcers. The patient reported a history of delayed puberty, abortion, hypertriglyceridemia, and juvenile cataracts. A clinical diagnosis of WS was made and subsequently confirmed. We discovered two WRN gene mutations in the patient, Variant 1 was the most common WRN mutation, nonsense mutation (c.1105C>T:p.R369Ter) in exon 9, which caused a premature termination codon (PTC) at position 369. Variant 2 was a frameshift mutation (c.1134delA:p.E379KfsTer5) in exon 9, which caused a PTC at position 383 and has no published reports describing. Patients with WS can show a wide variety of clinical and biological manifestations in endocrine-metabolic systems (DM, thyroid dysfunction, and hyperlipidemia). Doctors must be cognizant of early manifestations of WS and treatment options.

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 coronavirus disease 2019 (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 1 March 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 (interquartile range) age was 52.0 (41.0-62.0) years, and the time from discharge from hospital to first follow-up was 97.0 (95.0-102.0) days. 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), postactivity polypnoea (p= 0.04) and alopecia (p < 0.01) were more common in female than in male subjects. Dyspnoea during hospitalization was associated with subsequent physical decline/fatigue, postactivity polypnoea and resting heart rate increases but not specifically with alopecia. A history of asthma during hospitalization was associated with subsequent postactivity polypnoea sequela. A history of pulse ≥90 bpm during hospitalization was associated with resting heart rate increase in convalescence. The duration of virus shedding after COVID-19 onset and hospital length of stay were longer in survivors with physical decline/fatigue or postactivity polypnoea than in those without. CONCLUSIONS: Clinical sequelae during early COVID-19 convalescence were common; some of these sequelae might be related to gender, age and clinical characteristics during hospitalization.

Time gap between the onset and diagnosis in Werner syndrome: a nationwide survey and the 2020 registry in Japan.

Patients with Werner syndrome present with diverse signs of aging that begin in adolescence. A Japanese nationwide survey was conducted to establish a registry that could clarify the disease profile of patients with Werner syndrome. The questionnaires were sent to 7888 doctors. The survey identified 116 patients diagnosed with Werner syndrome based on the diagnosis criteria. Forty patients were enrolled in the registry. Data on clinical symptoms, treatment information, and laboratory examination from patients who provided informed consent were collected. The data at enrollment were analyzed. The patients' average age at enrollment was 50.1±7.5 years. The mean onset age was 26.1±9.5 years, but the mean age at diagnosis was 42.5±8.6 years. Average height and weight of the study patients were lower than those of Japanese individuals. Almost all patients experienced hair change and cataracts. More than 60% of patients presented with glycolipid abnormalities. Overall, 15% of patients had a history of foot amputation. Approximately 30% of the patients' parents had a consanguineous marriage. The average grip strength, walking speed, and skeletal muscle mass index met the diagnostic criteria for sarcopenia. The registry revealed that there are opportunities for early diagnosis and intervention; therefore, sensitization about the disease is needed.

Hair loss due to scalp ringworm irradiation in childhood: health and psychosocial risks for women.

BACKGROUND: Until 1960, hundreds of thousands of children worldwide had been treated for scalp ringworm by epilation via irradiation. The discovery of late health effects in adulthood prompted investigation of the medical aspects of irradiation in childhood and led to the establishment of strict protocols for the use of X-ray irradiation. These studies ignored alopecia, which affects some individuals who underwent irradiation for scalp ringworm as children. This study examined the impact of alopecia due to irradiation for scalp ringworm on the health and psychosocial status of affected women. METHODS: We analysed a random sample of 130 medical files of women recognised by Israel's state committees as suffering from permanent hair loss as a result of scalp ringworm irradiation in childhood. The coded medical data included demographic variables, self-reported mental health conditions, self-reported physical health conditions, self-reported social conditions, and spousal relationship. RESULTS: Compared with the general population of women in Israel, research participants reported significantly higher rates of depression, anti-depressant and/or anti-anxiety drug use, psychotherapy or psychiatric hospitalisation, attempted suicide, migraines, cancer, and divorce. Many described humiliating social experiences due to their appearance, both in childhood and adulthood, that led them to curtail their social interactions. The participants also reported that alopecia negatively affected their spousal relationships. CONCLUSIONS: Life with hair loss from scalp ringworm irradiation in childhood has a negative impact on women's health status and psychosocial state. Health policy-makers must broaden their approach to women who underwent scalp ringworm irradiation by addressing the effects of their hair loss in addition to the effects of the radiation treatment per se. This may be achieved by guiding physicians who provide medical services to these women to take into account the psychosocial and health risks related to hair loss in their diagnosis and treatment as well as by creating a cadre of specially trained mental health professionals who can address their unique psychosocial needs. They must also consider including the specialized mental health services tailored for these women's unique needs in the Healthcare Basket.

Comparison of mitochondrial transplantation by using a stamp-type multineedle injector and platelet-rich plasma therapy for hair aging in naturally aging mice.

The mechanism of hair loss caused by aging is related to mitochondrial dysfunction. Pep-1-mediated mitochondrial transplantation is a potential therapeutic application for mitochondrial disorders, but its efficacy against hair aging remains unknown. This study compared platelet-rich plasma (PRP) therapy with mitochondrial transplantation for hair restoration and examined the related regulation in naturally aging mice. After dorsal hair removal, 100-week-old mice received weekly unilateral injections of 200 µg of allogeneic mitochondria-labeled 5-bromo-2'-deoxyuridine with (P-Mito) or without Pep-1 conjugation (Mito) or human PRP with a stamp-type electric injector for 1 month. The contralateral sides were used as corresponding sham controls. Compared with the control and corresponding sham groups, all treatments stimulated hair regrowth, and the effectiveness of P-Mito was equal to that of PRP. However, histology revealed that only P-Mito maintained hair length until day 28 and yielded more anagen follicles with abundant dermal collagen equivalent to that of the PRP group. Mitochondrial transplantation increased the thickness of subcutaneous fat compared with the control and PRP groups, and only P-Mito consistently increased mitochondria in the subcutaneous muscle and mitochondrial DNA copies in the skin layer. Therefore, P-Mito had a higher penetrating capacity than Mito did. Moreover, P-Mito treatment was as effective as PRP treatment in comprehensively reducing the expression of aging-associated gene markers, such as IGF1R and MRPS5, and increasing antiaging Klotho gene expression. This study validated the efficacy of mitochondrial therapy in the restoration of aging-related hair loss and demonstrated the distinct effects of PRP treatment.

Current advances in stem cell-based therapies for hair regeneration.

Alopecia is resulted from various factors that can decrease the regeneration capability of hair follicles and affect hair cycles. This process can be devastating physically and psychologically. Nevertheless, the available treatment strategies are limited, and the therapeutic outcomes are not satisfactory. According to the possible pathogenesis of nonscarring alopecia, especially androgenetic alopecia, recovering or replenishing the signals responsible for hair follicle stem cells activation is a promising strategy for hair regeneration. Recently, stem cell-based therapies, especially those based on the stem cell-derived conditioned medium (CM), which is secreted by stem cells and is rich in paracrine factors, have been widely explored as the hair regenerative medicine. Several studies have focused on altering the composition and up-regulating the amount of secretome of the stem cells, thereby enhancing its therapeutic effects. Besides, stem cell-derived exosomes, which are present in the CM as message entities, are also promising for hair regrowth. In this review, the up-to-date progress of research efforts focused on stem cell-based therapies for hair regeneration will be discussed, including their therapeutic potentials with respective merits and demerits, as well as the possible mechanisms.

Physiology and Medical Treatments for Alopecia.

Androgenetic alopecia (AGA) is the most common hair loss disorder in men and women. The characteristic and reproducible balding pattern in AGA negatively affects self-image and the external perceptions of the balding patient. The phenotypical changes are driven by dihydrotestosterone (DHT) and its precursor testosterone. DHT induces follicle miniaturization and hair cycle changes until resulting hairs no longer extrude through the skin surface. AGA is inherited in a polygenetic pattern and is susceptible to epigenetic and environmental factors. Currently, minoxidil, finasteride, and photolaser therapy are the only Food and Drug Administration-approved medical treatments for AGA.

Platelet-Rich Plasma for Hair Restoration.

Platelet-rich plasma (PRP) is a promising treatment for hair restoration in patients with androgenic alopecia. Created from a platelet concentrate from an autologous blood draw, PRP is a safe therapeutic option for patients with hair loss. It is used alone or in conjunction with topical and oral therapies. Most studies of hair restoration with PRP report positive outcomes. Further research to optimize PRP preparation/administration procedures and identify patient populations that benefit most from this treatment are needed, as is long-term follow-up of objective hair loss outcomes. PRP appears to be a safe technology with excellent potential for promoting hair restoration.

Post-finasteride syndrome: a surmountable challenge for clinicians.

Post-finasteride syndrome (PFS) is a constellation of serious adverse side effects manifested in clinical symptoms that develop and persist in patients during and/or after discontinuing finasteride treatment in men with pattern hair loss (androgenetic alopecia) or benign prostatic hyperplasia. These serious adverse side effects include persistent or irreversible sexual, neurological, physical and mental side effects. To date, there are no evidence-based effective treatments for PFS. Although increasing number of men report persistent side effects, the medical community has yet to recognize this syndrome nor are there any specific measures to address this serious and debilitating symptoms. Here we evaluate the scientific and clinical evidence in the contemporary medical literature to address the very fundamental question: Is PFS a real clinical condition caused by finasteride use or are the reported symptoms only incidentally associated with but not caused by finasteride use? One key indisputable clinical evidence noted in all reported studies with finasteride and dutasteride was that use of these drugs is associated with development of sexual dysfunction, which may persist in a subset of men, irrespective of age, drug dose or duration of study. Also, increased depression, anxiety and suicidal ideation in a subset of men treated with these drugs were commonly reported in a number of studies. It is important to note that many clinical studies suffer from incomplete or inadequate assessment of adverse events and often limited or inaccurate data reporting regarding harm. Based on the existing body of evidence in the contemporary clinical literature, the author believes that finasteride and dutasteride induce a constellation of persistent sexual, neurological and physical adverse side effects, in a subset of men. These constellations of symptoms constitute the basis for PFS in individuals predisposed to epigenetic susceptibility. Indeed, delineating the pathophysiological mechanisms underlying PFS will be of paramount importance to the understanding of this syndrome and to development of potential novel therapeutic modalities.

Immune cell regulation of the hair cycle.

The ability to manipulate the mammalian hair cycle will lead to novel therapies and strategies to combat all forms of alopecia. Thus, in addition to the epithelial-mesenchymal interactions in the hair follicle, niche and microenvironmental signals that accompany the phases of growth, regression and rest need to be scrutinized. Immune cells are well described in skin homeostasis and wound healing and have recently been shown to play an important role in the mammalian hair cycle. In this review, we will summarize our current knowledge of the role of immune cells in hair cycle control and discuss their relevance to human hair cycling disorders. Increased attention to this aspect of the hair cycle will provide new avenues to manipulate hair regeneration in humans and provide better insight into developing better ex vivo models of hair growth.

Female Androgenetic Alopecia: An Update on Diagnosis and Management.

Female androgenetic alopecia (FAGA) is a common cause of non-scarring alopecia in women. The onset may be at any age following puberty and the frequency increases with age. Clinically, it shows a diffuse hair thinning over the central scalp, while the frontal hairline is usually retained. FAGA can have a significant psychological impact, leading to anxiety and depression. For this reason, early diagnosis is very important to stop the progression of the disease. The sex hormonal milieu is the main pathogenetic mechanism studied in FAGA. The role of androgens is not clearly defined and only one-third of women with FAGA show abnormal androgen levels. Endocrinological diseases with hyperandrogenism associated with FAGA comprise polycystic ovarian syndrome (PCOS), hyperprolactinemia, adrenal hyperplasia and, rarely, ovarian and adrenal tumours. Usually the diagnosis of FAGA is made clinically. A complete clinical examination and a blood examination can reveal other signs of hyperandrogenism. Trichoscopy shows the typical hair miniaturization. A scalp biopsy can be useful when the clinical evaluation does not provide a definitive diagnosis or when cicatricial alopecias with hair loss in the distribution of FAGA or alopecia areata are suspected. FAGA is a slowly progressive disease. The goal of therapy is to stop the progression and to induce a cosmetically acceptable hair regrowth. The most important drugs are topical minoxidil and oral anti-androgens. The purpose of this review is to provide an update on FAGA and to create a guideline on diagnosis and management of this frequent hair disease, not always easily recognizable from cicatricial alopecias with a similar distribution.

Progenitor-cell-enriched micrografts as a novel option for the management of androgenetic alopecia.

Regenerative medicine is a multidisciplinary field that combines engineering and life science principles to promote regeneration, potentially restoring the physiological condition in diseased tissues. Specifically, the developments of complex grafts enhance the intrinsic regenerative capacity of the host by altering its environment. Autologous micrografts obtained through Rigenera® micrografting technology are able to promote derma and bone regeneration. Androgenetic alopecia (AGA) leads to a progressive thinning of scalp hair affecting 60-70% of the adult population worldwide. Pharmacological treatment offers moderate results and hair transplantation represents the only permanent treatment option. The aim of this study was to demonstrate the role of dermis micrografting in the treatment of AGA by clinical and histological evaluations after 4, 6, and 12 months. Hair growth and density were improved at all indicated times. Those outcomes were also confirmed by the TrichoScan® analysis, reporting an increase of total hair count and density with an increase and reduction of anagen and telogen phases, respectively. Scalp dermoscopic analysis showed an improvement of hair density and histological analysis indicated a clear amelioration of the scalp, development of hair follicles, and a beginning of cuticle formation. Collectively, those results suggest a possible use of the micrografts as a novel therapeutic option in the management of AGA.

Alopecia em pacientes anticoagulados / Alopecia in anticoagulated patients

Resumo A alopecia é uma complicação comum da terapia anticoagulante que pode ter repercussões psicológicas importantes nos pacientes, especialmente nos do sexo feminino, e interferir na decisão de extensão da anticoagulação. Esta revisão tem como objetivo descrever os mecanismos potencialmente envolvidos na gênese da alopecia durante a terapia anticoagulante, pois eles ainda não estão totalmente esclarecidos, e as terapias existentes, para a adoção das condutas mais adequadas.

Abstract Alopecia is a common complication of anticoagulant therapy that may have important psychological repercussions for patients, especially female patients, and can interfere with the decision to extend anticoagulation. This review aims to describe the mechanisms potentially involved in the genesis of alopecia during anticoagulant therapy, since these are not yet fully understood, and discusses the existing therapies for the most appropriate management.

The diagnosis of androgenetic alopecia in children: Considerations of pathophysiological plausibility.

Androgenetic alopecia (AGA), one of the most common causes of hair loss in men and women, is an infrequent cause of alopecia in children. In AGA, patients generally start noticing hair thinning after the onset of puberty due to progressive miniaturisation of the hair follicle which leads to vellus transformation of terminal hair. However, the occurrence of prepubertal AGA has rarely been reported in the literature. The pathophysiology of AGA is tightly linked to androgen hormones; prepubertal children do not usually produce significant amounts of adrenal or gonadal androgens. When it does occur, an underlying abnormality should be suspected. Secondary causes of AGA must be excluded when evaluating a patient before the appearance of puberty. Premature puberty, polycystic ovarian syndrome and other causes of hyperandrogenism can present with hair loss in an androgenetic pattern. This article reviews the normal physiology of androgen hormones and their role in the pathophysiology of childhood AGA.