Recent Advances in Understanding of the Etiopathogenesis, Diagnosis, and Management of Hair Loss Diseases.

Hair-loss diseases comprise heterogenous conditions with respective pathophysiology and clinicopathological characteristics. Major breakthroughs in hair follicle biology and immunology have led to the elucidation of etiopathogenesis of non-scarring alopecia (e.g., alopecia areata, AA) and cicatricial alopecia (e.g., lichen planopilaris, LPP). High-throughput genetic analyses revealed molecular mechanism underlying the disease susceptibility of hair loss conditions, such as androgenetic alopecia (AGA) and female pattern hair loss (FPHL). Hair loss attracted public interest during the COVID-19 pandemic. The knowledge of hair loss diseases is robustly expanding and thus requires timely updates. In this review, the diagnostic and measurement methodologies applied to hair loss diseases are updated. Of note, novel criteria and classification/scoring systems published in the last decade are reviewed, highlighting their advantages over conventional ones. Emerging diagnostic techniques are itemized with clinical pearls enabling efficient utilization. Recent advances in understanding the etiopathogenesis and management for representative hair diseases, namely AGA, FPHL, AA, and major primary cicatricial alopecia, including LPP, are comprehensively summarized, focusing on causative factors, genetic predisposition, new disease entity, and novel therapeutic options. Lastly, the association between COVID-19 and hair loss is discussed to delineate telogen effluvium as the predominating pathomechanism accounting for this sequela.

The association of hair loss and coronavirus infection COVID-19 – facts and hypotheses

The main manifestations of COVID-19 are primarily interstitial pneumonia and respiratory failure. No less than 20% of patients have variable skin rashes, which try to be interpreted as markers and predictors of the peculiarities of the course of coronavirus infection. In addition, hair loss is a characteristic manifestation of COVID-19, and the salivary follicles are regarded as a target for SARS-CoV-2. The most common variants of alopecia in patients with a new coronavirus infection or vaccine-induced alopecia are acute telogenic, nondescript, and androgenetic alopecia. This review provides information on the most common variants of hair loss in patients with SARS-CoV-2 infection, the features of their manifestations, and possible mechanisms of development. Acute telogenic hair loss is the most common variant of SARS-CoV-2-induced alopecia, is characteristic of patients with subacute course of COVID-19 and can be combined with trichodynia, anosmia and aguvia, which are markers of nervous system damage. Given the variability in the time of onset after infection, a heterogeneous pathogenesis of alopecia can be assumed. Nested alo-pecia after COVID-19 is often a relapse of the disease, its severity and frequency do not correlate with the severity of the infectious disease, and its prevalence in women indicates the importance of hormonal factors in its development. Androgenetic alopecia may be a predictor of high risk of infection, severe course, and recurrence of COVID-19. The first two variants of alopecia may be associated with COVID-19 vaccination, and the latter is a predictor of inadequate immune response to vaccine administration. The mechanisms of the damaging effects of SARS-CoV-2 on hair follicles have not been fully deciphered and are most likely complex, with different leading links in different types of hair loss. Deciphering these mechanisms may provide prerequisites for understanding the mechanisms of COVID-19 damage to other tissues and organs. © Smirnova I.O. 2023.

The association of hair loss and coronavirus infection COVID-19 – facts and hypotheses

The main manifestations of COVID-19 are primarily interstitial pneumonia and respiratory failure. No less than 20% of patients have variable skin rashes, which try to be interpreted as markers and predictors of the peculiarities of the course of coronavirus infection. In addition, hair loss is a characteristic manifestation of COVID-19, and the salivary follicles are regarded as a target for SARS-CoV-2. The most common variants of alopecia in patients with a new coronavirus infection or vaccine-induced alopecia are acute telogenic, nondescript, and androgenetic alopecia. This review provides information on the most common variants of hair loss in patients with SARS-CoV-2 infection, the features of their manifestations, and possible mechanisms of development. Acute telogenic hair loss is the most common variant of SARS-CoV-2-induced alopecia, is characteristic of patients with subacute course of COVID-19 and can be combined with trichodynia, anosmia and aguvia, which are markers of nervous system damage. Given the variability in the time of onset after infection, a heterogeneous pathogenesis of alopecia can be assumed. Nested alo-pecia after COVID-19 is often a relapse of the disease, its severity and frequency do not correlate with the severity of the infectious disease, and its prevalence in women indicates the importance of hormonal factors in its development. Androgenetic alopecia may be a predictor of high risk of infection, severe course, and recurrence of COVID-19. The first two variants of alopecia may be associated with COVID-19 vaccination, and the latter is a predictor of inadequate immune response to vaccine administration. The mechanisms of the damaging effects of SARS-CoV-2 on hair follicles have not been fully deciphered and are most likely complex, with different leading links in different types of hair loss. Deciphering these mechanisms may provide prerequisites for understanding the mechanisms of COVID-19 damage to other tissues and organs. © Smirnova I.O. 2023.

Hair Loss and Androgen's Role in the Era of COVID-19

The new coronavirus (SARS-COV2), which causes coronavirus illness, has expanded globally, impacting millions of individuals. In comparison to female patients, males have a higher prevalence, morbidity, and death rate from this condition, according to international statistics. Androgens have been implicated in the pathophysiology of COVID-19. This review's objective is to explain the potential connection between the pathophysiology of androgen and the infectivity mechanism of the coronavirus as well as the association between SARS-COV2 and hair disorders. This might assist in clarifying androgen's involvement in COVID-19 prognosis and therapy.

Association of androgenetic alopecia with a more severe form of COVID-19 infection.

BACKGROUND: Individual susceptibility to develop acute respiratory distress syndrome is related to age and most frequent comorbidities. So far, it is known that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily infects the type II pneumocytes in humans, with the help of transmembrane serine protease type 2 (TMPRSS2). Up to now, the only known transcriptional promoters of genes coding TMPRSS2 are androgenic. Theoretically, the elevated level of androgens or androgen receptors would lead to a higher expression of TMPRSS2 and a higher level of viremia as a consequence. AIM: The aim of our research was to indirectly investigate if the severity of SARS-CoV-2 infection is dependent on the expression of androgen receptors. METHODS: This observational study analysed male patients hospitalized for SARS-CoV-2 infection with respect to the length of hospitalisation, the outcome of the disease, the type of necessary oxygen support and the presence of comorbidities and hairiness. In hairiness estimation, we used an adapted version of the Hamilton-Norwood scale and the presence of the Gabrin sign. RESULTS: In total, 208 patients were enrolled in the study. There were statistically significant differences comparing the average age of patients with the different types of alopecia when groups were divided according to the presence of the Gabrin sign (t = 4.958, p > 0.01). The outcomes and the type of needed minimal oxygen support, compared with the type of alopecia in the case of Gabrin + / - classification showed a statistically significant difference in the outcome of the disease (p = 0.027). There were no statistically significant differences in the distribution of comorbidities among alopecia groups, but hypertension was related to poor COVID-19 prognosis. CONCLUSION: Our findings suggest that the Gabrin sign and hypertension are related to a poor COVID-19 prognosis.

Co-Relation Between Androgenetic Alopecia and Severity of COVID-19 Disease-A Cross-Sectional Study

Objective: To find the correlation between the degree of androgenetic alopecia and the severity of COVID-19 disease. Study Design: Cross-sectional study. Place and Duration of the Study: Dermatology department, PEMH, Rawalpindi Pakistan from Feb to Aug 2021. Methodology: A total of 227 patients (male and female) of COVID-19 admitted in a Corona ward of Pak Emirates Military Hospital, Rawalpindi, Pakistan were selected randomly. The degree of androgenetic alopecia was assessed with the help of using the Hamilton-Norwood Scale (HNS) for men and the Ludwig Scale (LS) for women, and the severity of COVID-19 was graded based on CT severity score (CTSS). Results: Out of the total, 161 (71%) were male, and 66 (29%) were female. Out of 161 males, 31 (19.2%) had no alopecia, and 130 (80.7%) had some degree of alopecia. Out of patients with alopecia, 33 had moderate alopecia, and 97 had severe alopecia. Out of 66 females, 32 (48.5%) had no alopecia, while 34 (51.5%) had some degree of alopecia. Conclusion: High frequency of androgenetic alopecia in severely ill-hospitalized patients of COVID-19 suggests that androgen has a vital role in the disease severity of COVID-19. © 2022, Army Medical College. All rights reserved.

Hair Loss and Androgen's Role in the Era of COVID-19

The new coronavirus (SARS-COV2), which causes coronavirus illness, has expanded globally, impacting millions of individuals. In comparison to female patients, males have a higher prevalence, morbidity, and death rate from this condition, according to international statistics. Androgens have been implicated in the pathophysiology of COVID-19. This review's objective is to explain the potential connection between the pathophysiology of androgen and the infectivity mechanism of the coronavirus as well as the association between SARS-COV2 and hair disorders. This might assist in clarifying androgen's involvement in COVID-19 prognosis and therapy. © 2022, International Medical Research and Development Corporation. All rights reserved.

Alopecia in patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: COVID-19 is associated with androgenetic alopecia (AGA), telogen effluvium (TE), and alopecia areata (AA). No studies have analyzed the aggregate data to date. OBJECTIVE: We conducted a systematic review to characterize the types, incidence, timing, and clinical outcomes of COVID-19-associated alopecia. METHODS: We searched PubMed/MEDLINE, Scopus, and Embase for articles published between November 2019 and August 2021 using the key words "alopecia" or "hair" and COVID-19-related search terms, identifying 41 original articles describing patients with alopecia and COVID-19. RESULTS: The current review included 1826 patients with alopecia and COVID-19 (mean age, 54.5 years; 54.3% male). The most common types of alopecia identified were AGA (30.7%, 86.4% male), TE (19.8%, 19.3% male), and AA (7.8%, 40.0% male). AGA preceded COVID-19 symptoms. TE was usually newly triggered by COVID-19 (93.6%). AA usually occurred in patients with preexisting disease (95.1%). LIMITATIONS: Definitions of COVID-19 onset varied. Studies differed in methodology and were susceptible to reporting and sampling bias. Studies with large sample sizes may exert a disproportionate influence on data. CONCLUSION: AGA may be a risk factor for severe COVID-19, whereas TE presents as a sequela of COVID-19. AA generally occurs as a relapse in patients with preexisting alopecia.

Association of androgenetic alopecia and severity of coronavirus disease 2019.

OBJECTIVE: To establish the association of androgenetic alopecia (AGA) and the severity of coronavirus disease 2019 (COVID-19). DESIGN: Observational study. METHODOLOGY: A total of 300 hospitalized patients of COVID-19 were included. Scoring of AGA was done, and severity of COVID-19 was measured as better and worse hospital outcomes. Correlation between severity of AGA and severity of COVID-19 was noted. RESULTS: Out of 300 patients, 220 (73.33%) were male and 80 (26.67%) were female. In males, mild-to-moderate Hamilton-Norwood scale (HNS<3) and severe alopecia (HNS3-7) were noted among 43(20%) and 177(80.55%) patients, respectively. In females, 43(54%) had no AGA while 37(46%) had AGA. In 37 females with AGA, mild-to-moderate (Ludwig scale <2) and severe alopecia (Ludwig scale 2-3) were seen in 9(24.32%) and 28(75.68%) patients, respectively. We report a significant increase in frequency (95%) and severity of AGA and worse outcomes in males (p-value 0.000, chi-square: 18.90) compared with females (46%) (p-value 0.273, chi-square: 7.544), with notable adverse COVID-19 disease outcomes in the younger age group of men and also in few women of younger age group suffering from AGA without any comorbidities. CONCLUSION: Our study shows a significant increase in frequency and severity of AGA and worse outcomes in men compared with women. There was a significant association between AGA severity and hospital disease outcome in men compared with women. Younger age group patients with severe AGA particularly men also faced adverse outcomes while having no known comorbidities, supporting the hypothesis that anti-androgen drugs might be valuable in patients of COVID-19.

Platelet-Rich Plasma Treatment for Accelerated Androgenetic Alopecia Pattern Hair Loss After COVID-19 Infection: A Case Series.

BACKGROUND: Hair-related manifestations such as alopecia areata or telogen effluvium were reported during COVID-19 disease. Accelerated hair loss with androgenetic alopecia (AGA) pattern or management has not been discussed before. AIMS: This study aimed to examine the accelerated AGA pattern hair loss and management with PRP treatment. MATERIALS AND METHODS: This study was designed prospectively and nine patients included to study confirmed PCR test for COVID-19 infection. Patients underwent platelet-rich plasma (PRP) injections for 4 sessions. Results were accessed with the hair pull test (HPT) and self-administered hair growth questionnaire (HGQ). RESULTS: Nine patients were admitted with complaints of hair loss after an average of 220 ± 24.2 (min: 182 max: 264) day after recovery of COVID-19. Mean age of the patients was 33.8 ±8.4 years old (min: 26, max: 52). Six (66.7%) patients were male, and three (33.3%) of them were female. HPT score decreased to 6.0 ± 1.6 after the first PRP application (p = 0.007, CI 95%:2.7-5.2) and decreased to 1.2 ± 0.8 after the last PRP session (p = 0.008, CI 95%: 6.4-11.1). Five (55.5%) of the patients described the treatment as "very effective" after treatment with HGQ. CONCLUSIONS: Accelerated hair loss associated with COVID-19 continues in long term and PRP treatment provides a satisfactory solution.

Androgenetic alopecia and COVID-19: Is there a clinical connection?

BACKGROUND: During the coronavirus disease 2019 (COVID-19) outbreak, multiple studies showed higher rates of severe infection in adults and specifically in male patients, which may be related to differences in androgen receptor (AR) expression. Androgenetic alopecia (AGA) is one of the AR expression manifestations. AIM: To explore AGA severity as a possible risk factor for COVID-19 severity in hospitalized patients. METHODS: A total of 164 subjects (116 men and 48 females) with confirmed COVID-19 in need of hospitalization were included in this study. An experienced dermatologist examined the correlation of clinical signs of COVID-19 severity with AGA types. For evaluation of the association between categorical variables and comparison of the mean age in three groups of COVID-19 patients, the Fisher's exact test and the analysis of variance were used. RESULTS: Our cross-sectional study included 116 male patients (70.7%) with a median age of 65.5 (age range: 22-97) years. Among them, 13.8% required intubation, 15.5% needed intensive care unit (ICU) care, and 70.7% required inward hospitalization. The Hamilton-Norwood Scale (HNS) was as follows: HNS I 14.7%, HNS II 12.1%, HNS III 20.7%, HNS IV 19.8%, HNS IV 29.8%, HNS V 17.2%, HNS VI 13.8%, and HNS VII 1.7%. Also, 29.3% of the patients were female, possessing a median age of 72 (age range: 23-98) years. In this group, 8.3% required intubation, 6.3% required ICU care, and 85.4% needed inpatient ward admission care. The Ludwig Scale (LS) was as follows: LS I 52.1%, LS II 35.4%, and LS III 12.5%. CONCLUSION: The severity of AGA type did not correlate with the severity of COVID-19 among hospitalized patients. Our results were in contrast with other research that suggested AGA severity as a marker of unfavorable outcomes of COVID-19.

COVID-19 induced telogen effluvium.

COVID-19 is a febrile, infectious illness that has previously been associated with telogen effluvium (TE). However, to date, no study has been conducted to determine the incidence of TE in those who have had COVID-19. To assess the frequency of TE in post-COVID-19 patients and the correlation between the development of TE and the severity of COVID-19, to understand whether emotional stress or medications are responsible for the development of TE. Totally 204 patients with a history of SARS-CoV-2 infection in the last 3 months were included in the study. The diagnosis of TE was made by history of excessive hair shedding, hair pull test, diffuse or bitemporal thinning, and absence of anisotrichosis in trichoscopy. Patients who did not have any TE cause other than COVID-19 and whose hair loss started after COVID-19 were considered as "COVID-19 associated TE (CATE)." We found TE in 75 (36.7%) cases and androgenetic alopecia (AGA) in 85 (41.7%) cases. CATE was present in 27.9% of cases and developed on average 53.76 (± 23.772) days after COVID-19 real-time reverse transcription polymerase chain reaction (RT-PCR) positivity. The proportion of patients with CATE was numerically higher in hospitalized patients compared to outpatients (31.7% vs. 24.3%; p = 0.238); and significantly higher in women compared to men (42.3% vs. 6.2%; p < 0.001), in patients with hypertension compared to those without hypertension (40.4% vs. 23.1%; p = 0.014), and in patients who had respiratory symptoms compared to those who had not (31.7% vs. 14.0%; p = 0.021). The patients with and without CATE were similar in terms of stress level and usage of COVID-19 medications. Patients with AGA had a higher rate of hospitalization (69.4% vs. 35.3%; p < 0.001) and a higher incidence of fever (69.4% vs. 54.6%; p = 0.033) during COVID-19, compared to those without. TE developed in approximately one-quarter of people who have had COVID-19, and our study is the first to detect it. The time to onset of CATE, which was 7-8 weeks after the SARS-CoV-2 RT-PCR positivity, was not much different from post-infectious TE. Patients with severe COVID-19 seem to be more prone to develop TE. The presence of AGA is associated with a more severe COVID-19. During the pandemic, clinicians should consider a previous SARS-CoV-2 infection in patients presenting with hair loss.

Proxalutamide Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial.

Antiandrogens have demonstrated a protective effect for COVOD-19 patients in observational and interventional studies. The goal of this study was to determine if proxalutamide, an androgen receptor antagonist, could be an effective treatment for men with COVID-19 in an outpatient setting. A randomized, double-blinded, placebo-controlled clinical trial was conducted at two outpatient centers (Brasilia, Brazil). Patients were recruited from October 21 to December 24, 2020 (clinicaltrials.gov number, NCT04446429). Male patients with confirmed COVID-19 but not requiring hospitalization (COVID-19 8-point ordinal scale <3) were administered proxalutamide 200 mg/day or placebo for up to 7 days. The primary endpoint was hospitalization rate at 30 days post-randomization. A total of 268 men were randomized in a 1:1 ratio. 134 patients receiving proxalutamide and 134 receiving placebo were included in the intention-to-treat analysis. The 30-day hospitalization rate was 2.2% in men taking proxalutamide compared to 26% in placebo, P < 0.001. The 30-day hospitalization risk ratio was 0.09; 95% confidence interval (CI) 0.03-0.27. Patients in the proxalutamide arm more frequently reported gastrointestinal adverse events, however, no patient discontinued treatment. In placebo group, 6 patients were lost during follow-up, and 2 patients died from acute respiratory distress syndrome. Here we demonstrate the hospitalization rate in proxalutamide treated men was reduced by 91% compared to usual care.

Safety and efficacy of ALRV5XR in women with androgenetic alopecia or telogen effluvium: A randomised, double-blinded, placebo-controlled clinical trial.

BACKGROUND: Scalp hair loss (alopecia) in women is a common ageing and senescing condition. It usually presents as androgenetic alopecia (AGA) or telogen effluvium (TE) and often has pronounced psychological consequences. ALRV5XR is a novel treatment aiming to regenerate a normal hair phenotype by targeting multiple molecular pathways linked to hair growth promotion and hair follicle stem cell activation. The primary objectives of this 24-week trial were to evaluate the safety and efficacy of ALRV5XR in terminal hair (TH) regrowth in women with AGA or TE. METHODS: This randomised, double-blind, placebo-controlled trial was performed in a USA community clinic. Healthy women 18-65 years of age with AGA or TE of Ludwig classification I-II and Fitzpatrick skin type I-VI were enrolled. They were allocated in a 1:1 ratio into ALRV5XR or placebo treatment groups using a random number table. Masked dermatologist assessments, phototrichograms and blood samples were obtained at baseline, 12 and 24 weeks. Subjects were given a masked treatment regimen of oral capsules, shampoo, conditioner and follicle serum for daily administration. Main outcomes were absolute and per cent changes in TH density and response rates. The trial was registered with clinicaltrials.gov (NCT04450602) and is completed. FINDINGS: 46 subjects (23 ALRV5XR, 23 placebo) were enrolled between April 3 and October 20, 2018. Five subjects dropped out and two were non-compliant. Thirty-nine subjects completed the trial (18 ALRV5XR, 21 placebo). At 24 weeks, the absolute change in TH density improved by 30·1THs/cm2 (95% CI: 15·1-45·1; p=0·0002), and the relative density increased by 19·7% (95% CI: 8·0%-31·4%; p=0·0016). The odds ratio for being a responder (≥0 change) was 2·7. Efficacy increased 133% from week 12 to 24. Efficacy outcomes were similar in AGA and TE subjects. 66·7% of the ALRV5XR group responded by regrowing 40THs/cm2 or more hair. No adverse events were reported. INTERPRETATION: In women with AGA or TE, ALRV5XR treatment significantly increased hair regrowth without adverse events. ALRV5XR displayed a multi-fold improved efficacy and response rate when compared to published trials of standard therapy. Progressive acceleration of TH regrowth suggests regeneration of the structure and function of non-productive telogen follicles and prolonged treatment may restore a normal hair phenotype.

Androgenetic alopecia and COVID-19: A review of the hypothetical role of androgens.

The coronavirus disease 2019 (COVID-19) has become the most emerging health issue globally. A prompt investigation regarding disease management and treatment is crucial for decreasing the burden of the disease. Many explorations and hypotheses have been posed, but the definite treatment has not been determined for COVID-19. Recent studies described a substantial prevalence of COVID-19 and also a higher rate of morbidity and mortality in men afflicted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The gender-related discordance in COVID-19 infection may be due to hormonal differences, socioeconomic factors, genetic susceptibility, gender-related comorbidities, and habits like alcohol consumption. On the other hand, several studies proposed that androgens could improve the immune system and have a protective role in COVID-19, and decreased levels of androgens might be associated with unsatisfactory outcomes. In the field of dermatology, androgenetic alopecia (AGA) is correlated with a hyperandrogenic state and may be related to COVID-19 severity. Furthermore, recent research has assessed the plausible association of AGA and COVID-19. In this review, we investigate all evidence on AGA and its relationship with COVID-19, including the possible role of androgens in COVID-19 severity and outcomes as well as candidate androgen-related drugs for the treatment of COVID-19.

Proxalutamide Significantly Accelerates Viral Clearance and Reduces Time to Clinical Remission in Patients with Mild to Moderate COVID-19: Results from a Randomized, Double-Blinded, Placebo-Controlled Trial.

Background The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into type II pneumocytes is dependent on a modification of viral spike proteins by transmembrane protease serine 2 (TMPRSS2) expressed on the surface of human cells. TMPRSS2 is regulated by the androgen receptor, hence, SARS-CoV-2 infectivity is indirectly dependent on androgenic status and phenotype. Previously, we have reported that men affected by androgenetic alopecia (AGA) are overrepresented in severe coronavirus disease 2019 (COVID-19). Additionally, we have reported that men taking antiandrogenic drugs, e.g., 5-alpha-reductase inhibitors (5ARis), are less likely to have severe COVID-19. Here we aimed to test whether the androgen receptor antagonist, Proxalutamide, would be a beneficial treatment for subjects with SARS-CoV-2 infection. Methods Male and female subjects were recruited to a double-blinded, randomized, prospective, investigational study of Proxalutamide for the treatment of COVID-19. Mild to moderate, non-hospitalized subjects, who were confirmed positive for SARS-CoV-2, were treated with either Proxalutamide 200 mg/day or placebo. Endpoints for the study were remission time (days) and the percentage of subjects confirmed negative for SARS-CoV-2 on Day 7 after treatment. A negative SARS-CoV-2 test was defined by concentration-time (Ct)>40 determined by real-time reverse transcription-polymerase chain reaction (rtPCR). Results Two-hundred thirty-six (2360 subjects were included in the study (108 female, 128 male); 171 were randomized to the Proxalutamide arm and 65 were in the placebo group. On Day 7, SARS-CoV-2 became non-detectable with rtPCR (cT>40) in 82% of the subjects in the Proxalutamide group versus 31% in the placebo group (p < 0.001). The average clinical remission time for patients treated with Proxalutamide was 4.2 ±5.4 days versus 21.8 ±13.0 days in the placebo arm (p < 0.001). Conclusion Proxalutamide significantly accelerated viral clearance on Day 7 in mild to moderate COVID-19 patients versus placebo. Further, the time to clinical remission was significantly reduced in patients treated with Proxalutamide versus placebo.