Clinical Characterization and Treatment Response of Folliculitis Decalvans Lichen Planopilaris Phenotypic Spectrum: A Unicentre Retrospective Series of 31 Patients.

Folliculitis decalvans and lichen planopilaris phenotypic spectrum has been described as a form of cicatricial alopecia. The aim of this study is to describe the clinical and trichoscopic features and therapeutic management of this condition in a series of patients. A retrospective observational unicentre study was designed including patients with folliculitis decalvans and lichen planopilaris phenotypic spectrum confirmed with biopsy. A total of 31 patients (20 females) were included. The most common presentation was an isolated plaque of alopecia (61.3%) in the vertex. Trichoscopy revealed hair tufting with perifollicular white scaling in all cases. The duration of the condition was the only factor associated with large plaques (grade III) of alopecia (p = 0.026). The mean time to transition from the classic presentation of folliculitis decalvans to folliculitis decalvans and lichen planopilaris phenotypic spectrum was 5.2 years. The most frequently used treatments were topical steroids (80.6%), intralesional steroids (64.5%) and topical antibiotics (32.3%). Nine clinical relapses were detected after a mean time of 18 months (range 12-23 months). Folliculitis decalvans and lichen planopilaris phenotypic spectrum is an infrequent, but probably underdiagnosed, cicatricial alopecia. Treatment with anti-inflammatory drugs used for lichen planopilaris may be an adequate approach.

Folliculitis Decalvans Has a Heterogeneous Microbiological Signature and Impaired Immunological Response.

BACKGROUND: Folliculitis decalvans (FD) is a rare primary neutrophilic scarring alopecia whose etiology has not been completely elucidated yet. OBJECTIVE: The aim of the study was to determine if the follicular microbiota residing in FD-affected hair follicles had a distinct microbiological signature and if an aberrant immune response was present in the pathogenesis of FD. METHODS: We conducted a cross-sectional study of 10 patients affected by FD. Trichoscopy-guided follicular biopsies were taken from affected and healthy scalp to identify the follicular microbiome using next-generation sequencing. We searched for microbiological biomarkers of FD-affected follicles using the linear discriminant analysis (LDA) effect size (LEfSe) tool. Additionally, peripheral blood mononuclear cells were obtained, and their cytokine production was quantified after incubation with pathogen-associated molecular patterns isolated from patients' biopsies and compared with healthy controls. RESULTS: ß-diversity analysis showed statistically significant differences regarding bacteria comparing follicular microbiota of healthy and FD-affected hairs. Ruminococcaceae, Agathobacter sp., Tyzzerella sp., and Bacteriodales vadin HA21 family were good predictors of disease status. IL-10, TNF-α, and IL-6 levels were significantly decreased in patients after incubation with various strains of bacteria compared with controls. CONCLUSION: FD hair follicles have a specific heterogenous follicular bacterial microbiota signature. Additionally, these patients seem to have an impaired immunological response.

Genotyping of the rs1800440 Polymorphism in CYP1B1 Gene and the rs9258883 Polymorphism in HLA-B Gene in a Spanish Cohort of 223 Patients with Frontal Fibrosing Alopecia.

The pathogenesis of frontal fibrosing alopecia has been linked to specific genetic variants. CYP1B1 codes for a component of the cytochrome p450 machinery that is involved in the metabolism of xenobiotic oestrogens. The study of the prevalence of polymorphisms in this gene may help to understand their role in the development of frontal fibrosing alopecia. The aim of this study is to describe the frequency of genetic variations in the alleles HLA-B*07:02 and CYP1B1 in patients with frontal fibrosing alopecia. A cross-sectional study was designed to evaluate blood samples from patients with frontal fibrosing alopecia who attended the Dermatology Department at University Hospital Ramón y Cajal (Madrid, Spain), in search of the polymorphisms rs9258883 and rs1800440 in the alleles HLA-B*07:02 and CYP1B1, respectively. A total of 223 patients were included in the study. Among the 83.8% of patients who carried the rs9258883 polymorphism in HLA-B*07:02, 58.7% were heterozygous for this variant and it was not present in 14.8% of the cases. The majority of patients with frontal fibrosing alopecia lacked the protective rs1800440 polymorphism in CYP1B1 (75.2%). This suggests a relevant role of this variant in development of frontal fibrosing alopecia. The genetic approach to this condition might influence patient prognosis and therapy options.

Treatments for alopecia areata: a network meta-analysis.

BACKGROUND: Alopecia areata is an autoimmune disease leading to nonscarring hair loss on the scalp or body. There are different treatments including immunosuppressants, hair growth stimulants, and contact immunotherapy. OBJECTIVES: To assess the benefits and harms of the treatments for alopecia areata (AA), alopecia totalis (AT), and alopecia universalis (AU) in children and adults. SEARCH METHODS: The Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov and WHO ICTRP were searched up to July 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated classical immunosuppressants, biologics, small molecule inhibitors, contact immunotherapy, hair growth stimulants, and other therapies in paediatric and adult populations with AA. DATA COLLECTION AND ANALYSIS: We used the standard procedures expected by Cochrane including assessment of risks of bias using RoB2 and the certainty of the evidence using GRADE. The primary outcomes were short-term hair regrowth ≥ 75% (between 12 and 26 weeks of follow-up), and incidence of serious adverse events. The secondary outcomes were long-term hair regrowth ≥ 75% (greater than 26 weeks of follow-up) and health-related quality of life. We could not perform a network meta-analysis as very few trials compared the same treatments. We presented direct comparisons and made a narrative description of the findings. MAIN RESULTS: We included 63 studies that tested 47 different treatments in 4817 randomised participants. All trials used a parallel-group design except one that used a cross-over design. The mean sample size was 78 participants. All trials recruited outpatients from dermatology clinics. Participants were between 2 and 74 years old. The trials included patients with AA (n = 25), AT (n = 1), AU (n = 1), mixed cases (n = 31), and unclear types of alopecia (n = 4). Thirty-three out of 63 studies (52.3%) reported the proportion of participants achieving short-term hair regrowth ≥ 75% (between 12 and 26 weeks). Forty-seven studies (74.6%) reported serious adverse events and only one study (1.5%) reported health-related quality of life. Five studies (7.9%) reported the proportion of participants with long-term hair regrowth ≥ 75% (greater than 26 weeks). Amongst the variety of interventions found, we prioritised some groups of interventions for their relevance to clinical practice: systemic therapies (classical immunosuppressants, biologics, and small molecule inhibitors), and local therapies (intralesional corticosteroids, topical small molecule inhibitors, contact immunotherapy, hair growth stimulants and cryotherapy). Considering only the prioritised interventions, 14 studies from 12 comparisons reported short-term hair regrowth ≥ 75% and 22 studies from 10 comparisons reported serious adverse events (18 reported zero events and 4 reported at least one). One study (1 comparison) reported quality of life, and two studies (1 comparison) reported long-term hair regrowth ≥ 75%. For the main outcome of short-term hair regrowth ≥ 75%, the evidence is very uncertain about the effect of oral prednisolone or cyclosporine versus placebo (RR 4.68, 95% CI 0.57 to 38.27; 79 participants; 2 studies; very low-certainty evidence), intralesional betamethasone or triamcinolone versus placebo (RR 13.84, 95% CI 0.87 to 219.76; 231 participants; 1 study; very low-certainty evidence), oral ruxolitinib versus oral tofacitinib (RR 1.08, 95% CI 0.77 to 1.52; 80 participants; 1 study; very low-certainty evidence), diphencyprone or squaric acid dibutil ester versus placebo (RR 1.16, 95% CI 0.79 to 1.71; 99 participants; 1 study; very-low-certainty evidence), diphencyprone or squaric acid dibutyl ester versus topical minoxidil (RR 1.16, 95% CI 0.79 to 1.71; 99 participants; 1 study; very low-certainty evidence), diphencyprone plus topical minoxidil versus diphencyprone (RR 0.67, 95% CI 0.13 to 3.44; 30 participants; 1 study; very low-certainty evidence), topical minoxidil 1% and 2% versus placebo (RR 2.31, 95% CI 1.34 to 3.96; 202 participants; 2 studies; very low-certainty evidence) and cryotherapy versus fractional CO2 laser (RR 0.31, 95% CI 0.11 to 0.86; 80 participants; 1 study; very low-certainty evidence). The evidence suggests oral betamethasone may increase short-term hair regrowth ≥ 75% compared to prednisolone or azathioprine (RR 1.67, 95% CI 0.96 to 2.88; 80 participants; 2 studies; low-certainty evidence). There may be little to no difference between subcutaneous dupilumab and placebo in short-term hair regrowth ≥ 75% (RR 3.59, 95% CI 0.19 to 66.22; 60 participants; 1 study; low-certainty evidence) as well as between topical ruxolitinib and placebo (RR 5.00, 95% CI 0.25 to 100.89; 78 participants; 1 study; low-certainty evidence). However, baricitinib results in an increase in short-term hair regrowth ≥ 75% when compared to placebo (RR 7.54, 95% CI 3.90 to 14.58; 1200 participants; 2 studies; high-certainty evidence). For the incidence of serious adverse events, the evidence is very uncertain about the effect of topical ruxolitinib versus placebo (RR 0.33, 95% CI 0.01 to 7.94; 78 participants; 1 study; very low-certainty evidence). Baricitinib and apremilast may result in little to no difference in the incidence of serious adverse events versus placebo (RR 1.47, 95% CI 0.60 to 3.60; 1224 participants; 3 studies; low-certainty evidence). The same result is observed for subcutaneous dupilumab compared to placebo (RR 1.54, 95% CI 0.07 to 36.11; 60 participants; 1 study; low-certainty evidence). For health-related quality of life, the evidence is very uncertain about the effect of oral cyclosporine compared to placebo (MD 0.01, 95% CI -0.04 to 0.07; very low-certainty evidence). Baricitinib results in an increase in long-term hair regrowth ≥ 75% compared to placebo (RR 8.49, 95% CI 4.70 to 15.34; 1200 participants; 2 studies; high-certainty evidence). Regarding the risk of bias, the most relevant issues were the lack of details about randomisation and allocation concealment, the limited efforts to keep patients and assessors unaware of the assigned intervention, and losses to follow-up. AUTHORS' CONCLUSIONS: We found that treatment with baricitinib results in an increase in short- and long-term hair regrowth compared to placebo. Although we found inconclusive results for the risk of serious adverse effects with baricitinib, the reported small incidence of serious adverse events in the baricitinib arm should be balanced with the expected benefits. We also found that the impact of other treatments on hair regrowth is very uncertain. Evidence for health-related quality of life is still scant.

Imiquimod-enhanced immunotherapy with diphencyprone for patients with alopecia areata.

Topical immunotherapy with dyphencyprone (DPCP) is widely used in patients with alopecia areata (AA). It can produce a contact dermatitis that is believed to decrease Th1 response, predominant in AA. It has been shown that imiquimod (IMQ), a topical immunomodulator drug, can produce sensitization to DPCP in patients that do not show signs of contact dermatitis when exposed to DPCP. Nevertheless, there is no evidence as to whether it can improve DPCP efficacy in already sensitized patients. We present a series of 9 patients, (7 females [77%] and 2 males [22%]) with a mean age of 38.4 years (range, 19-60 years), successfully sensitized to DPCP, that were treated with a combination of DPCP and IMQ. The mean SALT (Severity of Alopecia Tool) score before adding IMQ was 43.3 (range, 10-60), and the mean number of months of DPCP use prior to the addition of IMQ was 6.8 (range 0-10). After adding IMQ to their DPCP treatment, 77% of the patients had further improvement, with a mean SALT reduction of 13.3 (range, [-50] - 40), and a mean duration of response of 5.2 months. No adverse effects were reported. According to this data, we believe that the combination of DPCP and IMQ can be a promising way of improving the efficacy of contact immunotherapy in AA, and requires further study.

Mesotherapy With Dutasteride for Androgenetic Alopecia: A Retrospective Study in Real Clinical Practice.

BACKGROUND: 5-alpha inhibitors are an effective treatment for androgenetic alopecia. Mesotherapy with dutasteride has been proposed as an effective method to improve hair loss and reducing systemic absorption. OBJECTIVE: The main objective was to describe the safety profile of mesotherapy with dutasteride in real clinical practice in a large cohort of patients with androgenetic alopecia. A secondary aim was to describe the effectiveness of this treatment. METHODS AND MATERIALS: A multicentric retrospective study was designed. Patients treated with at least 6 months of follow-up were included in the study. Side effects and response to the treatment were analyzed. RESULTS: A total of 541 patients were included. The commonest approach during the first year was to perform the treatment every 3 months. Response to the mesotherapy in monotherapy could be assessed in 86 patients (15.9%) after one year. Most of them presented clinical improvement, being a marked improvement in 33 patients (38.4%). Pain was the most frequent side effect of the treatment (246 patients, 45.5%). No serious or sexual adverse events were detected. CONCLUSION: Mesotherapy with dutasteride was effective in male and female hair loss in real clinical practice. Side effects related to the treatment were mild and self-limited. This therapy may be an effective option for select patients wishing to avoid oral treatment. J Drugs Dermatol. 2022;21(7):742-747. doi:10.36849/JDD.6610.

Effectiveness of dutasteride in a large series of patients with frontal fibrosing alopecia in real clinical practice.

BACKGROUND: Dutasteride has been proposed as an effective therapy for frontal fibrosing alopecia (FFA). OBJECTIVES: We sought to describe the therapeutic response to dutasteride and the most effective dosage in FFA compared with other therapeutic options or no treatment. METHODS: This was a retrospective observational study including patients with FFA with a minimum follow-up of 12 months. Therapeutic response was evaluated according to the stabilization of the hairline recession. RESULTS: A total of 224 patients (222 females) with a median follow-up of 24 months (range 12-108 months) were included. The stabilization rate for the frontal, right, and left temporal regions after 12 months was 62%, 64%, and 62% in the dutasteride group (n = 148), 60%, 35%, and 35% with other systemic therapies (n = 20), and 30%, 41%, and 38% without systemic treatment (n = 56; P = .000, .006, and .006, respectively). Stabilization showed a statistically significant association with an increasing dose of dutasteride (88%, 91%, and 84% with a weekly treatment of 5 or 7 doses of 0.5 mg [n = 32], P < .005). Dutasteride was well tolerated in all patients. LIMITATIONS: Limitations included the observational and retrospective design. CONCLUSIONS: Oral dutasteride was the most effective therapy with a dose-dependent response for FFA in real clinical practice compared with other systemic therapies or no systemic treatment.

Safety of low-dose oral minoxidil for hair loss: A multicenter study of 1404 patients.

BACKGROUND: The major concern regarding the use of low-dose oral minoxidil (LDOM) for the treatment of hair loss is the potential risk of systemic adverse effects. OBJECTIVE: To describe the safety of LDOM for the treatment of hair loss in a large cohort of patients. METHODS: Retrospective multicenter study of patients treated with LDOM for at least 3 months for any type of alopecia. RESULTS: A total of 1404 patients (943 women [67.2%] and 461 men [32.8%]) with a mean age of 43 years (range 8-86) were included. The dose of LDOM was titrated in 1065 patients, allowing the analysis of 2469 different cases. The most frequent adverse effect was hypertrichosis (15.1%), which led to treatment withdrawal in 14 patients (0.5%). Systemic adverse effects included lightheadedness (1.7%), fluid retention (1.3%), tachycardia (0.9%), headache (0.4%), periorbital edema (0.3%), and insomnia (0.2%), leading to drug discontinuation in 29 patients (1.2%). No life-threatening adverse effects were observed. LIMITATIONS: Retrospective design and lack of a control group. CONCLUSION: LDOM has a good safety profile as a treatment for hair loss. Systemic adverse effects were infrequent and only 1.7% of patients discontinued treatment owing to adverse effects.

An anti-hair loss treatment in the management of mild androgenetic alopecia: Results from a large, international observational study.

Androgenic alopecia (AGA) is a common and chronic condition. It may impact self-esteem, self-image and quality of life. Benefit, tolerability, cosmetic acceptance and patient satisfaction are key to ensure good treatment outcome. Hair loss improvement and hair quality with AC5 (2,4-Diamino-Pyrimidine-N-Oxyde, arginine, 6-O glucose linoleate (SP94), piroctone olamine and Vichy mineralizing water) once daily was assessed in 527 subjects with mild AGA in an open-label, observational, international real-life study. After 3 months, investigators evaluated the impact of AC5 on hair loss, product satisfaction and asked subjects about local tolerance; subjects assessed hair growth and quality and satisfaction. Data from 357 subjects were evaluable for the benefit analysis; 59.9% of subjects were female; the mean age was 33.6±8.7 years. Duration of hair loss was 1.62±2.24 years. 71.3% of women had a Ludwig score of 1 and 40.8% of men had a Hamilton Norwood score of 2. At the end of study, hair loss was reduced in 89.0% of subjects; it was slightly higher in women (92.5%) than in men (83.8%). Subject satisfaction on a scale from 0 (not satisfied at all) to 10 (completely satisfied) was 7.9±1.7. Tolerance was rated good to very good by 98.6% of all subjects. In conclusion, AC5 reduces mild AGA in both men and women with a pleasant texture. AC5 was well tolerated and highly appreciated.

Effectiveness and safety of oral dutasteride for male androgenetic alopecia in real clinical practice: A descriptive monocentric study.

The objective of our study was to describe the effectiveness and safety of oral dutasteride (OD) for male androgenetic alopecia in real clinical practice. A retrospective, monocentric, and descriptive study was designed. Male patients with androgenetic alopecia that had received OD for at least 12 months were included. Three or less capsules of 0.5 mg per week were considered low doses. Therapeutic response was assessed by comparison of pre- and post-treatment (at month 12) clinical images by three independent dermatologists with expertise in hair disorders, using a four-point scale (worsening, stabilization, mild improvement or marked improvement). In all, 307 patients with a mean age of 35.3 years (range 18-79) were included. Eight patients (2.6%) required the discontinuation of the drug due to decreased libido (n = 4), gynecomastia (n = 2), mood disorder (n = 1) and erectile dysfunction (n = 1). All these AE resolved after stopping the medication. No AE were detected in patients receiving low doses of OD. The effectiveness was evaluated in the subgroup of 42 patients (13.7%) who received OD in monotherapy: 38 patients improved (90%), 10 of them (23.8%) presenting a marked improvement, 4 patients (9.5%) were stable and none patient worsened. In conclusion, OD is an effective treatment for male androgenetic alopecia in real clinical practice, presenting a good safety profile, especially at lower doses.

Safety of low-dose oral minoxidil treatment for hair loss. A systematic review and pooled-analysis of individual patient data.

low dose oral minoxidil (OM) is an increasingly used treatment for androgenetic alopecia and other types of hair loss. to analyze available data of patients treated with OM, focusing on safety and adverse effects. a search in PubMed and EMBASE was performed for studies reporting the treatment of alopecia with OM. Individual patient data available for pooled-analysis were sex, dose of OM, presence of hypertrichosis and lower limb edema. 14 studies including 442 patients were analyzed. OM was used at doses between 0.25 and 5 mg, for eight different types of alopecia. Hypertrichosis was observed in 24% of patients. All doses had an increased odds ratio of hypertrichosis, compared to 0.25 to 0.5 mg (P < .001). Pedal edema was observed in 2% and was also associated with higher doses of OM (P = .009). Postural hypotension and heart rate alterations occurred only in 1.1% and 1.3% of the patients, respectively. Efficacy of OM could not be analyzed due to heterogeneous studies. However, four studies using OM for androgenetic alopecia reported a clinical response in 70% to 100% of the patients. Low dose OM is a safe and well-tolerated treatment for hair loss, presenting a lower adverse effect rate than standard doses.

Androgen sensitivity gateway to COVID-19 disease severity.

In this communication, we present arguments for androgen sensitivity as a likely determinant of COVID-19 disease severity. The androgen sensitivity model explains why males are more likely to develop severe symptoms while children are ostensibly resistant to infection. Further, the model explains the difference in COVID-19 mortality rates among different ethnicities. Androgen sensitivity is determined by genetic variants of the androgen receptor. The androgen receptor regulates transcription of the transmembrane protease, serine 2 (TMPRSS2), which is required for SARS-CoV-2 infectivity. TMPRSS2 primes the Spike protein of the virus, which has two consequences: diminishing viral recognition by neutralizing antibodies and activating SARS-CoV-2 for virus-cell fusion. Genetic variants that have been associated with androgenetic alopecia, prostate cancer, benign prostatic hyperplasia and polycystic ovary syndrome could be associated with host susceptibility. In addition to theoretical epidemiological and molecular mechanisms, there are reports of high rates of androgenetic alopecia of from hospitalized COVID-19 patients due to severe symptoms. Androgen sensitivity is a likely determinant of COVID-19 disease severity. We believe that the evidence presented in this communication warrants the initiation of trials using anti-androgen agents.

Tretinoin enhances minoxidil response in androgenetic alopecia patients by upregulating follicular sulfotransferase enzymes.

Minoxidil sulfate is the active metabolite required to exert the vasodilatory and hair growing effects of minoxidil. For hair growth, sulfotransferase enzymes expressed in outer root sheath of the hair follicle sulfonate minoxidil. The large intra-subject variability in follicular sulfotransferase was found to predict minoxidil response and thus explain the low response rate to topical minoxidil in the treatment of androgenetic alopecia. A method to increase minoxidil response would be of significant clinical utility. Retinoids have been reported to increase minoxidil response. The purported mechanism of action was retinoid modulation of skin permeation to minoxidil; however, evidence to the contrary supports retinoids increase dermal thickness. In order to elucidate the effect of topical retinoids on minoxidil response, we studied the effect of topical tretinoin on follicular sulfotransferase. In this study, we demonstrate that topical tretinoin application influences the expression of follicular sulfotransferase. Of clinical significance, in our cohort, 43% of subjects initially predicted to be nonresponders to minoxidil were converted to responders following 5 days of topical tretinoin application. To the best of our knowledge, this is the first study to elucidate the interaction mechanism between topical minoxidil and retinoids and thus provides a pathway for the development of future androgenetic alopecia treatments.

Development and validation of the Frontal Fibrosing Alopecia Severity Score.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a scarring alopecia characterized by recession of the frontotemporal hairline and loss of the eyebrows. OBJECTIVE: To design and validate a scoring system to assess the severity of FFA. METHODS: The Frontal Fibrosing Alopecia Severity Score (FFASS) was developed; criterion validity was assessed by the Investigator's Global Assessment, and construct validity was evaluated by the convergence of other measures of severity (the Patient's Global Assessment], the rest of the clinical features, the Lichen Planopilaris Activity Index, and quality of life measures (Dermatology Life Quality Index and Hospital Anxiety Depression Scale). Intraobserver and interobserver reliability were determined. RESULTS: In total, 103 female patients were included. The FFASS showed significant correlation to the Patient's Global Assessment, occipital involvement, and the Lichen Planopilaris Activity Index. Intraobserver reliability was completed for 31 subjects and showed good correlation (intraclass correlation coefficient, 0.86; 95% confidence interval, 0.7-0.95; P < .001). Interobserver reliability showed excellent correlation (intraclass correlation coefficient, 0.97; 95% confidence interval, 0.95-0.99; P < .001). LIMITATIONS: The study was performed at a single institution, and only female patients were assessed. CONCLUSIONS: The FFASS is a statistically validated scale and a reliable measure of FFA severity, and it can be used in clinical practice and future research studies as an assessment tool.

Folliculitis decalvans: Effectiveness of therapies and prognostic factors in a multicenter series of 60 patients with long-term follow-up.

BACKGROUND: Folliculitis decalvans (FD) is a rare neutrophilic cicatricial alopecia that poses a therapeutic challenge. OBJECTIVES: To describe the therapeutic response in a large number of cases of FD with long-term follow-up and analyze potential prognostic factors associated with severity of form and with a better therapeutic response. METHODS: This multicenter prospective study included patients with FD who had a minimum of 5 years of follow-up. Severity was assessed by the maximum diameter of the cicatricial area. Therapeutic response was evaluated according to stabilization of the size of the cicatricial areas and the improvement in clinical symptoms. RESULTS: A total of 60 patients (37 men [61.7%] and 23 women [38.3%]) with a mean age of 40 years were included. Earlier age of onset (P = .01) was statistically associated with severity of form. Treatment with rifampicin and clindamycin, tetracyclines, and intralesional steroids was the most effective. No statistically significant prognostic factors predicting a better therapeutic response were found. LIMITATIONS: Because FD is a rare disease, the main limitation was the sample size. CONCLUSIONS: An earlier age of onset was associated with the severe form of the disease. The proposed specific therapeutic protocol can be a very useful tool in clinical dermatologic practice.