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.

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.

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.

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.

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.

Treatment of flat and elevated pigmented disorders with a 755-nm alexandrite picosecond laser: clinical and histological evaluation.

The novel picosecond lasers, initially developed for faster tattoo removal, have also shown great efficacy in endogenous pigmentary disorders. To describe the efficacy and safety profile of an alexandrite (755-nm) picosecond laser in a wide range of pigmented flat and elevated cutaneous lesions. A retrospective study was performed in which we collected all the clinical images of patients treated with the 755-nm alexandrite picosecond laser for 12 months (November 2016-November 2017). Clinical features were obtained from their medical charts. Patients treated for tattoo removal were excluded. All the images were analyzed by three blind physicians attending to a visual analogue scale (VAS) from 0 to 5 (0, no change; 1, 1-24% clearance; 2, 25-49% clearance; 3, 50-74% clearance; 4, 75-99% clearance; 5, complete clearance). Patient satisfaction was obtained from a subjective survey including four items: very satisfied, satisfied, non-satisfied, and totally dissatisfied. Thirty-seven patients were included (12 males; 25 females). The mean age of the study was 42.35 years. Twenty-five patients (68%) were treated for different pigmented flat disorders such as solar and mucosal lentigines (5), stasis dermatitis (4), or nevus of Ota (4), among other diagnoses. Twelve patients (32%) were treated for epidermal elevated lesions such as warts (5), epidermal nevi (2), and seborrheic keratosis (3), among other elevated lesions. Mean number of laser treatment was 3.02 sessions while mean follow-up after last laser treatment was 4.02 months. Mean VAS score of the three observers was 3.44 (61% of clearance) for pigmentary flat disorders and 3.60 (67%) for elevated lesions. Adverse effects reported were mild blistering in the first 2-5 days following laser treatment in some of the patients. Overall satisfaction among the patients included was high. The novel 755-nm picosecond alexandrite laser is effective not only for the resolution of pigmented flat lesions of different nature but also for the treatment of the more difficult elevated pigmented lesions.

In situ production of ROS in the skin by photodynamic therapy as a powerful tool in clinical dermatology.

Photodynamic therapy (PDT) is a clinical modality of photochemotherapy based on the accumulation of a photosensitizer in target cells and subsequent irradiation of the tissue with light of adequate wavelength promoting reactive oxygen species (ROS) formation and cell death. PDT is used in several medical specialties as an organ-specific therapy for different entities. In this review we focus on the current dermatological procedure of PDT. In the most widely used PDT protocol in dermatology, ROS production occurs by accumulation of the endogenous photosensitizer protoporphyrin IX after treatment with the metabolic precursors 5-methylaminolevulinic acid (MAL) or 5-aminolevulinic acid (ALA). To date, current approved dermatological indications of PDT include actinic keratoses (AK), basal cell carcinoma (BCC) and in situ squamous cell carcinoma (SCC) also known as Bowen disease (BD). With regards to AKs, PDT can also treat the cancerization field carrying an oncogenic risk. In addition, an increasing number of pathologies, such as other skin cancers, infectious, inflammatory or pilosebaceous diseases are being considered as potentially treatable entities with PDT. Besides the known therapeutic properties of PDT, there is a modality used for skin rejuvenation and aesthetic purposes defined as photodynamic photorejuvenation. This technique enables the remodelling of collagen, which in turn prevents and treats photoaging stygmata. Finally we explore a new potential treatment field for PDT determined by the activation of follicular bulge stem cells caused by in situ ROS formation.