Mitogen-Activated Protein Kinase Inhibitor-Induced Inflammatory Alopecia in Woman With Ovarian Cancer.

Inflammatory alopecia is an increasingly reported side effect of targeted cancer therapies. Here we report one case of inflammatory alopecia secondary to mitogen-activated protein kinase kinase (MEK) inhibitor agent Trametinib in a woman with ovarian cancer. Biopsies of the scalp were consistent with early scarring alopecia compatible with drug-induced alopecia. Significant improvement in hair loss occurred after treatment with intralesional Kenalog (ILK) injections and oral isotretinoin. Though acute alopecia has been described in patients using MEK inhibitors, this is the first reported case of inflammatory alopecia.  J Drugs Dermatol. 2024;23(4):7802.     doi:10.36849/JDD.7802e  .

Aged polystyrene microplastics exacerbate alopecia associated with tight junction injuries and apoptosis via oxidative stress pathway in skin.

Microplastics (MPs) are pervasive pollutants in the natural environment and contribute to increased levels of illness in both animals and humans. However, thespecific impacts of MPs on skin damage and alopeciaare not yet well understood. In this study, we have examined the effects of two types of polystyrene MPs (pristine and aged) on skin and hair follicle damage in mice. UV irradiation changed the chemical and physical properties of the aged MPs, including functional groups, surface roughness, and contact angles. In both in vivo and in vitro experiments, skin and cell injuries related to oxidative stress, apoptosis, tight junctions (TJs), alopecia, mitochondrial dysfunction, and other damages were observed. Mechanistically, MPs and aged MPs can induce TJs damage via the oxidative stress pathway and inhibition of antioxidant-related proteins, and this can lead to alopecia. The regulation of cell apoptosis was also observed, and this is involved in the ROS-mediated mitochondrial signaling pathway. Importantly, aged MPs showed exacerbated toxicity, which may be due to their elevated surface irregularities and altered chemical compositions. Collectively, this study suggests a potential therapeutic approach for alopecia and hair follicle damage caused by MPs pollution.

Culprits of Medication-Induced Telogen Effluvium, Part 2.

Telogen effluvium (TE) is a common mechanism underlying medication-related alopecia. The inciting cause of TE may be difficult to identify due to delays in clinically apparent hair loss. Because medication-induced TE is a nonscarring alopecia that typically is reversible, appropriate management requires identification of the underlying trigger and cessation of potential culprit medications. In part 2 of this 2-part series on medication-induced TE, we focus on anticoagulant and antihypertensive medications.

Retrospective evaluation of Penguin Cold Caps for chemotherapy-induced alopecia.

BACKGROUND: Scalp cooling is an increasingly recognized non-pharmacologic approach to minimize chemotherapy-induced alopecia (CIA). Several commercially available machine-based and manual scalp cooling systems are available; however, literature reports of effectiveness are highly variable. The purpose of this study was to determine real-world tolerability and subjective effectiveness of a manual cold capping system in minimizing CIA across a variety of patient race and hair types. This study was a single-institution review of outcomes from manual cold capping. METHODS: We identified retrospective cohort of adult patients who presented to discuss cold capping between January 14, 2019, and March 31, 2022. Data collected from medical records included demographics, decision to pursue/continue cold capping, diagnoses, chemotherapy regimens, hair characteristics (length, thickness, coarseness, type), and subjective perception of percentage of hair retained. Those with successful vs. unsuccessful cold capping (≥ 50% vs. < 50% of hair retained) were compared based on the patient-level factors of interest. FINDINGS: A total of 100 patients initiated cold capping during the study period, and 95% of them completed cold capping. The majority of patients who started cold capping completed it. The median-reported percentage of hair maintained was 75%, and 82/89 (92.1% of patients) had favorable results, defined as ≥ 50% of hair retained. The only patient-level factor associated with favorable response was chemotherapy regimen, with fewer patients receiving doxorubicin-containing regimens having successful hair retention compared to other chemotherapy types (71.4% successful results vs. 95.7% for those receiving paclitaxel-containing regimens and 96.6% for those receiving docetaxel-containing regimens (p = 0.018). There was no difference in success based on patient race/ethnicity or hair characteristics. INTERPRETATION: The overall effectiveness (92.1%) in this study is consistent to higher than many literature reports. One possible reason for the high success in our cohort is compliance with cold capping protocols, meaning applying the cap in the appropriate manner and wearing the cap for the prescribed durations, which may impact effectiveness.

Microneedle Delivery Platform Integrated with Codelivery Nanoliposomes for Effective and Safe Androgenetic Alopecia Treatment.

Although topical application of minoxidil is a widely used, FDA-approved therapy for androgenetic alopecia (AGA) treatment, it suffers from low bioavailability, the requirement for frequent long-term use, and side effects. With a similar structure as minoxidil, kopexil and kopyrrol are less toxic and have been commercialized, but show an inferior hair regeneration effect compared to minoxidil. Herein, we developed a hyaluronic acid (HA)-based dissolvable microneedles (MNs) delivery platform integrated with kopexil and kopyrrol coencapsulated nanoliposomes (KK-NLPs) to effectively and safely treat AGA. Facilitated by nanoliposomes and MNs, the encapsulated KK-NLPs performed efficient skin penetration and enhanced cellular internalization into human dermal papilla cells. Furthermore, within the target cells, the codelivered kopexil and kopyrrol show synergistic effects by orchestrating an upregulation in the expression of Ki67, ß-catenin, vascular endothelial growth factor (VEGF), and CD31. These molecular responses collectively foster cell proliferation, migration, and antioxidative effects, thereby facilitating the expedited progression of hair follicles (HFs) into the anagen phase and promoting peripheral angiogenesis. Notably, the KK-NLPs-integrated MNs treatment group exhibits noteworthy enhanced hair regeneration in vivo, with identical or superior therapeutic effects at a much lower dosage than that of minoxidil. These results suggest the great potential of this kopexil and kopyrrol codelivery nanoliposomes-integrated MNs platform for AGA treatment in a safe and efficient way.

Cytoprotective role of human dental pulp stem cell-conditioned medium in chemotherapy-induced alopecia.

BACKGROUND: Chemotherapy-induced alopecia (CIA) is a distressing adverse effect of chemotherapy, with an estimated incidence of 65% and limited treatment options. Cyclophosphamide (CYP) is a common alopecia-inducing chemotherapy agent. Human dental pulp stem cells (DPSCs) secrete several paracrine factors that up-regulate hair growth. Conditioned medium (CM) collected from DPSCs (DPSC-CM) promotes hair growth; culturing mesenchymal stem cells under hypoxic conditions can enhance this effect. METHODS: The effect of DPSC-CM cultured under normoxic (N-) and hypoxic (H-) conditions against CYP-mediated cytotoxicity in keratinocytes was examined using cell viability assay, lactate dehydrogenase (LDH) cytotoxicity assay, and apoptosis detection. The damage-response pathway was determined in a well-established CIA mouse model by analyzing macroscopic effects, histology, and apoptosis. Reverse transcription-quantitative PCR and Caspase-3/7 activity assay were used to investigate the impact of DPSC-CM on the molecular damage-response pathways in CYP-treated mice. The effect of post-CIA DPSC-CM application on post-CIA hair regrowth was analyzed by macroscopic effects and microstructure observation of the hair surface. Furthermore, to investigate the safety of DPSC-CM as a viable treatment option, the effect of DPSC-CM on carcinoma cell lines was examined by cell viability assay and a subcutaneous tumor model. RESULTS: In the cell viability assay, DPSC-CM was observed to increase the number of keratinocytes over varying CYP concentrations. Furthermore, it reduced the LDH activity level and suppressed apoptosis in CYP-treated keratinocytes. DPSC-CM exhibited the cytoprotective role in vivo via the dystrophic anagen damage-response pathway. While both N-CM and H-CM downregulated the Caspase-3/7 activity level, H-CM downregulated Caspase-3 mRNA expression. The proportion of post-CIA H-CM-treated mice with > 90% normal hair was nearly twice that of vehicle- or N-CM-treated mice between days 50 and 59 post-depilation, suggesting that post-CIA H-CM application may accelerate hair regrowth and improve hair quality. Furthermore, DPSC-CM suppressed proliferation in vitro in certain carcinoma cell lines and did not promote the squamous cell carcinoma (SCC-VII) tumor growth rate in mice. CONCLUSIONS: The potentiality of DPSC-CM and H-CM as a promising cytoprotective agent and hair regrowth stimulant, respectively, for CIA needs in-depth exploration.

Topical minoxidil and dietary supplement for the treatment of chemotherapy-induced alopecia in childhood: a retrospective cohort study.

Chemotherapy-induced alopecia (CIA) is a common and debilitating condition in children, with limited research on its characteristics and treatment. Therefore, this study aims to describe the characteristics of pediatric patients with CIA and the treatment outcomes of topical minoxidil and L-cystine, medicinal yeast, and pantothenic acid complex-based dietary supplements (CYP). This retrospective cohort study analyzed data from patients who underwent high-dose conditioning chemotherapy followed by hematopoietic stem cell transplantation and were treated with either topical minoxidil or CYP for CIA between January 2011 and January 2022. Among the 70 patients evaluated, 61 (87.1%) experienced clinical improvement. Patients in the groups with superior treatment outcomes received a greater cumulative amount of minoxidil and underwent treatment for a more extended duration (P < 0.05) than those in the other groups. All 70 (100%) patients received topical minoxidil, and 42 (60%) were administered CYP. Hair thickness was significantly higher in the combination therapy group than in the minoxidil monotherapy group (21.4% vs. 9.3%, P = 0.02). However, only 3 (4.3%) patients reported mild and self-limiting adverse events. In conclusion, our study shows that minoxidil and CYP administration represent viable treatment options for pediatric CIA.

Observing the clinical efficacy of combined serum microneedle therapy for moderate to severe androgenetic alopecia in scalp repair.

OBJECTIVE: In this study, the safety and efficacy of scalp repair serum microneedles combined with oral drug administration and topical medication were investigated for the treatment of moderate to severe androgenetic alopecia. METHODS: Twenty patients, consisting of 4 males and 16 females, who sought treatment for moderate to severe androgenetic alopecia at our hair medicine research center alopecia specialty clinic between August and December 2022 were randomly selected for the study. Male patients underwent oral administration of finasteride topical application of 5% minoxidil, and biweekly scalp repair serum microneedle therapy. Female patients were administered spironolactone or Diane-35 orally and applied 2% minoxidil topically, paired with biweekly scalp repair serum microneedle therapy sessions. After seven treatments, the scalp repair serum microneedle was discontinued, but oral administration and topical applications were continued, followed by a 1-month follow-up. Using a hair dermoscopy, hair follicles in a fixed region on the top of the head were manually counted per unit area to evaluate the hair restoration status of the patients quantitatively. RESULTS: All 20 patients completed 3 months of combined therapy and a 1-month follow-up. On average, the patients experienced an increase of 42.6 hairs, with an efficiency rate of 100%. Significant differences were observed in hair count between any two of the first seven treatments (p < 0.001). A significant negative correlation was discovered between the initial pre-treatment hair count and the total improvement of hair (p < 0.001), indicating that the greater the degree of hair loss before treatment, the more pronounced the improvement. CONCLUSION: Scalp repair serum microneedle combined therapy in moderate to severe androgenetic alopecia significantly reduces the number of microneedle treatments required, enhances treatment efficacy, and improves therapeutic outcomes.

Therapeutic maintenance effect of finasteride 1 mg every other month regimen in androgenetic alopecia and study on the difference in response to finasteride treatment: A prospective cohort study.

Finasteride is commonly used for androgenetic alopecia (AGA) treatment. The aim of this study was to assess the therapeutic maintenance effect of a finasteride every other month (EOM) regimen and analyze clinical and laboratory differences in patients with AGA according to their treatment response. One hundred males with AGA who received finasteride 1 mg daily treatment for a year were enrolled in the study. At 1 year follow-up, treatment responses of patients who completed the visit schedule were assessed using five scales. The patients were assigned to good or bad response groups according to their assessment. Further, they were randomly divided into two groups (daily vs. EOM) and treated with finasteride (1 mg) for 1 more year. At 2 years follow-up, treatment efficacy was assessed. At 1-year follow-up, 36 patients completed the schedule, including eight and three patients in the good and bad response groups, respectively. At the 2-year follow-up, 23 patients completed the schedule, with nine in the daily group and 14 in the EOM group. Changes in global photographic assessment in the second year were 1.33 and 1.29 for the daily and EOM groups, respectively. The daily group showed an elevated hair density and lower concentration of dihydrotestosterone (DHT) and the DHT to testosterone ratio (DHT/T). However, the EOM group showed decreased hair density and elevated DHT and DHT/T. Following treatment response assessment after 1 year of treatment, the good response group showed early onset which was associated with maternal AGA. Analysis of serum androgen hormone magnitude of DHT reduction was much greater (54.4% vs. 44.4%). DHT/T was higher in the bad response group (1.98 vs. 2.33). We concluded that the finasteride EOM regimen showed similar maintenance effects to the daily regimen.

A cross-sectional analysis of medications used by patients reporting alopecia areata on the FDA adverse events reporting system.

BACKGROUND: Alopecia areata (AA) is an autoimmune condition that leads to patchy, nonscarring hair loss. Its etiology remains unknown; the condition can be debilitating for patients, impacting their psychosocial wellbeing. Various triggers have been reported, ranging from genetic predisposition and infections to environmental factors. Medications have also been thought to be an inciting factor in AA. METHODS: Using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), all cases reporting AA as an adverse event were used to capture associated medications and patient characteristics. RESULTS: There were 1,331 AA cases reported as an adverse event with medication use. Monoclonal antibodies accounted for 6 out of the top 10 drugs associated with the highest number of AA cases. Males were more likely to report AA when taking adalimumab (OR: 1.79, P = 0.04) and dupilumab (OR: 2.56, P = 0.03) compared to females. Individuals between 42 and 64 years old accounted for 46.7% of AA cases. Lastly, females in older age groups showed greater odds of developing AA compared to males (OR: 1.03, P < 0.01). CONCLUSIONS: Based on the FAERS, there has been a steady rise in AA cases, and monoclonal antibodies were the most frequently cited medication class tied to AA. With a dearth of literature on triggers and patient demographics, we sought to describe features of AA cases that could increase awareness and be used to improve future clinical outcomes in patients.

Post-Finasteride Syndrome And Post-Ssri Sexual Dysfunction: Two Clinical Conditions Apparently Distant, But Very Close.

Post-finasteride syndrome and post-SSRI sexual dysfunction, are two poorly explored clinical conditions in which men treated for androgenetic alopecia with finasteride or for depression with SSRI antidepressants show persistent side effects despite drug suspension (e.g., sexual dysfunction, psychological complaints, sleep disorders). Because of some similarities in the symptoms, common pathological mechanisms are proposed here. Indeed, as discussed, clinical studies and preclinical data obtained so far suggest an important role for brain modulators (i.e., neuroactive steroids), neurotransmitters (i.e., serotonin, and cathecolamines), and gut microbiota in the context of the gut-brain axis. In particular, the observed interconnections of these signals in these two clinical conditions may suggest similar etiopathogenetic mechanisms, such as the involvement of the enzyme converting norepinephrine into epinephrine (i.e., phenylethanolamine N-methyltransferase). However, despite the current efforts, more work is still needed to advance the understanding of these clinical conditions in terms of diagnostic markers and therapeutic strategies.

Effectiveness of oral tofacitinib treatment on patients with moderate-to-severe alopecia areata in Iran.

INTRODUCTION: Alopecia areata is an inflammatory hair loss and a common autoimmune disease. Conducting treatment studies on alopecia areata is difficult due to unpredictable periods and even spontaneous recovery from the disease. In this study, the effectiveness of tofacitinib in treating alopecia areata was investigated. MATERIALS AND METHODS: The severity of the disease was evaluated using the Alopecia Severity Tool (SALT), and based on the medical history and patient's documents and photos, the score before and after the treatment was obtained. The patients were prescribed tofacitinib tablets at a dose of 5 mg twice a day for at least 6 months and were followed for a minimum of 18 months. RESULTS: No side effect was observed in 97.9% of the patients. After 6 months, except for three patients who did not need any maintenance dose, others needed an average daily intake of 7 mg of tofacitinib. After 18 months, the hair loss decreased by 6.45 times compared to the beginning and by 0.5 times compared to the end of 6 months (p < 0.05). In addition, it was found that body hair loss decreased 4 times compared to the beginning and 0.6 times compared to the end of 6 months (p < 0.05). The reduction of nail involvement after 18 months and 6 months was 1.2 times and 0.6, respectively, (p < 0.05). CONCLUSION: Treatment of alopecia areata with tofacitinib is recommended due to its effectiveness in reducing hair loss on the head, body, and nail involvement with few reversible side effects.

Safety of Low-Dose Oral Minoxidil in Patients With Hypertension and Arrhythmia: A Multicenter Study of 264 Patients. / [Artíulo traducido] Seguridad de minoxidil oral a dosis bajas en pacientes con hipertensión o arritmias: estudio multicéntrico de 264 pacientes.

BACKGROUND AND OBJECTIVE: Systemic adverse effects (AE) are a major concern of low-dose oral minoxidil (LDOM) treatment, especially in patients with arterial hypertension or arrhythmia. The objective of this study was to evaluate the safety of LDOM in patients with hypertension or arrhythmia. PATIENTS AND METHODS: Retrospective multicenter study of patients with hypertension or arrhythmia treated with LDOM for any type of alopecia. RESULTS: A total of 254 patients with hypertension [176 women (69.3%) and 78 men (30.7%)] with a mean age of 56.9 years (range 19-82) were included. From them, the dose of LDOM was titrated in 128 patients, allowing the analysis of 382 doses. Patients were receiving a mean of 1.45 (range 0-5) antihypertensive drugs. Systemic AE were detected in 26 cases (6.8%) and included lightheadedness (3.1%), fluid retention (2.6%), general malaise (0.8%), tachycardia (0.8%) and headache (0.5%), leading to LDOM discontinuation in 6 cases (1.5%). Prior treatment with doxazosin (P<0.001), or with three or more antihypertensive drugs (P=0.012) was associated with a higher risk of discontinuation of LDOM. CONCLUSIONS: LDOM treatment showed a favorable safety profile in patients with hypertension or arrhythmia, similar to general population.

Safety of Low-Dose Oral Minoxidil in Patients With Hypertension and Arrhythmia: A Multicenter Study of 264 Patients.

BACKGROUND AND OBJECTIVE: Systemic adverse effects (AE) are a major concern of low-dose oral minoxidil (LDOM) treatment, especially in patients with arterial hypertension or arrhythmia. The objective of this study was to evaluate the safety of LDOM in patients with hypertension or arrhythmia. PATIENTS AND METHODS: Retrospective multicenter study of patients with hypertension or arrhythmia treated with LDOM for any type of alopecia. RESULTS: A total of 254 patients with hypertension [176 women (69.3%) and 78 men (30.7%)] with a mean age of 56.9 years (range 19-82) were included. From them, the dose of LDOM was titrated in 128 patients, allowing the analysis of 382 doses. Patients were receiving a mean of 1.45 (range 0-5) antihypertensive drugs. Systemic AE were detected in 26 cases (6.8%) and included lightheadedness (3.1%), fluid retention (2.6%), general malaise (0.8%), tachycardia (0.8%) and headache (0.5%), leading to LDOM discontinuation in 6 cases (1.5%). Prior treatment with doxazosin (P<0.001), or with three or more antihypertensive drugs (P=0.012) was associated with a higher risk of discontinuation of LDOM. CONCLUSIONS: LDOM treatment showed a favorable safety profile in patients with hypertension or arrhythmia, similar to general population.

Minoxidil sulfotransferase enzymatical activity in plants: A novel paradigm in increasing minoxidil response in androgenetic alopecia.

BACKGROUND: Minoxidil is the only US FDA approved topical drug for the treatment of androgenetic alopecia (AGA). Minoxidil is effective in hair re-growth in 30%-40% of patients and 50% of males. To exert its hair growing effect, minoxidil must be sulfonated in the scalp by the minoxidil sulfotransferase enzyme (SULT1A1). Low scalp SULT1A1 correlates with lack of minoxidil response; thus, supplementing the scalp SULT1A1 with naturally occurring minoxidil sulfotransferase enzymes could potentially improve treatment outcomes in AGA patients. METHODS: In this study, we set to characterize SULT1A1 activity in various plants. RESULTS: From the 10 common botanical extracts we have studied, seven exhibited significant activity toward minoxidil as a substrate; thus, providing a potential novel paradigm to increase minoxidil response with natural supplements. CONCLUSION: To the best of our knowledge, this is the first study to characterize naturally occurring minoxidil sulfotransferase enzymes in plants.

Reliability and validity of the Japanese version of the Chemotherapy-induced Alopecia Distress Scale.

BACKGROUND: The Chemotherapy-induced Alopecia Distress Scale (CADS) is a patient-reported outcome measure for assessing distress associated with Chemotherapy-induced alopecia (CIA). This study aimed to confirm the psychometric validity of the Japanese version of the CADS (CADS-J). METHODS: A total of 132 patients with breast cancer who developed CIA were asked to complete the CADS-J twice at 2 week intervals to confirm test-retest reliability. The body image domain of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) breast cancer-specific module, the self-esteem scale from the Rosenberg Self-Esteem Scale, and the emotional domain of the EORTC QLQ Core 30 were used to confirm the convergent validity of the CADS-J. The overall quality of life and physical domains of the EORTC QLQ Core 30 were used to confirm the discriminant validity of the CADS-J. RESULTS: In total, 125 participants provided valid responses. The mean age was 52.2 years. The overall Cronbach's alpha for the CADS-J was 0.903. The intraclass correlation coefficients of the first and second responses were r = 0.874, r = 0.952, r = 0.911, and r = 0.959 for the physical domain, emotional domain, activity domain, and relationship domain, respectively. In terms of convergent validity, the total CADS-J score was moderately correlated with body image (r = - 0.63), self-esteem (r = - 0.48), and the emotional domain (r = - 0.61). Regarding discriminant validity, the total CADS-J score was weakly correlated with the overall quality of life (r = - 0.34) and physical domain (r = - 0.24). CONCLUSIONS: The CADS-J is psychometrically reliable and valid for evaluating the distress caused by CIA. It is expected to be used in daily practice and as an endpoint in various studies.