Epigenetic mechanisms driving the pathogenesis of systemic lupus erythematosus, systemic sclerosis and dermatomyositis.

Autoimmune connective tissue disorders, including systemic lupus erythematosus, systemic sclerosis (SSc) and dermatomyositis (DM), often manifest with debilitating cutaneous lesions and can result in systemic organ damage that may be life-threatening. Despite recent therapeutic advancements, many patients still experience low rates of sustained remission and significant treatment toxicity. While genetic predisposition plays a role in these connective tissue disorders, the relatively low concordance rates among monozygotic twins (ranging from approximately 4% for SSc to about 11%-50% for SLE) have prompted increased scrutiny of the epigenetic factors contributing to these diseases. In this review, we explore some seminal studies and key findings to provide a comprehensive understanding of how dysregulated epigenetic mechanisms can contribute to the development of SLE, SSc and DM.

The Use of Natural Therapies in Patients With Skin Cancer: A Scoping Review.

Complementary and alternative medicine (CAM) use has become a field of growing interest in dermatology. However, the prevalence of CAM use is difficult to quantify as it varies based on many factors. Given the exploratory nature of the topic, a scoping review was conducted to identify studies that quantify biologically based CAM use in skin cancer patients. A comprehensive search of Embase, PubMed, and Web of Science databases from inception to August 28th, 2023, was performed. A total of 3,150 articles were identified through the database search. After article screening, 6 studies were suitable for inclusion in this review. Articles included were all questionnaire, survey, or interview style. Biologically based CAM use is prevalent in skin cancer patients. It can be associated with many factors such as location, stage of cancer, and age. CAM use can interact with conventional therapy; therefore, physicians should employ a culturally competent approach to inquiring about CAM use in order to improve patient outcomes and identify patterns and predictors of use.J Drugs Dermatol. 2024;23(5):322-326. doi:10.36849/JDD.8077.

Review of Superficial Cryotherapy for the Treatment of Alopecia Areata.

Cryotherapy has recently been examined as a potential treatment for alopecia areata (AA). AA is classically managed with intralesional or systemic steroids but relapse rates among those with longstanding disease are high. This narrative review serves to describe the existing studies evaluating cryotherapy for the treatment of AA and examine studies comparing cryotherapy with intralesional steroid injection for the treatment of AA. A review of the literature from 1990 to 2022 was conducted looking for keywords such as “alopecia areata” and “cryotherapy". A total of 8 studies were identified. Three studies assessed the efficacy of liquid nitrogen cryotherapy for the treatment of AA and found approximately 60% of patients responded to treatment and achieved hair regrowth. Three studies compared cryotherapy with intralesional corticosteroid injection, and 2 studies compared cryotherapy with topical corticosteroid therapy. There was no statistically significant difference in efficacy, but there is some evidence to suggest that relapse rates were lower in the cryotherapy group. Treatment protocols differed between studies regarding the number of cycles used for cryotherapy, dosage of intralesional steroids, and patient populations used. Some studies examined cases of recalcitrant AA while other studies examined all cases of AA. More research with larger sample sizes and with similar experimental procedures is necessary to assess the clinical efficacy of cryotherapy.Kaiser M, Issa N, Yaghi M, et al. Review of superficial cryotherapy for the treatment of alopecia areata. J Drugs Dermatol. 2023;22(8):802-809. doi:10.36849/JDD.7431.

A phase I safety study of topical calcitriol (BPM31543) for the prevention of chemotherapy-induced alopecia.

PURPOSE: Chemotherapy-induced alopecia (CIA) negatively affects psychosocial health and quality of life (QoL). Currently, there are no approved pharmacologic agents to prevent CIA. Here, we evaluated the safety, tolerability, and potential signal of efficacy of topical calcitriol (BPM31543) on CIA prevention. MATERIALS AND METHODS: This Phase 1 trial included 23 female patients with breast cancer, gynecologic cancer, or sarcomas receiving a taxane-based chemotherapy. Patients received a 3 + 3 dose-escalation regimen at 5, 10, 20, 40, 60, and 80 µg/mL, with 3-6 patients per group. Patients applied topical BPM31543 to the scalp twice a day for 2 weeks prior to chemotherapy and continued until chemotherapy treatment was completed. The maximum tolerated dose (MTD) during first 28 day application was determined. Adverse event (AE) monitoring, pharmacokinetics, blinded photographic assessments, and patient self-assessment were evaluated. RESULTS: Out of 23 patients treated with BPM31543, 8 patients experienced at least 1 treatment-related adverse event (AE). The majority of AEs were mild to moderate in severity. Only 1 patient experienced SAEs (vomiting, nausea, fever, and flank pain) considered treatment related. Alopecia < 50% from baseline was observed in 8 patients at Week 7, and, of which 2 patients had < 50% alopecia maintained at Week 15. There were no detectable effects of topical BPM31543 on serum levels of calcitriol. CONCLUSIONS: BPM31543 applied topically twice daily to the scalp is safe and well tolerated in patients receiving taxane-based chemotherapy. No DLT was observed at up to 80 µg/mL, and MTD was not reached. Based on the data from this trial, BPM31543 represents a promising therapy and warrants further investigation in Phase 2/3 trials.

Enhanced Delivery of Plasmid DNA to Skeletal Muscle Cells using a DLC8-Binding Peptide and ASSLNIA-Modified PAMAM Dendrimer.

Skeletal muscle is ideally suited and highly desirable as a target for therapeutic gene delivery because of its abundance, high vascularization, and high levels of protein expression. However, efficient gene delivery to skeletal muscle remains a current challenge. Besides the major obstacle of cell-specific targeting, efficient intracellular trafficking, or the cytosolic transport of DNA to the nucleus, must be demonstrated. To overcome the challenge of cell-specific targeting, herein we develop a generation 5-polyamidoamine dendrimer (G5-PAMAM) functionalized with a skeletal muscle-targeted peptide, ASSLNIA (G5-SMTP). Specifically, to demonstrate the feasibility of our approach, we prepared a complex of our G5-SMTP dendrimer with a plasmid encoding firefly luciferase and investigated its delivery to skeletal muscle cells. Luciferase assays indicated a threefold increase in transfection efficiency of C2C12 murine skeletal muscle cells using G5-SMTP when compared with nontargeting nanocarriers using unmodified G5. To further improve the transfection yield, we employed a cationic dynein light chain 8 protein (DLC8)-binding peptide (DBP) containing an internal sequence known to bind to the DLC8 of the dynein motor protein complex. Complexation of DBP with our targeting nanocarrier, that is, G5-SMTP, and our luciferase plasmid cargo resulted in a functional nanocarrier that showed an additional sixfold increase in transfection efficiency compared with G5-SMTP transfection alone. To our knowledge, this is the first successful use of two different functional nanocarrier components that enable targeted skeletal muscle cell recognition and increased efficiency of intracellular trafficking to synergistically enhance gene delivery to skeletal muscle cells. This strategy of targeting and trafficking can also be universally applied to any cell/tissue type for which a recognition domain exists.

Hair disorders in patients with cancer.

Cytotoxic chemotherapies, molecularly targeted therapies, immunotherapies, radiotherapy, stem cell transplants, and endocrine therapies may lead to hair disorders, including alopecia, hirsutism, hypertrichosis, and pigmentary and textural hair changes. The mechanisms underlying these changes are varied and remain incompletely understood, hampering the development of preventive or therapeutic guidelines. The psychosocial impact of chemotherapy-induced alopecia has been well documented primarily in the oncology literature; however, the effect of other alterations, such as radiation-induced alopecia, hirsutism, and changes in hair color or texture on quality of life have not been described. This article reviews clinically significant therapy-related hair disorders in oncology patients, including the underlying pathophysiological mechanisms, severity grading scales, patient-reported quality of life questionnaires, management strategies, and future translational research opportunities.

Hair disorders in cancer survivors.

With increasing survival rates across all cancers, survivors represent a growing population that is frequently affected by persistent or permanent hair growth disorders as a result of systemic therapies, radiotherapy, surgical procedures, and therapeutic transplants. These hair disorders include persistent chemotherapy-induced alopecia, persistent radiotherapy-induced alopecia, endocrine therapy-induced alopecia and hirsutism, postsurgery alopecia and localized hypertrichosis, and persistent stem cell transplantation and targeted therapy-induced alopecia. The information contained in this continuing medical education series should facilitate a better understanding on hair disorders in cancer survivors so that adequate support and therapies may be provided.

A new approach to the treatment of acute myeloid leukaemia targeting the receptor for growth hormone-releasing hormone.

Growth hormone-releasing hormone (GHRH) is secreted by the hypothalamus and acts on the pituitary gland to stimulate the release of growth hormone (GH). GHRH can also be produced by human cancers, in which it functions as an autocrine/paracrine growth factor. We have previously shown that synthetic antagonistic analogues of GHRH are able to successfully suppress the growth of 60 different human cancer cell lines representing over 20 cancers. Nevertheless, the expression of GHRH and its receptors in leukaemias has never been examined. Our study demonstrates the presence of GHRH receptor (GHRH-R) on 3 of 4 human acute myeloid leukaemia (AML) cell lines-K-562, THP-1, and KG-1a-and significant inhibition of proliferation of these three cell lines in vitro following incubation with the GHRH antagonist MIA-602. We further show that this inhibition of proliferation is associated with the upregulation of pro-apoptotic genes and inhibition of Akt signalling in leukaemic cells. Treatment with MIA-602 of mice bearing xenografts of these human AML cell lines drastically reduced tumour growth. The expression of GHRH-R was further confirmed in 9 of 9 samples from patients with AML. These findings offer a new therapeutic approach to this malignancy and suggest a possible role of GHRH-R signalling in the pathology of AML.

Treatment of Alopecia Areata with Simvastatin/Ezetimibe.

Alopecia areata (AA) is an autoimmune disorder characterized by T lymphocytic infiltrates around the bulbar region of hair follicles. Statins have surfaced as potential therapeutic agents for AA, partly because of their modulation of the JAK/STAT pathway. Some data indicate that statins are a possible option for acute, but not chronic, longstanding AA. Animal studies suggest that treatment with statins increases CD4+/CD25+/Foxp3+ populations in AA-affected mice.

Low-level laser therapy for the treatment of androgenic alopecia: a review.

There are many new low-level laser technologies that have been released commercially that claim to support hair regrowth. In this paper, we will examine the clinical trials to determine whether the body of evidence supports the use of low-level laser therapy (LLLT) to treat androgenic alopecia (AGA). A literature search was conducted through Pubmed, Embase, and Clinicaltrials.gov for clinical trials using LLLT to treat AGA. Thirteen clinical trials were assessed. Review articles were not included. Ten of 11 trials demonstrated significant improvement of androgenic alopecia in comparison to baseline or controls when treated with LLLT. In the remaining study, improvement in hair counts and hair diameter was recorded, but did not reach statistical significance. Two trials did not include statistical analysis, but showed marked improvement by hair count or by photographic evidence. Two trials showed efficacy for LLLT in combination with topical minoxidil. One trial showed efficacy when accompanying finasteride treatment. LLLT appears to be a safe, alternative treatment for patients with androgenic alopecia. Clinical trials have indicated efficacy for androgenic alopecia in both men and women. It may be used independently or as an adjuvant of minoxidil or finasteride. More research needs to be undertaken to determine the optimal power and wavelength to use in LLLT as well as LLLT's mechanism of action.

A review of monochromatic light devices for the treatment of alopecia areata.

There are many laser technologies that are being tested that claim to support hair regrowth for patients with alopecia areata (AA). In this paper, we will determine whether the body of evidence supports the use of devices using monochromatic light sources to treat AA. Articles were gathered from PubMed, Embase, and the Cochrane database using these keywords: lasers, excimer laser, low-level laser therapy (LLLT), low-level light therapy, alopecia, alopecia areata, and hair loss with a category modifier of English. Ten clinical trials and seven case reports/abstracts were assessed. Eight clinical trials and two case reports demonstrated hair regrowth with the 308-nm excimer laser/light in men, women, and children. One case report demonstrated hair regrowth with the ALBA 355® laser. One clinical trial and two case reports demonstrated hair regrowth with LLLT. While two case reports demonstrated hair regrowth with fractional laser therapy, one clinical trial showed no improvement. The 308-nm excimer laser is a safe and effective treatment for men, women, and children with refractory AA of the scalp and beard. Larger, double-blinded clinical trials should be conducted to compare excimer laser therapy to standard treatments. More data is needed to determine the efficacy of LLLT and fractional laser therapy in the treatment of AA.

Low-level laser therapy as a treatment for androgenetic alopecia.

BACKGROUND AND OBJECTIVES: Androgenetic alopecia (AGA) affects 50% of males by age 50 and 50% of females by age 80. Recently, the use of low-level laser therapy (LLLT) has been proposed as a treatment for hair loss and to stimulate hair regrowth in AGA. This paper aims to review the existing research studies to determine whether LLLT is an effective therapy for AGA based on objective measurements and patient satisfaction. STUDY DESIGN: A systematic literature review was done to identify articles on Medline, Google Scholar, and Embase that were published between January 1960 and November 2015. All search hits were screened by two reviewers and examined for relevant abstracts and titles. Articles were divided based on study design and assessed for risk of bias. RESULTS: Eleven studies were evaluated, which investigated a total of 680 patients, consisting of 444 males and 236 females. Nine out of 11 studies assessing hair count/hair density found statistically significant improvements in both males and females following LLLT treatment. Additionally, hair thickness and tensile strength significantly improved in two out of four studies. Patient satisfaction was investigated in five studies, and was overall positive, though not as profound as the objective outcomes. CONCLUSION: The majority of studies covered in this review found an overall improvement in hair regrowth, thickness, and patient satisfaction following LLLT therapy. Although we should be cautious when interpreting these findings, LLLT therapy seems to be a promising monotherapy for AGA and may serve as an effective alternative for individuals unwilling to use medical therapy or undergo surgical options. Lasers Surg. Med. 49:27-39, 2017. © 2016 Wiley Periodicals, Inc.

Laser therapy for the treatment of pearly penile papules.

Pearly penile papules (PPP) present as dome-shaped papules of no more than 3 mm in diameter that line the base of the glans of the penis. These benign lesions affect between 14.3 and 48 % of men. While often asymptomatic, PPP can cause a great deal of psychological distress that may warrant treatment. Current treatment options include cryotherapy, electrodessication, and curettage (ED&C). However, these modalities may have considerable adverse cosmetic effects, including scarring, pain, and pigmentary changes. Laser modalities offer clear potential for improved cosmetic outcome in PPP treatment, but is not routinely used. Thus, a systematic review of available literature using the National Library of Medicine database PubMed was completed to find articles relevant to the treatment of PPP with laser and light therapy. The systematic search and screening of articles resulted in inclusion of eight articles discussing a total of 55 patients with PPP treated by laser therapy. The present systematic review found that erbium:yttrium-aluminum-garnet (Er:YAG) and CO2 laser were the most commonly reported (n = 45 and 7, respectively). Furthermore, the use of CO2, Er:YAG, pulsed dye laser, and fractional photothermolysis therapies demonstrated complete clearance of PPP in all cases with minimal complications and discomfort. Thus, based on the currently available evidence, laser therapy is a well-tolerated and efficacious method for treating PPP with minimal long-term adverse effects and a cosmetically desirable outcome. Although the included studies are limited in power, this systematic review offers clinically relevant insight into the potential for laser therapy.

Laser and light therapies for the treatment of nail psoriasis.

Psoriatic involvement of the nail is notoriously refractory to conventional therapy. Nail psoriasis has a high incidence amongst patients with psoriasis. It remains a significant cosmetic problem and thus, has a significant impact on quality of life. More recently, light and laser therapies have emerged as modalities for treatment of nail psoriasis. In this study, the efficacies of light and laser therapies are systematically reviewed. Light therapies involve ultraviolet light (with or without photosensitizers) or intense pulsed light. Alternatively, laser therapy in nail psoriasis is primarily administered using a 595-nm pulsed dye laser. These modalities have demonstrated significant improvement in psoriatic nail lesions, and even complete resolution in some cases. Both laser and light modalities have also been tested in combination with other systemic or topical therapeutics, with variable improvement in efficacy. Both laser and light therapies are generally well tolerated. Side-effects of light therapies include hyperpigmentation, itching and erythema; whereas, side-effects of laser therapy are more frequent and include pain, purpura/petechiae and hyperpigmentation. Patterns of response to therapy were also seen based on presenting characteristics of the nail lesions: subungual hyperkeratosis and onycholysis appeared to be the most responsive to therapy, while nail pitting was the most resistant. Light or laser therapies have the potential to be an efficient and cost-effective in-office based treatment for nail psoriasis. However, more large-scale clinical trials are needed to assess their efficacy, particularly in combination with other therapeutic modalities.

Erythroplasia of Queyrat treated by laser and light modalities: a systematic review.

Erythroplasia of Queyrat (EOQ) is a squamous cell carcinoma in situ most commonly located on the glans penis or prepuce. EOQ accounts for roughly 10 % of all penile malignancies and may lead to invasive squamous cell carcinoma. Standard therapy includes local excision, partial or total penectomy, cryotherapy, and topical cytotoxic agents. Treatment of EOQ has proven to be challenging due to low response rates and recurrence. In addition, radical procedures can significantly affect sexual function and quality of life. Alternative laser treatments and photodynamic therapy (PDT) offer promising results for treating EOQ. A systemic review of the literature was performed for articles discussing laser and light therapy for EOQ. Among the patients treated with the CO2 laser, 81.4 % of cases had complete remission after one session of treatment. Patients treated with PDT presented with more variable results, where 62.5 % of those treated with methyl aminolevulinate photodynamic therapy (MAL-PDT) achieved complete remission. Aminolevulinic acid (ALA-PDT) treatment showed a similar rate of remission at 58.3 %. One study utilized the Nd:YAG laser, which resulted in a recurrence of the lesion in four of the five patients treated. Of the methods reviewed, the CO2 laser offered the most promising results with a cosmetically excellent prognosis. Further studies with larger power and longer follow-up times are needed to determine the optimal treatment regimen for this penile malignancy.

Low level laser therapy and hair regrowth: an evidence-based review.

Despite the current treatment options for different types of alopecia, there is a need for more effective management options. Recently, low-level laser therapy (LLLT) was evaluated for stimulating hair growth. Here, we reviewed the current evidence on the LLLT effects with an evidence-based approach, focusing more on randomized controlled studies by critically evaluating them. In order to investigate whether in individuals presenting with hair loss (male pattern hair loss (MPHL), female pattern hair loss (FPHL), alopecia areata (AA), and chemotherapy-induced alopecia (CIA)) LLLT is effective for hair regrowth, several databases including PubMed, Google Scholar, Medline, Embase, and Cochrane Database were searched using the following keywords: Alopecia, Hair loss, Hair growth, Low level laser therapy, Low level light therapy, Low energy laser irradiation, and Photobiomodulation. From the searches, 21 relevant studies were summarized in this review including 2 in vitro, 7 animal, and 12 clinical studies. Among clinical studies, only five were randomized controlled trials (RCTs), which evaluated LLLT effect on male and female pattern hair loss. The RCTs were critically appraised using the created checklist according to the Critical Appraisal for Therapy Articles Worksheet created by the Center of Evidence-Based Medicine, Oxford. The results demonstrated that all the performed RCTs have moderate to high quality of evidence. However, only one out of five studies performed intention-to-treat analysis, and only another study reported the method of randomization and subsequent concealment of allocation clearly; all other studies did not include this very important information in their reports. None of these studies reported the treatment effect of factors such as number needed to treat. Based on this review on all the available evidence about effect of LLLT in alopecia, we found that the FDA-cleared LLLT devices are both safe and effective in patients with MPHL and FPHL who did not respond or were not tolerant to standard treatments. Future randomized controlled trials of LLLT are strongly encouraged to be conducted and reported according to the Consolidated Standards of Reporting Trials (CONSORT) statement to facilitate analysis and comparison.

Exploring the role of GHRH antagonist MIA-602 in overcoming Doxorubicin-resistance in acute myeloid leukemia.

Acute myeloid leukemia (AML) is characterized by the rapid proliferation of mutagenic hematopoietic progenitors in the bone marrow. Conventional therapies include chemotherapy and bone marrow stem cell transplantation; however, they are often associated with poor prognosis. Notably, growth hormone-releasing hormone (GHRH) receptor antagonist MIA-602 has been shown to impede the growth of various human cancer cell lines, including AML. This investigation examined the impact of MIA-602 as monotherapy and in combination with Doxorubicin on three Doxorubicin-resistant AML cell lines, KG-1A, U-937, and K-562. The in vitro results revealed a significant reduction in cell viability for all treated wild-type cells. Doxorubicin-resistant clones were similarly susceptible to MIA-602 as the wild-type counterpart. Our in vivo experiment of xenografted nude mice with Doxorubicin-resistant K-562 revealed a reduction in tumor volume with MIA-602 treatment compared to control. Our study demonstrates that these three AML cell lines, and their Doxorubicin-resistant clones, are susceptible to GHRH antagonist MIA-602.

Induction of specific microRNAs inhibits cutaneous wound healing.

Chronic nonhealing wounds, such as venous ulcers (VUs), are a widespread and serious medical problem with high morbidity and mortality. The molecular pathology of VUs remains poorly understood, impeding the development of effective treatment strategies. Using mRNA expression profiling of VUs biopsies and computational analysis, we identified a candidate set of microRNAs with lowered target gene expression. Among these candidates, miR-16, -20a, -21, -106a -130a, and -203 were confirmed to be aberrantly overexpressed in a cohort study of 10 VU patients by quantitative PCR and in situ hybridizations. These microRNAs were predicted to target multiple genes important for wound healing, including early growth response factor 3, vinculin, and leptin receptor (LepR). Overexpression of the top up-regulated miRNAs, miR-21 and miR-130a, in primary human keratinocytes down-regulated expression of the endogenous LepR and early growth response factor 3. The luciferase reporter assay verified LepR as a direct target for miR-21 and miR-130a. Both miR-21 and miR-130a delayed epithelialization in an acute human skin wound model. Furthermore, in vivo overexpression of miR-21 inhibited epithelialization and granulation tissue formation in a rat wound model. Our results identify a novel mechanism in which overexpression of specific set of microRNAs inhibits wound healing, resulting in new potential molecular markers and targets for therapeutic intervention.

Low-level laser treatment accelerated hair regrowth in a rat model of chemotherapy-induced alopecia (CIA).

Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of antineoplastic chemotherapy for which there is no effective interventional approach. A low-level laser (LLL) device, the HairMax LaserComb®, has been cleared by the FDA to treat androgenetic alopecia. Its effects may be extended to other settings; we have demonstrated that LaserComb treatment induced hair regrowth in a mouse model for alopecia areata. In the current study, we tested whether LLL treatment could promote hair regrowth in a rat model for CIA. Chemotherapy agents cyclophosphamide, etoposide, or a combination of cyclophosphamide and doxorubicin were administered in young rats to induce alopecia, with or without LLL treatment. As expected, 7-10 days later, all the rats developed full body alopecia. However, rats receiving laser treatment regrew hair 5 days earlier than rats receiving chemotherapy alone or sham laser treatment (with the laser turned off). The accelerated hair regrowth in laser-treated rats was confirmed by histology. In addition, LLL treatment did not provide local protection to subcutaneously injected Shay chloroleukemic cells. Taken together, our results demonstrated that LLL treatment significantly accelerated hair regrowth after CIA without compromising the efficacy of chemotherapy in our rat model. Our results suggest that LLL should be explored for the treatment of CIA in clinical trials because LLL devices for home use (such as the HairMax LaserComb®) provide a user-friendly and noninvasive approach that could be translated to increased patient compliance and improved efficacy.

Beard Alopecia: An Updated and Comprehensive Review of Etiologies, Presentation and Treatment.

Facial hair is an important social and psychologic aspect of clinical appearance for men. The purpose of this review is to provide a comprehensive overview of the causes of alopecia of the beard including the prevalence, pathophysiology, clinical presentation, and treatment. In this review, we highlight more common causes of beard alopecia including alopecia areata and pseudofolliculitis barbae, infectious causes such as tinea barbae and herpes simplex folliculitis, and rare causes including dermatopathia pigmentosa reticularis and frontal fibrosing alopecia. This review serves as an important resource for clinicians when faced with patients suffering from beard alopecia.