Tongyu Cao Wikramanayake

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.

A novel rat model for chemotherapy-induced alopecia

Background.  More than half of all people diagnosed with cancer receive chemotherapy, and approximately 65% of these develop chemotherapy‐induced alopecia (CIA), a side‐effect that can have considerable negative psychological repercussions. Currently, there are very few animal models available to study the mechanism and prevention of CIA.

Prevention and treatment of alopecia areata with quercetin in the C3H/HeJ mouse model

Alopecia areata (AA) is an autoimmune non-scarring hair loss disorder. AA can be acute, recurrent, or chronic. Current therapeutic options for AA are limited, and there is no effective prevention for recurrent AA. We have previously shown a correlation between the expression of HSP70 (HSPA1A/B), a heat shock protein involved in the inflammatory response, and the onset of AA in the C3H/HeJ mouse model. In this study, we tested the effects of quercetin, a bioflavonoid with anti-inflammatory properties, on AA development and HSP70 expression in the C3H/HeJ model. Mice with spontaneous AA were treated with subcutaneous quercetin or sham injections. Hair regrowth was observed in lesional areas in all the quercetin-treated mice, but in none of the sham-treated mice. In addition, non-alopecic C3H/HeJ mice were heat-treated to induce alopecia, along with quercetin or sham injections. Whereas 24% of the heat-treated mice with sham injections developed alopecia, none of the mice receiving quercetin injections did. As expected, the level of HSP70 expression in quercetin-treated areas was comparable to control. Furthermore, we showed that systemic delivery of quercetin by intraperitoneal injections prevented/reduced spontaneous onset of AA. Our results demonstrated that quercetin provided effective treatment for AA as well as prevention of onset of AA in the C3H/HeJ model, and warrant further clinical studies to determine whether quercetin may provide both treatment for preexisting AA and prevention of recurrent AA. The ready availability of quercetin as a dietary supplement may lead to increased patient compliance and positive outcomes for AA.

Seborrheic Dermatitis and Dandruff: A Comprehensive Review

Seborrheic Dermatitis (SD) and dandruff are of a continuous spectrum of the same disease that affects the seborrheic areas of the body. Dandruff is restricted to the scalp, and involves itchy, flaking skin without visible inflammation. SD can affect the scalp as well as other seborrheic areas, and involves itchy and flaking or scaling skin, inflammation and pruritus. Various intrinsic and environmental factors, such as sebaceous secretions, skin surface fungal colonization, individual susceptibility, and interactions between these factors, all contribute to the pathogenesis of SD and dandruff. In this review, we summarize the current knowledge on SD and dandruff, including epidemiology, burden of disease, clinical presentations and diagnosis, treatment, genetic studies in humans and animal models, and predisposing factors. Genetic and biochemical studies and investigations in animal models provide further insight on the pathophysiology and strategies for better treatment.

Loss of Mpzl3 Function Causes Various Skin Abnormalities and Greatly Reduced Adipose Depots

The rough coat (rc) spontaneous mutation causes sebaceous gland hypertrophy, hair loss and extracutaneous abnormalities including growth retardation. The rc mice have a missense mutation in the predicted immunoglobulin protein Mpzl3. In this study, we generated Mpzl3 knockout mice to determine its functions in the skin. Homozygous Mpzl3 knockout mice showed unkempt and greasy hair coat and hair loss soon after birth. Histological analysis revealed severe sebaceous gland hypertrophy and increased dermal thickness, but did not detect significant changes in the hair cycle. Mpzl3 null mice frequently developed inflammatory skin lesions; however, the early onset skin abnormalities were not the results of immune defects. The abnormalities in the Mpzl3 knockout mice resemble closely those observed in the rc/rc mice, as well as mice heterozygous for both the rc and Mpzl3 knockout alleles, indicating that rc and Mpzl3 are allelic. Using a lacZ reporter gene, we detected Mpzl3 promoter activity in the companion layer and inner root sheath of the hair follicle, sebaceous gland, and epidermis. Loss of MPZL3 function also caused a striking reduction in cutaneous and overall adipose tissue. These data reveal a complex role for Mpzl3 in the control of skin development, hair growth and adipose cell functions.

Overcoming Obstacles for Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa

Recessive dystrophic epidermolysis bullosa (RDEB, OMIM ID #226600) is a severe blistering disease that affects quality of life and is associated with increased mortality, often from squamous cell carcinoma (Fine et al., 1999). Mutations in COL7A1, the gene that encodes type VII collagen, lead to blistering with resultant wounds and scarring. Treatment approaches have included tissue-, cell-, and gene-based therapies, including recent efforts at bone marrow ablation and allogeneic stem cell transplantation (Wagner et al., 2010). Because a single gene defect is responsible for the disease manifestations, researchers have focused on the development of gene therapy approaches. Unfortunately, several problems have hampered clinical development of vector-based gene therapy for this disease, including low transfer efficacy and the large size of the COL7A1 cDNA (Goto et al., 2006). In a previous study, a COL7A1 “minigene” that encoded a truncated type VII collagen was developed. This minigene was compatible size-wise with retroviral vectors and reversed the DEB phenotype to normal in transduced keratinocytes (Chen et al., 2000). An alternative to retroviral gene therapy is trans-splicing, an approach that employs the cell spliceosome to recombine an endogenous target pre-mRNA and an exogenously delivered RNA molecule called the pre-transsplicing molecule (PTM). A partial, wild-type coding sequence from the PTM is inserted to replace disease-causing sequences in order to generate a new, reprogrammed wild-type mRNA to correct the disease phenotype (Wally et al., 2008). In this issue, Murauer et al. report on their efforts with trans-splicing techniques to create a potential therapy for RDEB. These investigators introduced a partial, wild-type COL7A1 PTM via retroviral transduction of RDEB keratinocytes and achieved full-length type VII collagen expression. Transduced cells displayed functional correction of the RDEB phenotype, including normal morphology, reduced invasive capacity, normal localization of type VII collagen at the basement membrane, and assembly of collagen into anchoring fibril-like structures. Through the following questions, we examine this paper in greater detail. For brief answers, please refer to the supplementary information online

Cross-section Trichometry: A Clinical Tool for Assessing the Progression and Treatment Response of Alopecia

Background: To properly assess the progression and treatment response of alopecia, one must measure the changes in hair mass, which is influenced by both the density and diameter of hair. Unfortunately, a convenient device for hair mass evaluation had not been available to dermatologists until the recent introduction of the cross-section trichometer, which directly measures the cross-sectional area of an isolated bundle of hair. Objective: We sought to evaluate the accuracy and sensitivity of the HairCheck® device, a commercial product derived from the original cross-section trichometer. Materials and Methods: Bundles of surgical silk and human hair were used to evaluate the ability of the HairCheck® device to detect and measure small changes in the number and diameter of strands, and bundle weight. Results: Strong correlations were observed between the bundles cross-sectional area, displayed as the numeric Hair Mass Index (HMI), the number of strands, the silk/hair diameter, and the bundle dry weight. Conclusion: HMI strongly correlated with the number and diameter of silk/hair, and the weight of the bundle, suggesting that it can serve as a valid indicator of hair mass. We have given the name cross-section trichometry (CST) to the methodology of obtaining the HMI using the HairCheck® system. CST is a simple modality for the quantification of hair mass, and may be used as a convenient and useful tool to clinically assess changes in hair mass caused by thinning, shedding, breakage, or growth in males and females with progressive alopecia or those receiving alopecia treatment.

Effectiveness of Platelet-Rich Plasma for Androgenetic Alopecia: A Review of the Literature

Androgenetic alopecia (AGA) is a hair loss disorder affecting 80% of men and 50% of women throughout their lifetime. Therapies for AGA are limited and there is no cure. There is a high demand for hair restoration. Platelet-rich plasma (PRP), a treatment modality shown to promote wound healing, has also been explored as a treatment for AGA. This literature review was conducted to assess the effectiveness of PRP treatment for AGA. Twelve studies conducted from 2011 to 2017 were evaluated and summarized by study characteristics, mode of preparation, and treatment protocols. A total of 295 subjects were given PRP or control treatment in these studies, and evaluated for terminal hair density, hair quality, anagen/telogen hair ratio, keratinocyte proliferation, blood vessel density, etc. Some studies also provided subject self-assessment reports. Most of the studies reviewed showed effectiveness of PRP in increasing terminal hair density/diameter. Additional investigations are needed to determine the optimal treatment regimen for high efficacy of PRP in AGA.

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.

Loss of MPZL3 function causes seborrhoeic dermatitis‐like phenotype in mice

Seborrhoeic Dermatitis (SD) is a common inflammatory skin disorder. It is chronic and relapsing, affecting 1%–3% of the general adult population.1 SD presents as pink to red greasylooking skin with yellowish scales in seborrhoeic areas such as the scalp, face (nasolabial folds, upper lip, eyelids and eyebrows), retroauricular area and the upper chest. It can be pruritic and socially embarrassing. Current treatment includes antifungals, antiinflammatory and immune modulators, but treatment in some patients may cause adverse effects such as skin atrophy and telangiectasia if used long term. Sebaceous secretion, yeast Malassezia infection and individual susceptibilities such as host immunity and epidermal barrier integrity have all been identified as predisposing factors and may work together to worsen disease. In 2006, Birnbaum et al.2 demonstrated that a frameshift mutation in ZNF750, a zinc finger transcription factor and master regulator of epidermal differentiation, causes early onset (<10 years of age) autosomal dominant seborrhoealike psoriasiform dermatitis with 100% penetrance (OMIM #610227). Yet, how ZNF750 dysfunction causes the SD phenotype remains unknown. We have previously generated knockout mice to determine MPZL3 (myelin protein zerolike 3) function in the skin. Mpzl3 encodes an immunoglobulin protein and is expressed in the suprabasal layers of mouse epidermis, the sebaceous gland and anagen hair follicles.3,4 Not surprisingly, Mpzl3 knockout mice showed various skin abnormalities, including epidermal and sebaceous hyperplasia and hair loss.3–5 Interestingly, these mice also developed early onset skin inflammation with dandrufflike flakes.4 Importantly, ZNF750 was recently shown to directly bind to MPZL3 promoter and activate its transcription in cultured human keratinocytes.6 Therefore, Mpzl3 knockout mice can serve as a useful model to understand SD pathogenesis caused by ZNF750 dysfunction.