The AHRS Hair Research Highlights Summary

HAIR RESEARCH HIGHLIGHTS

The Hair Research Highlights Summary is a member-benefit of recent hair research highlights assembled by the NAHRS Hair Research Highlights Committee.

Edition 2: 2013 Summary

December 17, 2013

 

Editor: John T. Seykora MD, PhD
Co-Editor: Jennifer Nguyen, MD

Hair Research Highlights Committee: John Seykora, MD, PhD, Chair, George Cotsarelis, MD, Leonard Sperling, MD, Curtis Thompson, MD, Antonella Tosti, MD

  1. Shi, Q., Duvic, M., Osei, J., Hordinsky, M., Norris, D., Price, V., Amos, C., Christiano, C., and Mendoza, T. Health-Related Quality of Life (HRQoL) in Alopecia Areata Patients—A Secondary Analysis of the National Alopecia Areata Registry Data. Journal of Investigative Dermatology Symposium Proceedings (2013) 16, S49–S50. PMID: 24326555

Alopecia areata (AA) is a nonscarring and recurrent disease characterized by hair loss that may significantly affect patient health-related quality of life (HRQoL). Given the lack of reliable HRQoL status in AA patients, we analyzed data from 532 AA patients from the National Alopecia Areata Registry whose records included HRQoL assessments using three validated instruments: Skindex-16, brief version of the Fear of Negative Evaluation Scale, and Dermatology Life Quality Index. The mean HRQoL scores were compared with previously reported HRQoL levels from healthy controls and patients with other skin diseases. Two-step cluster analysis of Skindex-16 scales divided patients into two groups: 481 (57%) with good HRQoL and 361 (43%) with poor HRQoL. Multivariate logistic regression modeling revealed a set of risk factors for poor HRQoL: age <50 years (odds ratio (OR) 3.99, 95% confidence interval (CI) 1.66–9.58), female gender (OR 2.74, 95% CI 1.73–4.34), hair loss 25–99% (OR 2.47, 95% CI 1.12–5.45), family stress (OR 1.8, 95% CI 1.13–2.86), and job change (OR 2.01, 95% CI 1.02–3.94). The current analysis provides an overview of the HRQoL status of AA patients and may guide patient care in the future.

  1. Salsberg JM, Donovan J. The Safety and Efficacy of Diphencyprone for the Treatment of Alopecia Areata in Children. Arch Dermatol 148(9):1084-1085. 2012. PMID: 22986874

This study was a retrospective study of children over the period 2002 through 2011 to evaluate the efficacy of DPCP in the treatment of alopecia areata. All children followed the same immunotherapy protocol beginning with sensitization with DPCP, 2%, in acetone followed by a treatment with DPCP, 0.0001%, 2 weeks later. Thereafter, treatment continued on a weekly basis with increasing concentrations of DPCP. This study represents one of the largest studies of treatment responses to DPCP in patients younger than 18 years. Approximately one-third of children showed improvement in hair density with DPCP treatment. However, the response dropped off at between 6 months and 1 year of treatment, and overall, only 10% of our patients had complete hair regrowth. In general, adverse effects warranting discontinuation of DPCP treatment were not common.

Study limitations include the small number of patients, the retrospective nature of the study, and incomplete documentation in some cases. Although hair regrowth in a proportion of patients could be considered spontaneous, this is unlikely for the vast majority of patients. The study population consisted of children with advanced hair loss who were refractory to topical treatments, and many had the disease beyond the time at which spontaneous regrowth would be expected to occur

  1. Stephan F., Habre M. and Tomb R. Successful treatment of alopecia totalis with hydroxychloroquine: Report of 2 cases. J Am Acad Dermatol. 68(6):1048-9. 2013. PMID: 23680203

In this report, two cases of alopecia totalis (AT) showed an excellent response to hydroxychloroquine. This is the first report suggesting that hydroxychloroquine may be a treatment option in AA. This agent should be considered as an option after failure of all other strategies. Given the small sample size, further studies are needed to evaluate this therapeutic modality with a greater number of patients.

  1. Amoretti A., Laydner H., and Bergfeld W. Androgenetic alopecia and risk of prostate cancer: A systematic review and meta-analysis. J Am Acad Dermatol. 68:937-43. 2013. PMID: 23395589

This study examined 7 case-control studies including 8994 patients–4078 cases and 4916 controls. There was statistically significant association between vertex baldness and prostate cancer (OR 1.25; 95% confidence interval 1.09-1.44; Z = 3.13; P = .002). No statistically significant association between AGA (any pattern) and prostate cancer was identified (OR 1.03; 95% confidence interval 0.93-1.13; Z = 0.55; P = .58).Vertex pattern AGA was associated with a significant increased risk of prostate cancer.

  1. Yang CC., Hsieh FN., Lin LY, Hsu CK, Sheu HM, Chen W. Higher body mass index is associated with greater severity of alopecia in men with male-pattern androgenetic alopecia in Taiwan: A cross-sectional study. J Am Acad Dermatol. 2013 Oct 31. pii: S0190-9622(13)01031-1. PMID: 24184140

This study evaluated a potential link between body mass index (BMI) and alopecia severity in men with AGA and early-onset AGA. A cross-sectional study was performed by reviewing the medical charts and photographs of men with a diagnosis of AGA. In male-pattern AGA (n = 142), men with severe alopecia (grade V-VII) had higher BMI than those with mild to moderate alopecia (grade I-IV) (25.1 vs 22.8 kg/m2, P = .01). After multivariate adjustments, the risk for severe alopecia was higher in the overweight or obese (BMI ≥24 kg/m2) subjects with male-pattern AGA (odds ratio 3.52, P < .01). In early-onset male-pattern AGA (n = 46), the risk for having severe alopecia was also higher in the overweight or obese subjects (odds ratio 4.97, P = .03). Higher BMI was significantly associated with greater severity of hair loss in men with male-pattern AGA, especially in those with early-onset AGA.

This study assessed the efficacy of latanoprost on hair growth and pigmentation. The secondary objectives were to assess the effect on scalp pigmentation; investigate the treatment duration needed to affect hair growth, hair pigmentation, and scalp pigmentation; and assess safety of latanoprost. Sixteen men with mild androgenetic alopecia (Hamilton II-III) were included. Latanoprost 0.1% and placebo were applied daily for 24 weeks on two mini-zones on the scalp. At 24 weeks, an increased hair density on the latanoprost-treated site was observed compared with baseline (n = 16, P < .001) and placebo-treated site (P = .0004). Latanoprost significantly increased hair density (terminal and vellus hairs) at 24 weeks compared with baseline and the placebo-treated area. Latanoprost could be useful in stimulating hair follicle activity and treating hair loss.

  1. Chon SY, Champion RW, Geddes ER, and Rashid RM. Chemotherapy-induced alopecia. J Am Acad Dermatol. 67:e37-47. 2012. PMID: 22178150

Chemotherapy-induced alopecia is a distressing side effect of some treatment regimens in oncology. Unfortunately, chemotherapy-induced alopecia is an often overlooked or a minor factor in research and thus few advances in its treatment have been achieved. This review offers a comprehensive examination of the clinically relevant basic science, clinical research, and current management options for chemotherapy-induced alopecia. Alopecia secondary to chemotherapy is not nonspecific in patterns or extent of disease, as one would initially perceive. Patient support and education information and templates are provided to facilitate patient treatment.

  1. Lee Y, Lee HE, Shin JM, Sohn KC, Im M, Kim CD, Seo YJ, Lee YH, Lee JH. Clinical significance of serum high-mobility group box 1 level in alopecia areata. J Am Acad Dermatol 69:742-7. 2013. PMID: 23932647

High-mobility group box 1 (HMGB1), released by necrotic cells and in response to various inflammatory stimuli, is currently considered to be a significant target antigen in diverse autoimmune diseases. The investigators determined the clinical significance of serum HMGB1 levels in scalp specimens from 7 patients with AA and 8 healthy control subjects and in blood samples from 45 patients with AA and 10 healthy control subjects. The correlation between HMGB1 level and clinical severity was also evaluated. Immunohistochemical staining of scalp tissues from patients with AA revealed higher HMGB1 levels than in healthy control subjects. In addition, serum HMGB1 levels in the AA group were generally higher, and showed concordance with the patients' clinical characteristics, including onset, hair-pull test results, and treatment response. These results suggest that HMGB1 plays a role in the pathogenesis of AA, and that it is a promising predictor of prognosis and treatment response. This study identifies a HMGB1 as a new potential therapeutic target for the treatment of AA.

  1. Gilhar, A., Keren, A., Shemer, A., Ullmann, Y., and Paus, R. Blocking Potassium Channels (Kv1.3): A New Treatment Option for Alopecia Areata? J Invest Dermatol. 133: 2088–2091. 2013. PMID: 23636064

Alopecia Areata (AA) is a T-cell–dependent autoimmune disease in which hair follicles (HFs) are attacked by a dense lymphocytic infiltrate of activated CD4+ and CD8+ T cells. The investigators hypothesized that inhibiting T-cell function in AA using Kv1.3 channel blockers may constitute a therapeutic approach to AA. The investigators showed that Kv1.3+ T cells were greatly increased in lesional AA skin. The investigators also showed that Kv1.3-selective potassium channel blockade inhibits the development of AA lesions in a humanized mouse model of AA. These data suggest that Kv1.3 channel blockers may be useful in treating AA.

Edition 1: 2012 Summary

February 14, 2013

 

Editor: John T. Seykora MD, PhD
Co-Editor: Jennifer Nguyen, MD

Hair Research Highlights Committee: John Seykora, MD, PhD, Chair, George Cotsarelis, MD, Leonard Sperling, MD, Curtis Thompson, MD, Antonella Tosti, MD

  1. Dlova N, Goh CL, Tosti A. Familial frontal fibrosing alopecia. Br J Dermatol. 2013 Jan;168(1):220-2. PubMed PMID: 22716508.

Frontal fibrosing alopecia (FFA) primarily affects Caucasian postmenopausal women, and rare reports of familial cases have been described. In this article, four familial cases of FFA consisting of 10 total patients are reported and were confirmed by pathological examination. Affected members of the families either lived together or in the same town; ages ranged from 21- to 74-years-old. These familial cases suggest a role of common environmental triggers as a well as a genetic predisposition underlying the etiology of FFA.

  1. Chiang YZ, Tosti A, Chaudhry IH, Lyne L, Farjo B, Farjo N, Cadore de Farias D, Griffiths CE, Paus R, Harries MJ. Lichen planopilaris following hair transplantation and face-lift surgery. Br J Dermatol. 2012 Mar;166(3):666-370. PMID: 21985326.

The article describes 10 patients who developed new-onset LPP ⁄FFA following cosmetic scalp surgery. Seven patients (4 men, 3 women) developed LPP following hair transplantation, and three female patients developed FFA following face-lift surgery. The diagnosis of LPP/FF occurred 6 months to 9 years after hair transplantation and 3 to 18 months after face-lift surgery. Diagnoses were confirmed histopathologically in 9 of 10 patients. Explanations for this association include Koebner phenomenon induced by surgical trauma, an autoimmune process targeting a hair follicle antigen liberated during surgery, or a postsurgery proinflammatory microenvironment that compromises the immune privileged status of hair follicles in susceptible individuals.

  1. Kluger N, Jacot W, Frouin E, Rigau V, Poujol S, Dereure O, Guillot B, Romieu G, Bessis D. Permanent scalp alopecia related to breast cancer chemotherapy by sequential fluorouracil/epirubicin/cyclophosphamide (FEC) and docetaxel: a prospective study of 20 patients. Ann Oncol. 2012 Nov;23(11):2879-84. PMID: 22571858.

Alopecia is a common side effect of systemic chemotherapy and is usually reversible. However, reports of irreversible post-chemotherapy hair loss are more common. This study is a case series of 20 patients who developed permanent alopecia following treatment with breast cancer using an FEC and docetaxel regimen. The patients clinically presented with moderate-severe androgenetic alopecia, usually associated with eyebrow and eyelash hair loss; hair loss occurred within 2 weeks of the first FEC cycle and maintained until the end of docetaxel cycles. Scalp biopsies were normal or showed follicular miniaturization. Doxetaxel is presumed to be the offending agent, as similar cases of alopecia have been reported with taxane use. DLQI (dermatology life quality index) questionnaire scores reflected distressing psychological consequences in patients' lives. Various treatments, including vitamins, minoxidil, psoralen, and UVA therapy, were ineffective.

The antiviral agent cidofovir has been reported to induce localized alopecia when applied topically. This study evaluated the efficacy and safety of topical cidofovir in preventing beard hair growth in healthy men. Twenty men with beards scoring 4 (dense) or 5 (very dense) on the physician global assessment (PGA) of hair density were randomized to either 1% or 3% concentration of cidofovir. Cidofovir and placebo were applied once daily after shaving to a 2.5-cm area within the beard in a split-face design. Subjects were evaluated every 2 weeks during treatment for 6 two 8 weeks. Hair count changes did not differ significantly between the cidofovir and placebo sites. However, there was a negative trend in hair counts within the 3% group compared with placebo. Topical cidofovir was safe and well tolerated, and the 3% concentration may be promising for further studies of hair growth prevention.

  1. Ito T, Hashizume H, Shimauchi T, Funakoshi A, Ito N, Fukamizu H, Takigawa M, Tokura Y. CXCL10 produced from hair follicles induces Th1 and Tc1 cell infiltration in the acute phase of alopecia areata followed by sustained Tc1 accumulation in the chronic phase. J Dermatol Sci. 2012 Dec 26. PMID: 23312578.

This study investigated the molecular mechanism of peribulbar T-lymphocytic inflammation in alopecia areata (AA). In peripheral blood mononuclear cells (PBMCs), the frequency of CXCR3+CD4+ T cells (Th1) was significantly higher in acute-phase AA than in chronic-phase AA or healthy controls, while CXCR3+CD8+ T cells (Tc1) were significantly increased in chronic-phase AA. In the skin lesions of acute-phase AA, CXCR3+CD4+ and CXCR3+CD8+ T cells infiltrated in the juxta-follicular area. In chronic-phase AA, CXCR3+CD8+ T cells dominated the infiltrate around hair bulbs, possibly contributing to the prolonged state of hair loss. Lymphocytes obtained from lesional skin of acute-phase AA contained CXCR3+CD4+ and CXCR3+CD8+ T cells at higher percentages than those of PBMCs, suggesting preferential emigration from the blood. Hair follicles of acute-phase AA were shown to express a high level of the Th1-associated chemokine CXCL10 (a CXCR3 ligand). By chemotaxis assay, fresh PBMCs from acute-phase AA patients had an increased velocity of chemotaxis toward CXCL10. These results suggest that the increased production of CXCL10 from hair follicles induces infiltrates of highly chemoattracted Th1 and Tc1 cells in the acute phase of AA, and Tc1 infiltration remains prolonged in the chronic phase. Blockade of Th1 or Tc1 chemokines or chemokine receptors may give rise to new therapeutic approaches for the treatment of AA.

  1. Garza LA, Liu Y, Yang Z, Alagesan B, Lawson JA, Norberg SM, Loy DE, Zhao T, Blatt HB, Stanton DC, Carrasco L, Ahluwalia G, Fischer SM, FitzGerald GA, Cotsarelis G. Prostaglandin D2 inhibits hair growth and is elevated in bald scalp of men with androgenetic alopecia.Sci Transl Med. 2012 Mar 21;4(126):126ra34. PMID: 22440736.

Recent evidence demonstrates a role of prostaglandins in regulating hair growth. The authors illustrate that prostaglandin D2 synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of men with androgenetic alopecia (AGA). Levels of the product of PTGDS enzyme activity, prostaglandin D2 (PGD2), were also elevated in bald scalp. During normal follicle cycling in mice, Ptgds and PGD2 levels peaked in late anagen, immediately preceding the regression phase, suggesting an inhibitory effect on hair growth. PGD2 inhibited hair growth in explanted human hair follicles and when applied topically to mice. Hair growth inhibition requires the PGD2 receptor G protein-coupled receptor 44 (GPR44), but not the PGD2 receptor 1 (PTGDR). Furthermore, K14-Ptgs2 transgenic mice, which overexpress prostaglandin-endoperoxide synthase 2 in the skin, demonstrate elevated levels of PGD2 in the skin and develop alopecia, follicular miniaturization, and sebaceous gland hyperplasia, as seen in human AGA. These results define PGD2 as an inhibitor of hair growth in AGA and suggest the PGD2-GPR44 pathway as a potential target for treatment.

Hereditary hypertrichoses are a group of very rare hair overgrowth syndromes. The authors have previously demonstrated that a position effect on TRPS1 is associated with hypertrichosis in humans and mice. To gain insight into the functional role of Trps1, they analyzed the late morphogenesis vibrissae phenotype of Trps1Δgt mutant mice, which is characterized by follicle degeneration after peg downgrowth. They found that Trps1 directly represses expression of the hair follicle stem cell regulator Sox9 to control proliferation of the follicle epithelium. Furthermore, the authors identified a copy number variation upstream of SOX9 in a family with hypertrichosis that significantly decreases expression of the gene in the hair follicle, providing new insights into the long-range genomic regulation of SOX9. These results define a novel transcriptional hierarchy that regulates epithelial proliferation in the developing hair follicle and contributes to the etiology of hypertrichosis.

  1. Teta M, Choi YS, Okegbe T, Wong G, Tam OH, Chong MM, Seykora JT, Nagy A, Littman DR, Andl T, Millar SE. Inducible deletion of epidermal Dicer and Drosha reveals multiple functions for miRNAs in postnatal skin. Development. 2012 Apr;139(8):1405-16. PMID:22434867

MicroRNAs (miRNAs) regulate the expression of mammalian genes and play key roles in hair follicle development; however, little is known of their functions in postnatal hair growth. The authors compared the effects of deleting the essential miRNA biogenesis enzymes Drosha and Dicer in mouse skin epithelial cells at successive postnatal time points. Deletion of either Drosha or Dicer during an established growth phase (anagen) caused failure of hair follicles to enter a normal catagen regression phase, eventual follicular degradation and stem cell loss. Deletion of Drosha or Dicer in resting phase follicles did not affect follicular structure or epithelial stem cell maintenance, and stimulation of anagen by hair plucking caused follicular proliferation and formation of a primitive transient amplifying matrix population. However, mutant matrix cells exhibited apoptosis and DNA damage and hair follicles rapidly degraded. Hair follicle defects at early time points post-deletion occurred in the absence of inflammation, but a dermal inflammatory response and hyperproliferation of interfollicular epidermis accompanied subsequent hair follicle degradation. These data reveal multiple functions for Drosha and Dicer in suppressing DNA damage in rapidly proliferating follicular matrix cells, facilitating catagen and maintaining follicular structures and their associated stem cells. Although Drosha and Dicer each possess independent non-miRNA-related functions, the similarity in phenotypes of the inducible epidermal Drosha and Dicer mutants indicates that these defects result from a failure of miRNA processing. Consistent with this hypothesis, Dicer deletion resulted in the upregulation of multiple mRNA targets of the highly expressed epithelial miRNA miR-205.

  1. Woo W, Zhen H, and Oro A. Shh maintains dermal papilla identity and hair morphogenesis via a Noggin-Shh regulatory loop. Genes & Dev. 2012. 26: 1235-1246. PMID: 22661232

During hair follicle development, dermal papillae (DPs) function as mesenchymal signaling centers that regulate morphogenesis in overlying epithelium. While the DP regulates hair follicle formation, relatively little is known about the molecular basis of DP formation. The morphogen Sonic hedgehog (Shh) is known for regulating hair follicle epithelial growth. In this study, the authors determine how dermal-specific Shh signaling contributes to DP formation and hair growth. Using a Cre-lox genetic model and RNAi in hair follicle reconstitution assays, loss of dermal Smoothened (Smo) function results in the loss of the DP precursor, the dermal condensate, and a stage 2 hair follicle arrest phenotype reminiscent of Shh(-/-) skin. Molecular screening and immunostaining studies reveal that dermal Shh signaling controls the expression of a subset of DP-specific signature genes. Using a hairpin/cDNA lentiviral system, overexpression of the Shh-dependent gene Noggin, but not Sox2 or Sox18, can partially rescue the dermal Smo knockdown hair follicle phenotype by increasing the expression of epithelial Shh. These findings suggest that dermal Shh signaling regulates specific DP signatures to maintain DP maturation while maintaining a reciprocal Shh-Noggin signaling loop to drive hair follicle morphogenesis.

  1. Miteva, M. and Tosti, A. Hair and scalp dermatoscopy. J Am Acad Dermatol. 2012 Nov;67(5):1040-8. doi: 10.1016/j.jaad.2012.02.013. Epub 2012 Mar 8.

Dermatoscopy has been commonly used to evaluate whether a skin lesion may be benign or malignant, often in the assessment of melanocytic lesions. This article discusses the utility of dermatoscopy as a non-invasive tool to help diagnose hair disorders. Trichoscopy, a combination of scalp dermatoscopy and videodermatoscopy, is useful for the diagnosis and follow-up of hair and scalp disorders. This review provides updated information from the literature and our experience on the dermoscopic features of the most common hair and scalp disorders. This will enable dermatologists to make fast diagnoses of tinea capitis and alopecia areata, distinguish early androgenetic alopecia from telogen effluvium, and differentiate scarring from nonscarring alopecia.