Clinical observations in alopecia areata: Implications and hypotheses.

Alopecia areata (AA) is a T-cell-mediated hair loss disorder but the exact cause is unknown. In this report we describe patterns of onset, regrowth and relapse in AA and propose potential underlying mechanisms. We believe that these aspects of AA require integration into modern theories of AA pathogenesis.

Incidence and prevalence of non-melanoma skin cancer in Australia: A systematic review.

Non-melanoma skin cancer (NMSC), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is the most common cancer occurring in people with fair skin. Australia has been reported to have the highest incidence of NMSC in the world. Using a systematic search of the literature in EMBASE and Medline, we identified 21 studies that investigated the incidence or prevalence of NMSC in Australia. Studies published between 1948 and 2011 were identified and included in the analysis. There were six studies that were conducted on national level, two at state level and 13 at the regional level. Overall, the incidence of NMSC had steadily increased over calendar-years in Australia. The incidence of NMSC per 100,000 person-years was estimated to be 555 in 1985; 977 in 1990; 1109 in 1995; 1170 in 2002 and 2448 in 2011. The incidence was higher for men than women and higher for BCC than SCC. Incidence varied across the states of Australia, with the highest in Queensland. The prevalence of NMSC was estimated to be 2% in Australia in 2002. The incidence and prevalence of NMSC still need to be accurately established at both national and state levels to determine the costs and burden of the disease on the public health system in Australia.

SULT1A1 (Minoxidil Sulfotransferase) enzyme booster significantly improves response to topical minoxidil for hair regrowth.

BACKGROUND: Minoxidil is a widely used over-the-counter topical treatment for hair loss. The response rate for topical minoxidil is relatively low. Minoxidil is a pro-drug, converted to its active form, minoxidil sulfate, by SULT1A1 enzymes located in the scalp. Recently, a novel topical formula that increases the activity of SULT1A1 in hair follicles was reported. AIMS: To evaluate any benefit of applying the SULT1A1 enzyme booster prior to daily 5% minoxidil treatment. METHODS: Male androgenic alopecia patients were recruited to a randomized blinded placebo-controlled study. Patients were randomized to receive 5% topical minoxidil plus the novel formula or minoxidil plus a sham adjuvant. Patient's hair growth was monitored using global photography over 60 days. RESULTS: Twenty-four males with androgenic alopecia (Norwood scale average 4.4, range 2-6) were randomized and completed the trial: 12 in the active arm and 12 in placebo. 75% of the subjects who used the SULT1A1 adjuvant with their daily minoxidil treatments for 60 days regrew hair versus 33% of those using the placebo adjuvant (p = 0.023). CONCLUSIONS: In a small cohort of androgenetic alopecia men, adding the SULT1A1 adjuvant to their daily minoxidil treatment regimen improved hair regrowth.

Treatment of female pattern hair loss with the androgen receptor antagonist flutamide.

Female pattern hair loss is a common but difficult to manage condition. Commonly used treatments include oral antiandrogens such as spironolactone and topical minoxidil. The response to treatment is variable. We report a woman whose hair loss progressed while using spironolactone and topical minoxidil in combination, but reversed with flutamide, a potent androgen receptor antagonist.

Role of genetics and sex steroid hormones in male androgenetic alopecia and female pattern hair loss: an update of what we now know.

The role of genetic predisposition and the influence of sex steroid hormones are indisputable to the pathogenesis of male androgenetic alopecia (MAGA). The role of sex steroid hormones in female pattern hair loss (FPHL) is less known. A good knowledge of the pathophysiology underlying MAGA and FPHL empowers the clinician to confidently counsel patients and make informed therapeutic decisions. Vigorous research in recent years has provided greater insight into the role of genetics and sex steroids in physiological hair growth and cycling, as well as in hair follicle miniaturization, the histological hallmark of MAGA and FPHL. In the present review article directed towards clinicians, we discuss the current understanding of the role of androgens and oestrogens, as well as genetic associations with MAGA and FPHL. We also briefly discuss the interpretation of direct-to-consumer genetic testing for baldness to help clinicians understand the limitations of such tests.

Successful treatment of female-pattern hair loss with spironolactone in a 9-year-old girl.

A 9-year-old prepubertal girl with female pattern hair loss treated with spironolactone 100 mg orally per day had objective improvement demonstrated by regrowth observed clinically and on comparison of pre- and post-treatment stereotactic scalp photographs taken 6 months apart.

Androgenetic alopecia and prostate cancer: findings from an Australian case-control study.

The purpose of this study was to examine the relationship between androgenetic alopecia (AA) and prostate cancer with particular emphasis on early age at diagnosis and higher grade tumors. We conducted an age-stratified, population-based case-control study in Australia of men who were diagnosed before 70 years of age during 1994-1997 with histopathology-confirmed adenocarcinoma of the prostate, excluding well-differentiated tumors. Controls were selected from the electoral rolls, and the frequency was matched on age. After excluding subjects with missing values, the analysis was based on 1446 cases and 1390 controls of whom direct observations were made of their pattern of AA during face-to-face interviews. Our data suggest an association between prostate cancer and vertex baldness; compared with men who had no balding, the adjusted odds ratio (OR) was 1.54 (1.19-2.00). No associations were found between prostate cancer and frontal baldness or when frontal baldness was present concurrently with vertex baldness. The ORs were 0.98 (0.79-1.23) and 1.14 (0.90-1.45), respectively. The highest ORs were for high-grade disease in men 60-69 years of age: 1.80 (1.02-3.16) for frontal baldness; 2.91 (1.59-5.32) for vertex baldness; and 1.95 (1.10-3.45) for frontal and vertex baldness. This association between the pattern of AA and prostate cancer points to shared androgen pathways that are worthy of additional investigation.

Anticipating and managing the cutaneous side effects of epidermal growth factor receptor inhibitors.

AIMS: Epidermal growth factor receptor inhibitor (EGFRi) therapy for tumor suppression produces significant cutaneous toxicity that may necessitate dose reduction or treatment cessation. This manuscript aims to describe the skin toxicity associated with these agents and equip oncologists with the tools to best manage these patients. METHODS: A literature review of skin toxicity associated with EGFRi was conducted by a clinical dermatologist experienced in the management of these patients and a management strategy developed for EGFRi skin toxicity RESULTS: The sequence of development of EGFRi cutaneous toxicity is predictable. Many skin side effects can be ameliorated by prophylactic therapy. Management of established skin toxicity is complex and needs to be continued throughout the period of EGFRi drug treatment. CONCLUSION: Early referral to a dermatologist experienced in the management of these patients is recommended.

Age-dependent associations between androgenetic alopecia and prostate cancer risk.

BACKGROUND: Both prostate cancer and androgenetic alopecia are strongly age-related conditions that are considered to be androgen dependent, but studies of the relationship between them have yielded inconsistent results. We aimed to assess whether androgenetic alopecia at ages 20 and 40 years are associated with risk of prostate cancer. METHODS: At a follow-up of the Melbourne Collaborative Cohort Study, men were asked to assess their hair pattern at ages 20 and 40 years relative to eight categories in showcards. Cases were men notified to the Victorian Cancer Registry with prostate cancer diagnosed between cohort enrollment (1990-1994) and follow-up attendance (2003-2009). Flexible parametric survival models were used to estimate age-varying HRs and predicted cumulative probabilities of prostate cancer by androgenetic alopecia categories. RESULTS: Of 9,448 men that attended follow-up and provided data on androgenetic alopecia, we identified 476 prostate cancer cases during a median follow-up of 11 years four months. Cumulative probability of prostate cancer was greater at all ages up to 76 years, for men with vertex versus no androgenetic alopecia at age of 40 years. At age of 76 years, the estimated probabilities converged to 0.15. Vertex androgenetic alopecia at 40 years was also associated with younger age of diagnosis for prostate cancer cases. CONCLUSIONS: Vertex androgenetic alopecia at age of 40 years might be a marker of increased risk of early-onset prostate cancer. IMPACT: If confirmed, these results suggest that the apparently conflicting findings of previous studies might be explained by failure to adequately model the age-varying nature of the association between androgenetic alopecia and prostate cancer.

Hirsutism: from Brazil to a place near you.

IMPORTANCE OF THE FIELD: Hirsutism is the excess of terminal hairs in females and can result in immense distress. Women often spend significant time and funds seeking permanent hair removal. Commercially available physical therapies have usually already been accessed before presenting to the clinician for treatment. AREAS COVERED IN THE REVIEW: We give a brief outline of physical therapies in the treatment of hirsutism with an emphasis on recently emerging hand-held laser hair removal devices for home use, which will become an increasingly important hair removal modality. The current evidence for topical ornithine decarboxylase inhibitor, oral antiandrogens, ovarian suppression and insulin sensitizers in the treatment of hirsutism is also reviewed. WHAT THE READER WILL GAIN: With advances in home laser hair removal systems the role of the clinician will increasingly become the use of pharmacotherapy in the treatment of resistant hirsutism. This article provides a review of the current literature for the use of pharmacotherapy. TAKE HOME MESSAGE: Despite the availability of a range of physical and pharmacotherapies for the treatment of hirsutism, permanent hair removal remains elusive.

Loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript cause Marie Unna hereditary hypotrichosis.

Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant form of genetic hair loss. In a large Chinese family carrying MUHH, we identified a pathogenic initiation codon mutation in U2HR, an inhibitory upstream ORF in the 5' UTR of the gene encoding the human hairless homolog (HR). U2HR is predicted to encode a 34-amino acid peptide that is highly conserved among mammals. In 18 more families from different ancestral groups, we identified a range of defects in U2HR, including loss of initiation, delayed termination codon and nonsense and missense mutations. Functional analysis showed that these classes of mutations all resulted in increased translation of the main HR physiological ORF. Our results establish the link between MUHH and U2HR, show that fine-tuning of HR protein levels is important in control of hair growth, and identify a potential mechanism for preventing hair loss or promoting hair removal.