Medicine (St Vincent's) - Research Publications

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    Refractory lupus erythematosus tumidus responsive to tildrakizumab
    Ismail, FF ; Sinclair, RD ; Pinczewski, J (WILEY, 2019-09)
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    Novel shampoo reduces hair shedding by contracting the arrector pili muscle via the trace amine-associated receptor
    Kovacevic, M ; McCoy, J ; Goren, A ; Situm, M ; Stanimirovic, A ; Liu, W ; Tan, Y ; Vano-Galvan, S ; Shapiro, J ; Sinclair, R (WILEY, 2019-12)
    BACKGROUND: Approximately 40% of women experience excessive hair shedding when washing their hair. Previously, we have demonstrated that a topically applied α1 adrenergic receptor agonist can be used to contract the arrector pili muscle of the follicular unit (ie, produce "goose bumps"), increasing the force required to pluck hair by as much as 400%. Subsequently, we reported a topical cosmetic solution containing an α1 adrenergic receptor agonist that reduced hair shedding during brushing by a maximum of 77%. AIMS: In this communication, we explore a novel mechanism to contract the arrector pili muscle. Trace amine-associated receptors (TAAR) have been shown to regulate smooth muscle tone in blood vessels, but have not been reported to be present in the skin. Here, we report on the anti-shedding efficacy of a shampoo containing a selective TAAR agonist, tyramine hydrochloride. METHODS: A single-blinded crossover study was designed to test the efficacy of the novel shampoo versus placebo in reducing hairs lost during brushing. RESULTS: In this study, the novel TAAR shampoo reduced hair shedding during brushing by 31% in a cohort of 24 women with a maximum reduction of 77%. CONCLUSIONS: A shampoo formulated with a selective TAAR agonist was demonstrated to contract the arrector pili muscle and reduce hair shedding subsequent to washing.
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    Pilonidal sinus disease: an intergluteal localization of hidradenitis suppurativa/acne inversa: a cross-sectional study among 2465 patients
    Benhadou, F ; Van der Zee, HH ; Pascual, JC ; Rigopoulos, D ; Katoulis, A ; Liakou, AI ; Daxhelet, M ; Romanelli, M ; Iannone, M ; Kinyo, A ; Nikolakis, G ; Zouboulis, CC ; Dessinioti, C ; Zisimou, C ; Antoniou, C ; Alavi, A ; Mintoff, D ; Aquilina, S ; Matusiak, L ; Szepietowski, JC ; Sinclair, R ; Husein-ElAhmed, H ; von Laffert, M ; Revuz, J ; Danby, B ; Puig, L ; Theut Riis, P ; Jemec, GBE ; van Straalen, K ; Wigny, KMGJ ; del Marmol, V ; Guillem, P (WILEY, 2019-12)
    BACKGROUND: Hidradenitis suppurativa (HS), also referred to as acne inversa, is a debilitating skin disease characterized by inflammatory nodules, chronic abscesses and tunnels (fistulae and sinuses). The association with pilonidal sinus disease (PSD) is frequently reported but not well documented. OBJECTIVES: To determine the prevalence and characteristics of inflammatory skin lesions located in the intergluteal fold (IGF) of patients with HS. METHODS: This was an international multicentre retrospective cross-sectional study based on data collection from a large cohort of patients with HS with and without histopathology. Results From a total of 2465 patients with HS included in the study, 661 (27%) reported lesions in the IGF. These patients were significantly more often smokers and had more severe HS. Of the 238 patients with an available clinical diagnosis, intergluteal-HS (IG-HS) was diagnosed in 52 patients (22%) and PSD was diagnosed in 186 patients (78%). IG-HS was associated with the localization of HS in the proximity of the IGF, including the buttocks, genitals and the anus. There was a possibility of misclassification bias in this study as a clinical/image-based diagnosis or histopathology of the IGF lesions was not always available. CONCLUSIONS: The high prevalence of PSD suggests a strong link between both entities. Therefore, it may be useful to identify common pathophysiological mechanisms and develop common therapeutic strategies. What's already known about this topic? The occurrence of pilonidal sinus disease has not been clearly reported among patients with hidradenitis suppurativa/acne inversa. What does this study add? This is the first study that investigated the prevalence of pilonidal sinus disease among a large cohort of patients and identified the patient characteristics. Risk factors that might help to improve the management of patients were identified.
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    Tretinoin enhances minoxidil response in androgenetic alopecia patients by upregulating follicular sulfotransferase enzymes
    Sharma, A ; Goren, A ; Dhurat, R ; Agrawal, S ; Sinclair, R ; Trueeb, RM ; Vano-Galvan, S ; Chen, G ; Tan, Y ; Kovacevic, M ; Situm, M ; McCoy, J (WILEY, 2019-05)
    Minoxidil sulfate is the active metabolite required to exert the vasodilatory and hair growing effects of minoxidil. For hair growth, sulfotransferase enzymes expressed in outer root sheath of the hair follicle sulfonate minoxidil. The large intra-subject variability in follicular sulfotransferase was found to predict minoxidil response and thus explain the low response rate to topical minoxidil in the treatment of androgenetic alopecia. A method to increase minoxidil response would be of significant clinical utility. Retinoids have been reported to increase minoxidil response. The purported mechanism of action was retinoid modulation of skin permeation to minoxidil; however, evidence to the contrary supports retinoids increase dermal thickness. In order to elucidate the effect of topical retinoids on minoxidil response, we studied the effect of topical tretinoin on follicular sulfotransferase. In this study, we demonstrate that topical tretinoin application influences the expression of follicular sulfotransferase. Of clinical significance, in our cohort, 43% of subjects initially predicted to be nonresponders to minoxidil were converted to responders following 5 days of topical tretinoin application. To the best of our knowledge, this is the first study to elucidate the interaction mechanism between topical minoxidil and retinoids and thus provides a pathway for the development of future androgenetic alopecia treatments.
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    Efficacy of tildrakizumab for moderate-to-severe plaque psoriasis: pooled analysis of three randomized controlled trials at weeks 12 and 28
    Papp, KA ; Reich, K ; Blauvelt, A ; Kimball, AB ; Gooderham, M ; Tyring, SK ; Sinclair, R ; Thaci, D ; Li, Q ; Cichanowitz, N ; Green, S ; La Rosa, C (WILEY, 2019-06)
    BACKGROUND: Efficacy of tildrakizumab for plaque psoriasis was demonstrated in randomized, placebo-controlled trials. OBJECTIVE: To consolidate tildrakizumab efficacy results by pooling data. METHODS: Data (N = 2081) from tildrakizumab 100 mg, tildrakizumab 200 mg and placebo groups in three trials were pooled. RESULTS: Proportions of Psoriasis Area and Severity Index (PASI) 75 responders at week 12 were better with tildrakizumab 100 mg (62.3%) and tildrakizumab 200 mg (64.8%) vs. placebo (5.6%; P < 0.0001) and for PASI 90, PASI 100 and Physician's Global Assessment (PGA) 'clear' or 'minimal' vs. placebo (P < 0.0001). Responses increased from weeks 12 to 28. Week 12 PASI and PGA responses to tildrakizumab vs. placebo were numerically greater in patients with lower vs. higher bodyweight and were better with tildrakizumab 200 mg than tildrakizumab 100 mg for patients with higher bodyweight. Week 12 PASI 75 responses vs. placebo with tildrakizumab 100 mg were similar between patients with (55.0%) or without (56.7%) prior biologics. PASI 90, PASI 100 and PGA responses were generally higher in patients without prior biologics. Week 8 PASI 50 response predicted PASI 90 response. CONCLUSION: Pooled data confirmed the efficacy of tildrakizumab for moderate-to-severe plaque psoriasis.
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    Prostaglandins in androgenetic alopecia in 12 men and four female
    Villarreal-Villarreal, CD ; Sinclair, RD ; Martinez-Jacobo, L ; Garza-Rodriguez, V ; Rodriguez-Leon, SA ; Lamadrid-Zertuche, AC ; Rodriguez-Gutierrez, R ; Ortiz-Lopez, R ; Rojas-Martinez, A ; Ocampo-Candiani, J (WILEY, 2019-05)
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    Systemic treatments for alopecia areata: A systematic review
    Lai, VWY ; Chen, G ; Gin, D ; Sinclair, R (WILEY, 2019-02)
    A range of systemic treatments are used for alopecia areata with variable evidence supporting efficacy. In this systematic review, we evaluated the evidence surrounding systemic treatments for alopecia areata, alopecia totalis and alopecia universalis. A systematic search was conducted of the peer-reviewed literature published between 1946 and March 2018 via Medline, Embase, Amed, the Cochrane Central Register of Controlled Trials, PsychINFO and Lilacs. All randomised controlled trials (RCTs) that evaluated the effectiveness of systemic treatments for individuals with alopecia areata, totalis or universalis were included. Sixteen studies were included with a total of 768 participants. We found eight placebo-controlled RCTs, three RCTs comparing two systemic treatments and five RCTs comparing three treatments. A total of 15 different systemic therapies were investigated. The most frequently investigated therapy was oral prednisolone pulse therapy and oral inosiplex. There was significant variability in the definition of treatment success. No study evaluated the impact of pharmacotherapy on quality of life using complete quantitative quality of life instruments. Adverse events were reported in 13 studies and were corticosteroid related or otherwise well tolerated. Relapse rates were considerable in the four studies that reported this outcome. There is currently no specific systemic therapy that is supported by robust body of evidence from RCTs. The current evidence suggests efficacy of oral prednisolone pulse therapy and oral inosiplex. Evidence does not support the use of oral zinc sulphate, alefacept and efalizumab. Future RCTs should be adequately powered and employ clearly defined clinical response endpoints to allow future meta-analyses.
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    The Trichoscopy Derived Sinclair Scale: Enhancing visual assessment through quantitative trichoscopy
    Kasprzak, M ; Sicinska, J ; Sinclair, R (WILEY, 2019-05)
    INTRODUCTION: The Sinclair Scale of hair midline density is commonly used in clinical dermatology practice as a tool to evaluate the severity of female pattern hair loss (synonym androgenetic alopecia, AGA) and to monitor patient response to treatment. The Sinclair Scale involves a visual evaluation of central hair parting line width, that is performed quickly and with no optical instrumentation. Another approach used to score severity of hair loss is quantitative trichoscopy. While quantitative trichoscopy is more accurate in terms of reproducibility and objectivity, it is more time-consuming. MATERIALS AND METHODS: Patients with different stages of AGA were evaluated using both the Sinclair Scale and quantitative trichoscopy. A correlation analysis was performed between the Sinclair Scale and different parameters derived from statistical analysis of trichoscopy images. A novel parameter, cumulative hair thickness density was introduced. RESULTS: Very good correlation was observed between Sinclair Scale and the cumulative hair thickness density. The quality of correlation is sufficient to estimate Sinclair Scale from cumulative hair thickness density. A formula to calculate the 'Trichoscopy Derived Sinclair Scale' from trichoscopy statistics was derived. DISCUSSION: We propose the term 'Trichoscopy Derived Sinclair Scale' to describe the hair midline density as derived from trichoscopy and to differentiate this assessment of midline hair density from the traditional one based on visual inspection alone.
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