2020 Scientific Poster Abstracts from Skin of Color Update

Thin on Top: A Cross-Sectional Analysis of the Top Black Hair Loss Videos and Black Hair Loss Treatment Videos on YouTube

Esther B. Henebeng BS, Uzoamaka Okoro MD, MSc, Ogechi Ezemma BA, Kristina Monteiro PhD, Afiya M. Mbilishaka PhD, Chesahna Kindred MD, MBA

More than 50% of Black women experience hair loss, with a majority of women searching for treatment options from online resources instead of seeking care from a primary care physician or dermatologist. Our project evaluated the accuracy, quality, viewer engagement, and viewer experience of “black hair loss” and “black hair loss treatment” videos on YouTube with four validated instruments.

Our search yielded a total of 78 unique YouTube videos. Twenty-two (28.2%) of the videos were from health care sources, and fifty-six (71.8%) from non-health care sources. When compared to non-health care sources, health care sources had lower mean numbers of views (81,965 vs 330,113, P = 0.008), were less engaging (0.01± 0.01 vs 0.02 ± 0.02, P = 0.012), more accurate (Accuracy in Digital Health: 3.77 ± 0.43 vs 2.00 ± 1.57, P = <0.001; Accuracy Scale: 3.91 ± 0.30 vs 2.15 ± 1.25, P = <0.001), provided a superior viewer experience (Armstrong Viewer Assessment: 3.09 ± 0.53 vs 2.55 ± 1.01, P = 0.023) and were of higher quality (Global Quality Scale: 3.64 ± 0.85 vs 2.47 ± 1.09, P = <0.001). Our results underscore the need for dermatologists to work in tandem with non-health care sources (ex. hairstylists) who may have a larger following on social media in order to dispel misinformation online.

A 1% Colloidal Oatmeal OTC Cream is Clinically Effective for the Management of Mild to Moderate Atopic Dermatitis in African-American Children

Authors: T.Lisante¹, M.Kizoulis¹, P Zhang¹, C Nunez²
1 Johnson & Johnson Consumer, Inc | 2 . Janssen Pharmaceutical Research and Development

Introduction:

Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects diverse ethnic groups with varying prevalence.  The National Health and Nutrition Examination Survey, which evaluates the health and nutritional status of adults and children in the U.S., found that 19.3 percent of African American children have atopic dermatitis, compared to 16.1 percent of white and 7.8 percent of Asian children. Further analysis of this data revealed that U.S. African-American children are 1.7 times more likely to develop atopic dermatitis than white children even when adjusting for confounding factors such as socioeconomic background, environmental conditions and healthcare insurance coverage.  This disproportionate impact coupled with additional unique skin conditions in this population further highlights the need for research and identification of therapeutic agents that are effective on the multicultural skin.

Methods:

As part of a larger trial examining the efficacy and safety of a 1% OTC colloidal oatmeal compared to a prescription barrier cream, this investigation studied 49 AA children, ranging from 2 – 15 years of age with mild to moderate AD. Patients were randomly assigned to colloidal oatmeal (CO) or a prescription barrier repair cream (BRC) and were instructed to use assigned products at least twice daily or as needed for three weeks. Assessments of AD severity and improvement were made by the Investigator using the Eczema Area and Severity Index (EASI) at Baseline and Days 7, 14 and 21. Subjective assessment of itch and other eczema related assessments were made via questionnaires at each time point using a 10 point scale.

Results:

The Baseline EASI scores for the AA subjects (n=49) was 3.4 and for the non-AA subjects (n=41) was 3.0.  Colloidal oatmeal did provide rapid improvement in AD symptoms in the AA subjects by Day 7 – 63% and a 46.0% improvement in non-AA subjects by Day 7.  The parents’ subjective ratings of itch by Day 7 improved by an average of 2 points on a 10-point scale.  While all subjective assessments improved by day 7, the greatest improvements were seen for moisturization (2 pts), dryness and flakiness (2 pts).   Similar results was seen for the barrier cream.  Both treatments were well tolerated in the study.

Conclusion:

The results from this investigation suggest that colloidal oatmeal was effective provided rapid improvement in AD symptoms by Day 7 based on Investigator and subjective assessments in African American children when used daily.  Colloidal oatmeal cream is a safe, cost-effective over-the-counter (OTC) treatment approach for managing mild to moderate AD in the population studied.

Cytotoxic chemotherapy-induced hyperpigmentation in skin of color

Author Contact Information:
Amaris Geisler
[email protected]

Authors: Amaris N. Geisler, BS; Dulce M. Barrios, MS; Sarah J Noor, MD

Biographies:

Amaris N. Geisler:

Amaris N. Geisler is a fourth-year medical student at the CUNY School of Medicine in New York, New York. Amaris conducted two research fellowships during the 2019-2020 year at SUNY Downstate and Memorial Sloan Kettering Cancer Center. Her dermatologic interests lie in skin of color, onco-dermatology, and complex medical dermatology. Amaris was awarded mentorship through the Skin of Color Society and the American Academy of Dermatology Diversity Mentorship Award, as well as the American Society of Clinical Oncology Conquer Cancer Foundation Medical Student Rotation Award. Amaris remains active in research and mentorship and even created her own mentorship program for high school students in her hometown.

Dulce M. Barrios:

Dulce M. Barrios is a fourth-year medical student at Upstate Medical University in Syracuse, NY pursuing a career in Dermatology. Dulce has been engaged in clinical experiences and scholarship since college, including full-time research positions and a 1-year research fellowship in Dermatology at Memorial Sloan Kettering Cancer Center from 2019-2020. Her work over the years has produced over 10 peer-reviewed publications, with topics ranging from health literacy to obesity and dermatologic toxicities of cancer treatments in underserved Latino populations. Dulce was 1 of 10 students nationally to be awarded a 2019 ASCO Conquer Cancer Foundation Medical Student Rotation Award for a proposal that she wrote to study skin pigmentary changes in response to cancer therapy. Dulce is also the recipient of the 2020 Best Oral Presentation Advancing Skin of Color Dermatology “Facing the Future Award” for her work on Anticancer Therapy-induced Cutaneous Dyschromias in Oncology Patients with Skin of Color. More recently, she wrote a proposal for a Dermatology Foundation Diversity Research Supplement Award that was funded to support additional work she will do at Memorial Sloan Kettering Cancer Center.

Sarah J. Noor:

Sarah J. Noor is a board-certified dermatologist at Memorial Sloan Kettering Cancer Center who specializes in cutaneous lymphomas and management of skin, hair, and nail toxicities from cancer treatment including radiation, chemotherapy, targeted, and immunotherapies. In these roles, she is part of a multidisciplinary group that includes medical oncologists, radiation oncologists, and nurses who work together to provide comprehensive care to patients. She provides care both in the outpatient setting, as well as to patients admitted to the hospital who require dermatologic evaluation. Her clinical and research interests include understanding and addressing the impact that cutaneous symptoms and disease as well as treatment toxicities can have an impact on quality of life. She completed her dermatology residency training at New York Presbyterian/Weill Cornell in which she served as chief resident in her final year.

Combination cytotoxic chemotherapy with capecitabine and either docetaxel or paclitaxel is used for the treatment of locally advanced or metastatic breast cancer.1-6 Capecitabine is also used as a first-line treatment for metastatic colorectal carcinoma and taxanes (docetaxel, paclitaxel, nab-paclitaxel) are additionally used for the treatment of metastatic or locally advanced non-small cell lung cancer, prostate, gastric, head and neck, and ovarian cancers.1-9 Capecitabine is a prodrug of 5-fluorouracil (5-FU), and is converted to 5-FU by thymidine phosphorylase, an enzyme found in high levels in tumor cells.1,3-5 This conversion to the active metabolite increases the ability of the drug to target cancer and spare healthy surrounding tissue.3,4,6 Taxanes are antimicrotubule agents that promote the polymerization of tubulin into highly stable intracellular microtubules, disrupting mitosis and normal cell division, leading to cell death.7-10 Although they are effective against rapidly dividing cancer cells, they have similar effects on other cells with high turnover such as keratinocytes.8 Nab-paclitaxel is a novel, recently approved taxane that is solvent free, and thus, associated with less severe adverse reactions (AEs) including hypersensitivity reactions.7

Dermatologic adverse events (dAEs) of capecitabine mostly includes hand-foot syndrome (HFS) (53-60%) and hyperpigmentation.2-4,11-15 Hyperpigmentation has been known to occur at the same time as HFS, and there is a debate whether hyperpigmentation should be considered as part of the initial presentation of grade 1 or mild HFS, or whether it is a separate entity.2,4,5,12-15 Most cases of capecitabine-induced hyperpigmentation with associated HFS have been reported in patients phototype IV, V, and VI including African Americans, Indians, and Asians.2,3,5,11,16 These adverse effects often occur within a few weeks of capecitabine therapy and 11-17% of patients ultimately require dose adjustment or discontinuation with the administration of topical steroids and other anti-inflammatories to avoid progression.2-4,17-20

Several mechanisms have been proposed for these dAEs including mitochondrial dysfunction by capecitabine activated caspase-dependent apoptosis, local trauma to the small vessels from the mechanical stress of daily activities that allows the drug to leak into the surrounding tissue, and elimination of capecitabine by eccrine glands present in the hands and feet that damages local

tissue.3,4,20 Histopathologic analysis shows vacuolar degeneration of basal keratinocytes, dermal perivascular lymphocytic infiltration, apoptotic keratinocytes, and dermal edema.20

The true incidence of hair, nail, skin, and mucosal reactions to taxane therapy is largely unknown but has been estimated to be between 6-81%.7,21,22 Hyperpigmentation is one of the most common manifestations and various forms have been described including serpentine supravenous hyperpigmentation, flagellate and reticulate hyperpigmentation, and post inflammatory hyperpigmentation.7,9,10,23-26 A putative mechanism suggests that taxanes cause a loss of integrity of vascular endothelium, and leakage of the drug from the vessel to the overlying epidermis with subsequent hyperpigmentation.25,26 Histopathologic analysis shows interface dermatitis with isolated necrotic keratinocytes, papillary dermal edema, and superficial perivascular inflammatory infiltrates, with melanin incontinence and melanophages in the papillary dermis in later biopsies.25 Although the conditions are benign and self-limiting, topical corticosteroids have been found to provide some relief.10,25

Herein, we present an occurrence of hyperpigmentation on the cheeks of a 57-year-old Bangladeshi female (type V) with a history of breast cancer in the setting of capecitabine therapy, and a hyperpigmented rash in a 70-year-old Asian female (type IV) with a history of endometrial cancer in the setting of paclitaxel therapy. Diagnostic measures including histopathologic analysis and confocal microscopy, to characterize extent of inflammation versus post-inflammatory hyperpigmentation, as well as treatment paradigms are discussed.

In general, little is known about cutaneous toxicities to chemotherapies in patients of skin of color who are more prone to developing pigmentary changes. Our experience at MSKCC has shown that dyschromia from cancer treatment occurs not only as a result of post-inflammatory hyperpigmentation with rash resolution (e.g acneiform rash from epidermal growth factor inhibitors), but also as the initial clinical presentation. One of the challenges in evaluating these patients is determining whether this represents active inflammation or post-inflammatory pigmentary alteration, which is clinically relevant as this would lead to differing treatment approaches (skin lightening agents vs anti-inflammatory agents). A thorough understanding of the diagnosis and management of these dAEs in patients of darker skin types is crucial not only for minimizing dose modifications but also improving quality of life.

1. Lal HS. Hand and foot syndrome secondary to capecitabine. Indian J Dermatol Venereol Leprol. 2014;80(5):427-430.

2. Vickers MM, Easaw JC. Palmar-plantar hyperpigmentation with capecitabine in adjuvant colon cancer. J Gastrointest Cancer. 2008;39(1-4):141-143.

3. Peccerillo F, Pampena R, Giannetti L, Pellacani G, Longo C. Capecitabine-induced eruptive acral hyperpigmentation: Clinical and dermoscopic evaluation of two cases. Dermatol Ther. 2019;32(3):e12853.

4. Caprez J, Rahim U, Ansari A, Lodhi MU, Rahim M. Hyperpigmentation with Capecitabine: Part of Hand-Foot Syndrome or a Separate Entity? Cureus. 2018;10(3):e2397.

5. Tognetti L, Fimiani M, Rubegni P. Benign dermoscopic parallel ridge pattern in plantar hyperpigmentation due to capecitabine. Dermatol Pract Concept. 2015;5(2):79-81.

6. Tavares-Bello R. Capecitabine-induced hand-foot syndrome and cutaneous hyperpigmentation in an elderly vitiligo patient. J Eur Acad Dermatol Venereol. 2007;21(10):1434-1435.

7. Sibaud V, Lebœuf NR, Roche H, et al. Dermatological adverse events with taxane chemotherapy. Eur J Dermatol. 2016;26(5):427-443.

8. Ludwig C, Goh V, Rajkumar J, Au J, Tsoukas M. Drug eruptions associated with tumor therapy: Great imitators. Clin Dermatol. 2020;38(2):208-215.

9. Aydogan I, Kavak A, Parlak AH, Alper M, Annakkaya AN, Erbas M. Persistent serpentine supravenous hyperpigmented eruption associated with docetaxel. J Eur Acad Dermatol Venereol. 2005;19(3):345-347.

10. Chew L, Chuen VS. Cutaneous reaction associated with weekly docetaxel administration. J Oncol Pharm Pract. 2009;15(1):29-34.

11. Pui JC, Meehan S, Moskovits T. Capecitabine induced cutaneous hyperpigmentation: report of a case. J Drugs Dermatol. 2002;1(2):202-205.

12. Vázquez-Bayo C, Rodríguez-Bujaldón AL, Jiménez-Puya R, Galán-Gutiérrez M, Moreno Giménez JC. [Capecitabine-induced hyperpigmentation]. Actas Dermosifiliogr. 2007;98(7):491-493.

13. Goyal R, Chalamalasetty SB, Madan K, et al. Acral and palmo-plantar hyperpigmentation in a patient with disseminated hepatocellular carcinoma. Indian J Gastroenterol. 2007;26(6):292-293.

14. Ghosal N, Misra V. A case of capecitabine-induced hyperpigmentation and radiation recall phenomenon. Clin Oncol (R Coll Radiol). 2009;21(8):632.

    Agharbi FZ, Meziane M, Benhemmne H, et al. [Capecitabine-induced hyperpigmentation followed by hand-foot syndrome: a new case report]. Ann Dermatol Venereol. 2012;139(3):221-222.

15. Narasimhan P, Narasimhan S, Hitti IF, Rachita M. Serious hand-and-foot syndrome in black patients treated with capecitabine: report of 3 cases and review of the literature. Cutis. 2004;73(2):101-106.

16. Verma P. Capecitabine-induced acral and mucosal hyperpigmentation. Indian J Dermatol Venereol Leprol. 2017;83(5):583.

17. van Tienhoven G, Wilmink JW. [A woman with palmar and plantar hyperpigmentation]. Ned Tijdschr Geneeskd. 2011;155(45):A4100.

    Villalón G, Martín JM, Pinazo MI, Calduch L, Alonso V, Jordá E. Focal acral hyperpigmentation in a patient undergoing chemotherapy with capecitabine. Am J Clin Dermatol. 2009;10(4):261-263.

18. Lee SD, Kim HJ, Hwang SJ, Kim YJ, Nam SH, Kim BS. Hand-foot syndrome with scleroderma-like change induced by the oral capecitabine: a case report. Korean J Intern Med. 2007;22(2):109-112.

19. Huang KL, Lin KY, Huang TW, et al. Prophylactic management for taxane-induced nail toxicity: A systematic review and meta-analysis. Eur J Cancer Care (Engl). 2019;28(5):e13118.

20. Yang ST, Cheng M, Lee NR, Chang WH, Lee YL, Wang PH. Paclitaxel-related nail toxicity. Taiwan J Obstet Gynecol. 2019;58(5):709-711.

21. Sharma PK, Misra AK, Gupta A, Singh S, Dhamija P, Pareek P. A retrospective analysis of reporting of adverse drug reactions to oncology drugs: An experience from a national center of clinical excellence. Indian J Pharmacol. 2018;50(5):273-278.

22. Ghosh SK, Bandyopadhyay D, Ghoshal L, Basu S. Letter: Docetaxel-induced supravenous serpentine dermatitis. Dermatol Online J. 2011;17(11):16.

23. Das A, Kumar D, Mohanty S, Mondal AK, Chowdhury SN, Bandyopadhyay D. Serpentine supravenous hyperpigmentation induced by docetaxel. Indian J Dermatol Venereol Leprol. 2015;81(4):434.

24. Masson Regnault M, Gadaud N, Boulinguez S, et al. Chemotherapy-Related Reticulate Hyperpigmentation: A Case Series and Review of the Literature. Dermatology. 2015;231(4):312-318.

High patient satisfaction with adapalene 0.3%/ benzoyl peroxide 2.5% in the treatment of moderate or severe acne in subjects with skin of color

Authors: Janet DuBois, MD1; Gavin Chun Wei Ong, MD2; Gitanjali Petkar, MBBS, DDV3; Rajeev Chavda, MD4; Nabil Kerrouche, MSc5

1DermResearch, Inc., Austin, TX; 2Centre International De Developpement Pharmaceutique PTE Ltd (CIDP), Biopolis, Singapore; 3Centre International De Developpement Pharmaceutique Ltd (CIDP), Bio Park, Mauritius; 4Medical Evidence, Galderma S.A., Vevey, Switzerland; 5Department of Translational Sciences, Syneos Health, Sophia-Antipolis, France

Introduction

In skin of color subjects (Fitzpatrick skin phototypes [FST] IV to VI), the objective was to evaluate subject reported outcomes with a fixed combination treatment containing adapalene 0.3%/ benzoyl peroxide 2.5% (A0.3/BPO2.5) gel in the treatment of moderate to severe acne vulgaris of the face.

Methods

This was an open label, single arm, interventional study conducted in 3 countries (Mauritius, Singapore, USA) in subjects of Asian, Latin American, or Black/African-American ethnicity (planned enrollment 1:1:1), with an Investigator’s Global Assessment (IGA) of moderate or severe acne (planned enrollment 2:1), and FST IV to VI. For 16 weeks, subjects applied: A0.3/BPO2.5 gel (once daily, evening) and a skin care regimen (oil control foam wash and oil control moisturizer SPF30). Assessments included the Dermatology Life Quality Index questionnaire (DLQI), the Children’s Dermatology Life Quality Index (cDLQI) questionnaire (if ≤16 years old), subject questionnaires, IGA, investigator Global Assessment of Improvement (GAI), Post-Inflammatory Hyper-pigmentation (PIH; if present at baseline), tolerability, and safety.

Results

Subjects (N = 50) enrolled included 20 Asians, 17 African-Americans, and 13 Latin Americans. Most had FST IV (74%) or V (22%), with moderate (70%; IGA 3) or severe (30%; IGA 4) acne at baseline. A DLQI/cDLQI score indicating a moderate to extremely large effect on QoL was observed for approximately 50% of subjects at baseline compared to 15% at W16. At W16, 76.6% of subjects were overall satisfied or very satisfied with the study treatment.

At W16, 56% of subjects had an IGA score of 0 or 1 (clear/almost clear), and 87% had a good to excellent improvement in GAI score.

Of those subjects with PIH at baseline (60%), all were rated very mild to moderate. By W16, the majority (75%) had none or very mild PIH, and the mean percentage decrease in PIH was 27%. Seven subjects (14%) reported related adverse events but all were mild. Overall, 49% of subjects (W16) were not bothered at all by treatment side effects.

Conclusions

Subjects of Asian, African American, and Latin American ethnicities, with dark skin phototypes (FST IV‑VI), and moderate or severe facial acne reported high patient satisfaction with A0.3/BPO2.5 gel treatment. Subjects experienced good tolerability, improved QoL, acne treatment efficacy, and improvement in PIH.

Funding

Study funded by Galderma R&D.

Efficacy of certolizumab pegol in patients with psoriasis and skin of color: pooled data from four randomized, placebo-controlled phase 2/3 trials

Author Contact Information:
Michael Cronin
[email protected]

Authors: A. Blauvelt,1 F. Brock,2 T. Rosario-Jansen,3 A.B. Gottlieb,4 A. Alexis,5 A. Asahina6

1Oregon Medical Research Center, OR, USA; 2UCB Pharma, Slough, UK; 3UCB Pharma, Raleigh, NC, USA; 4Department of Dermatology, Icahn School of Medicine at Mount Sinai, NY, USA; 5Department of Dermatology, Mount Sinai Morningside and Mount Sinai West, NY, USA; 6Department of Dermatology, Jikei University School of Medicine, Tokyo, Japan

Introduction:

Certolizumab pegol (CZP), an Fc-free, PEGylated anti-tumor necrosis factor biologic, has demonstrated efficacy in plaque psoriasis (PSO) in predominately white populations. However, clinical presentations in more diverse populations vary, and data on treatment response in patients with skin of color are lacking. The objective of this analysis was to assess CZP efficacy in patients with PSO and skin of color using data from phase 2/3 trials.

Methods:

Data from all patients with skin of color and moderate to severe PSO were pooled from randomized, double-blinded, placebo-controlled studies: CIMPASI-1 (NCT02326298), CIMPASI-2 (NCT02326272), CIMPACT (NCT02346240) (North America/Europe phase 3 trials), and a phase 2/3 trial with Japanese patients only (NCT03051217). Patients received CZP 400 mg every two weeks (Q2W), CZP 200 mg Q2W, or placebo. Improvements of 75%, 90%, and 100% in Psoriasis Area Severity Index (PASI 75/90/100), Physician’s Global Assessment scores of “clear” (0) or “almost clear” (1; PGA 0/1), and Dermatology Life Quality Index remission rates (DLQI 0/1) from Weeks 2–16 are summarized descriptively for the pooled data and presented alongside overall CIMPASI/CIMPACT populations. PASI and PGA responder rates reflect simple averages, with missing data multiply imputed using Markov Chain Monte Carlo methodology. Missing data for DLQI remission rates were imputed using non-response imputation.

Results:

A total of 178 patients with skin of color were pooled (127 patients from the Japanese study; 51 patients from CIMPASI/CIMPACT); 146 (82.0%) of these patients were Asian, and 19 (10.7%) were Black. Others were American Indian, Pacific Islander, or mixed. Week 16 responder rates for CZP 400 mg (n=73) and CZP 200 mg (n=68) Q2W vs. placebo (n=37), respectively, were 87.4% and 71.9% vs. 6.8% for PASI 75; 67.8% and 50.4% vs. 0.8% for PASI 90; 18.2% and 22.0% vs. 0.6% for PASI 100; and 63.3% and 54.4% vs. 0.4% for PGA 0/1. Efficacy in the skin of color population was generally higher than in the overall predominately white (94.0%) CIMPASI/CIMPACT population; responder rates for CZP 400 mg (n=342) and CZP 200 mg (n=351) vs. placebo (n=157), respectively, in the overall population were 76.7% and 70.9% vs. 7.6% for PASI 75; 48.5% and 41.4% vs. 1.6% for PASI 90; 16.9% and 14.3% vs. 0.9% for PASI 100; and 61.2% and 52.7% vs. 3.3% for PGA 0/1. Week 16 DLQI remission rates for CZP 400 mg and CZP 200 mg Q2W vs. placebo, respectively, in patients with skin of color were 56.2% and 52.9% vs. 5.4%. Efficacy was generally numerically higher in patients in the Japanese study than those with skin of color in the CIMPASI/CIMPACT studies.

Conclusions:

CZP efficacy was numerically higher in patients with skin of color than the predominately white population. However, no formal statistical comparisons were performed, and there were few non Japanese patients. Low enrollment of Black patients highlights previously reported disparities in clinical trials. It will be important to collect real-world data on CZP efficacy in patients with PSO and skin of color.

Funding:

These studies were sponsored by Dermira, Inc. and UCB Pharma. Medical writing support was provided by Costello Medical, funded by UCB Pharma.

Disclosures:

A. Blauvelt has served as a scientific adviser and/or clinical study investigator for AbbVie, Aclaris, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dermira, Eli Lilly and Company, Forte, Galderma, Incyte, Janssen, Leo, Novartis, Ortho, Pfizer, Rapt, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma, and as a paid speaker for AbbVie. F. Brock and T. Rosario-Jansen are employees of UCB Pharma. A.B. Gottlieb received honoraria as an advisory board member and consultant for Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb Co., Eli Lilly, Incyte, Janssen, LEO Pharma, Novartis, Sun Pharma, UCB Pharma, and Xbiotech (only stock options which she has not used); research/educational grants from Boehringer Ingelheim, Incyte, Janssen, Novartis, Sun Pharma, UCB Pharma, and Xbiotech have been paid to her medical school. A. Alexis has received grant/research support (funds to institution) from Leo, Novartis, Almirall, Bristol Myers-Squibb, Celgene, Menlo, Galderma, Valeant (Bausch Health), and Cara; has served as a consultant for Leo, Novartis, Menlo, Galderma, Pfizer, Sanofi-Regeneron, Dermavant, Unilever, Celgene, Beiersdorf, Valeant, L’Oreal, BMS, Menlo, Scientis, Bausch health, UCB Pharma, Foamix, Cassiopea, Arcutis; and has received royalties from Springer, Wiley-Blackwell, and Wolters Kluwer (UpToDate). A. Asahina has served as a consultant and/or received speaker fees from Maruho Co., Ltd., AbbVie GK, Eisai Co., Ltd., Mitsubishi Tanabe Pharma, Janssen Pharmaceutical K.K., Kyowa Hakko Kirin Co., Ltd., Torii Pharmaceutical Co., Ltd., TAIHO Pharmaceutical Co., Ltd., LEO Pharma Japan, Eli Lilly Japan K.K., and UCB Pharma.

Alexis E. Carrington, MD, Jeanette Jakus, MD, FAAD, Marjon Vatanchi, MD, FAAD

In this manuscript, we research and highlight photographer Angélica Dass’ worldwide acclaimed Humanae project. Humanae is a compilation of portraits of people around the world, capturing the diversity in skin tones and creating awareness of viewing skin tones as a spectrum, rather than binary. We believe this manuscript is appropriate for publication by the Skin of Color Update because it highlights an innovative woman challenging racial misconceptions associated with differences in skin tones and by photographing the mosaic spectrum and beauty of human skin tones.

Photoprotective behaviors for the treatment and prevention of unwanted hyperpigmentation in skin of color patients

Author Contact Information:
Monica Williams
[email protected]

Monica N. Williams, MD, MPH, MS; Fritzlaine Roche, MPH; Susan C. Taylor, MD2

Introduction:

Hyperpigmentation is a common concern among skin of color patients and photoprotection is recommended for its prevention and treatment. Despite ultraviolet and visible light induced exacerbation of hyperpigmentation, patients of color with post-inflammatory hyperpigmentation (PIH) are least likely to utilize sunscreens when compared to other groups experiencing cutaneous hyperpigmentation. Physicians are also less likely to recommend sunscreen for disorders of pigmentation in people of color. We surveyed patients of color whose self-reported skin reactivity was consistent with Fitzpatrick skin types IV-VI to determine their methods of photoprotective prevention and treatment.

Objective:

We aimed to determine the methods of hyperpigmentation prevention and treatment among skin of color patients with particular focus on those with histories of unwanted hyperpigmentation.

Methods:

We designed a non-randomized cross-sectional convenience survey which was distributed via a generic anonymous online link in the dermatology clinic lobby at the Perelman School of Medicine at the University of Pennsylvania between September 2019 and November 2019.

Results:

Thirty-nine adult respondents, primarily of African American (92%) descent, female (80%), with sun reactivities and phenotypes consistent with Fitzpatrick skin-type IV- VI; met inclusion criteria, were consented, and completed the survey. Respondents were between the ages of 20 to 78 years old (mean age [standard deviation], 48.6 [8.8] years; and the majority completed at least some college (87%), had no history of sunburn (56%), at least one hour of sun exposure per week (87%). Nearly half of those surveyed had a history of unwanted dark spots (46%, n=18).

While individuals with a history of unwanted hyperpigmentation were more likely to be motivated to engage in photoprotection to prevent worsening of unwanted dark spots (χ21, P=.037); they were not more likely to engage in photoprotective behaviors overall (χ21, P= .52)

Photoprotective clothing was the most commonly reported treatment for unwanted hyperpigmentation among all respondents (23%) and those with a history of unwanted hyperpigmentation (N=18, 33%). While sunscreen use was the most common form of hyperpigmentation prevention (28%).

Overall, 82% of respondents engaged in photoprotective behaviors; with 33% engaging in photoprotection to treat unwanted hyperpigmentation and 56% engaged in behaviors to prevent it.

Discussion:

These results show that while patients of color are more motivated to use photoprotection for the prevention of their unwanted dark spots they are not more likely to actually engage in photoprotective behaviors overall.

Further research should investigate potential barriers to the use of photoprotection for the prevention of unwanted hyperpigmentation in skin of color patients with histories of unwanted dark spots in order to move them from motivation to action. Additionally, the knowledge, attitudes, and beliefs of skin of color patients concerning the use of photoprotection for treatment of unwanted dark spots should be investigated in order to develop targeted education and communication strategies concerning its utility in the treatment of unwanted hyperpigmentation.

Paradox in Assessing Smoldering Adult T-Cell Leukemia/Lymphoma: A Case Report

Authors: A. Blauvelt,1 F. Brock,2 T. Rosario-Jansen,3 A.B. Gottlieb,4 A. Alexis,5 A. Asahina6

Abstract

Introduction:

Smoldering Adult T-Cell Leukemia/Lymphoma (ATLL), the subtype of ATLL confined to the skin, poses a challenge to diagnose and treat due to asymptomatic onset, varied clinical manifestations, and indolent course of illness. Etiology can be dependent on carriage of the Human T-cell Lymphotropic Virus type 1 (HTLV-1) and carries a prognosis of 3-4 years. While serological testing and bone marrow biopsy can assess for systemic ATLL, a skin biopsy is necessary to diagnose smoldering ATLL. Chemotherapeutic options exist for systemic subtypes; however, few treatment options are available for smoldering ATLL.

Case Report:

A 63-year-old Panamanian female with Fitzpatrick skin type V presented with asymptomatic dyschromia of the neck for eight months duration. On exam, the patient displayed erythematous plaques with mild induration and areas of dyschromia with mixed hyper- and hypopigmented patches on the right neck extending to the bilateral breasts in a serpiginous pattern (image shown). Punch biopsies of the right jawline and left breast exhibited infiltrates of patchy lichenoid mononuclear cells filling the papillary dermis with exocytosis of atypical mononuclear cells arranged as nests throughout all levels of the epidermis (image shown). CD25+ antibody stain revealed numerous atypical CD25+ cells in the epidermis (image shown). With differential diagnoses including mycoses fungoides, contact dermatitis, nummular eczema, cutaneous lupus, and sarcoidosis, the patient received a final diagnosis of smoldering type ATLL. Her initial oncologist decided not to pursue treatment per oncology guidelines, however a second oncologist treated her with IFN-alpha/AZT resulting in clearance of her cutaneous symptoms within three months.

Discussion:

There are four clinical variants of ATLL: smoldering, acute, chronic, and lymphomatous. All four are associated with vertically transmitted chronic infection with HTLV-1. Despite infection with HTLV-1, the risk of developing ATLL is 2-4% regardless of the subtype. Due to varying cutaneous manifestations and an asymptomatic nature, diagnosis can be delayed prolonging initiation of appropriate treatment.

Key Words:

HTLV, adult t-cell leukemia lymphoma, cutaneous lymphoma, smoldering lymphoma, smoldering, treatment

Figures:

Figure 1:Baseline exam of the patient displaying indurated, erythematous plaques with dyschromia on the right jawline. (To be published in color.)
Figure 2: (A) Patchy lichenoid mononuclear cell infiltration of the superficial dermis. [Hematoxylin and Eosin stain, 40x magnification]; (B) Magnification of atypical mononuclear cells arranged as nests in the epidermis. [Hematoxylin and Eosin stain, 100x magnification] (To be published in color.)
Figure 3: Atypical mononuclear cells in the epidermis expressing CD25, a T-cell marker. [CD25 Antibody stain, 400x magnification] (To be published in color.)

Severity of Disease in Latino Patients Enrolled in University of California-Irvine Psoriasis Clinical Trials

Author Contact Information:
Alyssa Ashbaugh
[email protected]

Authors: Alyssa G. Ashbaugh, BA,1, 2 Gabrielle Brody, BA,1,2 Yessica Landaverde,1 Chloe Ekelem, MD, MPH,1,3 Natasha Atanaskova Mesinkovska, MD, PhD1

• 1 University of California, Irvine, School of Medicine
• 2 University of California, Irvine, Department of Dermatology
• 3 University of Utah, Department of Dermatology

Corresponding author:
Alyssa Ashbaugh
[email protected]

ABSTRACT

Purpose: Current evidence suggests that there are notable differences in the severity of psoriasis between racial and ethnic groups. While the US Latino population is growing faster than any other in the US, there has been a disproportionate lack of research targeting dermatologic health in Latino patients. In fact, compared to other dermatologic diseases, psoriasis studies have been found to be the least ethnically representative, particularly regarding Latino patients. This study aims to better elucidate the discrepancies in severity between Latino patients and white patients enrolled in psoriasis clinical trials at the University of California – Irvine (UCI). Design: This study is retrospective chart review of all Latino patients, as well as age- and gender-matched white patients, screened for psoriasis clinical trials at UCI. Demographic data, Psoriasis Area and Severity Index (PASI) scores, Body Surface Area (BSA), and comorbidities were documented for each patient and results were compared between Latino patients and white patients with a two-tailed Student’s t-test.

Findings:

21 Latino patients (7 female, 14 male; ages 29-80 years old) were screened for enrollment in psoriasis clinical trials at UCI with an average age of 52 years old and 67% male.

On average, Latino patients had lived fewer years with psoriasis compared to white patients (15.7 vs. 24.9, respectfully, p = 0.01). While 28.6% of White patients versus 42.9% of Latino patients versus had Investigator Global Assessment (IGA mod 2011) scores of “severe,” the average Psoriasis Area and Severity Index (PASI) score for the trunk/axilla/groin region was higher in White patients than in Latino patients (9.73 vs 4.74, respectively; p = 0.02). We did not observe any significant differences in comorbidities between Latino and White psoriasis patients.

Summary:

Latino psoriasis patients are disproportionately affected by increased psoriasis severity compared to white patients. Though white patients have, on average, lived more years with psoriasis, this could be explained by delayed diagnosis in Latino patients, who are known to have decreased access to health care and are more likely to have undiagnosed psoriasis compared to white patients. Future studies are necessary to evaluate genetic, environmental, and social factors that may contribute to psoriatic disease biology in US Latino patients and better meet the health care demands of an increasingly diverse patient population.

Author Biographies:

Alyssa Ashbaugh is an MS4 at the University of California-Irvine applying into Dermatology this fall. In the future she desires to sub-specialize within Skin of Color and provide care to underserved communities. Gabrielle Brody is an MS3 at UCI. Yessica Landaverde recently completed her undergraduate degree at UCI and was previously a Research Coordinator at UCI, Department of Dermatology. Dr. Chloe Ekelem is now a PGY2 Dermatology resident at the University of Utah and was previously a Research Fellow at UCI, Department of Dermatology. Dr. Natasha Mesinkovska is Assistant Professor and Director of Clinical Research at UCI, Department of Dermatology.

The Risk of Skin Cancer and the Use of Diuretic Blood Pressure Medications in the Nurses’ Health Study

Author Contact Information:
Nicole Negbenebor
[email protected]

Nicole A. Negbenebor MD, Terrence Vance, PhD, Abrar A. Qureshi MD
Department of Dermatology, Warren Alpert Medical School of Brown University, Providence, RI

BACKGROUND:

Diuretic blood pressure medications have recently been associated with an increased risk of non-melanoma and melanoma skin cancers; however, the data has been both conflicting and limited in the literature. Diuretics have been implicated in increasing the risk of skin cancer through drug-induced photosensitivity. We examined whether use of diuretics was associated with an increased risk of skin cancer in patients.

METHODS:

The 33,514 men and women in the Nurses’ Health Study provided information on diuretic use from 2003-2016. Our cohort was 25.7% Hispanic, 42.7% Non-Hispanic White, 21.9% Non Hispanic Black, and 9.8% “other”. We evaluated more than 40 different diuretic formulations. Medication use and duration were assessed on questionnaires. We confirmed 211 melanoma cases, 571 non-melanoma skin cancer (NMSC) cases, and had 287 reports of an “unknown skin cancer” type. We computed odds ratios (OR) and confidence intervals (CI) adjusted for age, race/ethnicity, gender, smoking, health insurance, poverty income ratio, and survey year.

RESULTS:

Diuretic use was not associated with a higher risk of melanoma, NMSC, or “unknown skin cancer” type, even for men and women who reported a high duration of use. As compared to non-diuretic users, we observed a similar risk for skin cancer among diuretic users who had used a diuretic <4yrs (OR = 0.91, 95 % CI 0.68-1.21) or >4 yrs (OR = 1.06, 95 % CI 0.84-1.32). There was also no association after adjusting for number of sunburns or sunscreen use (OR=0.65, 95 % CI 0.4-1.07).

CONCLUSIONS:

Diuretics were not associated with a higher risk of melanoma or NMSC in this diverse, nationally representative cohort. Our comprehensive prospective study does not provide evidence for an association between diuretic use and increased incidence of skin cancers.

Cysteamine: Non-cytoxic topical therapy for melasma & PIH on face and body in patients of Skin of Color Fitzpatrick III to VI.

Jeanine Downie MD, FAAD1, Megan Kera, PA-C1, Behrooz Kasraee, MD2, Deepa Sunkari, MD2
1Image Dermatology PC Montclair, NJ, USA , 2Scientis, USA

Abstract:

Introduction:

Cysteamine hydrochloride is known for its potent depigmenting effect since 1960’s when it was tested through injecting cysteamine into the black goldfish skin (1). A few years later, in vivo studies showed the higher depigmenting efficacy of this molecule compared to hydroquinone (2).

In addition, cysteamine also has known anti-carcinogenic and anti-melanoma effects.

Superiority to hydroquinone was recently confirmed in vivo (3). However, cysteamine has never been utilizable in humans for topical therapy mainly due to the very offensive odor.

An innovative technology has now been released to decrease the odor in cysteamine. Cysteamine thus became utilizable for the first time in a topical product. This product showed a significant melanogenesis inhibiting effect in different in vitro and in vivo models.

Cysteamine’s mechanism of action includes:
• Double enzyme inhibition: tyrosinase and peroxidase inhibitors
• Dopaquinone quenching: removing dopaquinone from the pathway
• Inhibition of Fenton-type reactions through iron and copper ion quenching
• Reduction of melanin in the stratum corneum into a lighter form through antioxidant effect

Cysteamine is biologically produced in mammalian cells and serves as an intracellular anti-oxidant. It has a long history of safety for human use. It is a natural compound and can even be founds in foods we eat, with highest concentrations in human breast milk. It has a proven tolerability profile with a high patient satisfaction.

Clinical Study Methods and Results:

In a 50 subject, randomized, double-blind placebo-controlled trial. This topical therapeutic modality has shown a 67% reduction of melanin index as measured by mexameter with sixteen weeks of continued use in patients twenty-three to fifty years old with Fitzpatrick types III to VI. In addition, there has been a 58% reduction of the Melasma Assessment Severity Index score. The evaluation methods included clinical assessment for pigmentation, Wood’s lamp for melasma diagnosis, mexameter, digital imaging, and MASI scoring.

Discussion:

Clinical applications with Cysteamine have been vast and very therapeutic for skin of color patients eager to try the latest novel therapies for hyperpigmentation. Case studies have included facial hyperpigmentation such as melasma, post-inflammatory hyperpigmentation due to acne, pseudofolliculitis barbae, periocular hyperpigmentation, as well as hyperpigmentation on the body. Visible improvements have been seen as early as two weeks, with maximum therapeutic benefits by week sixteen.

References:

1. Besouw, Martine; Masereeuw, Rosalinde; van den Heuvel, Lambert; Levtchenko, Elena (2013). “Cysteamine: an old drug with new potential”. Drug Discovery Today. 18 (15-16): 785–792
2. Chavin, W.; Schlesinger, W. (1966). “Some potent melanin depigmentary agents in the black goldfish”. Die Naturwissenschaften 53(16): 413–414.
3. Frenk E, Pathak MA, Szabo G, Fitzpatrick TB. (1968). “Selective action of mercaptoethylamines on melanocytes in mammalian skin: experimental depigmentation”. Arch Dermatol 97:465–77
4. Mansouri, P.; Farshi, S.; Hashemi, Z.; Kasraee, B. (2015).”Evaluation of the efficacy of cysteamine 5% cream in the treatment of epidermal melasma: a randomized double-blind placebo-controlled trial”. The British Journal of Dermatology. 173 (1): 209–217.

Halobetasol Propionate 0.01% Lotion in the Treatment of Moderate-to-Severe Plaque Psoriasis in a Hispanic Population: Post Hoc Analysis of Two Phase 3 Trials

Author Contact Information:
Abby Jacobson
[email protected]

Seemal Desai, MD1; Brad Glick, DO, MPH2; James Q Del Rosso, DO3; Abby Jacobson, MS, PA-C4
1Innovative Dermatology, PA, Plano, TX and The University of Texas Southwestern Medical Center, Dallas, TX; 2GSI Clinical Research, Margate, FL; 3JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; 4Ortho Dermatologics*, Bridgewater, NJ
*Ortho Dermatologics is a division of Bausch Health US, LLC

Topical corticosteroids are the mainstay of psoriasis treatment, though clinical data in Hispanic patients are limited. The objective of this analysis was to evaluate efficacy and safety of halobetasol propionate (HP) 0.01% lotion in Hispanic patients with moderate-to-severe plaque psoriasis. In two phase 3, multicenter, double-blind studies, patients were randomized 2:1 to receive HP or vehicle lotion once-daily for 8 weeks, with a 4-week posttreatment follow-up. A pooled, post hoc analysis was conducted in a subset of Hispanic participants (HP, n=76; vehicle, n=43). Efficacy assessments included treatment success (≥2‑grade improvement from baseline in the Investigator’s Global Assessment [IGA] score and score of ‘clear’ or ‘almost clear’ [primary endpoint]), impact on individual signs of psoriasis, and change in affected body surface area (BSA). Treatment-emergent adverse events (TEAEs) were evaluated. At week 8, 38.8% of participants achieved treatment success with HP lotion versus 10.3% on vehicle (P=0.001); significant differences versus vehicle were observed as early as week 4 and were sustained posttreatment. Psoriasis signs were also reduced at week 8, with more HP‑treated participants achieving ≥2-grade improvement in erythema (49.1%), plaque elevation (52.8%), and scaling (57.8%) compared with vehicle (13.1%, 25.3%, and 24.0%, respectively; P<0.05 all). Participants in the HP lotion group had a mean 33.1% reduction from baseline in affected BSA at week 8 versus a 9.7% reduction with vehicle (P=0.001), with significant differences observed as early as week 2. Treatment-related TEAEs with HP lotion through week 8 were application site infection and application site dermatitis (n=1 each). HP lotion was associated with significant, rapid, and sustained reductions in disease severity in a Hispanic population with moderate-to-severe psoriasis, with good tolerability and safety over 8 weeks of once-daily use.

Funding:

Ortho Dermatologics

Novel Polymeric Tazarotene 0.045% Lotion for Moderate-to-Severe Acne: Pooled Phase 3 Analysis by Race

Author Contact Information:
Eric Guenin
[email protected]

Fran E Cook-Bolden, MDa; Neal Bhatia, MDb; Jonathan S Weiss, MDc; Neil Sadick, MDd; Stephen K Tyring, MD, PhDe; Eric Guenin, PharmD, PhD, MPHf; Anya Loncaric, MSg; Susan Harris, MSh aFran E. Cook-Bolden, MD, PLLC and Department of Dermatology, Mount Sinai Hospital Center, New York, NY; bTherapeutics Clinical Research, San Diego, CA; cGeorgia Dermatology Partners, and Gwinnett Clinical Research Center, Inc., Snellville, GA; dDepartment of Dermatology, Weill Cornell Medical College, New York, NY and Sadick Dermatology, New York, NY; eUniversity of Texas Health Science Center, Houston, TX; fOrtho Dermatologics,* Bridgewater, NJ; gBausch Health US, LLC,* Petaluma, CA; hBausch Health US, LLC,* Bridgewater, NJ
*Bausch Health US, LLC is an affiliate of Bausch Health Companies Inc. Ortho Dermatologics is a division of Bausch Health US, LLC.

Character count (with spaces):

1,896

Acne vulgaris and inflammation-associated sequelae are highly prevalent in populations with skin of color. The objective of this analysis was to evaluate tazarotene 0.045% lotion by self-identified race in the pivotal trials. In two phase 3, double-blind, 12-week studies (NCT03168334; NCT03168321), participants with moderate-to-severe acne were randomized 1:1 to tazarotene 0.045% lotion or vehicle lotion (N=1,614). This pooled, post hoc analysis included subsets of participants segmented by white (n=1,191) or black race (n=262). Coprimary endpoints were inflammatory/noninflammatory lesion counts and treatment success (defined as at least a 2-grade reduction from baseline in Evaluator’s Global Severity Score and a score of ‘clear’ or ‘almost clear’). Treatment-emergent adverse events (TEAEs) and cutaneous safety and tolerability were also evaluated. At week 12, tazarotene 0.045% lotion led to significantly greater LS mean percent changes from baseline versus vehicle in inflammatory and noninflammatory lesions in white participants (tazarotene 0.045% vs vehicle; inflammatory: -57.6% vs -45.0%; noninflammatory: -56.1% vs -40.7%; P<0.001, both). Black participants had significantly greater reductions in noninflammatory lesions with tazarotene 0.045% versus vehicle (-52.6% vs 44.5%; P<0.05). Treatment success rates were higher for white and black tazarotene-treated participants (white: 31.2%; black: 29.6%) versus vehicle (16.7% and 19.6%, respectively). Similar TEAE rates were observed in tazarotene-treated white (28.7%) and black (24.8%) participants and most TEAEs were mild-to-moderate in severity. The incidence of hyperpigmentation decreased in black tazarotene-treated participants from baseline to week 12. Tazarotene 0.045% lotion demonstrated efficacy and was well tolerated across white and black subpopulations in this pooled analysis.

Funding:

Ortho Dermatologics

Novel Polymeric Tazarotene 0.045% Lotion for Moderate-to-Severe Acne: Pooled Phase 3 Analysis by Race

Fran E Cook-Bolden, MDa; Neal Bhatia, MDb; Jonathan S Weiss, MDc; Neil Sadick, MDd; Stephen K Tyring, MD, PhDe; Eric Guenin, PharmD, PhD, MPHf; Anya Loncaric, MSg; Susan Harris, MSh aFran E. Cook-Bolden, MD, PLLC and Department of Dermatology, Mount Sinai Hospital Center, New York, NY; bTherapeutics Clinical Research, San Diego, CA; cGeorgia Dermatology Partners, and Gwinnett Clinical Research Center, Inc., Snellville, GA; dDepartment of Dermatology, Weill Cornell Medical College, New York, NY and Sadick Dermatology, New York, NY; eUniversity of Texas Health Science Center, Houston, TX; fOrtho Dermatologics,* Bridgewater, NJ; gBausch Health US, LLC,* Petaluma, CA; hBausch Health US, LLC,* Bridgewater, NJ
*Bausch Health US, LLC is an affiliate of Bausch Health Companies Inc. Ortho Dermatologics is a division of Bausch Health US, LLC.

Character count (with spaces):

1,896

Acne vulgaris and inflammation-associated sequelae are highly prevalent in populations with skin of color. The objective of this analysis was to evaluate tazarotene 0.045% lotion by self-identified race in the pivotal trials. In two phase 3, double-blind, 12-week studies (NCT03168334; NCT03168321), participants with moderate-to-severe acne were randomized 1:1 to tazarotene 0.045% lotion or vehicle lotion (N=1,614). This pooled, post hoc analysis included subsets of participants segmented by white (n=1,191) or black race (n=262). Coprimary endpoints were inflammatory/noninflammatory lesion counts and treatment success (defined as at least a 2-grade reduction from baseline in Evaluator’s Global Severity Score and a score of ‘clear’ or ‘almost clear’). Treatment-emergent adverse events (TEAEs) and cutaneous safety and tolerability were also evaluated. At week 12, tazarotene 0.045% lotion led to significantly greater LS mean percent changes from baseline versus vehicle in inflammatory and noninflammatory lesions in white participants (tazarotene 0.045% vs vehicle; inflammatory: -57.6% vs -45.0%; noninflammatory: -56.1% vs -40.7%; P<0.001, both). Black participants had significantly greater reductions in noninflammatory lesions with tazarotene 0.045% versus vehicle (-52.6% vs 44.5%; P<0.05). Treatment success rates were higher for white and black tazarotene-treated participants (white: 31.2%; black: 29.6%) versus vehicle (16.7% and 19.6%, respectively). Similar TEAE rates were observed in tazarotene-treated white (28.7%) and black (24.8%) participants and most TEAEs were mild-to-moderate in severity. The incidence of hyperpigmentation decreased in black tazarotene-treated participants from baseline to week 12. Tazarotene 0.045% lotion demonstrated efficacy and was well tolerated across white and black subpopulations in this pooled analysis.

Funding:

Ortho Dermatologics

Quality of Life and Perceptions of Disease in Patients with Central Centrifugal Cicatricial Alopecia

Author Contact Information:
Abena Maranga
[email protected]

Mina-Abena Maranga1* and Fritzlaine C. Roche1,2*, MS, Maryam Alausa1, Tara McWilliams3, MS, Susan C. Taylor, MD**1
1Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104 2University of Rochester School of Medicine & Dentistry, Rochester, NY 14642
3Biostatistics Analysis Center, University of Pennsylvania, Philadelphia, PA 19104
*Contributed equally to this work.
**Corresponding Author:
Susan C. Taylor, MD
Associate Professor, Department of Dermatology
Perelman School of Medicine at the University of Pennsylvania
Room 768 South Tower
3400 Civic Center Blvd
Philadelphia, PA 19104

Poster Abstract

Background:

Central centrifugal cicatricial alopecia (CCCA) is a type of scarring hair loss that predominantly affects black women, with limited treatment options focused on preventing the progression of disease. There are limited data measuring the quality of life among patients with CCCA.

Objective:

To understand the impact of CCCA on patients’ quality of life (QoL) and identify specific concerns with increased influence on overall quality of life.

Methods:

A total of 241 patients over the age of 18 with a biopsy-proven diagnosis of CCCA were administered an anonymous survey. The 22-item questionnaire adapted specifically for patients with CCCA was administered to assess the impacts of subjective symptoms, relationship issues, and objective signs on overall QoL. The QoL was indexed using a hierarchical structural equation model (SEM) with a Newton-Raphson optimization technique. A QoL index (QLI) score > 50 was considered as significant impairment of quality of life.

Results:

Of the 56 respondents that completed the survey, 34 (60.7%) had a QLI score over 50, and the average QLI score was 55.64. Among the three areas in which the CCCA-QLI is divided, ‘subjective symptoms’ and ‘objective signs’ had scores indicating significantly impaired quality of life (78.74 and 56.13). Although these two categories had the highest QLI scores, ‘relationship issues’ was the highest overall driver of impaired quality of life in this population.

Limitations:

Equations generated through this modeling must be remodeled to fit the results of the new population, limiting the generalizability of our equations. Selection bias was another potential limitation, as participants were primarily recruited from a specialty hair clinic.

Conclusion:

Our analysis demonstrates that CCCA has a significant negative impact on QoL. Dermatologists caring for patients with CCCA should remain sensitive to the emotional and psychological toll this diagnosis has on its patients, and provide appropriate resources to better support patients with this diagnosis.

Character count:

1749 (100000 max)

Long-Term Efficacy and Safety of Dupilumab in Adolescents With Atopic Dermatitis: Results From an Open-Label Extension Trial (LIBERTY AD PED-OLE)

Andrew Blauvelt1, Iftikhar Hussain2, Zhen Chen3, Ana B. Rossi4, Ashish Bansal3
1Oregon Medical Research Center, Portland, OR, USA; 2Vital Prospects Clinical Research Institute, PC, Tulsa, OK, USA; 3Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 4Sanofi Genzyme, Cambridge, MA, USA

Introduction:

In the USA, dupilumab is approved for treatment of patients aged ≥12 years with moderate-to-severe atopic dermatitis (AD).1 Here, we report efficacy and safety data from 299 adolescent patients (≥12 to <18 years) with moderate-to-severe AD who had previously participated in a phase 2a study of dupilumab (AD-1412, NCT02407756) and subsequently enrolled in an open-label extension (OLE) study (LIBERTY AD PED-OLE, NCT02612454).

Methods:

In the phase 2a study, patients received a single weekly dose of dupilumab (2mg/kg or 4mg/kg) for 5 weeks. In the subsequent OLE study, patients continued weekly dupilumab (2mg/kg or 4mg/kg). We evaluated efficacy and safety data from the OLE study (n=299) with a data cutoff date of March 29, 2019.

Results:

At Week 52, 46/106 (43.4%) of patients achieved an Investigator’s Global Assessment (IGA) score of 0/1. The mean percent change (standard deviation) in Eczema Area and Severity Index (EASI) from the AD-1412 baseline to Week 52 of the OLE study (n=104) was −83.6% (23.3). 84/104 (80.8%) of patients achieved ≥75% reduction from baseline in EASI (EASI-75) relative to their AD-1412 baseline.

Treatment-emergent adverse events (TEAEs) were reported in 74.2% of patients; 18.1% of patients had a drug-related TEAE. The most common TEAEs were nasopharyngitis (21.1%), atopic dermatitis exacerbation (19.4%), upper respiratory tract infections (12.4%), headache (9.4%), and oropharyngeal pain (5.7%). Five patients reported serious TEAEs, of which none were treatment-drug related.

Conclusion:

Data from this open-label extension trial of dupilumab support the long-term efficacy and safety of dupilumab in adolescents with AD.

Pharmacokinetics, Safety, and Efficacy of Dupilumab in Children Aged ≥2 to <6 Years With Severe, Uncontrolled Atopic Dermatitis (LIBERTY AD PRE-SCHOOL)

Eric L. Simpson1, Benjamin Lockshin2, Mohamed Kamal3, John D. Davis3, Xian Sun3, Ana B. Rossi4, Ashish Bansal3
1Oregon Health and Science University, Portland, OR, USA; 2Georgetown University, Rockville, MD, USA; 3Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 4Sanofi Genzyme, Cambridge, MA, USA

Introduction:

Limited treatment options are available for children with moderate-to-severe atopic dermatitis (AD). Dupilumab is a fully human monoclonal antibody that inhibits signaling of interleukin-4 and interleukin-13, cytokines that are key drivers of type 2 inflammation.1,2 Dupilumab is approved for subcutaneous administration every 2 weeks for patients aged ≥12 years with moderate-to-severe AD in the USA.3 We report pharmacokinetics, safety, and efficacy of dupilumab in children with severe AD inadequately controlled with topical therapies from the LIBERTY AD PRE-SCHOOL trial (NCT03346434).

Methods:

Patients aged ≥ 6 months to <6 years (N=40), stratified by age and region, were randomized 1:1 to a single subcutaneous dose of dupilumab 3mg/kg or 6mg/kg. We report data for the ≥2- to <6-year-old cohort (n=10 per treatment group).

Results:

Treatment groups had similar baseline characteristics. Single doses of dupilumab resulted in a slightly less than dose-proportional increase in mean serum concentrations. Treatment-emergent adverse events were similar across groups. 1 serious adverse event (anaphylactic reaction due to existing peanut allergy) was reported in the 3mg/kg group. At Wk4, for the 3mg/kg and 6mg/kg treatment groups, respectively, patients had improvements from baseline in Eczema Area and Severity Index (EASI): mean percentage change (standard deviation) –26.6(47.4)/–48.7(28.9) (P=0.1097/P=0.0005); and EASI-50/EASI-75 was observed in 30%/40% and 20%/30% patients.

Conclusions:

Single doses of dupilumab in children aged ≥2 to <6 years showed a slightly less than dose-proportional increase in mean serum concentrations and caused improvements in AD signs and symptoms. Dupilumab was well tolerated; safety was generally consistent with previous findings in children.

Increased incidence of conjunctivitis with dupilumab treatment in adolescents appears to be specific to atopic dermatitis

Marjolein de Bruin-Weller1, Eric L. Simpson2, Jonathan Corren3, Zhen Chen4, Ana B. Rossi5, Kazuhiko Arima6, Faisal A. Khokhar4, Ashish Bansal4
1University Medical Center, Utrecht, Netherlands; 2Oregon Health & Science University, Portland, OR, USA; 3David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; 4Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA; 5Sanofi Genzyme, Cambridge, MA, USA; 6Sanofi K.K., Tokyo, Japan

Background:

To report the incidence of conjunctivitis in adolescents treated with dupilumab or placebo in clinical trials for atopic dermatitis (AD) or asthma.

Methods:

Patients aged ≥12 to <18 years received subcutaneous (SC) dupilumab 300mg every 4 weeks (q4w; n=83), 200/300mg every 2 weeks (q2w; n=82), or placebo (n=85) for 16 weeks for moderate-to-severe AD in the randomized, placebo-controlled LIBERTY AD ADOL trial (NCT03054428); or add-on SC dupilumab 200mg q2w (n=34), 300mg q2w (n=34), or placebo (n=39) for 52 weeks for uncontrolled moderate-to-severe asthma in the randomized, placebo-controlled LIBERTY ASTHMA QUEST trial (NCT02414854). Conjunctivitis events (MedDRA Preferred

Terms:

conjunctivitis, allergic conjunctivitis, bacterial conjunctivitis, viral conjunctivitis, adenoviral conjunctivitis, atopic keratoconjunctivitis) during the treatment period were summarized.

Results:

The proportion of patients with ≥1 conjunctivitis event was 4.7%/10.3% in the placebo/combined dupilumab (300mg q4w or 200/300mg q2w) groups in the AD ADOL trial, and 2.6%/2.9% in the placebo/combined dupilumab (200mg or 300mg q2w) groups in the ASTHMA QUEST trial. 2.4%/7.9% of patients (placebo/combined dupilumab) in the AD ADOL trial had ≥1 conjunctivitis event considered related to study drug; no events were considered related to study drug in the ASTHMA QUEST trial. Conjunctivitis cases in both trials were mostly mild or moderate in severity, most resolved during the treatment period, and none resulted in permanent discontinuation of study treatment. Dupilumab demonstrated significant efficacy and acceptable safety vs placebo in the AD ADOL and ASTHMA QUEST trials.

Conclusion:

A higher incidence of conjunctivitis was observed in adolescents treated with dupilumab than with placebo only in the AD clinical trial, whereas the incidence of conjunctivitis in adolescents in the asthma clinical trial was low and similar between dupilumab and placebo. Similar results were reported in adults

Dupilumab Improves Clinical Signs Including Lichenification in Patients with Atopic Dermatitis (CHRONOS)

Atsuyuki Igarashi1, Shinichi Imafuku2, Takafumi Etoh3, Thomas Bieber4, Seong-Jun Seo5, Zhen Chen6, Hiroyuki Fujita7, Kazuhiko Arima7, Ana B. Rossi8, Brad Shumel6
1NTT Medical Center Tokyo, Tokyo, Japan; 2Fukuoka University, Fukuoka, Japan; 3Tokyo Teishin Postal Services Agency Hospital, Tokyo, Japan; 4Department of Dermatology and Allergy, University of Bonn, Bonn, Germany; 5Chung-Ang University Hospital, Seoul, Republic of Korea; 6Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA; 7Sanofi K.K., Tokyo, Japan; 8Sanofi Genzyme, Cambridge, MA, USA

Aim:

The effect of dupilumab (DUP), a human anti-IL-4R mAb, on atopic dermatitis (AD) signs from the phase 3 study LIBERTY AD CHRONOS (NCT02260986) are reported.

Methods:

Adults with moderate-to-severe AD were randomized to DUP 300mg plus topical corticosteroids (TCS) weekly (qw; n=319), every 2 weeks (q2w; n=106), or placebo (n=315) for 52 weeks. Effects on AD signs were evaluated by Global Individual Signs Score (GISS).

Results:

At Week 52, DUP+TCS significantly improved erythema, infiltration/papulation, excoriation, and lichenification. LS mean (SE) changes from baseline in lichenification (scores of 0-3) were –1.5 (0.04) for qw, –1.5 (0.08) for q2w and –1.0 (0.07) with placebo, and LS mean (SE) percent changes from baseline were –66.6% (2.38), –69.7% (4.03) and –45.2% (3.38) (P < 0.0001 vs placebo+TCS). DUP was generally well tolerated.

Conclusion:

At Week 52 DUP+TCS significantly improved AD signs, including lichenification, compared with placebo+TCS in adults with moderate-to-severe AD.

Association of Breast Cancer in Patients with Central Centrifugal Cicatricial Alopecia: A Pilot Study

Author Contact Information:
Jessica Brown-Korsah
[email protected]

Jessica B. Brown-Korsah1,2, Fritzlaine C. Roche, MS1,3, Susan C. Taylor, MD1
1Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
2Case Western Reserve University School of Medicine, Cleveland, OH
3University of Rochester School of Medicine & Dentistry, Rochester, NY

Background:

Peptidyl arginine deiminase 3 (PADI3) expression has been shown to play a role in breast cancer and colorectal cancer pathogenesis. Nearly 25% of patients with central centrifugal cicatricial alopecia (CCCA) have reduced PADI3 expression. No studies to date have examined the association between breast and colorectal cancer and CCCA.

Objective:

We sought to evaluate the association between breast cancer (BC) and colorectal cancer (CRC) in black women with CCCA, compared to controls without CCCA within the University of Pennsylvania Health System.

Study Design:

In this cross-sectional study, EPIC’s Clarity database was queried from April 13, 2016 to April 13, 2020 to identify black women with CCCA, via ICD-10 code, L66.9. Patients with BC and/or CRC were identified using at least 1 ICD-9 or ICD-10 code. The electronic medical records (EMRs) of women with L66.9 were individually reviewed to identify biopsy proven CCCA. Rates of BC and CRC in black women with CCCA were compared to age-, sex-, race-matched controls.

Results:

Among 225416 black women, we identified 742 patients with the ICD-10 code, L66.9. Approximately 4.7% of women with L66.9 (CCCA) in their EMR had a history of BC, in comparison to 1.8% of controls (OR, 2.68; 95% CI, 1.90 – 3.76; P < .001). Of the patients with biopsy-proven CCCA (159 out of 742), 4.4% had a history of BC compared to 1.8% controls (OR, 2.49, 95% CI, 1.17 – 5.32; P = .03). The rate of CRC among women with a diagnostic code of L66.9 did not significantly differ in comparison to controls (OR, 0.43; 95% CI, 0.061 – 3.07; P = .73). The average age of diagnosis and the distribution of the age of diagnosis with BC among patients with CCCA compared to controls did not statistically differ.

Conclusion:

At our center, CCCA patients were nearly 3 times more likely to have a history of breast cancer when compared to controls. This association between BC and CCCA may be due to mutations in PADI3 or due to several unknown genetic and/or environmental factors. Genetic and multicenter studies are needed to further evaluate the relationship between BC and CCCA and the pathogenesis of CCCA.

Amitriptyline-Induced Multifocal Oral Mucosal Dyspigmentation—A Unique Case Bridging Pharmacopsychodermatology in Skin of Color

Author Contact Information:
Abrahem Kazemi
[email protected]

Kazemi Aa, Shulman Ka,b, and Russo Ma
a) Department of Dermatology, New York Medical College/Metropolitan Hospital Center. New York, NY
b) Dermpath Diagnostics, Port Chester, NY

Vulnerable ethnic patient populations in the dermatology clinic require special attention, provider cultural competency, and a thorough review of their history with the assistance of a certified foreign language interpreter where applicable. Herein, we present the case of a middle aged Bengali female whose chief complaint of periorificial hypopigmentation lead to an oral cavity examination, revealing a unique, hidden disease process.

A 43 year old South Asian, Bengali-only-speaking female with a past medical history of major depressive disorder and schizophrenia (i.e., schizoaffective disorder) well-controlled with compliant use of risperidone for 20 years and amitriptyline for 12 years presented to the dermatology clinic with a chief complaint of periorificial hypopigmentation of six months’ duration. She reported using a peroxide-containing toothpaste twice daily and a moisturizing SPF 15 facial cream. She denied use of tobacco, alcohol, illicit drugs, or chewing betel quid, paan or other exotic plants. On physical examination, a continuous, periorifical, mildly hypopigmented linear patch surrounding the vermilion border of the upper and lower cutaneous lips was noted in a patient with Fitzpatrick Skin Type (FST) IV.
On examination of the oral cavity, slate-gray pigmented, ill-defined macules and patches were noted on the superior and inferior mucosal lips, buccal mucosa, gingiva, and dorsal tongue without secondary changes which was unnoticed by the patient. A differential diagnosis of exogenous dyspigmentation versus black hairy tongue versus an ethnic variant of normal physiologic pigmentation was considered, and a biopsy was deemed the best next step in management.

Upon tangential shave biopsy of the inferior mucosal lip, dermatopathology results were obtained. A Fontana-Masson stain highlighted melanin in basal keratinocytes, and free granules of melanin as well as a few melanophages in the superficial dermis. Perl’s stain for iron was negative. Altogether, the clinical presentation, dermatopathology results, and a thorough review of the patient’s medications supported a diagnosis of drug-induced multifocal oral mucosal dyspigmentation associated with amitriptyline.

Due to stability of the patient’s major depressive disorder (MDD), it was in the best interest of the patient to continue amitriptyline despite knowledge of likely progression of the oral mucosal dyspigmentation. Cultural competency, effective communication with use of a certified language interpreter, and establishing trust with this patient ultimately facilitated clinching the diagnosis in this case and educating the patient regarding her condition.

Dermatologists must remember to provide well-rounded, culturally-sensitive, high-quality care to all skin of color patients, and especially those with a known, concomitant mental illness.

Natural Cosmeceutical Ingredients For Management Of Hyperpigmentation In Hispanic/Latino Women

Author Contact Information:
Aileen Dow
[email protected]

Aileen Dow¹; Emily López Santa, BS²; Michael Murphy, MD^2
1Si SKIN Organics, Canton, CT; ²Department of Dermatology, UConn Health, Farmington, CT

BACKGROUND:

Disorders of hyperpigmentation, such as melasma, post-inflammatory hyperpigmentation and lentigines, pose significant cosmetic concerns for women of Hispanic/Latino race and ethnicity. Natural ingredients are gaining popularity as alternative, safe and effective, topical depigmenting agents.

OBJECTIVE:

To review clinical studies evaluating the use of natural ingredients in topical management of hyperpigmentation in Hispanic/Latino women.

METHODS:

We performed a systematic review of scientific and medical electronic databases for randomized controlled trials (RCTs) and non-randomized reports on topical natural agents for the treatment of disorders of hyperpigmentation, using PRISMA guidelines.

RESULTS:

Review of the literature revealed relatively few (n=7) clinical studies (including 6 RCTs) that evaluated the topical management of hyperpigmentation using natural ingredients with specific reference to women of Hispanic/Latino race and ethnicity. Despite limited research data, a small number (n=7) of natural ingredients demonstrated efficacy and safety as depigmenting agents in this cohort. These include niacinamide, soy, azelaic acid, ascorbic acid, licorice, emblica, and belides.

CONCLUSIONS:

Several natural ingredients have scientific data supporting their potential efficacy as topical treatments for disorders of hyperpigmentation in women of Hispanic/Latino race and ethnicity. However, the paucity of robust cosmetic trials is this setting reflects the generalized under-representation of Hispanic/Latino subjects in clinical studies of other skin conditions. Many in vivo cutaneous trials of natural ingredients are limited by study design, including subject selection and short duration. Further research is needed to determine long term efficacy, safety, optimal concentration and formulation of natural ingredients for topical management of hyperpigmentation in Hispanic/ Latino women.

Angélica Dass’ Humanae, a Spectrum of Skin Tones

A Novel Skin Brightening Technology

Author Contact Information:
Zoe Draelos
[email protected]

Dr. Giorgiana Giancola, Ph.D.
[email protected]

Zoe Diana Draelos, MD, Aaron Cohen, PhD, Junhong Mao, PhD, Thomas Boyd, PhD2

Background Skin brightening is an important appearance enhancing attribute in all Fitzpatrick skin types. Skin brightening encompasses improving several criteria to include lightening of dyspigmentation, enhancing skin color evenness, smoothing the skin surface, and optimizing light reflection. This research examined a topical facial moisturizer formulation containing ascorbic acid to induce pigment lightening, hexylresorcinol to produce exfoliation and improve skin color evenness, and cyclopentasiloxane with other silicone-based polymers to create a light reflective film.

Methods 42 female subjects with normal or dry skin 35-55 years of age with Fitzpatrick skin types I-VI were enrolled. These subjects possessed signs of aging to include discoloration, uneven skin tone, and fine lines. Following completion of informed consent and after meeting all inclusion criteria and none of the exclusion criteria, subjects with lack of skin tone brightening, lack of skin tone evenness, fine lines, wrinkles, and global appearance issues were enrolled in the study. Subjects were provided with the study product for once daily use and sunscreen for use as needed during the study.

The dermatologist investigator evaluated lack of skin tone brightening, lack of skin tone evenness, fine lines, wrinkles, and global appearance issues at baseline, week 2, week 4, week 8, and week 12. Investigator tolerability was assessed in terms of erythema, edema, dryness, and peeling. Subject tolerability was assessed in terms of stinging, tingling, itching, and burning. All criteria were evaluated at baseline, week 2, week 4, week 8, and week 12 on a 5-point ordinal scale (0=none, 1=minimal, 2=mild, 3=moderate, 4-severe).

VISIA CR4.3 photography was conducted of the front, right, and left face with visible light at baseline, week 4, week 8, and week 12 and the investigator assessed the photos comparing facial pigmentation at baseline to week 12 using the following ordinal scale: 0-excellent improvement, 1=modest improvement, 2=slight improvement, 3=no change, 4=worsening.

Statistical significance was defined as p less than or equal to 0.05. The ordinal nonparametric data obtained was evaluated as change from baseline using a Wilcoxon signed rank test.

Results 42/42 subjects successfully completed the 12 week study with no adverse events. There was a statistically significant increase in subject reported facial stinging (p=0.008), tingling (p=0.004), and burning (p=0.016) at 2 weeks. These noxious sensory stimuli improved with continued use at week 12 with only stinging being a statistically significant concern (p=0.008). These sensory issues could be due to the hexylresorcinol, an ingredient used in face peels as a penetration enhancer. In order to decrease sensory issues, the dermatologist investigator advised subjects not to over apply the product, not to apply the product to a wet face, and not to apply the product too close to the eyes, nose, or mouth.

After 2 weeks of use, the dermatologist investigator noted a statistically significant improvement in facial brightening (p<0.001). More cumulative improvement was seen at week 4, with statistically significant improvement in brightening (p<0.001) and evenness (p=0.016). At week 8, there was significant improvement (p<0.001) in brightening, evenness, and global appearance with improvement also seen in fine lines (p=0.008). The greatest cumulative improvement was seen at week 12 in brightening, evenness, fine lines, and global appearance (p<0.001).

The investigator compared the week 12 photos to baseline for facial pigmentation and rated 36% of the subjects with excellent improvement, 21% with modest improvement, 29% with slight improvement, and 14% demonstrated no change. No subject demonstrated pigment worsening.

Discussion

Facial skin brightening encompasses abundant light reflection from an evenly pigmented skin surface conferring the visual appearance of healthy skin. Since skin brightening is multifactorial, this formulation was designed to brighten the skin by containing an innovative combination of active ingredients. Hexylresorcinol is a time-tested penetration enhancing ingredient in dermatology that also induces stratum corneum exfoliation. The hexylresorcinol in this moisturizer produced peeling of the pigment containing corneocytes while inhibiting tyrosinase and enhancing penetration of vitamin C. Vitamin C also inhibited tyrosinase, the rate-limiting step in melanin synthesis, improving skin pigmentation. These ingredients were placed in a silicone polymer base (cyclopentasiloxane, polysilicone-11, polymethylsilsesquioxane) to create a smooth film over the skin surface while delivering the active ingredients. Finally, the formulation contained a variety of antioxidants (tocopherol, Silybum Marianum fruit extract, Hordeum Distichon (barley) extract, Citrus Aurantium Dulcis (orange) oil, Phellodendron Amurense bark extract, Santalum Album (Sandalwood) wood extract) to stabilize the vitamin C, but also provide oxidative protection to the skin.

Conclusion

Hexylresorcinol and vitamin C in a silicone polymer moisturizing vehicle were effective in producing skin brightening in women of all Fitzpatrick skin types.
References Draelos ZD. Skin lightening preparations and the hydroquinone controversy. Dermatol Ther 2007;20(5):308-313

Rendon MI, Gaviria JI. Review of skin lightening agents. Dermatol Surg 2005;31(1s):886-889

Petit L, Pierard GE. Skin-lightening products revisited. Int J Cosmet Sci 2003;25:169 181

Disclosures

Zoe Diana Draelos, MD, received an educational grant from Colgate-Palmolive Co. and PCA Skin to conduct this research.