2019 dermMentors™ Resident of Distinction Award™

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Sponsored by Beiersdorf Inc

The dermMentors™ Resident of Distinction Award™ recognizes top residents in dermatology. DermMentors.org and the dermMentors™ Resident of Distinction Award™ are sponsored by Beiersdorf Inc and administered by DermEd, Inc. The 2019 dermMentors™ Residents of Distinction™ presented new scientific research during the general sessions of the 15th Annual Coastal Dermatology Symposium on October 5, 2019.

Overall Grand Prize
Chronic Inflammatory Skin Diseases Are Associated With Herpes Zoster in US Inpatients

Raj Chovatiya, MD, PhD; Jonathan I. Silverberg MD, PhD, MPH, Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
Disclosures: None.

Background
Herpes zoster (HZ) is a vaccine-preventable, viral eruption that affects 1 of every 3 people in the United States in their lifetime. Despite evidence-based guidelines and public health advocacy, many high-risk individuals remain unvaccinated and at risk for significant morbidity from HZ. Patients with chronic inflammatory skin diseases (CISDs), including allergic and autoimmune conditions, have potential risk factors for HZ, including long-term use of systemic corticosteroids and immunosuppressants, and immune dysregulation in the skin and periphery. We sought to determine whether CISDs are associated with HZ in hospitalized patients in the US.

Methods
Data were analyzed from the 2002-2012 Nationwide Inpatient Sample, a representative 20% cross-sectional cohort of US hospitalizations (N=68,490,364 children and adults).

Results
The estimated incidence of primary hospitalization for HZ in the US population was 5.0 per 100,000 persons from 2002-2012. In multivariable weighted logistic regression models including age, sex, race/ethnicity, insurance, mean household income, and long-term systemic corticosteroid use, primary hospitalization for HZ was associated with multiple CISDs: atopic dermatitis (adjusted odds ratio [95% confidence interval]: 1.38 [1.14-1.68]), psoriasis (4.78 [2.83-8.08]), pemphigus (1.77 [1.01-3.12]), bullous pemphigoid (1.77 [1.01-3.12]), mycosis fungoides (3.79 [2.55-5.65]), dermatomyositis (7.31 [5.27-10.12]), systemic sclerosis (1.92 [1.47-2.53]), cutaneous lupus erythematosus (1.94 [1.10-3.44]), vitiligo (2.00 [1.04-3.85]), and sarcoidosis (1.52 [1.22-1.90]). Lichen planus (3.01 [1.36-6.67]), Sézary syndrome (12.14 [5.20-28.31]), morphea (2.74 [1.36-5.51]), and pyoderma gangrenosum (2.44 [1.16-5.13]) showed increased odds in bivariable models but not in multivariable models. Whereas, hidradenitis suppurativa, chronic idiopathic/spontaneous urticaria, and alopecia areata were not associated with HZ. Similar results were seen in sensitivity analyses among adults age <60 and <50 years. Significant predictors of primary hospitalization for HZ among patients with CISDs included older age, female sex, non-white race/ethnicity, decreasing number of chronic comorbid conditions, and long-term systemic corticosteroid use. Inpatient length of stay and/or inflation adjusted cost of care were significantly higher in inpatients with CISD with vs. without a primary diagnosis of HZ.

Conclusion
CISDs are associated with increased hospitalization for HZ, prolonged length of inpatient stay and increased cost of hospital care. The associations of CISDs and HZ were significant even below the recommended ages (<60 and <50 years) for vaccination with live and recombinant HZ vaccine, respectively. Additional studies are needed to confirm these findings and determine the mechanisms of VZV reactivation. Patients with CISDs constitute a significant, previously under-recognized group that is high-risk for hospitalization for HZ. Dermatologists are the primary physicians who manage the vulnerable population of CISDs. They should be on the forefront of screening, intervention, and most importantly, vaccination for their patients. Future studies should explore implementation of outpatient HZ vaccination by dermatologists and revised disease-specific guidelines to cover the spectrum of CISDs.

Up next: Buyer Beware or You Might Get Burned...→

Buyer Beware or You Might Get Burned: Unregulated Photosensitizing Agents Available Without Prescription From Major Online Retailers

Kimberly Huerth, MD, MEd, Department of Dermatology, Howard University Hospital, Washington, DC; Olivia Ware, BA, Howard University College of Medicine, Washington, DC; Ginette A. Okoye, MD, Department of Dermatology, Howard University Hospital, Washington, DC; Sharon Bridgeman-Shah, MD, Department of Dermatology, Howard University Hospital, Washington, DC
Disclosures: None.

Background
According to the World Health Organization, the vast majority of the world’s population relies on plant-derived medicine as their primary form of healthcare. Closer to home, these alternative therapies are growing in popularity among American healthcare consumers, in concert with increasing access to such products by means of globalization and the growth of Internet retail. There are numerous reasons why an individual might eschew Western medicine in favor of a more naturopathic approach, including perceived health benefits, cost, prior failure of physician guided treatment, a lack of awareness about the risks these products carry, cultural norms, and desperation born of the psychosocial burden of one’s disease.

A 73-year-old Eritrean man presented to our outpatient dermatology clinic with a severe, acute, phototoxic reaction following the ingestion of Athamanta decoction for the self-directed treatment of vitiligo. The genus Athamanta is in the Apiaceae family and consists of 6 species of flowering plants native to Europe and North Africa. Furanocoumarins are the phototoxic compounds present in these plants, among which psoralen is perhaps the most notorious. The desiccated Athamanta leaves, sought in the absence of medical consultation, had been obtained from a mail order vendor in Egypt which had advertised them as a “miracle effect for curing vitiligo.”

Objective
To determine the extent to which unregulated photosensitizing agents for the treatment of vitiligo are available to consumers from online retailers, including major ones such as Amazon and eBay.

Methods
An online product search of eBay and Amazon, as well as an Internet pharmacy by the name of Cheap Generic, was conducted using search terms “vitiligo treatment,” “psoralen for vitiligo,” “furanocoumarin treatment,” “Athamanta vitiligo,” “Apiaceae vitiligo,” and “leukoderma.” Products generated by the search terms were examined for their route of delivery (topical vs systemic), key photosensitizing ingredient, parent plant, cost to consumer, and country of manufacture. Products that did not identify a known photosensitizing compound, or a plant known to contain a photosensitizing compound, on the list of ingredients were excluded from the analysis.

Results
We identified a total of 11 products—6 listed on Amazon, 3 listed on eBay, and 2 listed by Cheap Generic pharmacy—that had either a photosensitizing compound, or a plant known to contain a photosensitizing compound, on its list of ingredients. 27.3% of products were available in formulations intended for ingestion, such as tablets or powders. 90.9% of products listed psoralen, or a plant known to contain psoralen, as a major ingredient. Of the products that identified the main photosensitizing plant ingredient (72.7%), Psoralea corylifolia was the most common (75%). Products ranged in cost from $3 to $28. The terms “herbal” (54.5%) and “natural” (36.3%) were used most frequently on the packaging and/or website for promotional purposes. While 45.4% of products did not identify a country of origin, of those that did, 66.7% were manufactured in India, while the remainder were prepared in China.

Conclusion
Topically and systemically administered psoralen-containing products for the treatment of vitiligo are widely available without a prescription from several online vendors. These products are affordable and utilize suggestive packaging to tout the benefits of the products, without mention of their risks.

Up next: Collagen VII: A Link Between the Skin and Bone Marrow...→

Collagen VII: A Link Between the Skin and Bone Marrow Via Extracellular Vesicles

Jeffrey D. McBride, MD, PhD, Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, Florida
Disclosures: Dr. McBride has been a consultant with Aegle Therapeutics.

Extracellular vesicles—exosomes, microvesicles, and apoptotic bodies—are ubiquitous in human tissues, circulation, and body fluids. Of these vesicles, exosomes are of growing interest among investigators across multiple fields, including dermatology. The characteristics of exosomes, their associated cargo (nucleic acids, proteins, and lipids), and downstream functions are vastly different, depending on the cell of origin. Specifically, we have discovered that these extracellular vesicles from the bone marrow–derived mesenchymal stem cells stimulate production of basement membrane components by cells that genetically lacked the ability to do so before (ie, collagen VII from fibroblasts derived from patients with recessive dystrophic epidermolysis bullosa). In other words, our work shows that the bone marrow can replenish collagen VII by directly delivering protein but also by transferring messenger RNA, coding for collagen VII, to the epidermolysis bullosa fibroblasts, allowing them to make collagen VII for the first time. Extracellular vesicles, including exosomes, have immediate potential for serving as therapeutics in dermatology over the next decade.

Up next: Genetic Variations in Non-coding Regulatory Regions in Linear Morphea...→

Genetic Variations in Non-coding Regulatory Regions in Linear Morphea
Dawn Zhang Eichenfield, MD, PhD, University of California, San Diego, Medical Center, La Jolla, California
Disclosures: This research was funded by the Women’s Dermatologic Society and the Pediatric Dermatology Research Alliance.

Linear morphea is a chronic inflammatory and pro-fibrotic disease that can be debilitating and disfiguring. It generally presents at an earlier age of onset than other subtypes of morphea. Like other autoimmune diseases, linear morphea presents predominantly in females, has a familial contribution, and has been associated with particular environmental triggers. Beyond this, however, the full pathogenesis of this disease remains unknown. A more thorough understanding of the causes of linear morphea—genetic and environmental—is the first step toward improved diagnosis and treatment.

Lesions of linear morphea predominantly follow Blaschko’s lines, a pattern of lines on the skin thought to represent pathways of epidermal cell migration and proliferation during fetal development. This presentation suggests that genetic mosaicism may be at play, although studies utilizing whole exome sequencing have not found causative somatic genetic mutations in protein-coding regions.^1,2 Recent studies, however, have increasingly shown that genetic diseases, including autoimmune disorders, can be caused by mutations in non-protein coding regions. For example, Castellanos-Rubio et al³ recently identified a long non-coding RNA that plays an essential role in the maintenance of intestinal mucosal immune homeostasis and its genetic polymorphisms contribute to inflammation in celiac disease. New sequencing technologies further highlight the complexities of gene regulation. Recent studies of the ENCODE project estimate hundreds of thousands of non-promoter genomic elements that are regulated in a cell-specific and signal-dependent manner through different transcription factors, non-coding RNAs, as well as other transcriptional regulatory elements.⁴Taken together, this data suggests that genetic mutations in non-coding regulatory regions have the potential to initiate and perpetuate autoimmune disease.

Our hypothesis is that key somatic genetic mutations in non-coding regulatory regions result in altered transcription factor binding and downstream changes in gene expression, which produce a predisposition to development of linear morphea. To test this hypothesis, we are utilizing whole genome sequencing and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-Seq) on normal and lesional skin in a cohort of patients with linear morphea to identify disease-specific regulatory variants. If initial experiments yield candidate genes or regulatory regions, we will validate these loci through functional assays to identify variants that stimulate a pro-fibrotic response.

Altogether, these studies will help identify new insights into key genetic contributions to the pathogenesis and transcriptional regulation of linear morphea. Understanding the molecular and genetic basis of linear morphea is significant as it is the first step toward improved pharmacological treatments and preventive strategies for linear morphea.

References

Higgins R, Smith A, Walchli R, et al. Absence of somatic mutations in linear localized scleroderma. J Investig Dermatol. 2017;137:S271.
Higgins R, Theiler M, Smith A, et al. Genetic architecture of linear localized scleroderma. J Investig Dermatol. 2018;138:S138.
Castellanos-Rubio A, Fernandez-Jimenez N, Kratchmarov R, et al. A long noncoding RNA associated with susceptibility to celiac disease. Science. 2016;352:91-95.
Hoffman MM, Ernst J, Wilder SP, et al. Integrative annotation of chromatin elements from ENCODE data. Nucleic Acids Res. 2013;41:827-841.

Up next: Increasing Evidence for Omalizumab in the Treatment of Bullous Pemphigoid→

Increasing Evidence for Omalizumab in the Treatment of Bullous Pemphigoid

Sarah Lonowski, MD, MBA, Division of Dermatology, University of California Los Angeles, Los Angeles, California
Disclosures: None.

Introduction
Bullous pemphigoid (BP) is a common, debilitating autoimmune blistering disease which is often managed with prednisone and other systemic immunosuppressive medications. Here, we present the largest case series to date evaluating the use of omalizumab for the treatment of BP, providing novel insight and further support for use of this well-tolerated, minimally immunosuppressive agent.

Objective
To review and analyze the experience of patients with BP treated with omalizumab at a single academic institution.

Methods
Retrospective chart analysis of eleven patients with BP treated at a single academic institution over a 32-month period (April 2016–December 2018). Data was obtained through comprehensive review of pathology reports, laboratory data, and physician documentation. Standard descriptive statistics were performed on the data.

Results
Eleven patients were included in the analysis, 5 females (45.5%) and 6 males (54.5%) with a mean age of 78 years (range, 57-95 years). Patients had failed a mean of 2.3 systemic agents prior to initiation of omalizumab. Seven of 11 patients (63.6%) had experienced adverse effects related to prednisone prior to initiation of omalizumab. Six patients (54.5%) had complete clearance of skin lesions after a median duration of 4.4 months on omalizumab, 3 patients (27.3%) had partial response, and 2 patients (18.2%) did not respond to treatment. The median duration of treatment in all patients at the time of analysis was 12.6 months. All 10 patients on prednisone at the time of omalizumab initiation were able to reduce the dose of prednisone, and 5 of 10 patients (50%) were able to discontinue systemic steroids completely. Baseline serum immunoglobulin E (IgE) and eosinophil levels did not predict treatment response. There were no serious treatment-related adverse effects during the treatment period.

Conclusions/Relevance
Omalizumab is a well-tolerated, steroid-sparing agent which has a significant disease-modifying effect in the majority of patients. Baseline serum IgE and eosinophil levels do not appear to predict treatment response, therefore patient selection should not hinge on these lab values. Omalizumab should be considered as a treatment option for any patient requiring systemic treatment for BP, but especially for those who have experienced or are at risk for experiencing adverse effects from systemic steroids.

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