Oral diabetes medications other than dipeptidyl peptidase-4 inhibitors are not associated with bullous pemphigoid: a Finnish nationwide case control study J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-05-25 O. Varpuluoma, A.-K. Försti, J. Jokelainen, M. Turpeinen, M. Timonen, K. Tasanen, L. Huilaja
BackgroundDipeptidyl peptidase-4 inhibitors (DPP-4i) used to treat diabetes have been reported to be associated with an increased risk of bullous pemphigoid (BP). There are no previous reports analyzing the risk of BP in patients using other diabetes medications.ObjectiveTo evaluate the association between diabetes medications other than DPP-4i and development of BP.MethodsWe investigated prevalence of diabetes among BP patients, and the association between the use of diabetes drugs (excluding DPP-4i, metformin and insulin) and BP, by analyzing national Finnish registry data for 3397 BP patients and 12941 basal cell carcinoma patients as controls.ResultsOur results show that 19.6% of BP patients have type 2 diabetes. The use of none of the investigated medications was associated with an increased risk for BP.LimitationsSince this was a registry-based study, it was not possible to verify the accuracy of the diagnoses. The risk of BP in users of glucagon-like peptide-1 receptor agonists could not be analyzed.ConclusionOur study shows that the investigated diabetes drugs are not associated with increased risk of BP in a Finnish patient-base, indicating they can be safely used in this population. Generalization of these results to other populations will require further study.
Maintenance of Skin Clearance With Ixekizumab Treatment of Psoriasis: Three-Year Results From the UNCOVER-3 Study J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-05-25 Craig Leonardi, Catherine Maari, Sandra Philipp, Orin Goldblum, Lu Zhang, Nicole Burkhardt, Susan Ball, Lotus Mallbris, Pablo Gonzalez, Pablo Fernández-Peñas, Lluis Puig
Background Psoriasis, a chronic disease, may require long-term treatment. Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is an approved therapy for patients with moderate-to-severe plaque psoriasis. Objective To evaluate efficacy and safety of ixekizumab through 156 weeks from the UNCOVER-3 study in patients who received the recommended dose regimen [160 mg at Week 0, 80 mg every 2 weeks (IXE Q2W) to Week 12, and 80 mg every 4 weeks (IXE Q4W) thereafter. Methods Patients randomized to IXE Q2W, IXE Q4W, etanercept twice weekly, or placebo were switched to IXE Q4W during long-term extension period. Efficacy data were summarized using as-observed, multiple imputation (MI), and modified nonresponder imputation (mNRI) methods. Results At Week 156, response rates were 80.5%, 66.0%, and 45.1% for PASI 75, 90 and 100 using mNRI method, respectively, and 97.2% and 86.2 for PASI 75 using as-observed and MI methods, respectively.. Similar response rates were observed in patients with baseline scalp, nail, or palmoplantar involvement. No new safety signals were identiﬁed through Year 3. Limitations No placebo or active comparison after Week 12. Conclusion Ixekizumab sustained high responses with clearance of skin and nail lesions, with no new safety concerns through 3 years.
The Potential of Narrow Band UVB to Induce Sustained Durable Complete Remission off-Therapy in Stage I Mycosis Fungoides J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-05-23 Pavlotsky Felix, Dawood Marwan, Barzilai Aviv
Background Narrow Band UVB (NB UVB) is a first line therapy for stage I Mycosis Fungoides (MF) with complete response (CR) in 75%-85% of patients. However, long-term, off-therapy disease free survival (DFS) data are scarce. Objective To assess the long-term DFS following NB UVB treatment stage I MF. Methods An historic cohort of all stage I MF patients achieving CR with NB UVB and discontinuing any treatment prior to 2011. Age at the beginning of phototherapy, gender, stage, skin phototype, number of treatments, total dose and the length of DFS was collected. Results Of the 117 patients who started NB UVB, 93 patients (80%) had CR and 56 of them (60%) were disease free as of March 2017. In a multivariate analysis only age and disease stage independently affected DFS. The DFS was longer for patients younger than 50 years old (124 and 91 months respectively, p=0.01); and for stage IA patients (131 and 87.6 months respectively, p=0.001). Limitations The study was retrospective in nature Conclusions Following a single course of NB UVB, over a half of stage I MF patients achieve more than 5 years DFS period and potentially cured. Thus NB UVB can be considered as a disease modifying therapy.
Financial burden of emergency department visits for atopic dermatitis in the United States J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-05-23 Lauren Kwa, Jonathan I. Silverberg
Background Little is known about the utilization and financial-burden of emergency care visits for atopic dermatitis or eczema (AD-E) in the US. Objective To determine the prevalence, risk factors and cost of emergency care for AD-E in the US Methods Cross-sectional study of the 2006–2012 National Emergency Department Sample (NEDS), including a 20% sample of ED visits throughout the US (n=198,102,435). Results The mean annual incidence of ED visits with a primary diagnosis of AD-E was 3368.4 to 3553.0 per-million persons. The prevalence of ED visits for AD-E increased significantly from 2006 to 2012 (survey logistic regression; P<0.05). ED visits with vs. without a primary diagnosis of AD-E were associated with younger patient age, Medicaid or no insurance, lower household income-quartiles, and more likely to occur during weekends and summer months. The geometric mean and total costs of ED visits for AD-E significantly increased from $369.07 and $127,275,080 in 2006 to $642.10 and $265,541,084 in 2012, respectively Limitations NEDS did not include data on AD severity, recurrent ED visits, race/ethnicity or treatments provided. Conclusion There is a substantial and increasing financial-burden of ED visits for AD-E in the US. Interventions are needed to decrease ED visits for AD.
Basal Cell Carcinoma, PART II: Contemporary Approaches to Diagnosis, Treatment, and Prevention J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-05-19 Michael C. Cameron, Erica Lee, Brian Hibler, Cerrene N. Giordano, Christopher A. Barker, Shoko Mori, Miguel Cordova, Kishwer S. Nehal, Anthony M. Rossi
As the most common human cancer worldwide and continuing to increase in incidence, basal cell carcinoma is associated with significant morbidity and cost. Continued advances in research have refined both our insight and approach to this seemingly ubiquitous disease. This 2-part continuing medical education article will provide a comprehensive and contemporary review of basal cell carcinoma. Part II of this series will present both standard of care and newly developed approaches to diagnosis, treatment, and prevention of this disease.
Basal Cell Carcinoma: Part 1 J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-05-18 Michael C. Cameron, Erica Lee, Brian Hibler, Christopher A. Barker, Shoko Mori, Miguel Cordova, Kishwer S. Nehal, Anthony M. Rossi
As the most common human cancer worldwide and continuing to increase in incidence, basal cell carcinoma is associated with significant morbidity and cost. Continued advances in research have refined both our insight and approach to this seemingly ubiquitous disease. This 2-part continuing medical education article will provide a comprehensive and contemporary review of basal cell carcinoma. Part I of this series will describe our current understanding of this disease in regards to epidemiology, cost, clinical and histopathologic presentations, carcinogenesis, natural history, and disease associations.
Psoriatic patients with chronic viral hepatitis do not have an increased risk of liver cirrhosis despite long-term methotrexate use: real-world data from a nationwide cohort study in Taiwan. J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-05-10 Kuo-Tung Tang, Yi-Ming Chen, Shih-Ni Chang, Ching-Heng Lin, Der-Yuan Chen
Background Methotrexate (MTX) is commonly used in the treatment of patients with moderate to severe psoriasis. Objective We conducted a nationwide population-based cohort study to investigate the impact of long-term MTX use on the risk of chronic viral hepatitis-related cirrhosis among psoriatic patients in Taiwan. Methods This study obtained data from the National Health Insurance Research Database in Taiwan. We identified 2417 psoriatic patients with chronic hepatitis B (CHB) (370 MTX users and 2047 MTX non-users) and 1127 psoriatic patients with chronic hepatitis C (CHC) (174 MTX users and 953 MTX non-users) from January 1, 2000 to December 31, 2010. Results After a mean follow-up of more than 9 years since the diagnosis of chronic viral hepatitis, a total of 125 (5%) CHB patients and 120 (11%) CHC patients developed liver cirrhosis. A comparable proportion of MTX users and MTX non-users developed liver cirrhosis (4% vs. 5% in CHB patients and 11% and vs. 11% in CHC patients, both p < 0.05). Limitations There is possibly selection bias and medication nonadherence. Conclusion Our real-world data show that long-term MTX use may not be associated with an increased risk of liver cirrhosis among psoriatic patients with chronic viral hepatitis.
Ethnic differences and comorbidities of 909 Prurigo Nodularis patients J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-05-04 Emily Boozalis, Olive Tang, Shivani Patel, Yevgeniy R. Semenov, Manuel P. Pereira, Sonja Stander, Sewon Kang, Shawn G. Kwatra
BackgroundPrurigo Nodularis (PN) is a poorly understood, understudied pruritic dermatosis that reduces quality of life.ObjectiveTo characterize the demographics and comorbidities associated with PN.MethodsCross-sectional study of patients ≥ 18 years old seen at the Johns Hopkins Health System (JHHS) between 12/6/2012-12/6/2017.ResultsOver the last five years, 909 patients with PN were seen at JHHS. African-American patients were 3.4 times more likely to have PN than white patients (OR 3.4, 95% CI 2.9-3.9, p < 0.001). PN was significantly associated with a variety of systemic, cardiovascular, and psychiatric comorbidities when compared to race-matched controls, including: chronic kidney disease, chronic hepatitis C, chronic obstructive pulmonary disease, congestive heart failure, depression, and atopic dermatitis. Black patients with PN were 10.5 times more likely (OR 10.5, CI 7.9-13.9, p < 0.001) to have HIV than race-matched controls with atopic dermatitis, and eight times more likely (OR 8.0, 95% CI 5.7-11.1, p < 0.001) to have HIV than African-American patients with psoriasis.LimitationsOur data describes patients seen by one hospital system. Our data identifies associated conditions and comorbidities, but is unable to support a causal relationship.ConclusionPN disproportionately affects African-Americans and is associated with several systemic conditions including HIV, chronic kidney disease, and diabetes.
Certolizumab Pegol for the Treatment of Chronic Plaque Psoriasis: Results through 48 Weeks from Two Phase 3, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Studies (CIMPASI-1 and CIMPASI-2) J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-04-13 Alice B. Gottlieb, Andrew Blauvelt, Diamant Thaçi, Craig L. Leonardi, Yves Poulin, Janice Drew, Luke Peterson, Catherine Arendt, Daniel Burge, Kristian Reich
Background Certolizumab pegol, the only Fc-Free, PEGylated anti-tumor necrosis factor biologic, demonstrated clinically meaningful improvements and suggested a positive risk-benefit balance in phase 2 studies in adults with moderate-to-severe chronic plaque psoriasis. Objective Assess certolizumab efficacy and safety versus placebo in phase 3 studies. Methods Patients with moderate-to-severe chronic plaque psoriasis were randomized 2:2:1 to certolizumab 400 mg, 200 mg, or placebo every 2 weeks. At Week 16, certolizumab-treated patients achieving 50% reduction in psoriasis area and severity index continued treatment through Week 48. Coprimary endpoints were Week 16 responder rates, defined as 75% reduction in psoriasis area and severity index and physician’s global assessment 0/1 (‘clear’/‘almost clear’ and ≥2-point improvement). Safety was assessed by treatment-emergent adverse events. Results Week 16 endpoints were significantly greater for both doses of certolizumab versus placebo, and responses maintained through Week 48. For most measures, improvement was numerically greater for certolizumab 400 mg. No unexpected safety signals were identified. Limitations No active comparator. Conclusions Treatment with either certolizumab 400 mg or 200 mg every 2 weeks was associated with significant, clinically meaningful improvements in moderate-to-severe psoriasis. The 400 mg dose may provide additional clinical benefit. The safety profile was consistent with the therapeutic class.
Subcutaneous Infiltration of Carbon Dioxide (Carboxytherapy) for Abdominal Fat Reduction: A Randomized Clinical Trial J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-04-24 Murad Alam, Divya Sadhwani, Amelia Geisler, Imran Aslam, Inder Raj S. Makin, Daniel I. Schlessinger, Wareeporn Disphanurat, Marisa Pongprutthipan, Nataya Voravutinon, Alexandra Weil, Brian R. Chen, Dennis P. West, Emir Veledar, Emily Poon
Background Non-invasive fat removal is preferred because of decreased downtime and lower perceived risk. It is important to seek new non-invasive fat removal treatments that are both safe and efficacious. Objective To assess the extent to which carboxytherapy, the insufflation of carbon dioxide gas into subcutaneous fat, results in reduction of fat volume. Methods Randomized, sham-controlled, split-body study. Adults (BMI 22-29) were randomized to receive five weekly infusions of 1000 cc CO2 to one side of the abdomen, and five sham treatments to the contralateral side. Primary outcome measures were ultrasound measurement of fat layer thickness, as well as total circumference before and after treatment. Results Sixteen participants completed the study. Ultrasound measurement indicated less fat volume on the sides treated with carboxytherapy one week after the last treatment, (p=0.011), but was not maintained at 28 weeks. Total circumference decreased nominally but not significantly at Week 5 compared to baseline (p=0.0697). Participant body weights did not change over the entire course of the study (p=1.00) Limitations Limitations included modest sample size and some sources of error in circumference and fat layer measurements. Conclusion Carboxytherapy provides a transient decrease in subcutaneous fat that may not persist. Treatment is well-tolerated.
Red meat and processed meat intake and risk of cutaneous melanoma in white women and men: Two prospective cohort studies J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-04-24 Hsi Yen, Wen-Qing Li, Ashar Dhana, Tricia Li, Abrar Qureshi, Eunyoung Cho
Background Red and processed meat consumption has been associated with increased risk of several cancers, but association with cutaneous melanoma risk has been inconclusive. Objective To investigate the association between red and processed meat intake and melanoma risk. Methods Dietary information was assessed using food frequency questionnaires in two prospective cohorts – 75,263 women from the Nurses’ Health Study (1984 – 2010) and 48,523 men from the Health Professionals Follow-up Study (1986 – 2010). Melanoma cases were confirmed by review of pathological records. Pooled multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Results A total of 679 female and 639 male melanoma cases were documented during follow-up. Red and processed meat intake was inversely associated with melanoma risk (P for trend = 0.002); the pooled HRs (95% CIs) of the two cohorts were 1.00 (reference), 1.00 (0.87 – 1.14), 0.98 (0.86 – 1.13), 0.89 (0.77 – 1.02), and 0.81 (0.70 – 0.95) for increasing quintiles of intake. Limitations Findings may have limited generalizability, as the cohorts were limited to white health professionals. Conclusion Red and processed meat intake was inversely associated with melanoma risk in these two cohorts.
Analysis of Spin in the Reporting of Studies of Topical Treatments of Photoaged Skin J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-04-22 Catherine C. Motosko, Anna K. Ault, Laura L. Kimberly, M David Gothard, Roger S. Ho, Alexes Hazen
Background Spin—reporting that distorts the interpretation of results—is not unusual within scientific literature. Objective To appraise strategies of spin among placebo-controlled double-blind clinical trials of topical treatments for photoaged skin. Methods A systematic review of literature was performed to identify placebo-controlled double-blind clinical trials of topical treatments for photoaged skin. A survey of spin strategies was developed and applied to the cohort of identified studies. Results Systematic review identified 20 studies, all of which employed various spin strategies, broadly classified as either inappropriate statistical analysis or inappropriate interpretation of results. Most commonly used strategies included use of multiple primary outcomes (95%), inappropriate extrapolation of the results from specific outcome to global improvement (95%), focus on within-group comparison (75%), and focus on interim analyses to give more weight to nonsignificant findings (65%).Limitations: Classification of spin strategies is subjective and may not encompass all methods used by studies in the published literature. Conclusions Findings in this study may inform efforts to reduce spin in the dermatologic literature.
Topical Janus Kinase Inhibitors: A Review of Applications in Dermatology J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-04-16 Anna-Marie Hosking, Margit Juhasz, Natasha Atanaskova Mesinkovska
Background Janus kinase inhibitors (JAKi) have attracted attention for their role in treating inflammatory disorders. This new class of biologics has the potential to significantly impact the field of dermatology, especially with the development of topical formulations. Objective To summarize published evidence on the efficacy, safety, and tolerability of topical JAKi in the treatment of inflammatory skin conditions. Methods This is a review of PubMed and Cochrane Library up until November 2017. Results Fifty-five potential articles were identified; 11 articles were included for review, comprising an aggregate 924 patients. In randomized clinical trials (RCTs), topical JAKi demonstrate modest improvements in psoriasis and atopic dermatitis disease scores, patient-reported outcomes, and quality of life. Results for vitiligo are conflicting, with improvements seen only in facial vitiligo. Conclusive efficacy data for alopecia areata is lacking. Limitations It was not possible to perform a meta-analysis due to lack of standardization and low number of RCTs. Conclusions Topical JAKi provide an attractive treatment option for patients with psoriasis, atopic dermatitis, alopecia areata, and vitiligo. Although early phase clinical studies of this novel drug class are promising, large phase 3 and 4 studies are needed to further define the role of topical JAKi in dermatology.
Clinical features and prognosis of Asian patients with acral lentiginous melanoma who have nodal nevi in their sentinel lymph node biopsy specimen. J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-04-16 Ho-Jin Kim, Jeong-Wan Seo, Mee-Sook Roh, Ji-Hyun Lee, Ki-Hoon Song
Background Nodal melanocytic nevi (NN) encountered during sentinel lymph node biopsy (SLB) for malignant melanoma are usually difficult to distinguish from metastatic melanoma. However, NN have not been studied well in acral lentiginous melanoma (ALM) in Asian populations. Objective To investigate the clinical characteristics and significance of NN in SLBs from ALM patients. Methods We retrospectively analyzed 84 patients with ALM who underwent SLB between June 2010 and July 2017. Results Of the 84 ALM patients, 9 (10.7%) had NN in the SLB. NN were significantly more common in SLBs than in non-SLBs. The presence of pre-existing melanocytic lesions was found to be associated with NN (p<0.001). The 5-year overall survival was significantly higher in ALM patients with NN than SLB-positive patients (p=0.047). Distant recurrence in ALM patients with NN was significantly lower than patients who were SLB-positive (p=0.03). Limitations The small sample size, single-center study design, and retrospective nature of the study were the limitations. Conclusion In Asian populations, the prevalence of NN in ALM is similar to that reported in Europe and the United States. The distant recurrence rate and overall survival in patients with ALM who have NN are similar to those of patients who do not have metastatic melanoma.
Certolizumab Pegol for the Treatment of Chronic Plaque Psoriasis: Results Through 48 Weeks of a Phase 3, Multicenter, Randomized, Double-Blinded, Etanercept- and Placebo-Controlled Study (CIMPACT) J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-04-14 Mark Lebwohl, Andrew Blauvelt, Carle Paul, Howard Sofen, Jolanta Węgłowska, Vincent Piguet, Daniel Burge, Robert Rolleri, Janice Drew, Luke Peterson, Matthias Augustin
Background Phase 2 psoriasis studies with the Fc-free, PEGylated, anti-tumor necrosis factor biologic certolizumab pegol demonstrated meaningful clinical activity. Objective Assess safety and efficacy of certolizumab in adults with moderate-to-severe chronic plaque psoriasis. Methods Patients were randomized 3:3:1:3 to certolizumab 400 mg, 200 mg, or placebo every 2 weeks for 16 weeks or etanercept 50 mg twice-weekly for 12 weeks. Certolizumab-treated patients achieving ≥75% reduction in psoriasis area and severity index at Week 16 were re-randomized to certolizumab or placebo for 32 weeks. The primary endpoint was responder rate (≥75% reduction in psoriasis area and severity index) versus placebo (primary analysis) and etanercept (secondary analysis) at Week 12; secondary endpoints included responder rates on various measures versus placebo at Weeks 12, 16, and 48. Safety was assessed by treatment-emergent adverse events. Results All endpoints were significantly greater for certolizumab versus placebo with the greatest response seen with 400 mg. Certolizumab 400 mg was superior to and 200 mg was noninferior to etanercept. Adverse events were consistent with the anti-tumor necrosis factor class. Limitations Single-blind etanercept. Conclusion Both certolizumab regimens improved psoriasis symptoms with greater response at the higher dose. No new safety signals were observed.
Dermoscopic features of onychotillomania: A study of 36 cases J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-04-14 Austin John Maddy, Antonella Tosti
Background Onychotillomania is a nail-picking disorder characterized by nail dystrophy and abnormal morphology of the nail plate, nail bed, and periungual skin. Objective The purpose of this study was to describe the dermoscopic features of onychotillomania. Methods A retrospective study of the dermoscopy images of 36 patients affected by onychotillomania. The images were reviewed independently by both authors and a list of dermatoscopic findings was established. Results Scales were observed in 34 cases (94.4%); absence of nail plate was seen in 30 (83.3%); wavy lines were observed in 25 (69.4%); hemorrhages were observed in 23 (63.9%); crusts were seen in 22 (61.1%); nail bed pigmentation was observed in 17 (47.2%); speckled dots were observed in 14 (38.9%); nail plate melanonychia was observed in 4 (11.1%). Limitations Limitations included small sample size and retrospective study. Conclusion Absence of the nail plate with multiple obliquely oriented nail bed hemorrhages, nail bed gray pigmentation, and presence of wavy lines are characteristic findings of onychotillomania and not seen in other nail diseases.
Epidemiology of pediatric nickel sensitivity: Retrospective review of North American Contact Dermatitis Group (NACDG) data 1994-2014 J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-04-14 Erin M. Warshaw, Kelly A. Aschenbeck, Joel G. DeKoven, Howard I. Maibach, James S. Taylor, Denis Sasseville, Donald V. Belsito, Joseph F. Fowler Jr., Kathryn A. Zug, Matthew J. Zirwas, Anthony F. Fransway, Vincent A. DeLeo, James G. Marks Jr., Melanie D. Pratt, Toby Mathias
Background Nickel is a common allergen responsible for allergic contact dermatitis. Objective To characterize nickel sensitivity in children and compare pediatric cohorts (≤5, 6-12, and 13-18 years). Methods Retrospective, cross-sectional analysis of 1894 pediatric patients patch tested by the North American Contact Dermatitis Group from 1994 to 2014. We evaluated demographics, rates of reaction to nickel, strength of nickel reactions, and nickel allergy sources. Results The frequency of nickel sensitivity was 23.7%. Children with nickel sensitivity were significantly less likely to be male (P < .0001; relative risk, 0.63; 95% confidence interval, 0.52-0.75) or have a history of allergic rhinitis (P = .0017; relative risk, 0.74; 95% confidence interval, 0.61-0.90) compared with those who were not nickel sensitive. In the nickel-sensitive cohort, the relative proportion of boys declined with age (44.8% for age ≤5, 36.6% for age 6-12, and 22.6% for age 13-18 years). The most common body site distribution for all age groups sensitive to nickel was scattered/generalized, indicating widespread dermatitis. Jewelry was the most common source associated with nickel sensitivity (36.4%). Limitations As a cross-sectional study, no long-term follow-up was available. Conclusions Nickel sensitivity in children was common; the frequency was significantly higher in girls than in boys. Overall, sensitivity decreased with age. The most common source of nickel was jewelry.
CME Part 1: Hair disorders in cancer patients J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-04-14 Azael Freites-Martinez, Jerry Shapiro, Shari Goldfarb, Julie Nangia, Joaquin J. Jimenez, Ralf Paus, Mario E. Lacouture
Cytotoxic chemotherapies, molecularly targeted therapies, immunotherapies, radiotherapy, stem cell transplants, and endocrine therapies may lead to hair disorders (including alopecia, hirsutism, hypertrichosis, pigmentary and textural hair changes). The mechanisms underlying these changes are varied and remain incompletely understood, hampering the development of preventive or therapeutic guidelines. The psychosocial impact of chemotherapy -induced alopecia has been well-documented mainly in the oncology literature, however the effect of other alterations such as radiation-induced alopecia, hirsutism, changes in hair color or texture on quality of life have not been described. This article reviews clinically significant therapy-related hair disorders in cancer patients, underlying pathophysiological mechanisms, severity grading scales, patient reported quality of life instruments, management strategies, and future translational research opportunities.
CME Part 2: Hair disorders in cancer survivors Persistent chemotherapy-induced alopecia, persistent radiotherapy-induced alopecia, and hair growth disorders related to endocrine therapy or cancer surgery J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-04-14 Azael Freites-Martinez, Jerry Shapiro, Corina van den Hurk, Shari Goldfarb, Joaquin Jimenez, Anthony M. Rossi, Ralf Paus, Mario E. Lacouture
With increasing survival rates across all cancers, survivors represent a growing population that is frequently affected by persistent or permanent hair growth disorders as a result of systemic therapies, radiotherapy, surgical procedures, and therapeutic transplants. These hair disorders include persistent chemotherapy-induced alopecia, persistent radiotherapy-induced alopecia, endocrine therapy-induced alopecia and hirsutism, post-surgery alopecia and localized hypertrichosis, alopecia attributed to therapeutic transplants, and to novel anticancer therapies. The information contained in this continuing medical education article should facilitate a better understanding on hair disorders in cancer survivors, so that adequate support and therapies may be provided to cancer survivors.
Neutrophilic dermatoses. Part I. Pathogenesis, Sweet syndrome, neutrophilic eccrine hidradenitis, and Behçet’s disease J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-04-11 Caroline A. Nelson, Sasha Stephen, Hovik J. Ashchyan, William D. James, Robert G. Micheletti, Misha Rosenbach
Neutrophilic dermatoses are a heterogeneous group of inflammatory skin disorders that present with unique clinical features, but are unified by the presence of a sterile, predominantly neutrophilic infiltrate on histopathology. The morphology of cutaneous lesions associated with these disorders is heterogeneous, which renders diagnosis challenging. Moreover, a thorough evaluation is required to exclude diseases that mimic these disorders and to diagnose potential associated infectious, inflammatory, and neoplastic processes. While some neutrophilic dermatoses may resolve spontaneously, most require treatment to achieve remission. Delays in diagnosis and treatment can lead to significant patient morbidity and even mortality. Therapeutic modalities range from systemic corticosteroids to novel biologic agents, and the treatment literature is rapidly expanding. Part I of this continuing medical education activity explores the pathogenesis of neutrophilic dermatoses and reviews the epidemiology, clinical and histopathological features, diagnosis, and management of Sweet syndrome, neutrophilic eccrine hidradenitis, and Behçet’s disease.
Diversity in Dermatology: Roadmap for Improvement J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-04-10 Ellen N. Pritchett, Amit G. Pandya, Nkanyezi N. Ferguson, Shasa Hu, Alex G. Ortega-Loayza, Henry W. Lim
The American Academy of Dermatology (AAD) has taken an active stance in addressing the lack of racial and ethnic diversity in the specialty. At the AAD President’s Conference on Diversity in Dermatology held August 5, 2017, key action items were identified in three main areas in order to increase the number of practicing, board-certified dermatologists who are underrepresented in medicine (UIM). These include: increasing the pipeline of UIM students applying to medical school; increasing the exposure and level of interest of UIM medical students in dermatology; and increasing the number of UIM students recruited into dermatology residency programs.
Efficacy and Safety of Ixekizumab Over 4 Years of Open-Label Treatment in a Phase 2 Study in Chronic Plaque Psoriasis J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-04-10 Claus Zachariae, Kenneth Gordon, Alexandra Kimball, Mark Lebwohl, Andrew Blauvelt, Craig Leonardi, Daniel Braun, Missy McKean-Matthews, Russel Burge, Gregory Cameron
Background Ixekizumab has demonstrated improvement in moderate-to-severe psoriasis patients by selectively targeting interleukin-17A, a pro-inflammatory cytokine important in psoriasis pathogenesis. Objective To report 4-year efficacy and safety results from the open-label extension (OLE) of this phase 2 trial. Methods Analysis was by last observation carried forward. Patients received ixekizumab 120 mg then 80 mg subcutaneously once every 4 weeks. Results Ninety-three percent of patients who completed the randomized placebo-controlled trial entered the OLE. A 75% reduction on the Psoriasis Area Severity Index was reported in 82% of patients at OLE Week 208. A static Physician’s Global Assessment score of 0 or1 was reported in 64% and a score of 0 was reported in 45% at Week 208. Dermatology Life Quality Index and Itch Visual Analog Scale scores decreased when compared to baseline. Improvements were observed in other efficacy and health outcome measures. Serious adverse events were observed in 16.7% of patients, and 87% had ≥1 treatment-emergent adverse event. Three patients had serious infections. One patient reported 2 major cardiovascular events. Limitations The study was unblinded and lacked a placebo or active comparator. Conclusions Efficacy was shown to be maintained for up to 4 years of ixekizumab treatment.
A systematic review and meta-analysis of the effects of topical nitrates in the treatment of primary and secondary Raynaud's phenomenon J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-31 Paul Curtiss, Zachary Schwager, Gabriela Cobos, Kristen Lo Sicco, Andrew G. Franks Jr.
Background Multiple placebo-controlled trials have assessed locally applied topical nitrate preparations in treating Raynaud's phenomenon (RP). Objectives The objective of this meta-analysis was to assess the effects of local topical nitrates in primary and secondary RP with respect to a combined end point integrating parameters of digital blood flow and clinical severity. Methods A systematic review was performed using MEDLINE, Embase, and the Cochrane library. Only trials comparing locally applied topical nitrates with placebo comparators were included. Studies were appraised for bias by 2 independent reviewers. Results A total of 7 placebo-controlled trials including 346 patients were used in the meta-analysis; 4 trials used nitroglycerin ointments, 2 used the nitroglycerin gel vehicle MQX-503, and 1 used compounded nitrite. The meta-analysis results supported a moderate-to-large treatment effect in RP (standardized mean difference [SMD] = 0.70; 95% CI, 0.35-1.05; P < .0001). Subgroup analyses showed a large treatment effect in secondary RP (SMD = 0.95; 95% CI, 0.25-1.65; P = .008) and moderate effect in primary RP (SMD = 0.45; 95% CI, 0.05-0.85; P = .03). Limitations Limitations include the inclusion of multiple topical nitrate preparations and integration of different outcomes assessments. Conclusion Local topical nitrates have significant efficacy in the treatment of both primary and secondary RP.
Biologics for pityriasis rubra pilaris treatment: a review of the literature J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-30 Monica Napolitano, Damiano Abeni, Biagio Didona
Pityriasis rubra pilaris (PRP) is a rare inflammatory papulosquamous skin disease, often refractory to conventional therapies. The off-label use of biologics, such as anti-TNF, -IL-12/IL-23, -IL-17 agents, has been proven successful, in the last two decades, in PRP treatment. Our aim was to analyse the literature for the use of biologics in PRP treatment. We conducted a review by “Pubmed” and “clinicaltrial.gov” searches. 68 articles met our selection criteria and were herein discussed. Out of 86 PRP patients, the vast majority of which treated with anti-TNF, -IL-12/IL-23, and -IL-17 biologics, either alone or in combination therapy, a marked-to-complete response (50-78%), a partial response (11-25%) or no/poor response (11-25%) was observed. This review has several limitations including small sample sizes, with no shared study design criteria, and the fact that -in some instances- PRP may spontaneously resolve. Further, the presence of concomitant therapy and/or the lack of detailed data on previous treatments, makes it difficult to strictly define a therapeutic role per se of specific biologics in PRP. This review shows that biologics may be regarded as a tool for PRP treatment alone or in combination therapy although clinical trials are needed to better assess their efficacy and safety.
Dual neutralization of both IL-17A and IL-17F with bimekizumab in patients with psoriasis: results from BE ABLE 1, a 12-week randomized, double-blinded placebo-controlled phase 2b trial J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-30 Kim A. Papp, Joseph F. Merola, Alice B. Gottlieb, Christopher E.M. Griffiths, Nancy Cross, Luke Peterson, Christopher Cioffi, Andrew Blauvelt
Background Neutralizing interleukin (IL)-17F in addition to IL-17A may provide a more complete and specific approach to inhibiting inflammation. Objective Assess the efficacy and safety of bimekizumab, a monoclonal antibody that potently and selectively neutralizes IL-17A and IL-17F, in patients with moderate-to-severe plaque psoriasis. Methods Double-blinded, placebo-controlled phase 2b study (NCT02905006). Patients (randomized 1:1:1:1:1:1) received subcutaneous bimekizumab every four weeks at doses of 64mg, 160mg, 160mg with 320mg loading dose, 320mg, 480mg, or placebo. Primary endpoint was ≥90% reduction in Psoriasis Area Severity Index (PASI90) at Week 12. Results There was a significant (P<0.0001) dose-response for PASI90 (Week 12); more patients achieved PASI90 than placebo (46.2−79.1% versus 0%, P<0.0001 all doses). Across all doses, there were significant improvements from baseline for all secondary endpoints (PASI90 [Week 8], PASI75 and PASI100 [Week 12], Investigators Global Assessment “clear”/“almost clear” [Weeks 8&12]; P≤0.0003 versus placebo). More bimekizumab-treated patients achieved PASI100 (Week 12) than placebo (27.9−60.0% versus 0%; P≤0.0002 all doses). TEAEs were reported by 126/208 (61%) bimekizumab-treated patients and 15/42 (36%) placebo-treated patients. Limitations No active comparator. Conclusion Dual neutralization of IL-17A and IL-17F with bimekizumab provided rapid and substantial clinical improvements in patients with psoriasis, with no unexpected or dose-related safety findings.
A healthy diet in women is associated with less facial wrinkles in a large Dutch population-based cohort J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-27 Selma Mekic, Leonie C. Jacobs, Merel A. Hamer, M. Arfan Ikram, Josje D. Schoufour, David A. Gunn, Jessica C. Kiefte- de Jong, Tamar Nijsten
Background Little is known about the effects of different dietary patterns on facial wrinkling. Objective We aimed to investigate the association between diet and facial wrinkles in a population-based cohort of 2,753 elderly participants of the Rotterdam Study. Methods Wrinkles were digitally quantified as the area in facial photographs they occupied as a percentage of the total skin area. Diet was assessed using the Food Frequency Questionnaire. Adherence to the Dutch Healthy Diet Index (DHDI) was calculated. In addition, we used Principal Component Analysis (PCA) to extract relevant food patterns in men and women separately. All food patterns and the DHDI were analyzed for association with wrinkle severity using multivariable linear regression. Results Better adherence to the Dutch guidelines was significantly associated with less wrinkles among women but not in men. In women, a red meat and snack dominant PCA pattern was associated with more facial wrinkles whereas a fruit dominant PCA pattern associated with fewer wrinkles. Limitations Due to the cross-sectional design of our study, no causation can be proved. Health-conscious behavior could have influenced our results. Conclusion Dietary habits associate with facial wrinkling in women. Global disease prevention strategies might benefit from emphasizing that a healthy diet is also linked to less facial wrinkling.
Subungual Atypical Lentiginous Melanocytic Proliferations in Children and Adolescents: A Clinicopathologic Study J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-27 Sameer S. Khatri, Min Wang, Kelly L. Harms, Alison B. Durham, Timothy M. Johnson, Rosalynn M. Nazarian, Paul W. Harms, Douglas R. Fullen, Aleodor A. Andea, May P. Chan
Background Most subungual melanocytic lesions in children are benign, but some are difficult to classify due to prominent lentiginous growth and high-grade cytologic atypia. Objective To characterize the clinicopathologic features of these rare lesions. Methods Subungual atypical lentiginous melanocytic proliferations from patients under 20 years of age were collected for clinical and histopathologic review. Fluorescence in situ hybridization (FISH) was performed when possible. Results Eleven patients aged 2-19 years presented with expanding and/or darkening longitudinal pigmented streak(s) with or without Hutchinson sign. Microscopically, all revealed predominantly single-cell growth, pagetoid scatter, and poor circumscription. Eight (73%) cases showed focal/poor nesting, and 3 (27%) demonstrated confluence. Nuclear enlargement, hyperchromasia, and angulation were present in 8 (73%), 7 (64%), and 6 (55%) cases, respectively. One of 4 cases tested by FISH was positive. Three lesions recurred locally without other adverse outcome. Limitations Small sample size and short clinical follow-up. Two cases examined in partial biopsies only. Conclusion Some subungual melanocytic lesions in children and adolescents are histologically indistinguishable from adult subungual melanoma in situ. While the biologic potential remains elusive, FISH may aid in risk stratification. Awareness of this rare group of lesions is crucial in facilitating future investigation into its biologic behavior.
Non-malignant late cutaneous changes after allogeneic hematopoietic stem cell transplant in children J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-26 Jennifer T. Huang, Johanna S. Song, Elena B. Hawryluk, Wendy B. London, Dongjing Guo, Madhumitha Sridharan, David E. Fisher, Leslie E. Lehmann, Christine N. Duncan
Background There are limited pediatric data on non-malignant cutaneous changes, including autoimmune conditions and permanent alopecia, after hematopoietic stem cell transplantation (HSCT). Objective We sought to characterize late cutaneous changes and associated risk factors after allogeneic HSCT in children. Methods A cross-sectional cohort study of pediatric HSCT recipients was performed at a single institution. All participants underwent a full skin examination. Results Median visit age was 13.8 years with median time post-HSCT of 3.6 years. Of 85 patients, 14% (n=12) had vitiligo, 16% (n=14) had psoriasis/sebopsoriasis, 25% (n=21) had alopecia, and 6% (n=5) had nail changes. Factors significantly associated with vitiligo included a history of chronic graft-versus-host disease (cGVHD), transplant indication of primary immunodeficiency, and younger age at transplant (<10 years of age). Fifty-two percent of patients with alopecia had androgenetic alopecia patterns. Factors significantly associated with alopecia included cGVHD, busulfan conditioning, and family history of early male pattern alopecia. All patients with nail changes had cGVHD. Limitations The cross-sectional design did not allow time of onset identification. Histopathologic correlation was not performed. Conclusion Pediatric HSCT recipients, particularly those with cGVHD, are at risk for developing non-malignant late cutaneous changes.
Risk of skin cancer in HIV-infected patients: a Danish nationwide cohort study J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-26 Silje Haukali Omland, Magnus Glinvad Ahlström, Jan Gerstoft, Gitte Pedersen, Rajesh Mohey, Court Pedersen, Gitte Kronborg, Carsten Schade Larsen, Birgit Kvinesdal, Robert Gniadecki, Niels Obel, Lars Haukali Omland
Background The risk of skin cancer in HIV-infected patients has not been extensively studied. Objective To determine the risk of skin cancer in HIV-infected patients and compare it with the risk in the background population. Methods In a matched, nationwide population-based cohort study we compared the risk of skin cancer in 4280 HIV-infected patients from the Danish HIV cohort study with a background population cohort, according to the level of immunosuppression and route of transmission. Primary outcomes were time to first basal cell carcinoma (BCC), squamous cell carcinoma (SCC), or malignant melanoma (MM). Results HIV-infected patients had an increased risk of BCC and SCC with IRRs of 1.79 (95% CI 1.43 – 2.22) and 5.40 (95% CI 3.07 – 9.52), respectively, compared with the background population. We observed no increased risk of MM. Low nadir CD4 cell count was associated with an increased risk of SCC. The increased risk of BCC among HIV-infected patients was restricted to men who had sex with men. Limitations Observational design. Small number of patients with melanoma. Conclusion HIV-infected patients have an increased risk of BCC and SCC. Low nadir, but not current, CD4 cell count as a marker of immunosuppression was associated with an increased risk of SCC.
Stage IV Melanoma of Unknown Primary: A Population-Based Study in the United States from 1973 to 2014 J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-23 Jeffrey F. Scott, Ruzica Z. Conic, Cheryl L. Thompson, Meg R. Gerstenblith, Jeremy S. Bordeaux
Background Melanoma of unknown primary (MUP) is incompletely described on a population level. Objective We sought to characterize stage IV MUP in a population-based cancer registry. Methods We developed a novel search algorithm to identify cases of stage IV MUP in the Surveillance, Epidemiology, and End Results (SEER)-18 registries from 1973 to 2014. Stage IV melanoma of known primary (MKP) served as a comparison group. Age-standardized incidence rates, demographic characteristics, adjusted disease-specific survival (DSS), and Cox proportional hazard models were calculated for MUP and MKP. Results A total of 322 stage IV MUP cases and 12,796 stage IV MKP cases were identified in SEER-18 from 1973 to 2014. The incidence of stage IV MUP is increasing, particularly for patients less than 30 years of age. In multivariate analyses, age greater than 50 and a lack of surgical treatment were negative prognostic factors for stage IV MUP. Relative survival, but not 5-year adjusted DSS, was higher for stage IV MUP compared to MKP. Limitations Limitations include the retrospective study design and possible misclassification of MUP. Conclusions The incidence of stage IV MUP is increasing, and stage IV MUP shares similar prognostic factors as stage IV MKP, including age and surgical treatment.
Melanoma staging: Varying precision and terminal digit clustering in Breslow thickness data is evident in a population based study J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-23 Marit B. Veierød, Christian M. Page, Stein Aaserud, Assia Bassarova, Kari D. Jacobsen, Per Helsing, Trude E. Robsahm
Background Errors in Breslow thickness reporting can give misclassification of T category, an important classifier in melanoma staging. Objective Investigate precision (number of digits) and terminal digit clustering in Breslow thickness, and potential consequences for T category. Methods All first primary and morphologically verified invasive melanomas in Norway, 2008–2015, were included. A smoothing model was fitted to estimate the underlying Breslow thickness distribution without digit clustering. Results Thickness was reported for 13 057 (97.5%) patients, median 1.0 mm (range 0.09–85). It was reported as whole numbers (15.6%), to one decimal (78.2%) and two decimal places (6.2%); thin tumours with more precision than thicker. Terminal digit clustering was found with marked peaks in the observed frequency distribution for terminal digits 0 and 5, and with drops around these peaks. Terminal digit clustering increased proportions of patients classified with T1 and T4 tumours and decreased proportions classified with T2 and T3. Limitations Breslow thickness was not reported in 2.5% of cases. Conclusions Norwegian recommendation of measurement to the nearest 0.1 mm was not followed. Terminal digit clustering was marked, with consequences for T category. Pathologists, clinicians and epidemiologists should know that clustering of thickness data around T-category cut-points can impact melanoma staging with consequent effect on patient management and prognosis.
A 10 Point Plan to Demonstrate the Value of Dermatology in the Health Care System J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-22 Henry W. Lim, Karen E. Edison, Krista D. Kauper, Melanie Tolley Hall, Missy Lundberg, Katie Domanowski
In May 2017, the American Academy of Dermatology (AAD) convened a Dermatology Specialty Summit, with representatives from 15 dermatology specialty societies, the American Board of Dermatology, and the Coalition of Skin Diseases in attendance. The Summit’s goal was to identify opportunities to address and enhance the perception of dermatology in the House of Medicine, the role of data in the changing health care environment, and access to dermatologic care. Summit participants collectively identified a list of 10 action items that address opportunities in these areas of concern. These include active participation in the House of Medicine, increased interaction with and education of our primary care colleagues, efforts to support DataDerm, and creative ways to improve access.
Trends in phototherapy utilization among Medicare beneficiaries in the United States, 2000-2015 J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-21 Sally Tan, Elizabeth Buzney, Arash Mostaghimi
Background Phototherapy is a cost-effective treatment for many dermatoses, yet emerging alternative therapies such as biologics led many to think that phototherapy utilization was declining. Objective To characterize national, historical phototherapy utilization and costs among Medicare beneficiaries. Methods Longitudinal analysis of Medicare Part B National Summary Data File from 2000-2015 for phototherapy billing codes. Geographic distribution of clinics and provider type obtained from Medicare Provider Utilization and Payment Data for 2012-2015. Results Overall volume of phototherapy services billed to Medicare from 2000-2015 increased 5% annually, from 334,670 to 692,093. UVB comprised 77% of phototherapy volume, PUVA utilization declined 9% annually and excimer laser services grew by 29% annually. The number of phototherapy clinics is increasing but remains concentrated in only 11% of US counties. Between 2012-15, dermatologists accounted for 92% of phototherapy volume. Limitations Commercial payers and institutional claims (hospital-based physicians) are excluded. Clinical indications for phototherapy use are not reported in this database. Conclusion Phototherapy utilization has grown, though service mix has shifted towards UVB and laser excimer and away from PUVA. Dermatologists manage most phototherapy. Uneven geographic distribution of phototherapy clinics limits access in non-urban areas, and further evaluation is needed to determine its impact on rural communities.
Factors Associated with Advanced Stage Merkel Cell Carcinoma at Initial Diagnosis and the Use of Radiation Therapy: Results from the National Cancer Database J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-21 Oleksandr Trofymenko, Nathalie C. Zeitouni, Drew JB. Kurtzman
Background The stage of disease at initial diagnosis and the use of radiation therapy (RT) are important determinants of survival in patients with Merkel cell carcinoma (MCC). Objective To define factors that are associated with advanced stage MCC at the time of initial diagnosis and the use of RT. Methods Cross-sectional, retrospective analysis of MCC patients registered in the National Cancer Database during 2004-2013. Results A total of 11,917 patients were identified. 3,152 and 4,586 patients were excluded from the staging and RT analyses, respectively, due to lack of available data. African American ethnicity (OR, 1.49; 95% CI, 1.06-2.10; p=0.023), lack of medical insurance (OR, 2.15; 95% CI 1.40-3.30; p<0.001), a Charlson/Deyo comorbidity score of at least 1 (OR, 1.21; 95% CI, 1.09-1.34; p<0.001), residing more than 26 miles from a treatment facility (OR, 1.18; 95% CI, 1.03-1.35; p=0.015), tumor located on the lower limb/hip (OR, 1.59; 95% CI, 1.42-1.78; p<0.001) or trunk (OR, 2.05; 95% CI, 1.81-2.33; p<0.001), and poorly (OR, 2.57; 95% CI, 1.13-5.82; p=0.024) or undifferentiated (OR, 3.11; 95% CI, 1.36-7.15; p=0.007) tumor histology predicted advanced stage MCC at the time of initial diagnosis. The use of RT was associated with Native American ethnicity (OR, 5.04; 95% CI, 1.10-22.99; p=0.037), tumor size between 1.5-2.7 cm (OR, 1.27; 95% CI, 1.10-1.47; p=0.001), electing not to have surgery (OR, 2.77; 95% CI, 1.90-4.03; p<0.001), positive post-surgical margins (OR, 1.39; 95% CI, 1.18-1.63; p<0.001), and receiving treatment at a comprehensive cancer program (OR, 1.25; 95% CI, 1.03-1.50; p=0.020). Limitations Retrospective design limits generalizability of the results, and precise details of RT regimens utilized were not available. Conclusions and Relevance: A number of factors are associated with advanced stage MCC at initial diagnosis and the use of RT. Healthcare models should account for these factors, and efforts should be directed toward improving those that are modifiable.
Ustekinumab treatment is associated with decreased systemic and vascular inflammation in patients with moderate to severe psoriasis: Feasibility study using 18F-fluorodeoxyglucose positron emission tomography-computed tomography J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-17 Byung-Soo Kim, Won-Ku Lee, Kyoungjune Pak, Junhee Han, Gun-Wook Kim, Hoon-Soo Kim, Hyun-Chang Ko, Moon-Bum Kim, Seong-Jang Kim
Background Evidence suggests that psoriasis may be associated with metabolic syndrome and an increased risk of cardiovascular disease. Objective To determine whether ustekinumab reduces systemic and vascular inflammation associated with metabolic syndrome and cardiovascular disease, measured using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Methods Patients with psoriasis and healthy controls underwent baseline 18F-FDG PET/CT imaging. Among the patients with psoriasis, moderate to severe psoriasis was treated with ustekinumab, and the patients underwent 18F-FDG PET/CT again after a Psoriasis Area and Severity Index of 75 was achieved. Results After a Psoriasis Area and Severity Index of 75 was achieved with ustekinumab treatment, standardized uptake values were reduced in the liver, spleen, and five parts of the aorta (P<0.05). Limitations Our study does not provide outcome data concerning cardiovascular events or metabolic syndrome; it only shows surrogate markers in a limited (Korean) population. Conclusion Ustekinumab treatment was significantly associated with decreased systemic and vascular inflammation related to metabolic syndrome and cardiovascular disease among patients with psoriasis.
Mycoplasma pneumoniae-related erythema multiforme: clinical and histological features. A single center series of 33 cases compared to 100 cases induced by other causes J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-17 Reyhan Amode, Saskia Ingen-Housz-Oro, Nicolas Ortonne, Touda Bounfour, Sabine Pereyre, Frédéric Schlemmer, Emilie Bequignon, Gérard Royer, Pierre Wolkenstein, Olivier Chosidow
Background Mycoplasma pneumoniae (MP) infection has been documented in erythema multiforme (EM) and Stevens-Johnson syndrome-toxic epidermal necrosis (SJS-TEN). Clinical aspects of MP-related EM (MP-EM) have been poorly described in the literature. Objective To highlight differences between MP-EM and non-MP-EM. Methods This monocenter retrospective cohort study included all the patients admitted for EM from 2000 to 2015 in our dermatology department. We compared epidemiological, clinical, histological data and follow-up for MP-EM and non-MP-EM cases. Results 33 MP-EM were compared to 100 non-MP EM. Disease onset in winter was more frequent with MP-EM (p=0.003). Acrally distributed lesions and typical targets were less common in MP-EM (32% vs 88%, p<0.0001; 45% vs 74%, p=0.01 respectively). Multiple (≥2) mucous membrane involvement was more frequent in MP-EM (97% vs 60%; p<0.0001), as were mucosal and respiratory tract sequelae (p<0.05). The mean hospital stay was longer with MP-EM patients : 9.5 vs 5.1 days (p=0.0002). A “TEN-like pattern” was observed in all 14 (100%) MP-EM skin biopsies vs 10/27 (48%) non-MP EM biopsies (p<0.001). Limitations Retrospective design Conclusion MP-EM has a distinctive presentation compared with non-MP EM, with more diffuse and atypical targets, more mucositis and respiratory tract sequelae. Histological data show a “TEN-like pattern” in all MP-EM skin samples.
Ixekizumab treatment shows a neutral impact on cardiovascular parameters in patients with moderate-to-severe plaque psoriasis: results from UNCOVER-1, -2, and -3 J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-13 Alexander Egeberg, Jashin J. Wu, Neil Korman, James A. Solomon, Orin Goldblum, Fangyi Zhao, Lotus Mallbris
Background The impact of ixekizumab treatment for psoriasis on cardiovascular-related parameters in patients is unknown. Objective We investigated cardiovascular-related parameters in patients with psoriasis treated with ixekizumab. Methods In Phase 3 trials, patients with moderate-to-severe psoriasis were randomized and treated with placebo, ixekizumab, or etanercept during the induction period (Weeks 0-12; UNCOVER-1/-2/-3). At week 12, responders were re-randomized to receive placebo or ixekizumab through the maintenance period (Weeks 12-60; UNCOVER-1/-2). Laboratory measures (fasting lipid profiles, glucose, or high sensitivity C-reactive protein [hsCRP]), weight, blood pressure, and electrocardiograms were obtained through 60-weeks. Results Baseline parameters were within normal ranges with the exception of elevated triglycerides and hsCRP. After maintenance dosing, no significant changes were observed versus placebo for total cholesterol, LDL-cholesterol, HDL-cholesterol, VLDL-cholesterol, triglycerides, apolipoprotein A1/B, fasting glucose, or systolic/diastolic blood pressure at 60-weeks. Importantly, LDL/HDL ratios remained stable during induction and maintenance periods. HsCRP concentrations were significantly reduced versus placebo at 12-weeks and remained reduced at 60-weeks, although not significantly. While transient changes were observed for some parameters during the induction period, these changes did not persist into the maintenance period. Limitations A lack of echocardiogram evaluations. Conclusion Ixekizumab had a neutral impact on cardiovascular-related parameters in patients with psoriasis.
Increased Topical Generic Prices by Manufacturers: An Isolated Trend or Worrisome Future? J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-12 Mehul D. Bhatt, Birju D. Bhatt, James T. Dorrian, Beth N. McLellan
Background There is limited data regarding generic medication prices. Recent studies have shown price changes at the retail level, but much is not known about the pharmaceutical supply chain or price changes at the manufacturer level. Objective We sought to examine the extent of price changes for topical generic medications. Methods A comprehensive review of average wholesale prices (AWP) and manufacturers of topical generics and available corresponding branded medications was conducted for 2005 and 2016. Results A total of 51 topical chemical entities were examined. Between 2005 and 2016, the AWP of topical generics increased by 273% and the AWP of topical branded increased by 379%. The topical generic with the most price change increased by 2529%. Eight of the top twenty topical generics with the highest increase in AWP also had an increase in the number of manufacturers. Limitations These findings are not generalizable to medications used in other areas of medicine Conclusions Topical generic prices are rapidly increasing at the manufacturer level.
Inflammatory arthritis in pediatric patients with morphea J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-10 Sakeen W. Kashem, Colleen K. Correll, Richard K. Vehe, Patricia M. Hobday, Bryce A. Binstadt, Sheilagh M. Maguiness
Background Morphea, or ‘localized scleroderma’, is an inflammatory disorder resulting in fibrosis of the skin and subcutaneous tissues. Joint contractures, arthralgias and functional compromise are recognized associations of pediatric morphea. The co-existence of inflammatory arthritis and morphea is not well-described in the literature. Objective To investigate the relationship between pediatric morphea and inflammatory arthritis with regards to cutaneous, musculoskeletal and laboratory findings and treatment regimens. Methods A systematic retrospective chart review of 53 patients with pediatric morphea was performed and analyzed for morphea subtypes, arthritic joint involvement, serum autoantibodies and therapeutic interventions. Results Eleven out of 53 patients had polyarthritis that involved joints unrelated to the site of the cutaneous morphea. They were mostly female and presented with either the linear or generalized subtypes of morphea. Serum levels of antinuclear antibodies were more significantly elevated in patients with arthritis. All children were treated with methotrexate in addition to other systemic and/or topical immunosuppressive agents. Limitation This was a small, single center, retrospective study. Conclusion Pediatric morphea co-existed with inflammatory arthritis in 11/53 children. Further understanding and appreciation of this relationship may direct more intensive therapy and musculoskeletal screening
Surgical Site Identification with Personal Digital Device: A Prospective Pilot Study J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-07 Leon Chen, Adam M. Parsons, Alexander B. Aria, Ana M. Ciurea, Anisha B. Patel, Christopher Chan, John R. Griffin, Tri H. Nguyen, Michael R. Migden
Background Various means to facilitate accurate biopsy site identification have been proposed. Objective To determine the accuracy of biopsy site identification using photos taken with a patient’s digital device by a dermatologist versus professional medical photography. Methods Photographs of circled biopsy sites were taken with personal digital devices by the principal investigator (PI). Another set of photographs were taken by a professional photographer. Secondary photographs were taken of the biopsy site location pointed to by the staff and PI based on the personal digital device image and professional medical photography, respectively. Based on secondary photographs, two independent dermatologists determined if the skin biopsy locations pointed out by the staff were consistent with the ones pointed out by PI. Results Per Dermatologist A, the staff correctly identified all 53/53 biopsy sites. Per Dermatologist B, the staff were correct on 51/53 observations. Dermatologist C, the final arbiter, concurred with Dermatologist A in the two cases that Dermatologist B was not certain of the biopsy site location. Limitations The mean interval from initial biopsy to re-identification of the site was 36.2 days. Conclusion Utilizing patients’ personal digital devices is a cost-effective, HIPAA compliant, and readily available means to identify skin biopsy sites.
Pathologist Characteristics Associated with Accuracy and Reproducibility of Melanocytic Skin Lesion Interpretation J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-07 David E. Elder, Mike Piepkorn, Raymond L. Barnhill, Gary M. Longton, Heidi D. Nelson, Stevan R. Knezevich, Margaret S. Pepe, Patricia A. Carney, Linda J. Titus, Tracy Onega, Anna N.A. Tosteson, Martin A. Weinstock, Joann G. Elmore
Background Diagnostic interpretations of melanocytic skin lesions vary widely among pathologists, yet the underlying reasons remain unclear. Objective Identify pathologist characteristics associated with rates of accuracy and reproducibility. Methods Pathologists independently interpreted the same set of biopsies of melanocytic lesions on two occasions. Diagnoses were categorized into one of five classes according to the MPATH-Dx© system. Reproducibility was determined by pathologists’ concordance of diagnoses across two occasions. Accuracy was defined by concordance with a consensus reference standard. Associations of pathologist characteristics with reproducibility and accuracy were assessed individually and in multivariable logistic regression models. Results Rates of diagnostic reproducibility and accuracy were highest among pathologists with board certification and/or fellowship training in dermatopathology, and those with ≥5 years of experience. In addition, accuracy was high among pathologists with higher caseload composition and volume of melanocytic lesions. Limitations Data gathered in a test set situation using a classification tool not currently in clinical use. Conclusion Diagnoses are more accurate among pathologists with specialty training and those with more experience interpreting melanocytic lesions. These findings support the practice of referring difficult cases to more experienced pathologists to improve diagnostic accuracy, although the impact on patient outcomes of these referrals requires additional research.
Patient quality of life fluctuates before and after Mohs micrographic surgery: A longitudinal assessment of the patient experience J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-05 Junqian Zhang, Christopher J. Miller, Victoria O’Malley, Jeremy R. Etzkorn, Thuzar M. Shin, Joseph F. Sobanko
Background Changes in patient perceptions of quality of life (QOL) after Mohs micrographic surgery (MMS) may benefit from different counseling or treatment. Objective To measure QOL before and after MMS and to identify risk factors associated with impaired QOL. Methods Prospective observational study of 727 skin cancer patients who self-reported QOL via the Skin Cancer Index immediately before and at 1-2 weeks and 3 months after MMS. Results QOL fluctuated after MMS. At 1-2 weeks after surgery, overall QOL remained unchanged compared to before MMS. Patients reported reduced anxiety about skin cancer, but had increased distress about social interactions and physical appearance. At three months after surgery, patients reported an overall improvement in QOL compared to before MMS, (p = 0.0007). Age under 65 years (p = 0.0001), female gender (p = 0.0001), and tobacco use (p = 0.03) were associated with lower QOL scores at all assessment points. Limitations Single-site observational study. Significant loss to follow-up at both time points after MMS. Conclusion Skin cancer patients had persistent concerns about social interactions and physical appearance 1-2 weeks after MMS, but all aspects of QOL improved by three months after surgery. MMS patients who were less than 65 years old, female, or smoked were at increased risk for longitudinally impaired QOL.
Assessing the Safety of Superficial Chemical Peels in Darker Skin: A Retrospective Study J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-05 Shalini Vemula, Mayra B.C. Maymone, Eric A. Secemsky, Raphael Widjajahakim, Nicole M. Patzelt, Dana Saade, Neelam A. Vashi
Background Chemical peels have shown efficacy in the treatment of acne, photoaging, and pigmentary dyschromias; however, studies evaluating side effects, particularly in patients with skin of color, are limited. Objective We sought to determine the frequency of side effects and complications associated with superficial chemical peels in patients with skin types III-VI. Methods A 5-year single center retrospective analysis was performed. Results Of 473 chemical peel treatments included in this study, 18 (3.8%) were associated with short-term (≤2 weeks) or long-term (>2 weeks) complications. The most frequent complications were crusting (2.3%), post-inflammatory hyperpigmentation (PIH) (1.9%) and erythema (1.9%). All side effects resolved within 8 months of treatment and were located on the face. When stratified by season, side effects were noted to be less common during the winter. In the adjusted model, Fitzpatrick skin type VI was associated with a higher odds of side effects (OR, 5.14; 95% [CI], 1.21-21.8; P=0.0118). Limitations Single center retrospective design. Conclusion In this study, superficial chemical peels performed in patients with skin types III-VI had a relatively low complication rate, and skin type VI had higher odds of experiencing an adverse event. Side effects were noted to be less frequent during the winter months.
Somatic and psychiatric comorbidities of hidradenitis suppurativa in children and adolescents. J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-05 Hannu Tiri, Jari Jokelainen, Markku Timonen, Kaisa Tasanen, Laura Huilaja
Background Hidradenitis suppurativa (HS) is associated with various somatic and psychiatric comorbidities. Data regarding comorbidities in young HS patients are sparse. Objective We analyzed both somatic and psychiatric comorbidities in young patients in a nationwide HS cohort. Methods In this retrospective case-control study, data from cases of HS in young (aged ≥5 and <18 years) patients and age-matched controls with benign melanocytic nevi were collected from the Finnish Care Registry of Health Care. The prevalence of preselected comorbidities was compared between HS and control groups. Results A total of 153 HS cases were found in the specified age group. Of these, 34.0% had one or more somatic comorbidity compared with 4.9% of controls. At least one of the preselected psychiatric diagnoses was present before the age of 18 years in 15.7% of HS cases compared with 5.6% of controls. By the age of 23 years, at least one psychiatric comorbidity was identified in 23.5% of HS patients and 8.7% of controls. Limitations Despite being one of the largest HS cohorts ever studied, the number of young HS patients was relatively low. Since this was a registry-based study, it was not possible to verify the accuracy of International Classification of Diseases codes. Conclusion Physicians should monitor young patients with HS for both somatic and psychiatric comorbidities.
The Prognostic Significance of Tumor-Infiltrating Lymphocytes for Primary Melanoma Varies by Sex J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-05 Andrew J. Sinnamon, Cimarron E. Sharon, Yun Song, Madalyn G. Neuwirth, David E. Elder, Xiaowei Xu, Emily Y. Chu, Michael E. Ming, Douglas L. Fraker, Phyllis A. Gimotty, Giorgos C. Karakousis
Background The immune response to melanoma is manifested locally by tumor-infiltrating lymphocytes (TILs). Men and women are known to have varying patterns of immunity, yet sex-specific prognostic implications of TILs have not been explored. Methods Patients with clinically localized primary melanoma ≥0.76mm in Breslow thickness who underwent sentinel lymph node (SLN) biopsy at our institution were identified. Association between TILs (absent, nonbrisk, and brisk) and SLN positivity was evaluated using logistic regression. Overall survival (OS) was evaluated by TILs status and sex. Results Among 1,367 patients identified, 794 were men. TILs were brisk in 143 lesions, nonbrisk in 903, and absent in 321, which did not vary by sex (p=0.71). SLN positivity was associated with TILs among men (brisk 3.8%, nonbrisk 16.9%, absent 26.6%, p<0.001). In contrast, there was no association between SLN positivity and TILs among women (p=0.49). Interaction between brisk TILs and sex on SLN positivity was significant (p=0.029). Among men, presence of brisk TILs was associated with prolonged OS (p=0.038) but not after adjustment for SLN status (p=0.42). There was no association between TILs status and OS among women. Limitations Findings from this single-institution study have yet to be validated by other research groups. Conclusions The implications of TILs in predicting SLN positivity appear to be more relevant for men than women.
Patients prioritize local recurrence risk over other attributes for surgical treatment of facial melanomas - results of a stated preference survey and choice-based conjoint analysis J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-02 Jeremy R. Etzkorn, Scott D. Tuttle, Ilya Lim, Elea M. Feit, Joseph F. Sobanko, Thuzar M. Shin, Donald E. Neal, Christopher J. Miller
Background Surgical treatment options for facial melanomas include conventional excision with postoperative margin assessment (CE-POMA), Mohs micrographic surgery with immunostains (MMS-I) or slow Mohs. Patient preferences for these surgical options have not been studied. Objectives To evaluate patient preferences for surgical treatment of facial melanoma and to determine how patients value the relative importance of different surgical attributes. Methods Participants completed a two-part study consisting of a stated preference survey and a choice-based conjoint analysis (CBCA) experiment. Results Patients overwhelmingly (94.3%) rate local recurrence risk as “very important” and rank it as the most important attribute of surgical treatment for facial melanoma. Via CBCA, patients ranked the following surgical attributes from highest to lowest importance: local recurrence rate, out-of-pocket cost, chance of second surgical visit, timing of reconstruction, travel time, and time in office for the procedure. Consistent with their prioritization of low local recurrence rates, over 73% of respondents selected MMS-I or slow Mohs as their preferred treatment option for a facial melanoma. Limitations Data were obtained from a single health system. Conclusion Patients prefer surgical treatment options that minimize risk for local recurrence. Logistics for travel and treatment have less influence on patient preferences. Most survey participants chose MMS-I to maximize local cure and convenience of care.
Impact of Topical Fluorouracil Cream on Costs of Treating Keratinocyte Carcinoma (Nonmelanoma Skin Cancer) and Actinic Keratosis J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-02 Jean Yoon, Ciaran S. Phibbs, Adam Chow, Martin A. Weinstock
Background It is unknown whether treatment costs of Keratinocyte Carcinoma (KC) and Actinic Keratosis (AK) can be lowered by spending more on chemoprevention. Objective We examine the impact of one-course treatment of topical fluorouracil on the face and ears on KC and AK treatment costs over three years. Methods The VAKCC trial compared the efficacy of topical fluorouracil cream, 5%, vs vehicle control cream for reducing KC risk. Trial data and administrative data on costs and utilization were analyzed to measure post-randomization encounters and treatment costs for KC and AK care. Adjusted models were used to test for statistically significant differences between treatment arms for number of treatment encounters and costs. Results One year after randomization, the control arm had higher mean number of treatment encounters for SCC (0.04) than the intervention arm (0.01) (P<0.01). At one year the intervention arm had lower treatment and dermatologic costs of $2,106 (SD=$2,079) compared to $2,444 (SD=$2,716) for control patients (P=0.02). After three years, the intervention arm incurred $771 less per patient. Limitations Care not provided or paid by VA was not included. Results may not be generalizable to other payers. Conclusion We found significant cost savings for patients treated with 5-FU.
T-cell–mediated immune response to pneumococcal conjugate vaccine (PCV-13) and tetanus toxoid vaccine in patients with moderate-to-severe psoriasis during tofacitinib treatment J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-02 Kevin L. Winthrop, Neil Korman, William Abramovits, Scott T. Rottinghaus, Huaming Tan, Annie Gardner, Geoffrey Mukwaya, Mandeep Kaur, Hernan Valdez
Background Psoriasis is often treated with immunomodulatory therapies that can affect the immune response to common antigens. Tofacitinib is an oral Janus kinase inhibitor. Objective To characterize the effect of long-term exposure to tofacitinib 10 mg twice daily on T-cell function in psoriasis patients. Methods Patients completing at least 3 months' continuous treatment with tofacitinib 10 mg twice daily were vaccinated with T-cell–dependent vaccines (monovalent tetanus toxoid and 13-valent pneumococcal conjugate [PCV-13]). Patients were assessed at baseline (before vaccination) and then again 4 weeks after vaccination. For PCV-13, we evaluated serotype-specific, opsonophagocytic antibody responses, and for tetanus toxoid, we evaluated humoral responses. Results Among 60 patients who completed the study, the geometric mean fold rise from baseline for the 13 PCV serotypes at 4 weeks postvaccination varied from 8.3 (serotype 3) to 101.9 (serotype 6A). Similar results were observed for patients with and without lymphopenia at baseline. For tetanus toxoid, 51 (88%) patients had ≥2-fold and 35 (60%) patients had ≥4-fold rise in antibody concentration. Limitations There was no placebo control. Conclusion Most psoriasis patients who receive tofacitinib can mount satisfactory T-cell–dependent responses to PCV-13 and tetanus vaccines.
Interleukin-17, Inflammation, and Cardiovascular Risk in Patients With Psoriasis J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-02 Benjamin Lockshin, Yevgeniy Balagula, Joseph F. Merola
In addition to being recognized as a chronic inflammatory disease that manifests in the skin, psoriasis is increasingly understood to be a systemic disease that causes immune dysregulation throughout the body. The systemic nature of psoriasis is evidenced by the higher burden of comorbidities and shorter life expectancies of patients with psoriasis, particularly those with early onset and severe disease. Notably, psoriasis is associated with an increased risk for cardiovascular disease, which is the most common cause of morbidity and mortality in patients with psoriasis. In this review, we examine the association between psoriasis and cardiovascular disease and specifically focus on the role of interleukin-17–mediated inflammation as a potential mechanistic link between psoriasis and cardiovascular disease. Moreover, we describe potential treatment approaches to reduce the burden of cardiovascular disease in patients with psoriasis, and discuss the clinical importance of the association of these 2 diseases with respect to patient management and education.
A Spectrum Including Features of Psoriasis and Pityriasis Rubra Pilaris J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-01 Brittany G. Craiglow, Lynn M. Boyden, Ronghua Hu, Marie Virtanen, John Su, Gabriela Rodriguez, Catherine McCarthy, Paula Luna, Margarita Larralde, Stephen Humphrey, Kristen E. Holland, Marcia Hogeling, Benjamin Hidalgo-Matlock, Bruno Ferrari, Esteban Fernandez-Faith, Beth Drolet, Kelly M. Cordoro, Anne M. Bowcock, Richard J. Antaya, Kurt Ashack, Richard J. Ashack, Richard P. Lifton, Leonard M. Milstone, Amy S. Paller, Keith A. Choate
Background Heterozygous mutations in CARD14 have been shown to be associated with psoriasis and familial pityriasis rubra pilaris (PRP). Many patients with CARD14 mutations display features of both disorders, which can result in diagnostic uncertainty. In addition, these eruptions are often recalcitrant to conventional psoriasis therapies such as methotrexate, oral retinoids and TNF-α inhibitors. Objective We sought to describe the clinical characteristics, family history, and response to therapy in subjects with papulosquamous eruptions due to mutations in CARD14. Methods Subjects were referred for genetic testing as part of a registry of patients with inherited disorders of keratinization. DNA was isolated from blood or saliva, and multiplex targeted next generation sequencing or whole exome sequencing was performed. Clinical histories of subjects with CARD14 mutations were reviewed. Results We identified 15 kindreds with CARD14-associated papulosquamous eruption (CAPE). Characteristic features of CAPE include early age of onset, prominent involvement of the cheeks, chin and ears, family history of psoriasis or PRP, minimal response to conventional topical and systemic psoriasis therapies, and improvement with ustekinumab. Limitations Relatively small sample size. Conclusions Many subjects with CARD14 mutations display characteristics of both psoriasis and PRP. We propose the term CARD14-associated papulosquamous eruption (CAPE) to describe this spectrum of disease. Patients with clinical features suggestive of CAPE should undergo CARD14 sequencing and may benefit from treatment with ustekinumab.
Pregnancy Outcomes in Patients with Vitiligo: A Nationwide Population-based Cohort Study from Korea J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-01 Kui Young Park, Hyun Jung Kwon, Jeong Ha Wie, Han Hee Lee, Sung Bin Cho, Beom Joon Kim, Jung Min Bae
Background Vitiligo is a chronic autoimmune skin disorder affecting 1% of populations worldwide. Few large-scale studies have explored adverse pregnancy outcomes in patients with vitiligo. Objective To investigate adverse pregnancy outcomes in patients with vitiligo. Methods We performed a retrospective cohort study on 4,738 pregnancies of women with vitiligo and 47,380 pregnancies of age-matched controls without vitiligo using the Korean National Health Insurance (NHI) Claims database from 2007 to 2016. Multivariate logistic regression models were used to evaluate the associations between vitiligo and pregnancy outcomes, including live births, spontaneous abortion, cesarean delivery, preterm delivery, gestational diabetes, stillbirth, pre-eclampsia/eclampsia, and intrauterine growth retardation. Results Patients with vitiligo exhibited a significantly lower live birth rate (odds ratio [OR] 0.870, 95% confidence interval [CI] 0.816–0.927) and a higher incidence of spontaneous abortion (OR 1.250, 95% CI 1.148–1.362) than the control group. Limitation: The NHI Claims database lacks detailed clinical information on individual patients. Conclusion Vitiligo was significantly associated with an increased risk of spontaneous abortion. Further studies are needed to determine whether systemic autoimmunity explains our finding.
Title: Opioid, Alcohol, and Cannabis Misuse Among Patients with Hidradenitis Suppurativa: a population-based analysis in the United States J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-01 Amit Garg, Vassiliki Papagermanos, Margaretta Midura, Andrew Strunk, Jonathan Merson
Background Patients with hidradenitis suppurativa (HS) experience chronic pain and have significant physical, emotional and psychological disease impact. These patients may be at risk for substance abuse. Objective To evaluate substance use disorder (SUD) among HS patients in the United States. Methods Cross-sectional analysis of adult HS patients (n = 32,625) identified using electronic health records data from a population-based sample of over 50 million patients. Results The prevalence of SUD among patients with HS was 4.0% (1,315/32,625), compared to 2.0% (195,260/9,581,640) for patients without HS (p<0.001). The most common forms of substance misuse among HS patients were alcohol (630/1,315; 47.9% of SUD cases), followed by opioids (430/1,315, 32.7% of SUD cases) and cannabis (430/1,315, 29.7% of SUD cases). HS patients had 1.50 [95% CI 1.42-1.59] times the adjusted odds of SUD compared to patients without HS. HS patients had significantly greater odds of SUD across demographic subgroups. The association between HS and SUD was generally stronger for patients aged 45-64 years, non-whites, privately-insured, and those without depressive or anxiety disorder. Limitations SUD may not be accurately diagnosed. Conclusion Patients with HS have higher odds of SUD and may benefit from periodic screening for substance abuse.
The Risk of Cardiovascular Events in Psoriasis Patients Treated with Tumor Necrosis Factor-alpha Inhibitors versus Phototherapy: An Observational Cohort Study J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-01 Jashin J. Wu, Murali Sundaram, Martin Cloutier, Marjolaine Gauthier-Loiselle, Annie Guérin, Rakesh Singh, Arijit Ganguli
Background Psoriasis is a risk factor for cardiovascular events. Objective To assess the risk of major cardiovascular events and the effect of cumulative treatment exposure on cardiovascular event risk in psoriasis patients treated with tumor necrosis factor-alpha inhibitors (TNFis) versus phototherapy. Methods Adult psoriasis patients were selected from a large US administrative claims database (Q1:2000 - Q3:2014) and classified in two mutually exclusive cohorts, based on whether they were treated with TNFis or phototherapy. Cardiovascular event risk was compared between cohorts using multivariate Cox proportional hazards models. Cumulative exposure was defined based on treatment persistence. Results A total of 11,410 TNFi and 12,433 phototherapy patients (PUVA: 1,117; UVB: 11,316) were included in the study. TNFi patients had a lower risk of cardiovascular events compared to phototherapy patients (adjusted hazard ratio: 0.77; p<0.05). The risk reduction associated with 6 months of cumulative exposure was 11.2% larger for patients treated with TNFis compared to phototherapy (p<0.05). Limitations Information on psoriasis severity and mortality was limited/not available. Conclusions Psoriasis patients treated with TNFis exhibited a lower cardiovascular event risk than patients treated with phototherapy. Cumulative exposure to TNFis was associated with an incremental cardiovascular risk reduction compared to phototherapy.
Melanoma risk prediction using a multi-locus genetic risk score in the Women’s Health Initiative cohort J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-01 Hyunje G. Cho, Katherine J. Ransohoff, Lingyao Yang, Haley Hedlin, Themistocles Assimes, Jiali Han, Marcia Stefanick, Jean Y. Tang, Kavita Y. Sarin
Background Single-nucleotide polymorphisms (SNPs) associated with melanoma have been identified though genome-wide association studies (GWASs). However, the combined impact of these SNPs on melanoma development remains unclear, particularly in post-menopausal women who carry lower melanoma risk. Objective To examine the contribution of a combined polygenic risk score on melanoma development in post-menopausal women. Methods Genetic risk scores (GRS) were calculated using 21 GWAS-significant SNPs. Their combined effect on melanoma development was evaluated in 19,102 post-menopausal Caucasian women in the Clinical Trial (CT) and Observational Study (OS) arms of Women’s Health Initiative (WHI) dataset. Results Compared to the tertile of weighted GRS with lowest genetic risk, the women in the tertile with highest genetic risk were 1.9 times likely to develop melanoma (95% CI: [1.50, 2.42]). The incremental change in c-index from adding GRS to age were 0.075 (95%CI: [0.041,0.109]) for incident melanoma. Limitations Limitations include lack of information on nevi count, Fitzpatrick skin type, family history of melanoma, as well as potential reporting and selection bias in the WHI cohort. Conclusion Higher genetic risk is associated with increased melanoma prevalence and incidence in post-menopausal women, but current genetic information may have a limited role in risk prediction when phenotypic information is available.
Similar survival of patients with multiple vs. single primary melanomas based on Utah SEER data (1973-2011) J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-03-01 Douglas Grossman, James M. Farnham, John Hyngstrom, Marki E. Klapperich, Aaron M. Secrest, Sarah Empey, Glen M. Bowen, David Wada, Robert H.I. Andtbacka, Kenneth Grossmann, Tawnya L. Bowles, Lisa A. Cannon-Albright
Background Survival data are mixed comparing patients with multiple primary melanomas (MPM) to those with single primary melanomas (SPM). Objectives To compare MPM vs. SPM patient survival, using a matching method that avoids potential biases associated with other analytic approaches. Methods Records of 14,138 individuals obtained from the Surveillance, Epidemiology, and End-Results registry of all melanomas diagnosed or treated in Utah from 1973-2011 were reviewed. A single matched control patient was selected randomly from the SPM cohort for each MPM patient, with the restriction that they survived at least as long as the interval between the first and second diagnoses for the matched MPM patient. Results Survival curves (n=887 MPM, 887 SPM) without covariates showed a significant survival disadvantage for MPM patients (chi-squared = 39.29, p < 0.001). However, a multivariate Cox proportional hazards model showed no significant survival difference (hazard ratio = 1.07, p = 0.55). Restricting the multivariate analysis to invasive melanomas also showed no significant survival difference (hazard ratio = 0.99, p = 0.96). Limitations Breslow depth, ulceration status, and specific cause of death was not available for all patients. Conclusions Patients with MPM had similar survival time as patients with SPM.
Serlopitant for the treatment of chronic pruritus: results of a randomized, multicenter, placebo-controlled phase 2 clinical trial J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-02-17 Gil Yosipovitch, Sonja Ständer, Matthew B. Kerby, James W. Larrick, Andrew J. Perlman, Edward F. Schnipper, Xiaoming Zhang, Jean Y. Tang, Thomas Luger, Martin Steinhoff
Background The substance P/neurokinin 1 receptor (NK1R) pathway is critical in chronic pruritus; anecdotal evidence suggests antagonism of this pathway can reduce chronic itch. Objective To assess the safety and efficacy of the NK1R antagonist serlopitant in treating chronic pruritus. Methods Eligible patients with severe chronic pruritus who were refractory to antihistamines or topical steroids were randomized to serlopitant 0.25, 1, or 5 mg, or placebo, administered once daily for 6 weeks as monotherapy or with midpotency steroids and emollients. The primary efficacy end point was percentage change in Visual Analog Scale (VAS) pruritus score from baseline. Results Serlopitant treatment resulted in a dose-dependent decrease in pruritus. Mean percentage decreases from baseline VAS pruritus scores were statistically significantly larger for the 1- and 5-mg doses of serlopitant (P = .022 and P = .013) versus placebo at week 6. No significant safety or tolerability differences were detected among the groups. Limitations The sample size was insufficient for subgroup analyses of the efficacy of serlopitant for chronic pruritus based on underlying conditions. Conclusions Serlopitant 1 mg and 5 mg daily was associated with a statistically significant reduction in chronic pruritus and was well tolerated [NCT01951274].
Diagnosis and Management of Pemphigus: recommendations by an International Panel of Experts J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-02-10 Dedee F. Murrell, Sandra Peña, Pascal Joly, Branka Marinovic, Takashi Hashimoto, Luis A. Diaz, Animesh A. Sinha, Aimee S. Payne, Maryam Daneshpazhooh, Rüdiger Eming, Marcel F. Jonkman, Daniel Mimouni, Luca Borradori, Soo-Chan Kim, Jun Yamagami, Julia S. Lehman, Marwah Adly Saleh, Donna A. Culton, Annette Czernik, John J. Zone, David Fivenson, Hideyuki Ujiie, Katarzyna Wozniak, Ayşe Akman-Karakaş, Philippe Bernard, Neil J. Korman, Frédéric Caux, Kossara Drenovska, Catherine Prost-Squarcioni, Snejina Vassileva, Ron J. Feldman, Adela Rambi Cardones, Johann Bauer, Dimitrios Ioannides, Hana Jedlickova, Francis Palisson, Aikaterini Patsatsi, Soner Uzun, Savas Yayli, Detlef Zillikens, Masayuki Amagai, Michael Hertl, Enno Schmidt, Valeria Aoki, Sergei A. Grando, Hiroshi Shimizu, Sharon Baum, Guiseppe Cianchini, Claudio Feliciani, Pilar Iranzo
Background Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management, Objective We now present results from a subsequent Delphi consensus to broaden the generalizability of recommendations. Methods A preliminary survey, based on the European Dermatology Forum (EDF) and the European Academy of Dermatology and Venereology (EADV) guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology (AAD) conference. A second survey was sent following the meeting to more experts to achieve greater international consensus. Results The 39 experts participated in the first round of the Delphi-survey while 54 from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II based on Delphi results and meeting discussion. Limitations Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available. Conclusions We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first line therapy option for moderate to severe pemphigus.
The impact of underlying disease state on outcomes in patients with pyoderma gangrenosum: A national survey J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-02-10 Benjamin H. Kaffenberger, Alice Hinton, Somashekar Krishna
Background It is unclear if the underlying disease affects the outcomes in pyoderma gangrenosum. Objectives To determine the impact of comorbid disease associations and concomitant procedural treatments on patient outcomes in PG patient-hospitalizations. Methods A cross-sectional analysis of the Nationwide Inpatient Sample (NIS) for PG patient-hospitalizations from years 2002-2011, analyzing in-hospital mortality rate and health care resource utilization. Results Inflammatory bowel disease was the most frequent comorbid association, followed by inflammatory arthritis, hematologic malignancies/dyscrasias, and vasculitis. Multivariable modeling showed that vasculitis and hematologic malignancy/dyscrasia, when compared to subjects with IBD, were associated with a 4-6 fold increased risk of in-hospital mortality while increasing healthcare resource utilization. Inpatient procedural interventions including skin grafts, biopsies, and debridement did not impact mortality and were associated with an increased length of stay. Limitations The database does not account for outpatient follow-up, additionally there was a low rate of coded comorbid conditions. Conclusions Comprehensive evaluation to determine the underlying comorbidity for patients with PG is important for patient risk stratification.
Comparative Effectiveness of Targeted Immunomodulators for the Treatment of Moderate-to-Severe Plaque Psoriasis: A Systematic Review and Network Meta-Analysis J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-02-10 Anne M. Loos, Shanshan Liu, Celia Segel, Daniel A. Ollendorf, Steven D. Pearson, Jeffrey A. Linder
Background The comparative effectiveness of available targeted immunomodulators for moderate-to-severe psoriasis has not been evaluated. Objective To evaluate the comparative effectiveness of targeted immunomodulators for adults with moderate-to-severe plaque psoriasis. Methods Systematic literature review of placebo-controlled and head-to-head randomized trials of eight targeted immunomodulators that evaluated clinical benefits or harms. The primary outcome was a 75% improvement on the Psoriasis Area and Severity Index (“PASI 75”). We also conducted a network meta-analysis (NMA) adjusted for placebo response to perform indirect comparisons between agents. Results In the NMA, the targeted immunomodulators ordered by an increasing relative risk (demonstrating greater likelihood) of achieving PASI 75 relative to placebo were: apremilast (6.2), etanercept (9.6), adalimumab (13.0), ustekinumab (14.0), secukinumab (15.4), infliximab (16.2), brodalumab (17.3), and ixekizumab (17.9). Ixekizumab, brodalumab, and infliximab were all statistically superior to ustekinumab, adalimumab, etanercept, and apremilast; results were similar to head-to-head studies where data were available. Limitations Much of the evidence is short-term (10-16 weeks); limited direct comparisons. Conclusions The Interleukin-17A inhibitors are more effective in achieving clearance than ustekinumab, which are, in turn, generally more effective than etanercept, adalimumab, and apremilast.
Estimating the health care costs associated with recurrent cellulitis managed in the outpatient setting J. Am. Acad. Dermatol. (IF 7.002) Pub Date : 2018-02-07 Jessica St. John, Lauren Strazzula, Priyanka Vedak, Daniela Kroshinsky
Background Recurrent cellulitis is diagnosed in 22% to 49% of all cellulitis cases, but little is known about the costs associated with these cases. Objective To characterize patients with recurrent cellulitis in the outpatient setting and estimate the associated costs. Methods A retrospective chart review was conducted for adult patients who presented to the outpatient facilities at our institution from January 1, 2007, to December 31, 2011, with recurrent cellulitis. Data provided by the Centers for Medicare and Medicaid Services were used. Results A total of 157 patients were identified; 56% were male, with a mean age of 62.7 years. The mean number of episodes of cellulitis per patient was 3. Antibiotics were prescribed for all patients with a diagnosis of recurrent cellulitis, with 93% treated with oral antibiotics and 17.6% treated with intravenous antibiotics. A total of 1081 laboratory and 175 radiologic imaging tests were ordered. The minimum average cost per cellulitis episode was $586.91; the average cost per visit was $292.50. Limitations Retrospective study; use of a single, large academic institution; and utilization of cost estimates that may not adequately reflect the variation of costs across closed-system sites or geographic regions. There was no accounting for the nonfinancial or opportunity costs associated with hospitalization, such as lost days of employment or child care and any long-term morbidities, among others. Conclusions Recurrent cellulitis in the outpatient setting costs about $586.91 per episode. Although there is no criterion standard for diagnosis or treatment of cellulitis, our analysis demonstrates the need for more evidence-based management to achieve better outcomes and reduce the significant health care costs.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
- Acc. Chem. Res.
- ACS Appl. Mater. Interfaces
- ACS Biomater. Sci. Eng.
- ACS Catal.
- ACS Cent. Sci.
- ACS Chem. Biol.
- ACS Chem. Neurosci.
- ACS Comb. Sci.
- ACS Earth Space Chem.
- ACS Energy Lett.
- ACS Infect. Dis.
- ACS Macro Lett.
- ACS Med. Chem. Lett.
- ACS Nano
- ACS Omega
- ACS Photonics
- ACS Sens.
- ACS Sustainable Chem. Eng.
- ACS Synth. Biol.
- Acta Biomater.
- Acta Crystallogr. A Found. Adv.
- Acta Mater.
- Adv. Colloid Interface Sci.
- Adv. Electron. Mater.
- Adv. Energy Mater.
- Adv. Funct. Mater.
- Adv. Healthcare Mater.
- Adv. Mater.
- Adv. Mater. Interfaces
- Adv. Opt. Mater.
- Adv. Sci.
- Adv. Synth. Catal.
- AlChE J.
- Anal. Bioanal. Chem.
- Anal. Chem.
- Anal. Chim. Acta
- Anal. Methods
- Angew. Chem. Int. Ed.
- Annu. Rev. Anal. Chem.
- Annu. Rev. Biochem.
- Annu. Rev. Environ. Resour.
- Annu. Rev. Food Sci. Technol.
- Annu. Rev. Mater. Res.
- Annu. Rev. Phys. Chem.
- Appl. Catal. A Gen.
- Appl. Catal. B Environ.
- Appl. Clay. Sci.
- Appl. Energy
- Aquat. Toxicol.
- Arab. J. Chem.
- Asian J. Org. Chem.
- Atmos. Environ.
- Carbohydr. Polym.
- Catal. Commun.
- Catal. Rev. Sci. Eng.
- Catal. Sci. Technol.
- Catal. Today
- Cell Chem. Bio.
- Cem. Concr. Res.
- Ceram. Int.
- Chem. Asian J.
- Chem. Bio. Drug Des.
- Chem. Biol. Interact.
- Chem. Commun.
- Chem. Educ. Res. Pract.
- Chem. Eng. J.
- Chem. Eng. Sci.
- Chem. Eur. J.
- Chem. Mater.
- Chem. Phys.
- Chem. Phys. Lett.
- Chem. Phys. Lipids
- Chem. Rev.
- Chem. Sci.
- Chem. Soc. Rev.
- Chin. J. Chem.
- Combust. Flame
- Compos. Part A Appl. Sci. Manuf.
- Compos. Sci. Technol.
- Compr. Rev. Food Sci. Food Saf.
- Comput. Chem. Eng.
- Constr. Build. Mater.
- Coordin. Chem. Rev.
- Corros. Sci.
- Crit. Rev. Food Sci. Nutr.
- Crit. Rev. Solid State Mater. Sci.
- Cryst. Growth Des.
- Curr. Opin. Chem. Eng.
- Curr. Opin. Colloid Interface Sci.
- Curr. Opin. Environ. Sustain
- Curr. Opin. Solid State Mater. Sci.
- Ecotox. Environ. Safe.
- Electrochem. Commun.
- Electrochim. Acta
- Energy Environ. Sci.
- Energy Fuels
- Energy Storage Mater.
- Environ. Impact Assess. Rev.
- Environ. Int.
- Environ. Model. Softw.
- Environ. Pollut.
- Environ. Res.
- Environ. Sci. Policy
- Environ. Sci. Technol.
- Environ. Sci. Technol. Lett.
- Environ. Sci.: Nano
- Environ. Sci.: Processes Impacts
- Environ. Sci.: Water Res. Technol.
- Eur. J. Inorg. Chem.
- Eur. J. Med. Chem.
- Eur. J. Org. Chem.
- Eur. Polym. J.
- J. Acad. Nutr. Diet.
- J. Agric. Food Chem.
- J. Alloys Compd.
- J. Am. Ceram. Soc.
- J. Am. Chem. Soc.
- J. Am. Soc. Mass Spectrom.
- J. Anal. Appl. Pyrol.
- J. Anal. At. Spectrom.
- J. Antibiot.
- J. Catal.
- J. Chem. Educ.
- J. Chem. Eng. Data
- J. Chem. Inf. Model.
- J. Chem. Phys.
- J. Chem. Theory Comput.
- J. Chromatogr. A
- J. Chromatogr. B
- J. Clean. Prod.
- J. CO2 UTIL.
- J. Colloid Interface Sci.
- J. Comput. Chem.
- J. Cryst. Growth
- J. Dairy Sci.
- J. Electroanal. Chem.
- J. Electrochem. Soc.
- J. Environ. Manage.
- J. Eur. Ceram. Soc.
- J. Fluorine Chem.
- J. Food Drug Anal.
- J. Food Eng.
- J. Food Sci.
- J. Funct. Foods
- J. Hazard. Mater.
- J. Heterocycl. Chem.
- J. Hydrol.
- J. Ind. Eng. Chem.
- J. Inorg. Biochem.
- J. Magn. Magn. Mater.
- J. Mater. Chem. A
- J. Mater. Chem. B
- J. Mater. Chem. C
- J. Mater. Process. Tech.
- J. Mech. Behav. Biomed. Mater.
- J. Med. Chem.
- J. Membr. Sci.
- J. Mol. Catal. A Chem.
- J. Mol. Liq.
- J. Nat. Gas Sci. Eng.
- J. Nat. Prod.
- J. Nucl. Mater.
- J. Org. Chem.
- J. Photochem. Photobiol. C Photochem. Rev.
- J. Phys. Chem. A
- J. Phys. Chem. B
- J. Phys. Chem. C
- J. Phys. Chem. Lett.
- J. Polym. Sci. A Polym. Chem.
- J. Porphyr. Phthalocyanines
- J. Power Sources
- J. Solid State Chem.
- J. Taiwan Inst. Chem. E.
- Macromol. Rapid Commun.
- Mass Spectrom. Rev.
- Mater. Chem. Front.
- Mater. Des.
- Mater. Horiz.
- Mater. Lett.
- Mater. Sci. Eng. A
- Mater. Sci. Eng. R Rep.
- Mater. Today
- Meat Sci.
- Med. Chem. Commun.
- Microchem. J.
- Microchim. Acta
- Micropor. Mesopor. Mater.
- Mol. Biosyst.
- Mol. Cancer Ther.
- Mol. Catal.
- Mol. Nutr. Food Res.
- Mol. Pharmaceutics
- Mol. Syst. Des. Eng.
- Nano Energy
- Nano Lett.
- Nano Res.
- Nano Today
- Nano-Micro Lett.
- Nanomed. Nanotech. Biol. Med.
- Nanoscale Horiz.
- Nat. Catal.
- Nat. Chem.
- Nat. Chem. Biol.
- Nat. Commun.
- Nat. Energy
- Nat. Mater.
- Nat. Med.
- Nat. Methods
- Nat. Nanotech.
- Nat. Photon.
- Nat. Prod. Rep.
- Nat. Protoc.
- Nat. Rev. Chem.
- Nat. Rev. Drug. Disc.
- Nat. Rev. Mater.
- Natl. Sci. Rev.
- Neurochem. Int.
- New J. Chem.
- NPG Asia Mater.
- npj 2D Mater. Appl.
- npj Comput. Mater.
- npj Flex. Electron.
- npj Mater. Degrad.
- npj Sci. Food
- Pharmacol. Rev.
- Pharmacol. Therapeut.
- Photochem. Photobiol. Sci.
- Phys. Chem. Chem. Phys.
- Phys. Life Rev.
- PLOS ONE
- Polym. Chem.
- Polym. Degrad. Stabil.
- Polym. J.
- Polym. Rev.
- Powder Technol.
- Proc. Combust. Inst.
- Prog. Cryst. Growth Ch. Mater.
- Prog. Energy Combust. Sci.
- Prog. Mater. Sci.
- Prog. Photovoltaics
- Prog. Polym. Sci.
- Prog. Solid State Chem.