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Item Baseline Levels of Circulating Inflammatory Biomarkers Stratify Patients with Vitiligo Who Significantly Repigment after Treatment with Ruxolitinib Cream(Elsevier, 2023-09-13) Howell, Michael D.; Kuo, Fiona I.; Rumberger, Beth; Boarder, Erika; Sun, Kang; Butler, Kathleen; Harris, John E.; Grimes, Pearl; Rosmarin, David; Dermatology, School of MedicineBackground: Efficacy of ruxolitinib cream, a topical Jak1/Jak2 inhibitor, was demonstrated in a phase 2 trial in patients with vitiligo. Objective: This study aimed to characterize circulating inflammatory biomarker profiles in patients who demonstrated ≥50% improvement in facial Vitiligo Area Scoring Index scores by week 24 (group 1) and those who did not (group 2). Design: This was a posthoc analysis of a multicenter, randomized, double-blind, vehicle-controlled, phase 2 study in which screening was conducted between June 7, 2017 and March 21, 2018. Population: Patients aged between 18 and 75 years with vitiligo, including depigmentation affecting ≥0.5% of body surface area on the face and ≥3% of body surface area on nonfacial areas, were eligible. Intervention: Patients applied 1.5% ruxolitinib cream to lesions once or twice daily for 52 weeks. Main outcomes and measures: Patients were grouped by achievement of ≥50% improvement in facial Vitiligo Area Scoring Index at week 24. Proteomic analysis was performed on baseline serum samples. Results: Mean ± standard error facial Vitiligo Area Scoring Index in group 1 (n = 30) versus group 2 (n = 27) improved by 79.9 ± 4.0% versus 1.1 ± 7.3% and 91.9 ± 1.5% versus 25.1 ± 13.4% at weeks 24 and 52, respectively. Broad proteomic analysis revealed 76 proteins (of 1,104 tested) that were differentially expressed between groups 1 and 2 at baseline (P < 0.05). Ten distinct proteins were upregulated in group 1; 64 were elevated in group 2. Conclusion: This analysis identified potential differences between patients who achieved ≥50% improvement in facial Vitiligo Area Scoring Index at 24 weeks and those who did not that require deeper scientific interrogation and may be important in stratifying therapeutic benefit for patients with vitiligo.Item Correction to: Real-World Treatment Patterns in Patients with Vitiligo in the United States(Springer, 2023) Rosmarin, David; Soliman, Ahmed M.; Li, Chao; Dermatology, School of MedicineCorrection to: Dermatol Ther (Heidelb) (2023) 13:2079–2091 10.1007/s13555-023-00983-3 Authors would like to update the middle name of co-author as Ahmed M. Soliman. The original article has been corrected.Item Focal Adhesion Kinase Binds to the HPV E2 Protein to Regulate Initial Replication after Infection(MDPI, 2023-09-28) Jose, Leny; Gonzalez, Jessica; Kessinger, Emma; Androphy, Elliot J.; DeSmet, Marsha; Dermatology, School of MedicineHuman papillomaviruses are small DNA tumor viruses that infect cutaneous and mucosal epithelia. The viral lifecycle is linked to the differentiation status of the epithelium. During initial viral infection, the genomes replicate at a low copy number but the mechanism(s) the virus uses to control the copy number during this stage is not known. In this study, we demonstrate that the tyrosine kinase focal adhesion kinase (FAK) binds to and phosphorylates the high-risk viral E2 protein, the key regulator of HPV replication. The depletion of FAK with a specific PROTAC had no effect on viral DNA content in keratinocytes that already maintain HPV-16 and HPV-31 episomes. In contrast, the depletion of FAK significantly increased HPV-16 DNA content in keratinocytes infected with HPV-16 quasiviruses. These data imply that FAK prevents the over-replication of the HPV genome after infection through the interaction and phosphorylation of the E2 protein.Item Prevalence, Clinical Features, and Antibiotic Susceptibility of Group A Streptococcal Skin Infections in Schoolchildren in Urban Western and Northern Uganda(Wolters Kluwer, 2019) Chang, Aileen Y.; Scheel, Amy; Dewyer, Alyssa; Hovis, Ian W.; Sarnacki, Rachel; Aliku, Twalib; Okello, Emmy; Bwanga, Freddie; Sable, Craig; Maurer, Toby A.; Beaton, Andrea Z.; Dermatology, School of MedicineBackground: Group A Streptococcus (GAS) skin infections can lead to invasive sepsis, poststreptococcal glomerulonephritis, and potentially rheumatic heart disease (RHD). Within a study to identify predisposing factors of RHD in Ugandan schoolchildren, we determined the prevalence of skin infections and assessed the clinical features and antibiotic susceptibility of GAS skin infection. Methods: Cross-sectional study conducted at 3 urban primary schools in Western and Northern Uganda in March 2017. A dermatologist rendered clinical diagnoses and obtained a skin swab specimen from lesions with signs of bacterial infection. Beta-hemolytic colonies underwent Lancefield grouping, species identification by polymerase chain reaction and antimicrobial susceptibility testing. Results: From 3265 schoolchildren, we observed 32% with ≥1 fungal, 1.8% with ≥1 bacterial, 0.9% with ≥1 viral, and 0.2% with ≥1 ectoparasitic infection. Of 79, 25 (32%) specimens were GAS-positive, of which one-third demonstrated tetracycline resistance. Of 17 impetigo cases, 13 (76%) were located on the leg/foot and 3 (18%) on the head/neck. Prevalence of GAS skin infection was 0.8% (25 of 3265). In Northern Uganda, where subclinical definite RHD prevalence is 1.1%, GAS skin infection prevalence was 1.2% (4 of 343) and 0.9% (3 of 352). Conclusion: This study identifies tetracycline-resistant GAS in Ugandan communities, suggests modified skin examination of exposed anatomic locations may be appropriate for population-based GAS skin infection studies, and underscores need for clear case definitions of GAS skin infection. Future studies are needed to evaluate the role of GAS skin infection in development of RHD in Ugandan communities.Item Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2)(Wiley, 2021) Wollenberg, A.; Blauvelt, A.; Guttman-Yassky, E.; Worm, M.; Lynde, C.; Lacour, J.-P.; Spelman, L.; Katoh, N.; Saeki, H.; Poulin, Y.; Lesiak, A.; Kircik, L.; Cho, S. H.; Herranz, P.; Cork, M. J.; Peris, K.; Steffensen, L. A.; Bang, B.; Kuznetsova, A.; Jensen, T. N.; Østerdal, M. L.; Simpson, E. L.; ECZTRA 1 and ECZTRA 2 study investigators; Dermatology, School of MedicineBackground: Tralokinumab, a fully human monoclonal antibody, specifically neutralizes interleukin-13, a key cytokine driving peripheral inflammation in atopic dermatitis (AD). In phase II studies, tralokinumab combined with topical corticosteroids provided early and sustained improvements in AD signs and symptoms. Objectives: To evaluate the efficacy and safety of tralokinumab monotherapy in adults with moderate-to-severe AD who had an inadequate response to topical treatments. Methods: In two 52-week, randomized, double-blind, placebo-controlled, phase III trials, ECZTRA 1 and ECZTRA 2, adults with moderate-to-severe AD were randomized (3 : 1) to subcutaneous tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Primary endpoints were Investigator's Global Assessment (IGA) score of 0 or 1 at week 16 and ≥ 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. Patients achieving an IGA score of 0 or 1 and/or EASI 75 with tralokinumab at week 16 were rerandomized to tralokinumab Q2W or every 4 weeks or placebo, for 36 weeks. The trials were registered with ClinicalTrials.gov: NCT03131648 and NCT03160885. Results: At week 16, more patients who received tralokinumab vs. placebo achieved an IGA score of 0 or 1: 15·8% vs. 7·1% in ECZTRA 1 [difference 8·6%, 95% confidence interval (CI) 4·1-13·1; P = 0·002] and 22·2% vs. 10·9% in ECZTRA 2 (11·1%, 95% CI 5·8-16·4; P < 0·001) and EASI 75: 25·0% vs. 12·7% (12·1%, 95% CI 6·5-17·7; P < 0·001) and 33·2% vs. 11·4% (21·6%, 95% CI 15·8-27·3; P < 0·001). Early improvements in pruritus, sleep interference, Dermatology Life Quality Index, SCORing Atopic Dermatitis and Patient-Oriented Eczema Measure were observed from the first postbaseline measurements. The majority of week 16 tralokinumab responders maintained response at week 52 with continued tralokinumab treatment without any rescue medication (including topical corticosteroids). Adverse events were reported in 76·4% and 61·5% of patients receiving tralokinumab in ECZTRA 1 and ECZTRA 2, respectively, and in 77·0% and 66·0% of patients receiving placebo in ECZTRA 1 and ECZTRA 2, respectively, in the 16-week initial period. Conclusions: Tralokinumab monotherapy was superior to placebo at 16 weeks of treatment and was well tolerated up to 52 weeks of treatment.Item Cost Minimization Analysis of a Teledermatology Triage System in a Managed Care Setting(American Medical Association, 2021) Zakaria, Adam; Miclau, Theodore A.; Maurer, Toby; Leslie, Kieron S.; Amerson, Erin; Dermatology, School of MedicineImportance: Teledermatology (TD) enables remote triage and management of dermatology patients. Previous analyses of TD systems have demonstrated improved access to care but an inconsistent fiscal impact. Objective: To compare the organizationwide cost of managing newly referred dermatology patients within a TD triage system vs a conventional dermatology care model at the Zuckerberg San Francisco General Hospital and Trauma Center (hereafter referred to as the ZSFG) in California. Design, setting, and participants: A retrospective cost minimization analysis was conducted of 2098 patients referred to the dermatology department at the ZSFG between June 1 and December 31, 2017. Intervention: Implementation of the TD triage system in January 2015. Main outcomes and measures: The main outcome was mean cost to the health care organization to manage newly referred dermatology patients with or without TD triage. To estimate costs, decision-tree models were constructed to characterize possible care paths with TD triage and within a conventional dermatology care model. Costs associated with primary care visits, dermatology visits, and TD visits were then applied to the decision-tree models to estimate the mean cost of managing patients following each care path for 6 months. The mean cost for each visit type incorporated personnel costs, with the mean cost per TD consultation also incorporating software implementation and maintenance costs. Finally, ZSFG patient data were applied within the models to evaluate branch probabilities, enabling calculation of mean cost per patient within each model. Results: The analysis captured 2098 patients (1154 men [55.0%]; mean [SD] age, 53.4 [16.8] years), with 1099 (52.4%) having Medi-Cal insurance and 879 (41.9%) identifying as non-White. In the decision-tree model with TD triage, the mean (SD) cost per patient to the health care organization was $559.84 ($319.29). In the decision-tree model for conventional dermatology care, the mean (SD) cost per patient was $699.96 ($390.24). Therefore, the TD model demonstrated a statistically significant mean (SE) cost savings of $140.12 ($11.01) per patient. Given an annual dermatology referral volume of 3150 patients, the analysis estimates an annual savings of $441 378. Conclusions and relevance: Implementation of a TD triage system within the dermatology department at the ZSFG was associated with cost savings, suggesting that managed health care settings may experience significant cost savings from using TD to triage and manage patients.Item Evaluation of four chemotherapy regimens for treatment of advanced AIDS-associated Kaposi sarcoma in Kenya: a cost-effectiveness analysis(Elsevier, 2022) Freeman, Esther E.; McCann, Nicole C.; Semeere, Aggrey; Reddy, Krishna P.; Laker-Oketta, Miriam; Byakwaga, Helen; Pei, Pamela P.; Hajny Fernandez, Maya E.; Kiprono, Samson; Busakhala, Naftali; Martin, Jeffery N.; Maurer, Toby; Bassett, Ingrid V.; Freedberg, Kenneth A.; Hyle, Emily P.; Dermatology, School of MedicineBackground: The most effective treatment for advanced AIDS-associated Kaposi sarcoma is paclitaxel or pegylated liposomal doxorubicin (PLD); neither is routinely used in sub-Saharan Africa due to limited availability and high cost. We examined the clinical impact, costs, and cost-effectiveness of paclitaxel or PLD in Kenya, compared with etoposide or bleomycin-vincristine. Methods: In this study, we use the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-International Model to project clinical outcomes and costs among people living with HIV and advanced Kaposi sarcoma on antiretroviral therapy. We compared four different treatment strategies: etoposide, bleomycin-vincristine, paclitaxel, or PLD. We derived cohort characteristics and costs from the Kenyan Academic Model for Providing Access to Healthcare network, and adverse events, efficacy, and mortality from clinical trials. We projected model outcomes over a lifetime and included life expectancy, per-person lifetime costs, and incremental cost-effectiveness ratios (ICERs). We conducted budget impact analysis for 5-year total costs and did deterministic and probabilistic sensitivity analyses to evaluate the effect of uncertainty in input parameters. Findings: We found that paclitaxel would be more effective than bleomycin-vincristine and would increase life expectancy by 4·2 years per person. PLD would further increase life expectancy by 0·6 years per person. Paclitaxel would be the most cost-effective strategy (ICER US$380 per year-of-life-saved compared with bleomycin-vincristine) and would remain cost-effective across a range of scenarios. PLD would be cost-effective compared with paclitaxel if its price were reduced to $100 per cycle (base case $180 per cycle). Implementing paclitaxel instead of bleomycin-vincristine would save approximately 6400 life-years and would increase the overall 5-year Kenyan health-care costs by $3·7 million; increased costs would be primarily related to ongoing HIV care given improved survival. Interpretation: Paclitaxel would substantially increase life expectancy and be cost-effective compared with bleomycin-vincristine for advanced AIDS-associated Kaposi sarcoma in Kenya and should be the standard of care. PLD would further improve survival and be cost-effective with a 44% price reduction.Item Proposed guidelines for appropriate utilization of superficial radiation therapy in management of skin cancers. Zemtsov‐Cognetta criteria(Wiley, 2023) Zemtsov, Alexander; Cognetta, Armand; Marvel, John; Logan, Ann; Dermatology, School of MedicineObjective: To develop appropriate use criteria (AUC) for the treatment of basal cell and squamous cell carcinoma by superficial radiation therapy (SRT) technique. Material and methods: Delphi-type discussion of the experts. Results: Presented in Figure 1. Conclusion: These AUCs are in compliance both with the position statement of the American Academy of Dermatology (AAD) and the ASTRO Clinical Practice Guideline on this subject. It is further recommended that SRT will be only performed by either a dermatologist who is board certified in Mohs surgery (MDS) and who had adequate SRT training or by radiation oncologists. Hopefully, this publication will stimulate further discussion on this topic.Item Real-World Treatment Patterns in Patients with Vitiligo in the United States(Springer, 2023) Rosmarin, David; Soliman, Ahmed M.; Li, Chao; Dermatology, School of MedicineIntroduction: Vitiligo is an autoimmune disorder resulting in skin depigmentation, with limited approved treatment options. This study evaluated medication utilization and treatment patterns among patients in the first year following vitiligo diagnosis. Methods: This retrospective analysis of claims data from the Merative® MarketScan Research Databases included patients aged ≥ 12 years newly diagnosed with vitiligo. Patients were identified between October 1, 2016, and April 30, 2021, and had ≥ 12 months of continuous enrollment pre- and post-vitiligo diagnosis. Medication use, treatment line of therapy, time to and number of medication claims, and length of therapy were reported in the 12 months post-vitiligo diagnosis. Results are reported separately for treatment initiators post-vitiligo diagnosis, patients with moderate-to-severe vitiligo, and adolescents (aged 12-17 years). Results: A total of 19,335 patients were included in the analysis, with half (N = 9648, 49.9%) not receiving any treatment during the 12-month follow-up. Switching was minimal among treatment initiators (N = 5845) in the 12 months post-vitiligo diagnosis, with the most frequent first-line treatments being high-potency topical corticosteroids (25.4%), oral corticosteroids (23.1%), and topical calcineurin inhibitors (TCI, 14.7%). Adolescents initiating treatment (N = 486) most frequently received TCI (30.9%) as first-line therapy. Patients with moderate-to-severe vitiligo (N = 3462) were very likely to receive treatment during follow-up, with only 1.5% not receiving treatment. Among patients with no vitiligo treatment prior to diagnosis, time to first medication claim ranged from 51.9 days (standard deviation [SD], 84.0) for TCI to 178.6 days (SD 116.0) for systemic immunosuppressants; mean total days supplied ranged from 14.4 days (SD 27.1) for oral corticosteroids to 121.0 (SD 114.0) for immunosuppressants. Conclusion: In this real-world study, a high proportion of patients did not receive any treatment. Among those receiving treatment, most were unlikely to switch or use a combination of treatments within the first year of vitiligo diagnosis.Item Teledermatology Consults in a County Hospital Setting: Retrospective Analysis(JMIR, 2021-09-08) Funkhouser, Colton H.; Funkhouser, Martha E.; Wolverton, Jay E.; Maurer, Toby; Dermatology, School of Medicine