A phase 2a randomized vehicle-controlled multi-center study of the safety and efficacy of delgocitinib in subjects with moderate-to-severe alopecia areata.

Alopecia areata/AA is an autoimmune cause of nonscarring hair loss. The pathogenesis of AA involves many immune axes, including Th1/Th2 pathways. Delgocitinib is a pan-Janus kinase/JAK inhibitor that broadly blocks pro-inflammatory cytokines and has been effective in other inflammatory skin conditions. Recent human studies/reports have shown that use of some systemic JAK inhibitors led to hair regrowth, suggesting this medication class as a potential therapy for AA. However, topical treatment is desirable due to potential systemic side effects. To assess the efficacy and safety of topical delgocitinib in AA, we conducted a double-blind, randomized, vehicle-controlled clinical trial in 31 moderate-to-severe AA patients that were randomized 2:1 to receive delgocitinib ointment 30 mg/g (n = 20) or ointment vehicle (n = 11) for 12 weeks. The primary endpoint was change in severity of Alopecia Tool/SALT score from baseline to week 12. The secondary endpoint included safety profile by reported adverse events. Twenty-three subjects completed the trial, with eight discontinuing mostly due to voluntary withdrawal. Ten patients receiving delgocitinib ointment and three patients receiving vehicle showed SALT score improvements after 12 weeks, but the mean percent SALT improvement at week 12 compared to baseline between the two arms was not significant (p = 0.92). Our study suggests that delgocitinib ointment is not effective in moderate-to-severe AA, likely due to its inability to penetrate sufficiently deeply into the dermis of the scalp, but larger studies are necessary to assess whether a different formulation of topical JAK inhibitors may be suitable to treat mild or more localized forms of AA.

Long-Term Neurocognitive Outcomes in Sagittal Synostosis: The Impact of Reoperation.

INTRODUCTION: Optimal age at surgery in nonsyndromic sagittal craniosynostosis continues to be debated. Previous reports suggest that earlier age at whole vault cranioplasty more frequently requires reoperation. It is unknown, however, whether reoperation affects neurocognitive outcome. This study examined the impact of reoperation on neurocognitive outcome in children with nonsyndromic sagittal craniosynostosis using comprehensive neurocognitive testing. METHODS: Forty-seven school-age children (age 5-16 years) with nonsyndromic sagittal craniosynostosis who underwent whole-vault cranioplasty were included in this analysis. Participants were administered a battery of standardized neuropsychological testing to measure neurocognitive outcomes. RESULTS: Thirteen of the 47 participants underwent reoperation (27.7%); 11 out of the 13 reoperations were minor revisions while 2 reoperations were cranioplasties. Reoperation rate was not statistically different between patients who had earlier surgery (at age ≤6 months) versus later surgery (at age >6 months) (P > 0.05). Nonreoperated patients who had only one later-in-life surgery did not perform statistically better than reoperated patients on any outcome measure of neurocognitive function, including IQ, academic achievement, visuomotor integration, executive function, and behavior. Comparing reoperated earlier surgery patients with nonreoperated later surgery patients, reoperated earlier surgery patients had higher full-scale and verbal IQ (P < 0.05), scored higher on word reading, reading comprehension, spelling, numerical operations, and visuomotor integration (P < 0.05), and had fewer indicators of suspected learning disabilities (P < 0.01) compared to nonreoperated later surgery patients. CONCLUSION: Reoperation rate after whole vault cranioplasty was 27.7%, with few cases of repeat cranioplasty (4.2% of all patients). Reoperation was not associated with worse neurocognitive outcome. Reoperated earlier surgery patients in fact performed better in IQ, academic achievement and visuomotor integration when compared to nonreoperated later surgery patients.

Objective Evaluation of Skin Sensitivity Across Fitzpatrick Skin Types.

Context: Skin sensitivity may be best defined as self-reported intolerance to application of skincare products. It is commonly believed that individuals with darker skin are generally less sensitive, while those lighter skin are more sensitive. However, there is little objective data correlating sensitivity with skin type or with objective measures of sensitivity. Objective: This study assessed Fitzpatrick skin type and self-reported perception of skin sensitivity. Design: A single-blinded, lactic acid sting test was performed on the medial cheeks, where patients were randomized to receive room temperature 10% lactic acid on the left or right cheek with water applied to the contralateral cheek as a control. Outcome Measures: Stinging was assessed 1 minute after application of test solution to one cheek using a visual analogue scale (VAS). Results: There was a statistically significant difference in self-reported skin sensitivity in patients with Fitzpatrick skin types 1-3 vs 4-6 (73.6% vs 46.5%; P= 0.006). Patients who had higher perceived sensitivity were more likely to have objectively measured sensitivity as well, across all skin types (P<0.01). When stratified by skin type, a numerically higher percentage of subjects with Fitzpatrick skin types 1-3 experienced objective sensitivity compared to subjects with skin types 4-6 (45.6% vs 27.9; P=0.058). Conclusions: Patients with self-perceived skin sensitivity were more likely to develop objective stinging compared to those who did not report sensitivity. Skin sensitivity can occur across all skin types, and patients should be asked about self-perceptions of sensitivity as it is likely an indicator of true sensitivity. J Drugs Dermatol. 2020;19(7): doi:10.36849/JDD.2020.5880.

Dermatologist Use of Intralesional Triamcinolone in the Treatment of Acne.

OBJECTIVE: Despite common administration of intralesional triamcinolone to acne lesions, there is little published data or consensus on best practices. This study aimed to evaluate specific characteristics of intralesional triamcinolone for acne among various dermatology healthcare professionals. DESIGN: One hundred participants (82 attending physicians, 9 physician assistants, 8 other healthcare professionals, and 1 unidentified) from private practices and academic centers completed a 10-question survey to assess specific characteristics of intralesional triamcinolone injections, including frequency, indication, depth of injection, concentration, volume, as development of adverse events. RESULTS: The most common reported concentration of intralesional triamcinolone was 2.5mg/mL (52.5%). The most frequently used volume injected was 0.05mL (42.3%). In total, 61.6 percent of those surveyed answered that they inject into the center of the lesion. Additionally, 50.5 percent of respondents counsel patients on potential adverse effects of hypopigmentation and atrophy before every injection. The majority of respondents (88.8%) reported that less than one percent of their patients returned for adverse events resulting from triamcinolone usage, and 48.4 percent reported that atrophy lasted over six months (48.4%). CONCLUSION: The data collected from this study can offer guidance on best practices in administering intralesional kenalog to patients. While consistency exists for the concentration of triamcinolone used, there was significant discordance in the volumes and depth of triamcinolone injection. Observed skin atrophy rates are extremely low, but they are long lasting when it occurred. We can use these data to refine our treatment techniques as well as improve treatment outcomes and patient satisfaction.

Crisaborole 2% ointment for the treatment of intertriginous, anogenital, and facial psoriasis: A double-blind, randomized, vehicle-controlled trial.

BACKGROUND: Psoriasis of the intertriginous, anogenital, and facial regions remains a therapeutic challenge, with current algorithms lacking a topical agent that exhibits both high efficacy and minimal side effects. OBJECTIVE: To assess the safety and efficacy of crisaborole 2% ointment-a nonsteroidal phosphodiesterase 4 inhibitor-in the treatment of intertriginous, anogenital, and facial psoriasis. METHODS: A double-blind, randomized, vehicle-controlled trial was conducted in 21 participants. Participants were randomized 2:1 to receive 4 weeks of twice-daily treatment with either crisaborole 2% ointment (n = 14) or vehicle ointment (n = 7), followed by 4 weeks of open-label treatment with crisaborole 2% ointment. Disease severity was measured by using the Target Lesion Severity Scale (TLSS). RESULTS: After 4 weeks, participants in the crisaborole group demonstrated 66% improvement compared with 9% in the vehicle group (P = .0011). Participants in the crisaborole group continued to experience improvement through the open-label phase, demonstrating 81% lesional improvement by week 8, with 71% of these participants achieving clinical clearance. There were no adverse events. LIMITATIONS: The study was limited to a single tertiary care center and small sample size. CONCLUSION: Treatment with crisaborole 2% ointment was well-tolerated and led to clinical improvement in participants with intertriginous, anogenital, or facial psoriasis.

Nanoparticles in dermatologic surgery.

Nanotechnology is an emerging branch of science that involves the engineering of functional systems on the nanoscale (1-100 nm). Nanotechnology has been used in biomedical and therapeutic agents with the aim of providing novel treatment solutions where small molecule size may be beneficial for modulation of biologic function. Recent investigation in nanomedicine has become increasingly important to cutaneous pathophysiology, such as functional designs directed towards skin cancers and wound healing. This review outlines the application of nanoparticles relevant to dermatologic surgery.

The role of vitamins and supplements on skin appearance.

Skin appearance is affected by intrinsic factors (eg, aging) and extrinsic factors (eg, UV light). A myriad of treatments has been created to combat the phenotypic effects of these forces, including vitamins and supplements. This article reviews these therapies with a focus on carotenoids; vitamins C, E, and D; as well as collagen, ceramides, and mixed supplements.

Nonsurgical hair restoration treatment.

Patterned hair loss is common and can negatively impact quality of life. Patients often seek nonsurgical treatment options as a first-line measure to avoid undue risks and expense associated with surgery. This article discusses these noninvasive treatment options, with a focus on minoxidil, finasteride, dutasteride, spironolactone, low-level laser therapy (LLLT), platelet-rich plasma (PRP), microneedling, and oral supplements.

Airway Analysis in Apert Syndrome.

BACKGROUND: Apert syndrome is frequently combined with respiratory insufficiency, because of the midfacial deformity which, in turn, is influenced by the malformation of the skull base. Respiratory impairment resulting from Apert syndrome is caused by multilevel limitations in airway space. Therefore, this study evaluated the segmented nasopharyngeal and laryngopharyngeal anatomy to clarify subcranial anatomy in children with Apert syndrome and its relevance to clinical management. METHODS: Twenty-seven patients (Apert syndrome, n = 10; control, n = 17) were included. All of the computed tomographic scans were obtained from the patients preoperatively, and no patient had confounding disease comorbidity. Computed tomographic scans were analyzed using Surgicase CMF. Craniometric data relating to the midface, airway, and subcranial structures were collected. Statistical significance was determined using t test analysis. RESULTS: Although all of the nasal measurements were consistent with those of the controls, the nasion-to-posterior nasal spine, sphenethmoid-to-posterior nasal spine, sella-to-posterior nasal spine, and basion-to-posterior nasal spine distances were decreased 20 (p < 0.001), 23 (p = 0.001), 29 (p < 0.001), and 22 percent (p < 0.001), respectively. The distance between bilateral gonions and condylions was decreased 17 (p = 0.017) and 18 percent (p = 0.004), respectively. The pharyngeal airway volume was reduced by 40 percent (p = 0.01). CONCLUSION: The airway compromise seen in patients with Apert syndrome is attributable more to the pharyngeal region than to the nasal cavity, with a gradually worsening trend from the anterior to the posterior airway, resulting in a significantly reduced volume in the hypopharynx.

Combination Use of Systemic Therapies in Psoriasis: Baseline Characteristics from the Corrona Psoriasis Registry

IMPORTANCE: There are increasing options for systemic combination therapy for psoriasis but a lack of literature around the characteristics of patients who are started on these regimens. OBJECTIVE: We aimed to determine how combination systemic therapy patients differ from monotherapy patients in their social, medical, or treatment history. DESIGN: This was a cross-sectional study of patients enrolled in the Corrona Psoriasis Registry. Descriptive characteristics were compared in biologic monotherapy and combination therapy groups. SETTING: The Corrona PsO registry is a prospective multicenter observational disease-based registry with patients recruited from 154 private and academic practice sites in the US and Canada with 373 participating dermatologists. PARTICIPANTS: Patients 18 years of age or older who enrolled in the Corrona Psoriasis Registry between April 2015 and March 2017 and initiated an eligible biologic therapy at the time of enrollment were included. EXPOSURES: Eligible biologic therapies included adalimumab, etanercept, infliximab, ixekizumab, secukinumab, and ustekinumab. Non-biologic and small molecule adjunctive therapies included acitretin, apremilast, CsA, and MTX. RESULTS: Patients on combination therapy were more likely to identify as black, to have Medicaid, and to report disabled work status. While combination therapy patients were more likely to have concomitant PsA, no major differences were seen in disease morphology, duration, IGA, PASI, or BSA affected at treatment initiation. CONCLUSIONS: Various demographic and socioeconomic factors are associated with use of combination systemic therapy compared to use of systemic monotherapy for psoriasis. An association with commonly used disease severity indices was not observed. RELEVANCE: An understanding of which patients are more likely to be prescribed combination systemic therapy will provide important context for long-term efficacy and safety data as they become available.

Systemic Psoriasis Therapies and Comorbid Disease in Patients with Psoriasis: A Review of Potential Risks and Benefits.

Psoriasis is an inflammatory skin disease that is associated with many comorbidities. Several psoriasis treatments approved by the United States Food and Drug Administration have been shown to have beneficial effects on these comorbidities, while others might lead to an exacerbation of these conditions. In this article, we review studies of psoriasis treatments and their level of evidence for use in co-occurring diseases. An awareness of the multifaceted effects of certain psoriasis medications can enable physicians to provide more personalized treatment to their most complicated patients.

Treatment of Arsenic-Induced Bowen's Disease With Topical 5-Fluorouracil

Here, we present a case of arsenic-induced Bowen's disease treated with a regimen consisting of topical 5-fluouracil and oral nicotinamide. The use of this therapy modality resulted in near complete resolution of all of the patient's lesions except for those on her palms, soles, and scalp. Excellent wound care and treatment adherence were major factors contributing to the success of this treatment option. Our results ultimately provide an alternative approach to treating multiple arsenical keratoses in patients who are limited to a drug plan involving 5-FU and oral nicotinamide and who are able to be rigorously compliant with application of medication and wound care. J Drugs Dermatol. 2019;18(5):477-479.

Actinic Keratosis: Current Therapies and Insights Into New Treatments

Actinic keratosis (AK) develops on chronically sun-exposed skin and constitutes one of the most common diseases managed by dermatologists. The incidence of AKs continues to rise among aging as well as younger sun damaged populations worldwide, underscoring the importance of effective therapy options. Various treatments are available, including light-based therapies, topical therapies, and destructive therapies. Herein, we review the current management options for AKs and discuss emerging therapeutic agents. J Drugs Dermatol. 2019;18(5 Suppl 1):s161-166.

The role of diet in preventing photoaging and treating common skin conditions.

As interest in complementary and alternative medicine has grown, the relationship between diet and skin health has become an active area of research. Various supplements, plant derivatives, and antioxidants have gained attention as possible tools to prevent signs of aging and improve skin conditions. As such, knowledge of clinical trial data is important to counsel patients appropriately on risks and benefits of these complementary treatments and lifestyle modifications. Herein, we review the role of diet and supplements in preventing photoaging and treating common skin conditions.

Topical Treatment for the Management of Atopic Dermatitis

Atopic dermatitis affects up to 20% of children and continues to increase in prevalence. Effective disease control is aimed at decreasing symptoms and reducing the frequency of flares, which may be complicated by secondary bacterial infections. Although recent advances have produced a number of non-systemic treatment options, topical corticosteroids remain a fundamental component of treatment algorithms. J Drugs Dermatol. 2019;18(2 Suppl):s112-116.

Analysis of Airway and Midface in Crouzon Syndromes.

BACKGROUND: Crouzon syndrome is associated with severe respiratory impairment of the upper airway due in part to midfacial dysmorphology. We calculated the distinctive nasal diameter and pharyngeal airway volume in patients with Crouzon syndrome and compared them with age-matched control subjects. METHODS: Children with computed tomography scans in the absence of surgical intervention were included. Computed tomography scans were digitized and manipulated using Surgicase CMF (Materialise). Craniometric data relating to the midface and airway were collected. For all linear measurements, mean percent increases or decreases were calculated relative to the size of control subjects, and volumetric assessment of the airway was tabulated. Statistical analysis was performed using t test. RESULTS: Twenty-six computed tomography scans were included (control n = 17, Crouzon n = 9). All children were in early mixed dentition. Pharyngeal airway volume was decreased in patients with Crouzon syndrome relative to control subjects by 46% (P = 0.003). The distance from the posterior tongue to the posterior pharyngeal wall decreased 31% when comparing the Crouzon group versus the control (P = 0.04). CONCLUSIONS: Three-dimensional analysis revealed notably decreased pharyngeal and nasal airway volumes in patients with Crouzon syndrome, but nasal bone tissue and soft tissue measurements showed very little change between patients and control subjects.