Study investigators sought to determine if erythema assessment and percentage of ≥1-grade CEA improvement over time altered when assessment included a baseline facial photograph.

Introducing a baseline photograph to the critical evaluation of erythema reduction in clinical trials of oxymetazoline confirmed similar results, but led to significantly fewer participants achieving ≥1-grade Clinician Erythema Assessment (CEA) improvement, according to a study published in the British Journal of Dermatology.

Two phase 3 clinical trials of the once a day, topical cream oxymetazoline 1% showed that treatment significantly reduced facial erythema for patients with rosacea. These trials were identically designed and randomized and required live, static assessments of patients being treated once daily with oxymetazoline or vehicle. Study investigators sought to determine if erythema assessment and percentage of ≥1-grade CEA improvement over time altered when assessment included referring to a standardized, digital, baseline facial photograph.

Of the total 835 trial participants (oxymetazoline, n=415; vehicle, n=420), a significantly greater proportion of the oxymetazoline participants achieved ≥1-grade CEA improvement compared with vehicle (up to 85.3% vs 29.8%; P <.0001). When baseline photographs were used for reference during the evaluation of posttreatment photographs, oxymetazoline results were similar to phase 3 trial results, but with a significantly lower rate of ≥1-grade CEA improvement (up to 52.3% vs 29.7%; P <.001). At least a moderate improvement in erythema was achieved by up to 80.2% of oxymetazoline participants compared with up to 22.9% of vehicle participants, with a statistically significant association between participant satisfaction with facial redness and the percentage of erythema improvement (Spearman rank correlation, oxymetazoline, 0.1824; P <.0001; vehicle, 0.0623; P =.01).

Study investigators conclude, “In this study, a greater percentage of patients achieved improvement in persistent facial erythema of rosacea from baseline on the first day of application with oxymetazoline than with vehicle when investigators were allowed to reference the patient’s baseline photograph while evaluating posttreatment photographs to assess erythema severity over time.”

Disclosures: Study funding was provided by Allergan plc, Dublin, Ireland.

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Reference

Eichenfield LF, Del Rosso JQ, Tan JKL, et al. Use of an alternative method to evaluate erythema severity in a clinical trial: difference in vehicle response with evaluation of baseline and postdose photographs for effect of oxymetazoline cream 1.0% for persistent erythema of rosacea in a phase 4 study [published online November 30, 2018]. Br J Dermatol. doi: 10.1111/bjd.17462

Positive but weak associations were found between childhood atopic dermatitis and maternal history of depression, maternal alcohol abuse, and maternal illicit drug use.

Positive but weak associations were found between childhood atopic dermatitis (AD) and maternal depression, alcohol abuse, and illicit drug use, according to the results of a large, nationwide, case-control study conducted in Denmark and published in the Journal of the European Academy of Dermatology and Venereology.

The investigators sought to quantify the relationships between maternal and paternal psychiatric disease and the development of AD in children via use of nationwide health and social registries in Denmark. All Danish children who were born between January 1, 1996, and December 31, 2011, who developed AD prior to 5 years of age were identified and matched in a 1:10 ratio with control subjects from the general Danish population and with children receiving care in a similar ambulatory/hospital setting.

A total of 8602 pediatric patients with AD were matched with control subjects. Rates of parental psychiatric care were similar among those in the AD arm and those in the control arm. Compared with individuals in the general population, weak associations were reported among childhood AD and the following factors: (1) maternal history of depression or  depressive symptoms (odds ratio [OR] 1.18; 95% CI, 1.12-1.26; P <.0001); (2) maternal history of alcohol abuse (OR 1.37; 95% CI, 1.17-1.60; P <.0001); and (3) maternal history of illicit drug use (OR 1.34; 95% CI, 1.14-1.60; P =.0005). However, when the pediatric ambulatory/hospital group was used as the control arm, the associations were no longer significant: (1) OR 1.05; 95% CI, 0.99-1.13; (2) OR 1.14; 95% CI, 0.98-1.34; and (3) OR 1.03; 95% CI, 0.88-1.22, respectively.

Furthermore, no paternal psychiatric disease or prenatal maternal psychiatric disease was shown to be associated with the development of AD among the offspring evaluated.

The investigators concluded that the children of parents with substance abuse issues may be more inclined to receive a diagnosis of AD. A major strength of this study is that 2 separate control populations were used as comparators. A weakness of the current study is that it was limited to children who developed AD prior to 5 years of age, as well as to those who sought care at university- and hospital-based clinics. Moreover, based on the study design, causality cannot be determined.

Disclosure: Multiple authors disclosed affiliations with pharmaceutical companies. See the reference for complete disclosure information.

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Reference

Hamann CR, Egeberg A, Silverberg JI, Gislason G, Skov L, Thyssen JP. Exploring the association between parental psychiatric disease and childhood atopic dermatitis: a matched case-control study [published online November 1, 2018]. J Eur Acad Dermatol Venereol. doi: 10.1111/jdv.15321

Investigators noted that itch-related improvements occurred before treatment efficacy was observed using modified PASI scores.

Topical calcipotriol/betamethasone dipropionate foam (Cal/BD foam) offers more effective and rapid itch relief in people with moderate to severe psoriasis compared with foam vehicle delivery of corticosteroids, according to study results published in the Journal of the European Academy of Dermatology and Venereology.

The investigators sought to examine the efficacy of topical fixed-dose combination calcipotriol 50 µg/g plus betamethasone dipropionate 0.5 mg/g cutaneous foam vs foam vehicle on symptoms of itch, itch-related sleep loss, and quality of life in patients with moderate to severe psoriasis.

The investigators pooled data from 3 Phase II/III trials comparing the effectiveness of Cal/BD foam vs foam vehicle in a cohort of 837 adults with mild to severe psoriasis over a 4-week treatment period. Participants demonstrated the presence of itch as a key symptom with a baseline itch visual analogue scale (VAS) score of >0 or >40.

Outcomes of interest were the absolute itch reduction of VAS >40 and achieving ≥70% improvement in itch relief and itch-related sleep loss. Other outcomes included improvement in modified Psoriasis Area Severity Score (PASI) ≥75% and achieving a Dermatology Life Quality Index (DLQI) score of 0/1, representing no or minimal impact of psoriasis on quality of life. Itch-related outcomes were assessed at baseline, day 3, and day 5 (phase III trial pool only), and weeks 1, 2, and 4 (extended pool).

In the overall cohort, 800 participants had baseline itch VAS >0 (Cal/BD foam, n=610; foam vehicle, n=190); of these 800 participants, 484 had severe baseline itch VAS >40. At baseline, the investigators did not identify any correlation between itch VAS score >0 and modified PASI (R²=0.021), and itch severity was comparable among Cal/BD foam and vehicle foam groups. At week 4, itch VAS scores were lower in the Cal/BD foam group vs foam vehicle group (mean VAS: 9.8±19.3 vs 30.3±28.4).

More participants with baseline itch VAS >40 achieved itch VAS reduction >40 using Cal/BD foam vs foam vehicle as early as day 5 (57.5% vs 40.2%; P <.05) and through week 4 (83% vs 45.8%; P <.001). Similarly, a greater proportion of Cal/BD foam users achieved a ≥70% improvement in itch at day 3 (32.2% vs 22.5%; P <.05) and continuing through week 4 (19.3% vs 38.1%; P <.001). Improvements in itch-related sleep loss were greater in patients with baseline itch VAS >40 and sleep loss >20 in the Cal/BD foam group vs the foam vehicle group; the differences in improvement measures between groups was significant at week 4.

Investigators noted that itch-related improvements occurred before treatment efficacy was observed using modified PASI scores. As for quality of life, significantly more Cal/BD foam users vs foam vehicle users with baseline DLQI scores >10 (Cal/BD, n=172; vehicle, n=50) achieved DLQI ≤1 (25% vs 4%; P =.001) or DLQI 0 (17.4% vs 2%; P =.006).

Limitations to the study included lack of validated tools to measure itch-related sleep-loss, lower participant numbers for early time points (days 3 and 5), and missing information comparing the efficacy of Cal/BD foam with its individual components.

Compared with foam vehicle delivery of corticosteroids, Cal/BD foam is more effective and rapid to relieve itch-related symptoms in patients with moderate-to-severe psoriasis. The reduction of itch from Cal/BD foam was further associated with improvements in sleep and quality of life. The investigators recommend the increased use of itch assessment tools for outcomes in future clinical studies.

Disclosure: This study was sponsored by LEO Pharma.

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Reference                    

Jalili A, Lebwohl M, Gold LS, et al. Itch relief in patients with psoriasis: Effectiveness of calcipotriol plus betamethasone dipropionate foam [published online December 6, 2018]. J Eur Acad Dermatol Venereol. doi: 10.1111/jdv.15393

No significant differences in 2- or 5-year cumulative risk for keratinocyte carcinomas was reported among participants treated with 5-FU compared with those treated with imiquimod.

Although the use of 5-fluorouracil (5-FU) has been shown to reduce the overall risk for keratinocyte carcinoma (KC) compared with imiquimod therapy, in a real-life practice setting of patients with actinic keratosis (AK), no significant differences in the short- or long-term risk for site-specific KCs have been observed with 5-FU compared with imiquimod treatment.

A retrospective, longitudinal cohort study was conducted among all Kaiser Permanente Northern California health plan members aged 18 years or older who had been diagnosed with an AK in 2007 and had filled a prescription for 5-FU or imiquimod. Cohort members were followed for the development of any subsequent KC (ie, any KC, any basal cell carcinoma, or any squamous cell carcinoma). Results of the study were published in the Journal of the American Academy of Dermatology.

The investigators sought to compare the effectiveness of 5-FU vs imiquimod for the prevention of KCs. A total of 5700 patients participated in the study; 5062 of patients had filled a prescription for 5-FU and 638 had filled a prescription for imiquimod. They used an intention-to-treat analysis that controlled for potential confounding variables to calculate 2- and 5-year risk differences for the development of KCs overall and in field-treated areas.

The use of 5-FU was associated with a statistically significantly decreased risk for the development of any KC compared with the use of imiquimod (adjusted hazard ratio [aHR] 0.86; 95% CI, 0.76-0.97). In contrast, no significant differences in risk were reported according to tumor subtype: (1) squamous cell carcinoma: aHR 0.89; 95% CI, 0.74-1.07; (2) basal cell carcinoma: aHR 0.87; 95% CI, 0.74-1.03; or (3) site-specific KC: aHR 0.96; 95% CI, 0.81-1.14. Moreover, no significant differences in 2- or 5-year cumulative risk for KC was reported among participants treated with 5-FU compared with those treated with imiquimod.

A major limitation of the study is that generalizability of the findings to other practice settings may be limited. A major strength of the analysis is the use of Kaiser Permanente Northern California’s closed, prepaid, integrated healthcare system, which allowed for a real-world comparison of the efficacy of 5-FU and imiquimod within a well-characterized, stable population.

The investigators concluded that, in view of the burden that AKs pose to the healthcare system, including their high prevalence, significant cost, and potential for malignant progression, dermatologists should be aware of how available treatment options compare with respect to their effectiveness in the prevention of KCs.

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Reference

Neugebauer R, Su KA, Zhu Z, et al. Comparative effectiveness of treatment of actinic keratosis with topical fluorouracil and imiquimod in the prevention of keratinocyte carcinoma: a cohort study [published online November 17, 2018]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2018.11.024

Dermatologists should consider the higher risk for complications among immunosuppressed patients undergoing MMS when counseling them and managing their care.

According to a study conducted at the Dermatologic and Mohs Surgery Center of the University of California, San Diego, ,immunosuppression — in particular immunosuppression after solid organ transplant and the use of immunosuppressive therapy — in patients undergoing Mohs micrographic surgery (MMS) is linked to a higher risk for postoperative complications, including surgical site infection and wound dehiscence. The results of a retrospective, cross-sectional chart review of patient characteristics, clinical characteristics, and complications in immunosuppressed patients undergoing MMS for basal cell carcinoma or squamous cell carcinoma during a 4-year period were published in the Journal of the American Academy of Dermatology.

The investigators sought to establish the incidence and nature of postsurgical complications among immunosuppressed patients undergoing MMS. All patients who underwent MMS between July 2011 and June 2015 were evaluated, with data obtained via review of electronic medical records. Complications were defined as an adverse event (AE) that occurred within 2 weeks after MMS that was directly related to the procedure and was evaluated by the medical staff at a follow-up visit. Possible AEs included a clinical diagnosis of wound bleeding, dehiscence, tissue necrosis, and surgical site infection (including a combination of purulence, erythema, tenderness, and/or warmth at the site of the lesion, with or without fever).

The overall rate of complications among all those who participated in the analysis was 5.0%. Complications were significantly more likely to occur in older than in younger patients (70.7 vs 67.8 years of age; P =.005). No significant differences according to gender were reported. Surgical site infection (2.5%) and wound dehiscence (0.51%) were more prevalent among those who were immunosuppressed, with an overall complication rate of 5.4% in this population.

Per univariable analysis, in a comparison of immunocompetent and immunosuppressed individuals, immunosuppression was associated with a 9.6-fold greater likelihood of the development of a postoperative complication (P =.003). Solid organ transplant was associated with an 8.824-fold greater likelihood of a postsurgical complication (P =.006), whereas immunosuppressive therapy was associated with a 5.775-fold greater likelihood of a postsurgical complication (P =.021).

The investigators concluded that dermatologists should consider the higher risk for complications among immunosuppressed patients undergoing MMS when counseling them and managing their care. Administering the lowest possible dose of immunosuppressive therapy to facilitate transplant tolerance yet not promote cutaneous surgical complications is a key clinical consideration that warrants additional study.

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Reference

Basu P, Goldenberg A, Cowan N, et al. A four-year retrospective assessment of post-operative complications in immunosuppressed patients following Mohs micrographic surgery [published online November 28, 2018]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2018.11.032

All of the 7 studies reported an increased likelihood of at least 1 extracutaneous infection among patients with atopic dermatitis.

Patients with atopic dermatitis (AD) have an increased risk for development of extracutaneous infections, in particular ear infection, strep throat, and urinary tract infection (UTI). Moreover, some studies have also suggested that AD may be associated with the development of certain potentially life-threatening infections, including septicemia, endocarditis, and meningitis. Findings from the study were published in the Journal of the American Academy of Dermatology.

The investigators sought to establish whether the occurrence of extracutaneous bacterial and mycobacterial infections is elevated among patients with AD. A total of 7 studies met inclusion criteria for the meta-analysis. All of the 7 studies reported an increased likelihood of at least 1 extracutaneous infection among patients with AD, including meningitis, endocarditis, encephalitis, sepsis, and bone and joint infections.

In pooled meta-analysis, the presence of AD in both children and adults was associated with significantly higher odds for the development of ear infection (odds ratio [OR] 1.29; 95% CI, 1.16-1.43; P <.0001), UTI (OR 2.31; 95% CI, 1.66-3.22; P <.0001), and strep throat (OR 2.31; 95% CI, 1.66-3.22; P <.0001), but not for pneumonia (OR 1.72; 95% CI, 0.75-3.98; P =.20), compared with control subjects.

No evidence of publication bias was detected among the studies that provided sufficient data for inclusion in the meta-analysis. A major limitation of this analysis, however, is the fact that individual-level data were not available.

The investigators concluded that future translational studies on this issue are warranted in order to confirm these relationships and to determine the exact causal mechanisms of the association between AD and increased extracutaneous infections. The associations reported in this meta-analysis are clinically relevant, as many of the infections identified are linked to significant pain and discomfort, lost school and work productivity, and have the possibility of being life threatening.

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Reference

Serrano L, Patel KR, Silverberg JI. Association between atopic dermatitis and extra-cutaneous bacterial and mycobacterial infections: a systematic review and meta-analysisJ Am Acad Dermatol. doi: 10.1016/j.jaad.2018.11.028

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Researchers treated patients with a microneedle fractional radiofrequency device to determine its safety and efficacy to treat facial acne scars.

The use of a microneedle fractional radiofrequency (MFR) system for the treatment of atrophic facial acne scars has demonstrated efficacy and safety among a group of Turkish patients, according to the results of a retrospective study conducted at the Dermato-Cosmetology Department of Uludag University Medical School in Bursa, Turkey, from 2014 to 2018. Findings from the analysis were published in the Journal of Cosmetic Dermatology.

The investigators sought to examine use of the MFR device among 9 patients with atrophic facial acne scarring. The severity of acne scars was classified via use of the Goodman and Barron’s Global Qualitative Acne Scarring Grading System, as follows: 1, macular; 2, mild; 3, moderate; and 4, severe. The number of MFR treatment sessions varied among the participants, from 1 to 5 (median, 3), with 4-week intervals between sessions. The efficacy of the device was evaluated by physicians’ global assessment and patients’ self-assessment scales at 4 weeks after the last treatment.

Of the 9 participants, 7 were women and 2 were men. The mean patient age was 31.33±11.09 (range, 17-50) years. Among the participants, 2 had mild, 4 had moderate, and 3 had severe facial acne scars. The mean age of the acne scars was 13.22±8.79 (range, 4-30) years. According to the predominant scar subtype, 3 patients had V-shaped scars, 3 had U-shaped scars, and 3 had M-shaped scars.

Clinical improvement of >25% has been reported among 77.7% (7 of 9) and 88.9% (8 of 9) of the patients, according to physicians’ global assessment and patients’ self-assessment, respectively. Better clinical improvement was attained in those with U-shaped atrophic acne scars (22.2% rated as good improvement according to patients’ self-assessment, and 11.1% rated as good or excellent improvement according to physicians’ global assessment) compared with patients with M-shaped and V-shaped scars.

No severe adverse effects, including scarring, pigmentation changes, and wound infection, were reported among patients treated with the MFR system.

The investigators reported favorable efficacy and safety among a group of Turkish patients with atrophic facial acne scars who were treated with the MFR device. Use of the system had the advantage of a quick return to daily life among treated patients. Additional studies are warranted in a large number of patients, including patients with all subtypes of acne scars, to further evaluate the efficacy of the MFR device. Combination therapies with the MFR system and other treatment methods should also be evaluated, particularly among patients with recalcitrant types of scars.

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Reference

Bulbul Baskan E, Akin Belli A. Evaluation of the efficacy of microneedle fractional radiofrequency in Turkish patients with atrophic facial acne scars [published online November 11, 2018]. J Cosmet Dermatol. doi: 10.1111/jocd.12812

Overall, 43.8% of the participants healed with the use of topical therapy alone within the 6-month treatment period.

The use of high-potency topical corticosteroid therapy in patients with pyoderma gangrenosum (PG) is an effective first-line treatment that avoids the possible adverse effects associated with the use of systemic therapies, according to the results of a recent study. The large prospective cohort study included secondary care patients in the United Kingdom. All participants had a clinical diagnosis of PG and were deemed suitable for topical treatment. Results were published in the Journal of the American Academy of Dermatology.^1,2  

The prospective cohort analysis was conducted alongside a randomized controlled trial of systemic treatments for patients with PG (the Study of Treatments for Pyoderma Gangrenosum Patients [STOP GAP]), in which oral prednisolone was compared with cyclosporine.^2,3

The investigators sought to estimate the efficacy of topical corticosteroids compared with the topical calcineurin inhibitor tacrolimus for the treatment of PG, a painful ulcerating disease for which the current evidence base regarding treatment is limited.^1,2 All participants received topical therapy following normal clinical practice (mainly classes I to III topical corticosteroids or tacrolimus 0.03% or 0.1%).² The primary study outcome was speed of healing on evaluation at 6 weeks. Secondary outcomes included the following: (1) proportion of patients healed by 6 months, (2) time to healing, (3) global assessment, (4) quality of life, (5) pain, (6) inflammation, (7) recurrence, and (8) treatment failure.²

A total of 67 patients were enrolled in the study. Of those participating, 49 patients received clobetasol propionate 0.05%, 10 patients received tacrolimus 0.03%, and 8 patients received other topical interventions. All participants were age 18 years or older.²

Overall, 43.8% of the participants healed with the use of topical therapy alone within the 6-month treatment period.^1,2 The initial ulcer size was a significant predictor of time to healing (hazard ratio 0.94; 95% CI, 0.88-1.00; P =.043).² Among the participants with PG, 15% experienced a recurrence of disease.^1,2 The median time to the healing of ulcers was 145 days.²

The investigators concluded that clobetasol propionate 0.05% demonstrated potential use as a first-line treatment for patients with PG, particularly those with small lesions.^1,2 Whether more severe PG will respond adequately to topical treatment alone requires further elucidation,² with larger ulcerations possibly requiring more intensive therapy.¹ A major limitation of the study was that it did not contain a randomized comparator.²

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References

1. Lake E. Clinical outcomes and response of patients applying topical therapy for pyoderma gangrenosum: a prospective cohort study [published online November 14, 2018]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2018.11.003

2. Thomas KS, Ormerod AD, Craig FE, et al; UK Dermatology Clinical Trials Network’s STOP GAP Team.  Clinical outcomes and response of patients applying topical therapy for pyoderma gangrenosum: a prospective cohort study[CM1] . J Am Acad Dermatol. 2016;75(3):940-949.

3. Ormerod AD, Thomas KS, Craig FE, et al; UK Dermatology Clinical Trials Network’s STOP GAP Team. Comparison of the two most commonly used treatments for pyoderma gangrenosum: results of the STOP GAP randomised controlled trial. BMJ. 2015;350:h2958.

Poliosis may be induced among elderly persons with AA who have a poor melanocyte reservoir status.

Studies of poliosis — the regrowth of white hairs at the site of previous patches of AA — in patients with alopecia areata (AA) have been limited mostly to case reports of total or partial whitening with pigmented hair loss. In a retrospective analysis published in the Journal of the American Academy of Dermatology, investigators sought to characterize patients who had AA by comparing those with and without poliosis.¹

The medical records of 258 patients with AA who had visited Wonju Severance Christian Hospital, in Wonju, Korea, between March 2012 and June 2017 were examined retrospectively. All patients were divided into two subgroups: those with and those without poliosis. The demographic variables (age, gender, body mass index, smoking status, and alcohol use), comorbidities (diabetes mellitus, hypertension, and dyslipidemia), and disease-specific variables (age at onset of AA; extent, duration, recurrence, family history, and history of treatment of AA) of the two subgroups were then compared.

Overall, 13 of the 258 patients (5.04%) had poliosis. The average age of those in the poliosis subgroup was higher than the average age of those in the nonpoliosis subgroup. In addition, both the proportion of patients treated with diphenylcyclopropenone and the proportion of patients with less extensive lesions were higher in the poliosis group than in the nonpoliosis group. With respect to comorbidities, according to multivariate logistic regression analysis, only hypertension was significantly associated with poliosis (P =.032; adjusted P =.038).

In patients with AA, melanocyte-associated T-cell epitopes have been shown to behave like autoantigens. It is believed that hair whitening is caused by an interaction among various mechanisms, such as the dysregulation of signaling pathways and transcription factors in the microenvironment surrounding the hair follicle, including melanocyte stem cells, or by an imbalance in the management of oxidative stress.² Therefore, poliosis may be induced among elderly persons with AA who have a poor melanocyte reservoir status.

The investigators concluded that because the current analysis was conducted in a specific population of patients, future studies should consider genetic differences in the prevalence of AA and comorbidities according to ethnicity. Moreover, larger sample sizes need to be evaluated, given that the current study included only a small number of participants at a single institution.

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References

1. Lee YB, Jun M, Lee W-S. Alopecia areata and poliosis: a retrospective analysis of 258 cases [published online November 28, 2018]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2018.11.033

2. Harris ML, Fufa TD, Palmer JW, et al; NISC Comparative Sequencing Program. A direct link between MITF, innate immunity, and hair graying. PLoS Biol. 2018;16(5):e2003648.