Low-potency Topical Corticosteroids Research Articles

Trends of Diagnosis, Disease Course, and Treatment of Atopic Dermatitis 2012-2021: Real-World Data from a Large Healthcare Provider.

In the last decade, new treatments for atopic dermatitis (AD) have emerged. We aimed to describe trends of the diagnosis, disease course, and treatment of AD over a decade (2012-2021) using data from Maccabi Healthcare Services (a 2.7-million-member healthcare provider in Israel). The AD prevalence was stable (4.0% on 31 December 2021 vs. 4.3% on 31 December 2012). The annual AD incidence was also stable (5.8/1000 in 2012 and 5.7/1000 in 2021). AD-related treatment use was highest in the first year post-diagnosis, and it included, among children (n = 87,414) vs. adults (n = 36,865), low-potency topical corticosteroids (TCS) (41.8% vs. 27.1%), mid-potency TCS (30.1% vs. 28.1%), high-potency TCS (34.9% vs. 60.3%), topical calcineurin inhibitor (10.8% vs. 10.1%), phosphodiesterase-4-inhibitor (0.3% vs. 0.7% overall; approved in 2019), phototherapy (0.1% vs. 2.3%), and systemic/biologic treatments (13.0% vs. 13.3%). Among children diagnosed in 2012 and followed through to 2021 (n = 5248), 21.5% had ≥1 AD diagnosis/treatment 10 years later (among 3223 adults: 38.3%). We conclude that the incidence and prevalence rates of AD were comparable to those in similar database studies and remained relatively stable over the past decade. The results underscore the burden of medication use among children and adults, particularly in the first year after AD diagnosis, and the low rate of AD diagnosis among patients originally diagnosed as children 10 years earlier.

Pityriasis Rosea of Gibert: A Comprehensive Review of a Common, Self-Limiting Dermatologic Entity

Pityriasis rosea of Gibert is a common, self-limiting dermatologic entity that continues to raise questions regarding its etiology, diagnosis, and clinical management. This comprehensive review focuses on analyzing the distinctive clinical presentation of pityriasis rosea, characterized by the appearance of a herald patch followed by multiple secondary collarete or Christmas tree lesions. Although the exact cause of this disease remains unknown, a possible relationship with an immune reaction triggered by a previous viral infection or environmental factors yet to be identified is postulated. Through a thorough literature search, current findings on the epidemiology, pathogenesis and clinical diagnosis of pityriasis rosea are evaluated. The importance of the clinician's clinical judgment and accurate identification of the distinctive features of the skin lesions to reach an accurate diagnosis is emphasized. Although pityriasis rosea is usually asymptomatic or causes mild pruritus in most cases, symptomatic therapeutic options, such as the use of oral antihistamines and low potency topical corticosteroids, are described to alleviate patient discomfort when necessary. Patient education and psychological support are essential to decrease the anxiety associated with skin lesions and to provide reassurance during the self-limiting course of this condition. In the context of the clinical and epidemiologic relevance of pityriasis rosea, the need for continued research to improve understanding of its etiology and management arises. Although pityriasis rosea does not represent a serious health threat, its high frequency in the population and its distinctive clinical appearance underscore the importance of empathetic and compassionate medical care to ensure the patient's well-being during the process of spontaneous resolution.

Dupilumab Treatment Leads to Rapid and Consistent Improvement of Atopic Dermatitis in All Anatomical Regions in Patients Aged 6 Months to 5 Years.

Atopic dermatitis (AD) is heterogeneous in distribution pattern and clinical features. This analysis assessed the effect of dupilumab on the extent and severity of AD across various signs (erythema, edema/papulation, excoriation, lichenification) in different anatomical regions (head and neck, trunk, upper extremities, lower extremities) in patients aged 6months to 5years. In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled, phase III clinical trial, children aged 6months to 5years with moderate-to-severe AD were randomized 1:1 to subcutaneous dupilumab or placebo with concomitant low-potency topical corticosteroids (TCS) every 4weeks for 16weeks. Changes in AD signs across anatomical regions were assessed using unweighted Eczema Area and Severity Index (EASI) body region scores. Overall, 162 patients were randomized to dupilumab (n = 83) or placebo (n = 79). A significant improvement in least squares mean EASI area score was seen by week 2 in all four anatomical regions (P < 0.0001 for dupilumab vs. placebo) and sustained throughout treatment. Least squares mean EASI sign scores in erythema, excoriations, and infiltration/papulation showed significant improvement by week 2 in all regions (P < 0.001), while lichenification showed significant improvement in all regions by week 4 (P < 0.001). Dupilumab use with concomitant low-potency TCS treatment resulted in rapid and consistent improvement in AD signs in all anatomical regions, in patients aged 6months to 5years with moderate-to-severe AD. ClinicalTrials.gov Identifier: NCT03346434 Part B.

P73 Laboratory safety from a 16-week phase III study of dupilumab in patients aged 6 months–5 years with moderate-to-severe atopic dermatitis

Abstract Previous studies of dupilumab treatment in adults, adolescents and children aged 6–11 years with moderate-to-severe atopic dermatitis (AD) showed no clinically meaningful changes in laboratory parameters. Here, we evaluate laboratory safety data for dupilumab-treated children aged 6 months–5 years with moderate-to-severe AD. In LIBERTY AD PRESCHOOL (NCT03346434 part B), a placebo-controlled phase III trial, 162 children aged 6 months–5 years with moderate-to-severe AD were randomized to receive dupilumab 200 mg or 300 mg every 4 weeks (n = 83) based on baseline weight (200 mg: ≥ 5 to &amp;lt; 15 kg; 300 mg: ≥ 15 to &amp;lt; 30 kg), or placebo (n = 79) for 16 weeks. Low-potency topical corticosteroids were initiated from day −14. At baseline, mean (SD) haematology parameters were similar in both treatment groups: eosinophils [dupilumab: 1.1 × 109 cells L−1 (0.7); placebo: 1.1 × 109 cells L−1 (0.7)], platelets [dupilumab: 397.7 × 109 cells L−1 (103.2), placebo: 385.6 × 109 cells L−1 (112.9)] and neutrophils [dupilumab: 3.54 × 109 cells L−1 (1.56); placebo: 3.85 × 109 cells L−1 (1.73)]. Mean (SD) counts of neutrophils [dupilumab: 3.18 × 109 cells L−1 (1.94); placebo: 3.79 × 109 cells L−1 (1.91)] remained within the normal reference interval (RI) at week 16. Mean (SD) change in platelet count at week 16 was −16.3 × 109 cells L−1 (78.5) in the dupilumab group and 17.4 × 109 cells L−1 (106.6) in the placebo group. In the dupilumab group, the mean (SD) change in eosinophil count increased at week 4 [0.48 × 109 cells L−1 (1.8)] and trended downward by week 16 [0.31 × 109 cells L−1 (1.4)], while minimal changes were noted in the placebo group at week 4 [0.1 × 109 cells L−1 (0.7)] and week 16 [−0.2 × 109 cells L−1 (0.7)]. The mean (SD) values for creatine kinase [dupilumab: 144.2 U L−1 (84.8); placebo: 130.7 U L−1 (46.39)], alkaline phosphatase [dupilumab: 273.4 U L−1 (80.01); placebo: 233.2 U L−1 (65.98)] and lactate dehydrogenase [dupilumab: 283.8 U L−1 (44.74); placebo: 317.4 U L−1 (67.58)] at week 16 remained within the normal RI in all treatment groups. Two patients treated with dupilumab reported cases of severe and moderate eosinophilia. Neither event was associated with clinical symptoms nor led to the discontinuation of study treatment. No clinically meaningful changes in haematology or chemistry laboratory safety parameters in children aged 6 months–5 years with moderate-to-severe AD were seen with 16 weeks of dupilumab treatment. These data demonstrate that, as with adults, adolescents and older children, routine laboratory monitoring is unnecessary in this population. Funding sources: research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.

338 Laboratory safety from a 16-week phase 3 study of dupilumab in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis

Abstract Many systemic therapies used for moderate-to-severe atopic dermatitis (AD) have immunosuppressive properties and necessitate laboratory screening and monitoring, adding to the treatment burden. Previous dupilumab studies in adults, adolescents and children aged 6–11 years with moderate-to-severe AD showed no clinically meaningful adverse changes in laboratory parameters. Here we evaluate hematology and chemistry laboratory safety data for dupilumab-treated children aged 6 months to 5 years with moderate-to-severe atopic dermatitis. Patients aged 6 months to 5 years with inadequately controlled moderate-to-severe AD were enrolled in LIBERTY AD PRESCHOOL (NCT03346434 part B), a randomized, double-blind placebo-controlled phase 3 study. 162 patients were randomized to either dupilumab 200/300 mg every 4 weeks (q4w; N = 83; baseline weight ≥5 &amp;lt;15 kg: 200 mg; ≥15 to &amp;lt;30 kg: 300 mg) or placebo (N = 79) for 16 weeks. From Day –14, all patients initiated standardized treatment with low-potency topical corticosteroids. Laboratory data was collected at baseline, weeks 4 and 16. At baseline, mean (SD) counts of hematology parameters were similar in both treatment groups: haemoglobin (dupilumab: 129.4 gL−1 [12]; placebo: 127.2 gL−1 [11.4]), lymphocyte (dupilumab: 4.6 × 109 L−1 [1.8]; placebo: 4.5 × 109 L−1 [1.7]), basophil (dupilumab: 0.07 × 109 L−1 [0.03]; placebo: 0.07 × 109 L−1 [0.04]), platelet (dupilumab: 397.7 × 109 L−1 [103.2]; placebo: 385.6 × 109 L−1 [112.9]) and eosinophils (dupilumab: 1.1 × 109 L−1 [0.7]; placebo: 1.1 × 109 L−1 [0.7]). Mean (SD) haemoglobin count in the dupilumab (128.4 × gL−1 [11]) and placebo groups (128.2 × gL−1 [11.2]), lymphocyte count in the dupilumab (4.20 × 109 L−1 [2.06]) and placebo groups (4.29 × 109 L−1 [1.52]) and basophil count in the dupilumab (0.07 × 109 L−1 [0.04]) and placebo groups (0.06 × 109 L−1 [0.03]) remained with the normal reference range for this population at week 16. The mean change (SD) in platelet count at week 16 was −16.3 × 109 L−1 (78.5) in the dupilumab group and +17.4 × 109 L−1 (106.6) in the placebo group. In the dupilumab treatment group, the mean eosinophil count increased at week 4 (mean change from baseline [SD]; + 0.48 × 109 L−1 [1.8]) and trended downward by week 16 (+0.31 × 109 L−1 [1.4]) while minimal changes were noted in the placebo group at week 4 (0.1 × 109 L−1 [0.7]) and week 16 (−0.2 × 109 L−1 [0.7]). The values for creatine kinase, alkaline phosphatase, lactate dehydrogenase, blood urea nitrogen, albumin and protein at week 16 remained within the normal reference range in all treatment groups. Two patients in the dupilumab 200/300 mg q4w arm of this study reported treatment-emergent adverse events of severe and moderate eosinophilia. Neither event was associated with clinical symptoms nor led to the discontinuation of the study treatment. No clinically meaningful changes in hematology and chemistry parameters in children aged 6 months to 5 years with moderate-to-severe AD were seen with 16 weeks of dupilumab treatment. These data demonstrate that, as with adults, adolescents and older children, routine laboratory monitoring is unnecessary in this younger population. Dupilumab was generally well tolerated with an acceptable safety profile.

329 Efficacy and safety of dupilumab treatment with concomitant topical corticosteroids in children aged 6 months to 5 years with severe atopic dermatitis

Abstract There are limited approved systemic treatment options for children with atopic dermatitis (AD). Dupilumab is now approved in the United States for patients 6 months and older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies. European Medicines Agency is evaluating the use of dupilumab in children aged 6 months through 5 years with severe AD only. To report the efficacy and safety of dupilumab in the subgroup of children aged 6 months to 5 years with severe AD (IGA score = 4) at baseline in the LIBERTY AD PRESCHOOL trial (NCT03346434 part B). Patients aged 6 months to 5 years with inadequately controlled moderate-to-severe AD were enrolled in LIBERTY AD PRESCHOOL (part B), a randomized, double-blind placebo-controlled phase 3 study. Patients were randomized to either dupilumab 200/300 mg every 4 weeks (200 mg if baseline weight 5 to &amp;lt;15 kg, 300 mg if 15 to &amp;lt;30 kg) or placebo for 16 weeks. All patients initiated standardized treatment with low-potency topical corticosteroids (TCS) from day –14. This analysis reports efficacy and quality-of-life endpoints including a 75% reduction from baseline in the Eczema Area and Severity Index (EASI-75), Peak-Pruritus Numerical Rating Scale (PP-NRS), Children’s Dermatology Life Quality Index (CDLQI, for children aged 4 to &amp;lt;6 years), and Infant’s Dermatitis Quality Of Life (IDQOL, for children &amp;lt;4 years) in children with severe AD. Of the total trial population of 162 patients with moderate-to-severe AD, 125 patients with severe AD at baseline were randomized: 63 to the dupilumab + TCS treatment group and 62 to the placebo + TCS treatment group. Baseline demographics were similar. Mean (SD) baseline disease characteristics were also similar between the dupilumab and placebo groups: EASI (38.8 [13.7] vs. 35.4 [12]), body surface area (63.1% [21] vs. 58.9% [21.4]), weekly average PP-NRS (7.6 [1.4] vs. 7.6 [1.6]), CDLQI (17.5 [5.5] vs. 17.8 [6.4]) and IDQOL (18.4 [5.1] vs. 17.4 [5.4]). Dupilumab treatment resulted in a rapid and significant increase in the proportion of patients achieving EASI-75 compared with placebo treatment by week 4 (27% vs. 4.8%; P = 0.0009). By week 16, this improvement was further increased compared with the placebo group (46% vs. 7%; P &amp;lt; 0.0001). At week 16, dupilumab-treated patients had a significantly greater percent reduction from baseline in PP-NRS compared with the placebo group (LS mean (SE)–41.8 [5.4] vs. 0.5 [5.4]; P &amp;lt; 0.0001). Dupilumab also resulted in significant improvement in quality-of-life outcomes compared with placebo (LS mean [SE]) change from baseline to week 16 in CDLQI (−9.1 [1.1] vs. −2.6 [1.2]; P &amp;lt; 0.0001); IDQOL (−9.1 [1.3] vs. −0.6 [1.1]; P &amp;lt; 0.0001). Treatment-emergent adverse events (TEAEs) were reported in 42 (66.7%) patients in the dupilumab group and 45 (73.8%) patients in the placebo group. Most TEAEs were mild to moderate and deemed unrelated to the study drug by the investigator. The most common TEAE was atopic dermatitis in both the dupilumab group (10 [15.9%]) and placebo group (16 [26.2%]). Additionally, TEAEs in the conjunctivitis cluster were reported by 4 (6.4%) patients in the dupilumab group and none in the placebo group. In the placebo group, 3 (4.9%) serious adverse events were reported. No dupilumab-related adverse events were serious or led to treatment discontinuation. Dupilumab significantly improved AD signs, symptoms, and quality of life in children aged 6 months to 5 years with severe AD. The safety profile was consistent with that previously seen in adults, adolescents, and children aged &amp;gt; 6 years of age.

337 Dupilumab treatment is not associated with an increased overall risk of infections in patients aged 6 months to 5 years with moderate-to-severe atopic dermatitis

Abstract Patients with atopic dermatitis (AD) have an increased risk of infection, including skin infections. Previous studies in children aged 6–11 years and adolescents showed that dupilumab is not associated with an increased risk of overall infections and is associated with a lower incidence of skin infections compared with a placebo. This post-hoc analysis reports the impact of dupilumab treatment on infections, including skin infections, in children aged 6 months to 5 years with moderate-to-severe AD. In LIBERTY AD PRESCHOOL, a double-blind, placebo-controlled trial (NCT03346434, part B), children aged 6 months to 5 years with moderate-to-severe AD (Investigator’s Global Assessment score ≥3) were randomized 1 : 1 to subcutaneous dupilumab every 4 weeks (200 mg if baseline weight was ≥5 to &amp;lt;15 kg, 300 mg if weight was ≥15 to &amp;lt;30 kg) or placebo with concomitant low-potency topical corticosteroids for 16 weeks. Exposure-adjusted rates (patients with ≥1 event per 100 patient-years [nP/100 PY]) and systemic anti-infective medication use (nP/100PY) were used to compare treatment groups. 162 patients were randomized to dupilumab (n = 83) or placebo (n = 79). During the 16-week treatment period, total infections rates were numerically lower in the dupilumab-treated group (nP/100PY: 185.2) compared with the placebo-treated group (nP/100PY: 245.7). Fewer infections of skin-structure and soft tissues were reported in the dupilumab group (nP/100PY: 24.7) compared with the placebo group (nP/100PY: 40.2). Dupilumab-treated patients had significantly lower rates of non-herpetic skin infections (nP/100PY: 42.7) than placebo-treated patients (nP/100PY: 92.7; P &amp;lt; 0.05 vs. placebo). There was no significant difference in rates of herpetic skin infections between the dupilumab (nP/100PY: 20.0) and placebo groups (nP/100PY: 17.1; P = 0.817 vs. placebo). No helminthic infections were reported in either group. Systemic anti-infective medication use was significantly less frequent in the dupilumab group (nP/100PY: 104.7) compared with placebo (nP/100PY: 203.0; P &amp;lt; 0.05 vs. placebo). The overall safety of dupilumab was consistent with the known safety profile. Dupilumab treatment is associated with lower overall infections and significantly lower non-herpetic skin infections than placebo in children aged 6 months to 5 years with moderate-to-severe AD.

33006 Long-term improvement of patient-reported outcomes in adult patients with atopic dermatitis treated with baricitinib in the US and Canada

Objective: To evaluate long-term patient-reported outcome (PRO) improvements in patients with atopic dermatitis (AD) treated with baricitinib, a Janus kinase (JAK)1/JAK2 inhibitor. Methods: Data were derived from 2 phase 3 studies: double-blind placebo-controlled BREEZE-AD5 (NCT03435081) and long-term open-label extension BREEZE-AD6 (NCT03559270) through 52 weeks of treatment. Low-potency topical corticosteroids were permitted after Week 16 in BREEZE-AD5 and throughout BREEZE-AD6. PROs [Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), and Hospital Anxiety Depression Scale (HADS-anxiety and HADS-depression)] were assessed to Week 52 using descriptive statistics with missing data imputed by last observation carried forward. Results: In 146 patients receiving baricitinib 2 mg, the quality of life measure DLQI (mean ± standard deviation at baseline 15.0 ± 7.6) showed a mean change from baseline of −7.0 ± 8.2 at Weeks 48-52. Patient-reported improvements in skin symptoms as measured by POEM were −7.3 ± 8.8 at Weeks 48-52 from mean baseline value of 21.7 ± 5.4. By Weeks 48-52, 68.9% and 57.6% of patients had achieved a clinically meaningful ≥4-point improvement in DLQI and POEM, respectively. HADS-anxiety and HADS-depression scores were 7.0 ± 4.4 and 5.2 ± 4.3 at baseline, respectively, with patients reporting a change from baseline of −1.9 ± 3.7 and −1.8 ± 3.3 at Weeks 48-52. Conclusion: Patients with moderate to severe AD treated with baricitinib 2 mg experienced clinically meaningful PRO improvements in skin symptoms, quality of life, and anxiety and depression over 52 weeks.

Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: a randomised, double-blind, placebo-controlled, phase 3 trial

Current systemic treatments for children younger than 6 years with moderate-to-severe atopic dermatitis that is uncontrolled with topical therapies might have suboptimal efficacy and safety. Dupilumab is approved for older children and adults with atopic dermatitis and for other type 2 inflammatory conditions. We aimed to evaluate efficacy and safety of dupilumab with concomitant low-potency topical corticosteroids in children aged 6 months to younger than 6 years with moderate-to-severe atopic dermatitis. This randomised, double-blind, placebo-controlled, parallel-group, phase 3 trial was conducted in 31 hospitals, clinics, and academic institutions in Europe and North America. Eligible patients were aged 6 months to younger than 6 years, with moderate-to-severe atopic dermatitis (Investigator's Global Assessment [IGA] score 3-4) diagnosed according to consensus criteria of the American Academy of Dermatology, and an inadequate response to topical corticosteroids. Patients were randomly assigned (1:1) to subcutaneous placebo or dupilumab (bodyweight ≥5 kg to <15 kg: 200 mg; bodyweight ≥15 kg to <30 kg: 300 mg) every 4 weeks plus low-potency topical corticosteroids (hydrocortisone acetate 1% cream) for 16 weeks. Randomisation was stratified by age, baseline bodyweight, and region. Patient allocation was done via a central interactive web response system, and treatment allocation was masked. The primary endpoint at week 16 was the proportion of patients with IGA score 0-1 (clear or almost clear skin). The key secondary endpoint (coprimary endpoint for the EU and EU reference market) at week 16 was the proportion of patients with at least a 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Primary analyses were done in the full analysis set (ie, all randomly assigned patients, as randomly assigned) and safety analyses were done in all patients who received any study drug. This study was registered with ClinicalTrials.gov, NCT03346434. Between June 30, 2020, and Feb 12, 2021, 197 patients were screened for eligibility, 162 of whom were randomly assigned to receive dupilumab (n=83) or placebo (n=79) plus topical corticosteroids. At week 16, significantly more patients in the dupilumab group than in the placebo group had IGA 0-1 (23 [28%] vs three [4%], difference 24% [95% CI 13-34]; p<0·0001) and EASI-75 (44 [53%] vs eight [11%], difference 42% [95% CI 29-55]; p<0·0001). Overall prevalence of adverse events was similar in the dupilumab group (53 [64%] of 83 patients) and placebo group (58 [74%] of 78 patients). Conjunctivitis incidence was higher in the dupilumab group (four [5%]) than the placebo group (none). No dupilumab-related adverse events were serious or led to treatment discontinuation. Dupilumab significantly improved atopic dermatitis signs and symptoms versus placebo in children younger than 6 years. Dupilumab was well tolerated and showed an acceptable safety profile, similar to results in older children and adults. Sanofi and Regeneron Pharmaceuticals.

Follicular eczema and accentuation: A survey of published data

To the Editor: Follicular eczema or follicular atopic dermatitis presents with a predominant pattern of very pruritic follicular accentuation, usually over the chest, back, abdomen, and flanks (Fig 1). Distinguished from follicular keratosis by spongiotic dermatitis of the follicle, the differential diagnosis of follicular dermatitis also includes allergic contact dermatitis, follicular mucinosis, infundibulofolliculitis, and drug reactions. Clinically, follicular eczema has been reported to be poorly responsive to low-potency topical corticosteroids.

Efficacy and Safety of Qingpeng Ointment for Subacute and Chronic Eczema: A Systematic Review and Meta-Analysis.

Objective To evaluate the efficacy and safety of Qingpeng ointment for the treatment of subacute and chronic eczema. Method Randomized controlled trials (RCTs) on Qingpeng ointment for subacute and chronic eczema were searched on PubMed, the Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database, and Chinese Science and Technology Periodical Journal from their inception to 30 November 2020. Quality assessment and data analysis were performed by Review Manager 5.3. Results A total of 26 RCTs were included. Qingpeng ointment could significantly improve the total efficacy rate (TER) (RR = 2.60, 95% CI: 2.11 to 3.21, P < 0.00001), reduce the total symptom score (TSS) (SMD = −2.35, 95% CI: -3.74 to -0.97, P = 0.0009), and decrease visual analogue scale (VAS) for pruritus (MD = −3.86, 95% CI: -4.41 to -3.31, P < 0.00001) compared with the placebo. The TER of Qingpeng ointment was similar to that of topical corticosteroid (TCS) (RR = 0.96, 95% CI: 0.88 to 1.03, P = 0.25), and the TSSs between Qingpeng ointment and medium or low potency TCS were not significantly different (SMD = −0.05, 95% CI: -0.22 to 0.12, P = 0.54). However, Qingpeng ointment was not superior to TCS in reducing VAS score (SMD = 0.48, 95% CI: 0.00 to 0.96, P = 0.05). In addition, Qingpeng ointment combined with TCS performed better than TCS alone in all three outcomes. For safety, nothing but skin irritative reactions occurred in the Qingpeng ointment group, and its incidence of skin irritative reactions was similar to those of the placebo (RR = 1.47, 95% CI: 0.61 to 3.55, P = 0.40) and TCS (RR = 1.82, 95% CI: 0.79 to 4.22, P = 0.16). The combined therapy did not increase the risk of skin irritative reactions (RR = 0.69, 95% CI: 0.27 to 1.78, P = 0.44). Conclusion Qingpeng ointment is an effective and safe treatment for subacute and chronic eczema. It is also an add-on treatment to TCS for eczema. However, due to the suboptimal quality of the included studies, more large-sample and high-quality RCTs are needed to improve the evidence quality.

Safety and Efficacy of Upadacitinib in Combination With Topical Corticosteroids in Adolescents and Adults With Moderate-to-Severe Atopic Dermatitis: Results From a Pivotal Phase 3, Randomised, Double-Blind, Placebo-Controlled Study (AD Up)

Safety and Efficacy of Upadacitinib in Combination With Topical Corticosteroids in Adolescents and Adults With Moderate-to-Severe Atopic Dermatitis: Results From a Pivotal Phase 3, Randomised, Double-Blind, Placebo-Controlled Study (AD Up)

Frequent Versus Infrequent Bathing in Pediatric Atopic Dermatitis: A Randomized Clinical Trial

Studies evaluating bathing frequency in pediatric atopic dermatitis (AD) are limited. Parents of children with AD often receive conflicting information, leading to frustration and confusion. To evaluate efficacy of twice-daily soaking baths, followed by immediate application of an occlusive moisturizer (ie, soak-and-seal [SS]), versus twice-weekly SS baths, in the acute management of pediatric AD. We conducted a randomized, single-blind, crossover-controlled trial comparing frequent versus infrequent SS baths, in children 6 months to 11 years of age with moderate-to-severe AD. Children were randomized 1:1 into 2 groups: group 1 underwent twice-weekly SS baths, for 10 minutes or less, over 2 weeks ("dry method" [DM]) followed by twice-daily SS baths, for 15 to 20 minutes, over 2 weeks ("wet method" [WM]). Group 2 did the inverse. Patients received the same moisturizer, cleanser, and low-potency topical corticosteroid (TCS). Primary outcome was AD severity evaluated using the SCORing Atopic Dermatitis (SCORAD) index. Caregiver assessment of AD severity (Atopic Dermatitis Quickscore [ADQ]), quality of life, Staphylococcal aureus colonization, skin hydration, moisturizer, and TCS usage were assessed. Of the 63 children screened, 42 fulfilled inclusion criteria and were randomized. Forty (95%) completed the study. WM decreased SCORAD by 21.2 compared with DM (95% confidence interval [CI], 14.9-27.6; P < .0001). Secondary analysis showed a greater than 30% SCORAD improvement for WM versus DM (McNemar's χ2= 8.83, df= 1, P= .0030). SCORAD correlated with ADQ (r= 0.66), and ADQ also showed significant improvement with WM decreasing ADQ by 5.8 (95% CI, 1.8-9.7). No other secondary endpoints showed significance. As an acute treatment intervention, WM is superior to DM at improving disease severity in moderate-to-severe pediatric AD.

Evaluation of Hypothalamic-Pituitary-Adrenal Axis Suppression following Cutaneous Use of Topical Corticosteroids in Children: A Meta-Analysis

Background/Aims: A meta-analysis was performed to determine the likelihood of hypothalamic-pituitary-adrenal (HPA) axis suppression following short-term cutaneous treatment of atopic dermatitis with topical corticosteroids (TCS) in pediatric patients. Methods: All published pediatric clinical trials evaluating TCS use with pre- and post-treatment HPA axis assessment by cosyntropin stimulation testing were included. Results: Of 128 eligible trials, 12 were selected for meta-analysis with a total of 522 participants. There were 20 observed cases of HPA axis suppression (3.8%, 95% CI 2.4–5.8). The percentage of HPA axis suppression with low- (classes 6–7), medium- (classes 3–5) and high-potency (classes 1–2) TCS use was 2% (3 of 148 patients, 95% CI 0.7–5.8), 3.1% (7 of 223 patients, 95% CI 1.5–6.3), and 6.6% (10 of 151 patients, 95% CI 3.6–11.8), respectively. Conclusion: There is a low rate of reversible HPA axis suppression with the use of mid- to low-potency TCS compared to more potent formulations. In pediatric clinical practice, the limited use of mid- to low-potency TCS is rarely associated with clinically significant adrenal insufficiency or adrenal crisis. In the absence of signs and symptoms of adrenal insufficiency, there is little need to test the HPA axis of these patients.

Ibrutinib-Associated Rash: Single-Center Experience of Clinicopathologic Features and Management

▪Introduction:Ibrutinib is a Bruton tyrosine kinase inhibitor approved for previously treated chronic lymphocytic leukemia (CLL), CLL with del(17p), previously treated mantle cell lymphoma (MCL), and Waldenstršm macroglobulinemia. Cutaneous manifestations including purpuric eruptions have been reported in 8-27% of patients receiving ibrutinib, sometimes resulting in treatment delays or drug discontinuation. Guidelines regarding optimal clinical management have not been established.Methods:We identified patients who developed rash while receiving ibrutinib at our institution. Data were collected through retrospective chart review with IRB approval.Results:Characteristics of 14 patients (13 CLL, 1 MCL) identified are shown in Table 1. Two distinct purpuric rash subtypes were observed: 1) a non-palpable, largely asymptomatic petechial rash (Figure 1A), and 2) a palpable eruption characterized clinically by pruritic, non-blanching, purpuric papules (Figure 1B).The non-palpable, petechial rash was observed in 5 patients, all of whom had CLL; 4 patients were receiving single-agent ibrutinib, and 1 received ibrutinib with concurrent rituximab. The median onset of rash from first ibrutinib dose was 80 days, corresponding to the lymphocytosis resolution phase in all patients. The rash was grade 1 (n=4) or grade 2 (n=1) in severity, and was not associated with an allergic history or other mucocutaneous findings. All patients were able to continue receiving ibrutinib without dose interruptions, delays, or skin-directed therapy.Palpable skin eruptions were observed in 9 patients (8 CLL and 1 MCL); 4 patients were receiving ibrutinib monotherapy, and 5 received ibrutinib in combination with rituximab. The median onset of rash from first ibrutinib dose was 15 days, corresponding to the lymphocytosis phase in 6 of the CLL patients. The rash severity was grade 1 (n=1), grade 2 (n=4), or grade 3 (n=4). Two patients with grade 3 rash had concurrent symptoms concerning for a severe allergic drug reaction, including lip tingling and tongue swelling. Two patients with grade 3 rash underwent biopsy, demonstrating perivascular infiltration of lymphocytes, neutrophils, and eosinophils involving the papillary dermis (Figure 1C, 1D). All patients with palpable rash were referred to a dermatologist and received low-potency topical corticosteroids and/or oral antihistamines. In the 5 patients with grade 1-2 rash, these measures yielded rash resolution at a median of 21 days. In the 4 patients with grade 3 rash, these measures were employed and ibrutinib was interrupted until rash resolution, which occurred at a median of 12 days. Ibrutinib rechallenge was successful without rash recurrence in 2 of 4 patients with grade 3 rash. In the other 2 patients, rash recurred on ibrutinib rechallenge (both were patients with concurrent lip tingling and tongue swelling at initial presentation) and required therapy to be interrupted again with initiation of systemic steroids until rash resolution at 2 and 5 days. Both patients were able to resume treatment with ibrutinib with concomitant prednisone taper without rash recurrence.ConclusionsThis single-center study identified 2 presentations of ibrutinib-associated purpuric rash: a non-palpable, petechial eruption and a palpable purpuric rash. The non-palpable rash had a later onset, was mild, and did not require skin-directed therapy or ibrutinib dose adjustment. In contrast, palpable purpuric rash had an earlier onset and varied significantly in clinical presentation and severity; all patients were successfully managed with topical therapy, oral antihistamines, systemic corticosteroids, and temporary interruption of ibrutinib, and all were ultimately able to resume ibrutinib. Our study provides guidance for recognition and management of ibrutinib associated rash, which is important due to its increasing use after approval.Table 1Non-palpable (n=5)Palpable (n=9)Female34Underlying disease CLL MCL5 08 1Concurrent antiplatelet/anticoagulant13History of drug allergy25Baseline WBC, 109 cells/L - median (range)140 (54-280)22 (4-470)Rash onset - median, days (IQR)80 (63-146)15 (12-64)Rash severity Grade 1 Grade 2 Grade 34 1 01 4 4Associated with allergic findings02Ibrutinib dose modified Temporary interruption Dose reduction Discontinuation0 0 04 1 0Systemic steroids administered02Abbreviations: IQR, interquartile range. [Display omitted] DisclosuresCoutre:Janssen: Honoraria, Research Funding; Pharmacyclics: Honoraria, Research Funding.

Topical tacrolimus for atopic dermatitis.

Topical tacrolimus for atopic dermatitis.

Managing nappy rash

Approximately a quarter of infants develop nappy rash, which arises from the interaction between several mutually reinforcing factors. Three possible causes of nappy rash are: poor hygiene and skin care; sensitivity to detergents, fabric softeners and other external products; and infection. Once nappy rash develops, management aims to repair damage and prevent recurrence. The cornerstones of prevention and treatment are good routine skincare, frequent nappy changes, gentle cleansing and applying a barrier formulation at every nappy change. Candida albicans may cause moderate-to-severe nappy rash, for which topical antifungals may be appropriate. Brief courses of low-potency topical corticosteroids are suitable only when very inflamed dermatitis does not respond to other treatments. There is a need for further investigations of the pathogenesis (e.g. clarifying the role of C. albicans) and management of nappy rash, such as the relative efficacy of over-the-counter treatments.

Successful treatment of eczema coxsackium with wet wrap therapy and low-dose topical corticosteroid

Successful treatment of eczema coxsackium with wet wrap therapy and low-dose topical corticosteroid

Clobetasol Propionate, 0.05%, vs Hydrocortisone, 1%, for Alopecia Areata in Children

Alopecia areata is an idiopathic cause of hair loss with limited therapeutic repertoire. To compare the efficacy and safety of a high- vs low-potency topical corticosteroid in pediatric patients. This single-center, randomized, blind, 2-arm, parallel-group, superiority trial was carried out over a 24-week period at a tertiary referral academic dermatology clinic at The Hospital for Sick Children in Toronto, Ontario, Canada. Forty-two children attending the outpatients clinic, 2 to 16 years of age with alopecia areata affecting at least 10% of scalp surface area, were eligible; 1 declined to participate. There were no withdrawals from the study. INTERVENTIONS FOR CLINICAL TRIALS: Patients were randomly assigned to receive clobetasol propionate, 0.05% cream, or hydrocortisone, 1%, cream. Patients applied a thin layer of the assigned cream twice daily to the areas of hair loss for 2 cycles of 6 weeks on, 6 weeks off, for a total of 24 weeks. The primary outcome was the change in scalp surface area with hair loss over 24 weeks following enrollment. RESULTS All participants were assessed at 6, 12, 18, and 24 weeks (except 1 participant who missed the 6-week visit). After adjusting for baseline hair loss, the clobetasol group had a statistically significant (P < .001) greater decrease in the surface area with hair loss, compared with the hydrocortisone group at all time points except at 6 weeks. One patient with extensive alopecia areata experienced skin atrophy that resolved spontaneously in 6 weeks. There was no difference observed in the number of patients with abnormal urinary cortisol at the beginning and the end of the study. Topical clobetasol propionate, 0.05%, cream is efficacious and safe as a first-line agent for limited patchy childhood alopecia areata. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01453686.

Comparative Effectiveness of Topical Calcineurin Inhibitors in Adult Patients with Atopic Dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by extreme pruritis and lichenified papules and plaques that may begin in or persist into adulthood. Topical corticosteroids are first-line prescription therapy for AD; they are efficacious and have a well established safety profile. The topical calcineurin inhibitors tacrolimus and pimecrolimus were approved by the US FDA in 2000 and 2001, respectively, as second-line topical therapy for AD. This review evaluates the available studies on the comparative effectiveness, safety, cost, and impact on quality of life of topical corticosteroids and topical calcineurin inhibitors for the treatment of adult AD. Tacrolimus was found to be as effective as class III-V topical corticosteroids for AD of the trunk and extremities, and more effective than low-potency class VI or VII corticosteroids for AD of the face or neck. Pimecrolimus was less effective than both tacrolimus and low-potency topical corticosteroids for moderate to severe AD. The short-term safety studies found that, compared with topical corticosteroid-treated adults, patients treated with topical calcineurin inhibitors had an increased frequency of application-site reactions, an equivalent infection risk, and a decreased risk of skin atrophy. The long-term safety of topical calcineurin inhibitors remains under investigation. Currently published studies that evaluated the comparative cost and quality-of-life effects compared tacrolimus with less potent topical corticosteroids despite the availability of equivalent potency corticosteroids. Further cost and quality-of-life studies are needed that compare topical calcineurin inhibitors with stronger classes of topical corticosteroids over longer time periods. The available clinical trials data do not suggest an efficacy advantage for topical calcineurin inhibitors over topical corticosteroids in adults with AD of the trunk and extremities, and there is not yet adequate evidence to support topical calcineurin inhibitors as first-line therapy for adult AD.