Efficacy and Safety of Dupilumab Treatment with Concomitant Topical Corticosteroids in Children Aged 6 Months to 5 Years with Severe Atopic Dermatitis.

INTRODUCTION: Treatment options for children younger than 6 years with severe atopic dermatitis (AD) are limited, as systemic immunosuppressants may present safety concerns in this young age group. Dupilumab is the first systemic treatment option approved for infants and young children with severe AD in the European Union. This study reports the efficacy and safety of dupilumab with concomitant low-potency corticosteroids in children aged 6 months to 5 years with severe AD. METHODS: This was a pre-specified subgroup analysis of data for patients aged 6 months to 5 years with severe AD at baseline (Investigator's Global Assessment [IGA] = 4) from a randomised, double-blind, placebo-controlled, phase III trial of dupilumab. Patients were randomised to either subcutaneously administered dupilumab (200/300 mg) or matched placebo every 4 weeks, plus low-potency topical corticosteroids for 16 weeks. Co-primary endpoints at week 16 were the proportion of patients with IGA ≤ 1 (clear or almost clear skin) and the proportion of patients with ≥ 75% improvement from baseline in Eczema Area and Severity Index (EASI-75). Secondary endpoints at week 16 included mean changes in EASI, pruritus, skin pain, sleep loss and quality of life. RESULTS: The analysis included 125 patients (63 receiving dupilumab vs. 62 placebo). At week 16, significantly more patients receiving dupilumab vs. placebo had achieved IGA ≤ 1 (14.3% vs. 1.6%; P = 0.0085) and EASI-75 (46.0% vs. 6.6%; P < 0.0001). Significant improvements with dupilumab were observed in all secondary endpoints, including a least squares mean 48.9% reduction in pruritus. The overall incidence of adverse events (AEs) was similar between the dupilumab and placebo groups (66.7% vs. 73.8%). No dupilumab-related AEs were serious or led to treatment discontinuation. CONCLUSION: Dupilumab significantly improved AD signs, symptoms and quality of life in children aged 6 months to 5 years with severe AD with acceptable safety. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov with ID number NCT03346434, part B.

Atopic dermatitis (AD) is a chronic skin disease that is relatively common in infants and young children worldwide. Severe AD causes skin rashes and intense itch that strongly interfere with sleep quality and normal daily activities, thereby affecting the quality of life of patients and their families. When therapies for AD that are applied to the skin do not work, limited options are available to treat severe AD in children younger than 6 years. In this study, we evaluated the efficacy and safety of dupilumab in children aged 6 months to 5 years with severe AD, recruited from various sites in Europe and North America. Patients received 200 or 300 mg of dupilumab (based on the child's weight) or placebo, together with mild steroids applied to the skin, every 4 weeks for 16 weeks. At the end of treatment, AD severity was greatly improved in patients receiving dupilumab, with 14% of patients achieving almost clear skin. Patients receiving dupilumab also experienced significant improvements in itch intensity, sleep quality, skin pain, and quality of life. Furthermore, dupilumab did not increase the risk of infections. This study demonstrates that dupilumab can be effective at treating severe AD in infants and young children, with important benefits for the quality of life of patients and their families.

Operative Treatment of Severe Allergic Reactions to Red Tattoo Dye: Presentation and Comparison of Possible Surgical Procedures in Seven Patients.

Context: The treatment of allergic reactions to red tattoo dye is challenging in most cases, as local therapy often does not offer long-term improvement and laser therapy is considered relatively contraindicated by many authors owing to the risk of generalized side effects. Therefore, surgical removal of these tattoos is favored; shave excision is the method of choice, particularly for the removal of the entire dye. Aims: The aim of this article was to retrospectively analyze the best post-operative outcome after surgical removal of allergic tattoo reactions using different excision techniques. Materials and Methods: We compared the different surgical procedures performed on seven patients with single and multiple allergic tattoo reactions treated between 2013 and 2018. Results: The best aesthetic results were achieved by superficial ablation of the inflammatory reaction, partially leaving tattoo remains in the skin. Conclusion: Based on our experience with this small number of patients, a superficial removal of the tattoo without complete removal of the dye is, in most cases, sufficient to achieve healing. The remaining dye residues seem to be better tolerated by the immune system afterwards. Furthermore, the tattoo is often preserved in large parts.

Examination of Subungual Hematomas and Subungual Melanocytic Lesions by Using Optical Coherence Tomography and Dermoscopy.

INTRODUCTION: Examination of subungual pigmented lesions is sometimes a diagnostic challenge for clinicians. OBJECTIVES: The study was aimed to investigate characteristic patterns in optical coherence tomography (OCT) of subungual hematomas and determine distinctive features that can differentiate them from subungual melanocytic lesions. METHODS: VivoSight® (Michelson Diagnostics, Maidstone, UK) was used to examine 71 subungual hematomas and 11 subungual melanocytic lesions in 69 patients (18 female and 51 male patients). RESULTS: On OCT, bleeding was related to sharply defined black sickle-shaped (p < 0.001) or globular regions (not significant [ns]) with a hyperreflective margin (0.002), a grey center (0.013), hyperreflective lines in the area (ns) or periphery (p = 0.031), peripheral fading (p = 0.029), and red dots in the area (p = 0.001). In the 1 case of melanoma in situ examined, we found curved vessels with irregular sizes and distribution on the dermis of the nailbed, while subungual hematomas and subungual benign nevi presented as clustered red dots and/or regularly distributed curved vessels. CONCLUSION: Our findings indicate that the use of OCT in addition to dermoscopy provides high-resolution optical imaging information for the diagnosis of subungual hematoma and facilitates the differential diagnosis of subungual hematomas and subungual melanocytic lesions.

Effects of Intermittent Treatment with Topical Corticosteroids and Calcineurin Inhibitors on Epidermal and Dermal Thickness Using Optical Coherence Tomography and Ultrasound.

INTRODUCTION: Proactive therapy with topical corticosteroids (TCSs) is the standard treatment for chronic inflammatory diseases such as atopic dermatitis; however, skin atrophy as TCS side effect remains a concern. METHODS: This 16-week, evaluator-blinded, within-patient placebo-controlled, randomized study enrolled volunteers with healthy skin conditions. For 12 weeks, their volar forearm and the back of their hand were applied with hydrocortisone acetate 1% cream (HC), methylprednisolone aceponate 0.1% cream (MPA), betamethasone valerate 0.1% cream (BMV), or an active agent-free base cream (Dermatop® Basiscreme) once daily twice weekly, and pimecrolimus 1% cream (PIM) twice daily twice weekly. Epidermal and dermal thickness was measured by optical coherence tomography and high-frequency ultrasound, respectively. Furthermore, skin atrophy and telangiectasia were determined by contact dermatoscopic photography (Dermaphot®). RESULTS: After 8 and 12 weeks, only BMV led to significant epidermal thinning on both sites. Four weeks after the end of treatment, epidermal thickness returned to baseline. No dermal thinning, atrophy, or telangiectasia was observed. CONCLUSIONS: MPA, HC, and PIM may be more suitable for repeated and prolonged treatment, especially in chronic diseases.

[Successful treatment of cutaneous leishmaniasis with simulated daylight photodynamic therapy]. / Erfolgreiche Therapie der kutanen Leishmaniose mit simulierter Tageslicht-photodynamischer Therapie.

A 5-year-old Syrian boy , presented with a complex cutaneous leishmaniasis (CL) of the right ankle caused by Leishmania (L.) tropica. The patient received photodynamic therapy (PDT; 6 cycles with application of 5­aminolevulinic acid and foil occlusion for 3 h). Due to pain during exposure to red light, exposure was continued with simulated daylight (sDL-PDT). The lesion healed with an atrophic scar. Due to fewer side effects and less pain, sDL-PDT seems to be a good therapeutic strategy for CL caused by L. tropica.

Documentation of psoriasis in routine care - expert consensus on a German data set.

BACKGROUND AND OBJECTIVES: Documenting patient data in psoriasis clinical practice can improve care, but standardized and transparent documentation is rare. The current project aimed to develop a data set for the documentation of psoriasis in daily practice. MATERIAL AND METHODS: In four online Delphi rounds and one in-person meeting, 27 psoriasis experts allocated variables to a standard, an optimal and an optional data set. Most of the questions were standardized. Open questions were included to allow for the provision of reasons and to enlarge the data sets. Furthermore, in the in-person meeting we considered a) patients' attitudes and b) dermatologists' information on the current usage and acceptability in Germany. RESULTS: The consensus approach resulted in a data set with 69 variables. The standard data set includes 20, the optimal data set 31 and the optional data set 18 variables. In summary, the data set can mainly be grouped into master data, general status and medical history data, medical history of psoriasis, status of psoriasis, diagnostics and comorbidity, therapies and patient-reported outcomes. CONCLUSIONS: The consensus recommendation of a standard, an optimal and an optional data set for routine care of psoriasis intends to be a decision-making aid and an orientation for both daily practice and further development of documentation systems.

Beyond-Mild Psoriasis: A Consensus Statement on Calcipotriol and Betamethasone Dipropionate Foam for the Topical Treatment of Adult Patients.

INTRODUCTION: There are clear treatment options for mild psoriasis where topical therapies are the mainstay, and for severe psoriasis where systemic therapy (biologic or non-biologic) is necessary. However, there is less clarity in the 'grey zone' of patients in the moderate or so-called 'beyond-mild' segment. There are frequent delays to the initiation, discontinuation, switching and dose change in treatment, and many patients fail to continue treatment because of concerns about safety or lack of efficacy. Treatment with topical therapies, such as calcipotriol and betamethasone dipropionate (Cal/BD) combinations, may be suitable for these patients. METHOD: These consensus recommendations on the use of topical therapies including Cal/BD foam for beyond-mild psoriasis originated from a modified Delphi process of European clinical experts. In the process, the experts iteratively refined a series of draft statements, which had to receive ≥ 80% approval to be incorporated into the consensus. RESULTS: The experts identified three main themes: Cal/BD foam as monotherapy, as an add-on to non-biologic systemic therapies and as an add-on to systemic biologics. The consensus emphasises disease factors and patient preference in treatment choice, summarises the evidence base for Cal/BD foam monotherapy for flare treatment as well as long-term management, and identifies the potential for improved treatment outcomes, such as reduced time to onset of action and reduced systemic dose to minimise side effects for add-on Cal/BD therapy to non-biologic systemics. The recommendations regarding add-on Cal/BD foam to biologics are similar to those for non-biologic systemic therapies, but also include suggestions for patients on biologics who are late responders. As clinical choices of Cal/BD combination vary, we have here often used 'Cal/BD' without reference to any particular formulation. CONCLUSIONS: These recommendations aim to give practical guidance to those treating patients with beyond-mild psoriasis, to support patients' use of topical preparations and to optimise treatment outcomes.

Red light photodynamic therapy with BF-200 ALA showed superior efficacy in the treatment of actinic keratosis on the extremities, trunk, and neck in a vehicle-controlled phase III study.

BACKGROUND: Actinic keratoses (AK) may occur in all sun-exposed skin areas. Those occurring outside the head area are generally more resistant to treatment than those on the face. OBJECTIVE: To determine efficacy and safety of BF-200 ALA versus vehicle in the treatment of mild-to-severe AK located on extremities, trunk, and neck with red light photodynamic therapy (PDT). METHODS: This phase III study had an intra-individual design with 50 patients in 6 centers in Germany. Each patient received a maximum of 2 field-directed PDTs. Clinical end points and 1-year follow-up results were recorded. RESULTS: BF-200 ALA was superior to the vehicle with respect to total lesion clearance rates (86.0% vs 32.9%; P < .0001) and patient complete clearance per patient's side (67.3% vs 12.2%, P < .0001). One-year overall lesion recurrence rate was 14.1% versus 27.4% (BF-200 ALA vs vehicle; P = .0068). Patients were more satisfied by the cosmetic outcome of BF-200 ALA/PDT than the vehicle/PDT. Adverse events were consistent with the known safety profile of BF-200 ALA/PDT. LIMITATIONS: Small number of severe lesions; limited sample size; unbalanced but representative distribution of AK. CONCLUSION: BF-200 ALA showed significantly higher AK clearance rates on extremities, trunk, and neck than the vehicle and was well tolerated.

Tolerability and Efficacy of Clindamycin/Tretinoin versus Adapalene/Benzoyl Peroxide in the Treatment of Acne Vulgaris.

Acne vulgaris is the most common dermatological disorder worldwide, causing significant physical and psychological morbidity. Topical combination therapy has shown superior efficacy compared to monotherapy, especially when combined with retinoids. Few studies have directly compared combined formulations. This evaluator-blinded pilot study compared the efficacy and tolerability of two marketed topical combination acne gels, clindamycin 1%-tretinoin 0.025% (CT) and benzoyl peroxide 2.5%-adapalene 0.1% (BA) in 20 patients with mild to moderate acne vulgaris. Gels were applied daily on opposite sides of the face for 21 days. The primary outcome was difference in transepidermal water loss (TEWL) at the end of treatment. Secondary endpoints were skin moisture content measurement, Investigators' Global Assessment, subject self-assessments (SSA) of burning/stinging, itching, erythema, and dryness/scaling, and Comparative Participant Satisfaction Questionnaire (CPSQ). Efficacy was assessed by inflammatory and non- inflammatory acne efflorescences counts. TEWL increased significantly for both CT and BA (+57.74%, P=0.002; +58.77%, P<0.001); skin moisture content significantly decreased only for BA (-16.47%, P=0.02). Only BA showed a significant increase in erythema and dryness/scaling (P=0.027 and P=0.014) and in SSA burning/stinging (P=0.04). Patient satisfaction evaluation also reflected the strong BA irritation. Although CT and BA both reduced acne lesions (P<0.001) and more patients preferred to continue with CT, subject perception of acne improvement was higher for BA. These findings suggest that CT and BA have similar efficacy in the treatment of mild to moderate papulopustular acne. However, CT was better tolerated than BA by both medical and subject evaluation. CT is an effective and tolerated treatment option.J Drugs Dermatol. 2021;20(3):295-301. doi:10.36849/JDD.2021.5641.

Real-World Experience Using Topical Therapy-Calcipotriol and Betamethasone Dipropionate Foam in Adults with Beyond-Mild Psoriasis.

INTRODUCTION: Determining optimal treatment for moderate plaque psoriasis can be challenging. Recent studies have demonstrated the effectiveness of calcipotriol and betamethasone dipropionate (Cal/BD) foam in patients with moderate-to-severe plaque psoriasis. METHODS: This research explored the use of Cal/BD foam in patients with beyond-mild psoriasis (defined as patients eligible for topical treatment, systemic treatment, or combined topical/systemic treatments) using an online questionnaire, retrospective medical-record review, and by capturing the attitudes and treatment approaches of dermatology specialists. RESULTS: Data from 409 patients with beyond-mild psoriasis treated with Cal/BD foam were provided by 120 dermatology specialists from Germany, Spain, and the UK. Cal/BD foam was prescribed as monotherapy for most (58%) patients and was considered to be effective. Cal/BD foam was infrequently used in combination with biologics (7%) in this segment; 26% of patients received Cal/BD foam in combination with a non-biologic systemic treatment. Cal/BD foam prescribers generally use topical agents to bridge the waiting time to non-biologic/biologic systemic treatment, and as an add-on to systemic treatment for residual lesions. CONCLUSIONS: In patients with beyond-mild psoriasis, the most commonly prescribed topical medication was Cal/BD foam, which was regarded as an effective treatment. Further research is needed to determine optimal use of Cal/BD foam in these patients.

Type I Interferon Signature in Chilblain-Like Lesions Associated with the COVID-19 Pandemic.

Contemporarily to the new SARS-CoV-2 mediated COVID-19 pandemic, a rise in patients with acral chilblain lesions has been described. They manifest late after mild disease or asymptomatic exposure to SARS-CoV-2. Their pathogenic evolution is currently unknown. In biopsies from three patients with acral partially ulcerating chilblain lesions that occurred associated to the COVID-19 pandemic, we analysed the expression of type I interferon induced proteins and signal transduction kinases. Histology demonstrated perivascular and periadnexal lymphohistiocytic infiltrates and endothelial dominated MxA-staining, as well as pJAK1 activation. Our findings demonstrate induction of the type I IFN pathway in lesional sections of COVID-19-associated chilblain-like lesions. This may indicate a local antiviral immune activation status associated with preceding exposure to SARS-CoV-2.

Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Abrocitinib, an oral selective Janus kinase 1 inhibitor, was effective and well tolerated in adults with moderate-to-severe atopic dermatitis in a phase 2b trial. We aimed to assess the efficacy and safety of abrocitinib monotherapy in adolescents and adults with moderate-to-severe atopic dermatitis. METHODS: In this multicentre, double-blind, randomised phase 3 trial (JADE MONO-1), patients (aged ≥12 years) with moderate-to-severe atopic dermatitis (Investigator Global Assessment score ≥3, Eczema Area and Severity Index [EASI] score ≥16, percentage of body surface area affected ≥10%, and Peak Pruritus Numerical Rating Scale score ≥4) with a bodyweight of 40 kg or more, were enrolled at 69 sites in Australia, Canada, Europe, and the USA. Patients were randomly assigned (2:2:1) to oral abrocitinib 100 mg, abrocitinib 200 mg, or placebo once daily for 12 weeks. Randomisation was done using an interactive response technology system, stratified by baseline disease severity and age. Patients, investigators, and the funder of the study were masked to study treatment. The coprimary endpoints were the proportion of patients who had achieved an Investigator Global Assessment response (score of 0 [clear] or 1 [almost clear] with a ≥2-grade improvement from baseline), and the proportion of patients who achieved at least a 75% improvement in EASI score from baseline (EASI-75) score, both assessed at week 12. Efficacy was assessed in the full analysis set, which included all randomised patients who received at least one dose of study medication. Safety was assessed in all randomised patients. This study is registered with ClinicalTrials.gov, NCT03349060. FINDINGS: Between Dec 7, 2017, and March 26, 2019, 387 patients were enrolled: 156 were assigned to abrocitinib 100 mg, 154 to abrocitinib 200 mg, and 77 to placebo. All enrolled patients received at least one dose of study treatment and thus were evaluable for 12-week efficacy. Of the patients with available data for the coprimary endpoints at week 12, the proportion of patients who had achieved an Investigator Global Assessment response was significantly higher in the abrocitinib 100 mg group than in the placebo group (37 [24%] of 156 patients vs six [8%] of 76 patients; p=0·0037) and in the abrocitinib 200 mg group compared with the placebo group (67 [44%] of 153 patients vs six [8%] of 76 patients; p<0·0001). Of the patients with available data for the coprimary endpoints at week 12, compared with the placebo group, the proportion of patients who had achieved an EASI-75 response was significantly higher in the abrocitinib 100 mg group (62 [40%] of 156 patients vs nine [12%] of 76 patients; p<0·0001) and abrocitinib 200 mg group (96 [63%] of 153 patients vs nine [12%] of 76 patients; p<0·0001). Adverse events were reported in 108 (69%) of 156 patients in the abrocitinib 100 mg group, 120 (78%) of 154 patients in the abrocitinib 200 mg group, and 44 (57%) of 77 patients in the placebo group. Serious adverse events were reported in five (3%) of 156 patients in the abrocitinib 100 mg group, five (3%) of 154 patients in the abrocitinib 200 mg group, and three (4%) of 77 patients in the placebo group. No treatment-related deaths were reported. INTERPRETATION: Monotherapy with oral abrocitinib once daily was effective and well tolerated in adolescents and adults with moderate-to-severe atopic dermatitis. FUNDING: Pfizer.

Topical azithromycin for the prevention of Lyme borreliosis: a randomised, placebo-controlled, phase 3 efficacy trial.

BACKGROUND: Lyme borreliosis develops in 1-5% of individuals bitten by ticks, but with a diagnostic gap affecting up to 30% of patients, a broadly applicable pharmacological prevention strategy is needed. Topical azithromycin effectively eradicated Borrelia burgdorferi sensu lato from the skin in preclinical studies. We assessed its efficacy in human beings. METHODS: In this randomised, double-blind, placebo-controlled, multicentre trial done in 28 study sites in Germany and Austria, adults were equally assigned to receive topical 10% azithromycin or placebo twice daily for 3 consecutive days, within 72 h of a tick bite being confirmed. Randomisation numbers, which were stratified by study site, were accessed in study centres via an interactive voice-response system, by pharmacists not involved in the study. The primary outcome was the number of treatment failures, defined as erythema migrans, seroconversion, or both, in participants who were seronegative at baseline, had no further tick bites during the study, and had serology results available at 8 weeks (intention-to-treat [ITT] population). This study is registered with EudraCT, number 2011-000117-39. FINDINGS: Between July 7, 2011, and Dec 3, 2012, 1371 participants were randomly assigned to treatment, of whom 995 were included in the ITT population. The trial was stopped early because an improvement in the primary endpoint in the group receiving azithromycin was not reached. At 8 weeks, 11 (2%) of 505 in the azithromycin group and 11 (2%) of 490 in the placebo group had treatment failure (odds ratio 0·97, 95% CI 0·42-2·26, p=0·47). Topical azithromycin was well tolerated. Similar numbers of patients had adverse events in the two groups (175 [26%] of 505 vs 177 [26%] of 490, p=0·87), and most adverse events were mild. INTERPRETATION: Topical azithromycin was well tolerated and had a good safety profile. Inclusion of asymptomatic seroconversion into the primary efficacy analysis led to no prevention effect with topical azithromycin. Adequately powered studies assessing only erythema migrans should be considered. A subgroup analysis in this study suggested that topical azithromycin reduces erythema migrans after bites of infected ticks. FUNDING: Ixodes AG.

A Novel multivalent OspA vaccine against Lyme borreliosis is safe and immunogenic in an adult population previously infected with Borrelia burgdorferi sensu lato.

Lyme borreliosis (LB) patients who recover, as well as previously infected asymptomatic individuals, remain vulnerable to reinfection with Borrelia burgdorferi sensu lato. There is limited information available about the use of OspA vaccines in this population. In this study, a randomized double-blind phase I/II trial was performed to investigate the safety and immunogenicity of a novel multivalent OspA vaccine in healthy adults who were either seronegative or seropositive for previous B. burgdorferi sensu lato infection. The participants received three monthly priming immunizations with either 30 µg or 60 µg alum-adjuvanted OspA antigen and a booster vaccination either 6 months or 9 to 12 months after the first immunization. The antibody responses to the six OspA serotypes included in the vaccine were evaluated. Adverse events were predominantly mild and transient and were similar in the seronegative and seropositive populations. Substantial enzyme-linked immunosorbent assay (ELISA) and surface-binding antibody responses against all six OspA antigens were induced after the primary immunization schedule in both populations, and they were substantially increased with both booster schedules. The antibody responses induced by the two doses were similar in the seronegative population, but there was a significant dose response in the seropositive population. These data indicate that the novel multivalent OspA vaccine is well tolerated and immunogenic in individuals previously infected with B. burgdorferi sensu lato. (This study is registered at ClinicalTrials.gov under registration no. NCT01504347.).

Evaluation of the atrophogenic potential of hydrocortisone 1% cream and pimecrolimus 1% cream in uninvolved forehead skin of patients with atopic dermatitis using optical coherence tomography.

Topical corticosteroids are widely used to treat atopic dermatitis (AD), but their anti-inflammatory mode of action can be accompanied by several unwanted side effects including skin atrophy and telangiectasia. In this 8-week, investigator-blinded, intraindividual right-left comparison study with patients with mild-to-moderate AD, hydrocortisone 1% cream (HCT) was applied twice daily for 4 weeks on one side of forehead skin without clinical signs of AD and pimecrolimus 1% cream (PIM) on the other. Epidermal and dermal thickness were assessed by optical coherence tomography (OCT) and high-frequency ultrasound, respectively. Skin atrophy and telangiectasia were assessed by contact dermatoscopic photography (Dermaphot(®)). Treatment with HCT leads to a significant decrease in epidermal thickness after only 2 weeks of treatment, while the decrease in PIM-treated sites was less pronounced and was not statistically significant. By 4 weeks after the end of treatment, epidermal thickness returned to baseline values. No dermal thinning or development of telangiectasia could be observed by means of ultrasound or Dermaphot(®), respectively. In summary, this study indicates that a 2-week single course of topical treatment with a mildly potent steroid can cause transient epidermal thinning, an effect not seen in the PIM group. The slight decrease with PIM - although not significant - could be due to normalization of the increased skin thickness caused by a subclinical inflammation in AD. This study suggests that PIM may be safer for treatment of AD in sensitive skin areas like the face, especially when repeated application is required.