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Background Most children with atopic dermatitis(AD) suffer from sleep disturbance, but reliable and valid assessment tools are lacking. Objectives To test PROMIS (Patient Reported Outcomes Measurement Information System) sleep measures in pediatric AD and to develop an algorithm to screen, assess and intervene to reduce sleep disturbance. Methods A cross-sectional study was conducted with AD children ages 5-17 years and one parent(n=61), who completed sleep, itch, and AD-specific questionnaires; clinicians assessed disease severity. All children wore actigraphy watches for 1-week-objective sleep assessment. Results PROMIS sleep disturbance parent-proxy-reliability was high (Cronbach's α=0.90) and differentiated among Patient Oriented Eczema Measure (POEM)-determined disease severity groups (mean±SD in mild vs. moderate vs. severe was 55.7±7.5 vs. 59.8±10.8 vs. 67.1±9.5, p Limitations This was a local sample. Conclusions Sleep disturbance in pediatric AD should be screened using the POEM sleep question, with further assessment using the PROMIS sleep disturbance measure or objective sleep monitoring if needed.

BACKGROUND Accurate diagnosis of epidermolysis bullosa (EB) has significant implications for prognosis, management, and genetic counseling. OBJECTIVE To describe diagnostic testing patterns and assess diagnostic concordance of transmission electron microscopy (TEM), immunofluorescence mapping (IFM), and genetic analysis for EB. METHODS A retrospective cohort included patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2004, to July 8, 2019. Tests concluding the same EB type (EB simplex, junctional EB, dominant dystrophic EB, and recessive dystrophic EB) were considered concordant; those concluding different EB types were considered discordant; and those with nonspecific/nondefinitive results were equivocal. RESULTS A total of 970 diagnostic tests were conducted from 1984 to 2018 in 771 patients. Genetic analyses were performed chronologically later than IFM or TEM (P

Background The current classification for alopecia areata (AA) does not provide a consistent assessment of disease severity. Objective To develop an AA severity scale based on expert experience. Methods A modified Delphi process was utilized. An advisory group of 22 AA clinical experts from the United States was formed to develop this AA scale. Representatives from the pharmaceutical industry provided feedback during its development. Results Survey responses were used to draft severity criteria, aspiring to develop a simple scale that may be easily applied in clinical practice. A consensus vote was held to determine the final AA severity statement, with all AA experts agreeing to adopt the proposed scale. Limitations The scale is a static assessment intended to be used in clinical practice and not clinical trials. Conclusion The final AA disease severity scale, anchored in the extent of hair loss, captures key features commonly used by AA experts in clinical practice. This scale will better aid clinicians in appropriately assessing severity in patients with this common disease.

Topical and systemic retinoids are often used long-term in the treatment of ichthyoses and other disorders of cornification. The Pediatric Dermatology Research Alliance (PeDRA) Use of Retinoids in Ichthyosis Work Group was formed to address the numerous clinical concerns with use of these medications in children and adolescents and to establish best practices regarding the use of retinoids. Consensus was achieved using the Delphi process with recommendations based on the best available evidence and expert opinion. An executive summary of the results is presented herein.

Background Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking.Objectives Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN.Methods Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method.Results Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements.Conclusions We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

CARD14-associated papulosquamous eruption (CAPE) is a proposed term that encompasses features ranging from psoriasis to pityriasis rubra pilaris (PRP) in association with CARD14 mutations. The early onset of the disease, prominent facial involvement, family history of an autosomal dominant trait, and poor response to conventional treatment are characteristics of CAPE that distinguish it from classical psoriasis and PRP. We describe the clinical features, family history, and response to therapy in three unrelated children with CAPE and compare these characteristics with those of previously described pediatric patients. Testing for CARD14 mutations in children with early onset of features of psoriasis or pityriasis rubra pilaris and resistance to conventional therapy should be considered.

Introduction Pruritus is a common symptom across various dermatologic conditions, with a negative impact on quality of life. Devices to quantify itch objectively primarily use scratch as a proxy. This review compares and evaluates the performance of technologies aimed at objectively measuring scratch behavior. Methods Articles identified from literature searches performed in October 2020 were reviewed and those that did not report a primary statistical performance measure (eg, sensitivity, specificity) were excluded. The articles were independently reviewed by 2 authors. Results The literature search resulted in 6231 articles, of which 24 met eligibility criteria. Studies were categorized by technology, with actigraphy being the most studied (n = 21). Wrist actigraphy's performance is poorer in pruritic patients and inherently limited in finger-dominant scratch detection. It has moderate correlations with objective measures (Eczema and Area Severity Index/Investigator's Global Assessment: rs(ρ) = 0.70-0.76), but correlations with subjective measures are poor (r2 = 0.06, rs(ρ) = 0.18-0.40 for itch measured using a visual analog scale). This may be due to varied subjective perception of itch or actigraphy's underestimation of scratch. Conclusion Actigraphy's large variability in performance and limited understanding of its specificity for scratch merits larger studies looking at validation of data analysis algorithms and device performance, particularly within target patient populations.

Background The distribution of pediatric-onset morphea and site-based likelihood for extracutaneous complications has not been well characterized. Objective To characterize the lesional distribution of pediatric-onset morphea and to determine the sites with the highest association of extracutaneous manifestations. Methods A retrospective cross-sectional study was performed. Using clinical photographs, morphea lesions were mapped onto body diagrams using customized software. Results A total of 823 patients with 2522 lesions were included. Lesions were more frequent on the superior (vs inferior) anterior aspect of the head and extensor (vs flexor) extremities. Linear morphea lesions were more likely on the head and neck, whereas plaque and generalized morphea lesions were more likely on the trunk. Musculoskeletal complications were more likely with lesions on the extensor (vs flexor) extremity (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.2-3.4), whereas neurologic manifestations were more likely with lesions on the anterior (vs posterior) (OR, 2.8; 95% CI, 1.7-4.6) and superior (vs inferior) aspect of the head (OR, 2.3; 95% CI, 1.6-3.4). Limitations Retrospective nature and the inclusion of only patients with clinical photographs. Conclusion The distribution of pediatric-onset morphea is not random and varies with body site and within individual body sites. The risk stratification of extracutaneous manifestations by body site may inform decisions about screening for extracutaneous manifestations, although prospective studies are needed.

Background Persistent skin manifestations, especially calcinoses, contribute to morbidity in children with juvenile dermatomyositis. Objective To compare the course of skin and muscle involvement and document frequency of calcinosis in juvenile dermatomyositis. Methods Prospective cohort study of 184 untreated children with juvenile dermatomyositis (July 1971 to May 2019) at a single children's hospital. Results Disease Activity Scores (DASs) were persistently higher for skin versus muscle at all points; clinical inactivity (DAS ≤2) occurred earlier for muscle than skin. Among vascular features for DAS for skin, eyelid margin capillary dilatation was most frequent (54.3%) and persisted longest. Intravenous methylprednisolone reduced DAS for skin more than oral prednisone at 12 months (P = .04). Overall, 16.8% of patients (n = 31) had calcifications, with 4.9% at enrollment. Despite therapy, 25.0% of calcifications recurred and 22.6% failed to resolve; of the latter, 71.4% (n = 5) were present at enrollment. Children with persistent calcifications had longer duration of untreated disease than those whose calcifications resolved (mean 12.5 months) (P Limitations DAS does not quantify nailfold capillary dropout. Conclusions In juvenile dermatomyositis, skin disease presents with greater activity and is more recalcitrant to therapies than muscle disease. Early and aggressive treatment can limit the severity and persistence of calcifications identified later in the disease course.

Atopic dermatitis (AD) is a chronic and relapsing, inflammatory skin disease characterized by impaired skin barrier function and immune system dysregulation that results in dryness, skin microbiome dysbiosis, and intense pruritus. It is highly heterogeneous and its management is demanding. Patients with AD are at greater risk of comorbidities such as attention-deficit hyperactivity disorder as well as other atopic diseases. Early-onset AD cases typically improve or resolve in late childhood, however it is proposed that the prevalence of persistent or adult-onset AD is higher than previously thought. Basic therapy consists of emollient application and trigger avoidance, and when insufficient, topical corticosteroids (TCS) are the first-line treatment. However, corticophobia/steroid aversion and TCS side effects, particularly on sensitive skin areas, lead to low compliance and insufficient disease control. Several long- and short-term randomized controlled and daily practice studies have demonstrated that topical calcineurin inhibitors, such as pimecrolimus, have similar anti-inflammatory effects to low-to-medium strength TCS, reduce pruritus, and improve the quality of life of patients. In addition, pimecrolimus does not cause skin atrophy, is steroid-sparing, and has a good safety profile, with no evidence for an increased risk of malignancies or skin infections. In general, pimecrolimus cream is well accepted and well tolerated, encouraging patient adherence and leading to its use by many physicians as a preferred therapy for children and sensitive skin areas.

Background Tapinarof is a topical therapeutic aryl hydrocarbon receptor modulating agent under investigation for atopic dermatitis (AD) and psoriasis treatment. Methods A phase 2b, double-blind, vehicle-controlled study randomly assigned adolescents and adults with AD to receive tapinarof cream 0.5%, 1%, or vehicle, once or twice daily, for 12 weeks with a 4-week follow-up. Outcomes included Investigator Global Assessment (IGA), Eczema Area and Severity Index (EASI), body surface area affected, pruritus numeric rating scale scores, patients' impressions of AD and pruritus symptom severity, and Patient-Oriented Eczema Measure (POEM) scores. Results Overall, 191 of 247 randomized patients completed the study. Week 12 IGA responses were higher in the tapinarof groups versus the vehicle group, reaching statistical significance with tapinarof 1% twice daily, ≥75%/90% improvement in EASI from baseline were significantly higher in the tapinarof groups (except 0.5% once daily and 0.5% twice daily), EASI scores were significantly improved in all tapinarof groups, and body surface area affected was significantly reduced in the tapinarof groups (except 0.5% twice daily). More patients reported AD and pruritus symptom severity as very/moderately improved in tapinarof groups, and POEM improvements were observed in all groups. Most adverse events were mild or moderate. Limitations Larger prospective studies are required to confirm the reported analyses. Conclusions Tapinarof is a potential important advance in topical medicine development for AD.

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the United States population. This guideline addresses important clinical questions that arise in psoriasis management and care and provides recommendations based on the available evidence. The treatment of psoriasis with topical agents and with alternative medicine will be reviewed, emphasizing treatment recommendations and the role of dermatologists in monitoring and educating patients regarding benefits as well as risks that may be associated. This guideline will also address the severity assessment methods of psoriasis in adults.

Background/objectives Psoriasis is a chronic, immune-mediated dermatologic disorder with a prevalence among children estimated at 0.1%-0.45%, and a median age of onset at approximately 7-10 years. Pediatric psoriasis is known to have negative impacts on health-related quality of life. Among the most bothersome symptoms, itch has been measured using the Itch Numeric Rating Scale (NRS). This study explored the symptom and impacts of itch with pediatric psoriasis patients and evaluated the content validity of the Itch NRS in children. Methods Semi-structured qualitative interviews were conducted among a sample of pediatric patients diagnosed with plaque psoriasis. Results Concept elicitation interviews were completed with 22 children (ages 7-17 years). When asked about most frequent symptoms, 61% reported itching (n = 14) and 65% reported flaking (n = 15). The majority reported itching as bothersome; about half described impacts on their regular activities. Cognitive interviews were completed with 25 children (ages 8-17 years). Most reported that independently completing the Itch NRS would be easy, and all described the meaning of the response options similar to the intended value. Overall, the Itch NRS was received favorably, with comments that the scale was easy or relevant to their experience with psoriasis. Conclusions This qualitative study supports the content validity of the Itch NRS for use in a pediatric psoriasis population aged 8-17. Given the established importance of itch to pediatric psoriasis patients, future research exploring the impact of itch on the lives of pediatric psoriasis patients may provide a valuable contribution to the field.

Background An estimated 50% of children in the US are Medicaid-insured. Some of these patients have poor health literacy and limited access to medications and specialty care. These factors affect treatment utilization for pediatric patients with atopic dermatitis (AD), the most common inflammatory skin disease in children. This study assesses and compares treatment patterns and healthcare resource utilization (HCRU) between large cohorts of Medicaid and commercially insured children with AD. Methods Pediatric patients with AD were identified from 2 large US healthcare claims databases (2011–2016). Included patients had continuous health plan eligibility for ≥6 months before and ≥12 months after the first AD diagnosis (index date). Patients with an autoimmune disease diagnosis within 6 months of the index date were excluded. Treatment patterns and all-cause and AD-related HCRU during the observation period were compared between commercially and Medicaid-insured children. Results A minority of children were evaluated by a dermatology or allergy/immunology specialist. Several significant differences were observed between commercially and Medicaid-insured children with AD. Disparities detected for Medicaid-insured children included: comparatively fewer received specialist care, emergency department and urgent care center utilization was higher, a greater proportion had asthma and non-atopic morbidities, high- potency topical corticosteroids and calcineurin inhibitors were less often prescribed, and prescriptions for antihistamines were more than three times higher, despite similar rates of comorbid asthma and allergies among antihistamine users. Treatment patterns also varied substantially across physician specialties. Conclusions Results suggest barriers in accessing specialty care for all children with AD and significant differences in management between commercially and Medicaid-insured children. These disparities in treatment and access to specialty care may contribute to poor AD control, especially in Medicaid-insured patients.

Contains fulltext : 225356.pdf (Publisher’s version ) (Closed access) BACKGROUND: An Investigator Global Assessment (IGA) is recommended by health agencies for drug registration in atopic dermatitis (AD). Current IGA scales lack standardization. OBJECTIVES: To develop an IGA scale, training module, and clinical certification examination for use in AD trials; establish content validity; and assess reliability. METHODS: Expert dermatologists participated in the development of the validated IGA for AD (vIGA-AD(TM)). Reliability (interrater and intrarater) was assessed by 2 web-based surveys. Clinical certification for investigators consisted of a training module and examination. RESULTS: Expert consensus was achieved around a 5-point IGA scale including morphologic descriptions, and content validity was established. Survey 1 showed strong interrater reliability (Kendall's coefficient of concordance W [Kendall's W], 0.809; intraclass correlation [ICC], 0.817) and excellent agreement (weighted kappa, 0.857). Survey 2, completed 5 months after training of dermatologists, showed improvements in scale reliability (Kendall's W, 0.819; ICC, 0.852; weighted kappa, 0.889). In this study, 627 investigators completed vIGA-AD training and certification. LIMITATIONS: Ratings were assessed on photographs. CONCLUSION: A validated IGA scale and training module were developed with the intent of harmonizing assessment of disease severity in AD trials. Strong reliability and excellent agreement between assessments were observed.

BACKGROUND: Skin biopsies promote our understanding of atopic dermatitis/AD pathomechanisms in infants/toddlers with early-onset AD, but are not feasible in pediatric populations. Tape strips are an emerging, minimally invasive alternative, but global transcriptomic profiling in early pediatric AD is lacking. We aimed to provide global lesional and nonlesional skin profiles of infants/toddlers with recent-onset, moderate-to-severe AD using tape strips. METHODS: Sixteen tape strips were collected for RNA-seq profiling from 19 infants/toddlers (

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 2% of the world's population. In this guideline, we focus the discussion on systemic, nonbiologic medications for the treatment of this disease. We provide detailed discussion of efficacy and safety for the most commonly used medications, including methotrexate, cyclosporine, and acitretin, and provide recommendations to assist prescribers in initiating and managing patients on these treatments. Additionally, we discuss newer therapies, including tofacitinib and apremilast, and briefly touch on a number of other medications, including fumaric acid esters (used outside the United States) and therapies that are no longer widely used for the treatment of psoriasis (ie, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus).

Background Data regarding the course and treatment of pigmented purpuric dermatoses (PPD) in the paediatric population are limited. Although treatments for pigmented purpura are not well established, vitamin C and rutoside have been reported to be an effective treatment option and are widely utilized. Objective To assess the clinical course and utility of vitamin C and rutoside in paediatric patients with PPD treated at Ann & Robert H. Lurie Children's Hospital of Chicago between 2008 and 2018. Methods A retrospective review of all children with PPD managed at our hospital between 2008 and 2018 was performed. Additional follow-up was obtained via telephone interviews. Results A total of 101 patients met inclusion criteria. The female: male ratio was 1.3 : 1, and the median age at diagnosis was 8.8 years (IQR, 5.7-12.9). Median follow-up was 7.13 months (IQR, 3-17.4). The most common PPD subtypes were lichen aureus (43%) and Schamberg (34%). Fifty-three (52%) patients had evaluable follow-up documentation via their medical record or phone questionnaire. Twenty-eight patients were treated with vitamin C or rutoside or combination therapy. Twenty-five patients received no treatment. Clearance of the rash was noted in 24 (45.3%) patients overall, including 10 (42%) patients in the treated group and 14 (58%) patients in the untreated group. Recurrence was noted in seven (13.2%) patients. Treatment with vitamin C and/or rutoside was well tolerated without side effects. None of the patients were subsequently diagnosed with vasculitis, coagulopathy or cutaneous T-cell lymphoma. Conclusion Pigmented purpuric dermatosis in children is a benign disorder with high rates of complete resolution. Treatment with vitamin C and rutoside is well tolerated, but in this cohort, there did not appear to be an advantage over watchful waiting without therapy.

BACKGROUND: Accurately documenting pediatric atopic dermatitis (AD) severity is important, but research tools, such as Eczema Area and Severity Index (EASI), are too time consuming for clinical settings. Product of the Physician Global Assessment and affected percentage of body surface area (PGA×BSA) is a new, rapid measure of psoriasis severity. OBJECTIVE: To evaluate an Investigator Global Assessment and body surface area product (IGA×BSA) as an easy-to-use severity measure for pediatric AD. METHODS: Patient-reported and objective disease severity measures were collected from 195 caretaker/child dyads (child age range, 5–17 years) with almost clear (Validated Investigator Global Assessment for AD [vIGA] of 1) to severe (vIGA of 4) AD. Data were assessed with Spearman coefficients and plots. Severity strata were proposed by using an anchoring approach based on the EASI. RESULTS: IGA×BSA correlates better with the EASI than IGA alone (r = 0.924 vs r = 0.757, P < .001). Bland-Altman plot indicates high and consistent agreement between IGA×BSA and the EASI. Suggested severity strata for IGA×BSA are 0–30, mild; 30.1–130, moderate; and 130.1–400, severe (κ = 0.760). LIMITATIONS: The patient cohort was predominantly from the midwestern United States. CONCLUSIONS: IGA×BSA (using the vIGA) is a simple measure that correlates well with the EASI in patients with mild to severe pediatric AD. Future work is needed to affirm reliability across IGA scales and responsiveness to change.

Background/objectives The COVID-19 pandemic has raised questions about the approach to management of systemic immunosuppressive therapies for dermatologic indications in children. Change to: Given the absence of data to address concerns related to SARS-CoV-2 infection and systemic immunosuppressive therapies in an evidence-based manner, a Pediatric Dermatology COVID-19 Response Task Force (PDCRTF) was assembled to offer time-sensitive guidance for clinicians. Methods A survey was distributed to an expert panel of 37 pediatric dermatologists on the PDCRTF to assess expert opinion and current practice related to three primary domains of systemic therapy: initiation, continuation, and laboratory monitoring. Results Nearly all respondents (97%) reported that the COVID-19 pandemic had impacted their decision to initiate immunosuppressive medications. The majority of pediatric dermatologists (87%) reported that they were pausing or reducing the frequency of laboratory monitoring for certain immunosuppressive medications. In asymptomatic patients, continuing therapy was the most popular choice across all medications queried. The majority agreed that patients on immunosuppressive medications who have a household exposure to COVID-19 or test positive for new infection should temporarily discontinue systemic and biologic medications, with the exception of systemic steroids, which may require tapering. Conclusions The ultimate decision regarding initiation, continuation, and laboratory monitoring of immunosuppressive therapy during the pandemic requires careful deliberation, consideration of the little evidence available, and discussion with families. Consideration of an individual's adherence to COVID-19 preventive measures, risk of exposure, and the potential severity if infected must be weighed against the dermatological disease, medication, and risks to the patient of tapering or discontinuing therapies.

BACKGROUND Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced atopic dermatitis (AD) severity in a phase II study with concomitant topical corticosteroids. OBJECTIVES To evaluate the efficacy and safety of baricitinib in patients with moderate-to-severe AD who had an inadequate response to topical therapies. METHODS In two independent, multicentre, double-blind, phase III monotherapy trials, BREEZE-AD1 and BREEZE-AD2, adults with moderate-to-severe AD were randomized 2 : 1 : 1 : 1 to once-daily placebo, baricitinib 1 mg, 2 mg, or 4 mg for 16 weeks. RESULTS At week 16, more patients achieved the primary end point of Validated Investigator's Global Assessment of AD (0, 1) on baricitinib 4 mg and 2 mg compared with placebo in BREEZE-AD1 [N = 624; baricitinib 4 mg 16·8% (P < 0·001), 2 mg 11·4% (P < 0·05), 1 mg 11·8% (P < 0·05), placebo 4·8%], and BREEZE-AD2 [N = 615; baricitinib 4 mg 13·8% (P = 0·001), 2 mg 10·6% (P < 0·05), 1 mg 8·8% (P = 0·085), placebo 4·5%]. Improvement in itch was achieved as early as week 1 for 4 mg and week 2 for 2 mg. Improvements in night-time awakenings, skin pain and quality-of-life measures were observed by week 1 for both 4 mg and 2 mg (P ≤ 0·05, all comparisons). The most common adverse events in patients treated with baricitinib were nasopharyngitis and headache. No cardiovascular events, venous thromboembolism, gastrointestinal perforation, significant haematological changes, or death were observed with any baricitinib dosage. CONCLUSIONS Baricitinib improved clinical signs and symptoms in patients with moderate-to-severe AD within 16 weeks of treatment and induced rapid reduction of itch. The safety profile remained consistent with prior findings from baricitinib clinical development in AD, with no new safety concerns.

Standard clinical care in neonatal and pediatric intensive-care units (NICUs and PICUs, respectively) involves continuous monitoring of vital signs with hard-wired devices that adhere to the skin and, in certain instances, can involve catheter-based pressure sensors inserted into the arteries. These systems entail risks of causing iatrogenic skin injuries, complicating clinical care and impeding skin-to-skin contact between parent and child. Here we present a wireless, non-invasive technology that not only offers measurement equivalency to existing clinical standards for heart rate, respiration rate, temperature and blood oxygenation, but also provides a range of important additional features, as supported by data from pilot clinical studies in both the NICU and PICU. These new modalities include tracking movements and body orientation, quantifying the physiological benefits of skin-to-skin care, capturing acoustic signatures of cardiac activity, recording vocal biomarkers associated with tonality and temporal characteristics of crying and monitoring a reliable surrogate for systolic blood pressure. These platforms have the potential to substantially enhance the quality of neonatal and pediatric critical care. Soft electronic patches worn on the skin of infants or children in intensive-care units have a wide range of capabilities in aiding critical care, including monitoring of hemodynamic parameters, cardiac activity, movement and crying.

Background No oral systemic treatments are approved for pediatric patients with psoriasis. Objective To evaluate the pharmacokinetics and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in pediatric patients with psoriasis. Methods This phase 2, multicenter, open-label study enrolled pediatric patients with moderate to severe plaque psoriasis. Patients received apremilast twice daily without titration for 2 weeks (group 1 [age, 12-17 years; weight, ≥35 kg]: apremilast 20 or 30 mg; group 2 [age, 6-11 years; weight, ≥15 kg]: apremilast 20 mg), followed by a 48-week extension. Primary endpoints were pharmacokinetics and safety. Other endpoints were taste/acceptability and change from baseline in score on the Psoriasis Area and Severity Index. Results A total of 42 enrolled patients (21 adolescents [age, 12-17 years] and 21 children [age, 6-11 years]) received apremilast. Pharmacokinetics modeling and noncompartmental analyses showed that weight-based dosing with apremilast 20 mg twice daily in children or apremilast 20 or 30 mg twice daily in adolescents provides exposure (area under the concentration-time curve from time 0 to 12 hours after the dose) that is comparable to that achieved with apremilast 30 mg twice daily in adults. The safety profile was generally similar to that in adults. Most study participants liked the taste of the tablet. Improvements from baseline in mean Psoriasis Area and Severity Index score were 68% for adolescents (overall) and 79% for children. Limitations No children weighing less than 20 kg were enrolled. Conclusions This first-time-in-children phase 2 study supports weight-based apremilast dosing for future phase 3 studies of pediatric plaque psoriasis.

Background Porokeratosis is associated with mevalonate pathway gene mutations. Therapeutic options are few and often limited in efficacy. We hypothesized that topical therapy that aims to replenish cholesterol, an essential mevalonate pathway end-product, and block the accumulation of mevalonate pathway toxic metabolites could alleviate porokeratosis. Objective To study the efficacy of topical cholesterol/lovastatin in different variants of porokeratosis. Methods We enrolled a series of 5 porokeratosis patients,1 with disseminated superficial actinic porokeratosis, 2 with porokeratosis palmaris et plantaris disseminata, and 2 with linear porokeratosis. Patients were genotyped before initiation of therapy. Patients then applied topical cholesterol/lovastatin twice daily to a unilaterally defined treatment area for up to 3 months. The response was evaluated and patients photographed at every visit. Results Three patients had MVD mutations, and 2 patients had PMVK mutations. Treatment with topical cholesterol/lovastatin (but not cholesterol alone) resulted in near complete clearance of disseminated superficial actinic porokeratosis lesions after 4 weeks of therapy and moderate improvement of porokeratosis palmaris et plantaris disseminata lesions and linear porokeratosis lesions. There were no adverse events. Limitations Case series design with a small number of patients. Conclusion Topical cholesterol/lovastatin is an effective and well-tolerated therapy for porokeratosis that underscores the utility of a pathogenesis-based therapy that replaces deficient end products and prevents accumulation of potentially toxic precursors.

BACKGROUND: The circulating immune phenotype was defined in adults and young children with early atopic dermatitis/AD, but chronologic changes in blood of AD infants and children through adolescence have not been explored. OBJECTIVE: To compare immune activation and cytokine polarization in blood of 0–5y/o (n=39), 6–11y/o (n=26), 12–17y/o (n=21) and ≥18y/o (n=43) patients with AD vs. age-matched controls. METHODS: Flow cytometry was used to measure interferon-γ, interleukin (IL)-9, IL-13, IL-17, and IL-22 cytokines in CD4(+)/CD8(+) T-cells, with ICOS and HLA-DR defining mid- and long-term T-cell activation, respectively, within skin-homing/CLA(+) vs. systemic/CLA(−) T-cells. Unsupervised clustering differentiated patients based on their blood biomarker frequencies. RESULTS: While CLA(+) Th1 frequencies were significantly lower in infants with AD vs. all older patients (P

Background Hidradenitis suppurativa (HS), also known as acne inversa, is a recurring, painful, chronic, and sometimes disfiguring inflammatory skin disease. Objectives Our objective was to report the baseline clinical characteristics, natural history, and associated outcomes of patients with HS from the ongoing, prospective, non-interventional UNITE registry that is collecting data regarding the natural history and associated outcomes of HS. Methods Patients with inflammatory HS lesions were enrolled, including adolescents (aged 12 to

Psoriasis is a chronic, multisystem, inflammatory disease that affects approximately 1% of children, with onset most common during adolescence. This guideline addresses important clinical questions that arise in psoriasis management and provides evidence-based recommendations. Attention will be given to pediatric patients with psoriasis, recognizing the unique physiology, pharmacokinetics, and patient-parent-provider interactions of patients younger than 18 years old. The topics reviewed here mirror those discussed in the adult guideline sections, excluding those topics that are irrelevant to, or lack sufficient information for, pediatric patients.

Contains fulltext : 248294.pdf (Publisher’s version ) (Open Access) AIMS: Ixekizumab is a high-affinity monoclonal antibody that selectively targets interleukin-17A used in the treatment of adult and paediatric patients with moderate-to-severe psoriasis. This analysis evaluated the pharmacokinetics (PK) of ixekizumab and the exposure-efficacy relationship in paediatric patients aged 6 to

Background Atopic dermatitis is a chronic inflammatory condition with substantial burden and limited treatment options for adolescents with moderate-to-severe disease. Significantly more patients treated with dupilumab vs. placebo achieved Investigator’s Global Assessment 0/1 at week 16. Objective The objective of this study was to assess the impact of dupilumab treatment vs. placebo on the achievement of clinically meaningful improvements in atopic dermatitis signs, symptoms and quality of life. Methods R668-AD-1526 LIBERTY AD ADOL was a randomized, double-blinded, parallel-group, phase III clinical trial. Two hundred and fifty-one adolescents with moderate-to-severe atopic dermatitis received dupilumab 300 mg every 4 weeks (q4w; n = 84), dupilumab 200 or 300 mg every 2 weeks (q2w; n = 82), or placebo (n = 85). A post-hoc subgroup analysis was performed on 214 patients with Investigator’s Global Assessment > 1 at week 16. Measures of atopic dermatitis signs, symptoms, and quality of life were assessed. Clinically meaningful improvement in one or more of three domains of signs, symptoms, and quality of life was defined as an improvement of ≥ 50% in Eczema Area and Severity Index, ≥ 3 points in Peak Pruritus Numerical Rating Scale, or ≥ 6 points in the Children’s Dermatology Life Quality Index from baseline. Results Of patients receiving dupilumab q2w, 80.5% [66/82] experienced clinically meaningful improvements in atopic dermatitis signs, symptoms, or quality of life at week 16 (vs. placebo, 20/85 [23.5%], difference 57.0% [95% confidence interval 44.5–69.4]; q4w vs. placebo, 53/84 [63.1%], difference 39.6% [95% confidence interval 25.9–53.3]; both p 1 at week 16 (q2w, 46/62 [74.2%] vs. placebo, 18/83 [21.7%], difference 52.5% [95% confidence interval 38.5–66.6]; q4w, 38/69 [55.1%] vs. placebo, difference 33.4% [95% confidence interval 18.7–48.1]; both p 1 at week 16. Treatment responses should be interpreted in the context of such clinically relevant patient-reported outcome measures. Trial Registration ClinicalTrials.gov; NCT03054428. Video abstract Adolescents with atopic dermatitis: does dupilumab improve their signs, symptoms, and quality of life? (MP4 212916 kb) Electronic supplementary material The online version of this article (10.1007/s40257-019-00478-y) contains supplementary material, which is available to authorized users.

IMPORTANCE: Ichthyoses are clinically and genetically heterogeneous disorders characterized by scaly skin. Despite decades of investigation identifying pathogenic variants in more than 50 genes, clear genotype-phenotype associations have been difficult to establish. OBJECTIVE: To expand the genotypic and phenotypic spectra of ichthyosis and delineate genotype-phenotype associations. DESIGN, SETTING, AND PARTICIPANTS: This cohort study recruited an international group of individuals with ichthyosis and describes characteristic and distinguishing features of common genotypes, including genotype-phenotype associations, during a 10-year period from June 2011 to July 2021. Participants of all ages, races, and ethnicities were included and were enrolled worldwide from referral centers and patient advocacy groups. A questionnaire to assess clinical manifestations was completed by those with a genetic diagnosis. MAIN OUTCOMES AND MEASURES: Genetic analysis of saliva or blood DNA, a phenotyping questionnaire, and standardized clinical photographs. Descriptive statistics, such as frequency counts, were used to describe the cases in the cohort. Fisher exact tests identified significant genotype-phenotype associations. RESULTS: Results were reported for 1000 unrelated individuals enrolled from around the world (mean [SD] age, 50.0 [34.0] years; 524 [52.4%] were female, 427 [42.7%] were male, and 49 [4.9%] were not classified); 75% were from the US, 12% from Latin America, 4% from Canada, 3% from Europe, 3% from Asia, 2% from Africa, 1% from the Middle East, and 1% from Australia and New Zealand. A total of 266 novel disease-associated variants in 32 genes were identified among 869 kindreds. Of these, 241 (91%) pathogenic variants were found through multiplex amplicon sequencing and 25 (9%) through exome sequencing. Among the 869 participants with a genetic diagnosis, 304 participants (35%) completed the phenotyping questionnaire. Analysis of clinical manifestations in these 304 individuals revealed that pruritus, hypohydrosis, skin pain, eye problems, skin odor, and skin infections were the most prevalent self-reported features. Genotype-phenotype association analysis revealed that the presence of a collodion membrane at birth (odds ratio [OR], 6.7; 95% CI, 3.0-16.7; P

Accurate assessment of atopic dermatitis (AD) severity is critical when initiating and monitoring therapy. Use of existing research tools such as the Eczema Area and Severity Index (EASI) and Scoring Atopic Dermatitis (SCORAD) is complex and time-consuming in clinical practice. A previous analysis found the product of validated Investigator's Global Assessment (vIGA) and affected body surface area (BSA) to be an accurate and practical tool for routine assessment of paediatric AD.To evaluate the IGAxBSA composite as an alternative to EASI or SCORAD for assessment of AD disease severity and disease responsiveness.The relationship between IGAxBSA, EASI and SCORAD was assessed in a post hoc analysis of pooled data from the dupilumab clinical trial programme in adult and paediatric patients with moderate-to-severe AD who had received dupilumab or placebo, with or without topical corticosteroids (TCS). The trials are registered at ClinicalTrials.gov and EudraCT: LIBERTY AD SOLO 1 (NCT02277743, 2014-001198-15), LIBERTY AD SOLO 2 (NCT02277769, 2014-002619-40), LIBERTY AD SOLO-CONTINUE (NCT02395133, 2014-003384-38), LIBERTY AD CHRONOS (NCT02260986, 2013-003254-24), LIBERTY AD CAFÉ (NCT02755649, 2015-002653-35), LIBERTY AD ADOL (NCT03054428, 2015-004458-16), LIBERTY AD PEDS (NCT03345914, 2016-004997-16), LIBERTY AD OLE (NCT01949311, 2013-001449-15) and LIBERTY AD PEDS OLE (NCT02612454, 2015-001396-40).Using datapoints from pooled dupilumab randomized controlled trials (n = 3473) and open-label extension trials (n = 3045), we found that IGAxBSA correlated well with EASI and SCORAD, irrespective of treatment group and race (white, Asian, black). IGAxBSA correlated better with objective measures (EASI, SCORAD) than with patient- or caregiver-reported subjective measures. IGAxBSA correlated strongly with EASI and SCORAD in assessing disease change over time (r = 0·90, r = 0·76, respectively; P 0·0001), and concordance between IGAxBSA-50/75/90 and EASI-50/75/90 was excellent (88-94%).IGAxBSA is a valid alternative for assessment of AD disease severity and response over time, compared with EASI or SCORAD in patients with AD, irrespective of race.

Nail psoriasis (NP) has been proposed as a potential clinical predictor for a more severe disease course in children with psoriasis but data regarding NP in children is scarce.1-3 Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets interleukin-(IL)-17A, is an EMA and FDA approved treatment for pediatric (≥6 years old) and adult patients with moderate-to-severe psoriasis and provides rapid clinically meaningful improvements in skin, itch and quality of life (QoL) outcomes at week 12.

Background/objectives Psoriasiform eruptions after initiation of dupilumab have been previously described in adults. This report details the risk of developing or unmasking psoriasiform eruptions after initiation of dupilumab in children. Methods Records of patients ≤18 years of age with atopic dermatitis who developed psoriasiform dermatitis during treatment with dupilumab were reviewed retrospectively. Results Six children, 4-18 years of age, on dupilumab for severe atopic dermatitis developed new-onset psoriasiform dermatitis at a median duration of 8 months (range, 6-12 months) after dupilumab initiation. Typical locations of psoriasis were involved (face, scalp, trunk, and extensor extremities). The majority showed clearance or near clearance with the use of medium-strength to potent topical corticosteroid ointments and 83% continued use of the dupilumab. A 7th patient had psoriasis, in addition to severe atopic dermatitis, and the psoriasis was unmasked by its failure to respond to dupilumab. Conclusion Although unusual, psoriasiform lesions can appear during effective treatment with dupilumab for atopic dermatitis, potentially reflecting a shift toward cutaneous IL-23/TH 17 pathway activation with dupilumab-induced suppression of type 2 immunity.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with heterogenous presentation and often immense patient burden. Safe, targeted treatment options are currently limited. This focused review of the published literature, including clinical trial results, case reports, and abstracts, as well as presentations from scientific meetings and data from industry press releases, describes the use of topical and systemic Janus kinase (JAK) inhibitors in the treatment of AD. New topical JAK inhibitors include ruxolitinib (JAK1/2) and delgocitinib (pan-JAK). Ruxolitinib cream met all primary and secondary endpoints in phase 3 clinical trials for mild-to-moderate AD with minimal treatment-emergent adverse events. Delgocitinib ointment was recently approved in Japan for pediatric and adult AD. Oral JAK inhibitors include baricitinib (JAK1/2), abrocitinib (JAK1-selective), and upadacitinib (JAK1-selective). All 3 met primary and secondary endpoints across numerous trials for moderate-to-severe AD. Treatment-emergent adverse events were mainly mild to moderate and included acne, nausea, headache, upper respiratory tract infection, and to a lesser degree, herpes infection and selected laboratory abnormalities. JAK inhibitors hold great promise as the next generation of targeted AD therapy. While their outstanding efficacy is balanced by a favorable safety profile in clinical trials, real-world data are needed to better understand long-term safety, durability, and treatment success.

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 3.2% of the world's population. In this section of the guidelines of care for psoriasis, we will focus the discussion on ultraviolet (UV) light-based therapies, which include narrowband and broadband UVB, UVA in conjunction with photosensitizing agents, targeted UVB treatments such as with an excimer laser, and several other modalities and variations of these core phototherapies, including newer applications of pulsed dye lasers, intense pulse light, and light-emitting electrodes. We will provide an in-depth, evidence-based discussion of efficacy and safety for each treatment modality and provide recommendations and guidance for the use of these therapies alone or in conjunction with other topical and/or systemic psoriasis treatments.

Background Atopic dermatitis is highly prevalent in black/African American, Asian, and Hispanic patients, making assessment of these populations in clinical trials important. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis. In two pivotal phase III clinical trials in patients aged ≥ 2 years, crisaborole was superior to vehicle in reducing global disease severity. The most common treatment-related adverse event was application site pain. Objective The objective of this study was to investigate the efficacy and safety of crisaborole according to patient race and ethnicity. Methods A pooled post hoc analysis by race and ethnicity of the two pivotal trials and a safety extension trial was performed. Race included white or nonwhite (encompassing Asian/native Hawaiian/other Pacific Islander, black/African American, and other/American Indian/Alaskan native); ethnicity included Hispanic/Latino or not Hispanic/Latino. Results In white, nonwhite, Hispanic/Latino, and not Hispanic/Latino groups at day 29, more crisaborole- than vehicle-treated patients achieved improvements in global disease severity [Investigator’s Static Global Assessment of clear/almost clear with a ≥ 2-grade improvement (white: 33.5% vs. 22.3%, nominal p

International audience; Background Atopic eczema (also known as eczema) is a chronic, inflammatory skin condition that often afflicts patients’ health and well‐being. The Harmonising Outcome Measures for Eczema (HOME) initiative recommends that ‘long‐term control of eczema’ is measured in all clinical trials 3 months or longer in duration. However, little has been published on what eczema control means to those living with or treating atopic eczema. Objectives To (i) develop understanding of what eczema control means to patients, carers and clinicians and (ii) explore the feasibility and acceptability of different ways of measuring eczema control in the long term. Methods Online focus groups explored patients/carers experiences in the UK, the United States, the Netherlands, France, Sweden and Japan, and an international online survey gathered views of clinicians. The framework method was used to analyse the focus groups, and thematic analysis was used to analyse survey data. All findings were integrated into a theoretical framework to create overarching themes that cut across these diverse groups. Results Eight focus groups with patients (16 years+) and eight groups with carers of children took place (N = 97). Sixty‐two people took part in the survey. Eczema control was described as a multifaceted construct involving changes in disease activity, the treatment and management of the condition and psychological, social and physical functioning. Patient/carer measurement allows personal accounts and frequent measurement, whilst clinician measurement was deemed less subjective. The burden on patients/carers and issues for analysing and interpreting data should be considered. Conclusions This study formed the basis of judging the content validity and feasibility of measurement instruments/methods to assess control of eczema in clinical trials. This online approach to an international qualitative study is an example of how core outcome set developers with limited resources can engage with multiple stakeholder groups on an international basis to inform consensus meeting discussions.

Author(s): Thyssen, JP; de Bruin-Weller, MS; Paller, AS; Leshem, YA; Vestergaard, C; Deleuran, M; Drucker, AM; Foelster-Holst, R; Traidl-Hoffmann, C; Eyerich, K; Taieb, A; Su, JC; Bieber, T; Cork, MJ; Eichenfield, LF; Guttman-Yassky, E; Wollenberg, A | Abstract: BackgroundConjunctivitis is common in patients with atopic dermatitis (AD) in general and a commonly reported adverse event in AD clinical trials with dupilumab.ObjectiveTo survey opinions and experience about conjunctivitis occurring in AD, including those during dupilumab treatment in a group of AD experts from the International Eczema Council (IEC).MethodsElectronic survey and in-person discussion of management strategies.ResultsForty-six (53.5%) IEC members from 19 countries responded to the survey. Consensus was reached for several statements regarding diagnostic workup, referral and treatment. IEC members suggest that patients with AD should (i) routinely be asked about ocular complaints or symptoms, (ii) obtain information about the potential for conjunctivitis before starting dupilumab therapy and (iii) if indicated, be treated with dupilumab despite previous or current conjunctivitis. In cases of new-onset conjunctivitis, there was consensus that dupilumab treatment should be continued when possible, with appropriate referral to an ophthalmologist.LimitationsThe study relies on expert opinion from dermatologists. Responses from few dermatologists without dupilumab access were not excluded from the survey.ConclusionThe IEC recommends that dermatologists address conjunctivitis in patients with AD, especially during treatment with dupilumab.

Objectives A cleansing body wash containing diluted sodium hypochlorite (0.006% NaOCl) was evaluated for management of moderate‐to‐severe Staphylococcus aureus–colonized, atopic dermatitis in children. Methods A 6‐week, prospective, open‐label study was conducted with 50 evaluable participants (ages 6 months to 17 years) who had moderate‐to‐severe atopic dermatitis with S aureus skin colonization documented by culture. Participants were instructed to continue using their current medications while using the study product, 0.006% NaOCl body wash, once daily to affected areas for 6 weeks. Primary outcome measures were Investigator's Global Assessment, Eczema Area and Severity Index, and Body Surface Area scores. Secondary outcome measures were the Visual Analog Scale for pruritus, Family Dermatology Life Quality Index, and Patient Satisfaction Questionnaire for Problem Areas. A subject daily diary and a six‐item subject questionnaire that provided information on preferences for bleach bath vs body wash were secondary outcome measures. Results Daily use of the 0.006% NaOCl body wash led to improvement for all outcome measures comparing baseline to 2‐week and to 6‐week evaluations. Of the 50 skin S aureus‐positive subjects, 32/50 (64%) were still positive at 2 weeks. A 36.5% decrease in subject's daily record of topical corticosteroid application at end of study compared to baseline was found. Participant surveys indicated preferences for the body wash over bleach baths. Conclusions Sodium hypochlorite (NaOCl) body wash improved all outcome measures for moderate‐to‐severe S aureus–colonized AD in infants, children, and adolescents. The limited reduction in S aureus further suggests that sodium hypochlorite has ameliorative effects other than antimicrobial actions.

Background As novel systemic therapeutics for patients with atopic dermatitis (AD) are developed, ethical and methodological concerns regarding placebo‐controlled‐trials (PCT) have surfaced. Objective To guide the design and implementation of PCT in AD, focusing on trials with systemic medications. Methods A subgroup of the International Eczema Council (IEC) developed a consensus e‐survey, which was disseminated to IEC members. Results The response rate was 43/82 (52%). Consensus was reached on 24/27 statements and on 3/11 options from multiple‐selection statements, including: performing monotherapy studies in proof‐of‐concept phases; avoiding concomitant topical corticosteroids or calcineurin inhibitors until a predefined timepoint as rescue (borderline consensus); selection of sites and assessors with recognized expertise in AD clinical trials; clear definition and identification of baseline disease severity; minimizing time and proportion of patients on placebo; using daily emollients with several options provided; instigating open‐label extension studies for enrolment after a predefined timepoint; and including outcomes which set a higher bar for disease clearance. Conclusion Conducting PCT in AD requires balancing several, sometimes opposing principles, including ethics, methodology, regulatory requirements and real‐world needs. This paper can provide a framework for conducting PCT with systemic medications for patients with AD.

Background/Objective Compared with the adult psoriasis population, knowledge about the incidence of comorbidities in the pediatric psoriasis population is limited. The objective of this study was to assess the prevalence and incidence of comorbidities, including psychiatric comorbidities, in patients with pediatric psoriasis. Methods In this claims‐based, retrospective cohort study, patients with pediatric psoriasis were matched 1:3 with a nonpsoriasis cohort based on age, sex, and index date (the earliest of inpatient claims or the latter of two outpatient claims). Results Obesity, serious infection, and juvenile idiopathic arthropathy had higher prevalence and incidence rates in the psoriasis cohort than the nonpsoriasis cohort. Psychiatric comorbidities were also more common in the psoriasis cohort than the nonpsoriasis cohort, as were ulcerative colitis and Crohn disease. Stratifying the psoriasis cohort by disease severity—mild and moderate‐to‐severe—found no differences in incidence rates of comorbidities between the two subsets. Conclusion The incidence rates of many comorbid conditions were higher for patients with pediatric psoriasis compared with patients without pediatric psoriasis, and similar between patients with moderate‐to‐severe and mild pediatric psoriasis.