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Background: Moderate-to-severe atopic dermatitis (AD) often has a profound impact on the quality of life of young children and their caregivers. One of the most burdensome symptoms reported by patients is skin pain., Methods: This post hoc analysis focuses on the impact of dupilumab treatment on skin pain in young children using data from the LIBERTY AD PRESCHOOL part B (NCT03346434), a 16-week randomized, double-blind, placebo-controlled, phase 3 study in 162 children aged 6 months to 5 years with moderate-to-severe AD receiving dupilumab or placebo, plus topical corticosteroids (TCS). Analyses were performed on the full analysis set and subgroups of patients who did not achieve an Investigator's Global Assessment score of 0 or 1 (IGA >1 subgroup), or who did not achieve a 75% improvement from baseline in the Eczema Area and Severity Index (1 and

Background: Pediatric patients with moderate-to-severe atopic dermatitis (AD) often experience a high disease burden and have a high risk of persistent disease. Standard-of-care immunosuppressive systemic treatments have been used off-label for AD in pediatric patients despite concerns for suboptimal safety with continuous use and risk of relapse upon discontinuation. The biologic agent dupilumab is the first systemic treatment approved for moderate-to-severe AD in children as young as 6 months. Long-term safety and efficacy data in this patient population are needed to inform continuous AD management., Objectives: The purpose of this work was to determine the long-term safety and efficacy of dupilumab treatment up to 1 year in an open-label extension (OLE) study [LIBERTY AD PED-OLE (NCT02612454)] in children aged 6 months to 5 years with moderate-to-severe AD who previously participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434 part B; parent study) and were subsequently enrolled in PED-OLE., Methods: In PED-OLE, patients received dupilumab every 4 weeks according to a weight-tiered regimen (body weight ≥ 5 kg to < 15 kg: 200 mg; ≥ 15 kg to < 30 kg: 300 mg)., Results: Data for 142 patients were analyzed, 60 of whom had completed the 52-week visit at time of database lock. Mean age at baseline was 4.1 y [SD, 1.13; range, 1.0-5.9 years]. A majority (78.2%) of patients reported ≥ 1 treatment-emergent adverse event (TEAE), most of which were mild or moderate and transient. The most frequently reported TEAEs were nasopharyngitis (19.7%), cough (15.5%), and pyrexia (14.1%). One TEAE led to treatment discontinuation (severe urticaria, which resolved in 1 day). By week 52, 36.2% of patients had achieved an Investigator's Global Assessment score of 0/1 (clear/almost clear skin), and 96.6%, 79.3%, and 58.6% had at least 50%, 75%, or 90% improvement, respectively, in Eczema Area and Severity Index scores., Conclusions: Consistent with results seen in adults, adolescents, and older children (aged 6-11 years), treatment with dupilumab for up to 1 year in children aged 6 months to 5 years with inadequately controlled moderate-to-severe AD demonstrated an acceptable long-term safety profile and sustained efficacy. These results support the long-term continuous use of dupilumab in this patient population., Trial Registration: ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B)., (© 2024. The Author(s).)

Background: The summarized guidelines update the 2014 recommendations for the management of AD with phototherapy and systemic therapies., Methods: A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of the evidence and formulating and grading recommendations., Results: The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic therapies, including biologics, oral Janus Kinase inhibitors, and other immunomodulatory medications., Conclusions: The evidence supported strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib and conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids., Competing Interests: Conflict of interest The American Academy of Dermatology (AAD) strives to produce clinical guidelines that reflect the best available evidence supplemented with the judgment of expert clinicians. Significant efforts are taken to minimize the potential for conflicts of interest to influence guideline content. The management of conflict of interest for this guideline complies with the Council of Medical Specialty Societies' Code of Interactions with Companies. Funding of guideline production by medical or pharmaceutical entities is prohibited, full disclosure is obtained and evaluated for all guideline contributors throughout the guideline development process, and recusal is used to manage identified relationships. The AAD conflict of interest policy summary may be viewed at www.aad.org., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: For people with atopic dermatitis (AD) refractory to topical therapies, treatment with phototherapy and systemic therapies can be considered. Multiple biologic therapies and Janus kinase (JAK)inhibitors have been approved since 2014 to treat AD. These guidelines update the 2014 recommendations for management of AD with phototherapy and systemic therapies., Objective: To provide evidence-based recommendations on the use of phototherapy and systemic therapies for AD in adults., Methods: A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of evidence and formulating and grading recommendations., Results: The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic agents, including biologics, oral JAK inhibitors, and other immunomodulatory medications., Limitations: Most randomized controlled trials of phototherapy and systemic therapies for AD are of short duration with subsequent extension studies, limiting comparative long-term efficacy and safety conclusions., Conclusions: We make strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib. We make conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids., Competing Interests: Conflicts of interest Dr Drucker receives research grants paid to his institution from the National Eczema Association, Eczema Society of Canada, Canadian Dermatology Foundation, Canadian Institutes for Health Research, US National Institutes of Health, and Physician Services Incorporated Foundation. Dr Cohen serves on the board of directors for Timber and Evommune receiving stock options and/or fees; as a consultant for Asana Biosciences, Ferndale Laboratories, Inc, Novartis, Facilitation of International Dermatology Education, Dermavant Sciences, Leo Pharma, Inc, UCB, and Cosmetic Ingredient Review receiving honoraria and/or stock options. Dr Eichenfield serves on the board of directors for Forte Biosciences and Verrica Pharmaceuticals, Inc, receiving honoraria and/or stock options; as an investigator for AbbVie, Arcutis, Dermavant, Galderma Laboratories, Pfizer, and Bausch receiving research grants, fees, and/or honoraria; as a consultant for AbbVie, Almirall, Arcutis, Asana, Dermavant, Eli Lilly, Galderma, Ichnos/Glenmark, Incyte, Janssen, Leo Pharma, Novartis, Ortho Dermatologics, Otsuka, Pfizer, Regeneron, and Sanofi Genzyme, honoraria; as an independent contractor for Elsevier, Inc receiving royalties. Dr Paller serves as a consultant for Abbvie, Abeona, Almirall, Amagma, Anaptysbio, Arena, Bausch, Bristol Myer Squibb, Dermavant, Dermira, Eli Lilly, Exicure, Forte, Leo, Lifemax, Novartis, Phoenix, Pierre Fabre, Pfizer, Rapt, Regeneron, Sanofi, Sol-Gel, UCB, and Venthera receiving honoraria; as an investigator for Anaptysbio, Eli Lilly, Incyte, Janssen, Krystal Bio, Lenus, Regeneron, and UCB receiving no compensation. Dr Schwarzenberger is the founder of Pretel, Inc and serves as a data safety monitoring board member for Pfizer, Inc receiving fees. Dr Sidbury serves as an advisory board member for Pfizer, Inc receiving honoraria; as a principal investigator for Regeneron receiving grants and research funding; as an investigator for Brickell Biotech, Inc, and Galderma USA receiving grants and research funding; as a consultant for Galderma Global and Microes receiving fees or no compensation. Dr Silverberg serves as an advisory board member for BioMX, Boehringer Ingelheim, RAPT Therapeutics, Celgene, Ortho Dermatologics, TARGET Pharma, AFYX Therapeutics, Corrona, Inc, Dermira, Pfizer, Inc, Leo Pharma, Inc, and Menlo Therapeutics receiving honoraria and/or fees; as an investigator for DS Pharma, TARGET Pharma, Kiniksa Pharmaceuticals, Ltd, Menlo Therapeutics, GlaxoSmithKline, AbbVie, Leo Pharma, Inc, and Regeneron receiving research funding, honoraria, or no compensation; as a consultant for AOBiome, Bluefin Biomedicine, Bodewell, BiomX, Inc, Galderma Research & Development, LLC, Arena Pharmaceuticals, Dermavant Sciences, Incyte Corporation, DS Biopharma, Sun Pharmaceutical Industries, Ltd, AnaptysBio, Asana Biosciences, LLC, Pfizer, Inc, Glenmark Generics, Inc, Sanofi, Kiniksa Pharmaceuticals, Ltd, GlaxoSmithKlein, Eli Lilly and Company, AbbVie, Regeneron, and Medimmune receiving honoraria or fees; as a speaker for the Fall Clinical Dermatology Conference, Maui Derm, and Regeneron receiving honoraria or fees. Dr Singh serves as an advisory board member for Incyte receiving honoraria. DR Wu is an author for UpToDate, Inc receiving honoraria. Dr Davis, Dr Alikhan, Dr Bercovitch, Athor Darr, and Dr Frazer-Green have no conflicts of interest to declare., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory bone disease requiring immunosuppressive treatment in half of patients. Monoclonal tumor necrosis factor inhibitors (TNFi) are often used as effective second-line off-label therapies. However, paradoxical psoriasis can occur in a subset of patients exposed to monoclonal TNFi and can prompt conversion to alternate therapy if severe., Objective: The aim of this study was to determine the efficacy and safety of golimumab, a fully humanized TNFi, in children with CRMO, including those who develop paradoxical psoriasis after exposure to other monoclonal TNFi., Methods: A retrospective chart review was conducted of patients with CRMO who received golimumab in a single center between 01 June, 2018 and 31 December, 2020. Patients who were diagnosed before 21 years of age and followed up for CRMO at least once after receiving ≥ 3 months of golimumab were included. Extracted data included patient demographics, whole-body MRI lesion counts, clinically relevant data, laboratory results, patient-reported outcomes, and psoriasis burden. Linear mixed models with log-transformed outcomes were used to assess changes in the outcomes over time. The random effect is included in the model to account for the within-subject correlation of repeated measures. p-values and 95% confidence intervals were reported., Results: Eighteen patients were included. Patients were observed for a median of 9.95 months [interquartile range 3.84-15.64]. The median age at the initiation of golimumab was 10.95 years [9.86-13.77] and the median duration of disease between the disease onset and the initiation of golimumab was 2.60 years [1.66-3.62]. Ten patients received golimumab via intravenous route and eight patients received golimumab via subcutaneous route. The median dose was 1.64 mg/kg/month [1.46, 2]. Fourteen patients were previously treated with disease-modifying antirheumatic drugs and 17 with other TNFi. Patients treated with golimumab showed significant improvement in median physician global assessment for CRMO from 2.00 [1.00-3.00] to 0.00 [0.00-0.25] by the fourth visit (p < 0.001), with median erythrocyte sedimentation rate (ESR) decreasing significantly from 12.00 [6.75-23.75] to 5.00 [3.00-10.00] by the fourth visit (p < 0.05). The median number of lesions on MRI decreased significantly from 3.50 [2.00-5.50] to 0.50 [0.00-4.25] lesions per patient (p < 0.01). Nine out of 12 patients who had previous paradoxical psoriasis associated with adalimumab or infliximab had persistent active psoriasis at study baseline. For patients with psoriasis at study baseline, the prevalence of psoriasis had decreased from 100% to approximately 50-57% at the following visits. Of the 18 patients initiated on golimumab in this study, there was only one new case of mild psoriasis in a patient with previously resolved infliximab-associated paradoxical psoriasis. No serious infections or adverse events were noted during the study. Two patients in the study showed clinical improvement with concomitant golimumab and ustekinumab with no reported adverse side effects or increased effects in these patients over a 16-month interval, showing that this combination can be safe and effective for children with CRMO., Conclusion: In our experience, golimumab has been shown to be a safe and effective therapy for CRMO and demonstrated improvement in paradoxical psoriasis in many patients. Longer follow-up periods would be helpful to develop longer term outcomes data for patients with CRMO and overall paradoxical psoriasis risk., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: New evidence has emerged since the 2014 guidelines that further informs the management of atopic dermatitis (AD) with topical therapies. These guidelines update the 2014 recommendations for management of AD with topical therapies., Objective: To provide evidence-based recommendations related to management of AD in adults using topical treatments., Methods: A multidisciplinary workgroup conducted a systematic review and applied the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach for assessing the certainty of evidence and formulating and grading recommendations., Results: The workgroup developed 12 recommendations on the management of AD in adults with topical therapies, including nonprescription agents and prescription topical corticosteroids (TCS), calcineurin inhibitors (TCIs), Janus kinase (JAK) inhibitors, phosphodiesterase-4 inhibitors (PDE-4), antimicrobials, and antihistamines., Limitations: The pragmatic decision to limit the literature review to English-language randomized trials may have excluded data published in other languages and relevant long-term follow-up data., Conclusions: Strong recommendations are made for the use of moisturizers, TCIs, TCS, and topical PDE-4 and JAK inhibitors. Conditional recommendations are made for the use of bathing and wet wrap therapy and against the use of topical antimicrobials, antiseptics, and antihistamines., Competing Interests: Conflicts of interest David E. Cohen∗, MD, MPH serves on the board of directors for Timber and Evommune receiving stock options and/or fees and as a consultant for Asana Biosciences, Ferndale Laboratories, Inc, Novartis, Facilitation of International Dermatology Education, Dermavant Sciences, Leo Pharma, Inc, UCB, and Cosmetic Ingredient Review receiving honoraria and/or stock options. Lawrence F. Eichenfield∗, MD serves on the board of directors for Forte Biosciences and Verrica Pharmaceuticals, Inc, receiving honoraria and/or stock options; as an investigator for Abbvie, Arcutis, Dermavant, Galderma Laboratories, Pfizer, and Bausch, receiving research grants, fees, and/or honoraria; as a consultant for Abbvie, Almirall, Arcutis, Asana, Dermavant, Eli Lilly, Galderma, Ichnos/Glenmark, Incyte, Janssen, Leo Pharma, Novartis, Ortho Dermatologics, Otsuka, Pfizer, Regeneron, and Sanofi Genzyme, honoraria; and as an independent contractor for Elsevier, Inc receiving royalties. Amy S. Paller∗, MD serves as a consultant for Abbvie, Abeona, Almirall, Amagma, Anaptysbio, Arena, Bausch, Bristol Myer Squibb, Dermavant, Dermira, Eli Lilly, Exicure, Forte, Leo, Lifemax, Novartis, Phoenix, Pierre Fabre, Pfizer, Rapt, Regeneron, Sanofi, Sol-Gel, UCB, and Venthera receiving honoraria; and as an investigator for Anaptysbio, Eli Lilly, Incyte, Janssen, Krystal Bio, Lenus, Regeneron, and UCB receiving no compensation. Kathryn Schwarzenberger, MD is the founder of Pretel, Inc and serves as a data safety monitoring board member for Pfizer, Inc receiving fees. Robert Sidbury∗, MD serves as an advisory board member for Pfizer, Inc receiving honoraria; as a principal investigator for Regeneron receiving grants and research funding; as an investigator for Brickell Biotech, Inc, and Galderma USA receiving grants and research funding; and as a consultant for Galderma Global and Microes receiving fees or no compensation. Jonathan I. Silverberg∗, MD, PhD, MPH serves as an advisory board memberfor BioMX, Boehringer Ingelheim, RAPT Therapeutics, Celgene, Ortho Dermatologics, TARGET Pharma, AFYX Therapeutics, Corrona, Inc, Dermira, Pfizer, Inc, Leo Pharma, Inc, and Menlo Therapeutics receiving honoraria and/or fees; as an investigator for DS Pharma, TARGET Pharma, Kiniksa Pharmaceuticals, Ltd, Menlo Therapeutics, GlaxoSmithKline, AbbVie, Leo Pharma, Inc, and Regeneron receiving research funding, honoraria, or no compensation; as a consultant for AOBiome, Bluefin Biomedicine, Bodewell, BiomX, Inc, Galderma Research & Development, LLC., Arena Pharmaceuticals, Dermavant Sciences, Incyte Corporation, DS Biopharma, Sun Pharmaceutical Industries, Ltd, AnaptysBio, Asana Biosciences, LLC., Pfizer, Inc, Glenmark Generics, Inc, Sanofi, Kiniksa Pharmaceuticals, Ltd, GlaxoSmithKlein, Eli Lilly and Company, AbbVie, Regeneron, and Medimmune receiving honoraria or fees; and as a speaker for the Fall Clinical Dermatology Conference, Maui Derm, and Regeneron receiving honoraria or fees. Anne Marie Singh, MD as a consultant for Abbvie. Peggy Wu, MD serves as an author for UpToDate, Inc receiving honoraria. Drs. Alikhan, Bercovitch, Davis, and Frazer-Green, and Jennifer M. Darr, LCSW have no relationships to disclose., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

These guidelines update the 2014 recommendations for management of atopic dermatitis in adults with topical therapies. A multidisciplinary workgroup employed best practices for guideline development, including a systematic review of the evidence and application of the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading recommendations. The evidence on atopic dermatitis treatment supported strong recommendations for the use of nonprescription moisturizers, topical calcineurin inhibitors, topical corticosteroids, and topical PDE-4 and JAK inhibitors. Conditional recommendations are made for the use of bathing and wet wrap therapy and against the use of topical antimicrobials, antiseptics, and antihistamines., Competing Interests: Conflict of Interest The American Academy of Dermatology (AAD) strives to produce clinical guidelines that reflect the best available evidence supplemented with the judgment of expert clinicians. Significant efforts are taken to minimize the potential for conflicts of interest to influence guideline content. The management of conflict of interest for this guideline complies with the Council of Medical Specialty Societies' Code of Interactions with Companies. Funding of guideline production by medical or pharmaceutical entities is prohibited, full disclosure is obtained and evaluated for all guideline contributors throughout the guideline development process, and recusal is used to manage identified relationships. The AAD conflict of interest policy summary may be viewed at www.aad.org., (Copyright © 2023 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Importance: Psoriasis in children is increasingly treated with systemic medications, yet their risk of serious infection is not well characterized in clinical practice. Pediatric clinical trials for these medications were often small and placebo controlled., Objective: To estimate the 6-month rate of infections among children with psoriasis who started treatment with ustekinumab, etanercept, or methotrexate., Design, Setting, and Participants: This cohort study used insurance claims data from clinical practices across the US on children aged 17 years or younger with psoriasis who were receiving treatment with a topical medication for psoriasis and started new treatment with ustekinumab, etanercept, or methotrexate. The analysis was stratified by the time before pediatric labeling (2009-2015) and after pediatric approval (2016-2021). Patient follow-up started 1 day after initiating treatment and ended at 6 months., Exposures: New treatment with ustekinumab, etanercept, and methotrexate., Main Outcomes and Measures: During follow-up, the frequency of inpatient serious infections and outpatient infections requiring treatment was compared. Event rates and rate ratios were estimated after propensity score decile stratification., Results: After exclusions, we identified 2338 patients (1368 girls [57.8%]) who initiated new treatment with a targeted immunomodulating agent. In all, 379 patients started treatment with ustekinumab, 779 patients started treatment with etanercept, and 1180 patients started treatment with methotrexate from 2009 through 2021. The propensity score-adjusted incidence rate of serious infection was 18.4 per 1000 person-years (3 events) for ustekinumab users, 25.6 per 1000 person-years (9 events) for etanercept users, and 14.9 per 1000 person-years (8 events) for methotrexate users. The adjusted rate of outpatient infections was 254.9 per 1000 person-years (39 events) for ustekinumab users, 435.7 per 1000 person-years (139 events) for etanercept users, and 433.6 per 1000 person-years (209 events) for methotrexate users. The adjusted rate ratio of outpatient infections was 0.58 (95% CI, 0.41-0.83) for ustekinumab vs etanercept, 0.66 (95% CI, 0.48-0.91) for ustekinumab vs methotrexate, and 0.95 (95% CI, 0.75-1.21) for etanercept vs methotrexate. Rate ratios were similar during the off-label use era and after pediatric labeling., Conclusions and Relevance: Among children with psoriasis who started treatment with immunomodulating agents, serious infections were infrequent. This cohort study suggests that there was no increase in the risk of outpatient infections for children who started treatment with ustekinumab compared with etanercept or methotrexate.

Background: 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., Methods: 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., Findings: 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., Interpretation: 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., Funding: Sanofi and Regeneron Pharmaceuticals., Competing Interests: Declaration of interests ASP has been an investigator for AbbVie, AnaptysBio, Dermavant, Eli Lilly, Incyte, Janssen, Krystal Biotech, LEO Pharma, Regeneron Pharmaceuticals, and UCB; a consultant with honorarium for AbbVie, Acrotech, Almirall, Amgen, Amryt Pharma, Arcutis Antiobix, Arena Pharmaceuticals, Azitra, BioCryst, BiomX, Boehringer Ingelheim, Botanix, BridgeBio, Bristol Myers Squibb, Castle Creek Biosciences, Catawba Research, Eli Lilly, Exicure, Gilead, Incyte, Janssen, Johnson & Johnson, Kamari Pharma, LEO Pharma, Novartis, OM Pharma, Pfizer, Pierre Fabre Dermo-Cosmetics, RAPT Therapeutics, Regeneron Pharmaceuticals, Sanofi, Seanergy, UCB, and Union; and on the data and safety monitoring board for AbbVie, Abeona, Bausch, Galderma, and Novan. ELS has been an investigator for AbbVie, Eli Lilly, Incyte, Kyowa Hakko Kirin, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Trevi Therapeutics; received consultant fees from AbbVie, Amgen, Arena Pharmaceuticals, Aslan Pharma, Benevolent AI Bio Limited, BiomX, Bluefin Biomedicine, Boehringer Ingelheim, Boston Consulting Group, Collective Acumen, Coronado, Corevita, Dermavant, Eli Lilly, Evidera, ExcerptaMedica, Forté Bio RX, Galderma, GSK, Incyte, Janssen, Kyowa Hakko Kirin, LEO Pharma, Menlo Therapeutics, Merck, Novartis, Pfizer, Pierre Fabre Dermo-Cosmetics, Regeneron Pharmaceuticals, Roivant, Sanofi, SPARC India, Trevi Therapeutics, and Valeant; received study grants from AbbVie, Amgen, Arcutis, Aslan Pharma, Corevita, Eli Lilly, Incyte, Kyowa Hakko Kirin, LEO Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Trevi Therapeutics; served as a speaker for Eli Lilly, Incyte, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, and Sanofi; and served on advisory boards for Arena Pharmaceuticals, Eli Lilly, GSK, Janssen, Kyowa Hakko Kirin, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, and Sanofi. ECS has been a consultant for AbbVie, Dermavant, Eli Lilly, Pfizer, Regeneron Pharmaceuticals, and Verrica Pharmaceuticals; on the data and safety monitoring board for GSK, LEO Pharma, Novan, Pfizer, and USB; served on advisory boards for Sanofi; and a principal investigator in clinical trials for Eli Lilly, Regeneron Pharmaceuticals, and Verrica Pharmaceuticals. MJC has been an investigator and consultant for Astellas, Galapagos, Hyphens Pharma, Johnson & Johnson, LEO Pharma, L’Oréal, Novartis, Oxagen, Pfizer, Reckitt Benckiser, Regeneron Pharmaceuticals, and Sanofi; and a consultant for AbbVie, Almirall, Anacor Pharmaceuticals, Boots, Dermavent, Galderma, Menlo Therapeutics, and Proctor & Gamble; and received research grants from Hyphens Pharma, Johnson & Johnson, LEO Pharma, L’Oréal, Pfizer, Regeneron Pharmaceuticals, and Sanofi. AW has been an investigator for Beiersdorf, Eli Lilly, Galderma, LEO Pharma, MedImmune, Novartis, Pfizer, Regeneron Pharmaceuticals, and Sanofi; a consultant for AbbVie, Almirall, Anacor Pharmaceuticals, Eli Lilly, Galapagos, Galderma, LEO Pharma, MedImmune, Novartis, Pfizer, Regeneron Pharmaceuticals, and Sanofi; and received research grants from Beiersdorf, LEO Pharma, and Pierre Fabre. PDA has been an investigator for Regeneron Pharmaceuticals; and received a research grant and been an advisor for Sanofi. WS has been a speaker, advisory board member, and investigator for AbbVie, Amgen, AstraZeneca, GSK, LEO Pharma, Pfizer, Regeneron Pharmaceuticals, and Sanofi; a consultant for AbbVie, LEO Pharma, and Regeneron Pharmaceuticals; received investigator grants from AbbVie, Aimmune Therapeutics, Genentech, GSK, Incyte, LEO Pharma, Novartis, Pfizer, Teva, and Vanda Pharmaceuticals; a speaker for Teva; and an advisor for Genentech. MEG has been an investigator for AbbVie, Arcutis Biotherapeutics, Dermira, Dermavant, Eli Lilly, Incyte, Krystal Biotech, Regeneron Pharmaceuticals, Sun Pharma, and Verrica Pharmaceuticals; a speaker for Galderma, Pfizer, Primus Pharmaceuticals, Regeneron Pharmaceuticals, and Sanofi; and a consultant for Unilever and Verrica Pharmaceuticals. LCS has been an investigator for DBV Technologies and Regeneron Pharmaceuticals; received research support from Genentech; and has been a consultant for AbbVie, Alladapt Immunotherapeutics, LEO Pharma, Regeneron Pharmaceuticals, and Sanofi. RS has been an investigator for Galderma, Regeneron Pharmaceuticals, and UCB; an advisory board member for LEO Pharma and Pfizer; and speaker for Beiersdorf. BL has been an investigator for Castle, Dermira, Franklin Biosciences, and Pfizer; an investigator, speaker, and consultant for AbbVie, Dermtech, Eli Lilly, Incyte, LEO Pharma, Regeneron Pharmaceuticals, and UCB; an investigator and consultant for Strata; and a speaker and consultant for Dermavant and Sanofi. SM has been an investigator for AstraZeneca, Pfizer, and Regeneron Pharmaceuticals. ZW, YS, BA, MD, MPK, MAK, DMW, GDY, and AB are employees and shareholders of Regeneron Pharmaceuticals. LPM, EL, NP, AD-B, and JTO are employees of and may hold stock or stock options in Sanofi. NA is a former employee and shareholder of Regeneron Pharmaceuticals., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Studies found associations between atopic dermatitis (AD) and various comorbidities., Objective: To appraise evidence of the association between AD and comorbidities among adults., Methods: Our multidisciplinary work group conducted a systematic review of the association between AD and selected comorbidities. We applied the Grading of Recommendations, Assessment, Development, and Evaluation for prognosis approach for assessing the certainty of the evidence, providing statements of association based on the available evidence., Results: Analysis of the evidence resulted in 32 statements. Clear evidence of the association of AD in adults and select allergic, atopic, immune-mediated mental health and bone health conditions and skin infections was identified. There is some evidence supporting an association between AD and substance use, attention deficit hyperactivity disorder, and elements of metabolic syndrome. Evidence suggests a small association with various cardiovascular conditions. The association between AD in adults and autism spectrum disorders, myocardial infarction, stroke, and metabolic syndrome is inconclusive., Limitations: This analysis is based on the best available evidence at the time it was conducted. This guideline does not make recommendations for screening or management of comorbidities in adults with AD., Conclusions: Clinicians should be aware of comorbidities associated with AD. Further research is needed to determine whether screening or management of comorbidities is beneficial for adults with AD., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Nemolizumab, a new monoclonal antibody that targets the receptor alpha of the neuroimmune cytokine interleukin-31 (IL-31), has shown efficacy in atopic dermatitis (AD) in adults. This study evaluated the pharmacokinetics (PK) and safety of nemolizumab in adolescents with moderate to severe AD as well as the relationship between nemolizumab concentrations and clinical efficacy and the effect of nemolizumab on protein biomarkers., Methods: Open-label, 16-week study of nemolizumab in patients aged 12-17 years with moderate to severe AD (baseline EASI ≥ 16, IGA ≥ 3, and BSA ≥ 10%) and associated pruritus with baseline average daily peak pruritus numeric rating scale (PP-NRS) intensity of at least 4. Nemolizumab was administered subcutaneously as a loading dose of 60 mg at baseline, followed by 30 mg every 4 weeks until week 12 with background topical corticosteroids (TCS) or calcineurin inhibitors (TCI). Subsequently patients were followed for 8 weeks more. Stratum corneum (SC) and plasma samples were collected for biomarker assessments., Results: Twenty patients participated, with a mean age of 14.8 ± 1.6 years. The PK of nemolizumab was described by a one-compartment model with linear elimination, a first-order absorption, and a mean half-life of 16.7 ± 4.1 days. Mean trough concentrations ranged from 2935 ± 1029 ng/mL to 3292 ± 2018 ng/mL over the 16-week treatment period. There was a marked improvement in rash, itch, and sleep with a decrease from baseline to week 16 in EASI by 66.5 ± 32.5%, in PP-NRS by 43.2 ± 37%, and in sleep disturbance numeric rating scale by 53.5 ± 47.8%. The popPK and PK/PD analyses confirmed that model-predicted exposure and efficacy of nemolizumab were similar in adolescents compared to adults receiving the same dosing regimens. Age did not impact PK parameters, while the main source of PK variability was body weight. Analyses of SC samples identified a panel of AD-related pro-inflammatory biomarkers that were upregulated in lesional skin (compared to non-lesional skin) and correspondingly downregulated in clinical responders to nemolizumab (based on EASI75 and PP-NRS ≥ 4). Four biomarkers (CCL20, CCL22, CCL27, and VEGF) had changes that were 1.9-3.5-fold higher in EASI responders than in EASI non-responders (all p < 0.05). Analysis showed no significant correlation between plasma biomarkers and clinical scores. Adverse events were experienced by 33.3% of subjects (n = 6) and were primarily mild or moderate in severity., Conclusions: Nemolizumab PK and safety profiles in adolescents with moderate to severe AD are consistent with previous nemolizumab studies in adults. PK/PD models demonstrate similar exposure-response profiles in 12- to 17-year-old adolescents and adults for three clinical endpoints (EASI, IGA, and PP-NRS). Nemolizumab treatment reversed AD-related pro-inflammatory biomarkers in skin, indicating that the neuroimmune cytokine IL-31 is an important mediator of multiple pathways in AD., Clinical Trial Registration: Clinicaltrials.gov NCT03921411., (© 2022. The Author(s).)

Allergists are often asked to evaluate children with atopic dermatitis (AD) for allergen triggers to disease. Testing, particularly for food triggers, often leads to elimination diets in an effort to improve AD control. However, the dual exposure hypothesis suggests that oral tolerance to food antigens is promoted through high-dose oral exposure, where sensitization occurs through lower dose cutaneous exposure. This suggests that strict elimination diets may pose some risks in children with AD. In addition, emerging evidence suggests an important role of skin inflammation in further allergic disease and the importance of dietary exposure to maintain oral tolerance. This work group report reviews current guidelines-based management for children with moderate-to-severe AD, the evidence for current recommendations for the evaluation and management of these children, provides a nuanced examination of these studies, and addresses current knowledge gaps in the care of these children., (Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Importance: Dupilumab subcutaneous injection is approved for treating moderate-to-severe atopic dermatitis (AD) in adolescents, but there has been too little research on an efficacious systemic oral treatment with a favorable benefit-risk profile for adolescents with moderate-to-severe AD., Objective: To investigate the efficacy and safety of oral abrocitinib plus topical therapy in adolescents with moderate-to-severe AD., Design, Setting, and Participants: The phase 3, randomized, double-blind, placebo-controlled study JADE TEEN was conducted in countries of the Asia-Pacific region, Europe, and North America in patients aged 12 to 17 years with moderate-to-severe AD and an inadequate response to 4 consecutive weeks or longer of topical medication or a need for systemic therapy for AD. The study was conducted between February 18, 2019, and April 8, 2020. The data were analyzed after study completion., Interventions: Patients were randomly assigned 1:1:1 to receive once-daily oral abrocitinib, 200 mg or 100 mg, or placebo for 12 weeks in combination with topical therapy., Main Outcomes and Measures: Coprimary end points were achievement of an Investigator's Global Assessment (IGA) response of clear (0) or almost clear (1) with improvement of 2 or more grades from baseline (IGA 0/1) and 75% or greater improvement from baseline in Eczema Area and Severity Index (EASI-75) response at week 12. Key secondary end points included 4-point or greater improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4) at week 12. Adverse events (AEs) were monitored., Results: This study included 285 adolescents with moderate-to-severe AD (145 boys [50.9%] and 140 girls [49.1%]), of whom 160 (56.1%) were White and 94 (33.0%) were Asian; the median age was 15 years (interquartile range 13-17 years). Substantially more patients treated with abrocitinib (200 mg or 100 mg) vs placebo achieved an IGA response of 0/1 (46.2%; 41.6% vs 24.5%; P < .05 for both), EASI-75 (72.0%; 68.5% vs 41.5%; P < .05 for both), and PP-NRS4 (55.4%; 52.6% vs 29.8%; P < .01 for 200 mg vs placebo) at week 12. Adverse events were reported for 59 (62.8%), 54 (56.8%), and 50 (52.1%) patients in the 200 mg, 100 mg, and placebo groups, respectively; nausea was more common with abrocitinib, 200 mg (17 [18.1%]) and 100 mg (7 [7.4%]). Herpes-related AEs were infrequent; 1 (1.1%), 0, and 2 (2.1%) patients had serious AEs., Conclusions and Relevance: This randomized clinical trial found that oral abrocitinib combined with topical therapy was significantly more effective than placebo with topical therapy in adolescents with moderate-to-severe AD, with an acceptable safety profile., Trial Registration: ClinicalTrials.gov identifier: NCT03796676.

Tumor necrosis factor alpha inhibitors (TNFi) are widely used in children with autoimmune and autoinflammatory conditions. Although TNFi are approved to treat psoriasis, they have also been shown to paradoxically induce psoriasiform lesions. In this review, we aim to focus on the clinical presentation and management of paradoxical psoriasis after exposure to TNFi in children with juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), or chronic nonbacterial osteomyelitis (CNO). A narrative review of the literature was performed given the limited number of publications on this topic. Children with IBD, CNO, and JIA have a higher risk of developing psoriasis at baseline, which increases after TNFi use in those with JIA and IBD. Risk factors for paradoxical psoriasis remain incompletely defined, and patients with IBD and/or CNO develop paradoxical psoriasis more commonly than those with JIA. Sex, race, and family history were not significantly associated with paradoxical psoriasis. The most commonly implicated TNFi include infliximab and adalimumab. Paradoxical psoriasis occurs in a similar distribution on the body to isolated psoriatic lesions and is morphologically indistinguishable. In many instances, topical therapies are effective in treating psoriasis and children can continue on TNFi for their primary disease. If lesions are severe or unacceptable to patients, TNFi may be switched or discontinued. Further research is needed to better characterize risk factors and understand the mechanism of disease pathogenesis. Pediatric health care providers who prescribe TNFi should counsel families regarding the risk of paradoxical psoriasis prior to starting the medication and monitor for new cutaneous eruptions.

Background: Children with forehead port-wine stains (PWSs) are at risk of Sturge-Weber syndrome (SWS). However, most will not develop neurologic manifestations., Objective: To identify children at greatest risk of SWS., Method: In this retrospective cohort study of children with a forehead PWS, PWSs were classified as "large segmental" (half or more of a contiguous area of the hemiforehead or median pattern) or "trace/small segmental" (less than half of the hemiforehead). The outcome measure was a diagnosis of SWS., Results: Ninety-six children had a forehead PWS. Fifty-one had a large segmental PWS, and 45 had a trace/small segmental PWS. All 21 children with SWS had large segmental forehead PWSs. Large segmental forehead PWSs had a higher specificity (0.71 vs 0.27, P < .0001) and a higher positive predictive value (0.41 vs 0.22, P < .0001) for SWS than any forehead involvement by a PWS., Limitations: Retrospective study at a referral center., Conclusion: Children with large segmental forehead PWSs are at highest risk of SWS., (Copyright © 2020 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

RASopathies are a group of disorders characterized by mutations in the RAS-MAPK pathway. RAS-MAP signaling plays a critical role in cell differentiation, proliferation, and survival. Germline mutations can result in distinctive syndromes, including Noonan syndrome, Costello syndrome, and neurofibromatosis type 1. Mosaic RASopathies can present as localized cutaneous lesions like epidermal nevi and nevus sebaceous, or more extensive conditions such as encephalocraniocutaneous lipomatosis. We review the heterogenous presentation of RAS mutations, discuss new targeted therapies, and highlight areas of uncertainty, including carcinogenesis risk and appropriate screening., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Atopic dermatitis (AD) is the most common inflammatory skin condition in pediatric patients. AD has long been associated with comorbidities including food allergies, asthma, and allergic rhinitis, but recent literature has expanded this list to include attention-deficit/hyperactivity disorder and depression. AD has tremendous impact on quality of life for both affected children and their families. Improved understanding of AD pathogenesis, particularly regarding skin barrier dysfunction, the role of the cutaneous microbiome, and immune dysregulation, has spawned exciting new therapeutic directions. Although good skin care and appropriate use of topical corticosteroids remain first-line treatment, more precisely targeted treatments hold great promise. A recently approved topical phosphodiesterase inhibitor, crisaborole, and a subcutaneously administered interleukin-4/interleukin-13 blocker, dupilumab, are the first of what will likely be many new treatment options for patients with AD. [Pediatr Ann. 2020;49(3):e140-e146.]., (Copyright 2020, SLACK Incorporated.)

Objective: This study had 2 objectives. First, to determine the behavior of physicians evaluating premobile infants with bruises. Second, and most importantly, to learn whether infants with unexplained bruising who had been initially evaluated by primary care and emergency department (ED) physicians are as likely to have their bruises attributed to child abuse as those children evaluated by child abuse physicians., Methods: Primary care, ED, and child abuse pediatricians (CAPs) in King County, Washington, San Mateo, Calif, Albuquerque, NM, La Crosse, Wis, and Torrance, Calif prospectively identified and studied infants younger than 6 months with less than 6 bruises, which were judged by the evaluating clinician to be explained or unexplained after their initial clinical examination., Results: Between March 1, 2010, and March 1, 2017, 63 infants with initially explained and 46 infants with initially unexplained bruises were identified. Infants with unexplained bruises had complete coagulation and abuse evaluations less frequently if they were initially identified by primary care pediatricians or ED providers than by CAPs. After imaging, laboratory, and follow-up, 54.2% (26) of the infants with initially unexplained bruises, including 2 who had been initially diagnosed with accidental injuries, were diagnosed as abused. Three (6.2%) infants had accidental bruising, 6 (12.4%) abuse mimics, 1 (2.5%) self-injury, 1 (2.5%) medical injury, and 11 (22.9%) remained of unknown causation. None had causal coagulation disorders. A total of 65.4% of the 26 abused infants had occult injuries detected by their imaging and laboratory evaluations. Six (23.1%) abused infants were not diagnosed until after they sustained subsequent injuries. Three (11.5%) were recognized abused by police investigation alone. Thirty-eight percent of the abused, bruised infants had a single bruise. Clinicians' estimates of abuse likelihood based on their initial clinical evaluation were inaccurate. Primary care, ED, and child abuse physicians identified abused infants at similar rates., Conclusions: More than half of premobile infants with initially unexplained bruises were found to be abused. Abuse was as likely for infants identified by primary care and ED providers as for those identified by CAPs. Currently, physicians often do not obtain full abuse evaluations in premobile infants with unexplained bruising. Their initial clinical judgment about abuse likelihood was inadequate. Bruised infants often have clinically occult abusive injuries or will sustain subsequent serious abuse. Bruised infants should have full abuse evaluations and referral for Protective Services and police assessments.

Background/objectives: Curbside consultations are common in pediatric dermatology. There are both associated risks and benefits. Email, text messaging, and cell phone cameras have greatly facilitated this practice. We sought to characterize the nature of this practice among pediatric dermatologists and highlight concerns., Methods: A 21-question anonymous survey was sent to the 486 active members of the Society for Pediatric Dermatology., Results: There were 156 responses (32%). Over 45% of respondents received at least six consults per week. About half (49%) spent 6 minutes or more per case. Almost none of these consultations (3%) were compensated or captured in work relative value units. Most (87%) did not document or have a practice or institutional policy in place to address these consultations. A similar majority (80%) were uncertain if their existing liability insurance covered these activities. Over three-quarters (76%) of respondents did not think or were unsure that Health Insurance Portability and Accountability Act concerns were appropriately addressed., Conclusions: Curbside consultations in pediatric dermatology are common. They increase access, promote collegiality, and can be used for educational gain. They are also generally not compensated, consume considerable time, risk liability exposure for providers, and potentially compromise patient confidentiality. Effort should be made to standardize this practice so that the benefits are not outweighed by risks., (© 2019 Wiley Periodicals, Inc.)

Background: Infant death in keratitis-ichthyosis-deafness (KID) syndrome is recognized; its association with specific genotypes and pathophysiology is inadequately understood., Objective: We sought to discover characteristics that account for poor outcomes in lethal KID syndrome., Methods: We collected 4 new cases and 9 previously reported, genotyped cases of lethal KID syndrome. We performed new molecular modeling of the lethal mutants GJB2 p.A88V and GJB2 p.G45E., Results: Infant death occurred in all patients with GJB2 p.G45E and p.A88V; it is unusual with other GJB2 mutations. Early death with those 2 "lethal" mutations is likely multifactorial: during life all had ≥1 serious infection; most had poor weight gain and severe respiratory difficulties; many had additional anatomic abnormalities. Structural modeling of GJB2 p.G45E identified no impact on the salt bridge previously predicted to account for abnormal central carbon dioxide sensing of GJB2 p.A88V., Limitations: This clinical review was retrospective., Conclusion: GJB2 p.G45E and p.A88V are the only KID syndrome mutations associated with uniform early lethality. Those electrophysiologically severe mutations in GJB2 reveal abnormalities in many organs in lethal KID syndrome. All patients with KID syndrome may have subtle abnormalities beyond the eyes, ears, and skin. Early genotyping of KID syndrome births will inform prognostic discussion., (Copyright © 2018 American Academy of Dermatology, Inc. All rights reserved.)

Atopic dermatitis is an important and chronic skin condition that has recently been the subject of enormous volumes of basic science, clinical, and epidemiologic research. This field is undergoing rapid expansion, making it vitally important to integrate the emerging data with our current body of knowledge. In 2014, the American Academy of Dermatology published Guidelines of Care for the Management of Atopic Dermatitis, composed of four parts, reflecting the work of 17 experts from North America and the United Kingdom. 1-4 It uses a patient-oriented system, SORT (Strength of Recommendation Taxonomy), to provide evidence-based guidance in the management of this common, vexing dermatitis. These guidelines join a series of similar efforts published recently across the world, reflecting universal interest in distilling the tremendous volume of basic scientific and clinical data previously generated. 5-7 With new therapies rapidly emerging, clinicians require a current understanding of the field to be able to incorporate new treatments in their practice., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Atopic dermatitis is the most common chronic skin disease, and it primarily affects children. Although atopic dermatitis (AD) has the highest effect on burden of skin disease, no high-level studies have defined optimal therapy for severe disease. Corticosteroids have been used to treat AD since the 1950s and remain the only systemic medication with Food and Drug Administration approval for this indication in children, despite published guidelines of care that recommend against this option. Several clinical trials with level 1 evidence have supported the use of topical treatments for mild to moderate atopic dermatitis in adults and children, but these trials have had little consistency in protocol design. Consensus recommendations will help standardize clinical development and trial design for children. The Food and Drug Administration issues guidance documents for industry as a source for "the Agency's current thinking on a particular subject." Although they are nonbinding, industry considers these documents to be the standard for clinical development and trial design. Our consensus group is the first to specifically address clinical trial design in this population. We developed a draft guidance document for industry, Developing Drugs for Treatment of Atopic Dermatitis in Children (≥3 months to <18 years of age). This draft guidance has been submitted to the Food and Drug Administration based on a provision in the Federal Register (Good Guidance Practices)., (© 2018 Wiley Periodicals, Inc.)

We present the case of a 12-year-old-girl who developed lichenoid dermatitis approximately 1 year after starting leflunomide for juvenile idiopathic arthritis. The eruption resolved promptly with discontinuation of the suspected culprit agent, supportive of a lichenoid drug eruption, but she subsequently developed markedly dystrophic nails with lichen planus-like features. A biopsy of her cutaneous findings at the time of initial presentation demonstrated lichenoid dermatitis, and a nail matrix biopsy was deferred given clinical correlation. Prominent nail changes in lichenoid drug eruptions, particularly in children, are rare but should be considered in children with new-onset nail dystrophy., (© 2017 Wiley Periodicals, Inc.)

Purpose of Review: Tremendous advances have been made in the field of atopic dermatitis in the past 5 years. We will explore developments in burden of disease, co-morbidities, pathogenesis, prevention, and management., Recent Findings: The tremendous burden moderate to severe atopic dermatitis (AD) places on families from a medical, psychosocial, and financial perspective has been characterized. Epidemiologic studies have identified intriguing new associations beyond the well-characterized "atopic march" of food allergies, asthma, and hay fever. Studies of primary prevention have gained traction including the remarkable impacts of early emollient therapy. Basic advances have simultaneously elucidated the nature of atopic inflammation, setting the stage for an explosion of new potential therapeutic targets. After a fallow period of nearly 15 years without a substantial therapeutic advance, this year has already seen two new FDA-approved treatments for AD. AD has a tremendous impact on quality of life with an underappreciated burden of disease; there are important newly described co-morbidities including ADHD and anemia; new insights into etio-pathogenesis have paved the way for novel topical therapies like crisaborole, and new systemic interventions like dupilumab.

Trichodysplasia spinulosa (TS) is an uncommon skin disease characterized by a folliculocentric papular eruption and keratin spine formation, classically appearing on the central face and ears. It occurs in immunosuppressed patients and is linked to a viral etiology. Diagnostic tests including polymerase chain reaction (PCR) are available for detection of the TS-associated polyomavirus. Effective treatment options include topical cidofovir and oral valganciclovir. We present a case diagnosed using PCR with skin scrapings and treated using physical extraction of the keratin spicules. Significant improvement was noted, suggesting a safe, cost-effective treatment alternative., (© 2016 Wiley Periodicals, Inc.)

Background: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy., Objectives: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy., Results: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation., Conclusions: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy., (Published by Elsevier Inc.)

Background: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy., Objectives: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy., Results: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation., Conclusions: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy., (Published by Elsevier Inc.)

Background: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy., Objectives: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy., Results: The addendum provides three separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation., Conclusions: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy., (Published 2017. This article is a U.S. Government work and is in the public domain in the USA.)

Background: Food allergy is an important public health problem because it affects children and adults, can be severe and even life-threatening, and may be increasing in prevalence. Beginning in 2008, the National Institute of Allergy and Infectious Diseases, working with other organizations and advocacy groups, led the development of the first clinical guidelines for the diagnosis and management of food allergy. A recent landmark clinical trial and other emerging data suggest that peanut allergy can be prevented through introduction of peanut-containing foods beginning in infancy., Objectives: Prompted by these findings, along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases facilitated development of addendum guidelines to specifically address the prevention of peanut allergy., Results: The addendum provides 3 separate guidelines for infants at various risk levels for the development of peanut allergy and is intended for use by a wide variety of health care providers. Topics addressed include the definition of risk categories, appropriate use of testing (specific IgE measurement, skin prick tests, and oral food challenges), and the timing and approaches for introduction of peanut-containing foods in the health care provider's office or at home. The addendum guidelines provide the background, rationale, and strength of evidence for each recommendation., Conclusions: Guidelines have been developed for early introduction of peanut-containing foods into the diets of infants at various risk levels for peanut allergy., (Published by Elsevier Inc.)

There has been a surge of new data regarding the pathophysiology of skin diseases. We are appreciating the sophisticated interplay among the skin, the immune system, and the environment. More elegant and highly specific medicines have been designed to target certain immune mediators of the adaptive immune system. In parallel fashion, we are learning more about the elegance of the innate immune system and how nutrition as early as the prenatal period can affect the priming of other immune cells. Concerns about the long-term impact of new immune-modulating medicines-especially in the pediatric population-have patients asking their dermatologists for nutritional alternatives to medical therapies. Nutrients and nutritional therapies appear to play a role at different ages for different dermatoses. Probiotics are showing promise as a therapeutic option for patients older than 1 year for atopic dermatitis. Systemic contact allergens appear to be a bigger burden on the adult population with atopic dermatitis. Obesity is a growing concern for both children and adults with psoriasis. Milk and high glycemic foods have a strong impact on the teenage acne population. Vitamins A and D are addressed as piece of the alopecia areata puzzle. Zinc and homeopathy are presented finally as possible treatments to the everlasting wart., (Copyright © 2016. Published by Elsevier Inc.)

Objectives: Few genetic causes of exocrine pancreatic dysfunction have been described to date. We identified a family with multiple affected members manifesting exocrine pancreatic dysfunction. Additional associated features included facial rash, sparse hair, hypohidrosis, and swelling of the extremities. The transmission pattern of these clinical features was consistent with an autosomal dominant mode of inheritance. The 2 proband siblings also had transient elevated liver transaminases with hepatic steatosis early in life. This study identifies the genetic cause of exocrine pancreatic dysfunction in this family., Methods: Whole exome sequencing was performed to identify the genetic cause of exocrine pancreatic dysfunction., Results: A heterozygous germline in-frame deletion in the gene FAM111B (c.1261&#95;1263delAAG, p.Lys421del) cosegregated with the phenotype: the variant was present in all affected relatives genotyped and absent in all unaffected relatives genotyped. The variant is also absent from public control sequence databases., Conclusions: Our findings implicate FAM111B in autosomal dominantly inheritable exocrine pancreatic dysfunction.

Background: Periocular infantile hemangiomas (PIH) can induce anisometropic astigmatism, a risk factor for amblyopia. Oral beta-blocker therapy has largely supplanted systemic or intralesional corticosteroids. The purpose of this study was to evaluate the effect and time course of these treatment modalities on visual acuity and induced astigmatism., Methods: The medical records of patients with PIH treated with oral propanolol between November 2008 and July 2013 were retrospectively reviewed for data on visual acuity and astigmatism. Patients with incomplete pre- and post-treatment ophthalmic examinations were excluded. Results were compared to those of a similar cohort treated with intralesional corticosteroid injection., Results: Mean astigmatism in affected eyes was 1.90 D before propranolol and 1.00 D after; patients showed a monophasic reduction in astigmatism over 12 months. By comparison, patients treated with corticosteroid injection showed a biphasic response, with an immediate steep decrease followed by a slow monophasic decline, paralleling propranolol-treated patients. Oral propranolol treatment caused a 47% reduction in mean induced astigmatism, less than the 63% reduction reported for the cohort treated with corticosteroid. No patient had visual acuity in the affected eye more than 1 standard devation below the age-matched norm, and none experienced significant side effects when treated with oral propranolol., Conclusions: In this patient cohort oral beta-blocker was well-tolerated. Treatment was therefore often initiated prior to the induction of significant astigmatism, with treatment effects comparable to steroid treatment. Visual outcomes were good. Early treatment may minimize the potential effect of astigmatism on postnatal visual development., (Copyright © 2016 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Disorders of keratinization (DOK) show marked genotypic and phenotypic heterogeneity. In most cases, disease is primarily cutaneous, and further clinical evaluation is therefore rarely pursued. We have identified subjects with a novel DOK featuring erythrokeratodermia and initially-asymptomatic, progressive, potentially fatal cardiomyopathy, a finding not previously associated with erythrokeratodermia. We show that de novo missense mutations clustered tightly within a single spectrin repeat of DSP cause this novel cardio-cutaneous disorder, which we term erythrokeratodermia-cardiomyopathy (EKC) syndrome. We demonstrate that DSP mutations in our EKC syndrome subjects affect localization of desmosomal proteins and connexin 43 in the skin, and result in desmosome aggregation, widening of intercellular spaces, and lipid secretory defects. DSP encodes desmoplakin, a primary component of desmosomes, intercellular adhesion junctions most abundant in the epidermis and heart. Though mutations in DSP are known to cause other disorders, our cohort features the unique clinical finding of severe whole-body erythrokeratodermia, with distinct effects on localization of desmosomal proteins and connexin 43. These findings add a severe, previously undescribed syndrome featuring erythrokeratodermia and cardiomyopathy to the spectrum of disease caused by mutation in DSP, and identify a specific region of the protein critical to the pathobiology of EKC syndrome and to DSP function in the heart and skin., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Atopic dermatitis (AD), or eczema, is a chronic inflammatory skin condition characterized by relapsing pruritic, scaly, erythematous papules and plaques frequently associated with superinfection. The lifelong prevalence of AD is over 20 % in affluent countries. When a child with severe AD is not responding to optimized topical therapy including phototherapy, and relevant triggers cannot be identified or avoided, systemic therapy should be considered. If studies show early aggressive intervention can prevent one from advancing along the atopic march, and relevant triggers such as food allergies cannot be either identified or avoided, systemic therapy may also play a prophylactic role. Though the majority of evidence exists in adult populations, four systemic non-specific immunosuppressive or immunomodulatory drugs have demonstrated efficacy in AD and are used in most patients requiring this level of intervention regardless of age: cyclosporine, mycophenolate mofetil, methotrexate, and azathioprine. This article reviews the use of these medications as well as several promising targeted therapies currently in development including dupilumab and apremilast. We briefly cover several other systemic interventions that have been studied in children with atopic dermatitis.

Atopic dermatitis is a chronic, pruritic skin disease characterized by an improperly functioning skin barrier and immune dysregulation. We review proposed atopic dermatitis pathomechanisms, emphasizing how these impact current perspectives on natural history, role of allergic sensitization, and future therapeutic targets.

Atopic dermatitis is a common, chronic inflammatory dermatosis that can affect all age groups. This evidence-based guideline addresses important clinical questions that arise in its management. In this final section, treatments for flare prevention and adjunctive and complementary therapies and approaches are reviewed. Suggestions on use are given based on available evidence., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Epidemiologic and preclinical data, and a small randomized trial in Boston, suggest that vitamin D supplementation may improve winter-related atopic dermatitis (AD)., Objective: To determine the effect of vitamin D supplementation on winter-related AD., Methods: We performed a randomized, double-blind, placebo-controlled trial of Mongolian children with winter-related AD (clinicaltrials.gov identifier: NCT00879424). Baseline eligibility included age 2 to 17 years, AD score 10 to 72 using the Eczema Area and Severity Index (EASI), and winter-related AD (eg, history of AD worsening during the fall-to-winter transition). Subjects were enrolled in Ulaanbaatar during winter and randomly assigned to oral cholecalciferol (1000 IU/day) versus placebo for 1 month. All children and parents received emollient and patient education about AD and basic skin care. The main outcomes were changes in EASI score and in Investigator's Global Assessment., Results: The 107 enrolled children had a mean age of 9 years (SD 5), and 59% were male. Their median age of AD onset was 3 months (interquartile range 2 months to 1 year) and mean EASI score at baseline 21 (SD 9). One-month follow-up data were available for 104 (97%) children. Compared with placebo, vitamin D supplementation for 1 month produced a clinically and statistically significant improvement in EASI score (adjusted mean change: -6.5 vs -3.3, respectively; P = .04). Moreover, change in Investigator's Global Assessment favored vitamin D over placebo (P = .03). There were no adverse effects in either group., Conclusion: Vitamin D supplementation improved winter-related AD among Mongolian children, a population likely to have vitamin D deficiency in winter., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The past year has produced several new clinical guidelines germane to paediatric dermatology, as well as important work related to rheumatologic overlap disorders, psoriasis comorbidities, pigmented lesions and quality of life impact. This review highlights common diagnoses and treatments useful for the practicing paediatrician., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Atopic dermatitis is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2% to 3% of adults. This guideline addresses important clinical questions that arise in atopic dermatitis management and care, providing recommendations based on the available evidence. In this third of 4 sections, treatment of atopic dermatitis with phototherapy and systemic immunomodulators, antimicrobials, and antihistamines is reviewed, including indications for use and the risk-benefit profile of each treatment option., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

One of the early lessons learned in dermatology training is "any drug, any rash." This maxim quickly summarizes the vast array of cutaneous reactions that can be seen in response to systemic medications. We have reviewed common and unusual drug eruptions in pediatric patients that span the morphologic spectrum. These reactions can have an equally broad range of severity, from harmless to lethal, and by the end of this paper the reader will be better equipped to sort one from the other., (Copyright © 2014 Elsevier Inc. All rights reserved.)