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In a randomized double-blind controlled study, 19 patients applied 5% 5-fluorouracil (5-FU) cream to actinic keratoses (AK) on each arm twice daily, followed by nightly application of 0.05% tretinoin cream to one arm, and a control cream to the other arm until discomfort precluded further applications. After 3 months, the number of residual AK was compared to pre-treatment values. The tretinoin-treated arms had 15.7 ± 6. 1 AK before treatment and 3.4±2.6 AK following therapy. The control arms had 15. 3 ± 6.9 AK before therapy and 4.2 ± 2.5 lesions afterwards. Using a one-tailed paired t-test, the difference in response was statistically significant (0.03 <P< 0.04). It was concluded that daily application of 0.05% tretinoin cream appeared to enhance the efficacy of topical 5-FU in destruction of AK of the arms and may represent a useful treatment modality. [ABSTRACT FROM AUTHOR]

Importance: Chronic skin disorders in children frequently are visible and can cause stigmatization. However, the extent of stigmatization from chronic skin disease and association with mental health needs further study., Objective: To examine the extent of stigma, dependence on disease visibility and severity, and association with mental health and quality of life (QOL) in chronic pediatric skin disease., Design, Setting, and Participants: A cross-sectional, single-visit study was conducted at 32 pediatric dermatology centers in the US and Canada from November 14, 2018, to November 17, 2021. Participants included patients aged 8 to 17 years with chronic skin disease and 1 parent., Main Outcomes and Measures: Using the Patient-Reported Outcomes Measurement Instrumentation System (PROMIS) Stigma-Skin, the extent of stigma with child-, caregiver-, and physician-assessed disease visibility (primary outcome) and severity was compared, as well as reduced QOL (assessed by Skindex-Teen), depression, anxiety, and poor peer relationships (PROMIS child and proxy tools) (secondary outcomes)., Results: The study included 1671 children (57.9% female; mean [SD] age, 13.7 [2.7] years). A total of 56.4% participants had self-reported high disease visibility and 50.5% had moderate disease severity. Stigma scores significantly differed by level of physician-assessed and child/proxy-assessed disease visibility and severity. Among children with chronic skin disorders, predominantly acne, atopic dermatitis, alopecia areata, and vitiligo, only 27.0% had T scores less than 40 (minimal or no stigma) and 43.8% had at least moderate stigma (T score ≥45) compared with children with a range of chronic diseases. Stigma scores correlated strongly with reduced QOL (Spearman ρ = 0.73), depression (ρ = 0.61), anxiety (ρ = 0.54), and poor peer relationships (ρ = -0.49). Overall, 29.4% of parents were aware of bullying of their child, which was strongly associated with stigma (Cohen d = -0.79, with children who were not bullied experiencing lower levels of stigma). Girls reported more stigma than boys (Cohen d = 0.26). Children with hyperhidrosis and hidradenitis suppurativa were most likely to have increased depression and anxiety., Conclusions and Relevance: The findings of this study suggest that physician assessment of disease severity and visibility is insufficient to evaluate the disease impact in the patient/caregiver. Identifying stigmatization, including bullying, and tracking improvement through medical and psychosocial interventions may be a key role for practitioners.

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: 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.)

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.)

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 < .001), skin odor (OR, 2.8; 95% CI, 1.1-6.8; P = .02), hearing problems (OR, 2.9; 95% CI, 1.6-5.5; P < .001), eye problems (OR, 3.0; 95% CI, 1.5-6.0; P < .001), and alopecia (OR, 4.6; 95% CI, 2.4-9.0; P < .001) were significantly associated with TGM1 variants compared with other ichthyosis genotypes studied. Skin pain (OR, 6.8; 95% CI, 1.6-61.2; P = .002), odor (OR, 5.7; 95% CI, 2.0-19.7; P < .001), and infections (OR, 3.1; 95% CI, 1.4-7.7; P = .03) were significantly associated with KRT10 pathogenic variants compared with disease-associated variants in other genes that cause ichthyosis. Pathogenic variants were identified in 869 (86.9%) participants. Most of the remaining individuals had unique phenotypes, enabling further genetic discovery., Conclusions and Relevance: This cohort study expands the genotypic and phenotypic spectrum of ichthyosis, establishing associations between clinical manifestations and genotypes. Collectively, the findings may help improve clinical assessment, assist with developing customized management plans, and improve clinical course prognostication.

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions., Competing Interests: MA is employed by Sidra Medicine and Hamad Medical Corporation, Qatar. HB is employed by Labor Berlin GmbH, Germany. JH received grants from Immune Deficiency Foundation, the US immunodeficiency network, Chao-physician Scientist award, the Texas Medical Center Digestive Diseases Center and the Jeffrey Modell Foundation. JH received honorarium, consultation fees from Horizon, Pharming, Baxalta, CSL Behring, the National guard, and Al-Faisal University Hospital. TPA received consultation fees from Horizon, Pharming, CSL Behring. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Perelygina, Faisthalab, Abernathy, Chen, Hao, Bercovitch, Bayer, Noroski, Lam, Cicalese, Al-Herz, Nanda, Hajjar, Vanden Driessche, Schroven, Leysen, Rosenbach, Peters, Raedler, Albert, Abraham, Rangarjan, Buchbinder, Kobrynski, Pham-Huy, Dhossche, Cunningham Rundles, Meyer, Theos, Atkinson, Musiek, Adeli, Derichs, Walz, Krüger, von Bernuth, Klein, Icenogle, Hauck and Sullivan.)

In the dermatologic medical literature, there is an underrepresentation of conditions in individuals of color. Due to the lack of representation, it may be harder for clinicians to recognize certain diagnoses in patients with darker skin phototypes leading to misdiagnosis and affecting overall patient management, outcomes, and satisfaction. Here, we present four Black or Indigenous People of Color who were initially referred for hyperpigmentation, hemihyperplasia, or café au lait spots and found to have syndromic capillary malformations., (© 2021 Wiley Periodicals LLC.)

We present two infants with histologically confirmed congenital dermatomyofibromas. Congenital cases are rare with only one prior case reporting presence since birth. Given the benign nature of the lesions and propensity of dermatomyofibromas to resolve without intervention in young male patients, no additional treatments were pursued., (© 2021 Wiley Periodicals LLC.)

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., Competing Interests: Conflict of interest None disclosed., (Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Rubella viruses (RV) have been found in an association with granulomas in children with primary immune deficiencies (PID). Here, we report the recovery and characterization of infectious immunodeficiency-related vaccine-derived rubella viruses (iVDRV) from diagnostic skin biopsies of four patients. Sequence evolution within PID hosts was studied by comparison of the complete genomic sequences of the iVDRVs with the genome of the vaccine virus RA27/3. The degree of divergence of each iVDRV correlated with the duration of persistence indicating continuous intrahost evolution. The evolution rates for synonymous and nonsynonymous substitutions were estimated to be 5.7 x 10-3 subs/site/year and 8.9 x 10-4 subs/site/year, respectively. Mutational spectra and signatures indicated a major role for APOBEC cytidine deaminases and a secondary role for ADAR adenosine deaminases in generating diversity of iVDRVs. The distributions of mutations across the genes and 3D hotspots for amino acid substitutions in the E1 glycoprotein identified regions that may be under positive selective pressure. Quasispecies diversity was higher in granulomas than in recovered infectious iVDRVs. Growth properties of iVDRVs were assessed in WI-38 fibroblast cultures. None of the iVDRV isolates showed complete reversion to wild type phenotype but the replicative and persistence characteristics of iVDRVs were different from those of the RA27/3 vaccine strain, making predictions of iVDRV transmissibility and teratogenicity difficult. However, detection of iVDRV RNA in nasopharyngeal specimen and poor neutralization of some iVDRV strains by sera from vaccinated persons suggests possible public health risks associated with iVDRV carriers. Detection of IgM antibody to RV in sera of two out of three patients may be a marker of virus persistence, potentially useful for identifying patients with iVDRV before development of lesions. Studies of the evolutionary dynamics of iVDRV during persistence will contribute to development of infection control strategies and antiviral therapies., Competing Interests: The authors have read the journal's policy and have the following conflicts: Andrey Zharkikh is an employee of Myriad Genetics. This company works in cancer genetics and diagnostics without any relation to pathogen studies and treatments. This does not alter our adherence to all PLOS Pathogens policies on sharing data and materials.

Decision making in dermatology practice with adult patients is in most cases a relatively straightforward process, involving a back-and-forth exchange of information, ideas and opinions between the physician and patient. This process is more complex in the field of pediatric dermatology. It involves the triad of the patient, parent or guardian, and physician. It utilizes a model, common to many fields in pediatrics, whereby the physician seeks to obtain informed permission from the parent with the assent of the child, all the while endeavoring to act in the best interests of the child. This model can be challenged in many ways; from parents seeking interventions, which are not in the best interests of the child, to a child refusing to assent to a procedure that is deemed necessary by the parent and physician. We review the theory, terminology, and guidelines relevant to the ethics of decision making when working with children compared with adults. We explore approaches to a variety of ethically challenging situations that may be encountered by the dermatologist, through their work with pediatric patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Vascular tumors are among the most common neoplasms in infants and children; 5%-10% of newborns present with or develop lesions within the first 3 months of life. Most are benign infantile hemangiomas that typically regress by 5 years of age; other vascular tumors include congenital tufted angiomas (TAs), kaposiform hemangioendotheliomas (KHEs), and childhood lobular capillary hemangiomas (LCHs). Some of these lesions can become locally invasive and unresponsive to pharmacologic intervention, leading to significant complications. Recent investigation has revealed that activating mutations in HRAS, KRAS, NRAS, GNAQ, and GNA11 can cause certain types of rare childhood vascular tumors, and we have now identified causal recurrent somatic activating mutations in GNA14 by whole-exome and targeted sequencing. We found somatic activating GNA14 c.614A>T (p.Gln205Leu) mutations in one KHE, one TA, and one LCH and a GNA11 c.547C>T (p.Arg183Cys) mutation in two LCH lesions. We examined mutation pathobiology via expression of mutant GNA14 or GNA11 in primary human endothelial cells and melanocytes. GNA14 and GNA11 mutations induced changes in cellular morphology and rendered cells growth-factor independent by upregulating the MAPK pathway. Our findings identify GNA14 mutations as a cause of childhood vascular tumors, offer insight into mechanisms of oncogenic transformation by mutations affecting Gaq family members, and identify potential targets for therapeutic intervention., (Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Milia en plaque is a rare, benign, localized, entity typically seen in adults after the third decade of life. Although there have been a few cases described in children, we describe the first case in a newborn., (© 2016 Wiley Periodicals, Inc.)