16 results on '"Bercovitch L"'
Search Results
2. Rubella Virus Infected Macrophages and Neutrophils Define Patterns of Granulomatous Inflammation in Inborn and Acquired Errors of Immunity
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Ludmila Perelygina, Raeesa Faisthalab, Emily Abernathy, Min-hsin Chen, LiJuan Hao, Lionel Bercovitch, Diana K. Bayer, Lenora M. Noroski, Michael T. Lam, Maria Pia Cicalese, Waleed Al-Herz, Arti Nanda, Joud Hajjar, Koen Vanden Driessche, Shari Schroven, Julie Leysen, Misha Rosenbach, Philipp Peters, Johannes Raedler, Michael H. Albert, Roshini S. Abraham, Hemalatha G. Rangarjan, David Buchbinder, Lisa Kobrynski, Anne Pham-Huy, Julie Dhossche, Charlotte Cunningham Rundles, Anna K. Meyer, Amy Theos, T. Prescott Atkinson, Amy Musiek, Mehdi Adeli, Ute Derichs, Christoph Walz, Renate Krüger, Horst von Bernuth, Christoph Klein, Joseph Icenogle, Fabian Hauck, Kathleen E. Sullivan, Perelygina, L., Faisthalab, R., Abernathy, E., Chen, M. -H., Hao, L., Bercovitch, L., Bayer, D. K., Noroski, L. M., Lam, M. T., Cicalese, M. P., Al-Herz, W., Nanda, A., Hajjar, J., Vanden Driessche, K., Schroven, S., Leysen, J., Rosenbach, M., Peters, P., Raedler, J., Albert, M. H., Abraham, R. S., Rangarjan, H. G., Buchbinder, D., Kobrynski, L., Pham-Huy, A., Dhossche, J., Cunningham Rundles, C., Meyer, A. K., Theos, A., Atkinson, T. P., Musiek, A., Adeli, M., Derichs, U., Walz, C., Kruger, R., von Bernuth, H., Klein, C., Icenogle, J., Hauck, F., and Sullivan, K. E.
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Male ,inborn errors of immunity ,Neutrophils ,Immunology ,skin lesion ,primary immunodeficiency ,Cohort Studies ,Th2 Cells ,neutrophils ,granulomatous inflammation ,granuloma treatments ,Humans ,Immunology and Allergy ,Antigens, Viral ,Rubella ,Aged ,Original Research ,Inflammation ,Granuloma ,Tumor Necrosis Factor-alpha ,Macrophages ,Genetic Diseases, Inborn ,Hematopoietic Stem Cell Transplantation ,Immunologic Deficiency Syndromes ,Receptors, Interleukin-1 ,RC581-607 ,Middle Aged ,Immunohistochemistry ,macrophages ,vaccine-derived rubella viruses ,Cytokines ,Female ,Human medicine ,Disease Susceptibility ,Immunologic diseases. Allergy ,Rubella virus - Abstract
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.
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- 2021
3. Nodule on the knee of a young boy.
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Gibson J, Gaghan LJ, Henebeng EB, Bercovitch L, and DiMarco C
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- 2024
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4. Stigmatization and Mental Health Impact of Chronic Pediatric Skin Disorders.
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Paller AS, Rangel SM, Chamlin SL, Hajek A, Phan S, Hogeling M, Castelo-Soccio L, Lara-Corrales I, Arkin L, Lawley LP, Funk T, Castro Porto Silva Lopes F, Antaya RJ, Ramien ML, Vivar KL, Teng J, Coughlin CC, Rehmus W, Gupta D, Bercovitch L, Stein SL, Boull C, Tom WL, Liang MG, Hunt R, Luu M, Holland KE, Schoch JJ, Cella D, Lai JS, and Griffith JW
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- Humans, Female, Male, Child, Adolescent, Cross-Sectional Studies, Chronic Disease, Canada, Stereotyping, Severity of Illness Index, Depression epidemiology, Depression psychology, Depression etiology, United States, Anxiety psychology, Anxiety epidemiology, Anxiety etiology, Patient Reported Outcome Measures, Quality of Life, Skin Diseases psychology, Mental Health, Social Stigma
- Abstract
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.
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- 2024
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5. Executive summary: Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies.
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Davis DMR, Drucker AM, Alikhan A, Bercovitch L, Cohen DE, Darr JM, Eichenfield LF, Frazer-Green L, Paller AS, Schwarzenberger K, Silverberg JI, Singh AM, Wu PA, and Sidbury R
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- Adult, Humans, Cyclosporine therapeutic use, Immunosuppressive Agents therapeutic use, Methotrexate therapeutic use, Phototherapy, Dermatitis, Atopic drug therapy
- Abstract
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.)
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- 2024
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6. Guidelines of care for the management of atopic dermatitis in adults with phototherapy and systemic therapies.
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Davis DMR, Drucker AM, Alikhan A, Bercovitch L, Cohen DE, Darr JM, Eichenfield LF, Frazer-Green L, Paller AS, Schwarzenberger K, Silverberg JI, Singh AM, Wu PA, and Sidbury R
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- Adult, Humans, Cyclosporine therapeutic use, Immunosuppressive Agents therapeutic use, Methotrexate therapeutic use, Phototherapy, Dermatitis, Atopic drug therapy, Janus Kinase Inhibitors therapeutic use
- Abstract
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.)
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- 2024
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7. Ethical issues of patient images freely accessible on the internet.
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Ragi SD, Shah A, Grant-Kels JM, and Bercovitch L
- Abstract
Competing Interests: Conflicts of interest None disclosed.
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- 2023
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8. Guidelines of care for the management of atopic dermatitis in adults with topical therapies.
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Sidbury R, Alikhan A, Bercovitch L, Cohen DE, Darr JM, Drucker AM, Eichenfield LF, Frazer-Green L, Paller AS, Schwarzenberger K, Silverberg JI, Singh AM, Wu PA, and Davis DMR
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- Adult, Humans, Calcineurin Inhibitors therapeutic use, Administration, Topical, Glucocorticoids therapeutic use, Histamine Antagonists therapeutic use, Dermatitis, Atopic drug therapy, Dermatologic Agents therapeutic use, Anti-Infective Agents, Local therapeutic use
- Abstract
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.)
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- 2023
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9. Executive summary: American Academy of Dermatology guidelines of care for the management of atopic dermatitis in adults with topical therapies.
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Sidbury R, Alikhan A, Bercovitch L, Cohen DE, Darr JM, Drucker AM, Eichenfield LF, Frazer-Green L, Paller AS, Schwarzenberger K, Silverberg JI, Singh AM, Wu PA, and Davis DMR
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- Adult, Humans, Calcineurin Inhibitors therapeutic use, Glucocorticoids, Dermatitis, Atopic drug therapy, Dermatology, Dermatologic Agents therapeutic use
- Abstract
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.)
- Published
- 2023
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10. Young boy with a purple papule on the thigh.
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Abrantes TF, Robinson-Bostom L, and Bercovitch L
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- Male, Humans, Thigh, Hemangioma, Hemangiosarcoma, Exanthema, Skin Neoplasms, Hemangioendothelioma, Epithelioid
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- 2023
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11. American Academy of Dermatology Guidelines: Awareness of comorbidities associated with atopic dermatitis in adults.
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Davis DMR, Drucker AM, Alikhan A, Bercovitch L, Cohen DE, Darr JM, Eichenfield LF, Frazer-Green L, Paller AS, Silverberg JI, Singh AM, and Sidbury R
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- Adult, Comorbidity, Humans, United States epidemiology, Dermatitis, Atopic diagnosis, Dermatitis, Atopic epidemiology, Dermatology, Metabolic Syndrome diagnosis, Metabolic Syndrome epidemiology, Myocardial Infarction
- Abstract
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.)
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- 2022
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12. The Genomic and Phenotypic Landscape of Ichthyosis: An Analysis of 1000 Kindreds.
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Sun Q, Burgren NM, Cheraghlou S, Paller AS, Larralde M, Bercovitch L, Levinsohn J, Ren I, Hu RH, Zhou J, Zaki T, Fan R, Tian C, Saraceni C, Nelson-Williams CJ, Loring E, Craiglow BG, Milstone LM, Lifton RP, Boyden LM, and Choate KA
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- Cohort Studies, Female, Genomics, Humans, Male, Phenotype, Ichthyosis pathology, Ichthyosis, Lamellar genetics
- Abstract
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.
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- 2022
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13. Rubella Virus Infected Macrophages and Neutrophils Define Patterns of Granulomatous Inflammation in Inborn and Acquired Errors of Immunity.
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Perelygina L, Faisthalab R, Abernathy E, Chen MH, Hao L, Bercovitch L, Bayer DK, Noroski LM, Lam MT, Cicalese MP, Al-Herz W, Nanda A, Hajjar J, Vanden Driessche K, Schroven S, Leysen J, Rosenbach M, Peters P, Raedler J, Albert MH, Abraham RS, Rangarjan HG, Buchbinder D, Kobrynski L, Pham-Huy A, Dhossche J, Cunningham Rundles C, Meyer AK, Theos A, Atkinson TP, Musiek A, Adeli M, Derichs U, Walz C, Krüger R, von Bernuth H, Klein C, Icenogle J, Hauck F, and Sullivan KE
- Subjects
- Aged, Antigens, Viral metabolism, Cohort Studies, Cytokines metabolism, Disease Susceptibility, Female, Genetic Diseases, Inborn, Hematopoietic Stem Cell Transplantation, Humans, Immunohistochemistry, Immunologic Deficiency Syndromes, Male, Middle Aged, Receptors, Interleukin-1 antagonists & inhibitors, Rubella complications, Th2 Cells immunology, Tumor Necrosis Factor-alpha antagonists & inhibitors, Granuloma immunology, Inflammation immunology, Macrophages immunology, Neutrophils immunology, Rubella immunology, Rubella virus physiology
- Abstract
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.)
- Published
- 2021
- Full Text
- View/download PDF
14. Do health insurers have an ethical responsibility to cover treatment of vitiligo?
- Author
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Bercovitch L
- Subjects
- Humans, Insurance Carriers, Hypopigmentation, Vitiligo therapy
- Published
- 2021
- Full Text
- View/download PDF
15. A 12-year-old boy with bilateral reticulated hyperpigmentation of the thighs.
- Author
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Chan S, Robbins A, and Bercovitch L
- Subjects
- Child, Humans, Male, Hyperpigmentation diagnosis, Thigh
- Published
- 2021
- Full Text
- View/download PDF
16. Misdiagnosis of capillary malformations in darker skin phototypes.
- Author
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Nriagu BN, Sanders VR, Bercovitch L, Snyder K, Cross EA, Treat JR, and Sheppard SE
- Subjects
- Capillaries abnormalities, Diagnostic Errors, Humans, p120 GTPase Activating Protein, Arteriovenous Malformations, Hyperpigmentation, Port-Wine Stain diagnosis, Vascular Malformations diagnosis
- Abstract
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.)
- Published
- 2021
- Full Text
- View/download PDF
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