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1.
N Engl J Med ; 390(20): 1873-1884, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38810185

ABSTRACT

BACKGROUND: Autoimmune polyendocrine syndrome type 1 (APS-1) is a life-threatening, autosomal recessive syndrome caused by autoimmune regulator (AIRE) deficiency. In APS-1, self-reactive T cells escape thymic negative selection, infiltrate organs, and drive autoimmune injury. The effector mechanisms governing T-cell-mediated damage in APS-1 remain poorly understood. METHODS: We examined whether APS-1 could be classified as a disease mediated by interferon-γ. We first assessed patients with APS-1 who were participating in a prospective natural history study and evaluated mRNA and protein expression in blood and tissues. We then examined the pathogenic role of interferon-γ using Aire-/-Ifng-/- mice and Aire-/- mice treated with the Janus kinase (JAK) inhibitor ruxolitinib. On the basis of our findings, we used ruxolitinib to treat five patients with APS-1 and assessed clinical, immunologic, histologic, transcriptional, and autoantibody responses. RESULTS: Patients with APS-1 had enhanced interferon-γ responses in blood and in all examined autoimmunity-affected tissues. Aire-/- mice had selectively increased interferon-γ production by T cells and enhanced interferon-γ, phosphorylated signal transducer and activator of transcription 1 (pSTAT1), and CXCL9 signals in multiple organs. Ifng ablation or ruxolitinib-induced JAK-STAT blockade in Aire-/- mice normalized interferon-γ responses and averted T-cell infiltration and damage in organs. Ruxolitinib treatment of five patients with APS-1 led to decreased levels of T-cell-derived interferon-γ, normalized interferon-γ and CXCL9 levels, and remission of alopecia, oral candidiasis, nail dystrophy, gastritis, enteritis, arthritis, Sjögren's-like syndrome, urticaria, and thyroiditis. No serious adverse effects from ruxolitinib were identified in these patients. CONCLUSIONS: Our findings indicate that APS-1, which is caused by AIRE deficiency, is characterized by excessive, multiorgan interferon-γ-mediated responses. JAK inhibition with ruxolitinib in five patients showed promising results. (Funded by the National Institute of Allergy and Infectious Diseases and others.).


Subject(s)
AIRE Protein , Interferon-gamma , Janus Kinase Inhibitors , Polyendocrinopathies, Autoimmune , Adult , Animals , Female , Humans , Male , Mice , AIRE Protein/deficiency , AIRE Protein/genetics , AIRE Protein/immunology , Autoantibodies/blood , Autoantibodies/immunology , Chemokine CXCL9/genetics , Interferon-gamma/genetics , Interferon-gamma/immunology , Janus Kinase Inhibitors/therapeutic use , Mice, Knockout , Nitriles/therapeutic use , Polyendocrinopathies, Autoimmune/genetics , Polyendocrinopathies, Autoimmune/drug therapy , Polyendocrinopathies, Autoimmune/immunology , Pyrazoles/therapeutic use , Pyrazoles/pharmacology , Pyrimidines/therapeutic use , T-Lymphocytes/immunology , Transcription Factors/genetics , Transcription Factors/immunology , Pilot Projects , Disease Models, Animal , Child , Adolescent , Middle Aged
2.
Pediatr Dermatol ; 41(3): 410-420, 2024.
Article in English | MEDLINE | ID: mdl-38413364

ABSTRACT

Unwanted hair is a common concern among patients presenting to pediatric dermatology clinics, and parents and patients alike inquire about the safety of methods employed for elective removal. Various methods of hair removal exist with different levels of invasiveness and permanence, from simple mechanical depilation to light-based therapies. All methods of hair removal appear to be safe and generally well tolerated in children, and there are no age restrictions to any modality. In this review, we aim to address the available literature on the safety and efficacy of hair removal modalities in pediatric patients and propose guidance on how to manage requests for at-home and in-office therapies within an ethical framework.


Subject(s)
Hair Removal , Humans , Child , Hair Removal/methods
3.
Clin Exp Dermatol ; 48(6): 623-630, 2023 Jun 05.
Article in English | MEDLINE | ID: mdl-36794376

ABSTRACT

BACKGROUND: In two severe congenital ichthyosis subtypes, autosomal recessive lamellar ichthyosis (ARCI-LI) and X-linked recessive ichthyosis (XLRI), cutaneous manifestations include widespread scaling. Approved topical treatment options are limited to emollients and keratolytics. AIM: This analysis from the randomized phase IIb CONTROL study assessed whether the efficacy and safety of TMB-001, a novel topical isotretinoin ointment formulation, differed between ARCI-LI and XLRI subtypes. METHODS: Participants ≥ 9 years with genetically confirmed XLRI or ARCI-LI and ≥ 2 (of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with ≥ 3 scaling score were randomized 1 : 1 : 1 to TMB-001 0.05%/TMB-001 0.1%/vehicle, twice daily for 12 weeks. The proportion of participants with ≥ 50% reduction vs. baseline in VIIS scaling (VIIS 50; primary endpoint) and ≥ 2-grade reduction in Investigator's Global Assessment (IGA)-scaling score vs. baseline (key secondary endpoint) were evaluated. Adverse events (AEs) were monitored. RESULTS: Among enrolled participants (TMB-001 0.05%, n = 11; 0.1%, n = 10; and vehicle, n = 12), 52% had ARCI-LI and 48% XLRI subtypes. Mean age was 33.6 and 35.4 years for participants with ARCI-LI and XLRI, respectively. Overall, 33%, 50% and 17% of participants with ARCI-LI and 100%, 33% and 75% of participants with XLRI achieved VIIS 50 in the TMB-001 0.05%, TMB-001 0.1% and vehicle groups, respectively (nominal P = 0.24 for 0.05% vs. vehicle, intent-to-treat population). Improvement of ≥ 2-grade IGA score was observed in 33%, 50% and 0% of participants with ARCI-LI and 83%, 33% and 25% of participants with XLRI in the TMB-001 0.05%, TMB-001 0.1% and vehicle groups, respectively (nominal P = 0.03 for 0.05% vs. vehicle, intention-to-treat population). Most AEs were application-site reactions. CONCLUSION: Regardless of congenital ichthyosis subtype, TMB-001 demonstrated greater proportions of participants achieving VIIS 50 and ≥ 2-grade IGA improvement vs. vehicle.


Subject(s)
Ichthyosiform Erythroderma, Congenital , Ichthyosis, Lamellar , Ichthyosis, X-Linked , Ichthyosis , Humans , Adult , Ichthyosis, Lamellar/drug therapy , Ichthyosis, Lamellar/genetics , Isotretinoin/therapeutic use , Immunoglobulin A
4.
Clin Exp Dermatol ; 48(7): 765-769, 2023 Jul 07.
Article in English | MEDLINE | ID: mdl-36928932

ABSTRACT

BACKGROUND: Emollients and keratolytics are frequently used to manage symptoms of congenital ichthyosis (CI). Systemic retinoid treatment is complicated by teratogenicity and dose-limiting adverse effects. OBJECTIVES: This analysis from the randomized Phase IIb CONTROL study investigated the characteristics of participants who responded to treatment with TMB-001, a novel topical isotretinoin ointment formulation. METHODS: Participants ≥ 9 years of age with genetically confirmed CI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with ≥ 3 scaling score were randomized 1 : 1 : 1 to TMB-001 0.05%, TMB-001 0.1% or vehicle, twice daily for 12 weeks. Efficacy endpoints included the proportion of participants with ≥ 50% reduction in VIIS-scaling (VIIS-50) compared with baseline and ≥ 2-grade reduction in Investigator's Global Assessment (IGA)-scaling score compared with baseline. Changes in body surface area (BSA) involvement, Dermatology Life Quality Index (DLQI) scores and Itch-Numeric Rating Scale (I-NRS) scores were assessed. RESULTS: Among the 33 participants (11 randomized to TMB-001 0.05%, 10 to TMB-001 0.1% and 12 to vehicle), median age was 29 years (range 9-80), and most were male (64%) and White (79%). Baseline demographics were generally similar among participants who did or did not achieve TMB-001 treatment success. Participants who had lower mean BSA involvement and higher DLQI and I-NRS scores at baseline were more likely to achieve VIIS-50. Similarly, higher baseline DLQI and I-NRS scores were associated with IGA response; BSA involvement was similar for IGA responders vs. nonresponders. CONCLUSIONS: Higher DLQI and I-NRS scores at baseline were associated with participants achieving treatment success by VIIS-50 and IGA response. Lower BSA involvement was associated with VIIS-50 success.


Subject(s)
Ichthyosis, Lamellar , Isotretinoin , Humans , Male , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Infant, Newborn , Female , Isotretinoin/adverse effects , Ichthyosis, Lamellar/drug therapy , Emollients , Treatment Outcome , Pruritus , Immunoglobulin A , Severity of Illness Index , Double-Blind Method
5.
Pediatr Dermatol ; 40(5): 857-859, 2023.
Article in English | MEDLINE | ID: mdl-37495514

ABSTRACT

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is an inherited disorder of immunity which leads to increased risk for mucocutaneous candidiasis and multiorgan autoimmune disease. While alopecia areata (AA) has been described in some patients with APECED, the extent and timing of AA is not well established and extent and timing of concomitant vitiligo and hypothyroidism has not been described. We evaluated an APECED cohort followed at the National Institutes of Health for the timing of development of associated diseases. We found AA occurred earlier in those with APECED than in the general population, was rarely the first sign of APECED, and the timing of AA onset did correlate with the timing of onset of vitiligo or hypothyroidism which also occurred at high rates and early age.


Subject(s)
Alopecia Areata , Hypothyroidism , Polyendocrinopathies, Autoimmune , Vitiligo , Humans , Polyendocrinopathies, Autoimmune/complications , Polyendocrinopathies, Autoimmune/epidemiology , Alopecia Areata/complications , Alopecia Areata/epidemiology , Alopecia Areata/diagnosis , Vitiligo/complications , Vitiligo/epidemiology , Hypothyroidism/complications , Hypothyroidism/epidemiology
6.
Pediatr Dermatol ; 40 Suppl 1: 4-7, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37088541

ABSTRACT

The 10th Pediatric Dermatology Research Alliance (PeDRA) Annual Conference occurred November 3-5, 2022 in Bethesda, Maryland. This conference was the first in-person PeDRA conference after 2 years of a virtual format due to COVID-19. Fittingly, given the effects of the pandemic, the conference theme was "Reimagining Community." The conference included presentations and panel sessions on finding individual and collective purpose, leveraging community in pursuit of a shared goal, and creating a community of resources in collaboration with NIH. The goal of this meeting was to connect clinicians, basic scientists, patients, patient advocates, and industry partners. The reimagined community of pediatric dermatology research is a synergistic space for all members to better understand, prevent, treat, and cure dermatologic diseases and conditions in children. This two-and-a-half-day conference with over 300 attendees featured educational seminars including a keynote address, didactic lecture and panel sessions, skill-building workshops, 13 topic-specific breakout sessions, and an interactive poster session where 108 active and finished research projects could be discussed.


Subject(s)
COVID-19 , Dermatology , Physicians , Child , Humans , Patients , Research
7.
Pediatr Dermatol ; 40(3): 422-427, 2023.
Article in English | MEDLINE | ID: mdl-36579717

ABSTRACT

BACKGROUND/OBJECTIVES: The primary objective was to assess pain catastrophizing and functional disability in pediatric patients with epidermolysis bullosa (EB) and their parents/guardians. Secondary objectives included examining relationships between pain catastrophizing, functional disability, and correlations with other factors (e.g., age, disease severity, and percent of body surface area (BSA) involved). METHODS: Patients with EB ages 8-16 and their parents/guardians who were English or Spanish speaking completed a one-time online survey. Parent measures included: demographics questionnaire, Pain Catastrophizing Scale-Parent (PCS), and Parent Functional Disability Inventory (FDI). Child measures included: PCS child and child FDI. Higher scores on both scales indicate higher levels of catastrophizing and functional disability. RESULTS: Of 31 children, the mean age was 11.47 years and the majority (70.97%) had dystrophic EB. Mean scores were: 35.84 = PCS parent; 34.58 = PCS child; 30.87 = parent FDI; 29.77 = child FDI. Total scores for PCS parent, parent FDI, and child FDI increased significantly with disease severity and percentage of involved BSA (p < .01 for all). Total scores for PCS child increased significantly with percent of EB skin involvement (p = .04) but not disease severity. Older children reported more functional disability than their parents and younger children (p = .02). CONCLUSIONS: Our results demonstrate significant positive correlations between negative thoughts related to pain and the experience of functional difficulties in patients with EB and their caregivers. Psychological, psychiatric, and/or behavioral interventions to help managing chronic pain may be effective for patients with EB.


Subject(s)
Chronic Pain , Epidermolysis Bullosa , Child , Humans , Adolescent , Parents/psychology , Surveys and Questionnaires , Epidermolysis Bullosa/complications , Catastrophization/psychology
8.
Pediatr Dermatol ; 40(5): 789-808, 2023.
Article in English | MEDLINE | ID: mdl-37316462

ABSTRACT

Methotrexate (MTX) is a readily accessible drug, first used in 1948 and employed for a wide variety of indications since then. However, despite widespread off-label use, FDA labeling does not include approved indications for the use of MTX for many inflammatory skin diseases in pediatric patients, including morphea, psoriasis, atopic dermatitis, and alopecia areata, among others. Without published treatment guidelines, some clinicians may be hesitant to use MTX off-label, or uncomfortable prescribing MTX in this population. To address this unmet need, an expert consensus committee was convened to develop evidence- and consensus-based guidelines for use of MTX to treat pediatric inflammatory skin disease. Clinicians with experience and expertise in clinical research, drug development, and treating inflammatory skin disease in pediatric patients with MTX were recruited. Five committees were created based on major topic areas: (1) indications and contraindications, (2) dosing, (3) interactions with immunizations and medications, (4) adverse effects (potential for and management of), and (5) monitoring needs. Pertinent questions were generated and addressed by the relevant committee. The entire group participated in a modified Delphi process to establish agreement on recommendations for each question. The committee developed 46 evidence- and consensus-based recommendations, each with >70% agreement among members, across all five topics. These are presented in tables and text, along with a discussion of supporting literature, and level of evidence. These evidence- and consensus-based recommendations will support safe and effective use of MTX for the underserved population of pediatric patients who may benefit from this valuable, time-honored medication.


Subject(s)
Dermatitis, Atopic , Psoriasis , Humans , Child , Methotrexate , Consensus , Psoriasis/drug therapy , Dermatitis, Atopic/drug therapy
9.
J Am Acad Dermatol ; 86(5): 1063-1071, 2022 05.
Article in English | MEDLINE | ID: mdl-34634382

ABSTRACT

BACKGROUND: Accurate diagnosis of epidermolysis bullosa (EB) has significant implications for prognosis, management, and genetic counseling. OBJECTIVE: To describe diagnostic testing patterns and assess diagnostic concordance of transmission electron microscopy (TEM), immunofluorescence mapping (IFM), and genetic analysis for EB. METHODS: A retrospective cohort included patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database from January 1, 2004, to July 8, 2019. Tests concluding the same EB type (EB simplex, junctional EB, dominant dystrophic EB, and recessive dystrophic EB) were considered concordant; those concluding different EB types were considered discordant; and those with nonspecific/nondefinitive results were equivocal. RESULTS: A total of 970 diagnostic tests were conducted from 1984 to 2018 in 771 patients. Genetic analyses were performed chronologically later than IFM or TEM (P < .001). The likelihood of undergoing genetic analysis was greater for junctional EB and recessive dystrophic EB, and the same for dominant dystrophic EB as compared with EB simplex. TEM results in 163 patients were equivocal (55%), concordant (42%), and discordant (3%). IFM results in 185 patients were equivocal (54%), concordant (42%), and discordant (4%). LIMITATIONS: Retrospective design. CONCLUSIONS: Diagnostic testing has shifted in favor of genetic analysis. TEM and IFM frequently offer equivocal findings when compared to the specificity afforded by genetic analysis.


Subject(s)
Epidermolysis Bullosa Dystrophica , Epidermolysis Bullosa Simplex , Epidermolysis Bullosa, Junctional , Epidermolysis Bullosa , Epidermolysis Bullosa/diagnosis , Epidermolysis Bullosa/genetics , Epidermolysis Bullosa Dystrophica/diagnosis , Epidermolysis Bullosa Simplex/diagnosis , Fluorescent Antibody Technique , Humans , North America , Retrospective Studies
10.
J Am Acad Dermatol ; 86(2): 359-364, 2022 02.
Article in English | MEDLINE | ID: mdl-34474079

ABSTRACT

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


Subject(s)
Alopecia Areata , Alopecia , Alopecia Areata/diagnosis , Alopecia Areata/drug therapy , Consensus , Humans , Severity of Illness Index
11.
Pediatr Dermatol ; 39(3): 491-493, 2022 May.
Article in English | MEDLINE | ID: mdl-35229889

ABSTRACT

We report the case of a 2-year-old boy with mosaic trisomy 13 and immunodeficiency who developed severe hidradenitis suppurativa beginning at the age of 18 months. Unresponsive to standard therapies, he exhibited a partial response to immunoglobulin replacement therapy.


Subject(s)
Chromosomes, Human, Pair 13 , Hidradenitis Suppurativa/complications , Trisomy 13 Syndrome/diagnosis , Trisomy , Child, Preschool , Hidradenitis Suppurativa/diagnosis , Hidradenitis Suppurativa/genetics , Hidradenitis Suppurativa/therapy , Humans , Immunoglobulins/administration & dosage , Immunologic Deficiency Syndromes/genetics , Immunologic Deficiency Syndromes/therapy , Male , Trisomy 13 Syndrome/complications
12.
Am J Med Genet A ; 185(4): 1159-1167, 2021 04.
Article in English | MEDLINE | ID: mdl-33502802

ABSTRACT

Genodermatoses are inherited disorders with skin manifestations and can present with multisystem involvement, resulting in challenges in diagnosis and treatment. To address this, the expertise of dermatology and clinical genetics through a multidisciplinary clinic (Genodermatoses Clinic) were combined. A retrospective cohort study of 45 children seen between March 2018 and February 2019 in the Genodermatoses Clinic at The Children's Hospital of Philadelphia was performed. Patient demographics, referral information, genetic testing modality, diagnoses, and patient satisfaction scores were evaluated to assess the clinic's impact. The majority of patients (42.2%) were referred from Dermatology and 86.7% were referred for diagnosis. Two-thirds of the patients were recommended genetic testing, and subsequently 73.3% completed testing. Nearly three-quarters, 26 out of 36 patients (72.2%), of our undiagnosed patients received a clinical and/or molecular diagnosis, which is imperative in managing their care. Twenty-two individuals pursued genetic testing. In eight individuals (36%), molecular testing was diagnostic. However, in two individuals the molecular diagnosis did not completely explain the phenotype. However, there are still obstacles to genetic testing, such as cost of testing and insurance barriers. Almost all (91.4%) rated the Genodermatoses Clinic as "Very Good," the top Press Ganey score. High patient satisfaction scores suggest a positive impact of the Genodermatoses clinic, emphasizing the importance to increase support for the clinical and administrative time needed for patients with genodermatoses.


Subject(s)
Genetic Diseases, Inborn/genetics , Genetic Testing , Skin Diseases/genetics , Adolescent , Ambulatory Care Facilities , Child , Child, Preschool , Female , Genetic Counseling , Genetic Diseases, Inborn/diagnosis , Genetic Diseases, Inborn/pathology , Genotype , Humans , Infant , Male , Phenotype , Skin Diseases/diagnosis , Skin Diseases/pathology
13.
Curr Opin Pediatr ; 33(4): 416-422, 2021 08 01.
Article in English | MEDLINE | ID: mdl-34016809

ABSTRACT

PURPOSE OF REVIEW: The current review will address the different causes of localized hair loss in infancy. The data presented here will provide clinicians with the latest understanding of different disorders leading to localized hair loss and will provide recommendations for further management of infants who present with alopecia. RECENT FINDINGS: Localized hair loss in infancy is common, but its underlying causes vary greatly. Alopecia in infants can be categorized into congenital, genetic, inflammatory, mechanical, and physiologic causes. Decisions regarding further management are complex, as they often involve not only cosmetic concerns, but also work-up of possible systemic medical issues related to hair loss. SUMMARY: Clinicians must be able to distinguish between the different causes of infantile hair loss so that appropriate work-up and further management can be pursued. Factors such as physical appearance, timing of presentation, dermoscopic exam, histopathology, and associated systemic features can help lead clinicians to the correct diagnosis in the case of an infant with localized alopecia.


Subject(s)
Alopecia , Alopecia/etiology , Alopecia/genetics , Humans , Infant
14.
J Cutan Pathol ; 48(3): 390-395, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33063358

ABSTRACT

Basal cell nevus syndrome (BCNS) is an autosomal dominant condition caused most often by a loss-of-function mutation in the Patched-1 (PTCH1) gene. It is characterized by the development of varied benign and malignant tumors, including numerous cutaneous basal cell carcinomas (BCCs). The PTCH1 gene is integral in hair follicle development and loss of function mutation may lead to BCCs with an infundibulocystic histopathology in BCNS patients. Few studies have described the histopathological features of BCCs in BCNS. The recognition of these histopathologic features by dermatologists, dermatopathologists, and others caring for children will allow earlier and more effective identification of BCNS. We performed a retrospective analysis of 25 BCCs in 11 patients aged 5 to 19 years with BCNS and evaluated the histopathologic features on hematoxylin-eosin-stained sections. Our study found that 80% of BCCs in BCNS patients occurred on the head and neck with 64% of the specimens demonstrating infundibulocystic differentiation. Infundibulocystic differentiation is a common finding in BCCs found in BCNS. The finding of cutaneous neoplasms consistent with BCC with infundibulocystic differentiation in children is common in pediatric patients with BCNS and can be considered to be an early marker of the disorder, prompting further clinical investigation.


Subject(s)
Basal Cell Nevus Syndrome/complications , Carcinoma, Basal Cell/diagnosis , Skin Neoplasms/pathology , Adolescent , Basal Cell Nevus Syndrome/genetics , Carcinoma, Basal Cell/genetics , Carcinoma, Basal Cell/pathology , Cell Differentiation/genetics , Child , Child, Preschool , Early Diagnosis , Female , Humans , Male , Patched-1 Receptor/genetics , Retrospective Studies , Young Adult
15.
Pediatr Dermatol ; 38 Suppl 2: 58-64, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34250638

ABSTRACT

Sexual and gender minority individuals, including transgender and gender diverse people, are an underserved and vulnerable population in the field of dermatology. While the unique dermatologic needs for adult patients in this group are increasingly documented, the knowledge surrounding pediatric and adolescent transgender/gender diverse patients is lacking. We aim to summarize the unique dermatologic needs of transgender/gender diverse patients, with particular attention paid to the data available in younger groups. This review highlights the unique role pediatric dermatologists can play in the care of transgender and gender diverse youth including but not limited to treating acne and hair pattern changes as well as being knowledgeable about surgical and other cosmetic options for gender affirmation. It also highlights areas for potential future research including dermatologic effects of hormone therapy in children as well as treatments for those side effects.


Subject(s)
Acne Vulgaris , Sexual and Gender Minorities , Transgender Persons , Acne Vulgaris/drug therapy , Adolescent , Adult , Child , Gender Identity , Hair , Humans
16.
Pediatr Dermatol ; 38(5): 1178-1184, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34515353

ABSTRACT

BACKGROUND/OBJECTIVE: Dupilumab is highly effective in treating atopic dermatitis (AD). However, some patients experience difficulties with dupilumab therapy, such as inadequate clinical response, failure to achieve long-term disease control, or adverse events (AEs). Our objective is to assess inadequate response and AEs occurring in children on dupilumab therapy for AD. METHODS: This is a retrospective cohort study of children on dupilumab for AD. Collected variables included patient demographics, medical histories, and dupilumab therapy characteristics. Response analysis was conducted in those with ≥3 months of dupilumab therapy: primary poor responders were defined as those whose EASI scores did not decrease by >50%, and secondary poor responders were those who initially responded but had significant AD flares while on therapy. RESULTS: We included 200 patients on dupilumab for AD in our cohort; 192 received ≥3 months of therapy and were included in our response analysis. Twelve children experienced inadequate primary response, and 4 were secondary poor responders. Four of these 16 children discontinued therapy due to inadequate response. The most common dupilumab-associated AEs were facial erythema (n = 24, 12.0%) and injection-site reactions (n = 24, 12.0%). Female sex was significantly associated with experiencing injection-site reactions, and prior hospitalization was significantly associated with HSV infection on dupilumab. Eight patients discontinued therapy due to an AE. CONCLUSION: A small but significant number of patients experienced treatment difficulties while on dupilumab. The risk of inadequate response to dupilumab and dupilumab-associated AEs should be discussed thoroughly with patients and their families prior to initiation.


Subject(s)
Dermatitis, Atopic , Antibodies, Monoclonal, Humanized , Child , Dermatitis, Atopic/drug therapy , Female , Humans , Retrospective Studies , Severity of Illness Index , Tertiary Healthcare , Treatment Outcome
17.
Pediatr Dermatol ; 38(6): 1515-1522, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34647357

ABSTRACT

BACKGROUND/OBJECTIVES: Recruitment has been identified as a key barrier to conducting pediatric trials. However, no current guidelines have been used for evidence-based strategies to optimize the recruitment of children. In this review, we identify and codify strategies to enhance pediatric clinical trial participation in the current literature for future study in implementation trials. METHODS: Searches were conducted in MEDLINE/PubMed, EMBASE, and Web of Science. Studies were included if they focused on improving recruitment of children <18 years of age into clinical trials and were published prior to December 1, 2020. Data extracted included information on study design, recruitment population, key recruitment strategy recommendations, and motivators and barriers of trial participation. RESULTS: Out of the 80 included studies, strategies proposed to increase pediatric clinical trial participation were extremely varied in terms of strategy type and level of evidence. None of these studies were pediatric dermatology specific. We categorized strategies into the following groups: protocol development/pre-trial planning, trial marketing, educational tools, communication strategies, community involvement, incentives, or structural changes. CONCLUSIONS: We identified and codified strategies reported in the literature for increasing pediatric recruitment and found that few are evidence-based. Investigators should consider incorporating strategies to enhance recruitment in each stage of clinical trial conduct and tailor recruitment techniques to the specific population of interest. While some strategies should be employed broadly, others could benefit from further study in implementation trials to determine their comparative effectiveness in recruiting different groups of children.


Subject(s)
Clinical Trials as Topic , Patient Participation , Child , Humans
18.
Pediatr Dermatol ; 38(2): 390-394, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33426747

ABSTRACT

BACKGROUND/OBJECTIVES: Head and neck dermatitis after dupilumab therapy for atopic dermatitis has been frequently reported in adults and only rarely in adolescents. No cases detailing disease course and treatment response have previously been described in adolescents. METHODS/RESULTS: This case series presents five adolescent patients who developed new-onset or worsening head and neck dermatitis after dupilumab therapy for atopic dermatitis. All five patients improved after oral antifungal therapy. CONCLUSIONS: The clinical features, treatment response, and potential disease pathogenesis in pediatric patients are described. Adolescents with new-onset head and neck dermatitis after dupilumab therapy may clinically improve with antifungal therapy, suggesting that Malassezia species may be a contributing factor or antifungal therapy may be an effective antiinflammatory agent.


Subject(s)
Dermatitis, Atopic , Eczema , Adolescent , Adult , Antibodies, Monoclonal, Humanized , Child , Dermatitis, Atopic/drug therapy , Head , Humans
19.
Pediatr Dermatol ; 38(1): 137-142, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33230835

ABSTRACT

BACKGROUND/OBJECTIVES: Patients with rare diseases are challenged when it comes to finding physicians with expertise in their condition. The Foundation for Ichthyosis and Related Skin Types (FIRST) Tele-Ichthyosis program has provided telemedicine for patients and their families with keratinizing disorders since 2009. This study aims to characterize a decade of experience with the program. METHODS: This retrospective cohort study analyzed cases for demographics of patients and the clinicians who submitted their cases, nature of questions asked, number of expert responses, and characteristics of responses. Surveys were sent electronically to all users of the FIRST Tele-Ichthyosis service to assess experiences with the service and solicit constructive recommendations. Descriptive statistics were performed on the case review and responder surveys. RESULTS: Eighty-eight geographically diverse cases were reviewed showing increased use over time by various specialists for patients of all ages. Sixty-six percent of cases were definitively ichthyosis, and most submitters queried on diagnosis (47%) or treatment (72%). Most submitters described the service as easy to use (66.6%) and advice as timely (61.1%), clear (66.6%), and beneficial (61.1%). All submitters made suggestions for improvement (100%). Experts predominately worked with pediatric populations (70%) and reported self-motivation to volunteer and improve patients' lives (100%). Experts found technological barriers minor and provided feedback to enhance the service. CONCLUSIONS: This report highlights how a rare-disease patient advocacy group successfully supports physician collaboration and patient outcomes through secure and efficient telemedicine. Lessons learned are highly relevant in the current healthcare environment.


Subject(s)
Ichthyosis , Physicians , Telemedicine , Child , Humans , Patient Advocacy , Retrospective Studies
20.
Pediatr Dermatol ; 38 Suppl 2: 90-95, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34418155

ABSTRACT

BACKGROUND: Deficiencies in the skills necessary to diagnose and manage patients with skin of color may contribute to health disparities. The Pediatric Dermatology Research Alliance Special Interest Group in Pediatric Skin of Color (PSOCG) convened to generate a curriculum of topics required for basic pediatric skin of color (PSOC) education for medical students and residents in dermatology to improve the quality of education in PSOC. METHODS: A survey was distributed to the PSOCG members to assess expert opinion regarding critical topics for inclusion in a basic PSOC syllabus. Video conference and two rounds of survey were used to rank topics for inclusion and to highlight the underlying need for inclusion. RESULTS: Group members composed of academic pediatric dermatologists with teaching responsibilities including skin of color topics for dermatology residents and medical students. Learning objectives were developed for an educational lecture on basic science, and clinical conditions affecting PSOC were grouped by age-infantile, pediatric, and adolescent skin conditions affecting the PSOC population were identified for inclusion with rank score based on specific parameters including greater frequency in skin of color, nuances in skin of color, and need for medical workup. CONCLUSIONS: Increased focus on PSOC education is needed to improve quality of care for children of color through enhanced knowledge. Inflammatory, genetic, and particularly primary pigmentary disorders should be the focus of a broad curriculum in pediatric skin of color education for medical trainees. Objectives should include improved diagnosis, treatment, and ability to educate patients and their families regarding the nature of their conditions.


Subject(s)
Dermatology , Internship and Residency , Adolescent , Child , Curriculum , Dermatology/education , Humans , Public Opinion , Skin Pigmentation
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