Cutaneous reactions in children treated with MEK inhibitors, BRAF inhibitors, or combination therapy: A multicenter study.

BACKGROUND: Treatment with BRAF inhibitors (BRAFI) and MEK inhibitors (MEKI) causes cutaneous reactions in children, limiting dosing or resulting in treatment cessation. The spectrum and severity of these reactions is not defined. OBJECTIVE: To determine the frequency and spectrum of cutaneous reactions in children receiving BRAFI and MEKI and their effects on continued therapy. METHODS: A multicenter, retrospective study was conducted at 11 clinical sites in the United States and Canada enrolling 99 children treated with BRAFI and/or MEKI for any indication from January 1, 2012, to January 1, 2018. RESULTS: All children in this study had a cutaneous reaction; most had multiple, with a mean per patient of 3.5 reactions on BRAFI, 3.7 on MEKI, and 3.4 on combination BRAFI/MEKI. Three patients discontinued treatment because of a cutaneous reaction. Treatment was altered in 27% of patients on BRAFI, 39.5% on MEKI, and 33% on combination therapy. The cutaneous reactions most likely to alter treatment were dermatitis, panniculitis, and keratosis pilaris-like reactions for BRAFI and dermatitis, acneiform eruptions, and paronychia for MEKI. CONCLUSIONS: Cutaneous reactions are common in children receiving BRAFI and MEKI, and many result in alterations or interruptions in oncologic therapy. Implementing preventative strategies at the start of therapy may minimize cutaneous reactions.

Henoch Schonlein purpura in pediatric patients with inflammatory bowel disease: A case series.

Retrospective chart review was conducted to identify the clinical features of Henoch Schonlein purpura (HSP) in five children with inflammatory bowel disease (IBD). All five children, four of which were on anti-TNF therapies, experienced the onset of HSP after their IBD diagnosis. HSP averaged 20.8 months in duration. The patients in our cohort, particularly those on anti-TNF therapy for inflammatory bowel disease, experienced chronic and recurrent courses of HSP.

THE demographics and trends in pediatric melanoma in the United States: An analysis of the National Cancer Database.

BACKGROUND/OBJECTIVE: Relative to adults, rates of melanoma are lower in children. Due to its rarity, it is difficult to assess the incidence, trends, and outcomes of this malignancy. Much of our understanding comes from single institution or regional cancer registries which may not be large enough to detect subtleties in the burden of pediatric melanoma. METHODS: Data from the 2004 to 2016 National Cancer Database were analyzed; this database captures approximately 70% of all cancer diagnoses in the United States. RESULTS: Our analysis consisted of 1903 cases. A majority were White (89.8%), the mean age was 12.4 years, and the ratio of females: males was 1.2:1.0. The most common anatomic location was the trunk (31.1%). Between 2004 and 2016, a decreasing trend in the number of new melanoma cases was observed. Comparing histologic subtype by age, there was an increased percentage of nodular and epithelioid and spindle cell tumors in the pre-teen children and a greater percentage of superficial spreading tumors in teenagers. Overall, a majority of cases were stage 0 or I (56.9%), with relatively few stage IV cases (2.0%). A 5-year all-cause survival of greater than 90% was observed for stage I-III tumors, with stage IV tumors having a 5-year all-cause survival of 34.4%. CONCLUSION: Comparable to previous studies, pediatric melanoma occurred most often in Whites, females, and adolescents. However, we detected a decreasing trend in new cases, noted differences between histologic subtype and age, and observed a 5-year all-cause survival rate of greater than 90% for stage I-III tumors.

Restrictive dermopathy: Three new patients with ZMPSTE24 mutations and a review of the literature.

Restrictive dermopathy (RD) is a rare and lethal laminopathy caused by mutations in LMNA or ZMPSTE24. This series reports 3 patients with RD and reviews the literature of the 113 previously reported cases, including highlights of the unique constellation of clinical findings in RD, as well as histologic, radiographic, and genetic features. Early recognition of these characteristic features is vital to establish a prompt diagnosis and provide adequate family counseling for this terminal condition.

Use of telemedicine for ichthyosis: Patient advocacy group as conduit to expert physician advice.

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.

More than keratitis, ichthyosis, and deafness: Multisystem effects of lethal GJB2 mutations.

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

Pine tar callus: A mimicker of a melanocytic lesion.

We report a case of acral pigmented lesions due to pine tar, a common compound used on baseball bats to improve grip, deposition. The patient presented with an acute concern for a new melanocytic lesion, and dermoscopy revealed large brown globules, not typical of melanocytic neoplasms. We propose that the coupling of dermoscopy and a thorough clinical history of exogenous exposures in similar clinical presentations can provide reassurance in evaluating atypical appearing pigmented lesions.

Epidermal programmed cell death-ligand 1 expression in TEN associated with nivolumab therapy.

Nivolumab is a programmed cell death receptor-1 (PD-1) antibody used in the treatment of metastatic or unresectable melanoma. Cutaneous reactions are the most common adverse events reported with these agents and are rarely severe or life-threatening. Here we present a case report describing the clinicopathological findings of a patient with a fatal toxic epidermal necrolysis (TEN) eruption associated with use of nivolumab for treatment of metastatic melanoma. The patient developed a pruritic, morbiliform eruption, which slowly progressed over 3 months to a tender, exfoliative dermatosis. Histology initially showed interface dermatitis and subsequently revealed full thickness epidermal necrosis. The diagnosis of TEN was made. From initial biopsy to TEN presentation, there was an increase in the number of CD8+ lymphocytes within the dermal-epidermal junction and an increase of programmed death ligand 1 (PD-L1) expression in both lymphocytes and keratinocytes. Despite treatment with infliximab, high-dose steroids and intravenous immunoglobulin, the patient expired. Herein we describe what we believe is the second case of TEN associated with anti-PD1 therapy reported in the literature. Increased expression of PD-L1 by immunohistochemistry was observed as the eruption progressed to TEN. Early diagnosis and treatment is necessary in these fatal TEN reactions secondary to the anti-PD-1 antibody therapies.

An Atopic Dermatitis Management Algorithm for Primary Care Providers and Assessment of Its Usefulness as a Clinical Tool.

BACKGROUND/OBJECTIVES: There is a lack of primary care provider (PCP) understanding of atopic dermatitis (AD) treatments and topical steroid use. We designed an AD management algorithm for pediatric PCPs. We hypothesized that the algorithm would improve pediatric PCPs' knowledge of AD diagnosis and management. METHODS: Pediatric primary care resident and attending physicians at three residency programs were invited to participate in an electronic AD algorithm survey that contained demographic and 19 knowledge-based questions. Participants were randomized to intervention and control groups, with the intervention group receiving a short lecture and copy of our algorithm to use in an inpatient or outpatient setting for 2 months. Changes in scores between preintervention and postintervention surveys were compared. RESULTS: Of the 54 participants, those in the intervention group (n = 26) performed significantly better than those in the control group (n = 28) after controlling for pretest scores (ß = 1.19 [95% confidence interval 0.07, 2.32], p = 0.04). The intervention group had a higher average score on the posttest knowledge questions (71% correct) than the control group (65% correct) (p = 0.06). The majority of physicians who received the algorithm agreed or strongly agreed that they liked using the algorithm. CONCLUSION: The use of a management algorithm improved physician knowledge about the diagnosis and treatment of AD and was well accepted by physicians. Use of this management algorithm may lead to better recognition and management of AD, particularly earlier recognition of and therapy for superinfection, improving treatment outcomes and quality of life for patients and families.

Stigmatization and Mental Health Impact of Chronic Pediatric Skin Disorders.

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.

Introduction to the medical professions through an innovative medical student-run pipeline program.

Underrepresented minorities (URMs) make up a disproportionately small percentage of medical school applicants, matriculants, and physicians relative to the general US population. Preprofessional pipeline programs may help introduce URMs to careers in the medical field. MiniMeds was developed as a paracurricular enrichment program that targeted URM students. The curriculum was designed and administered by medical students, and 2 trials of this program were conducted. Data were collected pre and post program through a survey that assessed knowledge of medical concepts and knowledge of and interest in careers in medicine. Attendance at program sessions correlated with baseline knowledge about medical professions. Knowledge about medical concepts increased significantly from baseline to follow-up for boys, a group significantly represented by URMs in our cohort. Median scores for knowledge of medical careers increased significantly from baseline to followup for URMs as well as for boys and girls. Preprofessional pipeline programs such as MiniMeds are able to engage and develop medical knowledge in URM students at a critical developmental age. Further evaluation and implementation of programs that incorporate medical students to actively develop and lead pipeline programs are warranted.

Stevens-Johnson syndrome/toxic epidermal necrolysis associated with zonisamide.

This report highlights zonisamide as a potential cause of serious cutaneous reactions as well as its cross-reactivity with other sulfonamides. Here, we present a case of SJS-TEN due to zonisamide, which was effectively treated with IVIg. Subsequently, the patient was transitioned to levetiracetam for seizure control.

Influenza virus infection mimicking an acute abdomen in a female adolescent.

We report an adolescent with respiratory symptoms admitted for clinical signs of an acute abdomen. The only diagnostic finding was influenza A viral RNA detected in an upper respiratory tract specimen. Influenza should be considered in the differential diagnosis of children with respiratory illness and abdominal pain during influenza season.

Perceived barriers to care and attitudes towards shared decision-making among low socioeconomic status parents: role of health literacy.

OBJECTIVE: Although low parent health literacy (HL) has been linked to poor child health outcomes, it is not known whether differences in perceptions related to access to care and provider-parent partnership in care are potential contributing factors. We sought to assess whether parent HL is associated with differences in perceived barriers to care and attitudes regarding participatory decision-making with the provider. METHODS: This was a cross-sectional analysis of data collected from parents presenting with their child to an urban public hospital pediatric clinic in New York City. Dependent variables were caregiver-reported barriers to care (ability to reach provider at night/on weekends, difficult travel to clinic) and attitudes towards participatory decision-making (feeling like a partner, relying on doctor's knowledge, leaving decisions up to the doctor, being given choices/asked opinion). The primary independent variable was caregiver HL (Short Test of Functional Health Literacy in Adults [S-TOHFLA]). RESULTS: A total of 823 parents were assessed; 1 in 4 (27.0%) categorized as having low HL. Parents with low HL were more likely to report barriers to care than those with adequate HL: trouble reaching provider nights/weekends, 64.9% vs. 49.6%, (p < 0.001, adjusted odds ratio [AOR] 1.7, 95% confidence interval [95% CI] 1.2-2.4); difficult travel, 15.3% vs. 8.0%, (p = 0.004, AOR 1.8, 95% CI 1.1-3.0). Low HL was also associated with not feeling like a partner (28.8% vs. 17.1%; AOR 2.0; 95% CI 1.4-3.0), preference for relying on the doctor's knowledge (68.9% vs. 52.2%; AOR 1.7; 95% CI 1.2-2.4), and preference for leaving decisions up to the doctor (57.7% vs. 33.3%; AOR 2.2; 95% CI 1.6-3.1). CONCLUSIONS: Addressing issues of parent HL may be helpful in ameliorating barriers to care and promoting provider-parent partnership in care.

Health literacy assessment of labeling of pediatric nonprescription medications: examination of characteristics that may impair parent understanding.

OBJECTIVE: Poor quality and variability of medication labeling have been cited as key contributors to medication misuse. We assessed the format and content of labels and materials packaged with common pediatric liquid nonprescription medications. METHODS: Descriptive study. A total of 200 top-selling pediatric oral liquid nonprescription medications (during the 52 weeks ending October 30, 2009) categorized as analgesic, cough/cold, allergy, and gastrointestinal products, with dosing information for children <12 years (representing 99% of U.S. market for these products) were reviewed. The principal display panel (PDP) and FDA Drug Facts panel (side panel) of each bottle, and associated box, if present, were independently examined by 2 abstractors. Outcome measures were content and format of active ingredient information and dosing instructions of the principal display panel and Drug Facts panel. RESULTS: Although almost all products listed active ingredients on the Drug Facts panel (side panel), nearly 1 in 5 (37 [18.5%]) did not list active ingredients on the PDP. When present, mean (SD) font size for PDP active ingredients was 10.7 (5.0), smaller than product brand name (32.1 [15.0]) and flavor (13.1 [4.8]); P < .001. Most products included directions in chart form (bottle: 167 [83.5%], box: 148 [96.1%], P < .001); mean (SD) font size: 5.5 (0.9; bottle), 6.5 (0.5; box), P < .001. Few products expressed dosing instructions in pictographic form: 4 (2.6%) boxes and 0 bottles. Nearly all products included the Food and Drug Administration-mandated sections. CONCLUSIONS: The format and content of labels for nonprescription pediatric liquid medications could be improved to facilitate parent understanding of key medication information, including active ingredient information and dosing instructions.