A gain-of-function variant in SREBF1 causes generalized skin hyperpigmentation with congenital cataracts.

BACKGROUND: Lipid metabolism plays essential roles in skin barrier formation and the regulation of skin inflammation. Moreover, lipid homeostasis regulates skin melanogenesis, although the underlying mechanism remains largely unknown. Sterol regulatory element binding protein 1 (SREBP-1) is a key transcription factor essential for cellular lipid metabolism. Loss-of-function variants in SREBF1 are responsible for autosomal-dominant ichthyosis follicularis, alopecia, and photophobia syndrome, emphasizing the significance of lipid homeostasis in skin keratinization. OBJECTIVES: To identify the genetic basis of a new entity featuring diffuse skin hyperpigmentation with congenital cataracts, and to unravel the underlying mechanism for the pathogenesis of the SREBF1 variant. METHODS: Whole-exome sequencing was performed to identify the underlying genetic variants. Quantitative PCR, western blot, and immunofluorescent staining were employed to assess the expression and the subcellular localization of the SREBF1 variant. The transcriptional activity of the mutant SREBP-1 was determined by luciferase reporter assay. A transgenic zebrafish model was constructed. RESULTS: Two patients of different ethnicities presented with generalized skin hyperpigmentation with skin xerosis, congenital cataracts, and extracutaneous symptoms. We identified a de novo nonsense variant c.1289C>A (p.Ser430*) in the SREBF1 gene in both patients. The variant encoded a truncated protein which showed preferential nucleus localization, in contrast to wild-type SREBP-1 which is mainly localized in cytoplasm in sterol-sufficient conditions. Luciferase reporter assay revealed that the Ser430* mutant exhibited an enhanced transcriptional activity. The primary cultured melanocytes from the patient showed increased melanin synthesis compared to those from normal controls. The Ser430* transgenic zebrafish model exhibited more black spots, along with upregulated expression of melanogenic genes at 35 days post-fertilization. CONCLUSIONS: We demonstrated that a gain-of-function variant in SREBF1 caused a previously undescribed disorder characterized by generalized skin hyperpigmentation and congenital cataracts. Our study reveals the involvement of SREBP-1 in melanogenesis and lens development and paves the way for developing novel therapeutic targets for skin dyspigmentation or cataracts.

Appearance Dissatisfaction and Body Dysmorphic Disorder in the Dermatology Patient.

Dermatologists routinely see patients with inflammatory skin conditions and aesthetic concerns that involve substantial psychological comorbidity. However, most dermatologists do not receive formal training in this area, and many are unsure how to best help treat certain patients holistically. Body dysmorphic disorder (BDD) is a common and distressing psychiatric condition that disproportionately impacts dermatology patients, including patients living with chronic inflammatory skin conditions such as acne and atopic dermatitis. BDD is characterized by preoccupation with nonexistent or minimally noticeable flaws in physical appearance that cause clinically significant distress or impairment in functioning. Adolescent populations may be particularly vulnerable to clinically significant body image dissatisfaction, including BDD, due to the high prevalence of acne and the pervasive role of social media platforms. The rise of social media may exacerbate body image issues through repetitive exposure to idealized and often unrealistic beauty standards. Though screening questionnaires can assist dermatologists in recognizing BDD, dermatologists must collaborate with mental health providers to provide comprehensive care to vulnerable patients, including adolescents.J Drugs Dermatol. 2024;23(7):545-550.  doi:10.36849/JDD.8156.

Neutrophilic dermatosis in a patient with an IKZF1 variant and a review of monogenic autoinflammatory disorders presenting with neutrophilic dermatoses.

Monogenic diseases of immune dysregulation should be considered in the evaluation of children presenting with recurrent neutrophilic dermatoses in association with systemic signs of inflammation, autoimmune disease, hematologic abnormalities, and opportunistic or recurrent infections. We report the case of a 2-year-old boy presenting with a neutrophilic dermatosis, found to have a novel likely pathogenic germline variant of the IKAROS Family Zinc Finger 1 (IKZF1) gene; the mutation likely results in a loss of function dimerization defective protein based on reports and studies of similar variants. IKZF1 variants could potentially lead to aberrant neutrophil chemotaxis and development of neutrophilic dermatoses. Long-term surveillance is required to monitor the development of hematologic malignancy, autoimmunity, immunodeficiency, and infection in patients with pathogenic IKZF1 germline variants.

Pediatric consultative dermatology: A survey of the Society for Pediatric Dermatology workforce reveals shortcomings in existing practice models of pediatric dermatology consult services in the United States.

The rate of pediatric hospitalization for cutaneous pathology has been increasing in recent years, often requiring the expertise of consulting pediatric dermatologists; however, the infrastructure of inpatient pediatric dermatology consultative services remains poorly characterized. We sought to assess the structure, consult volume, physician compensation, and utilization of teledermatology in pediatric dermatology inpatient services to better understand the current care model. Our survey of 118 pediatric dermatologists revealed that 89% of respondents see between 1 and 10 new consults per week, 39% perform all inpatient consults including evening and weekends without assistance from other providers, 71% do not have protected time during the week to provide inpatient consultations, and only 10% receive financial compensation via stipend. By highlighting both the high demand for pediatric consultative dermatology as well as the significant burden placed on these providers by existing practice models, we hope to encourage a reappraisal of the current infrastructure of pediatric inpatient dermatology to increase structural and financial support for this vital service.

Knotted lanugo in a newborn: Cultural practices revealed.

Across the world, there are varied cultural practices applied in the newborn period that pediatric dermatologists need to be familiar with. This report details a 9-day-old girl who presented with black, spike-like hairs across the back after her mother had been rubbing breast milk on her back in a circular motion for the first 7 days of life. On dermatoscopic exam, these lesions were found to be tight bundles of lanugo hairs, consistent with a diagnosis of knotted lanugo. Improved understanding of cultural practices and newborn skin care routines is critical for diagnosis, treatment, and counseling.

Poliosis, hair pigment dilution, and premature graying of the hair: A diagnostic approach in pediatric patients and review of the literature.

Poliosis is defined as the absence of melanin in hair, and hair graying typically occurs with hair melanin reduction. Poliosis can occur at any age but presents in childhood in certain genetic and acquired conditions, with many families seeking evaluation from a pediatric dermatologist. Poliosis presents as white hair typically restricted to a certain location of the scalp. Children may also present with a reduction of expected hair pigmentation, referred to as pigment dilution, or the development of hair graying. This review aims to provide a streamlined diagnostic approach for pediatric dermatologists when presented with these hair findings. Poliosis should be recognized as a potential diagnostic feature or initial sign in many syndromes and thus can guide clinicians in diagnosing and managing conditions earlier in a patient's care. Since many of the genetic and acquired conditions that present with poliosis or hair pigment dilution have extracutaneous manifestations, early diagnosis is vital in establishing multidisciplinary care.

Anifrolumab for Adolescent Discoid Lupus Erythematosus.

This case series describes the outcomes among adolescent patients with systemic lupus erythematosus and refractory discoid lupus erythematosus treated with anifrolumab.

Evolving trends in inpatient paediatric dermatology.

PURPOSE OF REVIEW: This review provides updates in the evaluation and management of key dermatologic diseases encountered in the hospitalized child. RECENT FINDINGS: Our understanding of dermatologic disorders in children continues to evolve. Staphylococcal scalded skin syndrome (SSSS) is a potentially severe blistering disorder typically seen in children under the age of 4 with an incidence that is increasing in the United States. Recent research has highlighted that the majority of cases are due to methicillin-sensitive Staphylococcus aureus (MSSA) and most patients can be adequately managed with beta-lactams. Toxic epidermal necrolysis (TEN) is one of the most feared dermatologic disorders. Currently, there is a lack of consensus on the most efficacious first-line systemic therapy. Etanercept is increasingly being used based on studies showing a shorter time to re-epithelization and decreased mortality. Lastly, the COVID-19 pandemic introduced the novel inflammatory condition multisystem inflammatory syndrome in children (MIS-C) in which approximately three out of four children present with a mucocutaneous eruption. Early recognition of the dermatologic features of MIS-C is important in potentially establishing a diagnosis and differentiating it from the many other causes of childhood fever and rash. SUMMARY: There are no clear universal treatment guidelines for these rare diagnoses, and therefore, clinicians must remain informed of the latest findings in diagnosis and therapeutics.

Morbilliform Eruptions in the Hospitalized Child.

Morbilliform eruptions inspire a broad and varied differential spanning across inflammatory and infectious categories. The goal of this article is to help the clinician develop an approach toward the pediatric patient with a morbilliform eruption in the emergency room or hospital setting. The authors review several high-yield clinical scenarios with a focus on recently emerging and reemerging childhood diagnoses.

How we approach hemangiomas in infants.

Pediatric oncologists are increasingly involved in the management of benign vascular tumors and their associated life-threatening complications. Hemangiomas are the most common referring diagnosis to multidisciplinary vascular anomalies clinics. However, as contemporary research has revealed, hemangiomas are not a single, easily defined entity but rather a diverse set of related vascular tumors, each having a unique natural history, growth pattern, and response to therapy. This manuscript seeks to illustrate how we evaluate and manage these complex tumors, their complications, and associated syndromes, while remaining ever vigilant for malignant hemangioma mimickers such as soft tissue sarcomas and congenital leukemia.

Management of Pediatric Atopic Dermatitis by Primary Care Providers: A Systematic Review.

BACKGROUND: Primary care providers (PCPs), including pediatricians and general practitioners, are often the first to see children with eczema/atopic dermatitis (AD). Little is known about management of pediatric AD by PCPs and adherence to national guidelines. OBJECTIVE: To review existing literature examining management components of pediatric AD (topical corticosteroids [TCS], topical calcineurin inhibitors [TCIs], antihistamines, bathing, emollients, and diet) by PCPs. DATA SOURCES: PubMed/Medline and Embase. STUDY ELIGIBILITY CRITERIA: English-language articles dated 2015 to 2020 reporting outcomes addressing management of pediatric AD by PCPs. STUDY APPRAISAL AND SYNTHESIS METHODS: Two authors independently screened titles/abstracts, reviewed full-text articles, extracted relevant data, and evaluated study quality. Disagreements were resolved by a third author. RESULTS: Twenty articles were included. Surveys and national database analyses were the most common methodologies (n = 7 each). PCPs commonly prescribed TCS but had a preference for low-potency agents, overprescribed nonsedating antihistamines, and avoided TCIs. PCPs commonly recommended emollients, although this was not universal. Data characterizing nonmedication management were limited. LIMITATIONS: Most studies did not examine individual patient encounters, but rather relied on providers reporting their general behaviors. Provider behavior may vary based on country of practice. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Knowledge and management gaps exist among PCPs in treating pediatric AD in key areas including knowledge of TCS safety profiles and prescribing of TCIs. The current literature is largely limited to small studies that evaluate prescribing behaviors with limited data characterizing nonmedication management, highlighting the need for future research in this area.

Digital dermatoses: skin disorders engendered by social media in tweens and teens.

PURPOSE OF REVIEW: Photograph-based social media use among children and adolescents has skyrocketed over the past decade, raising concerns about the implications for self-confidence and behavior in this population. Social media 'challenges' encourage participants to complete potentially dangerous tasks while sharing their completion of the tasks on social media. Many of these challenges affect the skin and lead to recognizable findings on physical examination. This review discusses the history of prominent social media challenges and their effects on the skin. Attention is also given to the effects of social media trends on self-confidence and body image in children and adolescents. RECENT FINDINGS: Over the past several years, there have been several notable social media trends that can harm the skin. These include the Kylie Jenner lip challenge, salt and ice challenge, deodorant challenge, eraser challenge, fire challenge, and hot water challenge. Participation in these challenges can cause morbidity in children and adolescent that should be recognized by clinicians. SUMMARY: Social media has become an important platform for communication and self-expression among children and adolescents. Pediatricians should remain aware of social trends in this age group and look out for cutaneous findings that may signal dangerous behavior on social media.

Topical corticosteroid use for atopic dermatitis in the pediatric emergency department.

BACKGROUND/OBJECTIVES: To investigate the evaluation and management of atopic dermatitis (AD) in the pediatric emergency department (PED). METHODS: This retrospective chart review was performed at the PED of a single institution and examined data from 2012 to 2017. Of 335 visits from patients 18 years and younger coded for AD, 167 visits with documented findings that supported a diagnosis of AD according to guidelines from the American Academy of Dermatology were included. RESULTS: The mean age of presentation was 6.3 years (standard deviation [SD]: 5.9). Of 11 patients with multiple visits, the mean between-visit interval was 31 days (SD: 41). Topical corticosteroids (TCSs) were not prescribed or recommended in 63/167 visits. In an additional 46/167 visits, over-the-counter topical hydrocortisone was recommended. Of prescribed TCS, the mean TCS class was 5.5 (SD: 1.9). 61/104 recommended or prescribed TCSs were weak (Class 7), the most likely used class (P < .001). Dermatology consultation was requested in 14/167 visits and was associated with higher rates of TCS prescriptions (13/14 vs 91/153, P = .018), a higher mean class of TCS prescribed (3.1 vs 5.9, P < .001), higher prescription rates of systemic antibiotics (8/14 vs 10/153, P < .001), and higher recommendation rates for emollient usage (10/14 vs 46/153, P = .005). CONCLUSIONS: Most patients presenting to the PED for AD were either not prescribed a TCS or were prescribed a weak TCS, often one that is over-the-counter. While there may be a variety of explanations for these findings, it is possible they reveal a practice gap regarding AD management in the PED.

Mucocutaneous Manifestations of Multisystem Inflammatory Syndrome in Children During the COVID-19 Pandemic.

Importance: To date, no study has characterized the mucocutaneous features seen in hospitalized children with multisystem inflammatory syndrome in children (MIS-C) or the temporal association of these findings with the onset of systemic symptoms. Objective: To describe the mucocutaneous findings seen in children with MIS-C during the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City in 2020. Design, Setting, and Participants: A retrospective case series was conducted of 35 children admitted to 2 hospitals in New York City between April 1 and July 14, 2020, who met Centers for Disease Control and Prevention and/or epidemiologic criteria for MIS-C. Main Outcomes and Measures: Laboratory and clinical characteristics, with emphasis on mucocutaneous findings, of children who met criteria for MIS-C. The characterization of mucocutaneous features was verified by 2 board-certified pediatric dermatologists. Results: Twenty-five children (11 girls [44%]; median age, 3 years [range, 0.7-17 years]) were identified who met definitional criteria for MIS-C; an additional 10 children (5 girls [50%]; median age, 1.7 years [range, 0.2-15 years]) were included as probable MIS-C cases (patients met all criteria with the exception of laboratory test evidence of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection or known exposure). The results of polymerase chain reaction tests for SARS-CoV-2 were positive for 10 patients (29%), and the results of SARS-CoV-2 immunoglobulin G tests were positive for 19 patients (54%). Of the 35 patients, 29 (83%) exhibited mucocutaneous changes, with conjunctival injection (n = 21), palmoplantar erythema (n = 18), lip hyperemia (n = 17), periorbital erythema and edema (n = 7), strawberry tongue (n = 8), and malar erythema (n = 6) being the most common findings. Recognition of mucocutaneous findings occurred a mean of 2.7 days (range, 1-7 days) after the onset of fever. The duration of mucocutaneous findings varied from hours to days (median duration, 5 days [range, 0-11 days]). Neither the presence nor absence of mucocutaneous findings was significantly associated with overall disease severity. Conclusions and Relevance: In this case series of hospitalized children with suspected MIS-C during the COVID-19 pandemic, a wide spectrum of mucocutaneous findings was identified. Despite their protean and transient nature, these mucocutaneous features serve as important clues in the recognition of MIS-C.

The "bumpy" adolescent nose: Acne associated angiofibroma-like nasal papules.

BACKGROUND/OBJECTIVE: Papular scars are a recently described clinical phenotype of acne scarring characterized by papules occurring on the nose and chin. We have observed a similar presentation of nasal papules among patients seen in our clinic for acne and sought to further characterize the clinical and histopathological characteristics of this entity. METHODS: In this single-site case series, a retrospective review of electronic medical records of patients with nasal papules in association with acne vulgaris between April 2018 and April 2019 was performed. Clinical and histopathologic findings were recorded. RESULTS: We identified 20 patients who presented with a similar clinical phenotype of predominantly skin-colored, dome-shaped papules concentrated on the nose and chin in association with a history of more classic facial acne vulgaris. Papular lesions were seen predominately in adolescent Hispanic males. Concomitant acne on other areas of the face was identified in 18 patients at presentation while two patients had a history of adolescent acne. Biopsies were performed for five patients. Histopathologic examination demonstrated features of fibrosis and dilated thin-walled blood vessels, typical of angiofibromas. CONCLUSION: We present a series of adolescent patients with large, flesh-colored to erythematous papules seen predominantly on the nose. These lesions are histologically indistinguishable from angiofibromas and may represent an under-recognized yet disfiguring sequela of acne that may disproportionately affect adolescents with skin of color.

Dabrafenib-induced neutrophilic panniculitis in a child undergoing dual BRAF-MEK inhibitor therapy for glioblastoma multiforme.

BRAF inhibitor-induced neutrophilic panniculitis is a rare event that is well-characterized in adults undergoing therapy for metastatic melanoma. To date, there are very few reports of this event in children undergoing BRAF inhibitor therapy for low-grade gliomas, all of which were seen with vemurafenib. We report a case of dabrafenib-induced neutrophilic panniculitis in a 9-year-old girl that manifested within several weeks of initiating dual BRAF-MEK inhibitor therapy for glioblastoma multiforme. This case highlights neutrophilic panniculitis as a side effect of dabrafenib in children and serves as a reminder to consider cutaneous side effects of BRAF inhibitors as they are increasingly used to treat children with primary brain tumors.

Digital skin: The impact of modern-day photograph filtering applications on children with skin diseases.

Photograph editing has been present for centuries, but the past decade has seen an unprecedented rise in the practice, particularly on social media platforms. Common filters are able to soften complexion, remove blemishes, and even reshape facial features. Children and adolescents with skin conditions may find solace in using these applications to mask their disease online, but there is increasing concern about negative overall body image among those who filter their photographs. Pediatric dermatologists should remain aware of the practice of photograph editing among young people and consider asking patients about their social media presence.

Systemic immunosuppressive therapy for inflammatory skin diseases in children: Expert consensus-based guidance for clinical decision-making during the COVID-19 pandemic.

BACKGROUND/OBJECTIVES: The COVID-19 pandemic has raised questions about the approach to management of systemic immunosuppressive therapies for dermatologic indications in children. Change to: Given the absence of data to address concerns related to SARS-CoV-2 infection and systemic immunosuppressive therapies in an evidence-based manner, a Pediatric Dermatology COVID-19 Response Task Force (PDCRTF) was assembled to offer time-sensitive guidance for clinicians. METHODS: A survey was distributed to an expert panel of 37 pediatric dermatologists on the PDCRTF to assess expert opinion and current practice related to three primary domains of systemic therapy: initiation, continuation, and laboratory monitoring. RESULTS: Nearly all respondents (97%) reported that the COVID-19 pandemic had impacted their decision to initiate immunosuppressive medications. The majority of pediatric dermatologists (87%) reported that they were pausing or reducing the frequency of laboratory monitoring for certain immunosuppressive medications. In asymptomatic patients, continuing therapy was the most popular choice across all medications queried. The majority agreed that patients on immunosuppressive medications who have a household exposure to COVID-19 or test positive for new infection should temporarily discontinue systemic and biologic medications, with the exception of systemic steroids, which may require tapering. CONCLUSIONS: The ultimate decision regarding initiation, continuation, and laboratory monitoring of immunosuppressive therapy during the pandemic requires careful deliberation, consideration of the little evidence available, and discussion with families. Consideration of an individual's adherence to COVID-19 preventive measures, risk of exposure, and the potential severity if infected must be weighed against the dermatological disease, medication, and risks to the patient of tapering or discontinuing therapies.