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.

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.

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.

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.

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.

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.

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.

Cutaneous mosaic RASopathies associated with rhabdomyosarcoma.

Variants in RAS are known drivers of certain pediatric blood and solid cancers, including brain tumors. Though most RAS-driven cancers are thought to occur sporadically, genetic syndromes caused by germline RAS variants portend a slightly higher risk of rhabdomyosarcoma (RMS) development. Three new cases and a review of the literature demonstrate that in rare cases, certain somatic RAS variants are associated with an increased risk of RMS and that RMS development may be heralded by the presence of concomitant RAS-driven birthmarks. Further prospective studies are needed to establish incidence and recommend appropriate monitoring guidelines for patients at risk.

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.

Treatment of Impetigo and Antimicrobial Resistance.

BACKGROUND: Impetigo is a contagious bacterial infection that affects the superficial skin layers. Increasing worldwide antimicrobial resistance (AMR) to existing topical agents commonly prescribed to treat impetigo is central to treatment failure. The Worldwide Health Organization developed a global action plan on AMR, but omitted information about AMR stewardship programs for topical antibiotics. OBJECTIVES: The review aims to provide information to clinicians and stakeholders regarding AMR and antimicrobial stewardship on topical antimicrobial drugs for impetigo treatment. METHODS: The literature searches reviewed the status of AMR to current topical antibiotics in impetigo, current therapeutic behavior, and concordance with antimicrobial stewardship principles. Two international panels convened to discuss the output of the searches, and the results of the panel discussions were used in the development of the manuscript. RESULTS: The literature search included clinical trials, research studies, clinical guidelines, consensus papers, and reviews (if they provided original data), published between January 2008 and May 2019. The articles were selected based on clinical relevancy of impetigo management, clinical efficacy, and safety of the treatment and antimicrobial resistance. The searches resulted in one-hundred and ninety-eight articles. After applying the eligibility criteria, nineteen articles met inclusion criteria and were considered in the present review. CONCLUSIONS: While published antimicrobial stewardship guidelines have focused on systemic antibiotics, few studies have attempted to evaluate topical antibiotic prescribing practices for impetigo treatment. Many of the topical impetigo treatments currently in use have developed resistance. The appropriate use of topical ozenoxacin can help eradicate impetigo while minimizing AMR.J Drugs Dermatol. 20(4):366-372. doi:10.36849/JDD.5795.

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.

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.

Nevus psiloliparus: Newly described histopathological features from transverse sections.

Nevus psiloliparus is a rare fatty tissue nevus that is a marker for encephalocraniocutaneous lipomatosis, a neurocutaneous syndrome with ocular and central nervous system anomalies. Clinically, nevus psiloliparus is often described as a congenital alopecia and appears as an irregularly shaped, circumscribed area of alopecia on the scalp. Histopathology demonstrates a near-complete absence of mature hair follicles with preservation of arrector pili muscles and mature adipocytes within the dermis. The pathogenesis of nevus psiloliparus may be related to mosaic mutations in fibroblast growth factor receptor 1. Herein we report the histopathological features of a nevus psiloliparus in an 11-year-old girl diagnosed from transverse sections, which show "shadow" follicular units characterized by columns of loosely arranged collagen and a relative paucity of elastic fibers.

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.

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.

Neutrophilic panniculitis arising from hematogenous spread of methicillin-resistant Staphylococcus aureus.

Infectious panniculitis from hematogenous spread is uncommon and usually occurs in immunocompromised patients. Dissemination of gram-positive organisms to the subcutaneous tissue is rare with only several reports of disseminated panniculitis caused by Streptococcal species. We report a case of an immunocompetent 2-year-old boy presenting with diffuse neutrophilic panniculitis arising from methicillin-resistant Staphylococcus aureus septicemia. This case represents a highly atypical manifestation of severe MRSA infection and serves as a reminder to consider MRSA as a cause of disseminated neutrophilic panniculitis, particularly in high-risk populations.

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.

Acquired acrodermatitis enteropathica due to zinc-depleted parenteral nutrition.

Well-known causes of zinc deficiency, also referred to as acrodermatitis enteropathica (AE), include defects in intestinal zinc transporters and inadequate intake, but a rare cause of acquired zinc deficiency discussed here is an iatrogenic nutritional deficiency caused by parenteral nutrition administered without trace elements. While zinc-depleted parenteral nutrition causing dermatosis of acquired zinc deficiency was first reported in the 1990s, it is now again relevant due to a national vitamin and trace element shortage. A high index of suspicion may be necessary to diagnose zinc deficiency, particularly because early clinical findings are nonspecific. We present this case of acquired zinc deficiency in a patient admitted to a pediatric intensive care unit for respiratory distress and atypical pneumonia, who subsequently developed a severe bullous eruption due to iatrogenic zinc deficiency but was treated effectively with enteral and parenteral zinc supplementation, allowing for rapid re-epithelialization of previously denuded skin.

A case of recalcitrant pediatric Vogt-Koyanagi-Harada disease successfully controlled with adalimumab.

Vogt-Koyanagi-Harada (VKH) disease is uncommon in the pediatric population and can have an aggressive course with serious visual sequelae. A 12-year-old Han Chinese American female, who presented with mild headaches and panuveitis with diffuse serous retinal detachments, was diagnosed with VKH. Despite treatment with a combination of high-dose systemic corticosteroids, intravitreal triamcinolone injection, and mycophenolate mofetil, ocular inflammation was inadequately controlled. Addition of adalimumab allowed for inflammation remission, improvement of vision, and tapering of systemic corticosteroids. Escalation of immunosuppression until remission appears to be critical in this population. Further research is needed to understand the complex pathophysiology of VKH and investigation for similar efficacy of other anti-tumor necrosis factor-alpha agents will need to be performed.