Lichen Sclerosus: A Survey of Diagnosis and Management Among Pediatric Dermatologists and Gynecologists.

BACKGROUND/OBJECTIVES: Lichen sclerosus (LS) is a chronic condition that warrants close follow-up due to the risk of scarring. The optimal long-term management of pediatric vulvar and perianal lichen sclerosus (PVPLS) is unknown. This study aimed to identify diagnostic, treatment, and maintenance regimens among pediatric dermatologists and pediatric/adolescent gynecologists, as well as assess provider confidence and desire for guidance on long-term PVPLS management. METHODS: A cross-sectional 35-question survey was administered through the Pediatric Dermatology Research Alliance (PeDRA) and the North American Society for Pediatric and Adolescent Gynecology (NASPAG) between 7/13/2021 and 8/30/2021 to ascertain PVPLS diagnostic and management regimens. RESULTS: Most responders were attending-level pediatric/adolescent gynecologists (46%) and pediatric dermatologists (41%). Although 85% of participants felt completely or very confident in diagnosing PVPLS, the majority (86%) desired further management guidelines. While the initial treatment was similar among providers, maintenance regimens and follow-up varied considerably, with only 42% recommending lifelong monitoring despite potential persistence into adulthood. CONCLUSIONS: While initial treatment was similar among practitioners, there was variation by specialty in subsequent management and a lack of uniformity in long-term follow-up. Additional studies are needed to clarify the optimal management of PVPLS and to provide evidence-based guidelines regarding long-term follow-up.  J Drugs Dermatol. 2024;23(6):450-455.     doi:10.36849/JDD.8084.

Vulvar skin disease in the pediatric population.

PURPOSE OF REVIEW: Vulvar skin disease is an underrecognized pediatric condition encompassing a wide range of conditions, from isolated vulvar disease to vulvar manifestations of systemic illnesses. This review highlights the most current research discussing clinical features, risk factors, and treatments. RECENT FINDINGS: Recent studies confirm that labial adhesions resolve more quickly with estrogen treatment. Topical corticosteroids remain first-line for treatment of vulvar lichen sclerosus, and some procedural interventions are showing promising results. Latest evidence shows efficacy of biologic agents in hidradenitis suppurativa and vulvar Crohn's. Vaginal voiding remains an underrecognized cause of irritant vulvovaginitis. Lately vulvar aphthae have been associated with coronavirus disease 2019. Distinguishing between infantile perianal pyramidal protrusion, molluscum, and condyloma can be aided by differences in morphologic features. SUMMARY: Vulvar dermatoses have a high impact on children's health and wellbeing. Clinician familiarity with recognition and latest advancements in vulvar dermatoses can aid in prompt diagnosis, management, and appropriate referrals. Vulvar biopsy and vaginal cultures should be used prudently. Treatments include topicals, behavioral modification, systemic medications, and procedures.

Atopic Dermatitis: Managing the Itch.

Atopic dermatitis has a substantial impact on sleep, appearance, psychological well-being, and other qualities of life. The visual appearance of lichenification, cheilitis, hyperpigmentation, ichthyosis, and erythema can be socially stigmatizing, and treatment of these symptoms is challenging. In managing pruritus in patients, practitioners should assess and document pruritus through questionnaires at each routine visit. Initially, practitioners should advise patients to employ nonpharmaceutical treatments such as emollients with wet wraps, elimination of triggers, changing scratching habits, and psychological interventions. If these methods of treatment are not successful or if the disease presentation is severe, pharmacological therapies should be employed. This chapter describes the therapeutic ladder for pruritus in atopic dermatitis and discusses each treatment modality in further detail for practitioners to advise their patients.First-line topical pharmaceutical agents include topical glucocorticoids and topical calcineurin inhibitors. Second-line topical agents include coal tar, menthol, capsaicin, or doxepin. After the use of topical agents has been exhausted, primary systemic agents can be applied. These include sedating antihistamines, nonsedating antihistamines, oral glucocorticoids, or cyclosporine A. Finally, neuromodulating or immunomodulating agents can be attempted, including SSRI/SNRIs, TCAs, immunosuppressants, neural modulators, and opioid receptor modulators. Outside of pharmacological treatments, phototherapy has been shown to provide a dramatic improvement of pruritus in atopic dermatitis and can be used at any stage of treatment including as a first-line agent.

Pediatric Dermatology for People of Color.

When evaluating pediatric patients of color, it is essential to consider the unique diagnostic and treatment factors that apply to this population. Certain dermatologic conditions are more common in these patients, including postinflammatory hyperpigmentation, pityriasis alba, progressive macular hypomelanosis, tinea capitis, traction alopecia, keloids, hypertrophic scars, pseudofolliculitis barbae, acne keloidalis nuchae, and hidradenitis suppurativa. Furthermore, conditions such as vitiligo are more noticeable in people of color. This can lead to a significantly diminished quality of life, so these conditions should be quickly recognized and treated. Notably, inflammation can be difficult to recognize on the skin of people of color, which can lead to the underestimation of severity as well as inappropriate treatment. Treatment recommendations can also differ based on lifestyle or cultural norms, such as the use of tinted sunscreens and the consideration of hair care practices. Pediatricians should be aware of these conditions and treatment considerations to best treat pediatric patients of color. [Pediatr Ann. 2024;53(4):e146-e151.].

Topical Isotretinoin (TMB-001) Treatment for 12 Weeks Did Not Result in Clinically Relevant Laboratory Abnormalities in Participants with Congenital Ichthyosis in the Phase 2b CONTROL Study.

INTRODUCTION: Treatment with oral retinoids can be effective in patients with congenital ichthyosis (CI) but may be associated with clinically significant laboratory changes. In this Phase 2b CONTROL study analysis, we characterize the effects of TMB-001, a novel topical isotretinoin formulation, on laboratory values in participants with X-linked recessive (XLRI) and autosomal recessive lamellar (ARCI-LI) ichthyosis at 12 weeks. METHODS: A randomized, double-blind, vehicle-controlled, Phase 2b study was conducted with participants ≥ 9 years of age with confirmed XLRI and ARCI-LI. Participants were randomized 1:1:1 and stratified by CI subtype to receive TMB-001 0.05%:TMB-001 0.1%:vehicle twice daily for 12 weeks. Laboratory analyses were performed at screening and Week 12. RESULTS: Among 33 enrolled participants (TMB-001 0.05% n = 11, TMB-001 0.1% n = 10, and vehicle n = 12), 52% had ARCI-LI and 48% had XLRI. At 12 weeks, there were single reports of anemia, neutropenia, leukopenia, lymphocytosis, and leukocytosis after vehicle treatment; neutropenia was reported in one participant receiving TMB-001 0.1%. There were single reports of abnormal biochemistry values-liver enzymes, creatinine, urea nitrogen, hyperkalemia, and hyperproteinemia-across treatment cohorts. Non-fasting hyperglycemia was observed in three participants receiving TMB-001 0.1% and one participant receiving vehicle. Urinalysis abnormalities reported in > 1 participant included urobilinogen (TMB-001 0.1% n = 2, vehicle n = 2), protein (TMB-001 0.1% n = 3, vehicle n = 2), and leukocyte esterase (TMB-001 0.1% n = 2). Laboratory parameter changes were asymptomatic and did not require study discontinuation or drug withdrawal. CONCLUSION: There were no clinically significant laboratory changes in participants receiving TMB-001 isotretinoin ointment through 12 weeks of treatment, which differs from reported results for systemic isotretinoin. TRIAL REGISTRATION: NCT04154293.

Characteristics and outcomes for participants with congenital ichthyosis who responded to treatment with the topical isotretinoin formulation TMB-001: results from the Phase IIb CONTROL study.

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.

Phase IIb randomized CONTROL study demonstrates a novel topical isotretinoin formulation, TMB-001, is safe and effective in participants with either recessive X-linked or autosomal recessive lamellar congenital ichthyosis.

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.

Prevalence of delayed puberty and low bone density in patients with epidermolysis bullosa: Insight from a large single center's experience.

BACKGROUND: Epidermolysis bullosa (EB) is a group of rare genetic skin conditions that result in skin fragility. EB can be quite severe with chronic inflammation and malnutrition impairing growth and pubertal development. These factors have potential consequences for skeletal health. We aimed to determine the prevalence of delayed puberty and low bone mineral density (BMD) for age in children and young adults with EB. METHODS: Electronic medical records (EMR) of patients with confirmed EB <30 years of age at time of initial encounter at Cincinnati Children's Hospital Medical Center between January 1, 2010 and September 30, 2020 were reviewed. Natural language processing software was used to categorize pubertal status of patients with EB as early, normal or delayed. BMD was measured by dual energy x-ray absorptiometry and categorized as low if height adjusted Z-score was <-2.0 using age, sex and race specific reference ranges. RESULTS: 29% of individuals with EB had low BMD with most cases occurring prior to 10 years of age. Of patients who reached adolescence, 23% failed to develop any signs of puberty in the normal range (before age 13 in females or 14 in males) and BMD Z-scores further declined in these individuals. CONCLUSION: Delayed puberty is an under-recognized comorbidity of individuals with EB, especially in those with recessive dystrophic EB, and can have a significant impact on BMD.

Automated quantitative assessment of amorphous calcifications: Towards improved malignancy risk stratification.

BACKGROUND: Amorphous calcifications noted on mammograms (i.e., small and indistinct calcifications that are difficult to characterize) are associated with high diagnostic uncertainty, often leading to biopsies. Yet, only 20% of biopsied amorphous calcifications are cancer. We present a quantitative approach for distinguishing between benign and actionable (high-risk and malignant) amorphous calcifications using a combination of local textures, global spatial relationships, and interpretable handcrafted expert features. METHOD: Our approach was trained and validated on a set of 168 2D full-field digital mammography exams (248 images) from 168 patients. Within these 248 images, we identified 276 image regions with segmented amorphous calcifications and a biopsy-confirmed diagnosis. A set of local (radiomic and region measurements) and global features (distribution and expert-defined) were extracted from each image. Local features were grouped using an unsupervised k-means clustering algorithm. All global features were concatenated with clustered local features and used to train a LightGBM classifier to distinguish benign from actionable cases. RESULTS: On the held-out test set of 60 images, our approach achieved a sensitivity of 100%, specificity of 35%, and a positive predictive value of 38% when the decision threshold was set to 0.4. Given that all of the images in our test set resulted in a recommendation of a biopsy, the use of our algorithm would have identified 15 images (25%) that were benign, potentially reducing the number of breast biopsies. CONCLUSIONS: Quantitative analysis of full-field digital mammograms can extract subtle shape, texture, and distribution features that may help to distinguish between benign and actionable amorphous calcifications.

CYP4F22-Related Autosomal Recessive Congenital Ichthyosis: Clinical Presentation.

Autosomal recessive congenital ichthyosis (ARCI) is a group of hereditary, nonsyndromic disorders of keratinization. ARCI encompasses several different clinical presentations and is caused by various genetic mutations. Commonly, ARCI presents with a taut, thick, shiny stratum corneum called a collodion membrane, but patients with mutations in CYP4F22 frequently present only with erythroderma. We report the case of a patient who was heterozygous for a pathogenic variant and a variant of uncertain significance in the CYP4F22 gene and presented with a collodion membrane and developed a mild ichthyosis phenotype.

Epidermolytic ichthyosis complicated by staphylococcal scalded skin syndrome in the newborn.

Epidermolytic ichthyosis is characterized by erythema and blistering at birth. We present a neonate with epidermolytic ichthyosis who had a subtle change in clinical findings while hospitalized, including increased fussiness, erythema, and a change in her skin odor, which represented superimposed staphylococcal scalded skin syndrome. This case highlights the unique challenge of recognizing cutaneous infections in neonates with blistering skin disorders and emphasizes the importance of having a high suspicion for superinfection in this population.

NASPAG Clinical Opinion: Diagnosis and Management of Lichen Sclerosis in Pediatric and Adolescent Patients.

This Clinical Opinion replaces the NASPAG Clinical Recommendation: Pediatric Lichen Sclerosus published in 2014. The objective of this document is to provide guidance in the diagnosis and management of vulvar lichen sclerosus (LS) in the pediatric and adolescent patient in order to treat patient symptoms and reduce long-term sequelae. LS is a chronic inflammatory condition affecting the anogenital region that may present in the prepubertal or adolescent patient. Clinical presentations include significant pruritus, loss of pigmentation and vulvar adhesions with loss of normal vulvar architecture. Management includes topical agents for induction and maintenance therapy, as well as long-term follow-up for identification and treatment of recurrence and sequelae. This document is intended for use by both primary and specialty pediatric and adolescent gynecology (PAG) providers, including specialists in pediatrics, gynecology, adolescent medicine, and dermatology.

Streptococcal pneumonia meningitis as an initial presentation of X-linked agammaglobulinemia: A case report and discussion.

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by mutations in the gene for Bruton's tyrosine kinase (Btk), with affected males most commonly presenting with recurrent bacterial infections during the first few years of life. Here we present a 17-month-old male with a chief complaint of worsening rash and fever, whose history of streptococcal pneumonia meningitis at 5 months of age prompted suspicion for an underlying immunodeficiency and subsequent diagnosis of XLA. Bacterial meningitis is a rare initial presentation of XLA, and therefore physicians may easily overlook any underlying immunodeficiency. Prompt workup for immunodeficiency should be initiated in any vaccinated patient with a history of pneumococcal meningitis outside of the newborn period. Further discussion surrounding the various presentations of XLA, their related clinical manifestations and laboratory findings, and the importance of thorough chart review may encourage earlier diagnosis and initiation of treatment of this disease.

Most common pediatric skin conditions managed in outpatient dermatology clinics in the United States stratified by race and ethnicity.

A better understanding of what skin conditions are most commonly diagnosed in different pediatric racial and ethnic groups in outpatient dermatology clinics could help guide the development of pediatric dermatology educational initiatives for primary care providers and general dermatologists who have limited access to pediatric dermatologists. Using a nationally representative dataset, we evaluated the most common diagnoses in patients younger than 15 years of age (children) and 15-24 years of age (youth) who present to outpatient dermatology clinics, stratified by race and ethnicity. While acne and dermatitis were among the top ten most common diagnoses in all racial and ethnic groups studied, Black children were also commonly diagnosed with dermatophytosis and impetigo, and Black and Hispanic children were often diagnosed with seborrheic dermatitis; pigmentary disorders were among the top three most common diagnoses in Black, Asian, and Hispanic youth. Training more physicians how to evaluate and treat common skin conditions in children and youth of diverse racial and ethnic backgrounds may improve access to care for skin disease in the United States.

Diagnosis and Care of the Newborn with Epidermolysis Bullosa.

Epidermolysis bullosa (EB) is a group of rare genetic disorders that are characterized by fragile skin. Because of its rarity, many neonatologists may not be familiar with the current diagnosis and treatment recommendations for EB. The classification of EB was updated in 2020. The diagnosis of EB is now more heavily based on genetic rather than clinical or histologic features. In this review, we summarize the basic classification of EB, the preferred methods of diagnosis including a panel of next-generation sequencing for all types of EB, as well as specific immunofluorescence and electron microscopy of skin biopsies in special circumstances. We also review the principles of skin care for the newborn with EB and discuss the possible associated comorbidities including infectious, gastrointestinal, respiratory, and genitourinary complications. Lastly, we discuss the approach to educating the family about the diagnosis, prognosis, and care of an infant with EB and describe resources for the successful transition of the infant from the hospital to the home.

Epidemiology, Pathophysiology, and Management Strategies of Neonatal Wound Care.

Guidelines for neonatal skin care are scarce, and there is no consensus on the best management practices for neonatal skin breakdown. This review presents the pathology and phases of wound healing, reasons for neonatal skin fragility, and approaches to recognition of commonly encountered neonatal wounds. This review also provides general strategies for neonatal wound prevention, care, dressing, and management to avoid further damage to the fragile neonatal skin. The importance and role of retaining moisture in expediting wound healing is discussed, as well as updated classifications on how to grade and assess pressure ulcers and the role of negative pressure wound therapy and silver dressings. Lastly, this review discusses prevention and treatment options for surgical wounds, intravenous extravasation wounds, congenital wounds, and thermal injuries, in addition to how to differentiate these wounds from the common diaper dermatitis and contact dermatitis.

What the Pediatric and Adolescent Gynecology Clinician Needs to Know about Acne.

Acne vulgaris is a common skin condition encountered in specialties outside of dermatology, including obstetrics and gynecology. The pathophysiology of acne is complex and includes disruption of the cutaneous microbiome, abnormal keratinization, inflammation, and hormonal influences. Various topical and systemic treatment modalities target each component of acne pathophysiology. Clinically, acne can be broken down into noninflammatory, inflammatory, or mixed subtypes. The age of the patient at presentation and signs and symptoms of hormonal imbalance might prompt workup for underlying disorders. The severity as well as type of acne dictates the type of treatment.