Atopic Dermatitis in Children.

Atopic dermatitis (AD) is extremely common in the pediatric population, and most children with AD will first present to their primary care provider (PCP). The PCP can recognize AD by its clinical features, including itch, a chronic relapsing course, and the characteristic eruption. The cornerstone of AD therapy is dry skin care, typically a short daily bath/shower followed by an emollient applied to all skin. Most children with AD will also require topical medications, such as topical corticosteroids and/or topical nonsteroidal therapies. For children with more severe disease, systemic agents, including several novel therapies, may be required. In managing AD, the clinician must monitor for side effects of medications as well as complications of the AD itself, the most common of which is secondary infection. An understanding of the pathogenesis, treatments, and complications of AD is essential for the PCP, as untreated (or undertreated) AD has a significant impact on the quality of life of affected children and their caregivers. [Pediatr Ann. 2024;53(4):e121-e128.].

Melanoma in infants, caused by a gene fusion involving the anaplastic lymphoma kinase (ALK).

We describe the first cases of pediatric melanoma with ALK fusion gene arising within giant congenital melanocytic nevi. Two newborn boys presented with large pigmented nodular plaques and numerous smaller satellite nevi. Additional expansile nodules developed within both nevi and invasive melanomas were diagnosed before 10 months of age in both boys. Oncogenic driver mutations in NRAS and BRAF were absent in both cases. Instead, oncogenic ZEB2::ALK fusion genes were identified in both the nevus and melanoma developing within the nevus. In both cases, tumors were noted by ultrasound in utero, demonstrated significant nodularity at birth, and progressed to melanoma in the first year of life suggesting that congenital nevi with ALK fusion genes may behave more aggressively than those with other mutations. As ALK kinase inhibitors are effective against a range of tumors with similar ALK fusion kinases, identifying ALK fusion genes in congenital melanocytic nevi may provide an opportunity for targeted therapy.

Risk factors and outcomes of melanoma in children and adolescents: A retrospective multicenter study.

BACKGROUND: Pediatric melanoma presents with distinct clinical features compared to adult disease. OBJECTIVE: Characterize risk factors and negative outcomes in pediatric melanoma. METHODS: Multicenter retrospective study of patients under 20 years diagnosed with melanoma between January 1, 1995 and June 30, 2015 from 11 academic medical centers. RESULTS: Melanoma was diagnosed in 317 patients, 73% of whom were diagnosed in adolescence (age ≥11). Spitzoid (31%) and superficial spreading (26%) subtypes were most common and 11% of cases arose from congenital nevi. Sentinel lymph node biopsy was performed in 68% of cases and positive in 46%. Fatality was observed in 7% of cases. Adolescent patients with melanoma were more likely to have family history of melanoma (P = .046) compared to controls. LIMITATIONS: Retrospective nature, cohort size, control selection, and potential referral bias. CONCLUSION: Pediatric melanoma has diverse clinical presentations. Better understanding of these cases and outcomes may facilitate improved risk stratification of pediatric melanoma.

Subcutaneous fat necrosis of the newborn: A retrospective study of 32 infants and care algorithm.

OBJECTIVE: To describe the clinical and laboratory outcomes of infants with subcutaneous fat necrosis of the newborn (SCFN) and propose a care algorithm. METHODS: This single-center, retrospective study of infants diagnosed with SCFN at Ann & Robert H. Lurie Children's Hospital of Chicago from 2009 to 2019. RESULTS: Of 32 infants who met inclusion criteria, most were born full-term (84%), born via cesarean section (58%), had normal weight for gestational age (69%), and experienced delivery complications (53%). Twenty-nine infants (91%) had calcium drawn, and all had hypercalcemia. Three infants developed clinical symptoms of hypercalcemia, two required hospital admission, two developed nephrocalcinosis, and one developed acute kidney injury. The majority of infants (62%) had a peak ionized calcium between 1.5 and 1.6 mmol/L. No infants with peak ionized calcium less than 1.5 mmol/L developed complications of hypercalcemia. Most patients were diagnosed with hypercalcemia (86%) and demonstrated peak ionized calcium levels (59%) within the first 28 days of life. No patients developed hypercalcemia after 3 months of age. CONCLUSION: Hypercalcemia occurred in 100% of infants who had laboratory monitoring. We recommend obtaining an initial ionized calcium level when SCFN is suspected, and monitoring for the first 3 months of life if hypercalcemia has not been detected. In patients with asymptomatic hypercalcemia less than 1.5 mmol/L, there appears to be low likelihood of related complications. For symptomatic, markedly elevated (>1.6 mmol/L), or persistently elevated levels (>6 months) we suggest coordinated care with endocrinology or nephrology, consider hospitalization, and urinary system ultrasound.

Risk factors for the development of Spitz neoplasms.

BACKGROUND/OBJECTIVES: The principal environmental risk factor for conventional nevi and melanomas is ultraviolet exposure. However, little is known about genetic or environmental risk factors for developing Spitz tumors. This study investigates risk factors associated with Spitz neoplasms. METHODS: Patients with Spitz tumors seen at Northwestern Memorial Hospital and Lurie Children's Hospital were surveyed with a 16-item questionnaire about environmental and inherited factors. Spitz tumor patients were compared to a pediatric control cohort from a similar clinical setting. This was supplemented with a meta-analysis of genetic and environmental causes of Spitz neoplasms. RESULTS: One hundred and six Spitz and 58 control surveys were obtained and no statistically significant differences in genetic or environmental risk factors were found between Spitz and control groups. CONCLUSION: Our data and meta-analysis suggest that typical risk factors associated with melanoma are not significantly associated with Spitz tumors. Identification of relevant genetic or environmental risk factors will likely require larger and population-based studies.

Care of Congenital Melanocytic Nevi in Newborns and Infants: Review and Management Recommendations.

A pediatric dermatology expert working group performed a narrative review to describe care related to congenital melanocytic nevi (CMN) in neonates and infants. There are no published guidelines for most aspects of care, including routine skin care and visit intervals. Few guidelines exist for surgical management; newer recommendations favor conservative practice. Emerging evidence contributes to recommendations for screening MRI to evaluate for neural melanosis and related central nervous system complications, however, more research is needed. Risk for melanoma is generally low, but those with large, giant, or multiple CMN have a higher risk. Multidisciplinary care, with a focus on family and patient preferences, is of paramount importance. Without standardized screening and management guidelines, questions abound regarding appropriate physical examination intervals, potential treatment including full or partial excision, timing and frequency of imaging, melanoma risk, and assessment for neural melanosis. This review highlights the current state of knowledge concerning care of patients with CMN, reveals gaps in the literature surrounding skin care, and provides management recommendations. We additionally discuss cutaneous complications of CMN, such as pruritus, hypertrichosis, and wound healing. Resources and references for families and providers can help patients navigate this sometimes challenging diagnosis. Finally, we contribute expert care recommendations to the current body of literature as a foundation for the development of future, more comprehensive care guidelines.

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.

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.

Coconut allergy: Characteristics of reactions and diagnostic predictors in a pediatric tertiary care center.

BACKGROUND: Little is known on the clinical manifestations of coconut allergy. Our knowledge to date is mainly based on case reports. OBJECTIVE: To characterize the allergic reactions to coconut and suggest diagnostic cutoffs for specific immunoglobulin E (sIgE) and skin prick testing (SPT) to predict clinically reactive coconut allergy. METHODS: Methods include retrospective chart review at an urban tertiary care center of patients with positive testing result for coconut. Probability curves were computed by logistic regression for SPT and coconut sIgE. RESULTS: Of 275 records reviewed, 69 patients reported coconut reactions and 206 were sensitized only or nonallergic. The reactions occurred with breastfeeding (n = 2), contact (n = 10), or oral ingestion (n = 57). Approximately 50% of oral ingestion reactions were associated with mild/moderate anaphylaxis. Clinical reactivity vs sensitization was more common in topical coconut users (2-fold) (P = .02). Although not statistically significant, there was a trend toward more coconut allergy vs sensitization in Asian and African American patients. The probability of allergy with positive SPT result was approximately 50% and with sIgE was approximately 60%. At an SPT of 9 mm wheal or sIgE of 58 kU of allergen/L, there is a 95% probability of reaction. Cosensitization with tree nuts, legumes, and seeds was common. Macadamia nut had the strongest correlation with coconut (r = 0.81, P < .001, n = 101). CONCLUSION: Although the rate of reactivity to coconut in sensitized individuals is low, half of the reactions from consumption met the criteria for anaphylaxis. Clinicians should be aware of the spectrum of reactions and diagnostic use of sIgE and SPT.

A retrospective multicenter study of fatal pediatric melanoma.

BACKGROUND: Pediatric melanoma is rare and diagnostically challenging. OBJECTIVE: To characterize clinical and histopathologic features of fatal pediatric melanomas. METHODS: Multicenter retrospective study of fatal melanoma cases in patients younger than 20 years diagnosed between 1994 and 2017. RESULTS: Of 38 cases of fatal pediatric melanoma identified, 57% presented in white patients and 19% in Hispanic patients. The average age at diagnosis was 12.7 years (range, 0.0-19.9 y), and the average age at death was 15.6 years (range, 1.2-26.2 y). Among cases with known identifiable subtypes, 50% were nodular (8/16), 31% were superficial spreading (5/16), and 19% were spitzoid melanoma (3/16). One fourth (10/38) of melanomas arose in association with congenital melanocytic nevi. LIMITATIONS: Retrospective nature, cohort size, and potential referral bias. CONCLUSIONS: Pediatric melanoma can be fatal in diverse clinical presentations, including a striking prevalence of Hispanic patients compared to adult disease, and with a range of clinical subtypes, although no fatal cases of spitzoid melanoma were diagnosed during childhood.

Management of Atopic Dermatitis in Children Younger Than Two Years of Age by Community Pediatricians: A Survey and Chart Review.

OBJECTIVES: To characterize primary care providers' (PCPs) practice patterns for atopic dermatitis (AD) in children <2 years old and determine the need for AD guidelines for PCPs focused on this age group. STUDY DESIGN: This is a mixed-methods study consisting of a survey and a retrospective medical record review of PCP practices in the Chicago metropolitan area. The survey was analyzed using both quantitative and qualitative methods. RESULTS: In the survey (n = 52 respondents), PCPs reported management of AD is different in children <2 years compared with older children (88%). They were more likely to refer to a specialist (65%) and less likely to use high-potency topical corticosteroids (64%). In the chart review, PCP visits for children 2-5 years old (n = 50 914) vs those <2 years old (n = 71 913) for AD, older children had medium- and high-potency topical corticosteroids prescribed more frequently than younger children (0.66% vs 0.37%, P < .01 and .15% vs 0.05%, P < .01, respectively). In the subset of children <2 years of age who also were evaluated by a specialist (n = 109), medium- and high-potency topical corticosteroids were prescribed disproportionately at visits to providers in dermatology (57%) vs allergy (30%) vs pediatrics (15%) (P < .01). PCPs suggested that guidelines for this age group should include recommendations for preferred corticosteroids (39%), allergy management (35%), referral criteria (22%), and assessment of disease severity (11%). CONCLUSIONS: PCP management of AD in children <2 years is different from older children, with possible underuse of medium/high-potency topical corticosteroids. Clear guidelines for this age group are needed.

Topical calcineurin inhibitors for pediatric periorificial dermatitis.

BACKGROUND: Data regarding the treatment of periorificial dermatitis with topical calcineurin inhibitors (TCI) in the pediatric population are limited. OBJECTIVE: To assess the clinical utility of TCI in pediatric patients with periorificial dermatitis. METHODS: A retrospective medical record review of all pediatric patients with periorificial dermatitis treated with TCIs was performed. Follow-up via telephone was performed to capture missing data. RESULTS: A total of 132 patients met the inclusion criteria. The median age at diagnosis was 4.2 years (interquartile range, 2.3-8.2). The median follow-up was 5.2 months (interquartile range, 2.1-11.7). Seventy-two patients had evaluable follow-up data. Of these, 48 (67%) patients were treated with TCI alone, 12 (16.7%) were treated with a combination of TCI and topical metronidazole, and 9 (12.5%) were treated with a combination of TCI and a systemic antibiotic. Complete response was noted in 68.8% of patients treated with TCI alone, in 75% of patients treated with TCI and metronidazole, and in 77.8% of patients treated with TCI and a systemic antibiotic. Adverse events were rare and mild in severity. CONCLUSION: Topical calcineurin inhibitors are an effective therapeutic option for pediatric patients with periorificial dermatitis and were well tolerated in this cohort.

Integrating Next-Generation Sequencing with Morphology Improves Prognostic and Biologic Classification of Spitz Neoplasms.

The newest World Health Organization classification of skin tumors suggests the elimination of cases with BRAF and NRAS mutations from the categories of Spitz tumors (ST) and Spitz melanoma (SM). The objective of this study is to better characterize the genomics of Spitz neoplasms and assess whether the integration of genomic data with morphologic diagnosis improves classification and prognostication. We performed DNA and RNA sequencing on 80 STs, 26 SMs, and 22 melanomas with Spitzoid features (MSF). Next-generation sequencing data were used to reclassify tumors by moving BRAF and/or NRAS mutated cases to MSF. In total, 81% of STs harbored kinase fusions and/or truncations. Of SMs, 77% had fusions and/or truncations with eight involving MAP3K8. Previously unreported fusions identified were MYO5A-FGFR1, MYO5A-ERBB4, and PRKDC-CTNNB1. The majority of MSFs (84%) had BRAF, NRAS, or NF1 mutations, and 62% had TERT promoter mutations. Only after reclassification, the following was observed: (i) mRNA expression showed distinct clustering of MSF, (ii) six of seven cases with recurrence and all distant metastases were of MSFs, (iii) recurrence-free survival was worse in MSF than in the ST and SM groups (P = 0.0073); and (iv) classification incorporating genomic data was highly predictive of recurrence (OR 13.20, P = 0.0197). The majority of STs and SMs have kinase fusions as primary initiating genomic events. The elimination of BRAF and/or NRAS mutated neoplasms from these categories results in the improved classification and prognostication of melanocytic neoplasms with Spitzoid cytomorphology.

Complementary and alternative therapy for pediatric acne: A review of botanical extracts, dietary interventions, and oral supplements.

Many supplements and products containing botanical extracts are marketed to patients for the treatment of acne vulgaris. Additionally, increasing attention has been paid to the role of diet in acne vulgaris. Studies on this topic including pediatric patients are limited, with variable efficacy data. Despite these limitations, knowledge of alternative therapies in pediatric acne vulgaris is often expected from pediatric dermatologists. Here we review available data on the efficacy of complementary and alternative medicines for treatment of acne in pediatric patients, focusing on topical, oral, and dietary modifications.

Risk Factors and Outcomes of Nonmelanoma Skin Cancer in Children and Young Adults.

OBJECTIVE: To identify risk factors associated with nonmelanoma skin cancer (NMSC) occurrence and survival in children. STUDY DESIGN: This was a multicenter, retrospective, case-control study of patients <20 years of age diagnosed with NMSC between 1995 and 2015 from 11 academic medical centers. The primary outcome measure was frequency of cases and controls with predisposing genetic conditions and/or iatrogenic exposures, including chemotherapy, radiation, systemic immunosuppression, and voriconazole. RESULTS: Of the 124 children with NMSC (40 with basal cell carcinoma, 90 with squamous cell carcinoma), 70% had at least 1 identifiable risk factor. Forty-four percent of the cases had a predisposing genetic condition or skin lesion, and 29% had 1 or more iatrogenic exposures of prolonged immunosuppression, radiation therapy, chemotherapy, and/or voriconazole use. Prolonged immunosuppression and voriconazole use were associated with squamous cell carcinoma occurrence (cases vs controls; 30% vs 0%, P = .0002, and 15% vs 0%, P = .03, respectively), and radiation therapy and chemotherapy were associated with basal cell carcinoma occurrence (both 20% vs 1%, P < .0001). Forty-eight percent of initial skin cancers had been present for >12 months prior to diagnosis and 49% of patients were diagnosed with ≥2 skin cancers. At last follow-up, 5% (6 of 124) of patients with NMSC died. Voriconazole exposure was noted in 7 cases and associated with worse 3-year overall survival (P = .001). CONCLUSIONS: NMSC in children and young adults is often associated with a predisposing condition or iatrogenic exposure. High-risk patients should be identified early to provide appropriate counseling and management.

Ocular Complications in PHACE Syndrome: A True Association or a Coincidence?

OBJECTIVE: To characterize the risk for ocular complications in patients with PHACE syndrome. STUDY DESIGN: This study included consecutive patients with PHACE syndrome who were seen at Lurie Children's Hospital of Chicago from January 2000 through May 2017. A complete ophthalmic examination was performed in all patients, with extra attention for findings typically associated with PHACE syndrome. RESULTS: Thirty patients (67% female, median age of onset 0.08 months) were included: 38 (93%) demonstrated a segmental infantile hemangioma distribution. Twenty-one (70%) cases had a periocular involvement, and 47% had an infantile hemangioma with a deep component. Among 21 patients with periocular distribution, 9 had ocular complications secondary to the periocular location (mainly ptosis, nasolacrimal duct obstruction, and refractive errors), and one had an ocular complication specifically associated with PHACE syndrome (Horner syndrome). None of the patients without periocular distribution had an ocular complication. CONCLUSIONS: In patients with PHACE syndrome who have a periocular infantile hemangioma, a complete eye examination is recommended. Although specific ocular anomalies related to PHACE syndrome are rare, serious ocular complications secondary to the location of the hemangioma may be present. Eye examination in patients with PHACE syndrome without a periocular infantile hemangioma distribution is likely of low yield.

Neurocognitive function in moderate-severe pediatric atopic dermatitis: A case-control study.

BACKGROUND/OBJECTIVES: Epidemiological studies have shown an increased prevalence of attention deficit hyperactivity disorder (ADHD) in children with atopic dermatitis (AD), but many of the features of ADHD may occur as a result of the poor sleep and itch distraction associated with AD. METHODS: A case-control study was performed in children aged 6-17 years with moderate/severe AD compared with age-/sex-matched healthy controls. Participants were screened for ADHD using Vanderbilt assessments. RESULTS: Seventeen patients with AD and 18 controls completed the study. Two children with AD (11.7%) and one control (5.56%) met screening criteria for ADHD via parent-completed Vanderbilt assessments; AD patients were not significantly more likely to screen positive for ADHD (P = 0.47), or comorbid behavior disorders (P = 0.23). However, AD patients were more likely than controls to exhibit ADHD-associated behaviors, most significantly inattention. CONCLUSIONS: Our AD cohort did not have a significantly increased prevalence of ADHD. Certain neurocognitive symptoms are increased in children with moderate-to-severe AD compared to controls.