Multicenter Study of Long-Term Outcomes and Quality of Life in PHACE Syndrome after Age 10.

OBJECTIVE: To characterize long-term outcomes of PHACE syndrome. STUDY DESIGN: Multicenter study with cross-sectional interviews and chart review of individuals with definite PHACE syndrome ≥10 years of age. Data from charts were collected across multiple PHACE-related topics. Data not available in charts were collected from patients directly. Likert scales were used to assess the impact of specific findings. Patient-Reported Outcomes Measurement Information System (PROMIS) scales were used to assess quality of life domains. RESULTS: A total of 104/153 (68%) individuals contacted participated in the study at a median of 14 years of age (range 10-77 years). There were infantile hemangioma (IH) residua in 94.1%. Approximately one-half had received laser treatment for residual IH, and the majority (89.5%) of participants were satisfied or very satisfied with the appearance. Neurocognitive manifestations were common including headaches/migraines (72.1%), participant-reported learning differences (45.1%), and need for individualized education plans (39.4%). Cerebrovascular arteriopathy was present in 91.3%, with progression identified in 20/68 (29.4%) of those with available follow-up imaging reports. Among these, 6/68 (8.8%) developed moyamoya vasculopathy or progressive stenoocclusion, leading to isolated circulation at or above the level of the circle of Willis. Despite the prevalence of cerebrovascular arteriopathy, the proportion of those with ischemic stroke was low (2/104; 1.9%). PROMIS global health scores were lower than population norms by at least 1 SD. CONCLUSIONS: PHACE syndrome is associated with long-term, mild to severe morbidities including IH residua, headaches, learning differences, and progressive arteriopathy. Primary and specialty follow-up care is critical for PHACE patients into adulthood.

Regimen for accelerated propranolol initial dosing (RAPID).

BACKGROUND: Infantile hemangiomas are common vascular tumors in children. Propranolol has proven effective in treating infantile hemangiomas and while generally safe, has potential risk for more serious side effects of hypoglycemia, hypotension, bradycardia, bronchospasm, and cardiovascular or respiratory compromise. Current prescribing guidelines recommend initiating propranolol doses at 1 mg/kg/day, with up-titration to 2 mg/kg/day. This study aims to compare the incidence of adverse events in infants and children treated with propranolol initiated at 1 mg/kg/day versus being initiated directly at 2 mg/kg/day. METHODS: A retrospective cohort study was conducted using medical records of patients receiving propranolol therapy for infantile hemangiomas between October 2018-March 2021 at the Children's Hospital of Philadelphia. Patients were categorized by initial propranolol dosage: 1 or 2 mg/kg/day. The primary outcome measures included parent-reported adverse events, hypotension (defined by the Pediatric Advanced Life Support criteria), and bradycardia (defined as <1st percentile for age) following propranolol initiation. RESULTS: Out of the 244 patients identified, 123 were initiated at the 1 mg/kg/day dose, and 121 at the 2 mg/kg/day dose. There was no significant difference in the incidence of adverse events between the two groups (p = .057). Additionally, among patients initiated at 2 mg/kg/day, there were no significant differences in the incidence of age-related or weight-related adverse events for those younger than 2 months or those in the 1st or 2nd quartile for weight (p = .53). CONCLUSION: Infants and children initiated at 2 mg/kg/day did not demonstrate an increased incidence of adverse events associated with propranolol compared to those initiated at 1 mg/kg/day. These findings provide clinical evidence for the practice of accelerated propranolol initiation dosing.

Incomplete Kawasaki disease presenting with a cellulitis-like plaque: Lessons from an unusual presentation.

Kawasaki disease (KD) is an acute small to medium-vessel vasculitis that primarily affects children under the age of 5 years. The cause of KD is unknown, but it is hypothesized to be a systemic inflammatory illness triggered by infections in genetically predisposed individuals. Diagnosis of incomplete KD is made in patients with prolonged fever without a source who do not meet diagnostic criteria but have some findings consistent with KD such as elevated inflammatory markers, transaminitis, and echocardiographic findings. We present a 7-year-old boy who developed 10 days of fevers and rash that began 3 days after his first dose of hepatitis A vaccination and had notable features of a peculiar cellulitis-like plaque and peripheral eosinophilia.

Pediatric dermatologists versus AI bots: Evaluating the medical knowledge and diagnostic capabilities of ChatGPT.

This study evaluates the clinical accuracy of OpenAI's ChatGPT in pediatric dermatology by comparing its responses on multiple-choice and case-based questions to those of pediatric dermatologists. ChatGPT's versions 3.5 and 4.0 were tested against questions from the American Board of Dermatology and the "Photoquiz" section of Pediatric Dermatology. Results show that human pediatric dermatology clinicians generally outperformed both ChatGPT iterations, though ChatGPT-4.0 demonstrated comparable performance in some areas. The study highlights the potential of AI tools in aiding clinicians with medical knowledge and decision-making, while also emphasizing the need for continual advancements and clinician oversight in using such technologies.

Odyssey toward an understanding of acquired postinflammatory lentiginosis.

PURPOSE OF REVIEW: Acquired postinflammatory lentiginosis is a phenomenon that has been previously termed 'induction of lentiginosis in assorted dermatoses' or the ILIAD phenomenon. RECENT FINDINGS: Although some cases have been described as arising exclusively in those who applied topical calcineurin inhibitors (TCIs), other patients have presented with similar findings in other nonatopic disorders (contact dermatitis, psoriasis, lichen planus, focal dermal hypoplasia), and without antecedent use of TCIs. SUMMARY: Inflammatory skin disorders can produce localized areas of cutaneous lentiginosis, particularly as the inflammation retreats in response to treatment. This post-inflammatory lentiginosis or ILIAD phenomenon may be potentiated by use of topical and systemic anti-inflammatory medications, including TCIs, topical corticosteroids, methotrexate, and systemic biologic agents. Although this phenomenon has not been associated with melanocytic neoplasia, ongoing periodic monitoring for dysplastic changes is reasonable.

Shapiro xanthogranuloma: An essential diagnosis for dermatologists and dermatopathologists to recognize to avoid misdiagnosis of a hematopoietic malignancy in infants and neonates.

The Shapiro xanthogranuloma is a histopathologic form of xanthogranuloma that shows closely packed monomorphous cells, which can extend into the subcutaneous fat; it usually lacks routine diagnostic features of xanthogranuloma. Herein we describe two cases of Shapiro xanthogranuloma occurring in a neonate and in an infant, which were initially thought to be hematologic malignancies. One patient's presentation as a "blueberry muffin baby" added to the diagnostic confusion. Pediatric dermatologists, dermatologists, and dermatopathologists need to be aware of the Shapiro xanthogranuloma and its clinicopathologic features to avoid misdiagnosis of a hematopoietic malignancy in neonates and infants.

Carpet beetle dermatitis mimicking bullous impetigo.

A 13-year-old female patient presented with a 3-month history of recurrent blisters, which ruptured into multiple superficial erosions with overlying crust located on the face, neck, and shoulder. Treatment for presumed bullous impetigo showed no benefit. Samples collected from the patient's home revealed the presence of numerous carpet beetles in a wool rug. Carpet beetle dermatitis resembles papular urticaria but may occasionally present as skin lesions resembling bullous impetigo.

Acquired port-wine stains in six pediatric patients.

BACKGROUND/OBJECTIVES: Port-wine stains, also known as capillary malformations, are due to dermal vascular ectasia and dilation and are most commonly congenital; however, acquired port-wine stains (APWS) developing later in life have been noted in the literature, most commonly in the context of trauma. METHODS/RESULTS: This case series presents 6 pediatric patients with APWS who first developed lesions between ages 3 and 11 years in the absence of a traumatic or other etiologic trigger. CONCLUSIONS: The epidemiology, clinical features, and treatment response of these patients are compared to what has been previously described in other cases in the literature.

Cutaneous manifestations of congenital malignant rhabdoid tumor: Unusual papillomatous plaques and other skin presentations.

BACKGROUND/OBJECTIVES: Malignant rhabdoid tumors (MRT) are highly aggressive tumors with a predilection for the kidney, central nervous system, and soft tissues that usually affect young children under three years of age. Primary presentation in the skin is rarely reported, and features of the cutaneous manifestations are not well described. We report six cases of metastatic MRT that first manifested with congenital nodules and masses in the skin. METHODS: Retrospective case series. RESULTS: The cutaneous presentation of MRT may be heterogeneous and can present with solitary or multifocal skin lesions. Congenital polypoidal and papillomatous plaques, including those with histologic features of neurovascular hamartoma, appear to be a unique presentation of MRT in the infant. CONCLUSIONS: Malignant rhabdoid tumor should be considered in the differential diagnosis of unusual skin tumors in neonates and infants.

Association between fine mapping thymic stromal lymphopoietin and atopic dermatitis onset and persistence.

BACKGROUND: Atopic dermatitis (AD) is a common chronic relapsing skin disease. Genetic variants have been associated with skin barrier function and immune regulation. Thymic stromal lymphopoietin (TSLP), an immune regulator, has been previously associated with AD. OBJECTIVE: To fine map TSLP and evaluate associations with the onset and persistence of AD. METHODS: TSLP variation was determined using targeted massively parallel sequencing in a longitudinal cohort of children with AD. Evaluations included linkage disequilibrium and the persistence of AD for as many as 10 years of follow-up. The association between the presence of AD and rs1898671 variation was evaluated in a second independent cohort. RESULTS: The minor variant frequency for rs1898671 was 23.5% (95% CI, 21.4%-25.8%). This variant was not in linkage disequilibrium with other TSLP variants in the longitudinal cohort (n = 741). White children with AD were less likely to have rs1898671 variant (odds ratio [OR], 1.41; 95% CI, 1.20-1.66) than Genome Aggregation Database controls. Children with AD and the rs1898671 variant during follow-up were more likely to have remission than children who were wild type for rs1898671 (OR, 1.56; 95% CI, 1.26-1.91). In the second cohort (n = 585), the rs1898671 variant was less prevalent in those with AD than those without. The protective effect was greater in rs1898671 heterozygotes (OR, 1.91; 95% CI, 1.34-2.75) than homozygotes (OR, 1.28; 95% CI, 0.61-2.70). CONCLUSION: TSLP and specifically rs1898671 are important in the pathogenesis of AD and could represent a potential clinical target for the development of therapies to treat individuals with AD.

Longitudinal atopic dermatitis control and persistence vary with timing of disease onset in children: A cohort study.

BACKGROUND: Wide variation exists in the timing of atopic dermatitis (AD) disease onset among children. Distinct trajectories of early-onset, mid-onset, and late-onset AD have been previously described. OBJECTIVE: To evaluate longitudinal disease control and persistence with respect to age at onset of AD. METHODS: A cohort study was performed using the Pediatric Eczema Elective Registry, a prospective observational cohort of subjects with childhood-onset AD. AD control and persistence were assessed biannually for up to 10 years. RESULTS: A total of 8015 subjects with 41,934 person-years of follow-up were included. In longitudinal analyses using generalized linear latent and mixed modeling, older age at onset of AD was associated with better disease control and less-persistent AD. For each additional year of age at onset of AD, the adjusted odds ratios for poorer AD control and for persistent AD were 0.93 (95% confidence interval, 0.91-0.94) and 0.84 (95% confidence interval, 0.80-0.88), respectively. Differences in AD control and persistence among subjects with early-, mid-, and late-onset AD were most pronounced from early adolescence onward. LIMITATIONS: Misclassification bias may arise from using self-reported data on age at onset. Attrition and missing data in longitudinal studies may introduce bias. CONCLUSION: Early-, mid-, and late-onset pediatric AD appear to be clinically distinct subtypes of the disease.

Atenolol as an alternative to propranolol for the management of sleep disturbances in the treatment of infantile hemangiomas.

Infantile hemangiomas are the most common tumors of infancy and are often managed with oral beta-blockers to address or prevent associated complications. However, treatment with propranolol can occasionally be associated with sleep disturbances, which in some cases are severe enough to warrant discontinuation or replacement with another agent. We herein report four cases in which treatment with propranolol resulted in significant sleep disturbances prompting substitution with atenolol, which in some cases resolved these issues.

Evaluation of a modified outpatient model for using propranolol to treat infantile hemangiomas.

BACKGROUND: For infantile hemangiomas requiring treatment, existing recommendations advise initiation of propranolol followed by a 2-hour period of blood pressure and heart rate monitoring, resulting in prolonged office visits for both families and clinicians. OBJECTIVES: In order to reduce visit times, we evaluate our current practice of at-home or in-office propranolol administration followed by in-office vital sign monitoring. METHODS: We retrospectively reviewed the medical records of 157 patients with infantile hemangiomas (IH) who initiated propranolol under this outpatient protocol. Blood pressure (BP) and heart rate (HR) were obtained at a baseline visit and 1-2 hours after initial dose administration. We identified potential risk factors for clinically significant decreases in systolic blood pressure (SBP) and HR (defined as decrease of > 20 mm Hg and > 15 bpm, respectively) using logistic regression analysis, and adverse events were recorded. RESULTS: Fifty-five individuals (35.4%) showed a decrease in HR of more than 15 bpm, and 23 individuals (14.7%) showed a decrease in SBP of more than 20 mm Hg. Multivariable logistic regression suggested that younger age, history of preterm birth, and Caucasian race may slightly increase the odds of clinically significant changes in vital signs upon propranolol initiation. However, no clinically symptomatic adverse events occurred upon initiation of propranolol. CONCLUSIONS: Vital sign monitoring may be important when starting propranolol treatment in younger or historically preterm patients. However, routine mandatory in-office vital sign monitoring may not be necessary in healthy infants more than 45 weeks postconceptional age.

Pediatric leukemia cutis: A case series.

BACKGROUND: Pediatric leukemia cutis (LC) is often difficult to diagnose due to similarity in appearance to other dermatologic diseases. Several case reports and smaller case series have been published in the medical literature, but studies on larger cohorts of children with LC are lacking. OBJECTIVE: This study aimed to better characterize the clinical features, course, and prognosis of LC in the pediatric population. METHODS: We performed a retrospective case series of 31 patients diagnosed with LC at Boston Children's Hospital and the Children's Hospital of Philadelphia. RESULTS: The number and morphology of LC lesions varied among patients, with the head and lower extremities being the most common sites of involvement. Leukemia cutis presented concomitantly with systemic leukemia in the majority of cases. Most cases of LC arose during initial leukemia episodes, rather than with relapsed leukemia. Acute myeloid leukemia was the subtype most frequently associated with LC, followed by acute lymphoblastic leukemia. Diagnosis altered treatment timing and therapeutic decisions. CONCLUSION: Children most often present concomitantly with LC and systemic leukemia. Since the morphology and distribution of LC varies, physicians must maintain a high index of suspicion for this diagnosis, as the presence of LC may change the management of systemic leukemia.

Trachelas tranquillus envenomation with presumed bacterial superinfection in a child.

A 27-month-old girl with a history of congenital myopathy presented with two indurated, pink plaques involving the right arm and left thigh. Closer examination identified central puncta within these plaques, which reportedly occurred at sites of witnessed arachnid bites. After confirmation of the spider species as Trachelas tranquillus, she was treated to address cutaneous inflammation and suspected superinfection using oral and topical antibiotics as well as topical corticosteroid resulting in prompt resolution of her lesions. Trachelas tranquillus should be considered as a possible source of inflammatory spider bites that can become superinfected.

Aplasia cutis congenita: Evaluation of signs suggesting extracutaneous involvement.

Specific clinical features of aplasia cutis congenita may indicate the presence of underlying cranial or cerebrovascular defects, allowing for early recognition and intervention. Most information about aplasia cutis congenita exists as individual case reports, with few large-scale studies. We conducted a 7-year retrospective chart review of 90 cases of aplasia cutis congenita and identified clinical characteristics including morphology, number of lesions, anatomic location, presence of hair collar sign, associated cutaneous features, histology, and imaging results. The anatomic location of the lesion (vertex, midline) (P = .01), presence of hair collar sign (P < .001), vascular stains (P < .001), and nodules (P = .007) were found to be strong clinical indicators of skull or cerebrovascular involvement.

Angiomatoid and desmoplastic Spitz nevus presenting as a keloidal nodule.

Angiomatoid and desmoplastic Spitz nevi are rare histologic variants of Spitz nevi that present most frequently on the extremities of children and young adults. Although Spitz nevi are clinically heterogeneous, one presenting as a keloidal nodule has not been previously published. We present a case of an angiomatoid and desmoplastic Spitz nevus clinically akin to a keloid on an African-American teenager and describe its unique histopathologic features.

Unilateral hypertrophy of the labia minora: A case series.

Asymmetric hypertrophy of the labia minora is a variant of normal anatomy that has not been described in the pediatric dermatology literature. Although often asymptomatic, in some cases, it can cause functional, emotional, and psychological problems. We report the clinical characteristics and outcomes of four children who presented with unilateral labium minus hypertrophy. This case series aims to establish awareness of this condition among pediatric dermatologists and provide recommendations regarding management.

Holmes heart and tetralogy of Fallot in association with PHACE.

PHACE is an association between large infantile hemangiomas and brain, arterial, cardiac, and/or ocular abnormalities. Aortic or subclavian aberrations are the most common cardiovascular anomalies in PHACE, whereas complex congenital heart disease is rare. We report a case of Holmes heart and three cases of tetralogy of Fallot in PHACE association.