Development of an artificial intelligence algorithm for the diagnosis of infantile hemangiomas.

Prompt and accurate diagnosis of infantile hemangiomas is essential to prevent potential complications. This can be difficult due to high rates of misdiagnosis and poor access to pediatric dermatologists. In this study, we trained an artificial intelligence algorithm to diagnose infantile hemangiomas based on clinical images. Our algorithm achieved a 91.7% overall accuracy in the diagnosis of facial infantile hemangiomas.

Successful use of telemedicine for evaluation of infantile hemangiomas during the early COVID-19 pandemic: A cross-sectional study.

BACKGROUND/OBJECTIVES: The COVID-19 pandemic prompted a rapid expansion in the use of telemedicine. This study aimed to assess the experiences of hemangioma specialists utilizing telemedicine during the COVID-19 pandemic to evaluate and manage infantile hemangiomas (IH), including perceived effectiveness of different modalities and barriers to care delivery. METHODS: Multicenter cross-sectional study asking providers to describe their experiences using telemedicine for initial evaluation of IH from March to September 2020. RESULTS: The study included 281 patients from 15 medical centers internationally. Median time from referral to evaluation was 17 days. Median physician confidence in performing evaluations via telemedicine was 95.0 (IQR 90.0-100.0). Most evaluations were performed via video communication with photographs or audio communication with photographs; when not initially available, photographs were requested in 51.4%. Providers preferred follow-up modalities that included photographs. CONCLUSIONS: Physicians with extensive expertise in managing IH are confident in their abilities to assess and manage IH via telemedicine including initiating treatment in patients without risk factors for beta-blocker therapy. There was a preference for hybrid modalities that included photographs. The data suggest that telemedicine can be effective for managing IH and may decrease wait times and improve specialist reach to underserved areas.

Severe hypertriglyceridemia following sirolimus use in an infant.

Inhibitors of mammalian target of rapamycin function to downregulate cell growth and proliferation and have off-label use in pediatrics for vascular malformations. Hypertriglyceridemia is a known side effect of mammalian target of rapamycin (mTOR) inhibitors. Further studies to better understand the incidence and treatment of hypertriglyceridemia in infants and neonates are warranted.

Mapping of Segmental and Partial Segmental Infantile Hemangiomas of the Face and Scalp.

IMPORTANCE: Recognizing segmental infantile hemangioma (IH) patterns is important for risk stratification and provides clues to pathogenesis. Previously, segmental hemangiomas were mapped to 4 facial regions, 3 corresponding to known facial metameres. OBJECTIVES: To refine existing maps of facial segmental IHs, examine so-called indeterminate hemangiomas as they relate to known segmental patterns, and define a novel pattern of segmental scalp hemangiomas. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted at 4 pediatric dermatology centers (University of California, San Francisco; Indiana University; Medical College of Wisconsin; and Northwestern University/Ann & Robert H. Lurie Children's Hospital of Chicago) using photographic archives of patients younger than 12 years with segmental and indeterminate hemangiomas on the face and scalp. Clinical images were used to map hemangioma distribution onto standardized facial templates. Heat map densiometry identified recurrent patterns that were compared with previously published patterns of facial segmental hemangiomas. Patterns of indeterminate hemangiomas were compared with those of segmental hemangiomas. Data collection took place in 2017, and analysis took place from 2017 to 2019. MAIN OUTCOMES AND MEASURES: Distribution and patterning of segmental and indeterminate IHs of the face and scalp. RESULTS: A total of 549 IHs were mapped. The borders of the frontotemporal (S1) and frontonasal (S4) segments agreed with previous segmental maps; however, the maxillary (S2) and mandibular (S3) segment borders differed with respect to the preauricular skin. In contrast with previous reports, preauricular skin segregated with the mandibular (S3) rather than the maxillary (S2) segment. Indeterminate hemangiomas occurred within and respected the same borders as segmental hemangiomas. Hemangiomas on the lateral scalp commonly occurred in a C shape extending from the posterior auricular region. CONCLUSIONS AND RELEVANCE: This cohort study provides an updated map of facial segmental IHs with redefined maxillary (S2) and mandibular (S3) segment borders. It provides evidence that indeterminate hemangiomas are partial segmental hemangiomas respecting anatomic boundaries of their larger segmental counterparts. A newly recognized C-shaped pattern of segmental scalp hemangioma is reported.

Association of Demographic Factors and Infantile Hemangioma Characteristics With Risk of PHACE Syndrome.

Importance: A 2010 prospective study of 108 infants estimated the incidence of PHACE (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, eye anomalies) syndrome to be 31% in children with facial infantile hemangiomas (IHs) of at least 22 cm2. There is little evidence regarding the associations among IH characteristics, demographic characteristics, and risk of PHACE syndrome. Objectives: To evaluate demographic characteristics and comorbidities in a large cohort of patients at risk for PHACE syndrome and assess the clinical features of large head and neck IH that may be associated with a greater risk of a diagnosis of PHACE syndrome. Design, Setting, and Participants: This multicenter, retrospective cohort study assessed all patients with a facial, head, and/or neck IH who were evaluated for PHACE syndrome from August 1, 2009, to December 31, 2014, at 13 pediatric dermatology referral centers across North America. Data analysis was performed from June 15, 2017, to February 29, 2020. Main Outcomes and Measures: The main outcome was presence or absence of PHACE syndrome. Data included age at diagnosis, sex, patterns of IH presentation (including size, segment location, and depth), diagnostic procedures and results, and type and number of associated anomalies. Results: A total of 238 patients (mean [SD] age, 2.96 [4.71] months; 184 [77.3%] female) were included in the analysis; 106 (44.5%) met the criteria for definite (n = 98) or possible (n = 8) PHACE syndrome. A stepwise linear regression model found that a surface area of 25 cm2 or greater (odds ratio [OR] 2.99; 95% CI, 1.49-6.02) and involvement of 3 or more locations (OR, 17.96; 95% CI, 6.10-52.85) to be statistically significant risk factors for PHACE syndrome. Involvement of the parotid gland (OR, 0.39; 95% CI, 0.18-0.85) and segment S2 (OR, 0.38; 95% CI, 0.16-0.91) was associated with a lower risk. Race and ethnicity may also be associated with PHACE syndrome risk, although more studies are needed. Conclusions and Relevance: This cohort study further described factors associated with both a higher and lower risk of PHACE syndrome. The presence of multiple anatomical sites and large surface area were associated with greater risk, whereas S2 or parotid IHs were associated with lower, but still potential, risk. These findings can help in counseling families and decision-making regarding evaluation of infants with large head and neck IHs.

Neonatal lupus with left bundle branch block and cardiomyopathy: a case report.

BACKGROUND: Cardiac manifestations of neonatal lupus include an array of structural and conduction abnormalities due to placental transference of maternal anti-SSA/Ro and anti-SSB/La autoantibodies. Late-onset neonatal lupus cardiomyopathies, occurring outside the neonatal period, is an infrequently reported manifestation with unknown pathophysiology and poorly defined treatment regimens. Due to the rarity of this condition, additional studies and case reports are required to better understand and manage late-onset neonatal lupus cardiomyopathies. CASE PRESENTATION: A 4-week-old female, born to a mother with known anti-SSA/Ro and anti-SSB/La autoantibodies, presents with classic cutaneous manifestations for neonatal lupus and is found to have left bundle branch block, severely dilated cardiomyopathy with an ejection fraction of 25%, and a thin echogenic dyskinetic ventricular septum. Weekly second trimester and 30-week fetal echocardiograms showed no signs of structural or conduction abnormalities. There were no histologic signs of inflammation on cardiac tissue biopsy. After a complicated hospital course, she was successfully treated with biventricular pacemaker, intravenous immunoglobulin, and plasmapheresis. CONCLUSIONS: We present a case of late-onset neonatal lupus with severe dilated cardiomyopathy, a dyskinetic ventricular septum, and left bundle branch block. To our knowledge, the dyskinetic ventricular septum has never been reported and left bundle branch block is rarely reported in NL. This case further validates the need for long term cardiac follow up for patients born with NL, even if lacking cardiac manifestations in the peripartum period. We characterize a unique presentation of a rare clinical entity, highlighting the diagnostic challenges, and describe a successful treatment course.

Management of infantile hemangiomas during the COVID pandemic.

The COVID-19 pandemic has caused significant shifts in patient care including a steep decline in ambulatory visits and a marked increase in the use of telemedicine. Infantile hemangiomas (IH) can require urgent evaluation and risk stratification to determine which infants need treatment and which can be managed with continued observation. For those requiring treatment, prompt initiation decreases morbidity and improves long-term outcomes. The Hemangioma Investigator Group has created consensus recommendations for management of IH via telemedicine. FDA/EMA-approved monitoring guidelines, clinical practice guidelines, and relevant, up-to-date publications regarding initiation and monitoring of beta-blocker therapy were used to inform the recommendations. Clinical decision-making guidelines about when telehealth is an appropriate alternative to in-office visits, including medication initiation, dosage changes, and ongoing evaluation, are included. The importance of communication with caregivers in the context of telemedicine is discussed, and online resources for both hemangioma education and propranolol therapy are provided.

Bathing suit ichthyosis: Two Burmese siblings and a review of the literature.

Bathing suit ichthyosis (BSI) is a subtype of autosomal recessive congenital ichthyosis (ARCI) characterized by the development of large platelike scales mainly limited to the trunk. It is caused by temperature sensitive variants in transglutaminase 1, encoded by the gene TGM1. We describe a rare case of intrafamilial variation in phenotypic expressivity in two Burmese siblings with BSI that demonstrates the heterogeneity of the disorder within the same family and even in the same individual across time. We also present a concise review of the genotypic spectrum of BSI from 54 cases reported in the literature as evidence that both environmental and additional genetic factors can significantly alter the clinical phenotype.

Drug reaction with eosinophilia and systemic symptoms: Pediatric case series and literature review.

BACKGROUND: Pediatric Drug reaction with eosinophilia and systemic symptoms (DRESS) is an uncommon disease that can be difficult to diagnose. This case series and literature review highlights the clinical features of pediatric DRESS and underscores the differential diagnoses, culprit medications, and need for clinical follow-up to detect associated autoimmune sequelae. OBJECTIVE: To describe the clinical and laboratory features of pediatric DRESS, identify associated culprit medications, and discuss the natural history of disease. METHODS: Ten cases of pediatric DRESS were identified in the electronic medical record by searching the inpatient dermatology consultation list at Indiana University between 2013 and 2018. Clinical and laboratory data were collected including demographics, differential diagnoses, culprit medications, resolution of disease, and autoimmune sequelae. RESULTS: Pediatric patients with DRESS presented at a mean age of 11.5 years and demonstrated a mean time from drug initiation to onset of symptoms of 4 weeks. The most common inciting drugs included antibiotics (62.5%) followed by antiepileptics (37.5%). Rash and transaminitis resolved by 3 weeks, and 20% of patients, all female, developed autoimmune sequelae including Hashimoto's thyroiditis and an undifferentiated connective tissue disorder and occurred at an average of 14.5 weeks after diagnosis. LIMITATIONS: This was a small retrospective study of an uncommon clinical diagnosis at a single institution. CONCLUSIONS: Pediatric DRESS was most commonly caused by antibiotics which are being increasingly recognized in the literature as the predominant culprit medications. The development of autoimmune sequelae is a notable consequence that can present weeks after illness and may preferentially affect female patients.

Late growth of infantile hemangiomas in children >3 years of age: A retrospective study.

BACKGROUND: The proliferative phase of infantile hemangiomas (IHs) is usually complete by 9 months of life. Late growth beyond age 3 years is rarely reported. OBJECTIVE: To describe the demographic and clinic characteristics of a cohort of patients with late growth of IH, defined as growth in a patient >3 years of age. METHODS: A multicenter, retrospective cohort study. RESULTS: In total, 59 patients, 85% of which were female, met the inclusion criteria. The mean first episode of late growth was 4.3 (range 3-8.5) years. Head and neck location (55/59; 93%) and presence of deep hemangioma (52/59; 88%) were common characteristics. Posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities (PHACE) syndrome was noted in 20 of 38 (53%) children with segmental facial IH. Systemic therapy (corticosteroid or ß-blocker) was given during infancy in 58 of 59 (98%) and 24 of 59 (41%) received systemic therapy (ß-blockers) for late IH growth. LIMITATIONS: The retrospective nature and ascertainment by investigator recall are limitations of the study. CONCLUSION: Late IH growth can occur in children after 3 years of age. Risk factors include head and neck location, segmental morphology, and involvement of deep dermal/subcutaneous tissues.

Epidermolysis bullosa simplex-generalized severe type due to keratin 5 p.Glu477Lys mutation: Genotype-phenotype correlation and in silico modeling analysis.

BACKGROUND/OBJECTIVES: Epidermolysis bullosa is a group of diseases caused by mutations in skin structural proteins. Availability of genetic sequencing makes identification of causative mutations easier, and genotype-phenotype description and correlation are important. We describe six patients with a keratin 5 mutation resulting in a glutamic acid to lysine substitution at position 477 (p.Glu477Lys) who have a distinctive, severe and sometimes fatal phenotype. We also perform in silico modeling to show protein structural changes resulting in instability. METHODS: In this case series, we collected clinical data from six patients with this mutation identified from their national or local epidermolysis bullosa databases. We performed in silico modeling of the keratin 5-keratin 14 coil 2B complex using CCBuilder and rendered with Pymol (Schrodinger, LLC, New York, NY). RESULTS: Features include aplasia cutis congenita, generalized blistering, palmoplantar keratoderma, onychodystrophy, airway and developmental abnormalities, and a distinctive reticulated skin pattern. Our in silico model of the keratin 5 p.Glu477Lys mutation predicts conformational change and modification of the surface charge of the keratin heterodimer, severely impairing filament stability. CONCLUSIONS: Early recognition of the features of this genotype will improve care. In silico analysis of mutated keratin structures provides useful insights into structural instability.

Localized infantile hemangiomas of the face and scalp: Predilection for the midline and periorbital and perioral skin.

BACKGROUND/OBJECTIVES: Infantile hemangiomas are common vascular tumors. Identifying sites of predilection may provide insight into pathogenesis. Previous studies have suggested a predilection for the boundary of facial metameres. The objective was to observe patterns of localized hemangiomas on the face and scalp, determine sites of predilection, and place these patterns in a developmental context. METHODS: A retrospective review of photographic archives at 10 Hemangioma Investigator Group pediatric dermatology centers identified localized infantile hemangiomas of the face and scalp. Heat map software was used to identify areas of predilection. Dot maps were used to assess frequency, and densities of infantile hemangiomas were compared between facial units using t-testing. The scalp was divided into quintiles to assess relative frequencies. RESULTS: Four thousand one hundred fifty-three focal face and scalp infantile hemangiomas were mapped, of which 2962 (71%) were mapped to a frontal facial template. On the face, 73.8% (2186/2962) of hemangiomas occurred along the midline axis or perpendicularly across the ocular axis in a cross-shaped area of predilection intersecting at the glabella. Scalp hemangiomas show a predilection for the midline, with 149/295 (50.5%) noted on the top of the scalp at the midline (P < 0.001). Localized hemangiomas do not demonstrate a preferential laterality. CONCLUSION: The distribution of localized infantile hemangiomas of the face and scalp is not random. There is preferential involvement of the midline face and scalp and the ocular axis. The regions corresponding to the boundaries between the embryonic facial segments, including the maxillary and mandibular metameres, are not accentuated in the distribution of infantile hemangiomas.

Compound heterozygous mutations in desmoplakin associated with skin fragility, follicular hyperkeratosis, alopecia, and nail dystrophy.

Desmoplakin mutations are associated with a wide variety of phenotypes affecting the skin, nails, hair, and heart. A 21-month-old boy was born with multiple erosions resembling epidermolysis bullosa, complete alopecia, nail dystrophy, palmoplantar keratoderma, and areas of follicular hyperkeratosis. He was found to have two heterozygous mutations in the desmoplakin gene: c.478 C>T in exon 4 (p.Arg160X) and c.3630T>A in exon 23 (Tyr1210X). This case expands the clinical spectrum associated with desmoplakin mutations and highlights a mutation in exon 23 that has not been previously reported in the literature.

Peters anomaly in PHACE syndrome.

PHACE syndrome is a rare neurocutaneous disorder, with a complex pathogenesis. It presents with a large facial hemangioma associated with anomalies of the posterior fossa of the brain, arterial anomalies, cardiac anomalies, coarctation of the aorta, and eye anomalies. Ocular abnormalities are rare. We report the first published case of an infant with PHACE syndrome and Peters anomaly.

Utility of the Hemangioma Severity Scale as a Triage Tool and Predictor of Need for Treatment.

BACKGROUND/OBJECTIVES: Infantile hemangiomas (IHs) are commonly encountered in primary care and most often remain asymptomatic, resolving without sequelae. Certain characteristics are associated with a greater risk of complications, associated anomalies, and disfigurement. The heterogeneous presentation poses a clinical challenge for physicians in determining the need for treatment and subspecialty referral. This study aims to evaluate the utility of the previously published Hemangioma Severity Scale (HSS) to predict the need for treatment. METHODS: This retrospective study included 106 patients with IHs seen in the Indiana University Dermatology Clinic in 2011. Data from electronic medical records and clinical photographs taken at patients' initial visits were used to score the hemangiomas using the HSS. Treatments used over 9 to 14 months of follow-up were recorded. RESULTS: Four HSS score subgroups were identified. Higher HSS scores correlated with the need for treatment; 98% of patients with HSS scores of 10 or greater received local or systemic therapy. Higher HSS scores also correlated with greater frequency of complications and risks of associated structural anomalies and permanent disfigurement. Scores did not correlate with sex, age at initial presentation, history of bleeding or pain, or IH size. CONCLUSIONS: The HSS may be a useful tool for primary care physicians in identifying high-risk IHs that may benefit from therapy. This easy-to-use scale can improve clinical outcomes by identifying which patients need intervention to minimize complications. IHs with total HSS scores of 6 or greater should be referred for subspecialty evaluation.

Neurodevelopmental Outcomes in Children with PHACE Syndrome.

BACKGROUND: Practitioners who work with children with posterior fossa, facial hemangiomas, arterial anomalies, cardiovascular anomalies, and abnormalities of the eye (PHACE) syndrome need information about neurodevelopmental outcomes to provide appropriate anticipatory guidance and education for parents. This study aimed to determine the neurodevelopmental outcomes in children with PHACE syndrome and identify which children may be at greatest risk for delays. METHODS: Children with a diagnosis of PHACE syndrome (ages 4-18 yrs) were recruited from the PHACE Syndrome International Clinical Registry and Genetic Repository. Participants (n = 25) underwent a neurodevelopmental evaluation at a children's hospital tertiary care referral center between 2009 and 2013. Children completed standardized neurocognitive tests assessing multiple domains. Parents completed standardized questionnaires assessing behavioral and emotional functioning. RESULTS: Results were analyzed according to cohort and individual subject. Mean scores for the cohort did not differ significantly from test norms in most domains. The only subtest that the cohort scored lower on than test norms was Word Structure, a language task. Forty-four percent of the sample scored within the normal range in all domains, 28% had one score in the at-risk range (1-2 standard deviations [SDs] below the mean), 12% had two or more scores in the at-risk range, and 16% had at least one score in the impaired range (>2 SDs below the mean). CONCLUSION: Although most children in this cohort of patients with PHACE syndrome did not have significant neurodevelopmental deficits, a subset of patients had delays in multiple areas. Practitioners who work with these children should routinely ask about neurocognitive and developmental skills. Children with more severe phenotypes should be referred for appropriate evaluations and intervention services.

Rebound Growth of Infantile Hemangiomas After Propranolol Therapy.

BACKGROUND AND OBJECTIVES: Propranolol is first-line therapy for problematic infantile hemangiomas (IHs). Rebound growth after propranolol discontinuation is noted in 19% to 25% of patients. Predictive factors for rebound are not completely understood and may alter the management approach. The goal of the study was to describe a cohort of patients with IHs treated with propranolol and to identify predictors for rebound growth. METHODS: A multicenter retrospective cohort study was conducted in patients with IHs treated with propranolol. Patient demographic characteristics, IH characteristics, and specifics of propranolol therapy were obtained. Episodes of rebound growth were recorded. Patients' responses to propranolol were evaluated through a visual analog scale. RESULTS: A total of 997 patients were enrolled. The incidence of rebound growth was 231 of 912 patients (25.3%). Mean age at initial rebound was 17.1 months. The odds of rebound among those who discontinued therapy at <9 months was 2.4 (odds ratio [OR]: 2.4; 95% confidence interval [CI]: 1.3 to 4.5; P = .004) compared with those who discontinued therapy between 12 to 15 months of life. Female gender, location on head and neck, segmental pattern, and deep or mixed skin involvement were associated with rebound on univariate analysis. With multivariate analysis, only deep IHs (OR: 3.3; 95% CI: 1.9 to 6.0; P < .001) and female gender (OR: 1.7; 95% CI: 1.1 to 2.6; P = .03) were associated. Of those with rebound growth, 83% required therapeutic modification including 62% of patients with modifications in their propranolol therapy. CONCLUSIONS: Rebound growth occurred in 25% of patients, requiring modification of systemic therapy in 15%. Predictive factors for rebound growth included age of discontinuation, deep IH component, and female gender. Patients with these predictive factors may require a prolonged course of therapy.

Development and Validation of a Quality-of-Life Instrument for Infantile Hemangiomas.

Infantile hemangiomas (IH) are common tumors for which there is no validated disease-specific instrument to measure the quality of life in infants and their parents/caregivers during the critical first months of life. This study prospectively developed and validated a quality-of-life instrument for patients with IH and their parents/caregivers and correlated demographic and clinical features to the effects on the quality of life. A total of 220 parents/caregivers completed the 35-item Infantile Hemangioma Quality-of-Life (IH-QoL) instrument and provided demographic information. The dimensionality of the items was evaluated using factor analysis, with results suggesting four factors: child physical symptoms, child social interactions, parent emotional functioning, and parent psychosocial functioning. Each factor fit the Rasch measurement model with acceptable fit index (mean square <1.4) and demonstrated excellent internal consistency, with alpha ranging from 0.76 to 0.88. The final instrument consists of four scales with a total of 29 items. Content validity was verified by analyzing parents' responses to an open-ended question. Test-retest reliability at a 48-hour interval was supported by a total IH-QoL intraclass correlation coefficient of 0.84. Certain clinical characteristics of hemangioma, including those located on the head and neck, in the proliferative stage, and requiring treatment, are associated with a greater impact on QoL.

Pyoderma gangrenosum associated with an aseptic splenic abscess in a patient with neurofibromatosis.

Pyoderma gangrenosum (PG) is a painful, ulcerating neutrophilic dermatosis commonly associated with a variety of underlying systemic conditions. We report a child with neurofibromatosis-1 (NF-1) and an aseptic splenic abscess who developed multifocal PG in areas of iatrogenic skin trauma. There is no clinical evidence or theoretical basis to suggest a causal relationship between NF-1 and PG. Systemic corticosteroid and cyclosporine therapy led to complete resolution of the lesions.