Delphi Consensus on Diagnostic Criteria for LUMBAR Syndrome.

OBJECTIVE: To develop consensus on diagnostic criteria for LUMBAR syndrome, the association of segmental infantile hemangiomas that affect the Lower body with Urogenital anomalies, Ulceration, spinal cord Malformations, Bony defects, Anorectal malformations, Arterial anomalies and/or Renal anomalies. STUDY DESIGN: These diagnostic criteria were developed by an expert multidisciplinary and multi-institutional team based on analysis of peer-reviewed data, followed by electronic-Delphi consensus of a panel of 61 international pediatric specialists. RESULTS: After 2 Delphi rounds, a 92% or higher level of agreement was reached for each Delphi statement. 98% of panelists agreed with the diagnostic criteria, and 100% agreed the criteria would be useful in clinical practice. The diagnosis of LUMBAR requires the presence of a segmental, or patterned, infantile hemangioma of the lumbosacral, sacrococcygeal, or pelvic cutaneous regions plus one additional criterion of the urogenital, spinal, bony, anorectal, arterial, or renal organ systems. CONCLUSIONS: These diagnostic criteria will enhance clinical care by improving screening, detection, and overall awareness of this poorly understood neurocutaneous disorder. The criteria can be utilized by a wide variety of pediatric subspecialists. In addition, formal criteria will improve phenotypic uniformity among LUMBAR syndrome cohorts and a patient registry, allowing investigators to assess clinical features, long-term outcomes, and results of genetic sequencing in a standardized manner. Finally, these criteria will serve as a starting point for prospective studies to establish formal screening and management guidelines.

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.

Severity of multisystem inflammatory syndrome in children (MIS-C) in patients with and without mucocutaneous findings.

BACKGROUND: There are few studies comparing severity of MIS-C disease with mucocutaneous symptoms, age, race, and ethnicity. OBJECTIVE: To describe the mucocutaneous symptoms present on admission and evaluate whether these symptoms are correlated with a more severe MIS-C disease course. METHODS: Retrospective cohort study of hospitalized patients with suspected MIS-C between May 13, 2020 to April 21, 2021. RESULTS: Of the 66 patients who met the inclusion criteria, 84.8% (56/66) exhibited mucocutaneous findings. The most common mucocutaneous symptoms were rash, conjunctivitis, cracked lips, and sore throat. Children with mucocutaneous symptoms were younger (median 9.8 years) compared to those without (11.4 years), p = .39. The groups had similar proportions of pediatric intensive care unit admission, abnormal cardiology studies, and necessity of pressors. The presence of mucocutaneous findings on admission was associated with a lower troponin level on admission (median 0.08 ng/ml vs. 0.52, p = .003). Black children had higher odds of severe MIS-C compared to White children (odds ratio [95% CI]: 3.30 [1.02, 10.72], p = .047). Children ≥5 years of age had greater odds of severe MIS-C compared to children <5 years of age (odds ratio [95% CI]: 5.43 [1.39, 21.23], p = .02). LIMITATIONS: The sample size was relatively small, there was no dermatologist present on admission, initial diagnostic testing and management varied if patients presented at outside hospitals, and the CDC case definition for MIS-C was highly sensitive. CONCLUSION: The presence of mucocutaneous symptoms negatively correlated with troponin levels, but there was no significant association between these symptoms and other markers of cardiac involvement (echocardiogram, ejection fraction, electrocardiogram).

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.

A rare presentation of herpes simplex virus encephalitis occurring in a pediatric patient on dupilumab for atopic dermatitis.

A 4-year-old female with a history of atopic dermatitis developed herpes simplex virus (HSV) encephalitis while being treated with dupilumab and concomitant topical steroids. There was no prior history of HSV infections or immunodeficiency. To our knowledge, this is the first case of HSV encephalitis in a patient receiving dupilumab.

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.

Limited utility of repeated vital sign monitoring during initiation of oral propranolol for complicated infantile hemangioma.

BACKGROUND: Initial propranolol recommendations for infantile hemangioma published in 2013 were intended as provisional best practices to be updated as evidence-based data emerged. METHODS: A retrospective multicenter study was performed to evaluate utility of prolonged monitoring after first propranolol dose and escalation(s). Inclusion criteria included diagnosis of hemangioma requiring propranolol of greater than or equal to 0.3 mg/kg per dose, younger than 2 years, and heart rate monitoring for greater than or equal to 1 hour. Data collected included demographics, dose, vital signs, and adverse events. RESULTS: A total of 783 subjects met inclusion criteria; median age at initiation was 112 days. None of the 1148 episodes of prolonged monitoring warranted immediate intervention or drug discontinuation. No symptomatic bradycardia or hypotension occurred during monitoring. Mean heart rate change from baseline to 1 hour was -8.19/min (±15.54/min) and baseline to 2 hours was -9.24/min (±15.84/min). Three preterm subjects had dose adjustments because of prescriber concerns about asymptomatic vital sign changes. No significant difference existed in pretreatment heart rate or in heart rate change between individuals with later adverse events during treatment and those without. CONCLUSION: Prolonged monitoring for initiation and escalation of oral propranolol rarely changed management and did not predict future adverse events. Few serious adverse events occurred during therapy; none were cardiovascular.

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.

Segmental infantile hemangioma and concomitant hypertension in three African American neonates.

We present three African American infants with segmental, ulcerated infantile hemangiomas and concomitant, persistent hypertension. When treated with beta-blocker therapy, the hemangiomas decreased in size and the ulcerations resolved, but there was no impact on the elevated blood pressure in one of our patients. We failed to identify any associations between infantile hemangioma and hypertension in the literature.

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.

Seborrhea herpeticum: cutaneous herpes simplex virus infection within infantile seborrheic dermatitis.

Eczema herpeticum has been well described in the setting of atopic dermatitis (AD) and other dermatoses. We present the case of a 2-month-old infant boy with cutaneous herpes simplex virus (HSV) infection within existing diffuse infantile seborrheic dermatitis. Providers should be aware that cutaneous HSV can be confined to a seborrheic distribution and may represent underlying epidermal dysfunction secondary to seborrheic dermatitis.

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.