Looking at the variations in catching hearing loss

Catching hearing loss early is key to helping a child achieve optimal outcomes. However, a new report examines the variations that can occur for diagnosing and treating.

During the evaluation of a healthy 7-year-old boy, an asymptomatic brown “dirt-like” rash is found on the anterior neck. It has progressed over the last 2 months and does not clear with routine bathing and aggressive scrubbing by his mother with soap and water.

Age of exposure to household dysfunction could be linked to future adverse outcomes

A report examines whether the age a child is exposed to dysfunctional behavior in their homes was linked to future adverse outcomes.

Study examines if ASD increases substance use disorder risk

An investigation examines whether children with autism spectrum disorder (ASD) are at increased risk of substance use disorder.

Articles

It was a very busy week for the Contemporary Pediatrics team.

In case you missed it: January 11 to January 15

Ms. Hester is Content Specialist with Contemporary OB/GYN and Contemporary Pediatrics.

 more members to be appointed to the White House COVID-19 Response team, who will work to implement the Biden administration’s COVID-19 plan, which includes rapidly vaccinating as many Americans as possible, increasing testing rates, and restoring the public’s trust in the scientific information disseminated by the federal government.

David A. Kessler, MD, has been selected to be the Chief Science Officer of the COVID Response team. Kessler is currently a professor of pediatrics and epidemiology and biostatistics at the University of California, San Francisco and has served as the dean of medical schools at both Yale and University of California, San Francisco. He has previously served as the commissioner of the US Food and Drug Administration from 1990 to 1997 and was chair of the boards for both the Center for Science in the Public Interest and the Elizabeth Glaser Pediatric AIDS Foundation. He’s also an author of several books on public health.

In the press release for the announcement, President-elect Biden stated, “The individuals announced today will bolster the White House’s COVID-19 Response team and play important roles in carrying out our rescue plan and vaccination program. At a time when American families are facing numerous challenges I know these public servants will do all that is needed to build our nation back better.”

1. President-elect Joe Biden and Vice President-elect Kamala Harris announce additional members of the White House COVID-19 response team. President-Elect Joe Biden. Published January 15, 2021. Accessed January 15, 2021. 

https://buildbackbetter.gov/press-releases/president-elect-joe-biden-and-vice-president-elect-kamala-harris-announce-additional-members-of-the-white-house-covid-19-response-team/

The Biden transition team has named more members of the COVID-19 response team, including pediatrician and lawyer Dr. Kessler.

David A. Kessler, MD, named Chief Science Officer of the COVID Response team   

It is now 2021, and our understanding of the novel coronavirus first reported in Wuhan, China in December 2019 has drastically expanded due largely to the extensive number of individuals who have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide, as well as those who have exhibited symptoms of disease from this virus (COVID-19). Currently, the increase in incidence throughout the country is significantly impacting our health care system capacity. Whereas children in general have been reported to experience less disease from infection with SARS-CoV-2, the nationwide surge in cases has led to an increase in pediatric hospitalizations, as well as cases of multisystem inflammatory syndrome in children (MIS-C). Despite a growing number of cases throughout the United States, we have greatly improved our understanding of infection control measures to curb transmission, have better access to personal protective equipment (PPE), and have improved testing availability to aid in mitigating transmission. We must now reduce community, household, and workplace transmission to relieve the strain that an ill and reduced workforce is having on the health care system.

What we know right now: SARS-CoV-2 infection in children

Due to variation in public health reporting, accurate numbers of SARS-CoV-2 infected pediatric patients are a challenge to obtain. However, available data show a consistent increase in pediatric patients that tested positive for SARS-CoV-2 over the past year, and particularly the past several months. As of November 19, 2020, the American Academy of Pediatrics/Children’s Hospital Association (AAP/CHA) Children and COVID-19: State Data Report

 reported 1,183,609 cumulative child cases, representing 11.8% of total cases reported and 1572.6 cases per 100,000 children. Fifty-seven percent of these cases were reported since September 2020.

Despite climbing numbers of pediatric SARS-CoV-2 infections, children continue to be proportionally less affected by infection than adults. Although children represent about 22% of the United States population, they represent only 1.8% of total hospitalizations related to SARS-CoV-2.

 The scope of asymptomatic infections in children is challenging to fully represent due to the retrospective nature of current reports, but estimates range between 5% and 35%.

 Children presenting to care with symptoms and subsequently diagnosed with SARS-CoV-2 infection most commonly have fever or cough.

 There is variation in representation of other complaints, including pharyngitis, rhinorrhea, congestion, headache, or gastrointestinal (GI) complaints. Children with some underlying medical conditions (obesity, asthma or chronic lung disease, and immunosuppression) are at greater risk for severe illness from SARS-CoV-2 infection.

 This does not, however, discount the potential for healthy children to develop severe disease or require hospitalization.

Although rates of severe illness due to SARS-CoV-2 are generally lower in children than adults, a hyperinflammatory syndrome associated with SARS-CoV-2 infection has been identified as MIS-C.

 As of December 9, 2020, 23 of these cases in the United States resulted in death.

 More than 75% of reported cases of MIS-C occurred in children of Hispanic/Latino or Black, non-Hispanic reported race/ethnicity and the average age was 8 years.

 The most common symptoms reported for children with MIS-C include GI complaints (abdominal pain, vomiting, diarrhea), rash, and conjunctival injection. Whereas some MIS-C patients may present with symptoms overlapping with Kawasaki disease or toxic shock syndrome, multiple case series of patients with MIS-C demonstrate clear differences between these patients, including age distribution, prominence of GI symptoms, the degree of multisystem organ involvement, and cardiogenic shock with myocardial dysfunction.

 Multiple studies are ongoing to better understand the pathophysiology of this inflammatory syndrome.

Infection prevention in community and health care settings

Understanding of SARS-CoV-2 transmission has increased exponentially throughout the pandemic. Basic concepts of infection prevention such as wearing face coverings/masks, hand hygiene, not working when ill, and social distancing have proved to be of the utmost importance for the health care setting and for the public, including our patients and their families. Although children who cannot remove their mask in case of an emergency or those with sensory sensitivities should not use face coverings, children aged as young as 2 years can learn to don them when out in public or at school. The epidemiologic curve in relation to social distancing and masking guidance over the past 10 months supports the use of these infection prevention methods. Additionally, household contact with an individual with SARS-CoV-2 is a risk factor for transmission, likely due to individuals exposing one another during the pre-symptomatic period and lack of use of face coverings within the household.

In-school learning is dependent upon the level of community transmission and ability to mitigate transmission of infections. School attendance is important not only for education, but also for food security, access to other services, and physical activity. If open, schools should enforce the basic principles described above: Masking and social distancing (depending on the age group), as well as extensive cleaning of the environment. Creation of cohorts of students and teachers (“pods”) within schools has helped alleviate the need to close an entire school in some circumstances. Testing, contact tracing, and school or class closure policies are contingent upon local transmission rates and other factors. Unlike other viruses such as influenza, younger children appear to be less affected by and less likely to spread SARS-CoV-2 than older children.

 Age-based schooling recommendations may therefore be an appropriate consideration, with greater emphasis on the ability of younger school-aged children to continue in-person learning even if this cannot be maintained in older age groups.

In the health care setting, use of negative pressure rooms, PPE, social distancing, environmental cleaning with focus on high touch surfaces, and hand hygiene decrease the likelihood of transmission of SARS-CoV-2 between patient and provider. Nosocomial transmission is likely more associated with lack of PPE particularly during prolonged exposure and/or performing aerosol-generating procedures (AGP) without the recommended PPE.

 Transmission dynamics of SARS-CoV-2 to date support transmission via direct or indirect contact with secretions, respiratory droplets, or fomites unless a procedure is being performed that may generate aerosol. Use of a face mask and eye protection has been shown to reduce risk of transmission.

 Face masks prevent large droplets from being breathed in, but also to prevent any viral secretions from going out. However, if an AGP is being performed, a respirator (eg, N95 respirator) should be employed to keep generated aerosols from being inhaled. The Infectious Diseases Society of America has published a table of AGPs to aid in decision making around PPE use.

 It is yet unclear whether SARS-CoV-2 can be spread through aerosol other than those generated by medical procedures, though the transmission dynamics of this virus does not match those of known airborne infections such as measles or varicella. Implementation of these infection control strategies can mitigate transmission of SARS-CoV-2 between health care personnel and patients if they are followed.

 Fatigue from using PPE and laxity with social distancing have more recently become real concerns and problems. Universal mask use and social distancing guidelines have been adopted within many health care settings, yet transmission among health care workers has become a new challenge when mask use is inconsistent. A recent Cochrane Review reported that a key facilitator to adherence to infection prevention guidelines among medical personnel was understanding the rationale behind the guide-lines.

 Education of team members is therefore likely the most important approach to take in the coming months as we face PPE fatigue and burnout in health care.

In addition to the continuing SARS-CoV-2 pandemic, we are now within the winter respiratory virus season. Though some reports from the Southern Hemisphere have shown a mild influenza season,

 it is difficult to predict what the United States can expect with influenza or any of the other winter respiratory viruses. Given the overlap of symptoms between SARS-CoV-2 and influenza infections, use of SARS-CoV-2 and influenza testing is crucial. Results will aid in identifying people who require isolation, inform contact tracing efforts, particularly for schools, and for those requiring hospitalization, inform treatment for either virus. Communities with more infection mitigation measures in place and adherence to those measures may have less influenza circulation than typically would be expected. Reinforcing the basics of infection prevention, promoting influenza vaccine for health care providers, patients, and families, in addition to maintaining high rates of routine immunizations will be important to alleviate hospital admission rates and reduce strain on hospital bed availability.

Strategies for treatment and immune modulation of the effects of SARS-CoV-2 continue to develop. An Emergency Use Authorization (EUA) was granted by the FDA for the use of hydroxychloroquine for treatment of COVID-19 and revoked in June 2020 due to insufficient data to show efficacy. In parallel, an EUA was granted for the use of remdesivir in May 2020. Recommendation for use is with or without dexamethasone in patients who are hospitalized and require supplemental oxygen

 (Table). In October 2020, remdesivir became the first drug approved by the FDA for treatment of COVID-19 in individuals aged ­12 years and ­40kg. Safety and efficacy in children aged <12 years has not yet been established, so use in this group remains under EUA. In November, bamlanivimab, a neutralizing monoclonal antibody targeting the spike protein of the SARS-CoV-2 virus was issued an EUA for use in non-hospitalized patients with mild-to-moderate SARS-CoV-2 infection who are at high risk for adverse effects from the infection (Table). In December, as this article was going to press, the Pfizer and BioNTech mRNA vaccine had just been granted EUA: Shortly thereafter, doctors and nurses throughout the country were televised receiving the first vaccines and plans have been made to distribute to additional health care workers. By the time this article is published, a second vaccine, developed by Moderna, might very well have been approved as well.

The Advisory Committee on Immunization Practices recommends a phased approach with initial vaccine being made available to the groups most at-risk for SARS-CoV-2 infection, including inpatient and outpatient health care personnel, first responders, and a variety of other health care personnel.

 Initial vaccine uptake will help maintain the health and availability of health care personnel to continue to provide both acute and preventative care to patients. Subsequent phases of vaccination will then be able to mitigate spread among the general community. The Pfizer-BioNTech vaccine is approved for persons aged 16 years and older, and the company has begun trialing vaccine administration for children ­12 years of age. Emphasis for now will therefore remain on uptake by adults and older children.

There have been many successes and many “educational moments” in our journey through the SARS-CoV-2 pandemic. The speed with which our large health care and public health systems, as well as our governments and communities, have had to mobilize and adapt to continually new information is tremendous. Early in the pandemic, focus was primarily on creating protocols and gaining better understanding of the virus and its dynamics. We have confirmed that public health and infection control measures can positively impact infection rates. Our concern in the health care setting has shifted from acquisition of SARS-CoV-2 from our patients to its acquisition from coworkers, community, or household members.

In the coming months, we will be challenged with continuing to care for the growing number of patients with SARS-CoV-2 and increasing rates of hospitalization, as well as managing distribution of new vaccines. We will still encounter school closures, be challenged with our patients’ and colleagues’ mental health, and continue to seek preventative care. However, looking back over the past 11 months, it is evident that we have made tremendous strides in understanding COVID-19, mitigating spread, treating the virus and its sequelae, and connecting scientists to advance our knowledge of this virus and how to combat it.

Children’s Hospital Association and American Academy of Pediatrics. Children and COVID-19: State data report – November 19, 2020. Accessed November 30, 2020. 

https://downloads.aap.org/AAP/PDF/AAP%20and%20CHA%20-%20Children%20and%20COVID-19%20State%20Data%20Report%2011.19.20%20FINAL.pdf

Zimmerman P, Curtis N. COVID-19 in children, pregnancy and neonates: A review of epidemiologic and clinical features. 

Assaker R, Colas AE, Julien-Marsollier F, et al. Presenting symptoms of COVID-19 in children: a meta-analysis of published studies. 

. 2020;125(3):e330-e332. doi:10.1016/j.bja.2020.05.026

Foster CE, Moulton EA, Munoz FM, et al. Coronavirus disease 2019 in children cared for at Texas Children’s Hospital: Initial clinical characteristics and outcomes. 

Shekerdemian LS, Mahmood NR, Wolfe KK, et al. Characteristics and outcomes of children with coronavirus disease 2019 (COVID-19) infection admitted to US and Canadian pediatric intensive care units. 

. 2020;174(9):868-873. doi:10.1001/jamapediatrics.2020.1948

Kim L, Whitaker M, O’Halloran A, et al. Hospitalization rates and characteristics of children aged <18 years hospitalized with laboratory-confirmed COVID-19 – COVID-NET, 14 states, March 1-July 25, 2020. 

. 2020;69(32):1081-1088. doi: 10.15585/mmwr.mm6932e3

Verma S, Lumba R, Dapul HM, Gold-von Simson G, et al. Characteristics of hospitalized children with SARS-CoV-2 in the New York City metropolitan area. 

. 2020. Epub ahead of print. doi: 10.1542/hpeds.2020-001917.

CDC. Information for healthcare providers about multisystem inflammatory syndrome in children (MIS-C). Accessed November 30, 2020. 

CDC. Multisystem inflammatory syndrome in children: Cases in the US. Accessed November 30, 2020. 

https://www.cdc.gov/mis-c/cases/index.html

Kaushik A, Gupta S, Sood M, Sharma S, Verma S. A systematic review of multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection. 

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Bautista-Rodriguez C, Sanchez-de-Toledo J, Clark BC, et al. Multisystem inflammatory syndrome in children: an international survey. 

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Laws RL, Chancey RJ, Rabold EM, et al. Symptoms and transmission of SARS-CoV-2 among children – Utah and Wisconsin, March-May 2020. 

Grijalva CG, Rolfes MA, Zhu Y, et al. Transmission of SARS-COV-2 infections in households — Tennessee and Wisconsin, April–September 2020. 

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Leeb RT, Price S, Sliwa S, et al. COVID-19 trends among school-aged children – United States, March 1-September 19, 2020. 

 2020; 69(39):1410-1415. 10.15585/mmwr.mm6939e2

Coronado F, Blough S, Bergeron D, et al. Implementing Mitigation Strategies in Early Care and Education Settings for Prevention of SARS-CoV-2 Transmission — Eight States, September–October 2020. 

Heinzerling A, Stuckey MJ, Scheuer T, et al. Transmission of COVID-19 to health care personnel during exposures to a hospitalized patient - Solano County, California, February 2020. 

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Chu DK, Akl EA, Duda S, Solo K, Yaacoub S, Schünemann HJ. Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis. 

Lynch JB, Davitkov P, Anderson DJ, et al. Infectious Diseases Society of America guidelines on infection prevention for health care personnel caring for patients with suspected or known COVID-19. 

Baker MA, Fiumara K, Rhee C, et al. Low risk of COVID-19 among patients exposed to infected healthcare workers. 

Houghton C, Meskell P, Delaney H, et al. Barriers and facilitators to healthcare workers’ adherence with infection prevention and control (IPC) guidelines for respiratory infectious diseases: a rapid qualitative evidence synthesis. 

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Olsen SJ, Azziz-Baumgartner E, Budd AP, et al. Decreased influenza activity during the COVID-19 pandemic – United States, Australia, Chile, and South Africa, 2020. 

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https://www.covid19treatmentguidelines.nih.gov/

McClung N, Chamberland M, Kinlaw K, et al. The Advisory Committee on Immunization Practices’ ethical principles for allocating initial supplies of COVID-19 vaccine — United States, 2020. 

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What we knew about COVID-19 when the pandemic began, what we know now.

State of the union on COVID-19

A child’s language abilities are an important element to his or her academic outcomes, which have long-reaching health consequences. A 

 offers a look at how early life factors can impact these abilities later in life.

The researchers used participants that were in a prospective community cohort study of infants who were recruited at 8 to 10 months of age. Each child completed 11-year data collection; participated in language assessments at 2, 4, 5, and 7 years of age; and completed National Assessment Program – Literacy and Numeracy (NAPLAN) tests at any or all of the following year levels at school: grades 3, 5, and 7, on average approximately ages 8, 10, and 12 years of age. The early life factors examined included prematurity, birth weight, family history of language difficulties, and maternal vocabulary as well as education.

The researchers concluded that 11% to 12% of the variance in language scores seen in children at 11 years of age was explained by early life factors. This variance then increased to 47% to 64% if the language scores from the assessments at 2 and 7 years of age were also increased. They found that the largest variance increase could be explained with scores at 4 years of age. Same early life factors were found to explain 13% to 14% of academic scores for children aged 11 years. Additionally, early life factors were found to adequately discriminate between children with low and typical language scores, but these factors were much better at discriminating between children with typical and low academic scores.

They concluded that a child’s language outcome at 11 years of age can be accurately predicted using the child’s language ability at 4 years of age. Additionally, academic outcomes at age 11 years can be predicted using early familial and home environment factors. Children aged 11 years who were found to have low language abilities were found to consistently perform poorly on assessments of literacy and numeracy. The results highlight the need to begin assessment of a child’s language abilities early in life as well as understand the child’s family history and home environment to help the child achieve the optimal outcome.

1. Eadie P, Bavin E, Bretherton L, et al. Predictors in infancy for language and academic outcomes at 11 years. 

. January 11, 2021. Epub ahead of print. doi:10.1542/peds.2020-1712

A new report examines how early language abilities can successfully predict a child’s future facility with language, which can ensure good outcomes.

Early language ability predicts future language outcomes

The urgent need for more research in children has been a cause for concern for quite some time, particularly research into infants. However, it can be difficult to enroll children from this population. An 

 examines the differences between parents who enroll their infant in clinical trials versus parents who decide to not enroll.

The investigators used a survey in 12 US level 3 and 4 neonatal intensive care units to assess the parents of infants who had enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial as well as the parents who had infants who were eligible to be in the study, but had declined to be involved. The questions in the survey were created with the belief that parents who enrolled in the study versus those who didn’t were different in 4 different categories: trust in the clinicians and researchers, how the parent perceived the infant’s illness, the parent’s understanding of the study, and characteristics of the infant as well as the parent’s demographic information.

A total of 387 parents were eligible and 269 completed the survey, which included 183 parents who enrolled their child in HEAL and 86 parents who did not enroll their child. The researchers found that parents who enrolled in the study had a higher rate of having an annual income greater than $55,000 (94 [52.8%] vs 30 [37.5%]; 

 = .03) as well as lower rates of being a Medicaid participant (74 [41.1%] vs 47 [55.3%]; 

 = .04) than the parents who chose to decline. Additionally, Black parents had a lower enrollment rate than white parents (odds ratio [OR], 0.35; 95% CI, 0.17-0.73). Those who said that their child’s condition was more serious also had higher enrollment rates (OR, 5.7; 95% CI, 2.0-16.3). Trust in the medical researchers was also greater in parents who enrolled than in those who declined (mean difference, 5.3 [0.3-10.3]). Parental understanding of the study was not found to have any link to enrollment.

The reviewers concluded that a variety of factors impacted a parent’s decision to participate in clinical research. They believed that further research should be done to offer more confirmation of the results and understand the reasons behind the groups that declined, especially because these groups have often been underrepresented in clinical researcher.

1. Weiss E, Olszewski A, Guttmann K, et al. Parental factors associated with the decision to participate in a neonatal clinical trial. 

. 2021;4(1):e2032106. doi:10.1001/jamanetworkopen.2020.32106

With the drive to practice evidence-based medicine, the need for robust clinical research in pediatrics is more important than ever, but it can still be a struggle to get parents to enroll their children. An investigation offers insight into some factors that can influence the decision to enroll.

 Why parents choose not to enroll in clinical research

A newborn boy born via normal vaginal delivery at 38.6 weeks gestation to a 33-year-old G5P2022 mother presented at birth with an asymptomatic 8-mm red, papulonodule with central crusting on the right cheek (Figure 1). Pregnancy had been complicated by maternal type 2 diabetes mellitus and obesity. Delivery was uncomplicated and the patient was otherwise healthy.

Mother was otherwise healthy and the pregnancy was uneventful. Medications that were used during the pregnancy included prenatal vitamins, insulin, ranitidine, and diphenhydramine. All antenatal ultrasounds, serologies, and labs were unremarkable. Mother reported no relevant personal or family history, specifically no history of herpes simplex virus (HSV) infection, other viral infections, leukemia/lymphoma, or immunodeficiencies.

Initial physical examination revealed a well appearing infant. The Apgar scales were 9, 9, and 9 at 1, 5, and 10 minutes respectively. Patient weighed 3485 grams, an appropriate weight for his gestational age. Vital signs were within normal limits upon delivery.

Skin examination revealed an asymptomatic, round, red, non-blanching, 8-mm firm papulonodule on the right cheek. The lesion had an erythematous base with no drainage or crusting on initial exam. Central crusting later developed on the first day of life. The patient did not appear bothered by the lesion. Physical exam was otherwise unremarkable.

The patient received all routine neonatal labs. Hemoglobin and hematocrit levels were within normal limits. He required 2 oral glucose gels prior to glucose normalization. Metabolic screens were within normal limits. At 24 hours of life, C-reactive protein and a complete blood count were drawn and returned with no abnormalities.

Ultrasound of the lesion of the right cheek demonstrated a heterogeneous, hypoechoic lesion with no evidence of increased vascularity. Pediatric dermatology was consulted for further evaluation of the lesion and performed a biopsy that revealed Langerhans cells with surrounding inflammatory cells and eosinophils (Figures 2 and 3). A cutaneous proliferation of CD1a, CD68, and S100 positive cells was also confirmed via immunohistochemical staining (Figures 4 and 5). Fungal cultures, aerobe-anaerobe cultures, and an acid-fast bacilli culture were negative. These findings were typical of cutaneous Langerhans cell histiocytosis.

The initial differential diagnosis included several infectious and noninfectious etiologies that could account for such a skin lesion (Table). Infantile hemangiomas were high on the differential, as these are the most common skin neoplasms presenting in infancy.

 These are benign vascular tumors with a prevalence of 4%-10% worldwide.1 Ultrasound imaging may demonstrate an increase in internal vascularity. Ultrasound of our patient on day 1 of life indicated no prominent internal vascularity, making the diagnosis of infantile hemangioma less likely. Moreover, the presence of a nodule at birth and uniform blanching erythema with central crusting would not be typical of a classic infantile or congenital hemangioma.

Langerhans cell histiocytosis (LCH) was another diagnosis considered as it has a variable clinical presentation. Manifestations of this hematologic disorder can range from single cutaneous lesions to multiple cutaneous lesions, and to a multi-organ disease. Skin involvement is present in 33% of patients and appearance can vary from dry scaly lesions to crusted vesicles and red papules.

 Biopsy confirms characteristic histologic and immunohistochemistry findings.

Biopsy is also critical to exclude other diagnoses such as congenital juvenile xanthogranuloma. This is a form of non-Langerhans cell histiocytosis which can present as subcutaneous masses with overlying skin changes, papules, or nodules that are erythematous at presentation and become yellow in color over weeks to months.

 These lesions vary from a few mm in diameter to over 3cm, and most commonly involve the head, neck, or trunk.

Leukemia cutis describes skin manifestations that arise as a result of an underlying leukemia. These lesions can also have a variable presentation including red or violet papules, plaques, nodules or hemorrhagic lesions.

 These lesions commonly appear after a diagnosis of leukemia has already been made, but may also appear before there is any involvement of the peripheral blood or any systemic symptoms arise.

 Approximately two-thirds of patients presenting with neonatal acute myeloid leukemia also present with skin lesions, but lesions may be limited to the skin and resolve without treatment. However, these patients usually have other findings including hepatosplenomegaly or a high systemic tumor burden.

 Confirmation of this diagnosis is also completed via skin biopsy.

Other potential etiologies include congenital sarcomas, such as rhabdomyosarcoma. These soft-tissue neoplasms can present as red or violaceous nodules if they metastasize to involve the skin.

 Additionally, extramedullary hematopoiesis, or a “blueberry muffin rash”, can also present as similar papules and nodules that can be the result of an underlying infection (often TORCH infections), hemolysis, or malignancy.9

An infectious etiology also cannot be ruled out when a newborn presents with an abnormal skin lesion. Neonatal HSV needs to be considered due to the high morbidity and mortality rates associated with this infection.

 Patients with neonatal HSV usually present with clusters of vesicles localized to the skin, eyes or mouth. Failure to treat could lead to disseminated disease or spread to the central nervous system.

 Cutaneous lesions can also be the manifestation of infections caused by the other congenital TORCH infections, 

Infection could suggest that there is an underlying immunodeficiency such as HIV, malignancy, or a white blood cell disorder. Our patient did not present with any risk factors for these conditions and lab values were reassuring. Additionally, the patient was not exposed to any risk factors that would alter the function of the immune system at this age including maternal illness, prematurity, immunosuppressive medications or inadequate prenatal care.

Langerhans cell histiocytosis has an incidence of 2.6-8.9 cases per million amongst children aged younger than 15 years, and a median age of diagnosis of 3-4 years.

 This disorder is characterized by proliferation of CD1a, S100, CD68, and CD207 myeloid dendritic cells and has a highly variable clinical presentation.

 Any organ system can be affected, thus requiring a comprehensive evaluation of affected patients. Commonly affected sites include the bone, skin, central nervous system, pulmonary, hematopoietic, and hepatobiliary systems.

Among patients diagnosed with LCH, 33% present with skin findings.

 Skin lesions usually present as ulcerated, red papules, as was seen in our patient, but may also appear pustular, vesicular, or petechial in nature.

 In infancy skin manifestations may also resemble other skin disorders such as erythema toxicum neonatorum, eczema, or seborrheic dermatitis. As a result, it is important to accurately diagnose this condition to ensure appropriate treatment.

A rare variant of LCH named congenital self-healing reticulocytosis has also been identified. This condition was first described by Hashimoto and Pritzker and presents at birth or within the first few weeks of life.

 Patients may present with brown to violaceous papules located anywhere on the body. As with classic LCH, these lesions can be single or multiple. It is thought that the true incidence of this variant is underreported because most of these lesions resolve without treatment within the first 3-4 months of life.

Although children with lesions isolated to the skin usually have a good prognosis, patients with LCH who have isolated skin involvement also have an excellent prognosis, however, close observation is still required.

 In 40% of patients with similar isolated cutaneous findings progression to multi system disease or reactivation was observed.

Initial evaluation of patients with LCH requires determining whether there is single or multisystem involvement. Recommended testing includes a complete blood count with differential, complete metabolic panel including liver function tests, and coagulation studies. Imaging assessment should include a skeletal survey, ultrasound of the liver and spleen, and chest radiography.

 Treatment can then be tailored to the individual patient and extent of their disease.

Treatment for LCH is dependent on the site affected and the number of lesions. For patients presenting with isolated skin involvement, surgical resection can lead to cure. If lesions are multiple then topical corticosteroids are first line therapy, with second line agents including topical nitrogen mustard, oral thalidomide, and oral methotrexate.

 Additional studies need to be completed to further assess the efficacy of second line treatment options.

If skin involvement is diffuse or there are signs of multisystem disease, a systemic steroid with vinblastine for 6-12 months is first-line treatment. For patients with organ involvement (spleen, liver, bone marrow) 6-mercaptopurine may also be added to this treatment regimen.

 Prognosis for patients who fail these first-line treatment options is typically poor, and salvage therapy is indicated in these situations. This includes treatments such as hematopoietic stem cell transplant or a combination of cladribine and cytarabine.

Recent research has been investigating the use of therapies targeting BRAF-V600E mutations. Patients with this mutation are more likely to have higher risk LCH or have increased resistance to treatment.

 Vemurafenib, a BRAF inhibitor, has been shown to be efficacious, however further studies are required to determine appropriate dosing and duration of therapy.

Current recommendations for follow up for patients treated for isolated skin findings include evaluation of the lesion every 2 to 4 weeks. This includes monitoring for any signs of progression to multisystem involvement. Once the skin lesions have resolved, follow-up is recommended every 6 months for at least 5 years.

The cheek lesion was excised by pediatric dermatology and our patient was evaluated by the pediatric hematology-oncology service. Initial skeletal survey to assess for bone involvement showed a calvarial lesion suspicious for LCH. Follow up whole body positron emission tomography scan was completed and showed no findings of bone or other multisystem involvement. As a result, systemic therapy was not indicated as the cheek lesion was previously excised. It was determined that the patient likely had the congenital self-healing reticulocytosis variant of LCH. The patient continues to follow with serial skeletal surveys and labs, and remains in complete remission.

Acknowledgements: The authors thank Dr Kumaran Mudaliar, MD; Dr Wendy Kim, DO; and Dr Natalie Kamberos, DO for their valuable contributions to this case.

1. Rotter A, de Oliveira Z. Infantile hemangioma: pathogenesis and mechanisms of action of propranolol. 

2. Krooks J, Minkov M, Weatherall A. Langerhans cell histiocytosis in children. 

3. Papadopoulou M, Panagopoulou P, Papadopoulou-Alataki E. The multiple faces of Langerhans cell histiocytosis in childhood: A gentle reminder. 

4. El Demellawy D, Young JL, de Nanassy J, et al. Langerhans cell histiocytosis: a comprehensive review. 

5. Oza VS, Stringer T, Campbell C, et al. Congenital-type juvenile xanthogranuloma: A case series and literature review. 

6. Martínez-Leboráns L, Victoria-Martínez AM, Torregrosa-Calatayud JL, et al. Leukemia Cutis: A report of 17 cases and a review of the literature. 

7. Gru AA, Coughlin CC, Schapiro ML, et al. Pediatric Aleukemic Leukemia Cutis: Report of 3 cases and review of the literature. 

8. Roberts I, Fordham NJ, Rao A, et al. Neonatal Leukemia. 

9. Manning JR, Lee DH. Uncommon Neonatal Skin Lesions. 

10. Harris JB, Holmes AP. Neonatal Herpes Simplex Viral Infections and Acyclovir: An Update. 

11. Stanberry LR. Herpes simplex virus. In: Kliegman RM, Stanton BF, St. Geme JW, et al. 

 20th ed. Philadelphia, PA: Elsevier; 2016.

12. Collins A, Weitkamp JH, Wynn JL. Why are preterm newborns at increased risk of infection? 

13. Carlo WA, Ambalayanan N. High-risk pregnancies. In: Kleigman RM, Stanton BMD, St. Geme J, et al. 

14. Leung AKC, Lam JM, Leong KF. Childhood Langerhans cell histiocytosis: A disease with many faces. 

15. Hashimoto K, Pritzker MS. Electron microscopic study of reticulohistiocytoma: an unusual case of congenital, self-healing reticulohistiocytosis. 

16. Trung A, Ahmad RC, Jennings C, et al. Congenital cutaneous Langerhans histiocytosis with mixed cell populations. 

17. Lau L, Krafchik B, Trebo MM, et al. Cutaneous Langerhans cell histiocytosis in children under one year. 

18. Gadner H, Minkov M, Grois N, et al. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. 

19. Donadieu J, Bernard F, van Noesel M, et al. Cladribine and Cytarabine in Refractory Multisystem Langerhans Cell Histiocytosis: Results of an International Phase 2 Study. 

20. Heritier S, Emile JF, Barkaoui MA, et al. BRAF mutation correlates with high-risk Langerhans cell histiocytosis and increased resistance to first-line therapy. 

21. Kobayashi M, Tojo A. Langerhans cell histiocytosis in adults: Advances in pathophysiology and treatment. 

22. Morren MA, Vanden Broecke K, Vangeebergen L, et al. Diverse cutaneous presentations of Langerhans cell histiocytosis in children: a retrospective cohort study. 

A newborn boy born via normal vaginal delivery at 38.6 weeks gestation to a 33-year-old G5P2022 mother presented at birth with an asymptomatic 8-mm red, papulonodule with central crusting on the right cheek . What's the diagnosis?

 Red papulonodule with central crusting on a neonate’s cheek

Children and teenagers with autism spectrum disorder can be at increased risk for a number of concerns when compared to the general pediatric population. An 

 looks into whether pediatric patients with autism spectrum disorder could be at increased risk of substance use disorder and if this risk was tied to psychotropic treatment.

Researchers ran a retrospective, population-based, cohort study that used data from the Taiwan National Health Insurance Research Database and ran from January 2000 to December 2015. Each participant went to at least 3 outpatient visits within 1 year for symptomatic autism spectrum disorder, as denoted by the International Classification of Diseases, Ninth Revision, Clinical Modification. The participants with autism spectrum disorder and non-autism spectrum disorder controls were matched 1:4, using sex, index date, and age.

The study included 6599 patients with autism spectrum disorder with an average age of 11.9 years and were followed up for an average period of 8.1 years as well as 26,396 control participants who had an average age of 12.1 years and were followed up for an average of 8.6 years. Following multivariable-adjusted analysis, the adjusted hazard ratios (aHRs) for substance use disorder (2.33; 95% CI, 1.89-2.87), alcohol use disorder (2.07; 95% CI, 1.60-2.63), and drug use disorder (3.00; 95% CI, 2.15-4.58) were found to be much higher in the autism spectrum disorder than in the control group. Additionally, the aHRs for substance use in participants with 1 psychotropic agent (0.60; 95% CI, 0.43-0.66) as well as multiple psychotropic agents (0.37; 95% CI, 0.28-0.49) were significantly lower than in the subgroup that utilized no psychotropic agents. When patients with autism spectrum disorder were compared with controls who had the same comorbidities, there were higher aHRs for substance use disorder (range, 1.17-2.55). Furthermore, the investigators found that the mortality risk was significantly greater in patients with autism spectrum disorder than in the controls without substance use disorder (aHR, 3.17; 95% CI, 2.69-3.89).

The investigators concluded that the data indicate that patients with autism spectrum disorder could be vulnerable to developing substance use disorder.

1. Huang J, Yang F, Chien W, et al. Risk of substance use disorder and its associations with comorbidities and psychotropic agents in patients with autism. 

. January 4, 2021. Epub ahead of print. doi:10.1001/jamapediatrics.2020.5371

 Study examines if ASD increases substance use disorder risk

Most pediatricians have no trouble recommending healthy diets for their patients. However, as the days grow shorter and colder, children’s nutritional needs can change in ways that not everyone takes into account. Exposed to less sunlight, children may not make enough vitamin D. Natural production of melatonin shifts. As everyone spends more time indoors, influenza and upper respiratory infections become more common. Fresh fruits and vegetables may be harder to find. And in 2020, the rising incidence of COVID-19 has added a new risk to consider.

Human beings evolved outdoors eating fresh foods, and vitamin D deficiency may have resulted from our switch to living indoors and eating processed food. Considerations about supplementation with this nutrient start before conception and continue throughout a lifetime.

It’s not clear yet whether supplementing the diets of breastfeeding mothers can provide adequate vitamin D to their infants. Due to the risk of skin cancer, the American Academy of Pediatrics (AAP) recommends against sun exposure for infants. That leaves vitamin D supplements given directly to the breastfeeding infant as the best option.

Children aged 1 year and older may get enough vitamin D in their diets. Natural sources of vitamin D in food include salmon (wild is better than farmed), canned sardines, canned tuna, canned mackerel, and shiitake mushrooms. Most milk and some other foods are fortified with this nutrient. If, however, children aren’t getting enough vitamin D through food, they may need supplements, especially in winter, says Dr Cora Collette Breuner, professor of adolescent medicine at the University of Washington in Seattle, and a member of the American Academy of Pediatrics (AAP) Council on Integrative Health. “In areas where there is not a lot of sunshine and children have a lactose intolerance or they’re super picky eaters, and they won’t consume milk or calcium-containing vegetables, or they don’t eat fish, what do you do in those families? I believe it’s appropriate to supplement vitamin D and calcium.”

There is little risk of over-supplementing with vitamin D, and the AAP recommends that children take a supplement of 400 IU/day of vitamin D within the first few days of life and continue throughout childhood.

 For formula-fed infants and older children who are consuming less than 32 ounces per day of vitamin D-fortified formula or milk, it also recommends a vitamin D supplement of 400 IU a day. For adolescents who do not get 600 IU of vitamin D per day through foods, it recommends a supplement containing that amount.

The best documented consequence of vitamin D deficiency in children is rickets. Many studies have also linked the deficiency to an increased risk of respiratory tract infections including influenza, and even COVID-19. Although preliminary trials have suggested that vitamin D supplements can reduce the risk of some of these infections, the evidence is not yet strong enough to result in recommendations.

 The evidence for other supplements in preventing or treating respiratory tract infections has also not risen to the level where strong recommendations can be made, though the data for zinc is strong, Breuner says.

With less sunlight, patterns of natural melatonin production shift as well, Breuner says. This may be a consideration when children are taking melatonin for sleep disorders. Some research has explored the use of melatonin as a treatment for seasonal affective disorder as well. However, the AAP currently recommends melatonin only as a short-term therapy for sleep disturbances while the underlying causes of the problem—such as poor sleep hygiene—are addressed.2

Pediatricians should investigate their patients’ lifestyle and supplements before making recommendations, Breuner says. “People self-medicate their children all the time,” she says. “They don’t know what to do to prevent their kids getting COVID, not getting enough sleep, not eating organic foods. Parents just throw up their hands and say, ‘We’ll give them a multivitamin and we’re good.’” In her experience, parents of children with complex medical needs are even more likely to use alternative or complementary medicine, typically without telling their pediatrician.

Parents may feel especially inclined to hand their kids a bottle of vitamins in the winter in northern latitudes, when the selection of fresh fruits becomes less appealing. The 2017-2018 National Health and Nutrition Examination Survey, showed that 23.8% of children and teenagers were taking multivitamins.

The problem with this one-size-fits-all approach is that it doesn’t take into consideration what else a child may be consuming. Often children taking multivitamins still end up deficient in some nutrients while exceeding recommended levels of others. That’s why Breuner and the academy take a “less is more” approach when it comes to most supplements. Breuner also cautions against extrapolating from the research on adults. “The premise of pediatrics is they’re not little adults, so you can’t do that,” she says.

1. HealthyChildren.org. 2016. Vitamin D: On The Double. Accessed December 11, 2020. 

https://www.healthychildren.org/English/healthy-living/nutrition/Pages/Vitamin-D-On-the-Double.aspx#:~:text=All%20non%2Dbreastfed%20infants%2C%20as,a%20supplement%20containing%20that%20amount

How changing seasons affect children’s nutrition.

Red papulonodule with central crusting on a neonate’s cheek

Study examines if ASD increases substance use disorder risk

It’s winter: Are children getting enough Vitamin D?

Age of exposure to household dysfunction could be linked to future adverse outcomes

A pediatrician’s role in dyslexia: Where theory meets practice