As the COVID-19 pandemic continues to surge in many states around the United States and as the incidence of disease is significantly increasing in the 10- to 18-year-old population, the subject of the whether schools will reopen in the fall for in-person learning is at the top of the minds of a multitude of people including parents, teachers, students, pediatricians, and public health officials. This is a decision that needs a lot of thought in order to ensure that the setting for in-person learning is as safe as it can be for students, teachers, custodians, lunch room workers, school crossing guards, and other personnel that work in the school setting. It is a decision that is not “one size fits all” but needs to be individually adapted to specific school settings. Even though many national organizations including the American Academy of Pediatrics (AAP), the Centers for Disease Control and Prevention (CDC), the National Education Association (NEA), and the National Academy of Sciences (NAS) support the reopening of schools for the many social and psychological benefits of in-person learning, these benefits must be balanced with the threat posed by COVID-19 and schools should not be forced, under any conditions, to reopen in an unsafe manner. One of the key factors that needs to be considered is the level of COVID-19 disease that is circulating in the community at the time that a school district plans to reopen, especially the amount of disease being seen in children 10 to 18 years of age. If these levels are high, it would be unwise to reopen schools at that time. For many school districts, e-learning will be what is rolled out at the beginning of the year. For others, a hybrid model of part in-person and part e-learning will be feasible. The model of all in-person learning will probably comprise a minority of school districts.

As we continue to address the emerging issues that have been impacted by COVID-19, I want to personally thank all of our pediatric health care provider heroes for providing the safest and most comprehensive care to our patients. As the actor Christopher Reeve stated, “A hero is an ordinary individual who finds the strength to preserve and endure in spite of overwhelming obstacles.”

Please stay safe and well. I welcome your suggestions, comments, and questions.

The articles focusing on Back to School include:

 by Hallas and colleagues, which provide detailed guidance on different areas where protocols need to be developed and in place to ensure that the in-person learning environment is as safe as possible.

“Guidelines for the best hand sanitizers”

 dovetails nicely with the Safe Return to School articles as hand hygiene is critically important in any in-person learning protocol. The biggest obstacle will be the purchase of hand sanitizers, difficult to find in stores.

Articles

As the battle with COVID-19 continues, so does the difficult decision about how to educate our children this fall.

Back to school, or back to remote learning?

On the topic of ‘return to school’ this year, anxiety abounds for parents and children, as well as teachers, school staff and nurses, nurse practitioners (NPs), departments of health and legislators.

 Since school is considered “the work of children,”

 we must carefully consider all aspects of ‘return to school’ in light of the current, unprecedented COVID-19 pandemic. Many compelling questions emerge, but first and foremost the question to address is: 

Can children return to school and be in classroom environments that assure health and well-being for all?

The National Parent Union conducted an online COVID-19 survey of 500 parents with children from kindergarten through 12th grade on May 4 and 5, 2020.

 Lowe’s data revealed a significant level of anxiety among parents concerning return to school for their children. A 

 article reported that 6 of 10 parents are considering continuing with home learning rather than sending their children to school in Fall 2020.

 Some of the parental anxiety and decision making by parents may be attributed to uncertainty as the pandemic remains a viable threat throughout our country.

Planning, testing and masks are a critical component for safe return to school

Guidance from the Centers for Disease Control and Prevention (CDC) for opening schools was posted on the CDC website on March, 19, May 19, June, 3, and July 23, 2020.

 The guidance emphasizes the importance of school officials and administrators collaborating with local health officials for decision making regarding return to school and decisions about closing schools, while the most recent statement did stress the importance of reopening schools. The initial interim CDC guidelines

 did not address two major issues, masks and testing, that must be resolved either locally, or nationally by implementation of best available scientifically based health safety measures prior to any child’s/adolescents return to school. However, the CDC guidance on July 23, 2020 does recommend masks for children and staff in school settings, except those under 2 years old, and those with some medical conditions. Since wearing masks has been met with controversy, the work of health care professionals (HCPs) is to gain the support of parents, children and school personnel to wear masks during school. And, while recommendations presented in this paper are consistent with CDC guidelines and supports wearing masks, it also provides more stringent considerations for testing school personnel and children. All HCPs realize the ever evolving and changing health care recommendations as the pandemic moves across the country and the world. Thus, what is considered best practice today based on the available evidence, may be shown to be incorrect tomorrow. Making reasonable changes to tackle the twists and turns that emerge every day in this pandemic is a major challenge. Health care professionals at the local, state, regional, in helping non-HCPs make sensible decisions based on scientific data to protect all individuals. Return to school decisions must be based on the science with the overall goal of the health and well-being of the children/adolescents, the school personnel and the community as a whole. One size and one decision will not fit all.

The CDC guidance on COVID-19 from July 23, 2020 supports using “cloth face coverings” to prevent the spread of the COVID-19 virus, and includes in their practical recommendations that schools put “cloth face coverings on school supply lists and provide cloth face coverings as needed to students, teachers, staff, or visitors who do not have them.”

 Indeed, the scientific evidence from COVID-19 public health measures supports wearing masks as the new norm for all adults and for all children older than 2 years. Thus, we believe that wearing masks is an essential component of safe return to school. However, children with chronic illnesses, including pulmonary conditions, and those with disabilities may be advised by their physicians and NPs, not to wear face masks. Thus, some protection for children, who are too young to tolerate wearing a mask or are unable to wear masks, may be provided by other children and school personnel who can safely wear face masks in school settings.

The CDC guidance of July 23, 2020 also states that “[The CDC] does not currently recommend universal symptom screenings to be conducted by schools.”

 School NPs and school nurses are educated on public health screening measures and are ideally suited to appropriately screen students and all school personnel prior to entering school for the purpose of preventing exposure of individuals with COVID-19 or any communicable disease symptoms from spreading the virus to contacts at the school. The value of having a school nurse for every school was supported by the AAP policy statement in June 2016.

 In this pandemic, the school nurse is an essential part of the healthcare team (eg, private practice physicians, school based health centers, community clinics, and the department of health) overseeing the health of the children and school personnel and should be employed in every school.

Another major concern identified in the original CDC guidance

 is the recommendation to close schools for 2 to 5 days when there is a confirmed case of COVID-19 in the school system. Opening and closing schools for 2 to 5 days will be disruptive to everyone. Testing prior to return to school may prevent schools from opening and closing in a chaotic fashion.

Plans to reopen schools must be based on local and state public health data as well as primary and secondary prevention strategies that minimize the potential for viral spread, and avoid a cycle of frequent opening and closing of school systems due to outbreaks of COVID-19.

 The authors believe that testing of students and school personnel prior to reopening schools is the cornerstone of primary and secondary prevention strategies. And while the most recent CDC guidance does not recommend universal testing of children and staff, it however, proposes other testing strategies based on local and state data.

When the pandemic began, data from other countries led health care providers to believe that children were less affected by COVID-19 but may be asymptomatic carriers.

However, as the pandemic spread in the United States and Italy, there were news reports of chronically ill children hospitalized with severe symptoms. The most troubling occurrence is the new presentation of the COVID-19 complication of the syndrome, Multisystem Inflammatory Syndrome in children (MIS-C).

 The etiology of MIS-C remains unclear. According to reports from the CDC, children who developed MIS-C may have been infected weeks before the appearance of MIS-C symptoms, and/or were symptomatic carriers.

Thus, based on these presentations of COVID-19 in children, testing strategies for children must be considered on all levels to protect all children, school personnel, and the communities in which they live. As of this writing, data for widely testing children for COVID-19 in the United States is non-existent.

Innovation is an outcome of a crisis. New, non-invasive methods for testing for COVID-19 in children should be developed. Saliva sample testing may be a reasonable solution that can be developed, and, as of this writing, is under investigation as a point-of-care test.

Once testing policies and methods are in place, only then can we proceed with developing other policies that address a safe school environment for children and adolescents, and all school personnel that work every day to educate and care for our children/adolescents.

Screenings are critical to safely reopen schools

Children have been out of school since March 2020 and may not have had their usual access to health care throughout this pandemic. Screenings to identify problems in physical, emotional, social, and behavioral health are a critical strategy for the design and implementation of effective strategies for healthy children. Thus, we encourage all HCPs, including school nurses, to assume a leadership role in the design and implementation of screenings for the identification of children and school personnel who may present with problems that may have arisen during stay-at-home orders (eg, anxiety, school phobia, etc.).

Screening is a critical part of the process for prevention of transmission of COVID-19 within school systems. An innovative, reliable method for screening children and school personnel prior to going to school each day should be implemented. Some health care systems and other clinical practices have already implemented the use of a web-based application or ‘app’ that can be used to screen for temperature and emerging symptoms one-hour before reporting to work each day. This screening tool asks the individual to report the morning temperature, and also asks other pertinent questions about symptoms and possible exposure to an individual with COVID-19. If negative, the employee reports to work. If any portion of the screening is positive, the individual does not report to work that day. For parents who do not have access to cell phones or apps on their devices, a plan should be in place for the parents to call into the school and report the information to be reviewed by the school nurse prior to the children leaving for school. Once at work (school) and before entering the workplace (school environment), a second temperature screening is recorded. Such an app for school-based screenings for children and school personnel can easily be developed and implemented as best practice for early identification of possible COVID-19 exposure and/or infection for healthy children.

It has been theorized that COVID-19 viral shedding may persist for longer periods of time through the gastrointestinal tracts of in children.

 It is believed that children may be asymptomatic carriers and may shed the virus for days or even weeks, but too little testing has been done. Schools must be vigilant in preparation of the bathroom space of children and school personnel, preparing for the worst-case scenario. It is important for school systems to be proactive, rather than reactive. Leadership of school nurses and nurse practitioners is essential in policy preparation and enactment of policies for bathroom use.

Frequent cleaning and maintenance of modern bathrooms will reduce risks shedding and must be instituted prior to opening schools, and continue throughout the school day. Measures to help children become comfortable in the bathroom must be part of the curriculum. Soap, running water, and a clean toilet must be established.

 Bathrooms may increase risk of disease transmission without structural change (proper toilet design, adequate soap and water, frequent cleanings). Proper implementation of a plan will enable children and staff to better understand how to prevent other diseases (including influenza and other common gastrointestinal diseases), which should also help change attitudes and establish new norms.

COVID-19 brought to the forefront nationwide educational inequality. As HCPs, we know the importance of being lifelong learners and the importance of early childhood education and continued excellence in education throughout the K through 12 years. It was distressful to hear many parents report that their children did not have access to computers, tablets and/or the internet at home to continue their education virtually. To achieve meaningful societal change, social justice and educational parity, we encourage educators, parents, and all community members to analyze the local educational needs and to plan accordingly to meet the needs of all students.

As Erik Erickson said, “School is the work of children.”

 We value the education our children receive throughout the US each year preparing the children to develop into healthy, kind, valuable, innovative and productive members of society in whatever careers and professions they choose. The immediate closing of schools at the onset of the COVID-19 pandemic has further enlightened everyone on the value of educators and the school systems. All HCPs want children to return to school safely and free of the threats of contracting COVID-19 within the school environment. Thus, our recommendations are based on the best available evidence as of this date and time. Screening, non-invasive testing, masks for all children over 2-years old, eye protection, social distancing, cleaning, transportation, and bathroom use are critical to the health and well-being of the children, all school personnel, their parents, family members and the community in which they live and grow.

1. Lowe, B. New poll: Two-thirds of parents support keeping schools closed ‘until they are certain there is no health risk’. Published May 11, 2020. Accessed June 3, 2020. 

https://www.the74million.org/new-poll-two-thirds-of-parents-support-keeping-schools-closed-until-they-are-certain-there-is-no-health-risk/

2. Erikson, EH. Childhood and society (2nd ed.). 1963. W. W. Norton & Company.

3. The Editorial Board. How to reopen America’s schools. The New York Times. Published June 6, 2020. Accessed June 17, 2020. 

https://www.nytimes.com/2020/06/06/opinion/coronavirus-schools-reopen.html?referringSource=articleShare

4. Center for Disease Control and Prevention. Interim Guidance for Administrators of US K-12 Schools and Child Care Programs Plan, Prepare, and Respond to Coronavirus Disease 2019 (COVID-19). Published April 12, 2020. Accessed June, 3 2020 

https://www.cdc.gov/coronavirus/2019-ncov/community/schools-childcare/guidance-for-schools.html

5. Center for Disease Control and Prevention. National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases. Coronavirus Disease 2019 (COVID-19). Considerations for Schools. Published May 19, 2020. Accessed June 3, 2020. 

https://www.cdc.gov/coronavirus/2019-ncov/community/schols-childcare/schools.html

6. Centers for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19). K-12 Schools and child care program. Published June 3, 2020. Accessed June 17, 2020. 

https://www.cdc.gov/coronavirus/2019-ncov/community/schools-childcare/schools-faq.html?deliveryName=USCDC_2067-DM29945

7. AAP Council on School Health. Role of the School Nurse in Providing School Health Services. Pediatrics. Published June 2016. Accessed July 12, 2020. Accessed from 

https://pediatrics.aappublications.org/content/137/6/e20160852

8. Center for Disease Control and Prevention. Coronavirus disease 2019 (COVID-19). Interim considerations for K-12 school administrators for SARS-CoV-2 testing. Published June 30, 2020. Accessed July 12, 2020. 

https://www.cdc.gov/coronavirus/2019-ncov/community/schools-childcare/k-12-testing.html

9.Center for Disease Control and Prevention. For Parents: Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19. Published May 20, 2020. Accessed June 10, 2020. 

https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/children/mis-c.html

10. Hindson J. COVID-19: faecal-oral transmission?. 

. 2020:17(5):259. doi:10.1038/s41575-020-0295-7

11. WHO Water, Sanitation and Hygiene strategy 2018-2025. Geneva: World Health Organization; 2018 (WHO/CED/PHE/WSH/18.03). License: CC BY-NC-SA 3.0 IGO Published 2018. Accessed June 28, 2020. 

https://apps.who.int/iris/handle/10665/274273

As fall approaches, one of the biggest questions is: Can children return to school and be in classroom environments that assure health and well-being for all?

Safe return to school: A call to action

Using only intensive clinical examination for initial identification of early-onset sepsis (EOS) in late preterm and term neonates substantially decreases laboratory testing and antibiotic use with no adverse outcomes. These were the ­findings of investigators who analyzed the effect of such an approach at their California hospital during a 5-year period.

As part of this approach, late preterm and preterm neonates who appeared well at birth remained with their mothers, even when the infants had perinatal risk factors for EOS. Nurses provided all these babies with enhanced clinical monitoring, and a neonatal hospitalist performed the initial clinical assessment of infants born to mothers with chorioamnionitis. Early in the study period, such chorioamnionitis-exposed infants were admitted to the NICU, but later on these babies instead remained with their mothers for the entire hospitalization if they appeared well.

Antibiotic treatment was administered only if the treating physician decided it was appropriate because the neonate was clinically ill at birth or later developed clinical signs of illness that posed a risk of sepsis. In addition, neonates were not routinely screened using sepsis laboratory testing, and when such testing was performed it was only once antibiotic treatment was started. Finally, routine evaluation for EOS did not include lumbar puncture for cerebrospinal fluid studies and culture. These tests generally were performed only in the presence of neurologic signs, such as mental status changes or seizures, at presentation or when the blood culture became positive.

Analysis of outcomes in 20,394 neonates ≥35 weeks’ gestation found that the percentage of neonates exposed to ampicillin decreased from 11.1% in the period before the clinical-examination approach was instituted to 4.1% during the intervention period. In addition, C-reactive protein testing declined from 15.3% to 6.3%. Overall, during an almost 5-year period, implementation of the clinical-examination approach reduced the use of antibiotics by 63% and sepsis laboratory testing by 59% (

Frymoyer A, et al. J Pediatr. 2020. E pub ahead of print

This paper is a potentially seminal article in my view. I was taught that at-risk newborns required work-ups and antibiotics; this is a drastic change. I expect it will take time to become standard; more seasoned physicians will not necessarily adjust their approach based on articles. In time, the next generation of pediatricians can show how it can be done safely.

Examining how an intensive clinical examination can change the approach to early-onset sepsis.

New approach to EOS reduces testing and antibiotics

You are asked to evaluate a healthy 19-month-old boy with a history of recurrent blisters on his arms and legs for over a year that have now spread to his face. The blisters scab over quickly, ulcerate, and heal with post-inflammatory pigmentary changes.

Diagnosis: Chronic bullous disease of childhood (CBDC)

Chronic bullous disease of childhood, also known as linear IgA bullous dermatosis (LABD), is an uncommon disease that occurs in children between 6 months and 10 years.

 Chronic bullous disease of childhood presents with expanding annular erythematous plaques with blisters at the periphery, resulting in the string of pearls sign. Early lesions can develop in the flexural areas, although this may vary.

 Commonly involved areas include the face, abdomen, genital area, and extremities.

Chronic bullous disease of childhood is characterized by the linear deposition of IgA along the basement membrane zone (BMZ).

 This leads to neutrophilic infiltrate and subepidermal bullae, often with increased prevalence of eosinophils.

 LABD cannot be definitively diagnosed by light microscopy and should be confirmed with immunofluorescent studies which show linear staining for IgA at the basement membrane zone.

Conditions associated with LABD include autoimmune diseases, malignancy, and infections,

 with insufficient data to determine the statistical significance of these relationships.

 One known association is drug-induced LABD, especially with vancomycin.

 This condition differs from idiopathic LABD in both distribution and disease course.

The differential diagnosis for CBDC/LABD is extensive; the two most common conditions that mimic LABD are dermatitis herpetiformis and bullous pemphigoid, which may present with bullae or vesicles in similar distributions.

 Direct immunofluorescence is the gold standard for differentiating between these conditions in the absence of other clinical distinguishers.

 The linear deposition of IgA along the BMZ is pathognomonic for CBDC and LABD; dermatitis herpetiformis is characterized by granular IgA deposition in the dermal papillary tips or along the basement membrane and bullous pemphigoid is characterized by linear IgG deposition along the epidermal BMZ.

 Besides direct immunofluorescence, circulating anti-BMZ IgA antibodies may be found in 60% to 70% of LABD patients, not found in dermatitis herpetiformis or bullous pemphigoid.

Although CBDC is generally self-limited, it may lead to morbidity and requires systemic treatment.3 The standard of care for treatment is dapsone for controlling blistering without adverse reactions in most cases.

 Dapsone is initiated at low doses (<0.5mg/kg) and increased until symptoms are controlled.

 Adverse effects include hemolysis, especially in patients with glucose-6-phosphate dehydrogenase deficiency.

 Second-line therapies include erythromycin, dicloxacillin, oxacillin, colchicine, and systemic corticosteroids.

Chronic bullous disease of childhood was diagnosed clinically. Following bloodwork, this patient started on dapsone 12.5 mg, then 18.75 mg, with improvement of the lesions. A skin biopsy and direct immunofluorescence confirmed the diagnosis

Hull CM, Zone, JJ. Dermatitis herpetiformis and linear IgA bullous dermatosis. 

Kuechle, MK, Stegemeir, E, Maynard, B, et al. Drug-induced linear IgA bullous dermatosis: report of six cases and review of the literature. 

 1994;30(2):187–192. doi: 10.1016/s0190-9622(94)70015-x

Mintz, EM, Morel, KD. Treatment of chronic bullous disease of childhood. 

 29(4):699–700. doi: 10.1016/j.det.2011.08.013

You are asked to evaluate a healthy 19-month-old boy with a history of recurrent blisters on his arms and legs for over a year that have now spread to his face. The blisters scab over quickly, ulcerate, and heal with post-inflammatory pigmentary changes. What's the diagnosis?

Bully bullae in a toddler spreads across the body

Smartphone applications that address weight reduction have increased along with smartphone app use among pediatric patients. This led a team of pediatric practitioners to develop an evaluation tool (called Ped-WHAT) and rating system for these apps (16 currently are available), with the goal of giving health care providers a tool for assisting patients and their families in selecting apps that meet their needs and are based on scientific evidence. The Ped-WHAT tool evaluates apps based on whether they address 8 evidence-based behavior modification strategies that target weight management (such as self-monitoring, goal setting, and physical activity support) and 10 behavior strategies outlined by the American Academy of Pediatrics (such as eating 5 fruits and vegetables each day and getting 1 hour of daily physical activity). The team also developed a 5-star rating system to simplify interpretation of the evaluation criteria.

In addition, the team tested an educational in-service training session for practitioners, finding it significantly improved provider knowledge and confidence about using Ped-WHAT (

Apps for weight loss are promising, but so far strong evidence that any of them are effective is lacking. This article does not evaluate apps per se, but does give the interested provider guidance in deciding whether a given app might be worth suggesting to a family.

Smartphone applications addressing weight reduction have increased along with smartphone app use among pediatric patients. What's the best way to choose one? 

 Smartphone apps for weight control?: How to choose

A previously healthy 5-week-old former term newborn male presented to the emergency department with the chief complaint of fever ranging from 101-104°F for 2 days. He also had been fussy and not been eating well. The infant remained febrile despite his mother’s administration of Infant Tylenol every 4 hours at home. His mother denied any cough, rhinorrhea, bleeding or bruising, diarrhea, vomiting, and reported stool and urine had been normal.

Recent past medical history revealed the infant had been discharged 2 days ago after a 24-hour admission for observation following a linear skull fracture of the right parietal bone diagnosed by CT with no associated hemorrhage. These injuries were sustained after his mother fell on the stairs while carrying him. He had an additional prior admission at 9 days of age for fever which resolved after 48 hours of IV antibiotic therapy; no cause was determined as blood, urine and CSF cultures were all negative.

Family history revealed both parents have sensorineural hearing loss from nongenetic causes. The patient had received hepatitis B vaccine at birth. There was no other significant past medical history, family history or surgical history.

On exam, the patient was nursing and appeared fussy but consolable by his mother. Temperature was 102.5°F. Head circumference, weight, and length were all in 80th percentile. Abdominal exam was somewhat difficult to perform but abdominal tenderness was suspected. There was tachycardia and palpable hepatosplenomegaly. The physical exam was otherwise within normal limits.

Laboratory evaluation showed transaminitis with ALT of 325 Units/L (normal 5-45 Units/L), AST of 393 Units/L (normal 20-60 Units/L), total bilirubin of 3.4 mg/dL(normal 0.2-1.3 mg/dL) with direct bilirubin of 0.7mg/dL (normal 0.0-0.3 mg/dL), decreased albumin of 3.1 (normal 3.4-4.2g/dL), and lactate dehydrogenase and D-dimer were significantly elevated at 2007 Units/L (normal 500-920 Units/L) and 15,099 ng/ml (normal 215-500ng/ml) respectively. White blood cell count revealed pancytopenia with WBC count of 3.34x10^9/L (normal 7.7-13.7x10^9/L), RBC count of 2.65x10^6/­L (normal 3.0-4.3x10^6 ­L), Hgb of 8.1g/dL (normal 9.5-13.3g/dL), platelet count of 56x10^9/L (normal 150-500x10^9L). Differential count showed 22.1% neutrophils, 54.5% lymphocytes, 19.8% monocytes, 0.3% basophils, 0.3% eosinophils and 3% immature granulocytes. Reticulocyte count was mildly elevated at 5.43% (normal 0.90-3.80%). PT was elevated at 13.3 seconds (normal 9.6-12.5 seconds). Blood, urine and cerebrospinal fluid cultures were all negative. Triglycerides were normal at 118mg/dL (normal 40-160mg/dL), and all other labs were without significant abnormality. CXR was normal. Repeat head CT confirmed previously described skull fracture without intracranial hemorrhage. Abdominal ultrasound showed splenomegaly without hepatomegaly. Continued investigation over the next week included consultations from oncology and infectious disease services. Additional testing revealed elevated serum ferritin of 11,100ng/mL (normal 14-647ng/ml) and soluble CD-25 of 79,500pg/ml (normal 0-1033pg/mL). Histopathology of a bone marrow biopsy revealed mild histiocytic hyperplasia with increase in histiocytes with occasional hemophagocytosis. Epstein Barr Virus was positive by in situ hybridization (Figure 1: Images A-D).

Hemophagocytic lymphohistiocytosis (HLH) can be a primary disease driven by homozygosity or compound heterozygosity for verified HLH mutations, or a secondary disease occurring in the presence of chronic viral illness, autoimmune disease or lymphoma.

 Both forms are thought to require a triggering event involving either immune activation, most commonly Epstein-Barr infection, or an immune deficient state like human immunodeficiency virus infection.

 Regardless of the underlying etiology, HLH involves excessive activation of hyperplastic histiocytes resulting in excessive cytokine release. Additionally, there is often natural killer cell and cytotoxic lymphocyte abnormalities present, which result in decreased elimination of damaged or infected host cells.

 Elevated amounts of cytokines such as Il-6 result in characteristic fever as well as broad tissue damage and multiple organ failure. Though the liver and central nervous system are most often described as being involved, any organ system may be affected.

The clinical presentation of hemophagocytic lymphocytosis is consistent with a hyperinflammatory or dysregulated immune state. Most commonly the patient is less than 18 months old and presents with fever > 101.3°F splenomegaly, and peripheral blood cytopenia with at least two of either hemoglobin <10g/dL, platelets <100,000 microliter or absolute neutrophils <1,000 microliter.

 Further study typically reveals high ferritin levels as well as elevated CD255. There may also be hypofibrinogenemia and hypogammaglobinemia.

 Hemophagocytosis may be present in bone marrow, lymph nodes, liver and spleen, and reflects macrophages in a hyperactive state.

 There may also be a late finding of hypertriglyceridemia after the disease has damaged the liver. As many as 30% of patients may present with a variety of neurological abnormalities such as mental status changes and encephalitis, seizures, hemiparesis, nuchal rigidity and ataxia reflective of central nervous system involvement.

 Additionally, nonspecific findings in cerebrospinal fluid of increased protein and decreased glucose may be present in 50% of cases.

 Fever and pancytopenia in the presence of either elevated liver function tests or central nervous system involvement and without other explanation should prompt consideration of HLH workup.

There are a number of conditions that may present in an infant with a clinical picture of persistent fever, pancytopenia, liver abnormalities and splenomegaly including malignancies, rheumatoid disorders, and infections like Epstein-Barr virus (EBV) (Table 1). The additional findings of hyperferritinemia, elevated CD25 and hemophagocytosis are extremely suggestive of HLH.

Diagnosis is based on fulfillment of 5 or more of 8 established criteria (Table 2) or on an HLH gene panel comprised of verified HLH mutations in cases where 5 criteria are not met. Additional findings that may support a diagnosis of HLH include spinal fluid pleocytosis with or without elevated spinal fluid protein and liver biopsy findings consistent with chronic persistent hepatitis by histology.

 As swift initiation of treatment in cases of HLH is imperative for a good patient outcome, modified diagnostic criteria may also be used (Table 3) to determine if HLH treatment should be initiated.

Treatment of HLH is guided by the HLH 2004 treatment protocol. Initial therapy consists of 8 weeks of chemoimmunotherapy consisting of etoposide, dexamethasone, and cyclosporine A. In cases with CNS involvement at diagnosis, systemic therapy alone should be employed. After 2 weeks of therapy if CNS symptoms have worsened or not improved (based on repeat MRI showing new, increased or unchanged CNS involvement such as increased parenchymal lesions, leptomeningeal enhancement or global edema, and repeat lumbar puncture with cerebrospinal fluid analysis showing increased pleocytosis or other abnormality associated with HLH) intrathecal methotrexate and prednisolone should be added. Severity of serum ferritin elevation prior to treatment may correlate directly with severity of disease and overall probability of mortality. In patients without familial disease or with negative genetic testing who achieve complete resolution after initial therapy, no further treatment is necessary although close follow-up is imperative; patients with HLH are at risk of recurrence or development of secondary hematologic malignancy such as leukemia or lymphoma. We recommend follow-up every 3 months to assess for new history of fever, lymph node enlargement and hepatosplenomegaly. Patients should be monitored for neurologic changes as well as hematologic abnormalities suggestive of malignancy (especially leukemia). Patients with positive genetic testing or otherwise known familial disease or unresolved disease after initial treatment should undergo a hematopoietic stem cell transplant (HSCT) as soon as possible. In such patients, HSCT may be curative.

Our patient was found to meet all 8 of the diagnostic criteria previously discussed and underwent 8-week induction therapy and HLH genetic screening. Gene testing showed him to be a compound heterozygote with two different mutations on opposite copies of the UNC13-D gene. Though he is currently in remission and doing well, because he has been determined to have familial HLH, he is currently on continuation therapy and with plans to undergo a HSCT very soon.

Hemophagocytic lymphohistiocytosis is a rare syndrome characterized by excessive immune activation. Typically considered a disease of infancy and childhood, the condition may be observed in males and females at any age. Most commonly, presentation includes febrile illness and multiorgan involvement especially of the liver and/or the central nervous system. The combination of persistent fever, pancytopenia, splenomegaly and liver function abnormalities should prompt thoughts of possible HLH diagnosis as early detection and treatment are imperative if there is to be a positive outcome for patients with HLH.

Zhang K, Chandrakasan S, Chapman H, et al. Synergistic defects of different molecules in the cytotoxic pathway lead to clinical familial hemophagocytic lymphohistiocytosis. 

. 2014;124(8):1331–1334. doi:10.1182/blood-2014-05-573105

Henter JI, Horne A, Arico M, et al. HLH 2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. 

Filipovich A, McClain K, Grom A. Histiocytic disorders: recent insights into pathophysiology and practical guidelines. 

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Risma K, Jordan MB. Hemophagocytic lymphohistiocytosis: updates and evolving concepts. 

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Hemophagocytic Lymphohistiocytosis Study Group. Histiocyte Society. Treatment Protocol of the Second International HLH Study 2004. HLH; 2004.

Henter JI, Nennesmo I. Neuropathologic findings and neurologic symptoms in twenty-three children with hemophagocytic lymphohistiocytosis. 

Kieslich M, Vecchi M, Driever PH, Laverda AM, Schwabe D, Jacobi G. Acute encephalopathy as a primary manifestation of hemophagocytic lymphohistiocytosis. 

Jordan MB, Allen CE, Weitzman S, Filipovich AH, McClain KL. How I treat hemophagocytic lymphohistiocytosis. 

. 2011;118(15):4041–4052. doi:10.1182/blood-2011-03-278127

A previously healthy 5-week-old former term newborn male presented to the emergency department with the chief complaint of fever ranging from 101-104°F for 2 days. He also had been fussy and not been eating well. The infant remained febrile despite his mother’s administration of Infant Tylenol every 4 hours at home. His mother denied any cough, rhinorrhea, bleeding or bruising, diarrhea, vomiting, and reported stool and urine had been normal. What's the diagnosis?

A fever, liver abnormalities, and pancytopenia

Early in the COVID-19 pandemic, the US supply chain was stretched thin on many necessary products, including hand sanitizer. In response to this shortage, many health systems, manufacturers, and non-traditional institutions (eg, distilleries) sought to compound hand sanitizer to meet this need. To ensure safe compounding practices, in March 2020 the US Food and Drug Administration (FDA) released guidance for the temporary compounding of certain alcohol-based hand sanitizer products during the public health emergency.

 In addition, the United States Pharmacopeia (USP) provided recommendations on compounding alcohol-based hand sanitizer during the COVID-19 pandemic.

 These guidance documents provided recommendations regarding ingredients, facilities, and labeling in accordance with the World Health Organization’s (WHO) recommended recipe.

 These documents support the use of two formulas that result in either an ethanol antiseptic topical solution containing ethanol 80% (v/v) or an isopropyl alcohol antiseptic topical solution with a final concentration of 75% (v/v).1,2,3 According to the USP guidance, compounded hand sanitizers have a beyond use date of 30 days which is significantly shorter than commercially available products.

 The FDA does not recommend the public manufacture their own hand sanitizers due to risk for poor efficacy if made incorrectly and reports of skin burns.

 The hand sanitizer should be labeled with the alcohol percentage and can be stored at controlled room temperature.

The CDC recommends using alcohol-based hand sanitizer only when soap and water are unavailable. Therefore, it is crucial that the final concentration of hand sanitizer is at least 60% alcohol (ethanol or isopropyl alcohol) to avoid getting sick and spreading germs to others.

 Hand sanitizer should be used by covering all hand surfaces and rubbing one’s hands together, for approximately 20 seconds, or until they feel dry.

 Soap and water should be used whenever possible and always during food preparation, wound care, using the restroom, or caring for pets.

Hand sanitizer, when used by children, must be under the direct supervision of adults to prevent accidental ingestion.

 Numerous brands and types of hand sanitizers have emerged in the market place and they are NOT regulated by the FDA. It is extremely important to review all contents and their concentration to assure its effectiveness and safe use. The CDC and FDA are excellent resources for updated information for hand sanitizers (eg, potential harmful effects of methanol containing products). —Carlton Lee, PharmD, MPH, FASHP, FPPAG

Policy for Temporary Compounding of Certain Alcohol-Based Hand Sanitizer Products During the Public Health Emergency Immediately in Effect Guidance for Industry. U. S. Food and Drug Administration. 

https://www.fda.gov/media/136118/download

. Published in March 2020, Last Updated on June 1, 2020, Accessed on July 13, 2020.

Compounding Alcohol-Based Hand Sanitizer During COVID-19 Pandemic. United States Pharmacopoeia. 

https://www.usp.org/sites/default/files/usp/document/about/public-policy/usp-covid19-handrub.pdf

. Published on March 18, 2020. Last Updated on March 25, 2020. Accessed on July 13, 2020.

Guide to Local Production: WHO-recommended Handrub Formulations. World Health Organization. 

https://www.who.int/gpsc/5may/Guide_to_Local_Production.pdf

. Last Updated in April 2010. Accessed on July 13, 2020.

Q&A for Consumers: Hand Sanitizers and COVID 19: FDA. 

https://www.fda.gov/drugs/information-drug-class/qa-consumers-hand-sanitizers-and-covid-19

Show Me the Science – When & How to Use Hand Sanitizer in Community Settings, Centers for Disease Control and Prevention. 

https://www.cdc.gov/handwashing/show-me-the-science-hand-sanitizer.html

. Last Updated on March 3, 2020. Accessed on July 13, 2020.

Hand Sanitizer Use Out and About. Centers for Disease Control and Prevention. 

https://www.cdc.gov/handwashing/hand-sanitizer-use.html

. Last Updated on April 13, 2020, Accessed on July 13, 2020.

FDA Updates on Hand Sanitizers with Methanol. U. S. Food and Drug Administration. 

https://www.fda.gov/drugs/drug-safety-and-availability/fda-updates-hand-sanitizers-methanol?utm_campaign=FDA%20MedWatch%20-%20Hand%20Sanitizers%20with%20Methanol&utm_medium=email&utm_source=Eloqua#products

. Last Updated on July 2, 2020. Accessed on July 13, 2020.

Hand Sanitizers with Methanol: FDA Updates. MedWatch - The FDA Safety Information and Adverse Event Reporting Program. 

http://s2027422842.t.en25.com/e/es?s=2027422842&e=349602&elqTrackId=376c7bc788024cd5a73d955f2e3dcbdc&elq=2ea8b9246c7f46c89ae20013d2c01819&elqaid=13243&elqat=1

The COVID-19 pandemic led to a shortage of hand sanitizers and a push to make up the gap with compounded hand sanitizer ensued. Recommendations were released to ensure their efficacy.

Recommendations for compounded hand sanitizers during COVID-19

For patients, parents and pediatricians, the COVID-19 pandemic has been a surreal experience. In March of this year our society changed abruptly. Families were advised to stay home, and pediatricians quickly altered their practices to help safeguard staff and patients.

For over two months I’ve been practicing telehealth exclusively at home. I did so with the support of my partners, as I have risk factors which predispose me to more severe consequences from SARS-CoV-2 infection. Just recently, I emerged from seclusion, fearful, but eager to return to office practice. Following my return to the office, I’ve made some observations about pediatric practice worth sharing with our readers.

For months, as health care workers, we have been doing our best to care for patients in the midst of a pandemic. Without a means to diagnose COVID-19 at the point of care, treat suspected COVID-19 cases with a proven antiviral, and lacking an effective vaccine, we could do little to help patients with the crisis. Our battle plan included modifying our routine to implement telehealth services, triaging patients, using personal protective equipment (PPE) to see patients, and seeking loans to keep our offices afloat financially.

Telehealth during a pandemic: Lessons learned

While practicing telehealth at home, I quickly realized that parents and children were quite worried. Schools were closed, parents lost jobs, and life was now unsettling. Although most parents did their best to reassure children, I discovered that face-to-face video visits were a welcome experience for everyone. Sheltering in place, it seems, makes one keen for human interaction, and families appreciate when words of encouragement come from someone familiar. I knew my patients and their interests, and our telehealth visits were fun. I could joke about a patient’s long hair and ask how they were doing with their online classes. Like most pediatricians, I easily recalled the nuances of the lives of my patients and families. It was easy to ask about hobbies, parents’ jobs, and the whereabouts of older brothers and sisters who had aged out of the practice. During the visit I could smile at parents and patients, and receive warm smiles in return, while reassuring them that together we would get through the pandemic, and perhaps be better in many ways for the experience. No matter if the virtual visit was for an attention-deficit/hyperactivity disorder evaluation, or an acute visit for a fever and cough, the telehealth visit was effective, and in many ways better than an office-based visit. After all, there was no travel involved, patients did not need to be roomed by a nurse, and as vaccinations were never administered, visits were pain free. I was in my “safe space” and the patient was in theirs. I usually wore pajamas, and a hat to cover my-too-long-hair- needing-a-haircut, and my patients and parents were similarly attired. Showering (and shaving) became optional.

At the virtual visit, I soon came to realize that the most rewarding part of the visit was to see another person’s smile! Sheltering in place does make one appreciate the little things. More than hand sanitizer and toilet paper, sharing a smile is one of the true blessings of being a pediatrician. It took no less than a global pandemic to make one appreciate the importance of a simple smile.

Once back in the office, it was clear that resuming well-child exams would not be easy. No matter whether one wears full PPE for these visits or a face mask and shield, with parents and patients masked as well, conversations between exam room occupants is difficult. It is near impossible to share a smile and also difficult to do an examination so attired, and I do not remove a patient’s mask to examine the mouth or throat unless it is necessary. Young children unable to wear a mask are sometimes intimidated by the funny looking person doing doctor stuff, who sounds like that nice pediatrician he or she has seen before. Until such time that we can safely unmask—I now try a little harder to make my patients and parents laugh or giggle to make the office visit comforting.

Although the pandemic curve is flattening, there continues to be widespread COVID-19 cases in my community. Until the crisis is behind us, I suggest that front office staff and office nurses communicate with families via video visits whenever possible. Hopefully we will soon be able to greet families with a smile, a welcoming handshake and a warm hug.

The COVID-19 pandemic has been fraught with worry, depression, and sadness. It's a very difficult time, but a smile can still make a world of difference.

COVID-19: Keep smiling!

A nightly dose of pediatric prolonged-release melatonin (PedPRM) administered to children with autism spectrum disorder (ASD) moderated sleep disturbances, a trial in 80 children and adolescents from 2 to 17 years of age with ASD found. Participants had experienced at least 3 months of impaired sleep, defined as sleeping continuously for fewer than 6 hours or taking more than a half hour to fall asleep most nights. Before entering the study, all participants had tried standardized sleep hygiene and behavioral interventions.

The study comprised a 2-week placebo run-in followed by a randomized trial during which participants in the intervention group received a nightly dose of PedPRM (2 mg, 5 mg, or 10 mg) 30 to 60 minutes before bedtime for up to 104 weeks (most children were treated for 2 years). This was followed by a 2-week placebo period to assess withdrawal effects.

PedPRM was associated with improvements in participants’ sleep and caregiver satisfaction with their child’s sleep patterns, quality of sleep, and quality of life, benefits that were maintained throughout the treatment period, though they declined somewhat during the placebo phase. The most common treatment-related adverse events were fatigue (experienced by 6.3% of participants), somnolence (6.3%), and mood swings (4.2%). PedPRM was not associated with any detrimental effects on growth or pubertal development (

Melatonin has been a lifesaver for many parents, markedly improving quality of life, especially those whose children have developmental disabilities. Previously, at times I had been forced to use chloral hydrate. This study, while not exploring some possible side effects (eg, lab abnormalities), does support that melatonin can be used safely, in high doses, for at least two years.

A recent study examined the impact of a nightly dose of pediatric prolonged-release melatonin on sleep disturbances in children with autism spectrum disorder.

Melatonin helps children with ASD overcome insomnia

Over the past 20 years, pediatric and family nurse practitioners (PNPs & FNPs) have been providing primary health care services to children whose lives are often challenged by the social determinants of health (SDOH).

 COVID-19 has adversely impacted the health and well-being of grandparents, parents and close relatives of these children, with an overwhelming number of their relatives succumbing to COVID-19. In the last week of April 2020, the emergence of a new disorder, Multisystem Inflammatory Syndrome in Children (MIS-C)

 was identified in the United States (US) and the United Kingdom, and disproportionately affects children in these vulnerable, multi-ethnic, minority communities.

 Thus, because COVID-19 has demonstrated how adversely it can affect children, critical decisions must be made on the topic of safe ‘return to school.’

As fall approaches, one of the biggest questions is: Can children return to school and be in classroom environments that assure health and well-being for all? Here's how practitioners can help.

Vol 37 No 8