Cheryl Guttman Krader is a contributor to Dermatology Times, Ophthalmology Times, and Urology Times.

Cheryl Guttman Krader, BS, Pharm

One-third of pediatric patients with atopic dermatitis (AD) have moderate to severe disease, and the affected proportion increases with age. While systemic medications should be considered for these patients when optimal therapy using basic management strategies and topical agents fails, safety concerns with systemic medications have limited their appropriate use.

The current and future availability of more targeted therapy for AD, however, promises to lower the threshold for starting systemic therapy and improving quality of life for pediatric patients with moderate to severe disease, says Amy S. Paller, MD, Walter J. Hamlin professor and chair of the Department of Dermatology and professor of pediatrics at Northwestern University Feinberg School of Medicine in Chicago, Illinois.

“With its safety and lack of need for laboratory monitoring, dupilumab has revolutionized systemic treatment for moderate to severe AD in pediatric patients aged 6 years and older, and we can expect more advances in the future. Dupilumab is now being studied in children as young as 6 months of age, and pediatric trials are ongoing evaluating other biologics as well as oral Janus kinase (JAK) inhibitors,” Paller said.

She added: “In the future, identification of biomarkers, including those that can obtained noninvasively by tape stripping, may help predict the course of AD and its response to systemic medications and improve our therapeutic decision-making capabilities. In addition, pediatric-specific guidelines on AD reflecting new data are being developed to provide evidence-based recommendations. I expect these guidelines will be available within the next year.”

The algorithm for treatment of moderate to severe AD follows a stepwise approach that begins with topical anti-inflammatory medications and basic management strategies. If the AD is not responding, consideration should be given to nonadherence, misdiagnosis, the need to treat a secondary infection, or presence of a contact allergy or another allergic trigger, as well as intensity of topical treatment.

“We always want to ensure that topical therapy is optimized before considering commitment to a biologic,” Paller told 

. “I have seen many children with moderate to severe AD who dramatically improved with appropriate topical therapy. But there are risks associated with using potent topical steroids, especially if being applied in more sensitive areas. If topical steroids, often coupled with nonsteroidal topical alternatives, do not turn the situation around, dupilumab may be considered to offer a safer option than chronic application using large amounts of a topical steroid, especially with only partial improvement.”

When systemic therapy becomes indicated for AD in pediatric patients, the traditional options have been cyclosporine A, methotrexate, mycophenolate mofetil, and azathioprine.

“Outside the realm of pediatric dermatologists, treatment with systemic steroids remains the most commonly used approach, especially by primary care physicians. However, systemic steroids are too toxic for continued use in pediatric patients and AD rebounds once steroids are discontinued, so that use of systemic steroids in children with AD should be extremely restricted,” Paller said.

Cyclosporine has been the favored systemic treatment for AD among pediatric dermatologists because of its rapid onset and it remains the first option for children who cannot be on dupilumab (Dupixent; Sanofi Genzyme/Regeneron Pharmaceuticals) for any reason. However, cyclosporine is generally used for just 3 to 4 months to achieve control and then patients are transitioned to a less toxic agent, such as methotrexate, using an overlap period.

Offering advice for starting dupilumab, Paller suggested giving any required live immunizations at least 1 month before starting the biologic.

“It is not known that receiving a live immunization while on the biologic is unsafe and theoretically it is not, because dupilumab only blocks the Th2 signaling pathway. Nevertheless, the safety of live immunization while taking dupilumab has not been formally tested,” Paller said.

She called attention to the recommended age- and weight-based dosing schemes for dupilumab and cautioned against abruptly stopping any existing systemic treatment. With regard to the latter, Paller shared her practice of continuing any existing systemic agent (unless there is an adverse event) for 1 month and then reducing the dose by half for 1 month before discontinuation.

Topical steroids should be continued during the transition and until no longer needed to augment the effects of dupilumab. More potent topical steroids can be added for a short course as well to manage flares that may occur while the patient is on dupilumab, she said.

Excoriated erythematous papules on the antecubital area of a 10-year-old boy with severe atopic dermatitis. Photo courtesy of Amy Paller, MD.

Not all patients respond to dupilumab, and while evidence of improvement is usually seen by 2 months in those who are likely to benefit from the biologic, dupilumab should be continued for at least 3 to 4 months before it is deemed ineffective.

“We can see improvement in some children beyond 16 weeks. For those without adequate improvement, however, by 3 to 4 months, increasing the dose or frequency of administration might help if insurance allows access to the higher dosing,” Paller said.

When treatment is effective, Paller suggested continuing dupilumab for at least 1 year of disease control. But if the patient or family is interested in trying to stop the dupilumab, it should never be stopped abruptly. Rather, she advised tapering administration by increasing the interval between injections while monitoring for relapse.

“Some children have sustained improvement when taken off dupilumab, suggesting that in some, the biologic may ‘reset’ the immune system, at least for several months. However, a patient whose AD flares during a dupilumab taper or who is not clear on the full dose of dupilumab will likely not do well if the treatment is stopped completely,” she said.

Pretreating with a topical anesthetic can be considered when a child is battling the dupilumab injection and it may be possible to eliminate the topical anesthetic after using it a few times as patients gain comfort. The pen form of dupilumab is useful for giving older children the independence to treat themselves, Paller said. However, she has found that it can be more uncomfortable for younger children, especially those with less subcutaneous tissue.

Conjunctivitis, which is the second most common adverse reaction with dupilumab, is not a contraindication to using the biologic, and if it emerges during treatment, the conjunctivitis is generally self-limiting after a few months.

Paller said that in her experience, starting use of preservative-free artificial tears when starting the dupilumab and continuing for the first few months may be helpful in children in reducing risk of conjunctivitis, but has yet to be tested. She recommended referring patients to an ophthalmologist for treatment of conjunctivitis that exists or if needed to control a reaction to dupilumab. She also mentioned a suggestion in the literature to apply tacrolimus ointment to the eyelids, especially if the eyelids are affected by AD, which they often are when conjunctivitis develops.

When discussing initiation of dupilumab with families, she encourages families to contact her if any unusual side effects of dupilumab occur, given the possibility of persistent red face, psoriasis/psoriasiform reactions, and new onset of alopecia areata.

“Starting dupilumab in a patient with comorbid alopecia areata would involve shared decision-making with the family and child, taking into account that there are also reports of the hair loss improving in children treated with dupilumab for AD and that the AD tends to be the greater burden,” Paller said.

Pregnancy outcomes in patients exposed to dupilumab while pregnant are being monitored. To date there is no evidence of risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, but topical treatment is largely preferred during pregnancy, Paller said.

Two interleukin (IL)-13 inhibitors are being developed as treatment for AD in children and/or adolescents. Tralokinumab (LEO Pharma) has completed studies enrolling adolescent patients and is being investigated in a trial of children aged 6 years and above. Lebrikizumab (LY3650150; Eli Lilly and Company/Dermira, Inc) is being evaluated in ongoing trials including children aged 12 years and older. Studies to date suggest the same safety profile as dupilumab.

Nemolizumab (CD14152; Galderma), a monoclonal antibody targeting the receptor of IL-31, is now being studied in pediatric patients aged 12 years and older.

“IL-31 is itch-specific cytokine, and in studies of adults, nemolizumab had an early and dramatic effect on itch. It appears, however, that nemolizumab should be coupled with a topical corticosteroid to achieve the best effect on skin inflammation,” Paller said.

Three oral JAKs are also being investigated as treatment for AD in pediatric patients: abrocitinib (PF-04965842; Pfizer), which has completed a trial in patients aged 12 years and above; upadacitinib (Rinvoq; AbbVie Inc), which has completed a trial in the same age group and is now being studied in patients aged 6 months and above; and baricitinib (Olumiant; Eli Lilly and Incyte), which is in a study of adolescents aged 12 years and older.

Paller said available data from studies of the JAK inhibitors suggests high efficacy and a rapid and potent effect on itch. The JAK inhibitors are also attractive for their administration schedule and route—once daily by mouth—and because they are rapidly cleared from the body. Adverse events (AEs) may be the limiting factor for their use. The most common AEs in clinical trials have been nausea, headache, and acne.

“The opportunity to easily start and stop the JAK inhibitors suggests they may have a role for controlling AD flares or seasonal involvement,” Paller said.

“It remains to be seen if there are differences in side effect profiles among the JAK inhibitors that will favor using any one of these agents in the pediatric population. The good news is that there are no signals for malignancy, thromboembolism, or high-risk infections with their administration in the AD trials, although it remains to be seen what risks might emerge post-approval with expanded and longer-term use,” Paller said.

This was originally published by Dermatology Times.

Articles

New and forthcoming options bring opportunity for optimizing patient care.

Looking at systemic treatment for atopic dermatitis

Findings of a retrospective review of pediatric patients add to existing evidence suggesting a role for dupilumab (Dupixent; Sanofi/Regeneron Pharmaceuticals, Inc) as a systemic treatment for severe and refractory alopecia areata (AA).

ournal of the American Academy of Dermatology

, Leslie Castelo-Soccio, MD, PhD, reported on 16 children with coexisting atopic dermatitis (AD) and AA who were receiving subcutaneous dupilumab 300 mg every 2 weeks.1 Four children also had concurrent asthma.

Dupilumab was well tolerated and appeared safe in this small series of patients. The only adverse events were mild injection-site reactions.

Responses of patients with AA after starting dupilumab varied. Improvement occurred in 4 of 6 patients with flaring/active AA, and hair regrowth was seen in one additional patient. Six patients maintained hair regrowth. Among patients who experienced benefit, the Severity of Alopecia Tool (SALT) score improved by an average of 33.3 after 12 months.

“A single center trial [NCT03359356] at the Icahn School of Medicine at Mount Sinai led by Emma Guttman-Yassky, MD, PhD investigating dupilumab for treating AA in adults with and without concomitant AD has been completed, and the results should be available soon,”2 Castelo-Soccio, an assistant professor of pediatrics and dermatology at the University of Pennsylvania Perelman School of Medicine and dermatologist at Children’s Hospital Of Philadelphia in Philadelphia , Pennsylvania told 

. “I am continuing to use dupilumab to treat children with AA if it is comorbid with atopic disease for which benefits of dupilumab are clear, but a clinical trial investigating its use to treat AA in children is needed.”

Interest in dupilumab as a treatment for AA and an explanation for its possible benefit is supported by genome-wide association studies investigating susceptibility loci for AA that showed an interleukin (IL)-13 signature in some patients.3

“Dupilumab could control the inflammatory response in AA and help with AA flares because it blocks the IL-13 signaling pathway by binding to the IL-4Rα subunit shared by the IL-4 and IL-13 receptor complexes,” Castelo-Soccio explained.

Castelo-Soccio said she cares for many pediatric patients with AA in her patient population and that many of these patients who have concurrent atopic disease report that they experience AA flares whenever their eczema or atopic rhinitis flares.

“Dupilumab was being used more broadly at our center for treating children with severe AD, and anecdotally, I had noticed hair regrowth and reduction in flares among patients who also had AA,” Castelo-Soccio noted. “I undertook this retrospective review to get a clearer idea of how AA was responding.”

Among the 16 patients included in the review, the duration of AA prior to starting dupilumab ranged from less than 1 year to 11 years. Median number of prior therapies for AA was 4, and 8 children were on 1 or more additional therapies while being treated with dupilumab.

Types of AA among the 16 children included universalis (n = 7), ophiasis (n = 5), and patchy (n = 4). The AA was active in 6 patients. SALT scores at dupilumab initiation ranged from 0 to 100. The 2 patients with active disease who did not respond to dupilumab had SALT scores of 100 when starting dupilumab.

In 4 patients, AA worsened during the first 1 to 2 months after starting dupilumab, but it improved with time in the 2 patients who had further follow-up—and both patients had a SALT score of 0 at 12 months after starting dupilumab. Two patients with SALT scores of 0 when starting dupilumab were already receiving tofacitinib and were able to undergo dose reduction of the Janus kinase inhibitor without increased hair loss.

Exploring potential characteristics associated with a better response, Castelo-Soccio observed that all the patients who improved had moderate to severe AD when starting dupilumab. Compared to the nonresponders, the responders had a lower median age at AD diagnosis (6 years vs 13 years) and a longer median duration of AD (6 years vs 1 year).

“A previous report also found that patients whose AA responded to dupilumab had more severe and long-standing histories of AD,”3 Castelo-Soccio said. 

AA is the most prevalent autoimmune disorder, and comorbidity of atopic disease and AA is not uncommon.4 An analysis limited to children with AA found that 26.6% had atopy.5

Castelo-Soccio said that standard therapy for AA in children includes topical steroids and topical sensitizers, along with selected use of intralesional triamcinolone. Systemic therapy is considered for children with extensive hair loss (> 30% to 50%) or for those with less area of involvement but who are experiencing significant quality-of-life impairment because of the disease.

“Ultimately, the decision to use systemic medications in children is made jointly with the family and child following a thorough discussion of the benefits and risks,” Castelo-Soccio said. “I always remind families that we are treating the child and not the parents or guardians. In addition, I emphasize that AA is a medical disease and should be treated like one but that the visibility of the disease creates an enormous psychological burden, and so care addressing this part of the medical disease is also needed.

“The options for systemic therapy include steroids, methotrexate, Janus kinase inhibitors, or dupilumab. However, I do not think dupilumab is effective in children without an atopic component.”

This article was originally published by Dermatology Times.

Castelo-Soccio has no relevant financial interests to disclose.

1. McKenzie PL, Castelo-Soccio L. Dupilumab therapy for alopecia areata in pediatric patients with concomitant atopic dermatitis. 

. 2021;84(6):1691-1694. doi:10.1016/j.jaad.2021.01.046

2. Treatment of alopecia areata (AA) with dupilumab in patients with and without atopic dermatitis (AD). ClinicalTrials.gov. Updated January 7, 2021. Accessed June 9, 2021. 

https://clinicaltrials.gov/ct2/show/NCT03359356

3. Jagielska D, Redler S, Brockschmidt FF, et al. Follow-up study of the first genome-wide association scan in alopecia areata: IL13 and KIAA0350 as susceptibility loci supported with genome-wide significance. 

 2012;132(9):2192–2197. doi:10.1038/jid.2012.129

4. Marks DH, Mesinkovska N, Senna MM. Cause or cure? review of dupilumab and alopecia areata. 

 Published online June 13, 2019. doi:10.1016/j.jaad.2019.06.010

5. Villasante Fricke AC, Miteva M. Epidemiology and burden of alopecia areata: a systematic review. 

Hair regrowth was observed after starting dupilumab treatment in some pediatric patients with a history of severe and refractory alopecia areata and concomitant atopic dermatitis.

Using dupilumab for pediatric alopecia areata

Sudden unexplained death in infants and children is responsible for more deaths than pediatric cancer or heart disease and is the leading cause of postneonatal mortality in most advanced economies throughout the world. There are important questions about increased risks in other children in the family, while bereaved parents often experience severe and prolonged grief that may influence their parenting.

At the American Academy of Pediatrics (AAP) 2019 National Conference and Exhibition in New Orleans. Louisiana, in October, Richard Goldstein, MD, explained the complex needs of families whose children died from sudden infant death syndrome (SIDS) or sudden unexplained death in childhood (SUDC) and discussed the growing body of knowledge from biomedical and grief research as a basis for helping pediatricians provide improved care.

His session titled “Supporting families after the sudden unexpected death of a child” took place on Monday, October 28.

“Pediatricians are very attuned to the importance of giving sleep recommendations for preventing SIDS and are aware of the possible child abuse implications surrounding cases of sudden unexplained death. However, our field has not done as good of a job educating clinicians about how to interact with and help families who are in crisis after experiencing the unimaginable,” said Goldstein, program director, Robert’s Program on Sudden Unexpected Death in Pediatrics, and assistant professor of Pediatrics, Harvard Medical School, Boston, Massachusetts.

“These are our patients and their families. Sometimes they die following all our advice and, even when they don’t, many of us can feel unprepared about what to say or do,” said Goldstein. “Our educations typically leave us uninformed about strides made by research in this area. It is important that clinicians be prepared to understand and address the concerns of these families beyond just talking about risk factors in the sleep environment.”

Parents almost universally want to know why it happened, how their seemingly healthy child might have died this way, and what it means for their other children. Goldstein heads a program that investigates the possibility of undiagnosed diseases and vulnerabilities in cases of unexplained deaths. He shared research that provides some answers.

Brainstem vulnerability is a driving factor in many cases of SIDS, preventing infants from responding to what is otherwise a modest threat in their sleep environment and leading to a failure to autoresuscitate and arouse. “We have found reduced serotonin in the brainstems of SIDS infants and shown in animal models that this deficiency causes autoresuscitation failure,” said Goldstein.

His group’s SUDC research has found changes in the

hippocampus that are otherwise considered hallmarks of epilepsy. Related to this discovery, they have discovered a gene present in some SIDS cases linked to Dravet syndrome, a severe epilepsy syndrome.

“Whereas this research is significant and may provide direction for the future, to be a good pediatrician for these families requires an understanding of the psychological crisis they are going through,” said Goldstein, who also discussed his grief research that shows extremely high levels of grief-related symptoms that impede a mother’s function.

“We found that while approximately 10% of older adults experience pathologic grief 1 year after losing their life partner, 60% of mothers who lost a child to SIDS are suffering pathologic grief 1 year later, a burden that continues at high rates for years,” Goldstein points out.

His research has also found ways to identify mothers at higher risk.

Goldstein’s main message was to emphasize the need to remain a family’s pediatrician at an extremely difficult time. He provided practical help for how to reach out to families, help them pursue explanations, and provide needed support.

The death of a child is an unnatural event, defying life’s natural order. When the death is sudden and unexpected, there can be added trauma for parents, siblings, and extended family members as the entire family dynamic has changed.

At the AAP 2019 National Conference and Exhibition, Richard Goldstein, MD, addressed this important topic in a session titled “Supporting families after the sudden unexpected death of a child.” As Dr. Goldstein highlights, the pediatrician has a unique role to play in meeting the complex medical and psychosocial needs of the family. However, our training has not adequately prepared us for how to support families after these deaths.

When a child dies suddenly and unexpectedly, the family is faced with a multitude of professionals and agencies, including first responders, law enforcement, emergency department providers, child protective services, and medical examiners. The pediatrician can act as a liaison between these professionals and the family. In providing support for families, it is important for pediatricians to recognize that grief is not linear and that the families’ needs may change over time.

When the child is aged older than 1 year, there is the added challenge that there is limited awareness of the category of death of sudden unexplained death in childhood (SUDC), which is the sudden and unexpected death of a child aged between 1 and 18 years that remains unexplained after a thorough investigation including autopsy. It affects approximately 400 children annually and is the fifth-leading category of death in children aged 1 to 4 years. However, most of the research in sudden death in Pediatrics has focused on infant deaths. As a result of this lack of awareness, pediatricians may be unaware of how to connect families with important resources such as the SUDC Foundation (

In recognition of the need for more consistent investigations and the need for guidance for medical professionals handling these deaths, the SUDC Foundation provided a scientific grant for a collaboration between the AAP and the National Association of Medical Examiners to form consensus guidelines for sudden deaths in Pediatrics titled “Unexplained pediatric deaths: Investigation, certification, and family needs.” These guidelines, which will be published in January 2020 and available online (

), represent an important step in improving care to families affected by sudden pediatric deaths.

The consensus guidelines and Dr. Goldstein’s session are significant steps to addressing the gap in our education around supporting families after pediatric deaths and encouraging pediatricians to remember that their role as the child’s pediatrician should not end with the child’s death.

Erin Bowen, MD, is a pediatrician in practice in Ansonia, Connecticut. She is a member of the American Academy of Pediatrics (AAP) and a member of the AAP Section on Child Death Review and Prevention. She is also a member of the Sudden Unexplained Death in Childhood (SUDC) Foundation Board of Directors, working on the foundation’s Medical Education Initiatives, with a goal of increasing medical education of SUDC to professionals at the forefront of care for affected families.

Pediatricians can use the growing body of knowledge from biomedical and grief research as the basis for improving their care of bereaved parents in crisis.

Caring for parents after the sudden death of a child

Acute flaccid myelitis (AFM) is an uncommon but serious condition for which outbreaks have followed a biennial pattern since 2014. With the next surge of AFM cases predicted in 2020, it is important that pediatricians be familiar with its presenting features because early recognition has implications both for the prognosis of the affected child and for enabling research to understand AFM etiology, said 

, at the American Academy of Pediatrics (AAP) 2019 National Conference and Exhibition, October 28, in New Orleans, Louisiana.

In his session titled “Acute flaccid myelitis,” Messacar presented information on AFM epidemiology, diagnosis, prognosis, and management. He also discussed some recent research advances that are providing insight on infectious causative mechanisms for this recently described disease.

Messacar is assistant professor of Pediatrics at the University of Colorado, Denver, a hospitalist, and infectious disease consultant at Children’s Hospital Colorado Anschutz Medical Campus, Aurora. He told attendees that the term AFM was coined in 2014 after groups of children presented with paralysis of the arms, legs, or muscles of the face and throat. In response to reports of these cases, the Centers for Disease Control and Prevention (CDC) established a case definition to both identify cases and quantify their number. According to the CDC, AFM is defined as acute onset of flaccid limb weakness and magnetic resonance imaging (MRI) involvement of predominantly the gray matter of the spinal cord without identified etiology in individuals aged younger than 21 years.

Messacar said that pediatricians should suspect AFM in any child presenting with weakness in the arms or legs, particularly during late summer or early fall, which have been the peak periods for AFM outbreaks. The history provides another clue to diagnosis as most children will have had a recent febrile illness with respiratory or gastrointestinal symptoms, or signs of hand-foot-mouth disease. The features of the prodromal illness and the prognosis of AFM may vary depending on the associated virus, said Messacar.

The most common virus associated with AFM cases that have occurred throughout the country since 2014 has been enterovirus D68 (EV-D68), but in 2018 in Colorado there was a cluster of cases associated with EV-A71. Most children who had an EV-D68 infection had respiratory symptoms, whereas the initial prodromal illness associated with EV-A71 involved hand, foot, and mouth lesions. In addition, whereas the majority of children with EV-D68–associated AFM have persistent weakness, complete recovery was more common with EV-A71–associated cases.

When AFM is suspected, pediatricians should report cases to their state health department and order an MRI of the brain and spinal cord to confirm the diagnosis. Importantly, they should procure samples as soon as possible from the respiratory tract, blood, stool, and spinal fluid and submit the specimens to the CDC.

“It is hoped that prompt collection of samples from children with AFM will enable identification of its etiology. Unfortunately, the delay between the initial febrile illness and onset of AFM symptoms has been a major impediment to determining the underlying cause,” Messacar said.

“Children typically first experience muscle weakness about 5 to 7 days after the prodromal illness that is likely the inciting infection, and so by the time that AFM is suspected, the window of opportunity to identify a potential pathogen may have passed in some cases,” he said.

Early recognition is also the cornerstone for optimizing management of children with AFM, the mainstay of which is supportive care to maintain breathing, nutrition, and hydration.

“Progressive neurologic injury with AFM can occur quickly, sometimes within a matter of hours, with resulting paralysis of the muscles that support breathing and protect the airway, Messacar pointed out. “Consequently, a significant proportion of children with AFM require intubation and ventilation. Early recognition of AFM is critical so that the necessary support is provided in a timely manner.”

Rehabilitation therapies, including physical therapy, occupational therapy, and speech therapy, should be initiated as soon as the patient is clinically stable and maintained as long as needed to assist children in regaining as much function as possible.

“The majority of children with AFM do not have complete recovery and are left with long-term if not permanent weakness or paralysis. Pediatricians have an important role as quarterback for coordinating ongoing rehabilitation and the complicated care of these children,” Messacar said.

Acute flaccid myelitis (AFM) has captured national headlines since outbreaks were recognized in the United States in 2014, 2016, and 2018. Similar to poliomyelitis, patients can experience acute onset of flaccid weakness in one or more limbs, and the condition is most common in children.

Whereas the syndrome of flaccid myelitis can be caused by a number of viruses or immune-mediated pathologies, the late-summer outbreaks occurring on alternating years since 2014 are most associated with a specific enterovirus. This has raised a number of scientific questions and public health concerns. With those issues in mind, and because of the current emphasis on early recognition, reporting, and treatment, it is critical for pediatricians to be aware of AFM.

In a session on this topic at the AAP’s 2019 National Conference and Exhibition, Dr. Kevin Messacar discussed a number of important issues. An update on the current epidemiology and clinical presentations of AFM may be particularly valuable for pediatricians considering that early on, the signs of illness may be missed. Reviewing the differential of acute flaccid weakness is critical for pediatricians as patients may rapidly decline neurologically and suffer respiratory difficulties.

Messacar reviewed the data relative to etiology studies, pointing out that the likely cause in the majority of patients is enterovirus D68, which usually causes a mild upper-respiratory syndrome. He noted the prevalence of a prodromal illness in the majority of patients, followed by rapid neurologic decline a week later.

As Dr. Messacar pointed out, early reporting to public health officials and sampling of nasopharyngeal secretions, cerebrospinal fluid, and blood will be critical for CDC-led efforts to confirm the etiology of spinal cord damage. Pediatricians need to be aware of the public health needs and the individual patient needs. Messacar stressed the importance of supportive care, considerations for therapies to limit damage, and the need for early, albeit prolonged, rehabilitation services.

Benjamin M. Greenberg, MD, MHS, is Distinguished Teaching Professor of Neurology and Pediatrics, University of Texas Southwestern, Dallas, Texas.

Recent research advances are providing insight on infectious causative mechanisms for this recently described disease in children.

Update on acute flaccid myelitis

The climate crisis is affecting everyone, but no group has more at stake than children. That was the key message of Debra Hendrickson, MD, at the recent American Academy of Pediatrics (AAP) 2019 National Conference and Exhibition in New Orleans, Louisiana. Her talk, “A burning house: Children’s health in the warming world,” addressed conference attendees during the plenary session on Monday, October 28.

Hendrickson told the audience that she was inspired to write a book on the need for action after seeing how climate change was affecting her patients in Reno, Nevada, which in 2016 was named the fastest-warming city in the United States. From infants suffering from wildfire smoke to teenagers anxious about their future in a warming world, children are increasingly feeling the impacts of our changing climate, she said.

Hendrickson urged doctors to better recognize how certain illnesses-such as asthma, allergies, heat illnesses, and infectious diseases carried by ticks and mosquitoes-are being amplified by rising temperatures, more frequent wildfires, hurricanes, flooding, and other climate changes.

“Although the health consequences of climate change are being seen in our patients,” she said, “clinicians may not notice because, much like natural disasters themselves, these diagnoses have always been around but they’re occurring now with greater frequency or severity.”

As part of her talk, Hendrickson told the stories of several children affected by wildfires, hurricanes, or heat waves, and then used their cases to explain why children are more physiologically and developmentally vulnerable to the health problems created by climate change. She emphasized the importance of such storytelling in motivating parents and policymakers to act, arguing that the climate crisis is not just a global crisis, it’s also “a very personal crisis, multiplied many times.”

Hendrickson noted that, ironically, pediatricians today have extraordinary new medications and technology to keep their patients healthy, while at the same time children are facing an existential crisis. “Climate change is threatening everything we work to accomplish for our patients because it is altering the fabric of life itself,” she said.

Far from being a pessimist, Hendrickson emphasized the great potential for pediatricians, as trusted sources of information, to help promote solutions and lead the way, both in their practices and their daily lives. She noted that there are relatively easy steps that each person can take to reduce their own carbon emissions and build a broader movement toward sustainable energy.

For example, most utility companies now offer a “green energy” option that allows customers to choose all-renewable electricity with just a few clicks on their website. Wider adoption of electric cars, which can plug into these all-green homes, and reducing meat and dairy content in our diets would also help, Hendrickson said.

Finally, noting that children are rising up in protest around the world, demanding that governments and corporations act on this issue while there is still time, she called on pediatricians to stand with them.

“We care for the generation that will be most affected by this crisis,” Hendrickson said. “We have a moral obligation to fight for our patients.”

Pediatricians are increasingly facing a new issue in child health-climate change. More extreme heat is increasing the risk of heat illness and making it more hazardous for children to play outdoors. Increasing wildfires and rising pollen counts are challenging our ability to protect children’s respiratory health. Warming winters, earlier springs, and higher water temperatures are causing shifts in patterns of some climate-sensitive infectious diseases.

Whereas all people are affected by changing climate conditions, children are among the most vulnerable. It is estimated that children aged younger than 5 years bear greater than 80% of the global burden of disease caused by climate change. In recognition of this unique vulnerability, the American Academy of Pediatrics (AAP) was the first major medical society to publish a policy statement on this topic in 2007. The AAP Council on Environmental Health published an updated policy statement and technical report in 2015. These reports identify climate change as one of the greatest threats facing children in the United States and across the world.

Although most pediatricians are seeing affected children today, recognizing the signal of climate change in a busy pediatrician’s office remains challenging. That is because changing patterns in temperature, rainfall, and extreme weather generally amplify and shift conditions pediatricians have always seen, rather than create novel conditions. Noticing changes in seasonal timing, frequency, or severity of common conditions can be a challenge.

In her plenary session at the AAP’s 2019 National Conference, Dr. Debra Hendrickson helped pediatricians to make the connections between changes in the climate and changes in the health of their patients. Through the stories of children affected by extreme heat, weather disasters, and wildfires, she portrayed how changes in climate are affecting the lives of real children in diverse ways across the United States. Many pediatricians are witnessing similar stories but have not yet linked them to environmental change.

Climate change is not only an immediate health threat but is an unprecedented risk to children’s future. As such, it is a moral challenge for all who care for children.

The past year has brought this into focus as children across the world have engaged in school strikes to highlight the urgent need for climate solutions to protect their future. In the United States, children are suing the federal government for its inaction on climate change and the resulting depravation of their fundamental rights in the case of Juliana v. United States. The AAP signed an amicus brief in support of the children in this case.

Advocacy has been a top priority of the AAP since its inception. The voice of pediatricians has been instrumental in protecting children from a wide range of threats to their health and safety over the century. Dr. Hendrickson discusses the role of pediatricians in speaking out in support of climate solutions. From small changes in our personal lives and practice management, to advocacy in our communities, states, and our nation’s capital, pediatricians can protect every child by working to ensure a safe and healthy planet for their future.

Samantha Ahdoot, MD, FAAP, is a pediatrician in Alexandria, Virginia, and assistant professor of Pediatrics at Virginia Commonwealth University School of Medicine, Inova Campus, Falls Church, Virginia. She serves on the Executive Committee of the American Academy of Pediatrics (AAP) Council on Environmental Health and was lead author of the AAP’s policy statement and technical report “Global climate change and children’s health,” published in 2015.

Children are more physiologically and developmentally vulnerable to health problems created by climate change.

Climate change has adverse effects on children’s health

With autism spectrum disorder (ASD) affecting 1.7% of 8-year-old children, all pediatricians are likely to have many children with ASD under their care.

Pediatricians play an important role in optimizing outcomes for children with ASD, from facilitating early diagnosis, helping families access evidence-based treatments, identifying and treating comorbid medical and behavioral conditions, and serving as a resource to families about the safety and evidence relating to complementary and alternative medical treatments, said Lisa H. Shulman, MD, at the American Academy of Pediatrics (AAP) 2019 National Conference and Exhibition in New Orleans, Louisiana, in October.

In seminar sessions held on Monday, October 28, and Tuesday October 29, Shulman provided an overview of “Autism spectrum disorder: What every pediatrician should know” in 2019.

“Signs of ASD are often apparent by age 18 months or even younger, and yet it remains the case today that the diagnosis is typically not made until after age 4 years. Because of the frequency with which children are seen by their pediatricians when they are very young, the medical home is the perfect place for identifying children who may have ASD,” said Shulman, professor of Pediatrics, Albert Einstein College of Medicine, and interim director of the Rose F. Kennedy Children’s Evaluation and Rehabilitation Center at Montefiore Medical Center, Bronx, New York. “Each encounter over time is an opportunity to not only evaluate developmental milestones but also social functioning,”

Shulman noted the need for following the AAP guidelines on screening for ASD at 18 and 24 months to help improve early identification, and also for pediatricians to not rely solely on completed checklists but to “look with their own eyes” for early signs that are predictive of autism when present at 12 months. These signs include reduced eye contact, failure to respond to name, not pointing to request, and not pointing to show. How easy is it to obtain the child’s attention? To achieve a shared smile in response to a song? How does the child let you know that he/she wants a colorful object out of reach?

A hearing test is essential in the medical workup for a child when ASD is suspected. After hearing is cleared and there is concern about ASD, simultaneous referrals should be made for a diagnostic evaluation and for early intervention to the school district. “The diagnostic evaluation for ASD can take some time. So, do not wait for it to be completed before making the referral to early intervention or the school district,” Shulman said.

She encouraged pediatricians who do not work in a setting with access to an existing ASD diagnostic center to “make a team” of professionals who have an interest and expertise in early ASD diagnosis. The team can be informal and might include a developmental pediatrician, neurologist, or psychiatrist and a psychologist, and/or speech and language pathologist.

Diagnostic and Statistical Manual of Mental Disorders (DSM-5)

 diagnostic criteria and discussed the importance of genetic testing, which over time has led to an increasing number of findings relating to the multiple etiologies of ASD. “There are likely epigenetic or environmental second hits that contribute to the development of ASD in children at biologic risk, and we cannot rule out the possibility that there are unknown risk factors leading to an increase in the incidence of ASD,” she said.

Shulman also covered the evaluation and management of medical and emotional/behavioral issues that are common in children with ASD. “As the primary care provider, pediatricians are ideally positioned to monitor for the various conditions that are often comorbid with ASD, including attention-deficit/hyperactivity disorder, anxiety, restrictive eating habits, and constipation, as well as to give anticipatory guidance regarding relevant safety issues such as elopement,” she said.

With an ever-widening set of complementary and alternative medicine (CAM) interventions being promoted for ASD, and confusion over what is experimental and what is evidence based, Shulman reminded pediatricians to ask families about all the treatments they are accessing for their children.

“If you don’t ask, you may not hear about the various treatments families are utilizing,” she said. “Whereas some CAM treatments are quite safe, others may pose risk such as hyperbaric oxygen, chelation, immunoglobulins, stem cell therapies, bleach therapy, and so on. Building on a trusted relationship, pediatricians can be a resource to families to help them sort out safe and effective choices.”

Noting ongoing public concern about vaccination and ASD, Shulman also reviewed the literature on this topic, including the most recent nationwide cohort study that included more than 657,000 children born in Denmark.

“Consistent with previous research, the authors of the Danish study determined that their findings support the conclusion that the measles/mumps/rubella vaccine does not increase the risk for autism or trigger it in susceptible children,” she said.

Autism spectrum disorder (ASD) is relevant to every pediatrician given that it affects roughly 2% of children in the United States and has a significant impact on the lives of children and families. Most children are diagnosed after the age of 4, years after evidence-based ASD-specific therapy could have begun.

Pediatricians play a vital role in early identification of children with ASD and with ongoing care throughout childhood and adolescence. It is therefore important that every pediatrician have a sound working knowledge of this condition in order to facilitate early identification, maximize functional outcomes, and support children with ASD and their families.

In a session at the AAP 2019 National Conference and Exhibition, Dr. Lisa Shulman, a developmental pediatrician at Albert Einstein College of Medicine and current member of the AAP Autism Subcommittee, reviewed “What every pediatrician should know” about ASD. She emphasized developmental surveillance, a process in which pediatricians look for early signs of ASD during health supervision visits. Orienting to name and joint attention were identified as social skill milestones that are critical in identifying toddlers at risk for ASD. Screening all children for ASD at the 18- and 24-month visits, as recommended by the AAP, was also reviewed as a way to augment developmental surveillance in order to facilitate early identification.

Once a child is identified as at risk, Shulman provided important recommendations for the pediatrician regarding referrals for a comprehensive “team-based” ASD evaluation, along with simultaneous referrals to an early intervention program or to a special education program to get appropriate interventions started. She also reviewed aspects of the medical workup for children with ASD, including genetic testing.

Once the diagnosis is made, Shulman provided important information about identification and management of common co-occurring conditions, addressing questions about integrative, complementary, and alternative medications, and ways to inform parents about the lack of association between vaccines and ASD.

Paul S. Carbone, MD, is professor of Pediatrics, University of Utah, Salt Lake City, Utah, and chairperson of the AAP Council on Children with Disabilities Autism Subcommittee.

The pediatric medical home is the perfect place for early diagnosis of children who may have autism spectrum disorder.