Clinical characteristics and management of pediatric egg-induced anaphylaxis: A cross-sectional study.

BACKGROUND: Egg is the third most common food allergy in children; however, data on pediatric egg-induced anaphylaxis are sparse. OBJECTIVE: To describe the clinical characteristics, management, and outcomes of pediatric egg-induced anaphylaxis. METHODS: Children presenting with anaphylaxis were recruited from 13 emergency departments as part of the Cross-Canada Anaphylaxis Registry, from which data on anaphylaxis triggered by egg were extracted. Multivariate logistic regression was used to determine factors associated with prehospital epinephrine autoinjector (EAI) use and to compare anaphylaxis triggered by egg with other triggers of food-induced anaphylaxis (FIA). RESULTS: We recruited 302 children with egg-induced anaphylaxis. The mean age was 2.6 years (SD = 3.6), and 55.3% were male. Only 39.4% had previously been diagnosed with an egg allergy. Prehospital EAI use was 32.1%, but this was not significantly lower than in other triggers of FIA (P = .26). Only 1.4% of patients required hospital admission. Relative to other triggers of FIA, patients with egg-induced anaphylaxis were significantly younger (P < .001) and exhibited more vomiting (P = .0053) and less throat tightness (P = .0015) and angioedema (P < .001). CONCLUSION: To the best of our knowledge, this is the largest published cohort of pediatric egg-induced anaphylaxis. In this cohort, prehospital EAI use was very low. In addition, we identified certain symptoms that distinguish egg-induced from other triggers of FIA. Taken together, high suspicion is crucial in identifying egg-induced anaphylaxis, given the younger patient demographic and frequent lack of FIA history.

Milk-induced anaphylaxis among children presenting to Canadian emergency departments.

BACKGROUND: Cow's milk is one of the most common and burdensome allergens in pediatrics, and it can induce severe anaphylactic reactions in children. However, data on cow's milk-induced anaphylaxis are sparse. OBJECTIVE: To describe the epidemiology of pediatric cow's milk-induced anaphylaxis and to determine risk factors for repeat emergency department (ED) epinephrine administration. METHODS: Between April 2011 and May 2023, data were collected on children with anaphylaxis presenting to 10 Canadian EDs. A standardized form documenting symptoms, triggers, treatment, and outcome was used. Multivariate logistic regression was used. RESULTS: Of 3118 anaphylactic reactions, 319 milk-induced anaphylaxis cases were identified (10%). In the prehospital setting, 54% of patients with milk-induced anaphylaxis received intramuscular epinephrine. In those with milk-induced anaphylaxis, receiving epinephrine before presenting to the ED was associated with a reduced risk of requiring 2 or more epinephrine doses in the ED (adjusted odds ratio, 0.95 [95% CI, 0.90-0.99]). Children younger than 5 years of age were more likely to experience a mild reaction compared with that in older children, who experienced a moderate reaction more often (P < .0001). Compared with other forms of food-induced anaphylaxis, children presenting with milk-induced anaphylaxis were younger; a greater proportion experienced wheezing and vomiting, and less experienced angioedema. CONCLUSION: Prehospital epinephrine in pediatric milk-induced anaphylaxis is underused; however, it may decrease risk of requiring 2 ED epinephrine doses. Milk-induced anaphylaxis in children younger than 5 years of age may be less severe than in older children. Wheezing and vomiting are more prevalent in milk-induced anaphylaxis compared with that of other foods.

Management of anaphylaxis after pre-hospital epinephrine use in children with food-induced anaphylaxis.

BACKGROUND: Previous guidelines recommend prompt epinephrine administration, followed by observation in the emergency department (ED). The need for transfer in all cases of anaphylaxis has recently been challenged. OBJECTIVE: To evaluate the need for additional ED treatment among children with anaphylaxis who received prehospital epinephrine. METHODS: Between 2011 and 2023, data were collected on symptoms, triggers, comorbidities, and prehospital and in-hospital management from children (<18 years) with food-induced anaphylaxis who received at least 1 dose of prehospital epinephrine presenting at 7 pediatric EDs. Multivariable logistic regression assessed factors associated with the use of 2 or more prehospital epinephrine autoinjectors (EAIs), epinephrine use in the ED, and hospital admission. RESULTS: Of the 1127 children (mean 8.1 ± 5.3 years; 60.6% male sex) with food-induced anaphylaxis who used at least 1 EAI prehospital, the most common trigger was peanuts (25.3%). There were 209 (18.5%) children who received additional epinephrine in the ED, most of whom (88.0%) received 1 dose. A total of 30 (2.7%) patients were admitted to hospital. Among all patients, severe reactions (cardiovascular instability/cyanosis/loss of consciousness) (adjusted odds ratio [aOR] 1.22; 95% CI 1.12-1.33) and reactions to tree nuts (aOR 1.09; 95% CI 1.03-1.16) were associated with increased odds of in-hospital epinephrine use. Prehospital inhaled ß-agonists (aOR 1.08; 95% CI 1.01-1.16) use and severe reactions (aOR 1.13; 95% CI 1.05-1.22) were associated with the use of 2 or more EAI prehospital. CONCLUSION: A minority of anaphylaxis cases that used prehospital EAIs required additional treatment, supporting that shared decision making about transfer to ED works for most patients.

Should you test for urinary tract infection in children with respiratory symptoms?

QUESTION: An 8-month-old boy presented to our clinic with a 3-day history of fever. He has had a cough and rhinorrhea since the onset of the fever, and his 4-year-old sibling has recently had cough and cold symptoms. I have heard that the presence of respiratory symptoms means that urinary tract infection (UTI) is less likely. In infants with fever and respiratory symptoms, who should have a sample collected for urinalysis for UTI? ANSWER: The approach to diagnosing febrile infants who have respiratory symptoms varies by age. Urinalysis should be done for all febrile infants younger than 2 months of age, regardless of whether they have respiratory symptoms. Clinicians should assess risk factors for UTI in every infant between 2 and 24 months of age and should not exclude the diagnosis of UTI based on respiratory symptoms alone. Use of a predictive tool to estimate the pretest probability of UTI would aid decision making about patients in this population.

Screen time and sleep in children.

QUESTION: I continue to hear concerns from parents in my practice about the frequent use of light-emitting devices by their children. I have also found that many children suffer from sleep disturbances. What are the effects of screen time on sleep, and what are some best practices for sleep hygiene and screen use among children? ANSWER: Screen time is higher now than before the onset of the COVID-19 pandemic, and knowledge about the effects of screen time is evolving. Spending time in front of a screen may replace sleep time or sleep-promoting activities such as exercise, and the engaging content and social interactions on screens interfere with falling asleep. Evidence exists on the disruption of the circadian rhythm by light emitted by screens. Advice to families should include sleep hygiene activities as well as elimination of screen use at least 1 hour before sleep.

The acute care burden of asthma in children was profoundly reduced during the COVID-19 pandemic: A multi-centre Canadian retrospective study.

Objectives: Asthma is a chronic lung condition that can be exacerbated when triggered by viruses. Pandemic public health restrictions aimed to reduce COVID-19 transmission indirectly effected other circulating viruses. This study assessed the impact of the pandemic and associated public health measures on acute paediatric asthma across four tertiary sites in three Canadian provinces. We queried whether pandemic-related changes would impair preventive care and delay presentation to care, increasing asthma exacerbation severity. Methods: This retrospective study compared the frequency of acute care access and severity of presentation to emergency departments (ED) for acute asthma to four tertiary care children's hospitals during the COVID-19 pandemic (from March 17, 2020 to June 30, 2021) to a pre-lockdown control period (July 1, 2018 to March 16, 2020). Data was subjected to interrupted time series and Chi-square analysis. Results: Our study included 26,316 acute asthma visits to ED. Sites experienced a 63% to 89% reduction in acute asthma visits during the pandemic, compared with pre-lockdown controls, and a 17% to 85% reduction in asthma, that is out of proportion as a fraction of all-cause ED visits. For asthma, there was no difference in severity measured by rate of ward admission or rate of Paediatric Intensive Care Unit (PICU) admission. Conclusions: Public health measures appear to have resulted in a specific protective association on acute asthma with reduced acute care utilization over and above the reduction in all-cause presentations, without an increase in severity upon presentation. Our study indicates an importance to antiviral public health and engineering strategies to reduce viral transmission and thereby asthma morbidity.

Managing anaphylaxis: Epinephrine, antihistamines, and corticosteroids: More than 10 years of Cross-Canada Anaphylaxis REgistry data.

BACKGROUND: Epinephrine is the first-line treatment for anaphylaxis but is often replaced with antihistamines or corticosteroids. Delayed epinephrine administration is a risk factor for fatal anaphylaxis. Convincing data on the role of antihistamines and corticosteroids in anaphylaxis management are sparse. OBJECTIVE: To establish the impact of prehospital treatment with epinephrine, antihistamines, and/or corticosteroids on anaphylaxis management. METHODS: Patients presenting with anaphylaxis were recruited prospectively and retrospectively in 10 Canadian and 1 Israeli emergency departments (EDs) between April 2011 and August 2022, as part of the Cross-Canada Anaphylaxis REgistry. Data on anaphylaxis cases were collected using a standardized form. Primary outcomes were uncontrolled reactions (>2 doses of epinephrine in ED), no prehospital epinephrine use, use of intravenous fluids in ED, and hospital admission. Multivariate regression was used to identify factors associated with primary outcomes. RESULTS: Among 5364 reactions recorded, median age was 8.8 years (IQR, 3.78-16.9); 54.9% of the patients were males, and 52.5% had a known food allergy. In the prehospital setting, 37.9% received epinephrine; 44.3% received antihistamines, and 3.15% received corticosteroids. Uncontrolled reactions happened in 250 reactions. Patients treated with prehospital epinephrine were less likely to have uncontrolled reactions (adjusted odds ratio [aOR], 0.955 [95% CI, 0.943-0.967]), receive intravenous fluids in ED (aOR, 0.976 [95% CI, 0.959-0.992]), and to be admitted after the reaction (aOR, 0.964 [95% CI, 0.949-0.980]). Patients treated with prehospital antihistamines were less likely to have uncontrolled reactions (aOR, 0.978 [95% CI, 0.967-0.989]) and to be admitted after the reaction (aOR, 0.963 [95% CI, 0.949-0.977]). Patients who received prehospital corticosteroids were more likely to require intravenous fluids in ED (aOR, 1.059 [95% CI, 1.013-1.107]) and be admitted (aOR, 1.232 [95% CI, 1.181-1.286]). CONCLUSION: Our findings in this predominantly pediatric population support the early use of epinephrine and suggest a beneficial effect of antihistamines. Corticosteroid use in anaphylaxis should be revisited.

Impact of Time to Diagnosis on Morbidity and Survival in Children With Malignant Central Nervous System Tumors.

OBJECTIVE: The aim was to determine the impact of time to diagnosis (TTD) on morbidity and mortality and to identify factors associated with overall survival (OS) in pediatric patients with malignant central nervous system (CNS) tumors. METHODS: This is a retrospective review of all malignant CNS tumors presenting to 2 tertiary care pediatric hospitals from 2000 to 2019. Cox proportional hazard model analysis outcomes included TTD and OS as well as morbidity; stratified by tumor category, age, relapse, and presence of metastatic disease. RESULTS: There were 197 children with malignant CNS tumors (mean age 8.7 y, 61% male). Tumors included medulloblastoma (N=58, 29.4%), ependymoma (N=27, 13.7%), high-grade glioma (N=42, 21.3%), germ cell tumors (N=47, 23.9%), and other embryonal tumors (N=23, 11.7%). Median TTD from symptom onset was 62 (interquartile range: 26.5 to 237.5 d) and 28% had metastatic disease. Three-year progression free survival was 55% and 3-year OS was 73.1%. Increased OS was associated with increased TTD (parameter estimate 0.12; confidence interval [CI]: 0.019-7.06; P =0.019), high-grade glioma (hazard ratio [HR]: 2.46; CI [1.03-5.86]; P =0.042), other embryonal tumor (HR: 2.84; CI [1.06-7.56]; P =0.037), relapse (HR: 10.14; CI: 4.52-22.70; P <0.001) and metastatic disease (HR: 3.25; CI: 1.51-6.96; P =0.002). Vision change (HR: 0.58; CI: 0.313-1.06; P =0.078), hearing loss (HR: 0.71; CI: 0.35-1.42; P =0.355), and cognitive impairment (HR: 0.73; CI: 0.45-1.19; P =0.205) were not associated with TTD in this model. CONCLUSIONS: Increased median TTD is associated with higher OS in pediatric patients treated for malignant CNS tumors. Tumor biology and treatment modality are more important factors than TTD for predicting morbidity and long-term outcomes in pediatric patients with CNS tumors.

Neuroimaging to diagnose central nervous system tumours in children.

QUESTION: Headache, vomiting, lethargy, and seizures are common symptoms in healthy children with benign viral illnesses, but they are also signs that could represent a central nervous system (CNS) tumour. Primary care providers and guardians are hesitant to expose children to radiation associated with computed tomography scans or take on risks associated with the sedation frequently needed for magnetic resonance imaging. When should primary care providers order radiologic head imaging for children with common symptoms to identify those with a CNS tumour? ANSWER: Central nervous system tumours have no pathognomonic features, which often results in delays in diagnosis. Owing to the high prevalence of infratentorial tumours, children commonly present with symptoms of increased intracranial pressure, making a detailed history and a comprehensive physical examination, including ophthalmoscopy for papilledema, especially important. Magnetic resonance imaging is the criterion standard test but it may take time to access, and young children may need sedation. Hence, computed tomography may be a preferable first option.The HeadSmart initiative in the United Kingdom provides guidance to obtain brain imaging within 4 weeks of onset of persistent symptoms that are associated with CNS tumours. We advocate applying the same criteria in Canada in order to reduce delay in diagnosis of CNS tumours in children.

Corticosteroids for infectious mononucleosis.

QUESTION: Infectious mononucleosis (IM) is a common viral infection year round, and we see patients with it in our family medicine clinic frequently. With fatigue, fever, pharyngitis, and cervical or generalized lymphadenopathy causing prolonged illness and school absences, we always look for treatments that will shorten the duration of symptoms. Does treatment with corticosteroids benefit these children? ANSWER: Current evidence points to small and inconsistent benefits when using corticosteroids for symptom relief in children with IM. Corticosteroids alone or in combination with antiviral medications should not be given to children for common symptoms of IM. Corticosteroids should be reserved for those with impending airway obstruction, autoimmune complications, or other severe circumstances.

Management of acute supraventricular tachycardia in children.

QUESTION: Recently, a 3-year-old patient in my practice urgently needed to go to the emergency department. The patient was found to have supraventricular tachycardia (SVT) and needed immediate treatment with adenosine. What evidence is currently available for management of SVT in children? ANSWER: Supraventricular tachycardia is a common cardiac condition in the pediatric population that manifests as a narrow QRS complex tachycardia on electrocardiography. Symptoms may range from palpitations, poor feeding, and irritability to more substantial hemodynamic instability. Patients who are hemodynamically stable can benefit from interventions such as vagal maneuvers, which can be done in the office. Such maneuvers include the Valsalva maneuver, stimulation of the diving reflex (for infants), and unilateral carotid sinus massage. Other children may need pharmacologic therapies to restore normal heart rhythm, which usually consists of a rapid intravenous injection of adenosine under monitoring. For patients who are hemodynamically unstable, emergency cardioversion may be needed.

Antibiotic treatment duration for community-acquired pneumonia in children.

QUESTION: A 4-year-old child was seen in our clinic with a clinical presentation consistent with community-acquired pneumonia (CAP). He was prescribed oral amoxicillin and a colleague asked about the duration of treatment. What is the current available evidence for treatment duration for uncomplicated CAP in an outpatient setting? ANSWER: Previously the recommended duration of antibiotic treatment of uncomplicated CAP was 10 days. Recent evidence from several randomized controlled trials suggests that a 3- to 5-day duration is noninferior to a longer treatment course. In an effort to prescribe the shortest effective duration of antibiotics to minimize the risk of antimicrobial resistance associated with prolonged antibiotic use, family physicians should offer 3 to 5 days of appropriate antibiotics and monitor the recovery of children with CAP.

Anterior cutaneous nerve entrapment syndrome in children.

QUESTION: I frequently see adolescents with recurrent abdominal pain in my family medicine clinic. While the diagnosis frequently is a benign condition such as constipation, I recently heard that after 2 years of recurrent pain, an adolescent was diagnosed with anterior cutaneous nerve entrapment syndrome (ACNES). How is this condition diagnosed? What is the recommended treatment? ANSWER: Anterior cutaneous nerve entrapment syndrome, first described almost 100 years ago, is caused by entrapment of the anterior branch of the abdominal cutaneous nerve as it pierces the anterior rectus abdominis muscle fascia. The limited awareness of the condition in North America results in misdiagnosis and delayed diagnosis. Carnett sign-in which pain worsens when using a "hook-shaped" finger to palpate a purposefully tense abdominal wall-helps to confirm if pain originates from the abdominal viscera or from the abdominal wall. Acetaminophen and nonsteroidal anti-inflammatory drugs were not found to be effective, but ultrasound-guided local anesthetic injections seem to be an effective and safe treatment for ACNES, resulting in relief of pain in most adolescents. For those with ACNES and ongoing pain, surgical cutaneous neurectomy by a pediatric surgeon should be considered.

Sesame-induced anaphylaxis in pediatric patients from the cross-Canada anaphylaxis registry.

BACKGROUND: Sesame can cause severe allergic reactions and is a priority allergen in Canada. OBJECTIVE: To assess clinical characteristics and management of pediatric sesame-induced anaphylaxis and identify factors associated with epinephrine treatment. METHODS: Between 2011 and 2021, children with sesame-induced anaphylaxis presenting to 7 emergency departments (ED) in 4 Canadian provinces and 1 regional emergency medical service were enrolled in the Cross-Canada Anaphylaxis Registry. Standardized recruitment forms provided data on symptoms, severity, triggers, and management. Multivariate logistic regression evaluated associations with epinephrine treatment pre-ED and multiple epinephrine dosages. RESULTS: Of all food-induced anaphylactic reactions (n = 3279 children), sesame accounted for 4.0% (n = 130 children), of which 61.5% were boys, and the average (SD) age was 5.0 (4.9) years. Hummus containing sesame paste triggered 58.8% of reactions. In the pre-ED setting, 32.3% received epinephrine, and it was more likely to be used in boys (adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], 1.08-1.50) and those with a known food allergy (aOR, 1.36; 95% CI, 1.11-1.68]). In the ED, 47.7% of cases received epinephrine, with older children more likely to receive multiple epinephrine doses (aOR, 1.00; 95% CI, 1.00-1.02). CONCLUSION: In Canada, hummus is the major trigger of sesame-induced anaphylaxis. Knowledge translation focused on prompt epinephrine use and product-labeling policies are required to limit sesame reactions in communities.

Tree nut-induced anaphylaxis in Canadian emergency departments: Rate, clinical characteristics, and management.

BACKGROUND: Data are sparse regarding tree nut-induced anaphylaxis (TNA). OBJECTIVE: To characterize rate, clinical characteristics, and management of TNA in children (0-17 years old) across Canada and evaluate factors associated with severe reactions and epinephrine use. METHODS: Between April 2011 and May 2020, data were collected on children presenting to 5 emergency departments in Canada. Multivariate logistic analysis was used to evaluate factors associated with severe reactions (stridor, cyanosis, circulatory collapse, or hypoxia) and epinephrine use. RESULTS: Among 3096 cases of anaphylaxis, 540 (17%) were induced by tree nut. The median age was 5.2 (interquartile range, 2.5-9.5) years and 65.4% were of male sex. Among all reactions, 7.0% were severe. The major tree nuts accounting for anaphylaxis were cashew (32.8%), hazelnut (20.0%), and walnut (11.5%). Cashew-induced anaphylaxis was more common in British Columbia (14.0% difference [95% confidence interval (CI), 1.6-27.6]) vs Ontario and Quebec, whereas pistachio-induced anaphylaxis was more common in Ontario and Quebec (6.3% difference [95% CI, 0.5-12.2]). Prehospital and emergency department intramuscular epinephrine administration was documented in only 35.2% and 52.4% of cases, respectively. Severe reactions were more likely among of male sex (adjusted odds ratio [aOR], 1.05 [95% CI, 1.01-1.10]), older children (aOR, 1.00 [95% CI, 1.00-1.01]), and in reactions triggered by macadamia (aOR, 1.27 [95% CI, 1.03-1.57]). CONCLUSION: Different TNA patterns in Canada may be because of differences in lifestyle (higher prevalence of Asian ethnicity in British Columbia vs Arabic ethnicity in Ontario and Quebec). Intramuscular epinephrine underutilization urges for epinephrine autoinjector stocking in schools and restaurants, patient education, and consistent policies across Canada.

Seafood-induced anaphylaxis in children presenting to Canadian emergency departments: Rates, clinical presentation, and management.

BACKGROUND: There is a lack of data on seafood-induced anaphylaxis in children in Canada. OBJECTIVE: To evaluate the rate, clinical features, and management of seafood-induced anaphylaxis in children presenting to emergency departments across Canada. METHODS: Children with anaphylaxis were recruited at 6 emergency departments between 2011 and 2020 as part of the Cross-Canada Anaphylaxis REgistry. A standardized form documenting symptoms, triggers, comorbidities, and management was used to collect data. RESULTS: There were 75 fish-induced and 71 shellfish-induced cases of suspected anaphylaxis, most of which were caused by salmon and shrimp, respectively. Mucocutaneous symptoms were most common, whereas respiratory symptoms were associated with patients with fish-induced reactions who have comorbid asthma (adjusted odds ratio [aOR], 1.18; 95% confidence interval [CI], 1.02-1.36). Prehospital epinephrine was underused (<35%), whereas in-hospital epinephrine was given to less than 60% of the patients. Among those with a known fish or shellfish allergy, prehospital epinephrine use was associated with known asthma (aOR 1.39 [95% CI, 1.05-1.84] and aOR 1.25 [95% CI, 1.02-1.54], respectively). Among children who were assessed by either skin test or specific immunoglobulin E, 36 patients (76.6%) with suspected fish-induced anaphylaxis and 19 patients (51.4%) with suspected shellfish-induced anaphylaxis tested positive. CONCLUSION: Prehospital epinephrine is underused in the management of seafood-induced anaphylaxis. Among children with known seafood allergy, prehospital epinephrine use is more likely if there is a known asthma comorbidity.

Parental gender differences in attitudes and willingness to vaccinate against COVID-19.

AIMS: COVID-19 affects family life world-wide. Determinants of hesitancy around vaccinating children against COVID-19 are critical in guiding public health campaigns. Gender differences among parents may determine willingness to vaccinate children against COVID-19. METHODS: Secondary analysis of the COVID-19 Parental Attitude Study (COVIPAS) surveying care givers of children presenting for emergency care in 17 sites in 6 countries during peak pandemic (March-June, 2020). We assessed risk perceptions, vaccination history and plans to vaccinate children against COVID-19 once available. We compared responses given by father or mother and used multivariable logistic regression. RESULTS: A total of 2025 (75.4%) surveys were completed by mothers and 662 (24.6%) by fathers, 60 did not respond to question about future vaccination. Of 2627, 1721 (65.5%) were willing to vaccinate their children. In the multivariable analysis, both fathers and mothers were more willing to vaccinate their child if the parent was older and believed that social distancing is worthwhile, and if their child was up-to-date on childhood vaccines (odds ratio (OR) of 1.02, 3.90, 1.65 for mothers and 1.04, 4.76, 2.87 for fathers, respectively). Mothers (but not fathers) were more willing if they had more than a high school education (OR 1.38), and fathers (but not mothers) were more willing to vaccinate their male children (OR 1.62), compared to female children. CONCLUSION: Unique differences between mothers and fathers underscore the need to view vaccine hesitancy as an acceptable parental response. Public health should plan targeted educational information for parents about a COVID-19 vaccine for children.

Experience of cases with inhaled nitric oxide and therapeutic hypothermia.

BACKGROUND: Neonates with hypoxic-ischemic encephalopathy (HIE) on therapeutic hypothermia (TH) therapy may show persistent pulmonary hypertension of the newborn (PPHN). In Japan, the reported mortality rate is lower than in the US, possibly due to treatment differences of newborns with moderate to severe HIE and PPHN. This study aimed to determine the feasibility and long-term outcomes of inhaled nitric oxide (iNO) and TH therapy in newborns with moderate to severe HIE and PPHN. METHODS: This was a retrospective review of neonates with moderate to severe HIE that were treated with TH from 2008 to 2017 at a large medical center in Japan. We documented their long-term neurological prognosis, measuring their developmental and Gross Motor Function Classification System level at 18 months old. RESULTS: A total of 37 neonates with moderate to severe HIE underwent TH therapy and six of them were started with iNO therapy for PPHN. iNO with TH was safely administered to all six newborns with moderate to severe HIE with PPHN. In two neonates TH was discontinued because of intraventricular hemorrhage (IVH) and severe hypotension. Neurological outcomes were similar in newborns who were treated with iNO and TH and those who were treated with TH alone. CONCLUSION: These initial findings suggest that monitoring hematological and cardiovascular status is important with iNO for severe asphyxia in infants with PPHN. Safer and more feasible protocols are needed for when iNO and TH therapy are administered together.

Myocarditis and pericarditis after COVID-19 messenger RNA vaccines.

QUESTION: With the approval of coronavirus disease 2019 (COVID-19) vaccine for children 5 to 11 years of age and concerns among parents in the past year following reported cases of myocarditis and pericarditis in adolescents, should my office continue to encourage all children and young adults to receive the COVID-19 messenger RNA vaccine? ANSWER: Since April 2021 reports have documented cases of myocarditis and pericarditis in adolescents and young adults after messenger RNA COVID-19 vaccination, and several hundred such reports were documented in Canada. Clinical presentations were mostly mild, with rare instances of admission to the hospital, and were typically among male adolescents 16 years of age and older within several days after the second dose of the vaccine. After vaccination, children and adolescents with symptoms of chest pain, shortness of breath, or palpitations should be evaluated with a physical examination, an electrocardiogram, and measurement of cardiac troponin levels. If results are abnormal, an echocardiogram or cardiac magnetic resonance imaging should be considered. Myocarditis and pericarditis after vaccination are much less common, and much milder, than cardiac complications of COVID-19 infection, and vaccines should continue to be recommended to all those eligible.

Erythema multiforme in children.

QUESTION: Children who present with rashes with "target" lesions are frequently diagnosed with erythema multiforme (EM). This is a self-limiting condition in most children; how should primary care providers differentiate between this and urticaria or Stevens-Johnson syndrome, and what is the recommended course of treatment? ANSWER: While EM is common in children, urticaria is also very common and tends to be more "waxing and waning" compared with EM's fixed lesions. Stevens-Johnson syndrome and toxic epidermal necrolysis are more severe and distinct conditions; they have much more substantial mucous membrane involvement and contain widespread erythematous or purpuric macules with blisters. Since EM is a self-limiting condition, treatment of EM in children is generally supportive, and rarely do children need hospital admission for rehydration. In more severe cases involving mucous membranes or substantial pain, some patients will benefit from topical steroids or antihistamines. When children present with signs of herpes infection, antiviral treatment (acyclovir) may be of benefit. Systemic steroids should be reserved for the most challenging cases.