A 5-year-old female with no significant past medical history presented to the emergency department (ED) in 2016 with altered mental status, decreased activity, fever, and decreased oral intake. Her mother reports that she was in her usual state of health until 1 week prior to presentation when she developed low grade fevers and abdominal pain with associated complaints of headaches, neck pain, and muscle aches. She was able to tolerate water but her overall oral intake was diminished with a marked decrease in urine output, worsening to once daily.

The patient’s mother took her to a local hospital 4 days prior to her ED presentation with complaints of fever (maximum temperature 104°F), headache, and neck pain. She was discharged home when her influenza, streptococcal throat swab, chest x-ray, and urinalysis were all unremarkable. In the days following, she became increasingly too weak to get out of bed, was intermittently confused, refused to answer questions, and was more lethargic. The night before her ED presentation, her mother was extremely concerned when the patient could not remember her name or her parents’ names. Parents denied any rashes, vision changes, vomiting, or diarrhea.

The patient had no previous hospitalizations and was otherwise a healthy child. Her family history was reviewed and was non-contributory. She attended school and lived with her parents, aunt, and grandmother. The patient does not have any siblings. There were no reported sick contacts, allergies, recent travel, or new exposures. The patient’s immunizations were up to date.

On presentation to the ED, her vital signs were as follows: temperature 99.5°F; heart rate 135 beats/min; respiratory rate 24 breaths/min; blood pressure 71/52 mm Hg; oxygen saturation was 99% on room air; weight was 20.4 kg. On physical examination, she was awake, ill-appearing, but not toxic. She was not answering questions but would respond “ow” and “nothing is helping” to painful stimuli. Physical exam was otherwise significant for a normocephalic and atraumatic head, sunken eyes, and dry mucosal membranes. She was tachycardic with 2+ distal pulses bilaterally and a brisk capillary refill. Neurologically, she was altered and had positive Brudzinski and Kernig signs. Her Glasgow Coma Scale (GCS) was 13 (eyes 4, verbal 4, and motor 5).

Preliminary laboratory data in the ED revealed leukocytosis with a white blood cell count of 17,830/mm

, with 86% neutrophils, 6% lymphocytes and 6% monocytes. Her hemoglobin was low at 11.6 g/dL and she was thrombocytopenic with a platelet count of 22,000/mm

. A comprehensive metabolic panel revealed the following data: sodium 123 meq/L, potassium 5.0 meq/L, chloride 80 meq/L, carbon dioxide 13 meq/L, BUN 105 mg/dL, creatinine 2.5 mg/dL, glucose 105 mg/dL, calcium 8.2 mg/dL, total protein was 5.7 g/dL, and albumin were 2.8 g/dL. Her anion gap was elevated at 30 meq/L. All other metabolic panel results were unremarkable. Her C-reactive protein (CRP) was elevated at 20.8 mg/dL (normal range <0.5 mg/dL). Her lactic acid levels, PT and INR, and PTT were unremarkable. Due to her altered mental status, a computed tomography (CT) scan of her head was obtained and did not reveal any acute abnormalities.

The most common cause of altered mental status in children is infection

 which is consistent with this patient’s presentation of altered mental status in the setting of fever and found to have an elevated CRP and neutrophilia (Table 1). Given the patient’s positive Brudzinski and Kernig signs, bacterial, viral, fungal, and tubercular meningitides were possible sources of infection

 that could not be excluded because the patient was not a candidate for LP given her significant thrombocytopenia. Encephalitis commonly presents with decreased consciousness

 and could not be ruled out definitively without further infectious disease workup, including repeat head imaging. Other sources of infection included myocarditis, endocarditis, urinary tract infection, or pneumonia, but were less congruent with the patient’s presenting symptoms. Given the patients’ hypotension in the setting of infection, altered mental status secondary to sepsis should be considered. Sepsis-associated encephalopathy (SAE) is a term that refers to diffuse brain dysfunction resulting from cerebral hypoperfusion and/or alterations of the blood brain barrier due to systemic infection causing cognitive impairment.

 It is characterized by diffuse brain dysfunction elsewhere in the body without overt central nervous system infection.

 The source and etiology of infection are important factors in the development of SAE.

 The greatest risk of SAE is associated with biliary tract or intestinal infections followed by pulmonary infections. The most commonly implicated organisms are 

 More severe brain dysfunction and higher mortality rates were observed in patients with SAE infected with multiple bacteria or 

 Although not as well studied in children, SAE in adults presents with nonfocal neurologic manifestations and can present as a depressed state.

Another potential cause of altered mental status could be toxic exposure. Exploratory ingestions are common in children aged younger than 6 years. (Table 1).

 The clinical presentation of occult ingestion varies depending on the ingested substance and occult toxic exposure should be considered in the differential diagnosis of a child who presents with acute onset multisystem dysfunction, unexplained metabolic acidosis, and altered mental status.

 However, the likelihood of a toxic ingestion underlying this patient’s presentation was low as the patient was not in the “at risk” age group of incidental ingestions (aged 1 to 4 years old), lacked a history of previous ingestions, and did not have exposure to commonly ingested agents such as cleaning products, analgesics, cough medications, topical agents, or pesticides. Additionally, the timeline of the onset of her presentation was inconsistent with an acute toxic ingestion.

The patient’s basic metabolic panel was indicative of an anion gap metabolic acidosis and thus, metabolic disorders should be considered as a cause of her altered mental status (Table 1). Diabetic ketoacidosis could have been underlying her anion gap metabolic acidosis, but was less likely in the absence of polyuria, polydipsia, hyperglycemia, and a negative past medical history. Lactic acidosis in the setting of hypoperfusion due to sepsis could be considered, but her lactate levels were only mildly elevated suggesting that lactic acidosis was unlikely the underlying cause of her altered mental status. Other causes of anion gap metabolic acidosis include ingestion of toxic materials such as methanol, ethylene glycol, and salicylate poisoning. Her lack of exposure to these substances and more insidious onset of illness were inconsistent with toxic ingestion. Her presenting hypotension and elevated creatinine suggest that the most likely etiology of her anion gap metabolic acidosis was acute kidney injury (AKI) precipitated by severe dehydration. This may have contributed to her altered mental status, but would not account for the patient’s initial fever and lethargy that were more consistent with an infectious etiology.

The patient’s hypotension, tachycardia, and leukocytosis raised concern for sepsis. The incidence of sepsis, characterized by immune dysregulation, has been steadily increasing in children since the mid-1990s

 with an estimated global incidence of pediatric and neonatal sepsis of 25.2 million in 2017.

 Sepsis accounts for 4.4% of admissions to children’s hospitals with approximately 75,000 children hospitalized for severe sepsis each year.

 Definitions of sepsis and organ dysfunction developed by the International Consensus Conference on Pediatric Sepsis help physicians identify sepsis, determine its severity, and monitor progression of a child’s illness.

 The consensus criteria also divide sepsis into categories based on the severity of presentation: severe inflammatory response (SIRS), severe sepsis, and septic shock, and multiple organ failure.

 The definition and clinical markers of sepsis differs in children compared to adults. In adults, elevated lactate is an important marker of sepsis and reduction of lactate levels is associated with improved adult survival.

 However, little evidence supports the use of lactate as a marker of clinical significance in children.

 Other inflammatory biomarkers, such as c-reactive protein (CRP) and procalcitonin may be useful in identifying infection, especially in patients with no apparent infection source

 C-reactive protein is also useful as a guide for de-escalation of antibiotics in patients without an identifiable source of infection.

 There has been some literature supporting the use of molecular methods to distinguish between bacterial and viral infections, including polymerase chain reaction (PCR) and detection of bacteria 16S (RNA) genes. Some evidence suggests that these methods have the potential to differentiate bacterial from viral infection in children with high accuracy,

 which has potential benefits regarding antibiotic stewardship.

Early identification of sepsis is important to ensure timely administration of broad-spectrum antibiotics and identification of an infection source to enable more targeted treatment. Although mortality in children due to severe sepsis is less than 10%,

 morbidity is significant in pediatric patients with septic shock further emphasizing the importance of early identification and treatment of sepsis to prevent adverse outcomes. Because children can compensate for circulatory dysfunction, hypotension is a late finding and this can make early identification of sepsis difficult.

Non-bacterial infections may cause a systemic inflammatory response that mimics sepsis, which should be taken into account when considering a clinical picture of sepsis. Epstein-Barr Virus-associated hemophagocytic syndrome (HPS) can present with signs of severe sepsis.

 Hemophagocytic syndrome is a condition in which T-cells, natural killer cells, and macrophages are abnormally activated causing hypercytokinemia leading to cell death and eventually multiorgan failure.

 Epstein-Barr Virus is the most common infectious cause of HPS.

 Hemophagocytic symdrome should be considered in the differential in patients presenting with prolonged fever, pancytopenia, and a sepsis-like picture that is unresponsive to antibiotics.

In the ED, the patient was given intravenous (IV) ceftriaxone after blood cultures were drawn due to the high concern for meningitis and IV ketorolac for pain prior to the return of her laboratory results. The patient was not a candidate for LP given her thrombocytopenia. Vancomycin was held when her laboratory results revealed an AKI. She remained hypotensive after 3 normal saline boluses and was started on dopamine at 10 mcg/kg/min, titrated down to 5 mcg/kg/min for normotension. She was admitted to the pediatric intensive care unit for further management of her hypotension, which was thought to be due to septic shock and subsequently intubated due to concern for respiratory failure likely due to aggressive fluid resuscitation and infection (Figures 1a,b,c). Ceftriaxone was continued; vancomycin was started; and steroids were held given low likelihood of 

 as the patient was up to date on her vaccinations. She was also started on acyclovir given concern for viral meningitis. An echocardiogram ruled out myocarditis and endocarditis as an infectious source. Her AKI was thought to be caused by volume depletion secondary to decreased fluid intake prior to admission and exacerbated by home ibuprofen use and ketorolac administration in the ED. Her renal function and hyponatremia noted on her initial labs resolved quickly with fluid resuscitation and without further renal sequelae.

Given her altered mental status, a brain magnetic resonance imaging (MRI/MRA) was ordered and significant for a tiny focus of restricted diffusion in the white matter of the posterior left frontal lobe consistent with early subacute infarct (Figure 2a). On hospital day 5, she was extubated and found to have right-sided motor deficits. Repeat imaging revealed extensive skull base and cervical osteomyelitis and arteritis with complete occlusion of flow in the left carotid artery and limited flow in the right carotid artery with primary circulation through the posterior vessels (Figure 2b,c,d). The MRI also showed an extensive left side frontal lobe infarct (Figure 2b,c). The CT angiogram of her head and neck confirmed occlusion of the left internal carotid artery and marked narrowing of the right internal carotid artery. The CT was also significant for opacification of the sphenoid sinus and left mastoid air cells thought to be consistent with an infectious process. The following day, she had sphenoid abscess drainage via functional endoscopic sinus surgery and tympanostomy tubes placed by otolaryngology due to the extensive middle ear effusion noted on CT. She was treated with vancomycin, ceftriaxone, and clindamycin for 5 days, at which time the clindamycin was discontinued. Aerobic culture of sinuses was positive for coagulase positive 

 and anaerobic culture of sinuses was negative for growth. Cultures including blood cultures drawn in the ED and bacterial and viral CSF cultures were negative. The final diagnosis was skull base and cervical osteomyelitis caused by coagulase positive 

. Origin of her osteomyelitis remained unclear.

She was hospitalized for 6 weeks. Prior to discharge, she regained speech function; hemiparesis improved; renal function normal. She was treated with Lovenox for her infarcts. One month after discharge, she had no neurological deficits and returned to school. She has been seen in the ED for minor infections and injuries and is doing well without any sequelae from hospitalization.

1. Wong CP, Forsyth RJ, Kelly TP, Eyre JA. Incidence, aetiology, and outcome of non-traumatic coma: A population based study. 

2. Thompson C, Kneen R, Riordan A, Kelly D, Pollard AJ. Encephalitis in children. 

. 2012. doi:10.1136/archdischild-2011-300100

3. Semmler A, Widmann CN, Okulla T, et al. Persistent cognitive impairment, hippocampal atrophy and EEG changes in sepsis survivors. 

4. Chaudhry N, Duggal AK. Sepsis Associated Encephalopathy. 

5. Zhang LN, Wang XT, Ai YH, et al. Epidemiological features and risk factors of sepsis-associated encephalopathy in intensive care unit patients: 2008-2011. 

. 2012. doi:10.3760/cma.j.issn.0366-6999.2012.05.018

6. Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. 

7. Gofton TE, Bryan Young G. Sepsis-associated encephalopathy. 

8. Mowry JB, Spyker DA, Brooks DE, Mcmillan N, Schauben JL. 2014 annual report of the American association of poison control centers National Poison Data System (NPDS): 32nd Annual Report.

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9. Bryant S, Singer J. Management of toxic exposure in children. 

. 2003. doi:10.1016/S0733-8627(02)00083-4

10. Hartman ME, Linde-Zwirble WT, Angus DC, Watson RS. Trends in the epidemiology of pediatric severe sepsis. 

11. Rudd KE, Johnson SC, Agesa KM, et al. Global, regional, and national sepsis incidence and mortality, 1990–2017: analysis for the Global Burden of Disease Study. 

. 2020. doi:10.1016/S0140-6736(19)32989-7

12. Ruth A, McCracken CE, Fortenberry JD, Hall M, Simon HK, Hebbar KB. Pediatric severe sepsis: Current trends and outcomes from the pediatric health information systems database. 

13. Davis AL, Carcillo JA, Aneja RK, et al. American College of Critical Care Medicine clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock. 

14. Schuller KA, Hsu BS, Thompson AB. The Rate of Sepsis in a National Pediatric Population, 2006 to 2012. 

15. Levy B, Perez P, Gibot S, Gerard A. Increased muscle-to-serum lactate gradient predicts progression towards septic shock in septic patients. 

16. Luaces-Cubells C, Mintegi S, García-García JJ, et al. Procalcitonin to detect invasive bacterial infection in non-toxic-appearing infants with fever without apparent source in the emergency department. 

17. Juutilainen A, Hämäläinen S, Pulkki K, et al. Biomarkers for bacteremia and severe sepsis in hematological patients with neutropenic fever: Multivariate logistic regression analysis and factor analysis. 

18. Downes KJ, Weiss SL, Gerber JS, et al. A pragmatic biomarker-driven algorithm to guide antibiotic use in the pediatric intensive care unit: The optimizing antibiotic strategies in sepsis (OASIS) study. 

19. Herberg JA, Kaforou M, Wright VJ, et al. Diagnostic test accuracy of a 2-transcript host RNA signature for discriminating bacterial vs viral infection in febrile children. 

20. Stoller J, Halpin L, Weis M, et al. Epidemiology of severe sepsis: 2008-2012. 

21. Schwaitzberg SD, Bergman KS, Harris BH. A pediatric trauma model of continuous hemorrhage. 

22. Marik P, Spivack T, Chawla R. Epstein-Barr virus-associated hemophagocytic syndrome mimicking severe sepsis. 

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Articles

A 5-year-old female with no significant past medical history presented to the emergency department in 2016 with altered mental status, decreased activity, fever, and decreased oral intake. What's the diagnosis?

Bad to the bone: A case of altered mental status

As the COVID-19 pandemic continues, we are learning more about the various ways that the infection can manifest and the significant mental health impact that it is having on the pediatric population. There are various 

 that are unique to COVID-19 that the practicing clinicians should be aware of. These manifestations are discussed in the cover story of this issue by Dr Bellodi Schmidt and Ms Vivien Chen.

Other articles that are must-reads include:

The respiratory section study on how primary care providers are the key to 

 in teenagers. This is extremely important, given the increasing number of teenagers that vape, especially during the pandemic.

The nutrition section article that reports on the 

 and whether or not it had an impact on improving school lunch programs.

The mental/behavioral health section article in which Dr Jellinek discusses a 

 for pediatric health care providers to know when a child needs formal mental health services. This is a very timely article given the significant mental health impact that COVID-19 has had on children, especially those with underlying mental health issues.

Another issue that has recently come up is the US Department of Health and Human Services announcement authorizing state-licensed pharmacists to order and administer all vaccines to children and adolescents aged 3-18 years. The American Academy of Pediatrics (AAP) came out with a statement that strongly opposes this policy change. I am in complete agreement with the AAP who stated that “this move is incredibly misguided” and that “the action supersedes state laws governing the scope of pharmacists’ ability to administer vaccines, using the COVID-19 pandemic as justification to make policy change that goes well beyond care related to COVID-19.” This policy should be a call to action for all of us that provide care to the pediatric population. Now more than ever, we need to communicate with our patients and their parents and emphasize the importance of the medical home. We need to stress that pediatric health care provider offices are open and are the best, safest, and optimal places for children to be vaccinated and for the provision of routine care, developmental and mental health screenings, anticipatory guidance and counseling about nutrition, injury prevention, and chronic disease management. This is the time for us to make a statement that we are the best providers of all things that pediatric medicine has to offer with vaccines making up a big portion of the care that we provide.

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

Dr. Tina Tan addresses the recent change that allows pharmacists to administer vaccinations to pediatric patients.

COVID-19 and the future of vaccinations

When I started my pediatric residency, I knew my long-term career goal was to be a child and adolescent psychiatrist. I very much appreciated that the pediatric residency built my core identity as a physician, capable of caring medically for children whether in an intensive care unit or in primary care. However, my natural bent was to always include the psychosocial aspects of care and to ask more psychologically oriented questions after the necessary medical information was gathered, for example, when admitting a child to the hospital. When I went to my primary care clinic, I, of course, completed all the usual screening and vital sign measures. Height, weight, urine screening for infection and diabetes, as well as traditional vital signs were done at every visit. In infants and toddlers, developmental issues such as sitting, walking, first words, and toilet training were well noted. However, through working in both an academic and community clinic setting, I was increasingly convinced that there were psychosocial concerns unaddressed and not recognized by any available screening approach.

Most supervising attendings would ask 1 or 2 questions about school or friendships that had a ‘hit or miss’ quality. The director of the clinic was wonderfully intuitive and almost magically sensed which children needed a mini-psychiatric review. However, at the time, there was no training requirement in behavioral pediatrics and even the rotations now instituted could not train someone to select children in a primary care setting without some screening mechanism. Overall, the recognition of emotional problems in pediatrics was highly variable, and the research conducted in the late 1970s indicated that the identification of emotional problems in pediatric primary care was well below expectations set by epidemiological studies.

 I wondered if there could be a short, valid screening questionnaire that could fit into the flow of a busy clinic and identify children in need of further pediatric evaluation and potential mental health referral.

I knew the time pressure and workflow in primary care practice. Any screening process, like a urine dipstick or blood pressure, had to be brief, take no more than 3 or 4 minutes to administer and score, and not clog up the waiting room that had been built to accommodate the typical flow of patients. The screen had to be understandable and readily accepted by parents and teenagers and, if possible, one form had to be applicable to a broad age range. The front desk had enough paper to deal with (electronic records were still 30 years in the future) that there could not be different screening forms by age, gender, or other demographic factors. Using the metaphor of a urine dipstick, the screening had to be simple with one form on one shelf. Given the economics of practice, the screen had to be free to administer and score and potentially be reimbursable like other routine procedures.

1. What issues or problems should a set of screening questions identify?

As a psychiatrist, I was trained to look for sets of symptoms that met criteria for a disorder—a system better suited to adults than to children, given the complexities of development and family considerations. Pediatricians were not familiar with lists of symptoms, with a certain number of symptoms needed for a diagnosis, independent of family or developmental history, and with a diagnostic result of more than one mental health diagnosis. A child diagnosed with major depression from the psychiatric perspective could be 11 or 16 years of age, could have a strong family history of depression suggesting a largely biological etiology, or could be trying to cope with divorcing parents, bullying at school, an alcoholic, abusive father, or a family’s food insecurity. Many pediatricians had no experience with this psychiatric diagnostic approach, were uncomfortable with one or more diagnoses not grounded in an etiology, and/or found it of limited use in communicating with parents or colleagues.

Rather than lists of symptoms, pediatricians start by asking how old is the child and how are they functioning with friends, school, activities, in family life? What is the status of the child’s mood and self-esteem? Given the strong reluctance to use the psychiatric symptom-based approach, to be broadly accepted, psychosocial screening in primary care would have to be based on understandable questions regarding daily functioning. A child’s daily functioning is an expression of their strengths and stressors. A child’s functioning is the common pathway for the influences of genetics, their psychological development, social determinants of health, coping abilities, and resilience. In the context of the epidemiology of childhood psychosocial issues, a screen will find 10%-15% of all 4-16-year-old children “positive,” meaning the pediatricians should include assessing the child further as part of the pediatric visit.

The questionnaire items reflect difficulties in psychosocial functioning with the goal of coming to a score that reflects risk versus non-risk. The first version of the screening tool had 35 questions for parents to rate their child’s problems as occurring “never,” “sometimes,” and “often.” Naming the screening questionnaire, “The Pediatric Symptom Checklist” (PSC) emphasized that a child’s psychosocial functioning was a core and routine part of pediatric healthcare. The PSC was freely available with no charge for the tool, its use, or scoring. More than a decade after initial validation, some colleagues found that groups of questions on the PSC clustered together and could reliably identify risk in 3 different domains: externalizing, internalizing, and attention problems in a shorter 17-item format of the PSC.

Generally, a parent or legal guardian brings the child for the pediatric visit and is typically the person in the best position to assess the child’s functioning. The questionnaire reflects a parents’ perceptions and when considering the psychosocial functioning of a child, a parent is more like the umpire in a baseball game. A ball thrown by the pitcher is defined as a ball or strike by the umpire, and once defined, enters history as what the umpire indicated. Is a child more often alone, having fun, or not listening to rules? There are no objective counts, only a parents’ sense of the situation and that is why “often” scores are so relevant. The major area where parents’ perception is limited is with teenagers, when their thoughts are often private, and a related depressive mood may be hidden. A youth-completed version of the PSC has been developed and other instruments specific to adolescent depression such as the patient health questionnaire (PHQ-9 )are also available.

3. What is the clinical path of a primary care pediatrician if a screen is “positive”?

The goals for the clinician are to assess if the screen is a true positive (similarly to other positive screens, eg, repeating a higher than expected blood pressure), and, if deemed valid, assessing the level of severity and next steps. Questions answered “often” are a good starting point for the pediatrician to solicit the parent’s understanding, and to explore the impact of the behaviors on the child’s and family’s functioning. The next step is to have the pediatrician ask questions about other areas of functioning (school, friends, activities, family, and mood). Depending on these answers, it may be relevant to ask about family violence, any mental health treatment, family history of emotional disorders, and safety concerns (access to guns or dangerous adult medications). Usually, in about 15 minutes, pediatricians get a sense of whether this is a true positive, the general nature of the issue and the severity of impairment or suffering. Next steps might be to offer counseling, schedule a follow-up (“watchful waiting”), or refer to a mental health consultation. Repeat PSCs can be given at the appropriate interval to monitor watchful waiting or get some feedback on the course of treatment post referral. The PSC more than doubled both the recognition and referral rate for psychosocial dysfunction (See Figure).

Since its initial creation, over 35 years of research on the PSC in more than 200 studies has shown its validity and reliability in a wide range of settings,

 demonstrated that it is understood and well-accepted by parents and clinicians,

 is sensitive to the impact of social determinants of health and poverty on mental health,

 can be shortened from a 35- to a 17-item version, can be used in both a parent- and youngster-reported format,

 and that regular use of the PSC is associated with an increase in mental health treatment.

 The PSC is also used in specialty pediatric and mental health clinics, schools, Head Start, state agencies, and online.

In Massachusetts, the PSC was one of a handful of recommended screening questionnaires mandated by a Federal Court as part of a remedy to broaden mental health services for children with Medicaid.

 The PSC has been endorsed by the Massachusetts and California Medicaid programs, the American Academy of Pediatrics, and the National Quality Forum, both for overall screening and for screening adolescents for depression using its internalizing scale.

 The PSC is now included in many if not most US electronic medical record systems (EMR) including two of the most widely used (EPIC and Centricity).

Studies of the PSC in an EMR indicate that 70%-90% of children in large systems can be screened routinely, that pediatricians document their discussion of PSC scores in medical records, generally selecting the higher scoring children for mental health referral. The screen is now a routine feature of the visit and increases referrals for mental health services.

Many questions, however, still remain unanswered: Which children benefit the most from early recognition (those with the highest scores or those with lower levels of risk)? Can the PSC be used to track progress in treatment or highlight the need for more intensive treatment? What is the natural history of an individual’s scores over a decade or more of childhood and adolescence, how should outcomes in functioning be measured, and can the PSC be used more effectively to identify impending adolescent risk taking and suicidal behavior? The PSC is now widely used and is a major bridge between pediatric and mental health care. However, with the burden of mental health problems rising, especially during and post COVID, the bridge should be busier, better resourced, and refined by future research.

1. Gould MS, Wunsch-Hitzig R, Dohrenwend, B. Estimating the prevalence of childhood psychopathology: a critical review. 

2. Pediatric Symptom Checklist. Massachusetts General Hospital Website. 

https://www.massgeneral.org/psychiatry/treatments-and-services/pediatric-symptom-checklist

3. Gardner, W, Murphy, M, Childs, G, et al. (1999). The PSC-17: A brief pediatric symptom checklist with psychosocial problem subscales. A report from PROS and ASPN. 

4. Jellinek M, Murphy J. Screening for psychosocial disorders in pediatric practice. 

5. Murphy JM, Reede J, Jellinek MS, Bishop SJ. Screening for psychosocial dysfunction in inner-city children: further validation of the pediatric symptom checklist. 

6. Jellinek MS, Murphy JM, Little M, Pagano ME, Comer DM, Kelleher KJ. Use of the Pediatric Symptom Checklist to screen for psychosocial problems in pediatric primary care: a national feasibility study

7. Arauz-Boudreau A, Riobueno-Naylor A, Haile H, et al. How an electronic medical record system facilitates and demonstrates effective psychosocial screening in pediatric primary care. 

8. Spencer AE, Baul TD, Sikov J, et al. The relationship between social risks and the mental health of school-age children in primary care. 

9. Pagano ME, Cassidy LJ, Little M, Murphy JM, Jellinek MS. Identifying psychosocial dysfunction in school-age children: the pediatric symptom checklist as a self-report measure. 

10. Gall G, Pagano ME, Desmond MS, Perrin JM, Murphy JM. Utility of psychosocial screening at a school-based health center. 

11. Bergmann P, Lucke C, Nguyen T, Jellinek M, Murphy JM. Identification and utility of a short form of the pediatric symptom checklist-youth self-report (PSC-17-Y). 

12. Hacker KA, Penfold R, Arsenault L, Zhang F, Murphy M, Wissow L. Screening for behavioral health issues in children enrolled in Massachusetts Medicaid. 

13. Hacker KA, Penfold RB, Arsenault LN, Zhang F, Murphy M, Wissow LS. Behavioral health services following implementation of screening in Massachusetts Medicaid children. 

14. Hacker K, Penfold R, Arsenault L, et al. The impact of the Massachusetts behavioral health child screening policy on service utilization. 

15. Official Website of the Commonwealth of Massachusetts. Accessed June 22, 2020. 

https://www.mass.gov/info-details/learn-about-the-approved-masshealth-screening-tools#psc-(pediatric-symptom-checklist)-

16. Savageau JA, Keller D, Willis G, et al. Behavioral health screening among Massachusetts children receiving Medicaid. 

17. Kuhlthau K, Jellinek M, White G, VanCleave J, Simons J, Murphy M. Increases in behavioral health screening in pediatric care for Massachusetts Medicaid patients. 

A good approach to knowing when a child needs referral for mental health evaluation, the Pediatric Symptom Checklist has evolved over the years to better screen children.

Utilizing the Pediatric Symptom Checklist

Telemedicine (TM) video visits were off to a slow start in most offices and clinics in 2020. Then along came the COVID-19 pandemic and TM care took off. To prevent the spread of the virus, primary care providers (PCP) transitioned from in-person visits to providing as much definitive care as possible by video visits. Being able to bill at in-person rates was an added motivator. The PCPs quickly adapted, overcoming concerns about learning video visit technology. Reports that a significant percentage of contagious patients with the virus were asymptomatic increased their interest. Families who were afraid of catching COVID-19 in a medical setting welcomed a video visit option. Convenience was an added incentive. This report reviews how to optimize teamwork between telephone triage nurses and PCPs who provide video visits.

Repurpose telephone triage protocols to support telemedicine visits

Nurse triage continues to be a vital part of how we manage our patient populations. Nurses can use the triage questions and care advice as written but modify the dispositions to include a TM option. Most of the dispositions simply need to be changed by adding “or schedule a video visit” to the existing “in person visit” wording (Table 1).

1­. Triage questions that fall under the 911 or Go to emergency department (ED) Now dispositions. These indicators recognize serious conditions where delay in diagnosis and treatment could lead to adverse outcomes.

2. ­Patients who are nurse-triaged to the Home Care dispositions. They usually don’t need PCP involvement.

Use nurse triage to front-end PCP telemedicine visits

Office triage nurses can continue to independently manage most calls about well children (such as eating, sleep, behavior, vaccines, and new baby questions). During office hours, these may account for 30% of pediatric calls.

For calls about sick children, each practice will need to decide if nurses continue to triage all of them or just some of them. If the practice wants nurses to triage all sick child calls, up to 50% will be triaged to the Home Care disposition (mildly ill and don’t need to be seen). Nurses then refer the patients who need to be seen to the PCP for an in-person or video visit.

Some practices prefer to let the parent decide. After knowing the reason for the call, the front desk staff can ask: “Do you want an appointment with the doctor, or do you want to talk with our advice nurse?” If they want to be seen, schedule an in-person appointment. If a parent prefers a video visit, it can only be scheduled after a triage nurse or PCP confirms the main symptom is appropriate for TM. For TM visits, the timeframe should be similar to the protocol-recommended timeframe for office visits or sooner if TM is readily available. Many PCPs still prefer in-person visits over video visits, because they can provide definitive care more quickly in the office.

Help triage nurses select patients for a TM visit

Many will validly argue that TM can’t manage all patients who are triaged as needing to be seen. Some offices found a solution. It’s called a “split visit.” A TM visit is attempted on almost all patients who would be triaged to an office visit. Most of the time, it is successful without a complete physical exam or any lab tests. When not, the patient is sent to the office soon after the call. The office visit can then be a brief encounter, such as to perform a rapid strep test or an ear exam, sometimes in the office parking lot. If 2 visits are required, reassure payors, only 1 fee should be generated.

For offices who want the nurse to more carefully select candidates for TM visits, here are some guidelines. If we tried to establish inclusion criteria, it would be difficult to reach a consensus. Establishing exclusion criteria for TM visits has greater consensus and leads to a far shorter list.

Some offices where a physician and nurse have worked as a team for many years may not need such a list. Nurse judgment from working closely with a PCP might allow the triage nurse to select appropriate patients for TM visits. When in doubt, office nurses can ask for guidance. However, for triage nurses in many office practices, an exclusion list of patients not appropriate for a TM visit is helpful. See our suggested list as a place to start and modify to meet your needs.

Telemedicine exclusion list for office triage nurses

The Telemedicine Exclusion List in Table 2 is a work in progress. It will need to be customized by most primary care practices. Some software platforms with protocols in electronic format support customizing specific triage questions that are not appropriate for TM. Nurse awareness of PCP preferences also play a role in deciding who is appropriate to refer for TM. In our experience, most suspected COVID-19 calls and symptoms are being managed by TM visits.

Another decision is where to start. Table 3 lists the nurse triage protocols most amenable to TM care. They are protocol symptoms with high call volumes. They also have a high likelihood that a video visit can provide diagnosis and treatment.

Telemedicine video visits are part of the new normal. Most PCPs have learned how to provide them. Families appreciate their convenience and safety from COVID-19 contact. And they want the service provided by their PCP, not an unknown provider. In addition, the PCP can seamlessly convert a video visit into an office visit when needed.

During office hours, office triage nurses can schedule TM visits in real-time. On weekends and holidays, call center nurses can schedule patients triaged to the video visit within 24 hours disposition with on-call PCPs who are willing to provide this service during the day. These are the patients who otherwise might need referral to an ED or urgent care venter (UCC) over the weekend. In summary, what we have learned from managing calls about suspected COVID-19 infections is that there is no “going back”.

COVID-19 has brought telemedicine to the forefront of medical care. Here's some strategies that can help streamline the process, using teamwork.

Telephone triage nurses and telemedicine providers: Key strategies for teamwork in pediatric offices

Young children who wheeze from time to time (so-called early transient wheezers) are less likely to develop allergy in adolescence than their peers who never or only infrequently wheeze, according to a study conducted in Australia. Children with persistent wheeze, on the other hand, are at increased risk of having other allergic manifestations in later childhood and adolescence, researchers found.

The study was conducted in a longitudinal birth cohort of 620 children from families with a history of allergic disease, who were followed up to the age of 18 years. Researchers identified 5 wheeze patterns these children exhibited from the age of 4 weeks to 7 years: never/infrequent (47%), early transient (26%), early persistent (5%), intermediate onset (19%), and late onset (3%). Investigators collected data about participants’ wheezing 18 times in the first 2 years of life. They also conducted skin prick testing for common allergens at ages 6, 12, and 24 months and 12 and 18 years, measured fractional exhaled nitric oxide (FENO), a determinant of eosinophilic airway inflammation, and collected information about the existence of eczema and hay fever.

Analysis of the collected data, which took into account potential confounders, including sociodemographic factors and parental smoking and asthma, showed that compared with never/infrequent wheezers, early transient wheezers had reduced risks of hay fever and eczema at age 18 years, along with lower FENO levels and lower risk of sensitization. In contrast, both intermediate onset and late onset wheezers were at increased risk of having hay fever at 12 and 18 years of age, compared with never/infrequent wheezers, with youngsters’ having the intermediate onset pattern also at increased risk of sensitization and higher FENO levels. Although early persistent and intermediate onset wheezers were at increased risk of eczema at 12 years, no wheeze pattern was associated with eczema at 18 years. Overall, intermediate onset wheezers represented the most atopic group (

This impressive, very long-term study provides some indirect evidence for the ‘hygiene hypothesis,’ that early exposure (in this case, perhaps to respiratory viruses) helps protect against allergies. It would have been nice to see if early transient wheezers were less likely to have asthma when older.

An Australian study examines how childhood wheezing can impact the development of allergies.

Childhood wheezing may protect against future allergy

An account of 3 case studies illustrates how preputial skin may be an ideal graft for repairing syndactyly because the tissue is easily accessed and harvested and is hairless and free of subcutaneous fat; the procedure also is associated with low morbidity/mortality. Syndactyly release generally is performed with full thickness skin grafts from the groin region, which can result in growth of unwanted hair and subcutaneous fat.

The 3 patients, referred to urology at the request of the orthopedic surgeon, underwent circumcision at the time of syndactyly repair to provide preputial skin for graft coverage. The infants were 17-, 18- and 20-months-old, respectively, when they underwent the surgery. The skin grafts healed well in all 3 infants, and though the grafts were associated with some increased pigmentation, parents were satisfied with the outcomes. Given these results, the authors recommend “careful assessment for congenital anomalies that may require skin grafting, such as syndactyl, prior to ‘routine’ neonatal circumcision” (

This strikes me as a brilliant concept, another surgical reason, besides hypospadias, for sparing the foreskin. Please remember this, or inform your obstetrical colleagues, before doing a circumcision in a boy with syndactyly.

Three case studies look at the efficacy of using foreskin for syndactyly repair.

Consider the foreskin for syndactyly repair

"Perhaps” might be the best answer to this question, based on a review of the literature on use of botulinum toxin for treating pediatric chronic migraine. Seven studies with from 1 to 30 participants were included in the review: 2 retrospective analyses, 3 case series, a case report, and a single randomized controlled trial with 125 patients. The number of treatments ranged from 1 to 11, and dosing and injection protocols varied. Only the randomized controlled trial had fixed protocols; the other studies combined a fixed protocol with one that “followed the pain.” Dosages ranged from 100 to 215U, with treatment given about every 3 months.

The randomized controlled trial found no benefit to botulinum toxin compared with placebo. The other studies noted clinically significant benefits for headache frequency, migraine intensity, or migraine duration. Two studies found that headache frequency decreased 50% whereas others noted even greater decreases of 74% and 97%. Decrease in migraine intensity ranged from 25% to 100%. The one study that measured migraine duration showed a median decrease from 8 to 0.75 hours. Side effects were minimal in most studies, generally injection site pain and tenderness (

We can add botulinum toxin to the long list of proposed treatments for pediatric migraine that possibly are worth trying but are not yet proven in large enough randomized, controlled trials. Others on this list include antiepileptics, tricyclics, SSRIs, beta-blockers, and antihistamine medications, as well as cognitive behavioral therapy.

A new study examines the efficacy of the toxin for migraine treatment in pediatrics.

Is botulinum toxin effective for treating children’s migraines?

Disease caused by severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2), otherwise known as COVID-19, has rapidly emerged as an international public health emergency with over 12 million cases, 650,000 deaths,

 and varying states of lockdown among countries worldwide since the virus first appeared in December 2019. The novel coronavirus classically presents in symptomatic patients with signs of upper or lower respiratory tract infection (URI, LRI), varying in degree of severity and multi-organ involvement

Recent literature has reported a variety of dermatologic manifestations among children and adults associated with COVID-19 infection. In general, children with the virus reportedly have milder clinical manifestations and lower incidence of critical cases compared to adults

 Cutaneous manifestations seen in children may often differ from those seen in infected adults. Findings most commonly seen in children include chilblains-like lesions (or “COVID toes”) and viral exanthem variations (erythema multiforme-like, papulovesicular eruption, varicella-like eruption among others), as well as prominent mucocutaneous involvement in the more severe Kawasaki-like disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C). In this review, we aim to highlight the various pediatric cutaneous findings associated with COVID-19 thus far, in context of infection timeline and utility of recognizing these manifestations to alert suspicion of SARS-CoV-2 infection.

Vascular-related manifestations: the debate over COVID toes

One of the dermatological findings to first gain traction among COVID-19-related manifestations is chilblains-like lesions, or commonly referred to as “COVID toes” or pseudo-chilblains. Chilblains, also known as perniosis, is a localized vasculopathy that involves vasoconstriction of small arterioles and venules triggered by cold, most commonly affecting those with chronic exposure to low temperatures, damp exposure or poor peripheral circulation, in children, young women, and elderly patients. Lesions present as either single or multifocal erythematous, purplish edematous papules, nodules, macules or less commonly bullae, that may be pruritic, tender or accompanied by a paresthesia, commonly on the extremities such as the fingers, toes (Figure 1), and less commonly on nose and ears

 Treatment for primary chilblains includes conservative preventative care (warm clothing, gloves and socks), oral nifedipine and topical corticosteroids, and lesions usually resolve within 2 weeks but may recur seasonally.

 The past few months have seen an increase in outpatient cases of chilblains-like lesions in certain areas around the world, mostly among pediatric patients and young adults.

Variable COVID-19 testing results among reported patients, however, has sparked some debate on whether pseudo-chilblains are truly a sign of COVID-19 or rather secondary to quarantine-related lifestyle changes. Cordoro and colleagues

 reported clustered cases of pseudo-chilblains appearing within 1 week among 2 groups of siblings aged 12 to 17 years old, in Northern California, in the context of either mild viral URI symptoms (subjective fever, rhinorrhea) or contact with symptomatic persons 1-2 weeks before rash onset. However, SARS-CoV-2 PCR and IgG, IgM antibodies were negative for all patients. Similarly, a combined study of prospective testing in Eastern Spain and retrospective literature review of acral cases in both adults and children found only 13 out of 88 (14.8%) tested cases were positive for COVID-19.

 PCR/serology testing of 38 children (median age 13.5 years) with new onset pseudo-chilblains at a tertiary care university hospital in Italy found all patients negative for RT-PCR and IgM, IgG, IgA antibodies

 A potential confounding variable is lifestyle changes from staying indoors during a lockdown state, implemented by many countries in response to the COVID-19 pandemic. An in-depth study by Neri and colleagues

 of 8 adolescents with chilblains-like lesions revealed that they had increased risk factors for primary chilblains: BMI <50th percentile, increased cold exposure with barefoot or thin socks contacting with cold floors, and prolonged postural habits impeding robust peripheral circulation.

Quarantine-related habits may contribute to the rise in primary chilblains cases, but the association with COVID-19 cannot be entirely ruled out by the absence of positive PCR or serology. Initial viral testing is biased towards patients with URI symptoms, the timing of retrospective testing is variable, and much is still unknown about COVID-19 antibodies - including the percentage of who acquires these antibodies and the duration of positive serology.

 Reports of pseudo-chilblains associated with COVID-19 have presented consistent histological findings of superficial, deep, and perivascular lymphocytic infiltrate regardless of positive or negative COVID-19 testing in the patient,

 suggesting an inflammatory-based etiology that differs from the post-infectious perniosis histology commonly involving cold agglutinins and cryoglobulins.

 Interestingly, even in some pediatric cases with negative SARS-CoV-2 PCR, biopsies still demonstrated SARS-CoV-2 positive immunohistochemistry in endothelial cells.

 The positive immunohistochemistry was confirmed on electron microscopy with coronavirus particles present in endothelial cell cytoplasm,

 suggesting that the virus may still play a role in inducing lymphocytic vasculitis in pseudo-chilblains, despite negative PCR or serum serology.

Erythema multiforme-like lesions also presented in a case series of adolescents (aged 11 to 17 years), in conjunction with pseudo-chilblains and possible COVID-19 relation.

 Erythema multiforme (EM) is a hypersensitivity syndrome with distinct mucocutaneous manifestations in the setting of infection. It is characterized by acute onset of target lesions (sharply demarcated round plaques with 3 zones: outermost erythematous ring, middle pale zone, central dusking with possible blistering or crusting), that affects mostly the extremities and are most commonly triggered among children and young adults by viral infections, namely herpes simplex virus (HSV) and by 

 identified 4 out of 22 pediatric patients with pseudo-chilblains (18%) also presenting with concomitant erythema multiforme located on the extremities (hands, feet, knees, elbows). Similar to other pseudo-chilblains patients, despite negative COVID-19 testing, skin biopsy demonstrated immunohistochemistry for SARS-CoV-2 spike protein in endothelial cells. Most notably, histopathology also did not demonstrate the typical features of EM including necrotic keratinocytes and spongiosis, but rather features consistent with chilblains, with superficial, deep, and perivascular lymphocytic infiltrations.

The authors have proposed that vascular damage clinically manifesting as pseudo-chilblains may represent a late antigen-antibody reaction at a time when viral load is already low. This theory is supported by the relatively late onset of lesions and significant number of negative nasopharyngeal PCRs. In addition, these patients also seem to have an overall milder disease presentation.

 Whether caused by quarantine-related lifestyle changes or COVID-19 viral-induced vasculitis, there is still more to be studied. As many patients with chilblain-like lesions present asymptomatically or within a few weeks of mild URI symptoms, it is important to consider and screen for both classic risk factors present amongst quarantine living, and for potential SARS-CoV-2 infection in the context of the continued pandemic. In most cases reported, the pseudo-chilblains lesions were minimally symptomatic, did not require treatment, and resolved within a few days without sequelae.

The Pediatric Dermatology Research Alliance COVID-19 Response Task Force (PDCRTF) has developed an open registry for cases to study and better understand this phenomenon.

Other vascular related skin manifestations such as livedo-reticularis and purpuric or petechial eruptions have been reported in adults and were felt to be a thrombotic phenomenon related to viral infection, but a literature search has not revealed such cases among children up to date of this publication except for one case of petechiae presenting in relation to other morbilliform and annular lesions discussed later.

A series of cases highlights a varicella-like exanthem associated with COVID-19 among adult patients, particularly in Italy, who developed a monomorphic papulovesicular rash of the trunk that progressed to crusting over a few days with histology consistent with viral infection.

 detailed a similar varicella-like papulovesicular exanthem, distributed symmetrically along the bilateral trunk. The rash erupted in the patient aged 8 years, 3 days after the start of a cough, and self-resolved after 7 days. The patient and his asymptomatic family members all tested positive for SARS-CoV-2, the latter of whom developed URI symptoms shortly after.

Aside from the more widespread truncal papulovesicular lesions, there are also reports of more localized eruptions. Klimach et al

 described a COVID19 positive case of a boy aged 13 years, in the United Kingdom with an erythematous papular eruption involving the axillae and feet, as well as erythematous macules with associated petechiae and annular lesions on the distal lower extremities. The skin findings developed either before or within 24 hours of onset of mild flu-like symptoms (fever, myalgia and headache), and resolved within 2 weeks.

Of note, an early pruritic morbiliform eruption, with onset concomitant with other COVID-19 symptoms and lasting 3-10 days has been described in adults infected with SARSCoV-2

 In children, morbiliform eruptions have been most commonly described in the context of MIS-C, as discussed below. Although urticarial eruptions have been described in adults, to our knowledge at time of this publication, no isolated cases have been reported in children in relation to COVID-19.

COVID-19 has been seen as primarily a disease impacting the lungs, but more of the body's systems have been shown to be impacted by the disease. Here's a look at how the disease impacts the skin.

Vol 37 No 9