Children and headaches Red flags, triggers, and rescue treatments (Contemporary PEDS Journal, Vol 38 No 5)-Πονοκέφαλος στα παιδιά

Headaches are 1 of the top 5 health problems of childhood.Because 58.4% of children and adolescents aged 1 month or older will develop will develop headaches at some point, general pediatric practitioners may have many opportunities to evaluate and treat patients with headaches

Πονοκέφαλος στα παιδιά

 Οι πονοκέφαλοι στα παιδιά είναι συχνοί και συνήθως δεν είναι σοβαροί. Όπως οι ενήλικες, τα παιδιά μπορεί να αναπτύξουν διαφορετικούς τύπους πονοκεφάλων, συμπεριλαμβανομένων των ημικρανιών ή των πονοκεφάλων (τασης) που σχετίζονται με το στρες. Τα παιδιά μπορεί επίσης να έχουν χρόνιους καθημερινούς πονοκεφάλους.

 Σε ορισμένες περιπτώσεις, οι πονοκέφαλοι στα παιδιά προκαλούνται από μόλυνση, υψηλά επίπεδα στρες ή άγχους ή  τραύμα στο κεφάλι. Είναι σημαντικό να δίνετε προσοχή στα συμπτώματα πονοκεφάλου του παιδιού σας και να συμβουλευτείτε έναν γιατρό εάν ο πονοκέφαλος επιδεινώνεται ή εμφανίζεται συχνά.

  Οι πονοκέφαλοι στα παιδιά συνήθως μπορούν να αντιμετωπιστούν με παυσίπονα χωρίς ιατρική συνταγή (OTC) και υγιεινές συνήθειες, όπως ένα τακτικό πρόγραμμα ύπνου και φαγητού.

Οι περισσότεροι πονοκέφαλοι δεν είναι σοβαροί, αλλά αναζητήστε άμεση ιατρική φροντίδα εάν οι πονοκέφαλοι του παιδιού σας:

•     Ξυπνούν  το παιδί σας από τον ύπνο

•     Επιδεινώνονταιται ή γίνονται πιο συχνοί

•    Προκαλούν αλλαγές  στην προσωπικότητα του παιδιού σας

•    Αν εμφανιστούν μετά απο  έναν τραυματισμό, όπως ένα χτύπημα στο κεφάλι

•    Συνοδεύονται απο επίμονους εμετούς ή οπτικέςδιαταραχές

•    Συνοδεύονται από πυρετό και πόνο στον αυχένα ή δυσκαμψία
  

Τύποι κεφαλαλγίας

Πρωτοπαθής χωρίς συνυπάρχοντα αίτια

Δευτεροπαθής ή οργανική, που είναι αποτέλεσμα:

• Πυρετού, φυσικής καταπόνησης, έκθεσης στον ήλιο, λοιμώξεων ( μηνιγγίτιδα, ωτίτιδα, ιγμορίτιδα)

• Κρανιοεγκεφαλικών κακώσεων

• Αγγειακής αιμορραγίας

• Χωροκατακτητικών εξεργασιών

• Δηλητηριάσεων με φαρμακευτικές ουσίες

• Άγχους

Urgent versus nonurgent headaches

Many conditions can present initially with headache, so it is important to have a list of “red flag” risk factors, symptoms, and exam findings to keep in mind during the initial assessment. Red flag risk factors would include a patient aged younger than 6 years, history of neurocutaneous syndrome, systemic illness, immunodeficiency, known malignancy, or hypercoagulability.²

Red flag symptoms include new (< 1 month) or quickly worsening headache type, focal and sidelocked headache, headache maximal at onset (thunderclap headache), infectious symptoms (eg, fever, meningismus, sinus or ear pain), or pressure-dependent features (eg, positional headache), headache worse in the middle of the night or first thing in the morning, headaches triggered by cough or Valsalva maneuvers, vomiting that is persistent and increasing in frequency. Focal neurologic symptoms or exam findings (eg, seizures, vision changes, papilledema, ataxia) also require urgent evaluation. Etiologies that cannot be missed include mass lesions, infections (eg, meningitis/encephalitis, brain abscess), and vascular etiologies (eg, stroke, hemorrhage, aneurysm, arteriovenous malformation, cerebral venous sinus thrombosis). Any of these symptoms or exam findings should prompt urgent consideration of brain imaging and/or lumbar puncture. Less than 1% of brain abnormalities in patients present with chronic headache as the only symptom.³

Primary versus secondary headaches

Once urgent headache etiologies are no longer of concern, the next objective is to distinguish between primary and secondary headaches. Unlike secondary headaches, primary headaches, such as migraine and tension-type headaches, are not a symptom of an underlying issue. Whereas a child may develop migraine-type headaches due to obstructive sleep apnea, the diagnosis of primary headache is only made after excluding the possibility of a secondary headache disorder. Depending on the history and physical exam, as well as diagnostic testing when needed (eg, screening blood tests or sleep study), the differentiation between primary and secondary headache can be made.

Primary headaches

The diagnosis of primary headache is made primarily through identifying classic characteristics of the headache, as there are no confirmatory diagnostic tests. The International Headache Society has created an International Classification of Headache Disorders to aid clinicians and investigators.^4,5

The diagnosis of episodic childhood migraine is adapted from adult migraine. It is defined as an episodic headache with 5 or more attacks that last 2 to 72 hours. It must have 2 or more of the following: unilateral or bilateral location, pulsating quality, moderate to severe pain, or aggravation by routine physical activity. It must also have 1 or more of the following: nausea or vomiting, and photophobia and phonophobia. For childhood migraine, experts argue that headaches are often shorter, lasting 30 minutes or more, and often fitting 1 or more of each category.⁶ Premonitory signs also are different in childhood migraine than in adult migraine. They are most commonly fatigue, mood changes, neck stiffness, cranial autonomic symptoms, and cutaneous allodynia, rather than visual disturbance or dizziness.⁷

Diagnosing episodic childhood tension-type headache requires 10 or more episodes lasting from 30 minutes to 7 days. It must have 2 or more of the following: bilateral location, pressing or tightening quality (nonpulsating), mild or moderate intensity, and it cannot be aggravated by routine physical activity. There cannot be nausea or vomiting, and no more than 1 of photophobia or phonophobia.

Children and adolescents may present with both migraine and tension-type headaches, making it difficult to have separate treatment trials. In fact, it is unclear whether they are actual separate biological entities.⁸ Most treatments are geared toward migraine management, but the overall approach for both should be 3-pronged, addressing lifestyle modifications, a rescue plan, and a preventative plan.

Headache treatment: Lifestyle modification

The most common triggers for childhood headache include stress/anxiety, lack of sleep, warm climate, and video games.⁹ Other triggers include glare, eye strain, high altitude, menstruation, medications, fasting, dehydration, certain foods (eg, simple sugars, smoked meats, chocolate), caffeine use, and lack of exercise.

The first step in headache treatment is to better characterize the headaches and triggers by keeping a headache diary documenting possible triggers, time of day, days per month, headache intensity, and response to treatment. The number and/or intensity of headaches over time influences what types of treatment are needed. For example, episodic headaches (less than 2 times a week) can be treated with rescue medications alone, whereas headaches more frequent than that will require preventative treatment as well as rescue medications.

The general categories for lifestyle modifications are water and food intake, sleep regulation, daily exercise, and stress reduction.

Headache treatment rescue plan

Tip: Tell patients and their caregivers that the rescue plan should be implemented right at the beginning of the headache.

Because of the nature of the headache/pain cycle with amplification over time, the longer it takes to treat, the harder it is to break the cycle. Taking rescue measures early and taking the full dose of the abortive medication are more effective than waiting and then giving a half dose followed by another half dose.

Caregivers should be cautioned that these medications are only meant for rescue. Taking them more than 2 or 3 times a week over a month-long period can lead to medication overuse headache syndrome.

Nausea and vomiting are most common in younger children as part of the headache syndrome,¹⁰ and antiemetics can be used in conjunction with headache medications. As patients who are nauseated may not tolerate swallowing pills, many headache medications come in oral-dissolving or intranasal formulations.

The first line for abortive headache treatments includes acetaminophen, ibuprofen, and other nonsteroidal anti-inflammatory drugs. Randomized trials for pharmacologic rescue treatments efficacy show acetaminophen at 54% and ibuprofen at 68.76%.¹¹

Triptan medications, the second line for rescue headache treatments, were designed specifically to abort migraine headaches. Because they have selective activity on atypical 5HT1B and 5HT1D receptors, their mechanisms of action include cranial vasoconstriction, peripheral trigeminal inhibition, and inhibition of transmission via the trigeminal cervical complex. They are typically well tolerated. Common adverse effects include paresthesia, sleepiness, dizziness, and tightness in chest or throat. They should not be used more than 2 times a week and should be avoided in patients with cardiovascular disease, who are pregnant, or who have complicated migraines. Rizatriptan (efficacy 73-74%) is the only treatment approved for patients aged 6 to 12 years. Sumatriptan nasal spray (64-86%), combination sumatriptan/naproxen, almotriptan (72-73%), and zolmitriptan nasal spray (62%) are approved in patients aged 12 to 17 years.¹¹

Further pharmacologic rescue treatments typically have to be administered intravenously in the emergency department setting. Of the dopamine antagonists, prochlorperazine (Compazine) IV is the most effective abortive in randomized trials at 84.8% pain relief, followed by metoclopramide (Reglan) and promethazine (Phenergan).^12,13

Headache treatment-preventive plan

Whereas patients with episodic headache can often be treated with lifestyle changes and rescue medications alone, others with chronic headaches (> 15 days a month) and severe headaches will benefit from a preventive plan that aims to decrease both headache severity and frequency.

Tip: it is important to distinguish rescue from preventive treatment, so patients do not stop taking preventive treatments within few days when it “doesn’t work.”

Patients should understand that preventive treatment has to start at a low dose to minimize adverse effects and build up slowly. Within 6 to 8 weeks of taking it constantly, the goal would be a decrease in headache frequency and intensity by at least 50%.

For many years, the use of pharmacologic preventive medications in childhood headache was based on adult studies. A seminal paper published in The New England Journal of Medicine in 2018 based on the CHAMP trial (NCT01581281) compared children with episodic migraine in 3 prospective randomized groups taking placebo, topiramate 2 mg/kg, or amitriptyline 1 mg/kg.¹⁴ The trial was stopped early because the placebo group did as well as the other 2 groups with fewer adverse effects. It was noted that patients had an average of 11 days per month of headache (suggesting more of an episodic than chronic headache picture) and that the placebo group received appropriate lifestyle management and rescue plan counseling. This underscores the efficacy of lifestyle and rescue management independent of pharmacologic preventive therapy.

Following this study, many practitioners chose to offer nutraceuticals for headache prevention before going straight to pharmacologic treatments. Nutraceuticals include vitamins, minerals, herbal supplements, and dietary supplements. Magnesium, riboflavin (vitamin B₂), coenzyme Q10, and vitamin D₃ all have demonstrated efficacy in some pediatric trials for headache prevention,^15-18 although there are limited studies with a placebo group. Importantly, the adverse effect profile for nutraceuticals is better than for pharmacologic agents.

If headaches continue to be troublesome despite lifestyle management, good rescue therapy, and a sustained trial of nutraceuticals, it is reasonable to consider pharmacologic preventatives. Cyproheptadine (Periactin), an antihistamine, has no clinical trial data but has probably been used the longest for pediatric headache prevention. Although it is well-tolerated in younger children, patients 8 years of age and older typically experience too much sedation for it to be acceptable. Topiramate, an epileptic medication, received FDA approval in 2014 for the prevention of headaches in adolescents aged 12 to 17 years. Potential common adverse effects include cognitive slowing, paresthesias, appetite suppression, and renal stones. Amitriptyline, an antidepressant, can be helpful for patients with migraines who also have insomnia and/or depression. Besides somnolence, it can cause appetite increase, tachycardia, and dry mouth. Propranolol, a β-blocker, has 1 randomized control trial from 1974 showing efficacy, but subsequent studies have been negative. Possible adverse effects include exercise intolerance, depression, and light-headedness.

Finally, there are many other nonpharmacologic interventions that have been shown to be helpful in mitigating childhood headache and may have a synergistic effect with preventive medications. Cognitive behavioral therapy (CBT) in combination with amitriptyline was more beneficial than CBT alone for a group of adolescents.¹⁹ There is some convincing evidence for biofeedback (teaching patients to regulate physical responses to stress) in the prevention of pediatric migraine, sometimes in combination with relaxation therapy. At Stanford Children’s Health, occupational therapists and pediatric pain psychologists are trained in multiple modalities such at CBT, biofeedback, and relaxation therapy. If there is a history of neck/shoulder pain or tenderness to palpation of the scalp, neck, or shoulders, a physical therapist can help strengthen and realign a patient’s posture to prevent cervicogenic headache. There is 1 positive study on acupuncture for pediatric headache,²⁰ and many adult studies demonstrate efficacy in chronic pain and headache. It is important to explain to the patient that acupuncture needles are much thinner and less painful than typical needles; children who have had acupuncture before seem to prefer this method.

When to refer to a neurologist

Instances in which consultation with a neurologist could be helpful would include headaches that are severe, prolonged, or intractable. Neurology consultation would be indicated for patients with a complicated aura (eg, hemiplegic migraine or migraine with brainstem symptoms such as dysarthria, vertigo, tinnitus, or diplopia). Referral is advised when a pediatric practitioner is reconsidering the diagnosis of primary headaches and would like guidance on workup for secondary headaches. Finally, a practitioner may feel comfortable implementing first- or second-line therapies but will seek help with less conventional treatments, such as the new class of anti-cGRP monoclonal antibodies. These have not yet been approved in children but are increasingly being prescribed off label for adolescents with intractable migraines. The American Headache Society Section on Pediatric-Adolescent Headache offers guidelines for administering these new treatments.²¹ Several neuromodulatory devices have been developed for the headache population, with 2 approved by the FDA for adolescents, but the studies have very small sizes (9-45 patients) and the cost for renting these devices is often prohibitive.

Childhood headache can be dangerous, debilitating, or both. After excluding dangerous causes, it is important to provide the patient and caregiver with a plan for headache management that includes education on lifestyle management, rescue plan, and preventive measures. During the current pandemic, screen time and eye strain have become more significant triggers, whereas, conversely, being able to sleep in later on school days appears to be beneficial for teenagers.^22,23 The more that children and their caregivers are empowered to understand and manage childhood headaches, the better for all involved.

 

SOURCES: CONTEMPORARY PEDIATRICS, MAYO CLINIC,AAP

References

1. Abu-Arafeh I, Razek S, Sivaraman B, Graham C. Prevalence of headache and migraine in children and adolescents: a systematic review of population-based studies. Dev Med Child Neurol. 2010;52(12):1088-1097. doi:10.1111/j.1469-8749.2010.03793
2. Parisi P, Papetti L, Spalice A, Nicita F, Ursitti F, Villa MP. Tension-type headache in paediatric age. Acta Paediatr. 2011;100(4):491-495. doi:10.1111/j.1651-2227.2010.02115.x
3. Abu-Arafeh I, McLeod S. Serious neurologic disorders in children with chronic headache. Arch Dis Child. 2005;90(9):937-940. doi:10.1136/adc.2004.067256
4. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018;38(1):1-211. doi:10.1177/0333102417738202
5. Guidelines. International Headache Society. Accessed February 27, 2021. https://ihs-headache.org/en/resources/guidelines/
6. Özge A, Faedda N, Abu-Arafeh I, et al. Experts’ opinion about the primary headache diagnostic criteria of the ICHD-3rd edition beta in children and adolescents. J Headache Pain. 2017;18(1):109. doi:10.1186/s10194-017-0818-y
7. Karsan N, Prabhakar P, Goadsby PJ. Characterising the premonitory stage of migraine in children: a clinic-based study of 100 patients in a specialist headache service. J Headache Pain. 2016;17(1):94.doi:10.1186/s10194-016-0689-7
8. Monteith TS, Sprenger T. Tension type headache in adolescence and childhood: where are we now?Curr Pain Headache Rep. 2010;14(6):424-430. doi:10.1007/s11916-010-0149-z
9. Neut D et al. The prevalence of triggers in paediatric migraine: a questionnaire study in 102 children and adolescents. J Headache Pain. 2012;13(1):61-65. doi:10.1007/s10194-011-0397-2
10. Wilcox SL, Ludwick AM, Lebel A, Borsook D. Age- and sex-related differences in the presentation of paediatric migraine: A retrospective cohort study. Cephalalgia. 2018; 38(6):1107-1118. doi:10.1177/0333102417722570
11. Gelfand A, Goadsby PJ. Treatment of pediatric migraine in the emergency room. Pediatr Neurol. 2012;47(4):233-241. doi:10.1016/j.pediatrneurol.2012.06.001
12. Sheridan DC, Laurie A, Pacheco S, et al. Relative effectiveness of dopamine antagonists for pediatric migraine in the emergency department. Pediatr Emer Care. 2018;34(3):165-168. doi:10.1097/PEC.0000000000000718
13. Bachur RG, Monuteaux MC, Neuman MI. A comparison of acute treatment regimens for migraine in the emergency department. Pediatrics. 2015;135(2):232-238. doi:10.1542/peds.2014-2432
14. Powers SW, Coffey CS, Chamberlin LA, et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine. N Engl J Med. 2017;376(2):115-124. doi:10.1056/NEJMoa1610384
15. Wang F, Van Den Eeden SK, Ackerson LM, Salk SE, Reince RH, Elin RJ. Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial. Headache. 2003;43(6):601-610. doi:10.1046/j.1526-4610.2003.03102.x
16. Das R, Qubty W. Retrospective observational study on riboflavin prophylaxis in child and adolescent migraine. Pediatric Neurology. 2021;114:5-8. doi:10.1016/j.pediatrneurol.2020.09.009
17. Slater SK, Nelson TD, Kabbouche MA, et al. A randomized, double-blinded, placebo-controlled, crossover, add-on study of coenzyme Q10 in the prevention of pediatric and adolescent migraine. Cephalalgia. 2011;31(8):897-905. doi:10.1177/0333102411406755
18. Fallah R, Yazd SS, Sohrevardi SM. Efficacy of topiramate alone and topiramate plus vitamin D3 in the prophylaxis of pediatric migraine: a randomized clinical trial. Iran J Child Neurol. 2020;14(4):77-86. doi:10.22037/ijcn.v15i1.18017
19. Powers SW, Kashikar-Zuck SM, Allen JR, et al. Cognitive behavioral therapy plus amitriptyline for chronic migraine in children and adolescents: a randomized clinical trial. JAMA. 2013;310(24):2622-2630. doi:10.1001/jama.2013.282533
20. Pintov S, Lahat E, Alstein M, Vogel Z, Barg J. Acupuncture and the opioid system: implications in management of migraine. Pediatr Neurol. 1997;17(2):129-133. doi:10.1016/s0887-8994(97)00086-6
21. Szperka CL, VanderPluym J, Orr SL, et al. Recommendations on the use of anti-CGRP monoclonal antibodies in children and adolescents. Headache. 2018;58(10):1658-1669. doi:10.1111/head.13414
22. David A, Wujack T. Doctors seeing more eye strain and headaches from virtual learning and screen time during pandemic. WXYZ. December 4, 2020. Accessed March 19, 2021. https://www.wxyz.com/rebound/doctors-seeing-more-eye-strain-and-headaches-from-virtual-learning-and-screen-time-during-pandemic
23. Gelfand AA, Pavitt S, Ross AC, et al. Later high school start time is associated with lower migraine frequency in adolescents. Headache. 2021;61(2):343-350.doi:10.1111/head.14016

Παιδική υδροκήλη: Είναι επικίνδυνη για την υγεία του παιδιού; 

 

 Η εμφάνιση υδροκήλης είναι πολύ συχνή στα νεογνά, και μάλιστα στον πρώτο χρόνο ζωής. 

What is a hydrocele in children? A hydrocele is fluid buildup in the thin pouch that holds the testes in the scrotum. Up to 1 in 10 baby boys have a hydrocele at birth. In most cases, it goes away without treatment in the first year. 

Ως υδροκήλη ορίζεται η συλλογή υγρού μεταξύ των πετάλων του ιδίως ελυτροειδούς χιτώνα του όρχεως. Αποτέλεσμα αυτής είναι η προοδευτική συνήθως ανώδυνη διόγκωση του οσχέου. Η εμφάνιση υδροκήλης είναι πολύ συχνή στα νεογνά, και μάλιστα στον πρώτο χρόνο ζωής. Στα παιδιά υπάρχουν δύο ειδών υδροκήλες. Η επικοινωνούσα και η κλειστή. 

Στην επικοινωνούσα, το υγρό προέρχεται από την κοιλιά μέσω μια επικοινωνίας που υπάρχει με το όσχεο. Στην κλειστή, το υγρό βρίσκεται περιορισμένο μέσα στην κοιλότητα του οσχέου. 

Αιτιολογία 

Οι όρχεις αρχικά είναι μέσα στην κοιλιά και σταδιακά κατέρχονται στο όσχεο, μαζί με ένα σάκο που τους περιβάλλει και ο οποίος περιέχει κάποια ποσότητα υγρού. Ο σωλήνας (ελυτροπεριτοναϊκός πόρος) μέσα από τον οποίο περνάει ο όρχις στο όσχεο φυσιολογικά στη συνέχεια κλείνει. Εάν δεν κλείσει, υπάρχει επικοινωνία μεταξύ της κοιλιάς και του οσχέου. Μέσα από αυτόν το σωλήνα, περνάει το υγρό της κοιλιακής χωράς στον όρχι. Υδροκήλη στα παιδιά μπορεί όμως να παρατηρηθεί και δευτεροπαθώς σαν αντιδραστική εκδήλωση σε κάθε πάθηση του όρχεως ή της επιδιδυμίδας. Πώς θα καταλάβω ότι το παιδί μου έχει υδροκήλη; Συνήθως, η διάγνωση τίθεται μόνο με τη λήψη ιστορικού και με τη διενέργεια φυσικής εξέτασης. Κατά την ψηλάφηση του οσχέου ο παιδοχειρουργός ανακαλύπτει μία μάζα ανώδυνη, που κλυδάζει χωρίς συνήθως σημεία φλεγμονής. Μία από τις κλασικές μεθόδους διάγνωσης της υδροκήλης είναι η διαφανοσκόπηση, κατά την οποία τοποθετείται μία φωτεινή πηγή στη μία πλευρά του οσχέου και γίνεται έλεγχος της διαφάνειας αυτού από την άλλη πλευρά. Σαφή διάγνωση μπορεί να τεθεί επίσης με τη βοήθεια του υπερηχογραφήματος. 

Είναι επικίνδυνη η υδροκήλη για την υγεία του παιδιού μου; Συνήθως, η υδροκήλη είναι εντελώς ακίνδυνη και, εφόσον δεν πάρει σημαντικές διαστάσεις, δεν επηρεάζει τη γονιμότητα. Μόνο στην περίπτωση που μέσα από τον σωλήνα επικοινωνίας εισέλθει και το έντερο. Έχουμε έτσι την δημιουργία βουβωνοκήλης και τον κίνδυνο περίσφιξης αυτής. Σε αυτές τις περιπτώσεις η διόγκωση γίνεται ολοένα και μεγαλύτερη με συνοδό άλγος, ερυθρότητα δέρματος και έμετο. Απαιτείται άμεση χειρουργική επέμβαση. 

Πώς αντιμετωπίζεται και πότε; Για τα βρέφη συστήνεται απλή παρακολούθηση, γιατί συνήθως η υδροκήλη εξαφανίζεται μέχρι το δεύτερο χρόνο ζωής. Εφόσον συνεχίσει να υπάρχει υδροκήλη και το παιδί είναι μεγαλύτερο από δυο ετών συνιστάται χειρουργική αποκατάσταση. Η επέμβαση γίνεται με μια μικρή τομή στο ύψος της βουβωνικής χώρας όπου κλείνουμε με ραφές την επικοινωνία. Δεν απαιτείται νοσηλεία και το παιδί εξέρχεται από το νοσοκομείο σε 2-3 ώρες. 

 

Αλεξίου Ηλίας Χειρουργός Παίδων

Παιδιατρικό πολυσυστηματικό φλεγμονώδες σύνδρομο (MIS-C ή PIMS-TS)

Από Μιχάλη Ιασονίδη, παιδίατρο

(Multisystem inflammatory syndrome in children/ MIS-C ή Paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS)

Το παιδιατρικό πολυσυστημικό φλεγμονώδες σύνδρομο (που ονομάζεται για συντομία PIMS-TS ή MIS-C) είναι μια σπάνια πάθηση, που μπορεί να συμβεί σε ορισμένα παιδιά και εφήβους κάποια στιγμή μετά από λοίμωξη COVID-19. Αν και είναι μια σχετικά σπάνια πάθηση, είναι σημαντικό να εντοπιστεί έγκαιρα, ώστε να αντιμετωπιστεί με επιτυχία.

Η πάθηση είναι μια καθυστερημένη αντίδραση του οργανισμού, που προσπαθεί να εξοντώσει τον ιό και αυτό προκαλεί οίδημα και φλεγμονή σε όλο το σώμα.

Τα συμπτώματα του PIMS-TS δεν πρέπει να συγχέονται με αυτά του COVID-19. Εξάλλου πολλά παιδιά που εμφανίζουν PIMS-TS μπορεί να μην είχαν αντιληφθεί προηγουμένως ότι πέρασαν COVID-19.

Περιγράφηκε για πρώτη φορά ως νέα πάθηση τον Απρίλιο του 2020. Καθώς η πάθηση είναι νέα, χρειάζεται χρόνος και συλλογική δουλειά σε όλο τον κόσμο για να μάθουμε όσο γίνεται περισσότερα για αυτή. Αυτό θα οδηγήσει σε βελτίωση της αντιμετώπισης της και στην κατανόηση τυχόν μακροπρόθεσμων επιπτώσεων.

 

 Ποια είναι τα συμπτώματα;

Τα συμπτώματα του PIMS-TS μπορεί να περιλαμβάνουν:

• παρατεταμένο πυρετό (πάνω από 38^οC)
• πόνο στην κοιλιά

• διάρροια ή/και έμετο
• εκτεταμένο εξάνθημα (κηλιδοβλατιδώδες)
• έντονη ερυθρότητα επιπεφυκότων
• γλώσσα κόκκινη και οιδηματώδη σαν φράουλα
• κόκκινα σκασμένα χείλη (χειλίτιδα)
• οίδημα άκρων (χεριών και ποδιών)
• διαταραχές συμπεριφοράς.

Εάν το παιδί σας παρουσιάζει όλα ή ορισμένα από τα παραπάτω συμπτώματα, θα πρέπει να επικοινωνήσετε άμεσα με τον γιατρό σας. Εάν το παιδί σας εμφανίσει και πόνο στο στήθος, τότε η κατάσταση είναι πιο επείγουσα.

 

Πώς αντιμετωπίζεται;

Είναι κατάσταση, που λόγω της σοβαρότητας της, χρειάζεται νοσοκομειακή περίθαλψη, η οποία τις πιο πολλές φορές είναι πολυήμερη νοσηλεία, αλλά ευτυχώς με καλή ανταπόκριση στην αγωγή.

 

Αγωγή:

Ένας συνδυασμός φαρμάκων χρησιμοποιείται για να περιοριστεί η υπεραντίδραση του ανοσοποιητικού σύστηματος που οδηγεί στα οιδήματα και την έντονη κακουχία. Αυτά περιλαμβάνουν:

• ενδοφλέβια χορήγηση ανοσοσφαιρίνης (IVIG), που βοηθά στην καταπολέμηση της λοίμωξης και στη μείωση της φλεγμονής και του οιδήματος.
• ασπιρίνη, που βοηθά στη μείωση του κινδύνου δημιουργίας θρόμβων. Η ασπιρίνη πρέπει να συνεχιστεί για τουλάχιστον έξι εβδομάδες μετά την έξοδο από το νοσοκομείο.
• Στεροειδή (κορτιζόνη), όπως η ενδοφλέβια μεθυλπρεδνιζολόνη και η από του στόματος πρεδνιζολόνη, εκεί και όπου χρειάζεται. Βοηθά στη μείωση της φλεγμονής.

Μετά την έξοδο από το νοσοκομείο χρειάζεται τακτική παρακολούθηση και εξετάσεις για μεγάλο διάστημα.

 

What’s new in children’s drugs-( CONTEMPORARY PEDIATRICS)

What’s new in children’s drugs

December 9, 2021

Rachel Meyers, PharmD, Pooja Shah, PharmD, BCPPS

Contemporary PEDS Journal, December 2021, Volume 38, Issue 12

This past year has seen several important new drug approvals and labeling updates for children. Here is what you should know.

We are continuing to observe the effects of federal legislation, including the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act, which have increased the number of clinical trials conducted in children. This article summarizes recent (October 2020 to September 2021) labeling changes, new dosage forms, and new drugs that have potential for use in children. Table 1 includes information on newly approved drugs indicated for use in pediatric patients, whereas Table 2 lists newly approved drugs for adults with the potential for use in pediatric patients. Table 3 describes new dosage forms for medications, and Table 4 lists labeling changes to existing drugs with implications for pediatric patients.

Table 1, part 1

There have been major advancements in the treatment and prevention of COVID-19. Thus far, only remdesivir1 (Veklury) has received FDA approval for treatment of COVID-19 in adults and children 12 years and older, but its use in younger children is permitted only under an emergency use authorization (EUA). COVID-19 Vaccine, mRNA2 (Comirnaty) received approval as a vaccine for COVID-19 in adults and children 16 years and older and is available under an EUA for children 5 to 15 years old. More treatments and vaccines for younger children are expected to receive EUAs in the coming months, which may subsequently lead to full approvals.

Table 1, part 2

There has been a continuing trend in the development of drugs for orphan diseases affecting pediatric patients, such as lonafarnib (Zokinvy) or progeria, casimersen (Amondys 45) for Duchenne muscular dystrophy, fosdenopterin (Nulibry) for molybdenum cofactor deficiency type A, and avalglucosidase alfa-ngpt (Nexviazyme) for Pompe disease.

Additional developments include 2 treatments for infection caused by Zaire ebolavirus, ansuvimab-zykl (Ebanga) and atoltivimab, maftivimab, and odesivimab-ebgn (Inmazeb). Both are approved for patients as young as neonates born to mothers who have tested positive for Ebola on reverse transcriptase polymerase chain reaction tests. Both Ebanga and Inmazeb were studied in the PALM trial, which was conducted during the 2018-2019 Ebola outbreak in the Democratic Republic of the Congo.3 For Ebanga, the 28-day mortality was 35.1% compared with 49.7% in its comparator control group. The 28-day mortality was 33.5% in the Inmazeb group compared with 51.3% in its comparator control group.

Table 2

Some new alternatives to commonly used medications have also emerged. Dasiglucagon (Zegalogue) is a new treatment for severe hypoglycemia that is available as a pre-filled syringe or an autoinjector. In a clinical trial, Zegalogue was reported to raise blood glucose by at least 20 mg/dL in approximately 10 minutes compared with 12 minutes for traditional glucagon.4 Two new treatments for attention-deficit/hyperactivity disorder (ADHD) have also been approved. Serdex-methylphenidate and dexmethylphenidate (Azstarys) is a stimulant that contains an immediate-release dexmethylphenidate component in addition to serdex-methylphenidate, which is a prodrug of dexmethylphenidate.5 Serdex-methylphenidate is metabolized to dexmethylphenidate throughout the day, allowing for once-daily dosing. Viloxazine (Qelbree) is available as a nonstimulant, once-daily extended-release capsule.6 Both of these new treatment options for ADHD are available as capsules, which can be swallowed whole or opened and sprinkled on applesauce; Azstarys may also be sprinkled in water.

Labeling changes

This year, we have continued to observe drug labeling changes that include more of the younger pediatric patient population. These updates help increase the tools available for practitioners to administer these drugs safely and effectively in this vulnerable patient population.

ANALGESICS

Morphine in children has been considered off-label despite the high rates of use described in pediatric patients.7 Labeling information is finally available for morphine as an intravenous continuous infusion and as an oral solution. Morphine oral solution (2 mg/mL and 4 mg/mL) is now indicated for pediatric patients aged 2 to 17 years with acute pain severe enough to require an opioid analgesic when alternative treatments are inadequate.8 Safety and efficacy in this age group are supported by extrapolation from clinical evidence in adults and supportive data from an open-label safety and pharmacokinetic study in pediatric patients aged 2 to 17 years with postoperative acute pain. The recommended initial dosage is 0.3 mg/kg/dose orally, based on pharmacokinetic modeling and simulation, which will be equivalent to the maximum concentration of 10 mg in adult patients. With regard to safety, adverse effects are expected to be similar to those observed in adults. Morphine continuous intravenous infusion is now approved for pain in patients of all age groups. Use of morphine continuous intravenous infusion for pain management in pediatric patients is supported by evidence from randomized controlled studies in pediatric patients.9,10

 

Table 3

Additional pain medications that have expanded indications in the pediatric population include diclofenac potassium (Zipsor). The labeling has been expanded to include safety and effectiveness in pediatric patients aged 12 to 17 years, offering this population an alternative nonopioid pain medication.10,11 This indication was based on extrapolation of efficacy from studies in adult patients combined with pharmacokinetic and safety data from 2 open-label studies with a combined 49 patients aged 12 to 17 years and an active-controlled study in 76 pediatric patients aged 12 to 16 years.

Bupivacaine liposome (Exparel) is a postoperative local anesthetic with labeling updated to include a single-dose infiltration to contribute to postsurgical local analgesia in pediatric patients 6 years and older.10,12 This indication was based on the results of the phase 3 PLAY study, which included 98 pediatric patients undergoing spinal or cardiac surgeries. A dose of 4 mg/kg produced pharmacokinetics and safety outcomes similar to those in adult patients. This updated indication provides an alternative to opioids for postoperative pain control.

EXPANDED PEDIATRIC AGE GROUPS

Many of the drug labeling changes in 2021 have focused on expanding indications to include younger pediatric patients. Although initial FDA approvals in pediatric patients often include adolescent patients, these medications are often used in the younger populations. Below are highlights of updates for expanded indications in children.

Table 4, part 1

Brivaracetam (Briviact) is an anticonvulsant with a mechanism similar to that of levetiracetam; it binds specifically to synaptic vesicle protein 2A, but with a 15- to 30-fold higher affinity compared with levetiracetam. Brivaracetam oral and intravenous formulations are now indicated in patients 1 month or older for the treatment of partial-onset seizures.10,13 This indication was based on the results of an open-label follow-up pediatric study, in which an estimated 71.4% and 64.3% of patients aged 1 month to 17 years with partial-onset seizures remained on brivaracetam therapy at 1 year and 2 years, respectively.

Dalbavancin (Dalvance) is a unique glycopeptide antibiotic that is approved in all pediatric patients from birth.14 It is indicated for the treatment of acute bacterial skin and soft tissue infections caused by gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. It is the first single-dose option for this indication and is administered as a 30-minute infusion. This approval was based on a multicenter, open-label, randomized, active-controlled trial that was conducted in pediatric patients aged 3 months to 18 years with bacterial skin and soft tissue infections. The study compared single-dose or 2-dose dalbavancin against a comparator regimen that included intravenous vancomycin for methicillin-resistant gram-positive infections or intravenous oxacillin or flucloxacillin for methicillin-susceptible gram-positive infections.

Table 4, part 2

Another antimicrobial agent that recently received expanded age indications is peramivir10,15 (Rapivab). Based on the results of a randomized, open-label, active-controlled study comparing peramivir and oseltamivir in 97 patients aged 6 months to 17 years with acute uncomplicated influenza, the label was updated to include pediatric patients 6 months and older. There was a comparable time between the oseltamivir and peramivir groups to alleviation of symptoms and time to recovery of normal temperature. The recommended dose based on this study is 12 mg/kg/dose for patients 6 months to 12 years of age.

New dosage forms

As the need for pediatric dosage forms expands, pharmaceutical companies have begun exploring options beyond oral liquids. Three medications have been approved as “oral pellets” in the past year: dabigatran etexilate (Pradaxa), sofosbuvir/ velpatasvir (Epclusa), and glecaprevir/pibrentasvir (Mavyret). Pradaxa, originally approved in 2010 for the treatment and prevention of venous thromboembolism in adults, is now approved for pediatric patients aged 3 months to less than 12 years for the same indications.16 As the first direct-acting oral anticoagulant approved for use in the pediatric population, Pradaxa offers an alternative to injectable anticoagulants and warfarin. The oral pellets approved for this age group are available in packets of 20 mg, 30 mg, 40 mg, 50 mg, 110 mg, and 150 mg. The packet is opened and the pellets mixed in a soft food, such as baby rice cereal prepared with water or apple sauce; the pellets should not be mixed with milk or milk-containing foods. A spoon is then used to administer the dose. It should be noted that these pellets should not be administered with an oral syringe or through a feeding tube. Epclusa and Mavyret, both approved for the treatment of hepatitis C infection in children as young as 3 years, are also now available as oral pellets packaged in packets.17,18 It is important to read the instructions for use carefully, as only certain types of foods can be used to mix the pellets. For both Epclusa and Mavyret, it is important that the child not chew the pellets, as this will produce a bad taste.

Conclusion

We continue to see improvements in drug labeling for children and new dosage forms, which will help improve care for this patient population. New vaccines for the prevention of pneumococcal disease in adults may eventually receive approval in children. Novel pediatric-friendly oral dosage forms, such as oral pellets, may continue to become available for new drugs seeking approval for pediatric use. The coming months should see more approvals in the area of COVID-19. The continuing growth of clinical trials and approvals in children combined with the expansion of drug labeling to include children has been encouraging for pediatric practitioners.

 

SOURCE: https://www.contemporarypediatrics.com/view/what-s-new-in-children-s-drugs

Contemporary Pediatrics