key: cord-288567-1nmk9qhr
authors: Frieden, Ilona J.; Püttgen, Katherine B.; Drolet, Beth A.; Garzon, Maria C.; Chamlin, Sarah L.; Pope, Elena; Mancini, Anthony J.; Lauren, Christine T.; Mathes, Erin F.; Siegel, Dawn H.; Gupta, Deepti; Haggstrom, Anita N.; Tollefson, Megha M.; Baselga, Eulalia; Morel, Kimberly D.; Shah, Sonal D.; Holland, Kristen E.; Adams, Denise M.; Horii, Kimberly A.; Newell, Brandon D.; Powell, Julie; McCuaig, Catherine C.; Nopper, Amy J.; Metry, Denise W.; Maguiness, Sheilagh
title: Management of infantile hemangiomas during the COVID pandemic
date: 2020-05-16
journal: Pediatr Dermatol
DOI: 10.1111/pde.14196
sha: 
doc_id: 288567
cord_uid: 1nmk9qhr

The COVID‐19 pandemic has caused significant shifts in patient care including a steep decline in ambulatory visits and a marked increase in the use of telemedicine. Infantile hemangiomas (IH) can require urgent evaluation and risk stratification to determine which infants need treatment and which can be managed with continued observation. For those requiring treatment, prompt initiation decreases morbidity and improves long‐term outcomes. The Hemangioma Investigator Group has created consensus recommendations for management of IH via telemedicine. FDA/EMA‐approved monitoring guidelines, clinical practice guidelines, and relevant, up‐to‐date publications regarding initiation and monitoring of beta‐blocker therapy were used to inform the recommendations. Clinical decision‐making guidelines about when telehealth is an appropriate alternative to in‐office visits, including medication initiation, dosage changes, and ongoing evaluation, are included. The importance of communication with caregivers in the context of telemedicine is discussed, and online resources for both hemangioma education and propranolol therapy are provided.

The novel coronavirus (COVID-19) pandemic has drastically altered health care delivery including widespread reductions in ambulatory visits to minimize exposure to and transmission of COVID-19 resulting in unprecedented adoption of virtual care via telemedicine platforms. In light of these significant shifts in patient care, the Hemangioma Investigator Group (HIG) met with the goal of creating consensus recommendations to provide timely care for infants with infantile hemangioma (IH) via telehealth. The use of beta-blockers in the treatment of IH has revolutionized care, and recent American Academy of Pediatrics (AAP) clinical practice guidelines (CPG) emphasize that early therapeutic intervention is critical for complicated IH to prevent medical complications or permanent disfigurement. 1 In this statement, we review FDA/EMA-approved monitoring guidelines, information derived from several clinical practice guidelines, and other publications regarding initiation and monitoring of beta-blocker therapy, including newly published information which could help inform modification of these practices. We give recommendations to help guide decisions about when telehealth may be an alternative to in-office visits, including initiation, dosage changes, and continued evaluation for those patients requiring treatment. We also provide tools for patient communication in context of telemedicine. While these recommendations were prompted by the COVID-19 pandemic, we recognize that they might be relevant in analogous settings where there is a disruption of the normal delivery of medical care and potentially in settings with lack of access to practitioners with expertise in IH management.

The Hemangioma Investigator Group (HIG) met via videoconferencing on March 22, 2020 , and subdivided members into 3 groups: one to work on the introduction and discussion, one to create a table of inclusion and exclusion criteria for telemedicine use of betablockers, and one to curate available patient-education materials for practitioners and parents. Through an iterative process of review of these 3 domains, we were able to achieve unanimous consensus regarding the content of these recommendations.

The most rapid IH growth occurs between 1 and 3 months of age, and there is a "window of opportunity" to treat problematic IHs in order to prevent morbidities. Telemedicine has a critical role to play in facilitating early evaluation and risk stratification. In areas where access to specialists has long been challenging, telemedicine triage has the potential to improve care for high-risk IH. Early consultation ideally by 1 month of age or as soon as high-risk features are recognized is warranted. Table 1 , from the AAP CPG, delineates risk categories of IH and potential associated morbidities.

Oral beta-blockers are the gold standard when systemic treatment is indicated for IH and propranolol solution is the only FDA/EMAapproved treatment. Methods for initiation of oral propranolol have evolved over time. [2] [3] [4] [5] [6] [7] [8] [9] Consensus recommendations prior to the FDA/EMA approval in 2014 included the following 10 : (a) screening for contraindications to propranolol, (b) performing or obtaining documentation of, a recent normal cardiovascular and pulmonary history and examination, (c) obtaining key historical data including poor feeding, dyspnea, tachypnea, diaphoresis, wheezing, heart murmur, or family history of heart block or arrhythmia, and (d) prolonged in-office monitoring. The FDA/EMA-approved administration monitoring recommendations include in-office heart rate (HR) and blood pressure (BP) monitoring for 2 hours after the first dose of propranolol or for increasing the dose (>0.5 mg/kg/d) for infants 5 weeks of adjusted gestational age or older. 10, 11 More recent consensus statements 1,12-14 vary in specific recommendations for propranolol initiation. Both Australian and British guidelines 13, 14 recommend full-term healthy infants without comorbidities may undergo outpatient initiation without in-office monitoring with initial doses of 1 mg/kg/d. 13, 14 Both state that a thorough medical While rare, hypoglycemia, seen primarily with intercurrent illness or decreased feeding, is a serious potentially life-threatening risk, 16 other risks include bronchospasm and wheezing, usually in the context of a respiratory illness, cold hands and feet, gastrointestinal upset, and sleep disturbances. All of these potential adverse events require anticipatory guidance of parents, which should still be a part of clinical care, whether in person or via telemedicine.

Other non-FDA-approved beta-blocking agents, including oral atenolol and nadolol, have been used for the treatment of IH with several publications supporting their efficacy. However, the group was unable to reach consensus recommendation regarding telemedicine for initiation of either of these medications. Topical timolol has been widely used for treating IH with efficacy reported, particularly for small, superficial IH. 9, 15 Systemic absorption is variable but does occur, 17, 18 suggesting that similar prescreening should be performed to assure that infants are healthy and have had a normal cardiovascular and pulmonary examinations, for example, via recent history and physical examination (see discussion below).

Our recommendations regarding telemedicine initiation of betablocker therapy are summarized in Table 2 with an accompanying algorithm ( Figure 1 ). They were developed after review of relative and absolute contraindications for propranolol, reported adverse events, FDA/EMA labeling recommendations, and published guidelines, with group consensus. They are made with the goal of supporting practicing clinicians in delivering high-quality care in a dramatically altered

Highest • Large (>5 cm) or segmental facial or scalp: a. higher risk of airway hemangiomas (if beard area), b. may be associated with PHACE syndrome, c. high risk of scarring and/or disfigurement. • Large or segmental lumbosacral or perineal: a. may be associated with LUMBAR syndrome, b. high risk of ulceration and scarring. • Multifocal IHs (≥5) and abdominal ultrasonography reveals hemangiomas:

a. may be associated with abdominal compartment syndrome, high-output b. congestive heart failure, and hypothyroidism. • Periocular IH causing eyelid asymmetry, lid closure or ptosis, proptosis, or other findings with potential impact on visual axis: a. risk of astigmatism, anisometropia, and amblyopia a In ordinary circumstances, infants are being seen regularly for well-child visits by primary care providers, who weigh and measure infants and perform heart and lung examinations as a standard part of their care. If these examinations are not occurring due to disruptions in healthcare, it becomes much more difficult to ascertain whether there is a normal cardiovascular or pulmonary examination, if normal growth is occurring and other baseline characteristics. In such cases, decisions about initiating therapy must be done on a case-by-case basis. b During this pandemic and other unusual circumstances, in-person visits may not be possible in a timely fashion. In these settings, triage and management decisions need to be made on a case-by-case basis, ideally in conjunction with relevant specialists as needed (eg, ENT and cardiology). 

Topical timolol is efficacious for smaller, thin IH. 17, 19, 20 Although rigorous safety studies have not been performed, if used in small amounts, the rate of adverse events is very low. 19 Systemic absorption occurs to varying degrees measurable in both urine and plasma; plasma concentrations demonstrated to have measurable systemic β-blocking activity in adults have been reported. 17, 18, 21 Based on this information, we recommend that timolol application should be limited to the dose for which safety data have been most often reported, 1 drop twice daily of timolol 0.5%. Timolol is not recommended for the treatment of thick or deep IH, both because it is less effective and systemic absorption may be greater. 18 Because of the potential for systemic exposure of topical application, pre-screening should be performed to assure that infants are healthy with normal cardiopulmonary examinations via recent history and physical examination. As with oral beta-blockers, temporary discontinuation is recommended if patients experience respiratory or gastrointestinal symptoms. Infants under 3 months of age, and those whose history suggests ongoing IH growth, should be monitored via frequent visits or photographs submitted by parents to assure that therapy does F I G U R E 1 Algorithm for management not need to be switched from topical to oral. Such follow-up visits can often be done via telemedicine.

The COVID-19 pandemic has caused an abrupt shift from ambulatory visits to telemedicine platforms. This consensus statement provides guidance on timely treatment for patients with IH requiring early intervention while prioritizing patient safety. While we acknowledge the benefits of in-person visits when health care systems are operating normally, there was group consensus that telehealth visits could provide an alternative method of evaluation and treatment as long as safeguards are in place to minimize risks. Our recommendations are based upon first ensuring that there are no contraindications for therapy, documentation of a recent normal physical examination, and no signs or symptoms of active illness ( Table 2 ). We suggest that these patients are amenable to initiation of therapy through a process of limited physical examination coupled with virtual counseling and education about the natural history, treatment options, administration of medication, and potential adverse reactions to therapy.

We recognize that there are other circumstances in which these recommendations may be applicable including natural disasters (eg, earthquakes, hurricanes). In addition, there are patients whose access to specialty care is severely limited due to geographic constraints (eg, living many hours away from a center with expertise in the evaluation and management of IH) where these recommendations may prove beneficial.

With or without telemedicine, all patients with IH require careful consideration of risks and benefits of any proposed treatment, discussion with families regarding treatment options, and recommendations and information about possible adverse events from prescribed medications (Table 3) . For IH still in the rapid growth phase, we recommend particularly close follow-up, ideally within 1-2 weeks. Telemedicine is particularly well-suited for these typically brief follow-up visits to assure that the IH is behaving as anticipated.

Parents should be advised to reach out to practitioners in the context of changes in the IH (eg, ulceration, ongoing growth, development/ progression of functional impairment). If the patient develops respiratory symptoms (eg, cough, wheezing, respiratory distress), gastrointestinal symptoms (eg, vomiting, diarrhea, decreased intake), or lethargy, medication should be immediately discontinued and a physician notified. 22 Beta-blocker therapy information • https://heman gioma educa tion.org/heman gioma -treat ment/newhig-propr anolo l-educa tion-video -for-careg ivers • https://pedsd erm.net/site/asset s/files /1028/12_spd_propr anolol_color_web-final.pdf • https://heman gioma educa tion.org/syste mic-treat ment/ • https://heman gioma educa tion.org/topic al-and-local -treat ment/ a These links created or vetted by HIG members. 

Sheilagh Maguiness

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