Management of Infantile Hemangiomas During the COVID-19 Pandemic

The COVID-19 pandemic has caused significant shifts in patient care, including a dramatic shift from ambulatory visits together with a marked increase in the use of telemedicine. The Hemangioma Investigator Group (HIG) met via videoconferencing on March 22, 2020 to draft recommendations to help practitioners managing infants with infantile hemangiomas (IH) and subsequently reached consensus re: these recommendations. Ordinarily, recommendations such as those we are proposing undergo a rigorous process of development, peer review, and refinement. Due to the extraordinary circumstances we find ourselves in, we felt that there was an immediate need for recommendations regarding the evaluation and management of IH, particularly the initiation of systemic beta-blockers. The HIG has worked as a group for nearly 20 years and members have participated in many studies and several consensus statements. The statement was reviewed by all HIG members and consensus was reached regarding its recommendations.

This is a summary of recommendations with the full text to be submitted for expedited review and (we hope) publication shortly in Pediatric Dermatology. In deciding which infants with IH have higher-risk IH and may require treatment, please refer to the American Academy of Pediatrics (AAP) Clinical Practice Guidelines (CPG) which reviews risk stratification and consensus treatment recommendations. It has several useful graphics and tables to help guide referral and treatment decisions¹.

The AAP guidelines also stress the importance of timing of intervention, when needed, as IH growth in the first weeks to few months of life can be very rapid. For higher risk IH, delaying treatment can result in poorer clinical outcomes. This is the central reason for this consensus statement, because delaying care until regular ambulatory visits are again the routine would undoubtedly result in increased morbidity for some patients with IH. Teletriage can be very useful in IH². A validated tool for IH referral, the so-called IH Referral Score (IHReS), has been developed for use by primary care physicians but can also be used by specialists who may occasionally see IH but do not see them regularly enough to feel comfortable in risk-stratifying them³. Telemedicine as a way of delivering care to infants with IH has not been systematically studied so we have had to rely on current evidence and our collective personal experience for this statement.

Oral or Topical Beta-Blocker Therapy Via Telemedicine

Central to our consensus recommendations are decisions about initiation of oral or topical beta-blocker therapy via telemedicine. We reviewed current FDA/EMA monitoring guidelines, published clinical practice guidelines (CPG) and other relevant publications regarding initiation and monitoring of beta-blocker therapy to determine the appropriate utilization of telemedicine in managing IH. FDA/EMA guidelines call for in-office cardiovascular monitoring for up to 2 hours, however there is now a growing body of experience in healthy infants without health risk factors suggesting that cardiovascular complications from propranolol use are rare, and that prolonged monitoring during initiation has limited clinical utility⁴.

Our recommendations are summarized in Table 1 with an accompanying algorithm. It divides patients into 2 groups. Group 1 includes patients with characteristics conferring a standard risk. As such these infants can be considered as appropriate candidates for telemedicine initiation of oral or topical beta-blocker therapy. Group 2 includes patients with higher risk characteristics. For these infants initiation of medication via telemedicine, particularly systemic beta-blockers, should be avoided or used only in exceptional circumstances. This approach recognizes that there are features which may increase risk of beta-blocker therapies and/or IH co-morbidities which are important to recognize. Our recommendations for these evaluations for standard versus higher risk can also be applied to the use of topical timolol as it is widely used as an off-label therapy, but does have a potential for significant percutaneous absorption⁵.

There was broad consensus that in-person evaluation for new patients, particularly young infants, is still the best approach when it is feasible: physical examination can be more thorough and may provide a more accurate assessment of baseline status including subtle clues (such as duskiness) that may indicate impending ulceration, the presence of deeper hemangioma not evident with photographs or video without palpation, as well as responses to previously-initiated treatment. Other advantages of in-person assessment include more accurate assessment of weight, respiratory and cardiovascular examinations at the time, and the opportunity for face-to-face counseling and establishing rapport with families, which is particularly important for infants who need treatment, since the medications used are typically continued for many months or longer.

At the same time, there was also group consensus that visits via telehealth platforms 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) and thus 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 of therapy.

With or without telemedicine, all patients with IH need to carefully consider risks and benefits of any proposed treatment, discussion with families regarding treatment options, recommendations and information about possible adverse events from prescribed medications. In those cases where IH are still in the growth phase, we recommend particularly close follow-up, ideally within 1-2 weeks. Telemedicine can be particularly well-suited to 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 (e.g. ulceration, ongoing growth, development/progression of functional impairment).

If the patient develops respiratory symptoms (e.g. cough, wheezing, respiratory distress), gastrointestinal symptoms (e.g. vomiting, diarrhea, decreased intake) or lethargy, medication should be temporarily discontinued and the prescribing practitioner should be notified. Comprehensive counseling and communication of potential risks and benefits of treatment are of paramount importance both for anticipatory guidance and to help minimize side effects. Online resources can be very helpful both in reinforcing education regarding the diagnosis of IH as well as specifics of treatment and possible side effects.

We hope that this information is useful to you in managing patients with infantile hemangiomas during this pandemic.

Sincerely,
Members of the Hemangioma Investigator Group

Drs. Ilona Frieden, Katherine Püttgen, Beth Drolet, Maria Garzon, Sarah Chamlin, Elena Pope, Anthony Mancini, Christine Lauren, Erin Mathes, Dawn Siegel, Deepti Gupta, Anita Haggstrom, Megha Tollefson, Eulalia Baselga, Kimberly Morel, Sonal Shah, Kristin Holland, Denise Adams, Kimberly Horii, Brandon Newell, Julie Powell, Catherine McCuaig, Amy Nopper, Denise Metry, Sheilagh Maguiness

General Hemangioma Information:

• SPD Infantile Hemangiomas Patient Perspectives Handout
• HIG: Infantile Hemangioma Education
• Wikipedia Hemangioma Reference Page
• AAP Health Initiatives: Infantile Hemangiomas

Beta-Blocker Therapy Information

• SPD Propranolol for Infantile Hemangiomas Patient Perspectives Handout
• HIG: Infantile Hemangioma Systemic Treatment
• HIG: Infantile Hemangioma Topical & Local Treatment

Table of Standard and Higher Risk Factors for Propranolol and other Beta-Blocker Therapy

Group 1: Standard Risk (Inclusion Criteria): Checklist of baseline patient & IH characteristics: May consider telemedicine initiation of oral or topical beta-blocker therapy* as long as infant does not have additional features listed for Group 2

• Adjusted gestational age > 5 weeks
• Normal birth weight
• Recent documented weight (within 2 weeks)
• Normal cardiovascular exam within previous 4 weeks (including >1 documented HR after nursery discharge)
• Normal respiratory exam within previous 4 weeks
• Healthy in the 24-48 hours prior to scheduled telemedicine visit (especially, no respiratory and gastrointestinal signs and symptoms
• IH pattern and distribution does not confer risk of PHACE or LUMBAR syndrome
• Lack of ulceration or minimal/superficial ulceration
• Caregiver is able to understand instructions and demonstrate comprehension (e.g. by repeating instructions provided during visit)
• Multiple IH with normal liver ultrasound and without cutaneous IH conferring risks noted in Group 2

Group 2 High Risk (Relative or Absolute Exclusion Criteria): If one or more of these findings is present, in-person ambulatory evaluation is recommended unless local circumstances make this impossible prior to initiation of systemic beta-blocker therapy*

• Corrected gestational age <5 weeks
• Abnormal cardiovascular exam or investigations OR those who lack documentation of this in the post-natal period
• Medium to high risk of PHACE (i.e. large segmental facial or scalp IH in segments S1, S3, S4)
• Medium to high risk of LUMBAR syndrome (i.e. segmental perineal and/or lumbosacral body IH +/- visible associated anatomic abnormalities
• Significant IH ulceration
• Ongoing poor oral feeding or poor weight gain
• IH with symptoms of airway compromise (e.g. stridor) or bilateral S3 (beard area IH at high risk for airway IH).
• Known pulmonary disease including ongoing respiratory compromise (e.g. dyspnea, frequent wheezing or history of bronchospasm)
• Persistent or ongoing hypoglycemia
  • Known or suspected congenital heart disease or suggestive symptoms
  • Known or suspected aortic coarctation
  • History of pathologic heart murmur or abnormal echocardiogram
  • Ongoing diaphoresis
  • Ongoing tachypnea
  • Ongoing tachycardia
  • History of syncope
• Extensive hepatic hemangiomas including those resulting in consumptive hypothyroidism or congestive heart failure
• Known brain malformation
• Family history in first degree relative of:
  • Congenital heart disease
  • Sudden death or arrhythmia
• Maternal history of connective tissue disorder (e.g. systemic lupus, Sjogren's, polymyositis, or other)

*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 made on a case-by-case basis.

**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 (e.g. ENT, cardiology, etc).

Selected References:

Krowchuk DP, Frieden IJ, Mancini AJ et al. Clinical Practice Guideline for the Management of Infantile Hemangiomas. Pediatrics. 2019 Jan;143(1). pii: e20183475. doi: 10.1542/peds.2018-3475.

de Graaf M, Knol MJ, Totté JE, et al. E-learning enables parents to assess an infantile hemangioma. J Am Acad Dermatol. 2014 May;70(5):893-8.

Léauté-Labrèze C, Baselga Torres E, Weibel L, et al. The Infantile Hemangioma Referral Score: A Validated Tool for Physicians. Pediatrics. 2020 April; 145(4). pii: e20191628. doi: 10.1542/peds.2019-1628.

Püttgen KB, Hansen LM, Lauren C, MD, Stefanko N et al. Utility of Repeated Vital Sign Monitoring During Initiation of Oral Propranolol for Complicated Infantile Hemangioma JAAD 2020 In Press.

Drolet BA, Boakye-Agyeman F, Harper B, et al. Systemic timolol exposure following topical application to infantile hemangiomas. J Am Acad Dermatol. 2020 Mar;82(3):733-736.