PICO #1 Population(s): Children with infantile hemangiomas (IHs) Intervention(s): Early referral Comparator(s): Delayed referral Outcomes(s): Minimization of functional impairment and/or cosmetic deformity

PICO #2 Population(s): Children with infantile hemangiomas (IHs) Intervention(s): Systemic (enteral) medical therapy using propranolol Comparator(s): Systemic (enteral) medical therapy using corticosteroids Outcomes(s): Minimization of functional impairment and/or cosmetic deformity, enhancement of IH involution, safety

PICO #3 Population(s): Children with infantile hemangiomas (IHs) Intervention(s): Pulsed dye laser treatment Comparator(s): Observation Outcomes(s): Healing of ulceration and/or pain reduction, minimization of cosmetic deformity, enhancement of IH involution, safety

PICO #4 Population(s): Children with infantile hemangiomas (IHs) Intervention(s): Imaging by use of MRI, CT, or ultrasound Comparator(s): No use of imaging Outcomes(s): Accuracy of diagnosis, identification of complications or potential complications

Questions: 1) Which IHs should undergo early evaluation by a specialist in vascular anomalies? (Consider orbital lesions, ulcerated lesions, segmental lesions, syndromic lesions [PHACE], lesions of lip and nasal tip)

2. When medical therapy (corticosteroids or propranolol) is justified for treatment of IH, considering both efficacy and safety, is one therapy superior to the other?

3. Is laser treatment safe in the treatment of proliferating IH?

4. When is imaging indicated in the evaluation of IH? Traditionally, IH management has been governed by the concept of "benign neglect"; that is, left alone, these lesions will simply go away. More recent information suggests these lesions should be managed expectantly, including early referral to a vascular anomalies specialist for lesions likely to develop complications. We would like to assess the difference in outcomes in patients referred early vs. those for whom referral may have been delayed or not recommended.

The other analyses would compare: 1) safety and efficacy of the two primary medical interventions for IHs, propranolol and corticosteroids, 2) safety and efficacy of pulsed dye laser treatment of IHs to that of no treatment, and 3) safety and efficacy of imaging to that of no imaging

The population includes all infants under 12 months of age with IH. The subgroups to which the question would apply include children with PHACE or other IH syndromes, as well as those with IH of specific morphology as described in Part 1 above. Specific outcomes to consider include reductions in:

1. Life-threatening complications of IH (i.e. high output cardiac failure)
2. Ocular complications (astigmatism, strabismus, amblyopia, ptosis or visual field cuts)
3. Scarring and residual fibrofatty changes causing long-term cosmetic deformity
4. Pain and/or bleeding associated with ulceration
5. Avoidance of unnecessary sedation and/or radiation exposure for imaging Harms include:
6. Risks associated with non intervention are described above
7. Risks of medical therapy including beta-blockers and corticosteroids
8. Risks of laser treatment (changes in skin pigmentation, ulceration)
9. Risks associated with sedation and/or radiation exposure for imaging

Infantile hemangiomas (IHs) are the most common tumors of childhood. Unlike other tumors, they have the unique ability to involute after proliferation, often leading primary care providers to assume they will resolve without intervention or consequence. Unfortunately, a subset of IHs rapidly develops complications that cause pain, functional impairment, or permanent disfigurement.

IHs typically become apparent prior to 4 weeks of age. Although they proliferate for variable periods of time, most IH growth appears to occur between one and two months of age, and 80% of IH size is generally reached by 3 months. By the time the need for specialist evaluation is determined and an appointment for such evaluation is made and completed, IHs have often already resulted in complications.

There is currently no algorithm to aid clinicians in determining which IH lesions require specialist evaluation, how early and to whom referral should be made, and what early intervention, if any, is most appropriate. The function of the proposed document is to provide such guidance.

The Sections on Otolaryngology-Head & Neck Surgery, Dermatology, and Plastic Surgery recently authored a Clinical Report on Infantile Hemangiomas. In the course of its preparation, it became apparent that there is still considerable variability in the treatment of IH. For example, while propranolol has become popular as the primary medical modality, corticosteroids are still favored by some clinicians. The response rates to both medications are not 100%, and indications for alternatives including systemic agents, topical agents, and lasers remain unclear.

Furthermore, interaction during Continuing Medical Education activities has suggested that primary providers of pediatric care have had limited experience with the diversity of vascular lesions in children, to new data regarding growth rates of IH, to the potential complications of IH and the urgency for early referral, and to the indications for and process of initiating medical therapy for IH. Strong support for such a guideline comes from the Vascular Birthmarks Foundation (VBF) and the National Organization for Vascular Anomalies (NOVA).

As indicated above, there is considerable variability in care for IH among pediatric primary care providers. It is hoped that a guideline will, at least to a limited degree, provide some standardization in the approach to these lesions. In addition, insurers often deny care for IHs on the basis that such intervention is "cosmetic". A guideline based on the recent Clinical Report will clarify that interventions for IH are more appropriately considered reconstructive rather than cosmetic. At a consensus meeting in Bethesda, MD in 2005, an ad hoc group of basic science and clinical researchers in IH identified early specialist referral as the single most important factor that would improve clinical management of IHs. We continue to work across disciplines through the American Academy of Pediatrics to achieve this goal. In addition, recent research suggests that changes in evaluation and medical management of IH are warranted. The answers to the proposed research questions will serve as the foundation for an AAP Clinical Guideline that, publicized using the resources of the AAP, should effect significant change in the management of IH.

A clinical guideline and evidence based approach is needed within the year.

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