Elsevier

Seminars in Perinatology

Volume 37, Issue 1, February 2013, Pages 49-58
Seminars in Perinatology

Update on infantile hemangiomas

https://doi.org/10.1053/j.semperi.2012.11.003Get rights and content

Abstract

Infantile hemangiomas are the most common tumors of infancy. The serendipitous discovery of the therapeutic efficacy of propranolol in the management of infantile hemangiomas has revolutionized the care and understanding of these lesions, and greatly improved the prognosis for a good cosmetic outcome. In addition, there has been an expansion of indications for treatment of hemangiomas, taking into account not only those hemangiomas that can cause airway compromise, amblyopia, and cardiac overload, but also those lesions that can lead to unsatisfactory cosmetic outcome or deformity after involution. Current concepts of pathogenesis of infantile hemangiomas, of segmental hemangiomas with systemic associations, of hepatic hemangiomas, and of the use of systemic and topical beta-blockers for the management of IH are all reviewed.

Introduction

Infantile hemangiomas (IH) are the most common tumor of infancy, affecting up to 4–5% of infants.1 These tumors are more common in female infants, in Caucasians, in multiple births, and in infants of low birth weight, regardless of gestational age. Although typically benign, both microscopically and in clinical behavior, these tumors can compromise breathing or feeding, obstruct vision leading to amblyopia, cause high-output cardiac failure or hypothyroidism due to visceral involvement, produce painful ulceration and bleeding, be associated with tethering of the spinal cord or severe genitourinary abnormalities, or lead to permanent and significant residual cosmetic deformity. Infantile hemangiomas are described as localized (focal), meaning that they are spatially confined, or segmental, covering a neurovascular territory (Fig. 1). Sometimes, the lesions are indeterminate. They may be superficial (in the dermis), deep (in the adipose tissue), or demonstrate mixed superficial and deep morphology. This review seeks to provide an update on the pathogenesis, clinical manifestations, and treatment options for IH.

Section snippets

Pathogenesis

The pathogenesis of IH has been recently reviewed.2 Infantile hemangiomas arise from endothelial stem cells,3, 4 and later proliferate by vasculogenesis, the recruitment of endothelial precursor cells to the sites of new vessel formation followed by maturation of the cells. Hemangiomas evolve through three phases: proliferation, involution, and involuted. The proliferative phase lasts from shortly after birth until up to one year, but is usually shorter, and occasionally longer. During this

Segmental hemangiomas with systemic involvement

Although the majority of IH affect only the territory in which they are situated, i.e., the skin and underlying structures, there are segmental hemangiomas that are associated with regional congenital anomalies or systemic complications, some of which can be quite deleterious. Segmental hemangiomas are associated with developmental neuroectodermal segments and respect embryologic anatomic boundaries, rather than being focal (i.e., limited to one area). These can be linear or geographic,

Treatment

Treatment is indicated for any infant with IH that obstruct vital structures such as the airway or visual pathway, symptomatic ulcerated hemangiomas, complex hepatic hemangiomas, asymptomatic lesions that continue to grow in size, mid-facial lesions that threaten permanent disfigurement, or large lesions that cause cardiac overload. Prompt treatment during the proliferative phase has the potential to arrest growth, leading to involution of the hemangioma. Use of propranolol for late hemangiomas

Conclusion

The serendipitous discovery of the therapeutic efficacy of propranolol in the management of infantile hemangiomas has revolutionized the care and understanding of these lesions, and greatly improved the prognosis for a good cosmetic outcome. The rapidity with which it has become first-line therapy, and its striking effectiveness in numerous published series, have made conducting randomized controlled trials problematic. Indeed, the same can also be said of other revolutionary therapies in the

References (92)

  • J.Q. Mo et al.

    GLUT1 endothelial reactivity distinguishes hepatic infantile hemangioma from congenital hepatic vascular malformation with associated capillary proliferation

    Hum Pathol

    (2004)
  • J. Mazereeuw-Hautier et al.

    Efficacy of propranolol in hepatic infantile hemangiomas with diffuse neonatal hemangiomatosis

    J Pediatr

    (2010)
  • M. Saint-Jean et al.

    Propranolol for treatment of ulcerated infantile hemangiomas

    J Am Acad Dermatol

    (2011)
  • N. Raol et al.

    Propranolol for the treatment of subglottic hemangiomas

    Int J Pediatr Otorhinolaryngol

    (2011)
  • D.J. Hermans et al.

    Propranolol, a very promising treatment for ulceration in infantile hemangiomas: a study of 20 cases with matched historical controls

    J Am Acad Dermatol

    (2011)
  • R. Buchhorn et al.

    Propranolol treatment of congestive heart failure in infants with congenital heart disease: The CHF-PRO-INFANT Trial. Congestive heart failure in infants treated with propanol

    Int J Cardiol

    (2001)
  • A.S. Pickoff et al.

    High-dose propranolol therapy in the management of supraventricular tachycardia

    J Pediatr

    (1979)
  • E.A. Palmer

    How safe are ocular drugs in pediatrics?

    Ophthalmology

    (1986)
  • C.D. McMahon et al.

    Timolol and pediatric glaucomas

    Ophthalmology

    (1981)
  • R.J. Olson et al.

    Apneic spells associated with timolol therapy in a neonate

    Am J Ophthalmol

    (1979)
  • C. Kilcline et al.

    Infantile hemangiomas: how common are they? A systematic review of the medical literature

    Pediatr Dermatol

    (2008)
  • L.C. Uihlein et al.

    Pathogenesis of infantile hemangiomas

    Pediatr Ann

    (2012)
  • J. Bischoff

    Progenitor cells in infantile hemangioma

    J Craniofac Surg

    (2009)
  • Z.A. Khan et al.

    Multipotential stem cells recapitulate human infantile hemangioma in immunodeficient mice

    J Clin Invest

    (2008)
  • J.K. Wu et al.

    A switch in Notch gene expression parallels stem cell to endothelial transition in infantile hemangioma

    Angiogenesis

    (2010)
  • J.K. Wu et al.

    A potential role for notch signaling in the pathogenesis and regulation of hemangiomas

    J Craniofac Surg

    (2009)
  • D. Xu et al.

    Isolation, characterization, and in vitro propagation of infantile hemangioma stem cells and an in vivo mouse model

    J Hematol Oncol

    (2011)
  • S. Greenberger et al.

    Corticosteroid suppression of VEGF-A in infantile hemangioma-derived stem cells

    N Engl J Med

    (2010)
  • D.S. Cheung et al.

    Hemangioma in twins

    Ann Plast Surg

    (1997)
  • J.F. Grimmer et al.

    Familial clustering of hemangiomas

    Arch Otolaryngol Head Neck Surg

    (2011)
  • M.J. Dillon et al.

    Plasma renin activity and aldosterone concentration in children

    Br Med J

    (1975)
  • M.M. Tollefson et al.

    Early growth of infantile hemangiomas: what parents’ photographs tell us

    Pediatrics

    (2012)
  • L.C. Chang et al.

    Growth characteristics of infantile hemangiomas: implications for management

    Pediatrics

    (2008)
  • Couto RA, Maclellan RA, Zurakowski D, Greene AK. Infantile hemangioma: clinical assessment of the involuting phase and...
  • R.E.G.E. Bowers et al.

    Arch Dermatol

    (1960)
  • R.A. Couto et al.

    Infantile hemangioma: clinical assessment of the involuting phase and implications for management

    Plast Reconstr Surg

    (2012)
  • M.J. Razon et al.

    Increased apoptosis coincides with onset of involution in infantile hemangioma

    Microcirculation

    (1998)
  • I. Iacobas et al.

    LUMBAR: association between cutaneous infantile hemangiomas of the lower body and regional congenital anomalies

    J Pediatr

    (2010)
  • I.J. Frieden et al.

    PHACE syndrome. The association of posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities

    Arch Dermatol

    (1996)
  • D.W. Metry et al.

    A prospective study of PHACE syndrome in infantile hemangiomas: demographic features, clinical findings, and complications

    Am J Med Genet A

    (2006)
  • A.N. Haggstrom et al.

    Risk for PHACE syndrome in infants with large facial hemangiomas

    Pediatrics

    (2010)
  • D.W. Metry et al.

    PHACE syndrome: current knowledge, future directions

    Pediatr Dermatol

    (2009)
  • D. Metry et al.

    Consensus statement on diagnostic criteria for PHACE syndrome

    Pediatrics

    (2009)
  • Hess C.P., Fullerton H.J., Metry D.W., et al. Cervical and intracranial arterial anomalies in 70 patients with PHACE...
  • D.H. Siegel et al.

    Stroke in children with posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities (PHACE) syndrome: a systematic review of the literature

    Stroke

    (2012)
  • R.P. Rao et al.

    PHACES association: a vasculocutaneous syndrome

    Pediatr Cardiol

    (2008)
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