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Propranolol for Infantile Hemangiomas

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					                                                                                     GLOBAL ADVANCES IN HEALTH AND MEDICINE
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                            Case RepoRt


                            propranolol for Infantile Hemangiomas
                            Moise L. Levy, MD, United States



     author affiliation
                            aBstRaCt                                                摘要                                                              sInopsIs
   Moise L. Levy, MD, is
    physician in chief in   Hemangiomas are common vascular                         血管瘤是常见的血管胎记,通常                                                  Los hemangiomas son marcas de
   Pediatric/Adolescent     birthmarks that usually present a pre-                  以一种可预测的模式进行增殖和                                                  nacimiento comunes de origen vascu-
   Dermatology at Dell      dictable pattern of proliferation and                   最终退化。大多数血管瘤都无需                                                  lar que acostumbran a seguir un
     Children’s Medical
Center of Central Texas,
                            ultimate involution. Most do not                        任何治疗。当干预治疗得到临床                                                  patrón predecible de proliferación y,
          Austin, Texas.    require any treatment. When inter-                      证明时,即可选择进行医药和手                                                  en última instancia, involución. La
                            vention is clinically indicated, medi-                  术治疗。从历史观点上来说,糖                                                  mayoría no requiere tratamiento y, en
               Citation     cal and surgical options exist.                         皮质激素已被用于并已被证实能                                                  los casos en que se aconseja realizar
Global Adv Health Med.
                            Historically, corticosteroids have                      够,减缓或停止大多数血管瘤的                                                  una intervención por motivos clínic-
        2012;1(2):14-16.
                            been used and have been shown to                        生长;但随之出现的生长问题和                                                  os, existen opciones médicas y quirúr-
              Key Words
                            slow or stop the growth of a majority                   感染性并发症使该类药物的使用                                                  gicas. Históricamente, se ha demostra-
          Hemangioma,       of hemangiomas; however, growth                         变得更加复杂。在 2008 年,刊登                                              do que el uso de corticosteroides
      propranolol, beta     concerns and infectious complica-                       在《新英格兰医学期刊》(The New                                             reduce o detiene el crecimiento de la
blocker, corticosteroids,
                            tions have complicated their use. In                    England Journal of Medicine) 上                                  mayoría de los hemangiomas; sin
    segmental, PHACE,
         posterior fossa    2008, a letter to the editor in The New                 的一封致编者信介绍了研究人员                                                  embargo, las complicaciones infeccio-
          malformation,     England Journal of Medicine described                   在九个病例中就非选择性 β 受体                                                sas y las preocupaciones en torno al
   arterial, cardiac, eye   another serendipitous observation of                    阻滞剂普萘洛尔治疗血管瘤的疗                                                  crecimiento han complicado su uso.
    anomalies, vascular
    birthmarks, timolol
                            the effect of the nonselective beta-                    效所偶然观察到的另一项结果。                                                  En el año 2008, una carta dirigida al
                            blocker, propranolol, on hemangio-                      这一发现由上述最初观察结果及                                                  editor publicada en The New England
                            mas in 9 cases. This finding has been                   其他结果的作者予以阐述。                                                    Journal of Medicine describía otra obser-
                            expanded by the authors of this origi-                                                                                  vación fortuita advertida en nueve
                            nal observation as well as others.                                                                                      casos sobre el efecto del betablo-
                                                                                                                                                    queante no selectivo propranolol en
                                                                                                                                                    los hemangiomas. Se han efectuado
                                                                                                                                                    trabajos de ampliación de este hallaz-
                                                                                                                                                    go por parte de los responsables de esta
                                                                                                                                                    observación original, entre otros.




                            B
                                   irthmarks are common and are seen in approxi-                                    Treatment of wound-related complications is also
                                   mately 8% of all newborns.1 Though they are                                      important for some such cases.
                                   usually of little significance from a clinical per-                                   This report will focus on medical therapies for
                            spective, they often are of concern to families.                                        hemangiomas. Historically, corticosteroids have been
                            Fortunately, a relatively small number of these are of                                  used after an early observation of their effect on the
                            medical significance. Clinicians describe hemangio-                                     proliferative phase of such lesions.6 A majority of
                            mas according to their growth characteristics, loca-                                    hemangiomas have been seen to slow in their growth
                            tion, and any associated complications, such as ulcer-                                  phase or stop altogether with the use of corticoste-
                            ation.2 Discrete hemangiomas are described as focal                                     roids. Due to often high-dose and long-term use, how-
                            and are distinguished from a broader or widespread                                      ever, growth concerns and infectious complications
                            growth pattern called segmental. Segmental heman-                                       associated with corticosteroids have complicated their
                            giomas, when occurring over particular areas of the                                     use.7 In 2008, a report in The New England Journal of
                            body, such as the face, often can be associated with                                    Medicine described another serendipitous observation
                            internal structural brain, vascular, cardiac, and/or eye                                of the effect of the nonselective beta-blocker, propran-
                            abnormalities.3 The association known as PHACE syn-                                     olol, on hemangiomas.8 Since that time, multiple
                            drome is now well characterized to describe the find-                                   reports have confirmed its often remarkable effects on
                            ings of posterior fossa malformation, (segmental)                                       the growth and evolution of these common birth-
                            hemangioma, arterial, cardiac, and eye anomalies.4,5                                    marks.9,10 Concerns regarding potential side effects
                            With any hemangioma, management options include                                         and the most appropriate means of administration
                            observation for the expected ultimate resolution, med-                                  continue to guide ongoing clinical experience with
                            ical treatments, laser treatment, or surgical removal.                                  this very exciting new treatment modality.


            14              Volume 1, Number 2 • May 2012 • www.gahmj.com                                                                                                                    Case Report
                                                 ProPrANoLoL for INfANTILe HemANgIomAS




                                                                                                         




                       July 2008 – april 2009                                                  July 2008 – april 2009




                                                                                                        




                    March 2009 – January 2012                                               March 2009 – January 2012


Figure Videos showing patient prior to and during treatment with propranolol. reprinted with permission from AngelPHACe.com.

HIstoRy                                                                  was noted by ultrasound performed at 20 weeks. She was
     A 1-month-old girl was first seen for evaluation of a               delivered by Cesarean section at 39 weeks.
facial birthmark. Her history was significant for a fetal                     An erythematous plaque was seen on the right face,
magnetic resonance imaging study at 24 weeks’ gestation                  upper and lower lips, and back of her head. She was felt to
that showed absent corpus callosum after hydrocephalus                   have a large segmental facial hemangioma, and due to the


Case Report                                                                                  www.gahmj.com • Volume 1, Number 2 • May 2012   15
                                                 GLOBAL ADVANCES IN HEALTH AND MEDICINE




     nature and location of the hemangioma, concern for              patients with large facial segmental lesions are noted to
     PHACE syndrome was discussed with the family. Further           have PHACE syndrome.14 In this setting, often significant
     imaging of the head and neck, as well as the heart, was         head and/or neck arterial anomalies can occur, which
     ordered, and options for management of the hemangioma           might cause concern about the use of medications such as
     were discussed. An ophthalmologic examination was also          propranolol. While there is increasing experience with
     conducted. Based upon imaging and eye-examination               this agent for the management of large hemangiomas, a
     findings, PHACE syndrome was diagnosed. Laser and               variety of methods of evaluation prior to its use exist.
     corticosteroids were reviewed and wound care for a small        Similarly, some physicians begin treatment with pro-
     area of ulceration of the upper lip was discussed.              pranolol on an outpatient basis and others (usually for
                                                                     selected patients) use it in the inpatient setting. At this
     tReatMent                                                       time, the use of propranolol for this indication must be
           Corticosteroids were begun at the time of the initial     considered on an individual basis with respect to clinical
     visit at a dose of 2 mg/kg/day. Enrollment in the PHACE         need and available resources and expertise for follow-up.
     syndrome registry was also suggested. Patients with a                 Finally, this patient also received topical timolol,
     diagnosis of PHACE syndrome may have any or all of the          which is a topical beta blocker indicated for ophthalmo-
     conditions associated with it (eg, large segmental/patchy       logic use. Reports have cited its utility for some cases of
     facial hemangiomas, eye, brain, head/neck vessel abnor-         hemangioma.11,12 Again, matching its use to individual
     malities, heart abnormalities). Diagnostic criteria are now     lesions has not been clearly defined. Issues relative to its
     well described.5                                                potential absorption at certain skin sites and for particular
           The hemangioma stabilized over the next month.            lesions, such as ulcerated hemangiomas, also need to be
     When the dose of the medication was decreased, the              clarified. In this instance, there have been no complica-
     lesion’s growth resumed, requiring an increase in the dose      tions with its use, and some utility for ongoing manage-
     of the medication. After several months of therapy, the         ment of this hemangioma has been noted by the child’s
     hemangioma again stabilized. After approximately 4              parents and this physician.
     months of therapy, the report in The New England Journal of
     Medicine about propranolol use for infantile hemangiomas        ConClusIon
     was discussed with the family.8 The patient was begun on             This brief report reviews the successful use of pro-
     a low dose of the medication with a slow advance of the         pranolol for a complicated segmental hemangioma in
     dose concurrent with a decrease in the dose of the cortico-     the setting of PHACE syndrome. Careful monitoring of
     steroid 1 month after publication of that report.               blood pressure and serum glucose appears to be appropri-
           When the patient was seen in the office 1 week later,     ate for ongoing use of this medication. Pretreatment
     dramatic response of the hemangioma was noted. A cau-           evaluation is of importance for all patients being consid-
     tious decrease of the corticosteroid was continued over         ered for such treatment and should be individualized
     the next several months, and the propranolol was contin-        based upon each child.
     ued with periodic adjustments of the dose consistent with
                                                                     ReFeRenCes
     her growth. Approximately 10 months after starting the            1. Alper JC, Holmes LB. The incidence and significance of birthmarks in a cohort
     propranolol, a tapering schedule of the medication was               of 4,641 newborns. Pediatr Dermatol. 1983;1(1):58-68.
                                                                       2. Chang LC, Haggstrom AN, Drolet BA, et al. Growth characteristics of infantile
     begun (when the patient was 15 months old). She was off
                                                                          hemangiomas: implications for management. Pediatrics. 2008;122(2):360-7.
     of the medication approximately 1 month later.                    3. Haggstrom AN, Lammer EJ, Schneider RA, Marcucio R, Frieden IJ. Patterns of
           When the patient was seen in the office 6 to 7                 infantile hemangiomas: new clues to hemangioma pathophysiology and
                                                                          embryonic facial development. Pediatrics. 2006:117(3):698-703.
     months later, some further ulceration of the hemangioma           4. Metry DW, Haggstrom AN, Drolet BA. A prospective study of PHACE syn-
     and discomfort were noted. Wound care and timolol solu-              drome in infantile hemangiomas: demographic features, clinical findings, and
     tion were started.11,12 The topical care was continued for           complications. Am J Med Genet A. 2006;140(9):975-86.
                                                                       5. Metry D, Heyer G, Hess C. Consensus statement on diagnostic criteria for
     several months with very good results (Figure).                      PHACE syndrome. Pediatrics 2009;124(5):1447-56.
           During the management of the hemangioma, the                6. Fost NC, Esterly NB. Successful treatment of juvenile hemangiomas with pred-
     patient was also seen by neurology, ophthalmology, and               nisone. J Pediatr. 1968;72(3):351-7.
                                                                       7. Frieden IJ, Eichenfield LF, Esterly NB, Geronemus R, Mallory SB. Guidelines for
     developmental specialists.                                           care of hemangiomas of infancy. American Academy of Dermatology
                                                                          Guidelines/Outcomes Committee. J Am Acad Dermatol. 1997;37(4):631-7.
                                                                       8. Leaute-Labreze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB,
     DIsCussIon
                                                                          Taïeb A. Propranolol for severe hemangiomas of infancy. N Engl J Med.
          Several issues must be emphasized regarding this                2008;358(24):2649-51.
     case. First of all, when clinicians evaluate patients with        9. Sans V, de la Roque ED, Berge J, et al. Propranolol for severe infantile hemangio-
                                                                          mas: Follow-up report. Pediatrics. 2009;124(3):e423-31.
     vascular birthmarks, arriving at the correct diagnosis is        10. Hogeling M, de la Roque ED, Berge J, et al. A randomized controlled trial of pro-
     key to considering appropriate treatments. While most of             pranolol for infantile hemangiomas. Pediatrics. 2011;128(2):e259-66.
     such lesions can be easily classified, this is not always the    11. Guo S, Ni N. Topical treatment for infantile hemangioma of the eyelid using
                                                                          beta-blocker solution. Arch Ophthal. 2010;128(2):255-6.
     case.13 Secondly, when infantile hemangiomas are diag-           12. Pope E, Chakkittakandiyil A. Topical timolol gel for infantile hemangiomas: a
     nosed, physicians should be aware of the implications of             pilot study. Arch Dermatol. 2010;146(5):564-5.
     segmental (vs focal) lesions. As noted above, criteria for       13. Hassanein AH, Mulliken JB, Fishman SJ, Greene AK. Evaluation of terminology for
                                                                          vascular anomalies in current literature. Plast Reconstr Surg. 2011;127(1):347-51.
     consideration of PHACE syndrome must be kept in mind             14. Haggstrom AN, Garzon MC, Baselga E, et al. Risk for PHACE syndrome in
     and the diagnosis pursued. Approximately 30% of                      infants with large facial hemangiomas. Pediatrics. 2010;126(2):e418-26.




16   Volume 1, Number 2 • May 2012 • www.gahmj.com                                                                                          Case Report

				
DOCUMENT INFO
Description: Moise L. Levy, MD, is physician in chief in Pediatric/Adolescent Dermatology at Dell Children’s Medical Center of Central Texas, Austin, Texas.