Diagnosis and Management of Infantile Hemangioma

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137. Poetke M, Philipp C, Berlien HP. Flashlamp-pumped pulsed dye laser for hemangiomas in infancy: treatment of superficial vs mixed hemangiomas. Arch Dermatol 2000 May;136(5):628-32. PMID: 10815856. 138. Blei F, & Chianese, J. Corticosteroid toxicity in infants treated for endangering hemangiomas: experience and guidelines for monitoring. International Pediatrics 1999;14:146-53. 139. Boon LM, MacDonald DM, Mulliken JB. Complications of systemic corticosteroid therapy for problematic hemangioma. Plast Reconstr Surg 1999 Nov;104(6):1616-23. PMID: 10541160. 140. Zide BM, Glat PM, Stile FL, et al. Vascular lip enlargement: Part I. Hemangiomas--tenets of therapy. Plast Reconstr Surg 1997 Dec;100(7):1664-73. PMID: 9393462. 141. Gangopadhyay AN, Sharma SP, Gopal SC, et al. Local steroid therapy in cutaneous hemangiomas. Indian Pediatr 1996 Jan;33(1):31-3. PMID: 8772948. 142. Sadan N, Wolach B. Treatment of hemangiomas of infants with high doses of prednisone. J Pediatr 1996 Jan;128(1):141-6. PMID: 8551406. 143. Chowdri NA, Darzi MA, Fazili Z, et al. Intralesional corticosteroid therapy for childhood cutaneous hemangiomas. Ann Plast Surg 1994 Jul;33(1):46-51. PMID: 7944196. 144. Morelli JG, Tan OT, Yohn JJ, et al. Treatment of ulcerated hemangiomas infancy. Arch Pediatr Adolesc Med 1994 Oct;148(10):1104-5. PMID: 7921107. 145. Preeyanont P, Nimsakul N. The Nd:YAG laser treatment of hemangioma. J Clin Laser Med Surg 1994 Aug;12(4):225-9. PMID: 10147482. 146. Morrell AJ, Willshaw HE. Normalisation of refractive error after steroid injection for adnexal haemangiomas. Br J Ophthalmol 1991 May;75(5):301-5. PMID: 2036349. 147. Kushner BJ. Infantile orbital hemangiomas. International Pediatrics 1990;5(3):249-57. 148. Sloan GM, Reinisch JF, Nichter LS, et al. Intralesional corticosteroid therapy for infantile hemangiomas. Plast Reconstr Surg 1989 Mar;83(3):459-67. PMID: 2919200. 149. Kushner BJ. The treatment of periorbital infantile hemangioma with intralesional corticosteroid. Plast Reconstr Surg 1985 Oct;76(4):517-26. PMID: 4034770. 150. Healy G, McGill T, Friedman EM. Carbon dioxide laser in subglottic hemangioma. An update. Ann Otol Rhinol Laryngol 1984 Jul-Aug;93(4 Pt 1):370-3. PMID: 6431866. 151. Sharma LK, Dalal SS. Corticosteroid therapy in the treatment of cutaneous hemangioma of infancy and childhood. Indian J Pediatr 1983 Mar- Apr;50(403):153-6. PMID: 6618575. F-25
Appendix G. Applicability Tables Table G-1. Applicability of studies assessing imaging modalities Domain Description of applicability of evidence Population Intervention Comparator s Outcomes Setting Infants with hemangiomas (with mean ages of 30 days and 34 weeks). Fair distribution of male and female patients. Radiologic evaluation of hepatic hemangioma to determine which lesions required intervention and radiologic evaluation of lumbosacral cutaneous hemangiomas to evaluate which were associated with occult spinal dysraphism Comparators included ultrasound, magnetic resonance imaging, computed tomography and angiography. If different modalities were utilized on the same patient, it was sometimes not at the same time point making comparison between methods difficult. Studies assessed imaging and clinical findings and with need for intervention for hepatic hemangiomas and the second study reviewed incidence of occult spinal dysraphism found in patients with lumbosacral hemangioma Studies were conducted in the US, Canada and Spain at tertiary care centers with referral programs for hemangiomas / vascular malformations Table G-2. Applicability of studies assessing steroids Domain Description of applicability of evidence Population Intervention Comparator s Outcomes Setting IH-infantile hemangioma Infants and children with IH (ages ranging from less than one to 72 months). Typically more females. Corticosteroids including topical, intralesional, intravenous, and oral forms. Comparators included another steroid or observation. Studies generally assessed change in lesion size and/or appearance and rebound growth. Two studies assessed vision outcomes. Comparative studies and case series also reported harms. One comparative study was conducted in Canada and the others in the Netherlands, Germany, Turkey, Pakistan, and India. Applicability of some findings may be limited given differences in the systems of care in lower resource countries. Several comparative studies were also published between 2001 and 2010 and may not reflect current standards of care. Table G-3. Applicability of studies assessing beta-blockers Domain Description of applicability of evidence Population Studies typically included infants of both sexes ages 1 to 12 months of age (range: 1 month to 9 years of age) with infantile hemangiomas which included superficial, deep, and mixed lesions primarily involving the head and neck and occurring as focal or segmental lesions. Intervention Patients were treated with a variety of beta-blockers including propranolol at various doses and administrations (oral, intralesional, or topical), timolol (topical), atenolol (oral), or nadolol (oral) for a variety of treatment durations most commonly up to 6 months duration. Comparator s Outcomes Setting Comparators included other formulations of the same beta-blocker, other beta-blockers, untreated historical controls, treated historical controls, and non-beta-blocker comparators (topical imiquimod, oral and intralesional steroids, laser, and intralesional bleomycin). Studies commonly assessed final response based on size, volume, and/or coloration of IH, resolution of ulceration if present at initiation of therapy, and visual acuity or resolution of ptosis for periocular lesions. Assessments were obtained throughout therapy but final outcome assessments were typically performed following 24 weeks of treatment. Additional assessments for serious harms including bronchial hyperreactivity, hypoglycemia, bradycardia, and hypotension and less severe harms including sleep disturbances, cold extremities, and gastrointestinal complaints were monitored in the majority of studies. Studies were conducted globally, often in speciality referral centers. G-1
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Comparative Effectiveness Review Nu
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This report is based on research co
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Acknowledgments The authors gratefu
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Peer Reviewers Prior to publication
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BCI; moderate SOE for effects of pr
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Overview of the Literature ........
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Executive Summary Introduction Infa
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for contextual questions as few eff
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Figure B. Analytic framework for KQ
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Table A. Inclusion criteria (contin
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precision (precise, imprecise), and
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Figure D. Estimates of expected IH
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majority of studies to date have in
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effectiveness outcomes. The evidenc
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changes. We considered the strength
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Table C. Summary of evidence in stu
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Table D. Summary of evidence in stu
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Applicability We set inclusion crit
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quantitative meta-analyses. Researc
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surgically. Lesion characteristics
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References 1. Wassef M, Blei F, Ada
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39. Yu L, Li S, Su B, et al. Treatm
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modalities. The questions of imagin
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KQ2. Among newborns, infants, and c
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of data, and compiling evidence. We
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We only included studies published
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a standardized form (Appendix B) th
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Determining Quality Ratings • We
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Results We present results for Cont
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defects, urogenital anomalies, ulce
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Results of Literature Searches for
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Table 3. Characteristics of include
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scans, had a sensitivity of 20 perc
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of the model fit to all studies, bu
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Detailed Analysis Effectiveness of
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Table 6. Key resolution outcomes in
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with prednisolone included endocrin
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children in 8 studies), skin atroph
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hypopigmentation, impaired wound he
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fair quality for effectiveness outc
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studies of nadolol and atenolol. No
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Table 10. Key resolution outcomes i
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old. 100 Thirty percent of children
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Table 11. Resolution outcomes in st
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Table 15. Key outcomes in studies c
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Table 22. Harms/adverse effects in
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Table 24. Adverse effects in case s
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Table 24. Adverse effects in case s
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• In two RCTs reporting level of
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Nd:YAG Laser With Cooling Compared
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long term follow information was av
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Discussion State of the Literature
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Table 34. Strength of evidence for
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Effectiveness and Harms of Beta-Blo
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older children. One comparative stu
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case series reporting on rarer pres
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agents is critical, especially as u
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References 1. Wassef M, Blei F, Ada
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39. Chen TS, Eichenfield LF, Friedl
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80. Mai HM, Zheng JW, Wang YA, et a
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119. Sharma LK, Dalal SS. Corticost
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162. Snir M, Reich U, Siegel R, et
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198. Chen ZG, Zheng JW, Yuan ML, et
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237. Healy G, McGill T, Friedman EM
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Abbreviations and Acronyms Used in
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Appendix A. Search Strategies Searc
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Searches for Comparative Effectiven
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Appendix B. Screening and Quality A
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Harms Risk of Bias Assessment Form
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QUADAS Diagnostic Accuracy Rating T
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Infantile Hemangioma CER: Risk of B
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20. Grundfest-Broniatowski S, Carey
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65. Dachman AH, Lichtenstein JE, Fr
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111. Yoshida T, Kuratomi K, Mitsuma
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160. Newman SL, Goodwin CD. Colonic
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204. Crockett DM, Healy GB, McGill
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253. Wright GL, Smith RJ, Katz CD,
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301. Paley D, Jackson RW. Synovial
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346. Dombrowski MP, Budev H, Wolfe
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390. Stringel G. Giant hemangioma:
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436. Liu HC, Chang MH, Lue HC, et a
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480. Casale AJ, Menashe DS. Massive
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526. Taylor RS, Joseph DB, Kohaut E
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571. Goldstein MH. The elastic flap
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614. Salloum E, Flamant F, Caillaud
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659. Fellows KE, Hoffer FA, Markowi
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706. Weatherford DA, Abrams RS, Wal
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749. Keleti D, Flickinger JC, Hobso
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793. Van Campenhout I, Patriquin H.
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836. Goldman MP, Fitzpatrick RE, Ru
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880. Schulman SR, Jones BR, Slotnic
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3243. Soltani AM, Reinisch JF. Algo
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3286. . Derm Dx. Clinical Advisor.
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3326. Chang YT, Lin JY, Lee JY, et
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3407. Kupeli S. Use of propranolol
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3448. Raches D, Hiscock M, Chapiesk
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3490. Traivaree C, Lumkul R, Torcha
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3614. Hyland RM, Komlosi K, Alleman
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Page 363 and 364: 3851. Khorsand K, Backus S, Sidbury
Page 365 and 366: 3890. Phillips RJ, Lokmic Z, Crock
Page 367 and 368: 3930. Weil AG, Bhatia S. Resection
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Page 403: 120. Pandey A, Gangopadhyay AN, Gop
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Page 417 and 418: Timoptic® (timolol maleate) 15 Tim
Page 419 and 420: Harms Data for Medications Included
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Page 425 and 426: thromboembolism, thrombophlebitis,
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Page 431 and 432: Discontinuations Patients utilizing
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Diagnosis and Management of Infantile Hemangioma

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