Infant’s growing birthmark causes blurry vision

Infant presents with a repidly growing birthmark on the left upper eyelid.

The Case

You are asked to see a healthy 3-month-old boy with a rapidly growing lump on his left upper eyelid. At birth there was a red macule that was diagnosed as a small port-wine birthmark. The infant was seen by a pediatric ophthalmologist who noted significant astigmatism of the left eye.

DERMCASE diagnosis } Infantile hemangioma

Pathogenesis, epidemiology, and classification

Infantile hemangiomas are benign vascular tumors that result from the proliferation of endothelial-like cells that express high levels of glucose transporter isoform 1 (GLUT1) and placenta-associated vascular antigens.¹ They develop early in life in 4% to 5% of infants.^2,3 There is a higher prevalence in females, non-Hispanic whites, premature infants (<37 weeks gestational age), infants of low birth weight (<2500g), and infants of multiple gestations.⁴ There also seem to be associations with older maternal age (≥30 years), placenta previa, and preeclampsia during the prenatal period.⁴

Hemangiomas are often classified morphologically as superficial, deep, or mixed.^5,6 A superficial hemangioma is red, nodular, and raised above the normal skin. A deep hemangioma typically presents as a subcutaneous skin-colored nodule or tumor with overlying bluish discoloration, with or without associated telangiectasia. Mixed hemangiomas contain both superficial and deep components.

Hemangiomas can be focal (localized and usually round or oval and relatively small); multifocal (same as focal but multiple hemangiomas); and segmental (covering a specific territory and usually large).⁶

Segmental hemangiomas are more likely to be associated with developmental abnormalities, including PHACE syndrome (posterior fossa malformations, large segmental hemangiomas, and arterial/cardiac/eye abnormalities).⁷ Therefore, these children require more intensive monitoring; are more likely to require medical therapy; and tend to have more complications (eg, ulceration) than children with localized hemangiomas.⁶

Children with multiple lesions can have as many as 30 focal hemangiomas or more, but visceral involvement appears to be rare and rates of complications in these children are comparable to those with localized types.⁶

Natural course

The natural progression of hemangiomas includes 2 phases: proliferation and spontaneous involution. The average hemangioma will reach 80% of its full size by 3 months with the majority of growth completed by 5 months of age.⁸ Following proliferation, the majority of hemangiomas begin to regress by 1 year of age. Involution is characterized by a change in color from bright red to dark, dull red with central graying, and softening and flattening of the lesion. Although most hemangiomas do not require treatment, half will leave some residual change such as telangiectasias, loose baggy skin, and/or fibrofatty tissue.

Hemangiomas must be distinguished from vascular malformations. A hemangioma is a vascular neoplasm that grows by cellular hyperplasia; a vascular malformation is a result of defective vascular morphogenesis.⁹ The differences are outlined in Table 1.^8-10

Complications and indications for referral

Hemangiomas in certain locations may have an increased risk of developing complications or being associated with other anomalies (Table 2).^10,11 These lesions often require closer follow-up, and timely referral to a pediatric dermatologist during the early proliferation phase (first few weeks to months of life) is essential in order to reduce morbidity and prevent long-term sequelae.

Management

Management of infantile hemangiomas is individualized based on size, morphology, and location. Because most lesions are benign and self-limited, the benefits of treatment must outweigh the potential risks.

Many pediatric dermatologists use oral propranolol as the first-line treatment for complex hemangiomas including large segmental hemangiomas; hepatic hemangiomas; and focal lesions associated with potential disfigurement and obstruction of vital structures such as the orbit, airway, external ear canal, anus, and genital area.¹ Most commonly reported adverse effects from oral propranolol therapy are sleep disturbances (reported in 3.7% of patients), asymptomatic hypotension (2.8%), and somnolence (2.2%).¹²

Other options for management include systemic glucocorticoids, intralesional glucocorticoids, and topical beta-blockers.¹ Rarely, vincristine and interferon alpha are indicated for aggressive, life-threatening hemangiomas that are unresponsive to propranolol or systemic glucocorticoids. While pulsed dye laser is occasionally used to treat ulceration, postinvolution erythema, and telangiectasia, there is controversy regarding its efficacy for the treatment of infantile hemangiomas.¹³ Finally, surgical excision is sometimes warranted for large pedunculated lesions or residual fibrofatty tumors.¹

Your patient

Growth of the patient’s hemangioma stopped within 2 days of initiating oral propranolol at 2 mg/kg/day in 2 divided doses, and you will continue to monitor his progress closely. He is tolerating the medication well, and you hope to taper him off propranolol in 6 to 9 months.

REFERENCES

1. Chen TS, Eichenfield LF, Friedlander SF. Infantile hemangiomas: an update on pathogenesis and therapy. Pediatrics. 2013;131(1):99-108.

2. Kilcline C, Frieden IJ. Infantile hemangiomas: how common are they? A systematic review of the medical literature. Pediatr Dermatol. 2008;25(2):168-173.

3. Munden A, Butschek R, Tom WL, et al. Prospective study of infantile haemangiomas: incidence, clinical characteristics and association with placental anomalies. Br J Dermatol. 2014;170(4):907-913.

4. Hemangioma Investigative Group, Haggstrom AN, Drolet BA, Baselga E, et al. Prospective study of infantile hemangiomas: demographic, prenatal, and perinatal characteristics. J Pediatr. 2007;150(3):291-294.

5. Drolet BA, Esterly NB, Frieden IJ. Hemangiomas in children. N Engl J Med. 1999;341(3):173-181.

6. Chiller KG, Passaro D, Frieden IJ. Hemangiomas of infancy: clinical characteristics, morphologic subtypes, and their relationship to race, ethnicity, and sex. Arch Dermatol. 2002;138(12):1567-1576.

7. Metry D, Heyer G, Hess C, et al; PHACE Syndrome Research Conference. Consensus statement on diagnostic criteria for PHACE syndrome. Pediatrics. 2009;124(5):1447-1456.

8. Chang LC, Haggstrom AN, Drolet BA, et al; Hemangioma Investigator Group. Growth characteristics of infantile hemangiomas: implications for management. Pediatrics. 2008;122(2):360-367.

9. Richter GT, Friedman AB. Hemangiomas and vascular malformations: current theory and management. Int J Pediatr. 2012;2012:645678. Epub May 7, 2012.

10. Habif TP. Vascular tumors and malformations. In: Clinical Dermatology: A Color Guide to DIagnosis and Therapy. 5th ed. Philadelphia, PA: Mosby/Elsevier; 2010:891-912.

11. Smolinski KN, Yan AC. Hemangiomas of infancy: clinical and biological characteristics. Clin Pediatr (Phila). 2005;44(9):747-766.

12. Drolet BA, Frommelt PC, Chamlin SL, et al. Initiation and use of propranolol for infantile hemangioma: report of a consensus conference. Pediatrics. 2013;131(1):128-140.

13. Batta K, Goodyear HM, Moss C, Williams HC, Hiller L, Waters R. Randomised controlled study of early pulsed dye laser treatment of uncomplicated childhood haemangiomas: results of a 1-year analysis. Lancet. 2002;360(9332):521-527.

Ms Chung is a fourth-year medical student at Johns Hopkins University School of Medicine, Baltimore, Maryland. Dr Cohen, section editor for Dermcase, is professor of pediatrics and dermatology, Johns Hopkins University School of Medicine, Baltimore. The authors have nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in any part of this article. Vignettes are based on real cases that have been modified to allow the authors to focus on key teaching points. Images also may be edited or substituted for teaching purposes.