754 Pediatric Dermatology Vol. 31 No. 6 November/December 2014

REFERENCES

Figure 2. Resolution of the keratoderma of the feet persisting 16 weeks after combination ivermectin and permethrin therapy.

dystrophy and no recurrence of her keratoderma (Fig. 2).

1. Gulbakke KK, Khachemoune A. Crusted scabies: a clinical review. J Drugs Dermatol 2006;5:221–227. 2. Roberts LJ, Huffman SE, Walton SF et al. Crusted scabies: clinical and immunological findings in seventyeight patients and a review of the literature. J Infect 2005;50:375–381. 3. Chouela E, Abeldano A, Pellerano G et al. Diagnosis and treatment of scabies: a practical guide. Am J Clin Dermatol 2002;3:9–18. 4. Jaramillo-Ayerbe F, Berrio-Munoz J. Ivermectin for crusted Norwegian scabies induced by use of topical steroids. Arch Dermatol 1998;134:143–145. 5. Meinking TL, Elgart GW. Scabies therapy for the millennium. Pediatr Dermatol 2000;17:154–156. Vanessa Fonseca, M.D.* Harper N. Price, M.D.* Michelle Jeffries, M.D.† Steven L. Alder, M.D.‡ Ronald C. Hansen, M.D.* *Department of Dermatology, Phoenix Children’s Hospital, Phoenix, Arizona, †Beatrice Keller Clinic, Peoria, Arizona, ‡Clin-Path Associates, Tempe, Arizona

DISCUSSION The clinical presentation of crusted scabies is variable. Keratoderma over acral surfaces, onychodystrophy, and erythrodermic dermatitis should prompt consideration of crusted scabies (1). A patient with crusted scabies may harbor more than a million mites (2), so scraping any affected site is highly likely to yield a definitive diagnosis. Mite eradication methods have classically involved topical scabicides. Permethrin 5% cream is the topical treatment of choice (3). Ivermectin as an oral scabicidal therapy has become increasingly common over the past decade (4). The standard recommended dose of ivermectin is 200 μg/kg administered as a single dose and repeated 10 to 14 days later (5). Although the U.S. Food and Drug Administration has not approved it for use in children younger than 5 years old (4), ivermectin was used because of our patient’s severe, full-body involvement. Crusted scabies should be considered in the differential diagnosis of any generalized erythrodermic, scaling dermatitis. Immunocompromised patients and those with developmental disability, including Down syndrome, are at risk. Our patient’s marked associated failure to thrive is unusual. She had no other comorbid conditions accounting for her weight loss and she demonstrated weight gain once her infestation was addressed. This case highlights the need for early diagnosis and treatment. Avoiding misdiagnosis and the potential deleterious side effects of improper therapeutic interventions is imperative.

Address correspondence to Vanessa Fonseca, M.D., Department of Dermatology, Phoenix Children’s Hospital, 1919 E. Thomas Rd., 2nd Floor, Clinic F, Phoenix, AZ 85016, or email: [email protected].

Ulcerated Infantile Hemangioma: Novel Treatment with Topical Brimonidine-Timolol Abstract: We report a 2-month-old boy with a painful ulcerated hemangioma on the lower mucosal lip extending to the vermillion border that caused feeding difficulty. It was successfully treated with topical brimonidine 0.2% and timolol 0.5%, a combination selective a2-adrenergic agonist and nonselective b-blocker. After 6 weeks of treatment, the lesion reepithelialized and the patient’s symptoms and functional complications resolved. Brimonidine 0.2% timolol 0.5% ophthalmic solution is an emerging alternative treatment for hemangiomas, offering the potential to target hemangioma growth through two synergistic mechanisms (b-inhibition and a2-agonism) that may be especially effective for ulcerated lesions, the most common complication of infantile hemangiomas.

A 2-month-old full-term Caucasian boy presented with a growing, painful, ulcerated infantile hemangioma (IH) on the lower lip that was interfering with feeding. It was first noticed at 1 week of age. Examination revealed a dusky red, slightly elevated

Brief Reports 755

to monitor for decreased appetite, wheezing, difficulty breathing, cool extremities, drowsiness, hypotension, and central nervous system depression (adverse effects as included in the prescribing information). Within 6 weeks, the ulcerated hemangioma dramatically improved, reepithelialized, flattened, and faded (Fig. 2). Most importantly, the patient was feeding well without associated pain. No side effects were observed during treatment. Figure 1. A 2-month-old boy with a slightly elevated 2.0cm 9 3.0-cm plaque with central erosion involving the right side of the lower lip and vermillion border. This lesion was first noted at 1 week of age and had been gradually enlarging, becoming painful and thus interfering with feeding. This photograph was taken before treatment with brimonidine 0.2% timolol 0.5%.

3.0-cm 9 2.0-cm plaque with central erosion involving the right lower mucosal lip, crossing the vermillion border (Fig. 1). The risk and requirements for initiating oral propranolol seemed disproportionately high for this small lesion, and although a randomized control trial has documented the efficacy of topical timolol (1), we have observed an excellent response in three nonulcerated IHs treated using topical brimonidine 0.2% timolol 0.5% (2). After reviewing the potential side effects and treatments of topical brimonidine 0.2% timolol 0.5%, topical timolol, and oral propranolol, the parents choose combination topical treatment with brimonidine 0.2% timolol 0.5% for their child’s high-risk ulcerated lesion. They were instructed to apply two drops from a fingertip to the lesion twice daily for 4 weeks (Equivalent to a little more than one 5 mL bottle of brimonidine–timolol per month. If 1 drop = 0.05 mL, then a 5-mL bottle contains 100 drops. Applying 2 drops twice a day for 30 days = 120 drops per month.) and were counseled

Figure 2. Six weeks after treatment with brimonidine 0.2% timolol 0.5%, the ulcerated hemangioma had completely reepithelialized, with the lesion becoming smaller and flatter and fading to a pink-gray color. The parents reported that the patient was no longer in pain and was feeding well.

DISCUSSION Ulceration is the most common complication of IH, often causing severe pain with functional impairment (3). Oral propranolol has become the standard of care for high-risk IH (3,4), whereas topical timolol is common for smaller lesions to minimize systemic side effects (1,3). Standard treatments for ulcerated IH have not been well defined; even the most recent clinical trials have excluded ulcerated lesions and limited study to superficial hemangiomas only (1,3). The combination of brimonidine 0.2% timolol 0.5% is more effective than either agent alone in treating glaucoma and may have similar additive efficacy in treating ulcerated IH. A direct mechanism of action for the treatment of IH could be through a2agonism and b-inhibition of tumoral IH endothelial cells (3). An indirect benefit may be prolonging the local action of timolol through synergistic vasoconstriction. Ulceration and a mucosal location of IH are risk factors for high systemic absorption. Anticipatory guidance and close monitoring for side effects are important for the safe use of topical b-blockers, a-agonists, or combination therapy, especially in infants. With combination therapy, two drops per application is comparable to one-tenth of the medication exposure of brimonidine in a single application of brimonidine 0.33% gel or oral propranolol at 1 mg/ kg per dose (at two drops per dose, medication exposure is 0.05 mL 9 2 drops = 0.1 mL). With brimonidine 0.2% solution (2 mg/mL), 0.1 mL or 2 drops equals 0.2 mg. A typical small single application of brimonidine 0.33% gel equals 3.3 mg/g. With timolol 0.5% solution (5 mg/mL), 0.1 mL or 2 drops equals 0.5 mg. A 1 mg/kg oral dose of propranolol equals 5 mg for a 5-kg infant. The decision to use topical rather than oral treatment must be made on a case-by-case basis, weighing the risk of treatment against the risk of a proliferating IH (5). Infants with small superficial lesions are the best candidates for initial topical treatment.

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In summary, we report the first use of topical combination therapy with a b-blocker and an a2agonist to treat an ulcerated IH. Topical treatment reduces drug exposure and minimizes the risks of medication-related side effects. Additional studies are needed to compare the safety and efficacy of combination therapy with the safety and efficacy of topical and oral b-blockers for ulcerated IH.

REFERENCES 1. Chan H, McKay C, Adams S et al. RCT of timolol maleate gel for superficial infantile hemangiomas in 5- to 24-week-olds. Pediatrics 2013;131:e1739–e1747. 2. Chu MB, Searcy G, Siegfried E. Efficacy of topical brimonidine-timolol for hemangioma of infancy and perils of off-label prescribing. BMJ Case Rep 2013 Apr 17;2013. pii: bcr2013009365. doi: 10.1136/bcr-2013009365. 3. Chen TS, Eichenfield LF, Friedlander SF. Infantile hemangioma: an update on pathogenesis and therapy. Pediatrics 2013;131:99–108.

4. Leaute-Labreze C, Frieden IJ. Propranolol in infantile hemangiomas: results from an international randomized, placebo-controlled, multidose adaptive phase 2/3 study. Poster presented at the 71st annual meeting of the American Academy of Dermatology Meeting, March 4, 2013, Miami, FL. 5. McMahon P, Oza V, Frieden IJ. Topical timolol for infantile hemangiomas: putting a note of caution in “cautiously optimistic”. Pediatr Dermatol 2012;29:127– 130. Brandon T. Beal, B.S.* Melinda B. Chu, M.D.† Elaine C. Siegfried, M.D.à,¶ *School of Medicine, Saint Louis University, St. Louis, Missouri, †Department of Dermatology, Saint Louis University, St. Louis, Missouri, àDepartment of Pediatrics, Saint Louis University, Cardinal Glennon Children’s Hospital, St. Louis, Missouri, ¶Department of Dermatology, Saint Louis University, Cardinal Glennon Children’s Hospital, St. Louis, Missouri Address correspondence to Melinda B. Chu, M.D., Department of Dermatology, Saint Louis University, Anheuser-Busch Institute, 1402 South Grand Boulevard, 4th floor, St. Louis, MO 63104, or e-mail: [email protected].

Ulcerated infantile hemangioma: novel treatment with topical brimonidine-timolol.

We report a 2-month-old boy with a painful ulcerated hemangioma on the lower mucosal lip extending to the vermillion border that caused feeding diffic...
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