150 Pediatric Dermatology Vol. 32 No. 1 January/February 2015
REFERENCES 1. Song M, Kim SH, Jung DS, et al. Structural correlations between dermoscopic and histopathological features of juvenile xanthogranuloma. J Eur Acad Dermatol Venereol 2011;25:259–263. 2. Llambrich A, Zaballos P, Terrasa F, et al. Dermoscopy of cutaneous leishmaniasis. Br J Dermatol 2009;160:756– 761. 3. Argenziano G, Zalaudek I, Corona R, et al. Vascular structures in skin tumors: a dermoscopy study. Arch Dermatol 2004;140:1485–1489.
Figure 1. Friable papule on the cheek of a 5-month-old.
Grant K. Ghahramani, M.D. Brian L. Swick, M.D. Heather Ciliberto, M.D. Department of Dermatology, University of Iowa Hospitals and Clinics, Iowa City, Iowa Address correspondence to Grant K. Ghahramani, M.D., Department of Dermatology, University of Iowa, 200 Hawkins Drive/40024 PFP, Iowa City, IA 52242, or e-mail: [email protected].
Pyogenic Granuloma in a 5-Month-Old Treated with Topical Timolol Abstract: A 5-month-old healthy female presented with a pyogenic granuloma on the cheek. The lesion was treated with topical 0.5% gel-forming solution, resulting in regression of the lesion after 1 month of treatment and no recurrence at 8 months. This case suggests that treatment of pyogenic granulomas with topical timolol may be considered, especially when other treatment modalities are challenging or could result in significant scarring.
CASE REPORT A 5-month-old healthy girl presented for evaluation of a vascular growth on the left cheek. The growth had appeared at 1 month of age, had grown and bled, with the superficial papule detaching after trauma then recurring. On examination there was a 7-mm pink friable papule with hemorrhagic crust (Fig. 1). History and morphology were most consistent with a pyogenic granuloma. The location of the lesion on the face and the broad base made shave removal or surgical excision a less favorable option because of the likelihood of significant scarring. Topical timolol gel was suggested as an alternative treatment to try to encourage involution of the lesion. The lesion involuted over 1 month of treatment with timolol 0.5% gel-forming solution, leaving a 7-mm hyperpigmented
Figure 2. Residual erosion and surrounding hyperpigmentation after 1 month of topical timolol.
patch with a 3- to 4-mm erythematous slightly eroded center (Fig. 2). The patient’s family was encouraged to continue topical treatment with timolol until full re-epithelization of the area occurred. Follow-up by telephone at 8 months of age revealed that the lesion had not recurred. DISCUSSION Pyogenic granulomas are common vascular lesions in children and appear most often on the face and upper extremities (1). They are typically small, friable, red papules or nodules. Although the differential diagnosis of a vascular lesion at this age includes infantile hemangioma or Spitz nevus, we favored the diagnosis of a pyogenic granuloma based on the history of being easily friable and morphology. The exact pathogenesis remains unknown but may be due to an unregulated angiogenic stimulus, and some develop at sites of trauma. If untreated, these lesions most often persist and may enlarge and continue to bleed intermittently (2). They may infrequently resolve on their own, but most mature, increase their fibrous component, and persist indefinitely (3). Current treatment options for pyogenic granulomas include shave removal with electrodesiccation to the base, surgical excision, pulsed dye laser, cryotherapy, and topical silver nitrate; one case series has reported the use of topical imiquimod (4). Surgical excision often leads to localized scarring and the potential for infection, limiting
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its applicability to sensitive locations such as the face. Painful procedures can be difficult to perform on young patients without sedation, particularly for periocular lesions. High recurrence rates limit other therapies, such as topical silver nitrate and cryotherapy (2). Systemically delivered nonselective beta-blockers have shown great promise in the treatment of infantile hemangiomas, a distinct vascular tumor (5). Topical nonselective beta-blockers, specifically timolol 0.5%, have also produced regression of small superficial infantile hemangiomas (6), and the gel vehicle (timolol 0.5% gel for 24 weeks duration) has been used efficaciously with no significant differences in heart rate or systolic or diastolic blood pressure from placebo (7). A recent study confirmed beta-adrenergic receptor expression in vascular tumors, providing a potential therapeutic pathway explaining the success of beta-blockade in producing lesion regression (8). This study also demonstrated expression of betaadrenergic receptors in pyogenic granulomas, albeit less consistently than in infantile hemangiomas (8). To our knowledge there are no previous reports of cutaneous pyogenic granulomas being treated with propranolol or topical timolol. Our case suggests that treatment of pyogenic granulomas with topical timolol may induce regression of the lesion and may be of use in locations where other treatment options are challenging or could result in significant scarring. Further studies are needed to assess the true efficacy of topical timolol in the treatment of pyogenic granulomas. REFERENCES 1. Pagliai KA, Cohen BA. Pyogenic granuloma in children. Pediatr Dermatol 2004;21:10–13. 2. Craig L, Alster T. Vascular skin lesions in children: a review of surgical and medical treatment. Dermatol Surg 2013;39:1–10. 3. Davies MG, Barton SP, Atai F, Mark R. The abnormal dermis in pyogenic granuloma. J Am Acad Dermatol 1980;2:132–142. 4. Tritton SM, Smith S, Wong LC et al. Pyogenic granuloma in ten children treated with topical imiquimod. Pediatr Dermatol 2009;26:269. 5. Leaute-Labreze C, Dumas de la Roque E, Hubiche T et al. Propranolol for severe hemangiomas of infancy. N Engl J Med 2008;358:2649–2651. 6. Chakkittakandiyil A, Phillips R, Frieden I et al. Timolol maleate 0.5% or 0.1% gel-forming solution for infantile hemangiomas: a retrospective, multicenter, cohort study. Pediatr Dermatol 2012;29:28–31. 7. Chan H, McKay C, Adams S, Wargon O. RCT of timolol maleate gel for superficial infantile hemangiomas in 5- to 24-week-olds. Pediatrics 2013;121:e1739.
8. Chisholm K, Chang K, Truong M et al. Beta-adrenergic expression in vascular tumors. Mod Pathol 2012;25: 1446–1451. Kate Khorsand, B.Sc.* Morgan Maier, P.A.-C.† Heather A. Brandling-Bennett, M.D.† *WWAMI Clinical Medical Education, University of Washington, Seattle, Washington, †Division of Dermatology, Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, Washington Address correspondence to Heather A. Brandling-Bennett, M.D., Division of Dermatology, Department of Pediatrics, Seattle Children’s Hospital, University of Washington, 4800 Sand Point Way NE, OC.9.835, Seattle, WA 98105, or e-mail: heather.brandlingbennett@ seattlechildrens.org.
A Retrospective Study of Propranolol Therapy in 635 Infants with Infantile Hemangioma Abstract: Six hundred thirty-five patients underwent oral propranolol treatment for infantile hemangioma. The efficacy rate was 91.2% and 162 of the patients recovered completely. No significant adverse effects were observed and the overall incidence of adverse effects was 2.1%.
Infantile hemangioma (IH) is a common benign tumor of infancy, with therapeutic intervention required in approximately 10% of patients (1). Propranolol has shown promise in IH treatment, but its efficacy and side effects are not well established because of the small number of individuals with IHs enrolled in previous studies. We performed a retrospective analysis of a large number of individuals with IH to evaluate the efficacy and safety of propranolol in IH treatment. Six hundred thirty-five patients with IH (ages 16 days to 3 yrs, 204 boys, 431 girls) admitted to Hunan Children’s Hospital from December 2009 to March 2012 were enrolled. They were treated with propranolol at 2 mg/kg/day in two divided doses. They were discharged if no cardiovascular or metabolic side effects were observed after 3 or 4 days. They were reevaluated once a month and blinded investigators evaluated the therapeutic effects on a 4-point scale (2). Average follow-up was 18.6 7.9 months (range 5–32 mos). Efficacy was judged as positive if the lesions regressed more than 26% of their initial size after propranolol therapy.
REFERENCES 1. Song M, Kim SH, Jung DS, et al. Structural correlations between dermoscopic and histopathological features of juvenile xanthogranuloma. J Eur Acad Dermatol Venereol 2011;25:259–263. 2. Llambrich A, Zaballos P, Terrasa F, et al. Dermoscopy of cutaneous leishmaniasis. Br J Dermatol 2009;160:756– 761. 3. Argenziano G, Zalaudek I, Corona R, et al. Vascular structures in skin tumors: a dermoscopy study. Arch Dermatol 2004;140:1485–1489.
Figure 1. Friable papule on the cheek of a 5-month-old.
Grant K. Ghahramani, M.D. Brian L. Swick, M.D. Heather Ciliberto, M.D. Department of Dermatology, University of Iowa Hospitals and Clinics, Iowa City, Iowa Address correspondence to Grant K. Ghahramani, M.D., Department of Dermatology, University of Iowa, 200 Hawkins Drive/40024 PFP, Iowa City, IA 52242, or e-mail: [email protected].
Pyogenic Granuloma in a 5-Month-Old Treated with Topical Timolol Abstract: A 5-month-old healthy female presented with a pyogenic granuloma on the cheek. The lesion was treated with topical 0.5% gel-forming solution, resulting in regression of the lesion after 1 month of treatment and no recurrence at 8 months. This case suggests that treatment of pyogenic granulomas with topical timolol may be considered, especially when other treatment modalities are challenging or could result in significant scarring.
CASE REPORT A 5-month-old healthy girl presented for evaluation of a vascular growth on the left cheek. The growth had appeared at 1 month of age, had grown and bled, with the superficial papule detaching after trauma then recurring. On examination there was a 7-mm pink friable papule with hemorrhagic crust (Fig. 1). History and morphology were most consistent with a pyogenic granuloma. The location of the lesion on the face and the broad base made shave removal or surgical excision a less favorable option because of the likelihood of significant scarring. Topical timolol gel was suggested as an alternative treatment to try to encourage involution of the lesion. The lesion involuted over 1 month of treatment with timolol 0.5% gel-forming solution, leaving a 7-mm hyperpigmented
Figure 2. Residual erosion and surrounding hyperpigmentation after 1 month of topical timolol.
patch with a 3- to 4-mm erythematous slightly eroded center (Fig. 2). The patient’s family was encouraged to continue topical treatment with timolol until full re-epithelization of the area occurred. Follow-up by telephone at 8 months of age revealed that the lesion had not recurred. DISCUSSION Pyogenic granulomas are common vascular lesions in children and appear most often on the face and upper extremities (1). They are typically small, friable, red papules or nodules. Although the differential diagnosis of a vascular lesion at this age includes infantile hemangioma or Spitz nevus, we favored the diagnosis of a pyogenic granuloma based on the history of being easily friable and morphology. The exact pathogenesis remains unknown but may be due to an unregulated angiogenic stimulus, and some develop at sites of trauma. If untreated, these lesions most often persist and may enlarge and continue to bleed intermittently (2). They may infrequently resolve on their own, but most mature, increase their fibrous component, and persist indefinitely (3). Current treatment options for pyogenic granulomas include shave removal with electrodesiccation to the base, surgical excision, pulsed dye laser, cryotherapy, and topical silver nitrate; one case series has reported the use of topical imiquimod (4). Surgical excision often leads to localized scarring and the potential for infection, limiting
Brief Reports 151
its applicability to sensitive locations such as the face. Painful procedures can be difficult to perform on young patients without sedation, particularly for periocular lesions. High recurrence rates limit other therapies, such as topical silver nitrate and cryotherapy (2). Systemically delivered nonselective beta-blockers have shown great promise in the treatment of infantile hemangiomas, a distinct vascular tumor (5). Topical nonselective beta-blockers, specifically timolol 0.5%, have also produced regression of small superficial infantile hemangiomas (6), and the gel vehicle (timolol 0.5% gel for 24 weeks duration) has been used efficaciously with no significant differences in heart rate or systolic or diastolic blood pressure from placebo (7). A recent study confirmed beta-adrenergic receptor expression in vascular tumors, providing a potential therapeutic pathway explaining the success of beta-blockade in producing lesion regression (8). This study also demonstrated expression of betaadrenergic receptors in pyogenic granulomas, albeit less consistently than in infantile hemangiomas (8). To our knowledge there are no previous reports of cutaneous pyogenic granulomas being treated with propranolol or topical timolol. Our case suggests that treatment of pyogenic granulomas with topical timolol may induce regression of the lesion and may be of use in locations where other treatment options are challenging or could result in significant scarring. Further studies are needed to assess the true efficacy of topical timolol in the treatment of pyogenic granulomas. REFERENCES 1. Pagliai KA, Cohen BA. Pyogenic granuloma in children. Pediatr Dermatol 2004;21:10–13. 2. Craig L, Alster T. Vascular skin lesions in children: a review of surgical and medical treatment. Dermatol Surg 2013;39:1–10. 3. Davies MG, Barton SP, Atai F, Mark R. The abnormal dermis in pyogenic granuloma. J Am Acad Dermatol 1980;2:132–142. 4. Tritton SM, Smith S, Wong LC et al. Pyogenic granuloma in ten children treated with topical imiquimod. Pediatr Dermatol 2009;26:269. 5. Leaute-Labreze C, Dumas de la Roque E, Hubiche T et al. Propranolol for severe hemangiomas of infancy. N Engl J Med 2008;358:2649–2651. 6. Chakkittakandiyil A, Phillips R, Frieden I et al. Timolol maleate 0.5% or 0.1% gel-forming solution for infantile hemangiomas: a retrospective, multicenter, cohort study. Pediatr Dermatol 2012;29:28–31. 7. Chan H, McKay C, Adams S, Wargon O. RCT of timolol maleate gel for superficial infantile hemangiomas in 5- to 24-week-olds. Pediatrics 2013;121:e1739.
8. Chisholm K, Chang K, Truong M et al. Beta-adrenergic expression in vascular tumors. Mod Pathol 2012;25: 1446–1451. Kate Khorsand, B.Sc.* Morgan Maier, P.A.-C.† Heather A. Brandling-Bennett, M.D.† *WWAMI Clinical Medical Education, University of Washington, Seattle, Washington, †Division of Dermatology, Department of Pediatrics, Seattle Children’s Hospital, University of Washington, Seattle, Washington Address correspondence to Heather A. Brandling-Bennett, M.D., Division of Dermatology, Department of Pediatrics, Seattle Children’s Hospital, University of Washington, 4800 Sand Point Way NE, OC.9.835, Seattle, WA 98105, or e-mail: heather.brandlingbennett@ seattlechildrens.org.
A Retrospective Study of Propranolol Therapy in 635 Infants with Infantile Hemangioma Abstract: Six hundred thirty-five patients underwent oral propranolol treatment for infantile hemangioma. The efficacy rate was 91.2% and 162 of the patients recovered completely. No significant adverse effects were observed and the overall incidence of adverse effects was 2.1%.
Infantile hemangioma (IH) is a common benign tumor of infancy, with therapeutic intervention required in approximately 10% of patients (1). Propranolol has shown promise in IH treatment, but its efficacy and side effects are not well established because of the small number of individuals with IHs enrolled in previous studies. We performed a retrospective analysis of a large number of individuals with IH to evaluate the efficacy and safety of propranolol in IH treatment. Six hundred thirty-five patients with IH (ages 16 days to 3 yrs, 204 boys, 431 girls) admitted to Hunan Children’s Hospital from December 2009 to March 2012 were enrolled. They were treated with propranolol at 2 mg/kg/day in two divided doses. They were discharged if no cardiovascular or metabolic side effects were observed after 3 or 4 days. They were reevaluated once a month and blinded investigators evaluated the therapeutic effects on a 4-point scale (2). Average follow-up was 18.6 7.9 months (range 5–32 mos). Efficacy was judged as positive if the lesions regressed more than 26% of their initial size after propranolol therapy.
