Beta-Blockers for Pyogenic Granuloma: A Systematic Review of Case Reports, Case Series, and Clinical Trials

Pyogenic granuloma (PG) or lobular capillary hemangioma, is an acquired benign vascular growth on the skin and mucous membranes, occurring more often in children and young adults.¹ PG can arise spontaneously, in sites of injury, as a result of chemotherapy, or within capillary malformations.² Even though PG is a benign tumor, treatment is required due to associated risk of ulceration and bleeding, cosmetic concerns, and the low likelihood of spontaneous regression.³ Treatment options include excisional surgery, cryotherapy, electrocautery, laser ablation, and topical medical therapy with silver nitrate, phenol, podophyllin, or imiquimod.⁴ Recurrence however is a major problem. Hence, there is a need for alternative noninvasive treatments that offer a lower recurrence rate and are convenient to be applied, especially in the pediatric population.

The use of beta blockers for vascular growths was first reported in 2008 when two infants taking propranolol for cardiac reasons experienced dramatic involution of severe hemangiomas.^5,6 Follow-up studies resulted in the approval of oral propranolol for severe infantile hemangioma by The Food and Drug Administration. It was found that infantile hemangiomas highly express beta-adrenergic receptors, a potential explanation for why beta-blockers are effective in infantile hemangiomas regression. In the same study, pyogenic granulomas were found to also express beta adrenergic receptors, albeit less than what is seen in infantile hemangiomas.⁷ Hence, several publications have reported the use of oral and topical beta blockers such as timolol, propranolol, and betaxolol, for the treatment of PG. In this study, we aim to summarize the literature with regards to the effectiveness of topical beta blockers for the treatment of PG, and included all published case reports, case series, and open-label single-arm trials.

The study protocol was performed based on PRISMA 2009 guidelines for systematic reviews. We searched the following electronic databases for publications through March 2019: PubMed (Medline), Central, Embase, Web of Science, and EBSCO host. Medical Subject Headings (MeSH) and free text words were applied during the search. To search suitable studies assessing beta-blockers in PG treatment, the keywords used were as follows: ‘timolol’, ‘propranolol’, ‘betaxolol’, ‘beta-blocker’, ‘adrenergic receptor’, ‘pyogenic granuloma’, ‘lobular capillary hemangioma’. The inclusion criteria were as follow: (i) studies describing PG patients at any age treated with oral or topical beta-blocker; (ii) no comparator was limited; (iii) clear description of the outcomes or side effects; (iv) study type was not limited due to the absence of randomized controlled trial. Studies such as abstracts, posters, conference reports, as well studies in languages other than English were excluded. All studies were reviewed and for each suitable study, the following data were collected: last name of the first author, publication year, type of PG (solitary, multifocal, agminated, periungual, or ocular), location of PG, number of patients, and response.