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Increasing evidence for the use of topical timolol for pyogenic granulomas

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By Warren R. Heymann, MD
May 16, 2016

There are multiple approaches to treating pyogenic granulomas (PGs). If possible, I usually perform a shave biopsy and electrodesiccate the base of the lesion. Certainly there are times when that approach may not be optimal, such as a PG the face of a very young child. There is increasing evidence that topical timolol may be a reasonable option.

Wine Lee et al were the first to use timolol 0.5% (twice daily) on 7 children with PGs (6 cutaneous, 1 mucosal). There was variability in the time of response to therapy, although all showed at least a partial response within 2 months. The presumption was that the therapeutic mechanism for timolol was due to vasoconstriction and its effect on VEGF (1).

The most recent study by Gupta et al reported 10 patients with PG who were treated with timolol 0.5% solution (applied 4 times a day). Four patients showed a complete response within 3-24 days, with no recurrence at 3-month follow-up. Three patients had a partial response, and the remaining 3 did not respond to therapy. No local or systemic side effects, including abnormalities of heart rate, EKG, or hypoglycemia were noted (2).

Systemic absorption of topical timolol has been studied regarding its use for the treatment of infantile hemangiomas. The following are the results from the study by Weibel et al (3):

“Forty infants with a median age of 18 weeks (range 2-35 wks) were included; 23 (58%) had superficial and 17 (42%) mixed-type hemangiomas. The median size was 3 cm 2 (range 0.1-15 cm2) and nine hemangiomas were ulcerated. The hemangiomas improved significantly during treatment, with a median increase in visual analog scale of 7 points after 5 months (p < 0.001). Urinalysis for timolol was performed in 24 patients and was positive in 20 patients (83%). In three infants, serum levels of timolol were also measured and were all positive (median 0.16 ng/mL [range 0.1-0.18 ng/mL]). No significant side effects were recorded.”

It would be therefore be reasonable to assume that there is some systemic absorption of timolol when utilized in treating PGs, as most are ulcerated, friable lesions  Indeed 83% of patients in Weibel’s study demonstrated absorption of timolol, when only 9 pf 40 lesions were ulcerated. Clinically, however, there were no clinically significant adverse reactions.

I have not yet tried timolol for treating PGs. As I have been somewhat impressed with its efficacy for small infantile hemangiomas. I believe that there is now enough supportive literature to consider trying topical timolol 0.5% (gel or solution) for patients with PGs, where this may be preferable to standard therapy. Despite the fact that there is some absorption, I have not gotten baseline monitoring studies when utilizing topical timolol for infantile hemangiomas. Other than explaining the potential adverse reactions signs of   beta-blockers to parents, I do not plan on performing detailed cardiovascular or serum glucose monitoring of PG patients either.

1. Wine Lee L, et al. Treatment of pediatric pyogenic granulomas using b-adrenergic receptor antagonists. Pediatr Dermatol 2014; 31: 203-7.
2. Gupta D, et al. Is timolol an effective treatment for pyoderma gangrenosum. Int J Dermatol 2016; 55: 592-5.
3. Weibel, L, et al. Topical timolol for infantile hemangioma: Evidence for efficacy and degree of systemic absorption. Pediatr Dermatol 2016; 184-90.

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