Management of infantile hemangiomas

This lecture was an invited presentation at XIX Brazilian Congress of Cancerology (CONCAN), in 2012.

Hemangiomas are common pediatric tumors often described as birthmarks, more frequent in infants and at the head and neck region. Most of them regress spontaneously without any sequelae. A third of all infantile hemangiomas will be problematic, presenting with complications due to their size and/or topography or leaving sequelae (fibrofatty masses, discoloration, laxity, telangiectasia or scarring due to ulceration). The treatment of problematic infantile hemangiomas at Brazil was recently regulated by an administrative rule from the Ministry of Health (number 849, December 5th, 2011). The first choice was deemed to be oral prednisone. The other choices are interferon and beta-blockers. Surgery is indicated in selected cases. Non-problematic cases should be followed carefully without any treatment.

For this lecture, I have made a brief review of the evidence behind these treatment choices. I used primarily the Oxford Centre for Evidence Based Medicine 2011 levels of evidence, ranging from A (best quality evidence available) to D (only limited evidence available, or no evidence). I reviewed therapeutic studies and extracted information about efficacy and safety profiles.

I have found two major studies using prednisone/prednisolone. Bennet et al (2001) published a rigorous systematic review of observational studies, however there was confounding in the dose-response relation evaluation. Pandey et al (2009) published an observational study with 2013 patients, but the case definition, response evaluation and treatment duration were unclear. Both reported efficacy around 80-90%. Once there were no high quality evidence from randomized, double-blind trials, I gave prednisone/prednisolone a C level grade for efficacy, and a D level grade for safety.

I have found very limited evidence for the use of interferon, mostly from small number of cases observational reports. Thus, I gave it a D level grade. Due to the ocurrence of serious neurologic complications in patients that used interferon for hemangiomas, this treatment is currently widely contraindicated.

For propranolol, the main beta-blocker used to treat problematic infantile hemangiomas, I have found a myriad observational reports, ranging from a few to many hundreds of cases described. Additionally, Hogeling et al (2011) have published the first randomized, double-blind clinical trial comparing propranolol to placebo. It was a small sized, phase I-II equivalent clinical trial. Nonetheless, it reported clear evidence of efficacy and acceptable safety of propranolol treatment for infantile hemangioma; Because of this study, I gave propranolol treatment a C “plus” level grade.

Note: this lecture was presented in 2012. Since then, other high quality level trials reported their results, and my updated grade, as for 2015, would be certainly B.

I have been treating pediatric patients with problematic infantile hemangiomas with off-label propranolol since 2009. I published a small report with observational retrospective evaluation of results in Treatment of children and adolescents with hemangioma using propranolol: preliminary results from a retrospective study. JC Albuquerque, RA Magalhaes, JA Felix, MVR Bastos (…) - Sao Paulo Medical Journal, 2014 – doi:10.1590/1516-3180.2014.1321575 (this report was referred in this lecture as ‘submitted to publication’ and awaiting approval).