Advice for Parents Regarding Hemangiomas:  Time to change our approach in Pediatrics?

Advice for Parents Regarding Hemangiomas:  Time to change our approach in Pediatrics?

by | Mar 9, 2015 | Dermatology

The story is typical.  A family notices a small red spot in the weeks following delivery which enlarges over the next month.  They present to their family doctor or Pediatrician who identifies the most common skin lesion in childhood; a hemangioma affecting about 3-10% of all children depending on the population observed.  As a resident I was given the following advice regarding hemangiomas; “As long as the hemangioma is not of cosmetic concern, sight threatening, multiple in number or causing anemia or thrombocytopenia watchful waiting is recommended.”  Furthermore I recall the following general advice that while they tend to enlarge over the first year of life, 40% are gone by 4 years, 60% by 6 years and 90% by 9 years.  After my training I started a practice passing along the same advice to the infants I now cared for.

Then something happened similar to the serendipitous discovery of penicillin.  In 2008, Leaute-Labreze et al published a case report in which they described a child being treated for a facial hemangioma with corticosteroids.  Unfortunately the hemangioma did not respond to treatment but rather led to a cardiomyopathy requiring treatment with propranolol. Curiously the hemangioma demonstrated significant regression on propranolol.  The results of this case report prompted further treatments with propranolol in an unblinded fashion.  Since this time propranolol and more recently topical Timolol (sample size 41) have been studied both in observational and small randomized controlled trials.  Propranolol while effective has potential side effects such as hypotension, bradycardia and bronchospasm which has limited it’s widespread application except for those patients with either large, sight threatening or multiple hemangiomas. Topical timolol in the RCT above was demonstrated to be safe and when given locally, free of such side effects making it a seemingly ideal treatment for smaller hemangiomas that may have some cosmetic concerns later in life as they regress. That being said, the time of onset for regression was noted to be after 12-16 weeks of therapy and the target they aimed for was a reduction of >5% which is certainly modest.  While only a small improvement it was seen 60% of the time in the treatment group and 11% in the placebo arm. From personal experience I have used topical Timolol with patients in the NICU with varying success but in some cases the results were quite impressive.  Looking at the RCT by Chan, timolol was only applied to those hemangiomas that were small and deemed unsuitable for treatment with propranolol.

This leaves us with the question; what does one use if anything for larger hemangiomas which traditionally don’t fit into the category of needing treatment vs patient observation.  Secondly, is it wise to systematically treat all larger hemangiomas with propranolol as outpatients, given the potential severity of the side effects, some of which may be life threatening.

This past week in the New England Journal of Medicine we have come full circle as Leaute-Labreze et all have published a large prospective RCT http://bit.ly/1ACqn2C to determine the optimal dose and duration of propranolol for treatment of hemangiomas requiring systemic treatment. The number of patients enrolled in this study was 456 which makes it the largest study to date in this field.  This study sought to determine whether 1 mg/kg/day vs 3 mg/kg/day divided twice a day for 3 or 6 months would provide the best resolution without unacceptable side effects.  Eligible patients were between 1-5 months of age with a proliferating hemangioma and were treated for either 3 or 6 months depending on which arm of the study they were on. The results of this trial were striking and found that the best balance of benefit and risk was with 3 mg/kg/day for 6 months and is shown below graphically compared to placebo.

results propranolol

This difference translates into a number need to treat to cause regression = 1.7 or rounded up 2.  For every two patients that you treat with propranolol you will cause one hemangioma to regress.  Try finding a therapeutic benefit like that in another trial!

But what about safety?  Side effects were rare compared to placebo but not negligible. The most common side effect was diarrhea and with respect to life threatening adverse effects the only one really noted was bradycardia but in a patient with enterocolitis.  My take on this treatment is that it appears to have great impact with little downside!

How do we apply these results though to “real life” situations.  We now have as I see it a “one-two punch”.  Hemangiomas that are deemed to require no systemic treatment can be treated with a safe topical drop that has been used for years for glaucoma patients.  Patients with larger more significant hemangiomas may be treated with a highly efficacious treatment that may have very few side effects.

The downside of systemic therapy at least in Winnipeg is that treatment with propranolol generally requires a hospital admission at the start of treatment to monitor for side effects that would be considered life threatening.  With an incidence of 5% of children it would be impractical to admit 600 children a year for such treatment based on an estimated 12000 births in the region a year.

I do believe the time is upon us for change though.  As I see it, gone are the days where we tell parents that we will see what develops when their child has a small hemangioma.  If you have a willing parent who is concerned about the hemangioma and it is < 1.5 cm in size I believe topical Timolol should be offered to the family for a period of 6 months treatment.  Anything larger than that would merit treatment with propranolol.  Nine years is potentially a very long time to wait for a lesion to regress and potentially leave a scar or telangiectasia behind.  If we can do something about it now with such a high rate of success and minimal risk to the patient, why wait?

My advice to you if you either have a child with a hemangioma or know someone else with one is to have them ask their doctor whether Timolol or Propranolol would be right for them.  Given these findings I know my practice will change.

Can we prevent atopic dermatitis in susceptible patients?

by | Mar 3, 2015 | Dermatology

atopic_dermatitis_3_080322-e1362868660632

When I was growing up it was quite the rare thing to hear that someone had a food allergy. I knew of a few children with eczema or asthma but these days one can’t help but notice the warnings everywhere at schools, camps etc to avoid bringing high risk allergens into close proximity with potentially susceptible children.  As a Neonatologist I don’t profess to be an expert in the area of Atopic conditions but I do believe as others have suggested that society’s obsession with antibacterial soaps and not playing the sandbox so to speak has led to an over development of the allergic response of our immune system due to lack of stimulation on the “infection fighting side” during our infant and toddler years.  As a Pediatric resident I recall treating many children in clinic for atopic conditions and certainly atopic dermatitis was extremely common and incredibly frustrating for parents not to mention the children.

In October of 2014, in the Journal of Allergy and Clinical Immunology Simpson et al reported a pilot study that could change the approach from treatment to prevention for many children if the results hold true in larger studies. The article abstract can be found here with the full article being free as well: http://1.usa.gov/1BR1typ

In this pilot randomized control trial emolients were used in the treatment arm once a day for the first 6 months of life and had to be started within three weeks of life.  All of these children were deemed to be high risk by having a first degree relative with allergic disease.  The emolients used in the US group were sunflower oil, cetaphil cream and aquafor ointment and were applied to all skin surface except for the head.  The theory was that skin breaks in newborns and infants allow allergens to reach the subcutaneous tissue and elicit an immune response thus creating allergic skin disease no different than an exposure to peanuts, tree nuts, dust mites etc can later trigger the immune system to cause allergic rhinitis or food allergy (Fig 1 from quoted paper below).  Previous observational studies had yielded some support to this theory so the RCT was an attempt to answer the question as to whether keeping the skin smooth without breaks could prevent atopic eczema from happening.

gr1

The study was not powered to show a difference but the results of the study make this comment irrelevant.  If a study is underpowered and no difference is seen between two groups one cannot say with certainty if no effect is seen that there was in fact no effect.  If a difference is seen in even the smallest study between two groups in the primary outcome this is in fact significant as it was in this study.

The study found that the treatment group incidence of atopic dermatitis at 6 months was 22% vs a 43% incidence in controls.  This corresponds to a 50% reduction in risk with a number needed to treat to prevent 1 case of atopic dermatitis of about 6 but with wide confidence intervals due to the small size of the study (3-1138).  This speaks to the issue with small studies.  Although the results seem impressive at first when you examine how confident you are with the estimate of the benefit it may be much less than originally thought.  One thing to note though is that about 20% of families did not adhere to the daily application of emolient so one has to wonder if the results would have been even more impressive had the use been more consistent.

That all being said, applying a cream or ointment once a day to keep your newborns’ skin smooth and free of cracks seems to me to be something that many parents (especially those of us who live in the North) do anyway. Atopic dermatitis is a terrible condition that causes a lot of stress and discomfort for children and their families.  If applying a cream or ointment once a day for the first 6 months of life was able to achieve such dramatic results and avoid such a condition I see very little harm in trying.  Of course a larger study will now need to be done to confirm the cited paper here but I think this is a potentially exciting simple treatment to prevent a terrible condition!

I am a fan of simple treatments and even more so of simple interventions to prevent children from ever experiencing a condition at all.  Might early use of emolients be one of these strategies?