Friendly Debates Spark Discussion on Infantile Hemangioma, Vitiligo, and Atopic Dermatitis

Laughter and applause could be heard from outside the room as different dermatology experts took to the stage to argue that certain ways of treating skin conditions or proposed causes of skin conditions were more valid than others. A session from The Society for Pediatric Dermatology Annual Meeting, which takes place from July 11 to July 14, 2024, in Toronto, Ontario, Canada, introduced the new debates segment to encourage discussion among the top doctors in the space.

Propranolol vs Nadolol in Infantile Hemangioma

Sarah Chamlin, MD, professor of pediatrics and dermatology at Lurie Children’s Hospital and Northwestern Feinberg School of Medicine, opened the segment by arguing for the use of propranolol in the treatment of infantile hemangioma. Propanolol, primarily used for blood pressure and heart problems, can also be used to treat this skin condition.

“I would like to say that I’m pro–beta-blocker, I’m pro-propranolol, and I popped 20 mg an hour ago so I’m able to be here,” Chamlin joked as she began her presentation to a laughing audience.

Chamlin began by explaining that treatment of infantile hemangioma prior to 2008 was difficult due to a lack of feasible options. Treatment for the condition often failed after using treatments such as topical radium, cryotherapy, cautery, and sclerosing injections in the before the 1960s and systemic corticosteroids between the 1960s and 2008, all of which did not work. After asking for everyone to raise their hands if they were practicing before 2008, Chamlin quipped, “Everybody else in the room should pity us.”

Propranolol was a game-changing discovery, said Chamlin. The effectiveness of the medication was published in a study in the New England Journal of Medicine, which found 11 patients who had improvements.¹ The FDA approved the medication for use in infantile hemangioma in 2014.

However, there are potential adverse effects that can occur in children taking propranolol, which include cardiac effects, hypoglycemia, sleep disturbance, neurodevelopmental effects, and even death. Neurocognitive effects are particularly important to look into, as propranolol can cross into the blood-brain barrier, unlike nadolol. Chamlin presented 4 different studies that showed that there were no significant differences in intelligence, memory, development, or psychosocial problems between children receiving propranolol and children not taking the medication. However, a study found that 20 male children had lower intelligence quotient scores, albeit when the study was not powered.

“I think more work needs to be done on males with angiomas and long term effects [of propranolol],” said Chamlin.

Death was also reported in several children, including 1 death in nadolol and 10 deaths in propranolol, 4 of which were unrelated to the medication and 6 of which were unexplained. In 3 of the children who had unexplained deaths, 3 of them were tested and had levels of propranolol below toxicity levels.

Chamlin said that perspective in the treatment of infantile hemangioma is warranted. Propranolol is a highly efficacious medication for this population and the adverse effects leading to discontinuation are rare.

“I think our next steps using beta blockers in kids are to fine tune our expertise,” she said. “How should we dose for alteration: low dose or high dose? Understanding the non-responders and who rebounds, how [we can] adjust dosing and timing of administration to mitigate side effects. And should we really be initiating this at home or with office administration?”

Elena Pope, MSc, FRCPC, head of pediatric dermatology at The Hospital for Sick Children, argued instead for nadolol. Propranolol, she argued, has the highest central nervous system concentration of any of the other beta blockers, included nadolol, which ranks fourth. Pope acknowledged that sleep problems have been reported to varying degrees in different studies, ranging from up to 29% of patients having sleep problems to no problems being reported.

Her biggest argument, however, was that nadolol was more effective than propranolol. In her own study, published in JAMA Pediatrics,² nadolol was found to be more efficacious at both 6 and 12 months after initiation of treatment.

“We feel that nadolol is not only non-inferior but in the randomized control trials shown, it is more efficacious. It is definitely an option for propranolol intolerance or lack of response,” said Pope. “I think we definitely need more long-term data overall of the safety of beta blockers.”

Dermatology experts held a friendly debate on various interesting topics | Image credit: Right 3 - stock.adobe.com

Does Food Affect Atopic Dermatitis?

The second segment of the debate centered on whether food could trigger atopic dermatitis in children with the condition. Jim Treat, MD, professor of clinical pediatrics and dermatology at the Children’s Hospital of Philadelphia, took up the side of food not triggering atopic dermatitis.

“So do foods trigger atopic dermatitis. Nope. So, we could stop here,” Treat joked to a laughing audience. “But I’m going to try to kind of walk through why I don’t actually think that they are a trigger to atopic dermatitis.”

Scratching, he argued, was more of a trigger for flares in atopic dermatitis than any food. Atopic dermatitis is more about the skin barrier and a lot of atopic dermatitis can be mostly prevented by introducing moisturizers into a child’s life early if they are a high risk of atopic dermatitis. Therefore, it doesn’t make sense that food can automatically cause a worsened skin barrier simply by eating something.

However, he noted that some foods can affect the cytokine profiles. For example, if you eat a food and get a maximal response, your body can release histamine which can cause you to scratch more and indirectly could cause a flare. “So is it causing atopic dermatitis? No. But is it causing you to scratch more which might lead to your atopic dermatitis flare? Sure, but it’s not directly because of the food. It’s more of the secondary response to the urticarial response that you get.”

Treat concluded that foods should not break the skin barrier and patients shouldn’t get atopic dermatitis because of eating that food.

Vikash S. Oza, MD, director of pediatric dermatology at NYU Grossman School of Medicine, took the opposing view. A complaint expressed by so many patients should have some grain of truth, he said.

“The bedrock of my argument comes from 1 of the great American films, ‘Dumb and Dumber,’” he said with a smile. “And while this link might not be 1 in 10 or 1 in a million, is not perceivable that there is a chance? And that is what we’re going to talk about.”

Oza cheekily said that the link between food and atopic dermatitis has been expressed by many patients, which doctors should listen to. In a more serious argument, guidelines for food allergies in the United States have pointed out that food allergies should be considered if infants, young children, and older children present with moderate to severe atopic dermatitis. “It’s quite clear that we are to at least consider food as an allergen for the sheer presence of moderate to severe atopic dermatitis that comes into our door,” he said.

Other children can have delayed reactions to food in terms of their allergies. He also said that elimination diets, such as eliminating eggs, wheat, or milk from a child’s diet, can cause a mild improvement in atopic dermatitis in children.

Oza concluded by saying that eating your allergens and using your triamcinolone will likely result in children with atopic dermatitis being fine in the long run.

Treating Advanced Vitiligo

The last part of the session focused on treating vitiligo and whether to approach the condition with a more aggressive approach or a gentler approach. Nanette Silverberg, MD, from Mt Sinai Health Systems, took a more aggressive approach to vitiligo treatment whereas Leslie Castelo-Soccio, MD, PhD, from National Institute of Health, took a more slow and steady approach.

Both agreed that the treatment of vitiligo depends on timely diagnosis. “We know that patients just see their lesions expand over time and if we don’t intervene, that’s the natural course,” said Silverberg. For her, treating vitiligo more aggressively is a way of offering hope for getting better and quicker. Castelo-Soccio, meanwhile, believed that a minimalist approach can also be effective. This includes light therapy, low-risk topicals, anti-inflammatory topicals, and types of camouflage and cosmetics.

Reducing the risk of steroids can be done by using vitamin D analogues and coal tar, said Castelo-Soccio. Silverberg believed that being aggressive early could pay dividends over time. “You have to think about how vitiligo functions over time. Over time, the melanocyte reservoir is depleted and if you hit vitiligo early, you may prevent the long-term phase of development of salts in cells and lymphocytes in the skin,” she said. “You may produce a possible cure if you start early [and] you can prevent therapeutic fatigue.”

They both acknowledged that new treatments are being introduced all the time and so patients who are being treated now could come back in the future to try other therapies.

The session concluded the meeting day with applause and provided an end cap to the first day of the 3-day conference.

References

1. Léauté-Labrèze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taïeb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008;358(24)2649-2651. doi:10.1056/NEJMc0708819
2. Pope E, Lara-Corrales I, Sibbald C. Noninferiority and safety of nadolol vs propranolol in infants with infantile hemangioma: a randomized clinical trial. JAMA Pediatrics. 2022;76(1):34-41. doi:10.1001/jamapediatrics.2021.4565