Consider Risks for Some Topical Ingredients in Children

TORONTO — Lawrence A. Schachner, MD, would like pediatric dermatologists to adopt a “toxic agent of the year” to raise awareness about the potential harm related to certain topical treatments in babies and young children.

Schachner, director of the Division of Pediatric Dermatology in the Department of Dermatology & Cutaneous Surgery at the University of Miami, Coral Gables, Florida, said he got the idea from the American Contact Dermatitis Society, which annually names the “Allergen of the Year.”

In pediatric dermatology, the list of potentially toxic products includes topical analgesics such as Castellani paint used for skin infections, alcohols used for umbilical care in newborns, and henna dye used in cosmetics, said Schachner, professor of pediatrics and dermatology at the University of Miami.

“Any one of those would be excellent toxic substances of the year” that could be the focus of an educational campaign, he told Medscape Medical News following his presentation on “Toxicology of Topical Ingredients in Pediatric Dermatology” at the Society for Pediatric Dermatology (SPD) 2024 Annual Meeting on July 14.

Benzene might also be a good candidate for the list, although the jury seems to be still out on its toxicity, said Schachner.

He talked about the “four Ps” of poisoning — the physician, pharmacy, parents, and pharmaceutical manufacturing — which all have some responsibility for errors that lead to adverse outcomes but can also take steps to prevent them.

During his presentation, Schachner discussed how babies are especially sensitive to topical therapies, noting that a baby’s skin is thinner and more permeable than that of an adult. And children have a greater body surface-to-weight ratio, so they absorb more substances through their skin.

He also noted that babies lack natural moisturizing factors, and their skin barrier isn’t mature until about age 3-5 years, stressing the need for extreme care when applying a topical agent to a baby’s skin.

Tragic Stories

Schachner pointed to some instances of mishaps related to toxic topical substances in children. There was the outbreak in the early 1980s of accidental hexachlorophene poisoning among children in France exposed to talc “baby powder.” Of the 204 affected children, 36 died.

The cause was a manufacturing error; the product contained 6.3% hexachlorophene, as opposed to the 0.1% limit recommended by the US Food and Drug Administration (FDA).

Local anesthetics, including lidocaine, dibucaine, and prilocaine, can cause local anesthetic systemic toxicity, a syndrome with symptoms that include central nervous system depression, seizures, and cardiotoxicity. Schachner described the case of a 3-year-old who developed methemoglobinemia, with seizures, after treatment with an excessive amount of eutectic mixture of local anesthetics (EMLA) cream, which contains both lidocaine and prilocaine.

EMLA shouldn’t be used with methemoglobinemia-inducing agents, such as some antimalarials, analgesics, anesthetics, and antineoplastic agents. It’s not recommended in neonates or for those under 12 months if receiving methemoglobinemia-inducing agents, “and I would keep an eye on it after 12 months of age,” said Schachner.

He cited a retrospective review of topical lidocaine toxicity in pediatric patients reported to the National Poison Data System from 2000 to 2020. It found 37 cases of toxicity, the most common from application prior to dermatologic procedures (37.5%), which led to two deaths.

Not Benign Agents

“These are not benign agents; we have to use them correctly,” Schachner stressed. When discussing alcohols and antiseptics, he noted that phenol is found in a variety of household disinfectants, gargling products, ointments, and lip balms. Phenol can be used as a chemical peel and is the antiseptic component of Castellani paint.

Schachner also referred to cases of alcohol intoxication linked to umbilical care in newborns.

Benzene at elevated levels has been found in some topical benzoyl peroxide acne products and in some sunscreens. There have been suggestions, not strongly substantiated, that benzene may increase the risk for cancer, especially leukemias.

But there is sparse data on the absorption and toxicity of benzene exposure with sunscreen use. The data, he said, include an analysis of National Health and Nutrition Examination Survey data, which found that people who regularly used sunscreens were less likely to have elevated benzene levels compared with those who didn’t use sunscreens.

Turning to insecticides, Schachner discussed N,N-diethyl-m-toluamide (DEET), the active ingredient in many insect repellents. It helps avoid “some terrible diseases,” including mosquito-borne illnesses such as malaria and tick-borne conditions such as Lyme disease, and is available in several convenient formulations, he said.

When used on children, the American Academy of Pediatrics (AAP) recommends products with no more than 30% DEET. And insect repellants are not recommended for children younger than 2 months, or under clothing or damaged skin, he said.

Schachner referred to a case series of 18 children who developed DEET-induced encephalopathy; 13 (72%) involved dermal exposure. Three of those with cutaneous exposure died, mostly from neurologic, respiratory, and cardiac issues. “What’s very striking is that 55% of the kids were exposed to DEET of 20% or less, even though the AAP approves DEET at 30%, so maybe that’s something we have to look at,” he said.

Medication Patches

When it comes to medication patches, much can go wrong when it comes to kids, especially with fentanyl transdermal patches. This was highlighted by the cases Schachner cited, including an infant who developed acute cytotoxic cerebellar edema from fentanyl patch intoxication.

In another case, emergency room staff found a fentanyl patch stuck to the back of a 3-year-old girl. A CT scan showed global cerebral edema, and the patient progressed to brain death. “This is not a unique case; there have been over 10 such cases in the United States,” said Schachner. “We should be doing better with fentanyl.”

Nicotine patches can also be dangerous to children, he added. As for other topical agents, there have been reports of toxicity and deaths linked to salicylic acid, commonly used by dermatologists because of its bacteriostatic, fungicidal, keratolytic, and photoprotective properties.

Schachner cited the case of a 2-month-old where the pediatrician prescribed 50% salicylic acid for seborrheic dermatitis of the scalp, under occlusion. “It’s amazing this child survived; that’s clearly a physician error,” he said.

Henna, a reddish-brown dye derived from the crushed leaves of Lawsonia alba, is used cosmetically for the hair, skin, and nails. Many henna products are mixed with additives, including para-phenylenediamine, which has been associated with dermatitis, asthma, renal failure, and permanent vision loss.

Asked to comment on the presentation, Sheilagh Maguiness, MD, professor of dermatology and pediatrics and chair of pediatric dermatology at the University of Minnesota, Minneapolis, recalled a particularly concerning story in 2008, when the FDA issued a warning about Mommy’s Bliss, a cream containing chlorphenesin and phenoxyethanol as preservatives, promoted to nursing mothers for soothing cracked nipples. There were reports of the cream causing respiratory distress, vomiting, and diarrhea in nursing infants.

Schachner is chair of Stiefel Laboratories and is an investigator with: Astellas, Berg Pharma, Celgene, Ferndale Labs, Lilly, Medimetriks Pharmaceuticals, Novartis, Organogenesis, Pfizer, Sciton; is a c onsultant for: Alphyn, Amryt Pharma, Beiersdorf, Brickell, Cutanea, Hoth, Lexington, Mustela, TopMD, Noble Pharma; a speaker for: Novartis, Sanofi-Regeneron, CeraVe; is on the advisory boards of: Almirall, Alphyn, Apogee, Aslan, Biofrontera, CeraVe, Krystal Biotech, Mustela, Noble Pharma, Pfizer, Pierre Fabre, Sanofi-Regeneron; and owns stocks in: TopMD and Alphyn. Maguiness had no relevant conflicts of interest.