Ilona Frieden, MD

 has been transformed over the past 15 years by advances in genomics and the repurposing of targeted cancer therapies. Somatic mutations occurring during fetal development, rather than inherited, have been identified as drivers of conditions like venous and arteriovenous malformations, opening the door to pathway-specific treatment.

 granted accelerated approval to alpelisib (Vijoice; Novartis) for adult and pediatric patients aged ≥ 2 years with severe manifestations of PIK3CA-related overgrowth spectrum who require systemic therapy.

 This is 1 example of how oncology-derived agents are now reaching this patient population. Other agents, including oral sirolimus and the MEK inhibitor trametinib, are also being used or studied in this space, often in multidisciplinary settings alongside hematology and oncology.

, Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, offered an update on where the science stands and what clinicians should know.

 In the following Q&A, the third in a series covering her session at the meeting, Frieden outlines which mutations are implicated, how and when to consider testing, and which therapies are being used or studied. Read the first two parts of the interview on 

pearls for using drugs for common conditions

Can you walk us through your session on vascular birthmarks and the role of genomics?

 In the last 15 years, we've been able to identify mutations in tissue that cause vascular birthmarks, just in a region of the body. These are called somatic mutations. It's not a germline mutation; it's not passed from parent to child, but these are mutations that occur during the course of development.

Everyone is a mosaic in some form or other, and that's what we mean by that. In this case, these mutations cause dilated veins, capillaries, arteries—things like that.

Understanding what the genes are that result in these conditions has allowed us to look for medications that can target them. I talk about testing and how one goes about testing for these mutations and when you should consider testing. Then I talk about some of the emerging medications that can be used for treatment.

Which treatments are currently being used or studied for these conditions?

 Sirolimus is available in an oral form and is one of the main ones we use because it does target 1 of the major pathways involved in the formation of these conditions. Oral sirolimus is not FDA approved for that use, but it's very widely used.

Then there are drugs like MEK inhibitors [and] drugs like alpelisib. Alpelisib is approved for treating breast cancer, but the PIK3 gene mutation that causes certain forms of breast cancer also causes these birthmarks in a developmental sense. Not because they're going to [develop] cancer, but because if you have a mutation in development, it can lead to a specific kind of birthmark. You can use drugs that inhibit PI3K, block these pathways, and improve people's lives considerably.

Alpelisib is now actually FDA approved for the treatment of certain vascular malformations, even down to 2 years of age. There are others emerging that are not yet FDA approved, including one called trametinib, which is a MEK inhibitor used for treating arteriovenous malformations and other vascular malformations.

How should clinicians approach prescribing these medications?

 The idea [here is] not that we do these on our own. I personally think that you always want to be partnering with a hematologist or oncologist when you are giving these kinds of medications.

These are examples that really need to be done in a multidisciplinary setting where you have additional expertise. [This session is] really to give people an update on what's on the horizon because more of these are in clinical trials and will be used in the near future.

Frieden I. Pediatric Dermatology Update 2026. Session presented at the Maui Derm Summer 2026 meeting in Colorado Springs on June 26.

Frieden I. Expanding Use of Dupilumab in Pediatric Patients, With Ilona Frieden, MD. HCPLive. Published on June 27, 2026. Accessed June 30, 2026. 

https://www.hcplive.com/view/expanding-use-dupilumab-pediatric-patients-ilona-frieden-md

Frieden I. Pearls for Using Drugs for Common Conditions, With Ilona Frieden, MD. HCPLive. Published on June 30, 2026. Accessed July 7, 2026. 

https://www.hcplive.com/view/pearls-drugs-common-conditions-ilona-frieden-md

Singh S, Bradford D, Li X, et al. FDA Approval Summary: Alpelisib for PIK3CA-Related Overgrowth Spectrum. 

Articles

Frieden discusses somatic mutations driving vascular malformations and how repurposed cancer therapies like alpelisib and sirolimus are changing care.

How Genomics Is Changing the Way Clinicians Treat Vascular Birthmarks in Children

Beyond newer biologics, some of the most useful tools in

are drugs already sitting on the shelf. At 

, Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, shared practical pearls on repurposing topical timolol and sirolimus.

 Her examples spanned common conditions like spider angiomas to keratosis pilaris rubra.

In the following Q&A, Frieden discusses where the evidence stands for these off-label approaches. She also touches on why they may be worth considering for difficult-to-treat patients and what research is still underway. In the first part of the interview, Frieden discussed 

 in conditions including epidermolysis bullosa pruriginosa, epidermal differentiation disorder, Netherton syndrome, and solid facial edema.

What pearls do you have for using existing drugs to treat more common conditions?

 I had a couple of examples. One is using topical timolol, which we now use quite commonly as an off-label treatment for infantile hemangiomas. There's a very large body of literature [showing] more than 1000 patients [were] treated with topical timolol very safely in infancy.

Now there are reports of that medication—which is a topical beta blocker… basically a repurposed glaucoma eye drop—being used for spider angiomas and pyogenic granulomas. These are 2 vascular conditions where the blood vessels are dilated or proliferating, and in both there's evidence that [they] can be effective.

 What does that look like in practice for a condition like spider angiomas?

Spider angiomas [are] something we see commonly: dilated little blood vessels often on the hands or face of young children. Pulsed dye laser is a great treatment for that, but it's not a great treatment for a 4-year-old, because you have to hold them completely still and cover their eyes, and that's hard to do. So topical timolol could be tried in those kinds of patients just to see if it's effective.

There's one small case series where [in] 2 out of… 6 or 7 patients, it was completely effective, and in some of the others, it was partially effective. It sort of falls into the "worth a try" category for a pretty common condition, and it's been used very safely. If you use just 1 or 2 drops a day, it's very safe on the skin, and we know that from our experience with hemangiomas.

 Are there other conditions where this kind of off-label repurposing applies?

Another condition I'm going to talk about is keratosis pilaris rubra. These are people who have…very rough, red cheeks. Prince Harry is the leading example of a famous person with keratosis pilaris rubra on the face. It can be a really disturbing condition to people because their face is either partly red all the time or turns red very easily [with] heat.

There's a very small number of cases that have now been treated with topical sirolimus as an off-label treatment. Sirolimus is an mTOR inhibitor. We use it orally [for] treating [severe] vascular birthmarks… often being treated at major tertiary care centers. Topical sirolimus is [FDA] approved in children [ages] 6 and up for treatment of angiofibromas, which is a complication of tuberous sclerosis.

How early are we in understanding sirolimus's potential for KP rubra?

This medication topically may be repurposed… for treating KP rubra, and it's very early. But there are some open-label, investigator-initiated trials ongoing to look at this further, so it's just something to think about that might be useful in the future.

Frieden I. Expanding Use of Dupilumab in Pediatric Patients, With Ilona Frieden, MD. HCPLive. Published on June 27, 2026. Accessed June 30, 2026. 

Frieden shares practical tips on repurposing topical timolol and sirolimus for pediatric skin conditions.

Pearls for Using Drugs for Common Conditions, With Ilona Frieden, MD

Dupilumab (Dupixent; Sanofi/Regeneron) received FDA approval on June 7, 2022, for children aged 6 months to 5 years with 

. Its utility, however, may extend well beyond labeled indications.

, Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, outlined a growing body of evidence supporting off-label use of dupilumab across a range of pruritic and inflammatory pediatric skin conditions.

 In the following Q&A, Frieden discusses which conditions are generating the most interest, how she weighs the risk-benefit calculus in pediatric patients, and why safety data borrowed from other specialties can help guide decision-making.

Can you walk us through what you're covering on the expanding use of dupilumab?

 With dupilumab, I really talk about the fact that it's FDA-approved for atopic dermatitis, down to just a few months of age. It's also approved for children age 12 and over for chronic spontaneous urticaria.

We see children who have prurigo nodularis as a disease manifestation, but it's only approved for adults with prurigo nodularis. Certainly, we use drugs commonly off label, and so we would consider it for that.

There’s a whole list of expanded indications that have been reported in small case series or sometimes larger case series for things that are itchy for other reasons. There's a rare form of epidermolysis bullosa that's very itchy—it's really life-transforming for that. It's called EB pruriginosa, which stands for pruritic EB. There's also a form of ichthyosis, what's now called epidermal differentiation disorder, [and] Netherton syndrome, another rare disease [with] severe pruritus, where it can be transformative.

HCPLive: Can you provide examples of which conditions use the expanded use of dupilumab?

One is a disease called solid facial edema, which is considered to be possibly a form of lymphatic disruption, often due to acne on the face. It's a very rare disease, but there's a report in the literature from last year, and I show a very dramatic case of a patient of ours where it was truly incredibly effective.

We don't really know why, because dupilumab has a very narrow spectrum as an antagonist of IL-4 and 13. But there's a lot we don't know about biology, and anything that has some degree of inflammation or itch is certainly something we can consider. We know it's a very safe medication in children because it's been used in tens of thousands of pediatric patients at this point for atopic dermatitis.

I also show an example of older patients who have chronic irritation in the groin area, sometimes from leaking of urine. These are children who have an increased propensity for accidents, and sometimes they have developmental disabilities, so they don't control their bowel and bladder very well, and sometimes they're in diapers. Anecdotally, we've seen that some of those patients improve a lot with dupilumab, which is not something we would necessarily expect, but it might be something worth trying in some of these tough management cases.

HCPLive: What is your central principle in evaluating whether you are going to try a new medication?

 One of the central principles I use in evaluating whether I'm going to try a new medication is what’s our experience in children in other diseases? Because we can have a lot of safety data even if we don't have data about a specific illness. In many conditions we borrow—for example, other biologic agents—pediatric rheumatologists or gastroenterologists will be using drugs like Humira long before we do. They have a lot of safety data in children, and we can borrow from them and say, ‘well, this is the experience in children that's already been looked at, even if it's not for the condition we're treating.’

That's one of the ways that, as pediatric dermatologists, we try to extrapolate whether or not it's worth taking the risk [or] whether the benefit might outweigh the risk for very difficult cases.

Butera A. FDA Approves Dupilumab as Add-On for Youngest Atopic Dermatitis Patients. HCPLive. Published on June 7, 2022. Accessed June 26, 2026.

Pediatric Dermatology Update 2026. Session presented at the Maui Derm Summer 2026 meeting in Colorado Springs on June 26.

Dupilumab is FDA-approved for pediatric atopic dermatitis down to 6 months and for chronic spontaneous urticaria in patients ≥12 years, yet mounting pediatric dermatology experience supports broader off-label exploration. Reported benefits span intensely pruritic, inflammatory, and rare genodermatoses, sometimes with life-altering itch reduction. Despite its relatively narrow IL-4/IL-13 blockade, clinical responses have been observed in conditions with unclear pathobiology. Off-label decision-making is guided by disease severity, therapeutic need, and extrapolated pediatric safety data from other specialties’ biologic use.

Frieden on expanding dupilumab use in pediatric skin conditions: prurigo nodularis, EB pruriginosa, and more.