Long underserved by a narrow armamentarium, patients with pigmentary disorders could soon see a new wave of oral and topical solutions to treat even the most challenging cases.
The range of treatment modalities for pigmentary disorders has been frustratingly limited, according to Seemal Desai, MD, FAAD. “In fact, the lack of choice has been horrible,” he said. Desai is a clinical assistant professor in the Department of Dermatology at the University of Texas Southwestern Medical Center in Dallas.
The next 12 to 24 months could start resolving that problem. “We are truly on the cusp of some revolutionary changes, particularly as clinical trial results for topical and oral Janus kinase [JAK] inhibitors continue to evolve as possible treatments for vitiligo and other conditions,” Desai noted during his session on pigmentary disorders with fellow presenter Janiene Luke, MD, FAAD, at the Fifth Annual Skin of Color (SOC) Society Media Day, held virtually November 9, 2021.1
Desai credited heightened public awareness of both the physical and psychological impact of pigmentary disorders for creating a sense of urgency around expanding the armamentarium. Equally important, he said, is the effort to increase insurers’ and regulatory agencies’ willingness to classify pigmentary disorders as medical conditions, not cosmetic concerns.
The numbers, both in terms of patients and economic impact, provide hope that progress will continue. Drivers ranging from increased prevalence of pigmentary disorders—these conditions are the third and fourth most common dermatoses in Black and Hispanic patients, respectively2—to growing expenditures on dermatologic treatments are among the factors that could build the treatment market from $5.6 billion in 2020 to a forecast $8.6 billion by 2026.3
New Hope for Patients With Vitiligo
The earliest beneficiaries of this wave of innovation could be patients with vitiligo. The National Clinical Trials registry reported that 46 vitiligo-related clinical trials were at some stage of development as of November 30, 2021.4 Although study outcomes for the topical JAK inhibitor ruxolitinib (Opzelura; Incyte), which was FDA approved to treat atopic dermatitis (AD) in September 2021, and oral JAK inhibitors are getting the most attention, investigators are examining options such as combining topical prostaglandin F2⍺ analogues with fractional CO2 and excimer lasers and pairing oral vitamin D with phototherapy, as well as exploring new approaches using red or UV light therapies.
The availability of wider choices opens the way for a more proactive patient conversation, Desai said. “Ask the patient what their goals are and then discuss how you, as the doctor partner, can help achieve those goals,” he advised. “Does that individual just want to achieve repigmentation of their face? Some patients are self-conscious about the way people look at their face, but they’re not really worried about areas of their body that are usually covered. Others may be bothered more by vitiligo on their hands or even their genital area. You need that information to develop an effective treatment plan for that individual.”
In an interview with Dermatology Times®, Desai also recommended conducting a full-body examination and asking the patient how many lesions emerged in the past 4 to 6 weeks. “If there was a significant increase or if the disease is covering 1% of their body surface area, in my opinion, that means the patient is unstable,” he said.
Patients with rapidly spreading vitiligo need prompt action. “They have to be stabilized as soon as possible so that the pigmentation disorder doesn’t continue to spread,” Desai said. “Right now, systemic steroids are what I use most. The shorter the response time, the better the chance of repigmentation. Potentially, the JAK inhibitors will be another option. I have used JAK inhibitors off label in patients with unstable disease, and they did very nicely in stabilizing their vitiligo.”
Even though JAK inhibitors produce efficacy benefits in clinical trials, some challenges remain. If these agents receive FDA approval, the agency is likely to require the same black box warning about adverse effects (eg, major adverse cardiovascular events, thrombosis, cancer, and all-cause mortality) that was applied to ruxolitinib’s approval to treat AD. Desai echoed the recommendations of many dermatologists by advising physicians to discuss the different absorption rates of topical vs oral medications, weighing the risks and reward for the individual patient’s case, as well as assessing efficacy and safety compared with other options.
Although JAK inhibitors hold promise, the FDA noted that the approvals thus far are “for certain patients who have not responded or cannot tolerate 1 or more TNF [tumor necrosis factor] blockers.”5 Desai agreed with that stance. “If it’s early on, I would still use systemic steroids because they do work well in stabilizing the patient,” he told Dermatology Times®. “I would probably wait to go to the JAK inhibitors for a patient with widespread disease.”
It will take some time and more research to better define when and how to make that switch; which patients would be the best candidates for the changeover; and how to manage the fact that the JAK inhibitors are not approved as ongoing, long-term treatments. “We don’t have answers for questions like these at this juncture,” Desai said, “but I’m hopeful we’ll see some data soon.”
There is still conjecture about the age range for eligible patients with vitiligo, according to Desai. “It may be 18 and up, but I’m hoping it’s 12 and up,” he added.
Desai is also watching studies on phototherapy and light energy advances. “We are going to see continued enhancements in targeted devices,” he predicted. “Some of the most exciting studies involve wavelengths in UV-B. These are narrowband wavelengths—308 to 311 nm. We will be able to focus on a lesion and, potentially, treat it with a scatter of rays.”
Also on his radar: studies on therapies that would block IL-15 and research on CXCL10 signaling. “There is a lot on the horizon for vitiligo,” he said. “I’m very hopeful.”
Turning to melasma, Desai pointed out that new triggers are emerging. Although underlying hormonal abnormalities, genetic abnormalities, UV exposure, and vascular characteristics still play a major role, environmental factors may also affect this skin disease. “We are seeing new research relating to visible light, [light-emitted diodes], and incandescent light,” he said. “People are sitting in front of a webcam for 10 hours a day. Does that affect patients’ melasma? The answer is that it probably does, but we need more data to support that premise and consider appropriate treatment.”
Advances in Aesthetic and Adjunctive Solutions
Photoprotection remains an important part of preventing and managing pigmentary disorders. In addition to following standard photoprotection protocols, Desai said, physicians should be ready to counsel patients on alternatives such as oral or topical Polypodium leucotomos extract, made from ferns native to Central and South America. Available in the United States since 2006, this nutraceutical hit the headlines more recently after results of a 2021 study showed positive outcomes for reducing inflammation and exerting photoprotective effects.6
Going forward, Desai identified sunscreens with better visible light blockers as an unmet need. “Iron oxide is the best filter we have to block visible light,” he said. “We can’t just focus on UV-A and UV-B. We have to prioritize evolving sunscreens with sensory filters that block visible light because visible light can trigger melanin production.”
Luke, who is an associate professor and residency program director in the Department of Dermatology at Loma Linda University in California, noted that aesthetic procedures such as new types of chemical peels, microneedling, and injection of platelet-rich-plasma “have all been studied and have somewhat mixed results.” Lasers, especially nonablative fractional technological and surfacing devices, may play a role in increasing the literature on pigmentary conditions, she said. “Whatever the device, physicians need to be judicious and use the most conservative device settings when dealing with patients with skin of color,” she added.
Research directions that could open new options include further study on inhibitors that target tyrosinase and limit melanin synthesis and alternatives to hydroquinone. “In terms of what’s new and what’s next, topical and oral tranexamic acid is really exciting,” Luke said.
Both Desai and Luke cautioned that even with this wave of innovation, treating pigmentary disorders is about care, not cure. “While these advances can be helpful,” Luke said, “it is crucial for patients to understand that, even with medical prescriptions and aesthetic procedures, pigmentary disorders can flare from time to time.”
Desai and Luke reported no relevant disclosures in relation to this presentation.