Q&A: Treating Vitiligo in Difficult Sites Requires Patience and Precision

Vitiligo presents unique therapeutic challenges, particularly in areas with limited hair follicle density or high cosmetic visibility. Topical ruxolitinib (Opzelura; Incyte) has offered clinicians and patients a new long-term, nonsteroidal option, but real-world management often involves individualized strategies and combination regimens. In a recent interview with Dermatology Times, Marc Serota, MD, a dermatologist, allergist/immunologist, pediatrician, and obesity medicine specialist practicing in Littleton, Colorado, discusses his clinical experience optimizing ruxolitinib therapy, managing expectations, and exploring the future landscape of vitiligo treatment.

Q&A

Dermatology Times: In challenging anatomical areas, what modifications to application or adjunctive therapies do you use, and how do outcomes compare to less difficult sites?

Serota: Certain difficult sites, like the palms or certain areas of the face, are harder to treat because they don’t have many hair follicles. Hair follicles are where melanocyte stem cells originate, so areas with fewer follicles tend to respond more slowly. In these situations, I want patients to be able to treat themselves longer and with confidence, without fear of side effects like atrophy, striae, or telangiectasia. Historically, patients have been conditioned not to use steroids excessively because of those concerns, but with ruxolitinib, they can use the medication as needed to generate results without developing those fears.

DT: What is your approach to combining topical ruxolitinib with other modalities such as phototherapy, topical steroids, or calcineurin inhibitors to maximize repigmentation?

Serota: For vitiligo, which is such an impactful disease, you can take a more aggressive “kitchen sink” approach. If you want to jumpstart treatment with a potent topical steroid, that’s reasonable. But having something like ruxolitinib on board allows patients to maintain their improvement long term. Combining phototherapy is also a great idea because you’re targeting different pathways. Patients can get stable on phototherapy while also using a topical agent. I think the future is exciting; we’ll likely have systemic options where we can combine an FDA-approved topical for non-segmental vitiligo with a systemic agent to target immune responses more broadly.

DT: Have you encountered any off-label use of ruxolitinib, and what has been your experience in those situations?

Serota: Yes. The on-label uses for ruxolitinib are atopic dermatitis down to age 2 and non-segmental vitiligo down to age 12. Off-label use generally involves patients who don’t fall within those categories but still deserve quality treatment. As a pediatrician before becoming a dermatologist, I’m used to advocating for patients to receive medications off-label when appropriate. For instance, I would advocate for a vitiligo patient under 12 to get ruxolitinib if clinically indicated. Other off-label uses include perioral dermatitis or other inflammatory skin conditions, not just atopic dermatitis.

DT: How do you balance patient expectations regarding the speed and extent of repigmentation versus realistic timelines, especially in areas that are classically refractory?

Serota: I tell patients that outcomes vary based on body area, follicle density, and natural sunlight exposure. Overall, it’s a marathon, not a sprint. Unlike some treatments where response plateaus at week 16, with ruxolitinib, you see slow, steady repigmentation past 36 weeks. So the more consistent a patient is with therapy, the higher the chance of reaching measurable endpoints. Counseling patients that improvement is gradual helps maintain adherence and realistic expectations.

DT: What are the early signs that a patient is unlikely to reach a high repigmentation threshold with topical therapy, and when do you consider adjunct or alternative treatments?

Serota: Early signs of response include “islands” of repigmentation, which can initially concern patients because it looks like polka-dot skin. I counsel them that this is positive—it means melanocytes are regenerating from stem cells. If these islands do not appear at key time points—around 16, 24, or 36 weeks—we consider adding other modalities, such as localized phototherapy or a short course of a potent topical steroid.

DT: Considering ongoing regulatory scrutiny, what is your standard conversation with patients about ruxolitinib’s boxed warning and its relation to tofacitinib?

Serota: I explain that the boxed warning comes from systemic JAK inhibitor data, particularly tofacitinib in older rheumatoid arthritis patients with multiple comorbidities. That doesn’t directly apply to topical ruxolitinib, which has minimal systemic absorption. Once patients understand that context, they’re reassured. It’s a quick, but important conversation.

DT: Do you have any examples where a patient with vitiligo in a difficult area achieved an unexpected level of repigmentation?

Serota: Yes. The hands are among the hardest areas to repigment. I’ve had patients who didn’t fully respond initially, but when we added a home phototherapy unit, we saw improvement. These devices are easy to use, affordable, and portable, even for travel. Using a combination of topical therapy and accessible phototherapy often leads to successful repigmentation in challenging areas.

DT: Outside of currently available or on-label treatments for vitiligo, what developments are you most excited about in the near future?

Serota: Systemic JAK inhibitors are at the top of the list. They’ve already been life-changing for alopecia areata, and I hope we’ll see similar data and FDA approvals for vitiligo. I’m also excited about integrating metabolic and dermatologic care. For example, obesity contributes to inflammation, which drives conditions like psoriasis. Using therapies that target both skin and systemic inflammation, like GLP-1 receptor agonists, can improve both skin outcomes and long-term health. I see that integrated approach as the future for vitiligo care as well.

Conclusion

Serota emphasizes a patient-centered, flexible approach to vitiligo treatment: combining topical therapy, phototherapy, and, where appropriate, short-term corticosteroids or future systemic agents. His strategy balances efficacy with safety, manages realistic expectations, and addresses challenging anatomical sites, reflecting a broader trend in dermatology toward individualized, multimodal care.