Vitiligo: Combination Therapies and Emerging Treatments

CARLSBAD, Calif. — When patients with vitiligo see Jessica Shiu, MD, PhD, for the first time, some mention that prior healthcare providers have told them that vitiligo is merely a cosmetic issue — much to her dismay.

“Vitiligo is not a cosmetic disease,” Shiu, assistant professor of dermatology at the University of California, Irvine, said at the annual meeting of the Pacific Dermatologic Association. “It is associated with significant depression, stigmatization, and low self-esteem. I have patients who say that vitiligo has affected their marriage…. In certain cultures, it also affects their job prospects.”

As the most common pigmentary disorder, vitiligo is an autoimmune condition that often results in the recruitment of CD8+ T cells into the skin. These cells destroy melanocytes, depleting melanocytes in the epidermis. “Over time, this results in milky white patches of skin that we often see in our patients,” Shiu said.

There are two main subtypes of vitiligo. The segmental form is unilateral and presents in younger people, while the more common nonsegmental form usually involves both sides of the body and can involve different sites. “Depending on the site that is involved, the nonsegmental form can be further divided into focal, acrofacial, mucosal, generalized, and universal subtypes,” she said. The first step in your initial management is to determine if the vitiligo is active or stable, which can be challenging. Clinical signs of active disease include the presence of trichome vitiligo, confetti vitiligo, and koebnerization.

“Another sign of active disease is when patients tell you that their vitiligo is expanding rapidly,” Shiu added. “Stable vitiligo is more difficult to define. Many patients think their lesions don’t change, but we’re now appreciating that there can be some sites in those patients such as the hands and feet that are more susceptible to change in activity.” In general, she noted, vitiligo is considered stable when there is no change in activity for at least 12 months, and “lesions are usually completely depigmented with sharp borders.”

The level of vitiligo disease activity drives medical management. For patients with nonsegmental vitiligo who have clinical signs of active disease, the first goal is to stabilize the active disease and stop further spread of depigmentation. “This is key because losing pigment can occur very quickly, but gaining pigment back is a very slow process,” she said. Stabilization involves suppressing immune responses with topical steroids, topical calcineurin inhibitors, or 1.5% ruxolitinib cream, a JAK inhibitor that became the first US Food and Drug Administration (FDA)–approved pharmacologic treatment for nonsegmental vitiligo, in 2022, for patients aged 12 years or older.

“The choice here depends somewhat on insurance coverage and shared decision-making with the patient,” Shiu said. Meanwhile, clinical trials evaluating the effect of the oral JAK inhibitors ritlecitinib, upadacitinib, povorcitinib, and baricitinib on vitiligo are underway.

Combining Phototherapy With Topical Treatment

A mainstay therapy for nonsegmental vitiligo is phototherapy, which can induce the migration of melanocyte stem cells from hair follicles. “There’s good data to show that combining topical treatment with phototherapy can augment the repigmentation that you see,” she said. “So if it’s possible, try to add phototherapy for your vitiligo patients, but sometimes, logistics for that are a challenge.”

Discussing treatment expectations with patients is key because it can take up to 1 year to see a significant response with topical immunosuppressants and narrowband ultraviolet B treatment. The head and neck areas are often the first sites to repigment, she said, followed by the extremities or the trunk. “The hands and feet are generally last; they are usually the most stubborn areas,” Shiu said. “Even when you do see repigmentation, it usually happens on the dorsal surfaces. The tips of the fingers and toes are difficult to repigment. Luckily, the face is one of the top responders, so that helps a lot.”

While some treatment efforts result in “complete and beautiful” repigmentation, she added, many yield uneven and incomplete results. “We don’t understand why repigmentation occurs in some areas but not in others,” she said. “We don’t have any biomarkers for treatment response. That is something we are looking into.”

For a patient with rapidly progressing active disease, consider an oral steroid mini-pulse 2 consecutive days per week for a maximum of 3-6 months. “I usually recommend that patients do this on Saturday and Sunday,” Shiu said. “Studies have shown this strategy can halt progression in 85%-91% of cases if patients are on it for at least 3 months.”

Relapse after successful repigmentation occurs in about 40% of cases following discontinuation of treatment, so she recommends biweekly application of 0.1% tacrolimus ointment as maintenance therapy. “Studies have shown this is enough to decrease the relapse rate to around 9%,” she said.

Tissue, Cellular Grafts

Surgical repigmentation strategies rely on transplanting normal skin to areas affected by vitiligo. In general, more than 50% of patients achieve more than 80% repigmentation. Options are divided into tissue grafts vs cellular grafts. “The old methods are tissue grafting such as punch grafting, tissue blister grafting, and spit thickness grafting, which can treat limited areas of skin,” Shiu said. Newer approaches include cellular grafting using the melanocyte-keratinocyte transplantation procedure, which can treat larger areas of skin.

The main drawback of this approach is that it is expensive and there is no insurance code for it, “but I hope that this becomes an option for our patients in the future because data indicate that repigmentation is maintained for up to 72 months after treatment,” she said.

In June 2023, an autologous cell harvesting device known as RECELL received FDA approval for repigmentation of stable vitiligo lesions. According to a press release from the manufacturer, AVITA Medical, a clinician “prepares and delivers autologous skin cells from pigmented skin to stable depigmented areas, offering a safe and effective treatment for vitiligo.”

Shiu disclosed that she received research support from AbbVie.