Vitiligo Updates

Vitiligo remains one of the most difficult conditions for both patients and dermatology providers. As a chronic, autoimmune inflammatory response to unknown triggers, it may be affected by stress, physical skin trauma, exposure to chemicals, or sun exposure. Vitiligo presents with depigmented, well-defined, non-scaly patches in either segmental or non-segmental patterns. Segmental vitiligo often includes depigmentation of involved hairs and can present in a dermatomal or blaschkoid pattern. A form of underlying cutaneous mosaicism, the blaschkoid pattern corresponds to ectodermal or

neuroectodermal embryological migration cell patterns [1]. Non-segmental vitiligo often involves both sides of the body in a symmetrical pattern. Hairs remain pigmented in non-segmental vitiligo, but may become depigmented in more advanced disease. A combination of both segmental and non-segmental

patterns is also seen in some patients. Most patients with vitiligo will have onset of disease prior to age 30. Vitiligo affects all skin types and ethnicities and may be associated with thyroid disease or other autoimmune conditions. When treating vitiligo patients, it is imperative that we consider the

psychosocial impact of their disease, especially in those with facial, hand, or genital involvement.

For many years, vitiligo specific treatment options have eluded us, but with recent developments in the JAK-STAT pathway, we have opened the door to new possibilities for vitiligo management. To review vitiligo pathophysiology, an environmental trigger combined with genetic predisposition leads to

melanocyte distress. The melanocyte distress signals an immune inflammatory response via activation of CD8+ T-Cells that target melanocytes and release interferon gamma. Interferon gamma then binds to JAK1 and JAK2, activating the JAK-STAT pathway, and inducing the release of hemokine ligand 9/10 (CXCL 9/10), which continue to attract more CD8+ T-cells to the site and creates more inflammation. T-cell mediated melanocyte death leads to the depigmentation we see in vitiligo [2].

Repigmentation requires suppression of the inflammatory cascade (via inhibition of the JAK-STAT pathway) and stimulation of melanocyte precursors to become mature melanocytes. In July 2022, 1.5% ruxolitinib cream became the first FDA approved topical JAK inhibitor for the treatment of nonsegmental

vitiligo in adult and pediatric patients 12 years of age and older. The most effective areas for stimulation of repigmentation are in the epidermis and follicular unit within vitiligo lesion borders. Areas with increased density of hair follicles, such as the trunk and extremities, typically repigment most quickly. Conversely, areas with low density of hair follicles (palms, soles, genitals, volar wrists, mucosa) are less likely to regain pigment.

It is truly an exciting time to be in dermatology. Recent developments in previously unchartered pathways have led to new treatment options across a variety of disease states. Just as we have seen the psoriasis landscape explode over the past several years, we can hope to someday be able to offer a portfolio of options for our vitiligo patients as well. The JAK-STAT pathway may be just the beginning!

References:

1. Palanisamy A, Singh B, Kothandapany S. Vitiligo and lines of Blaschko. Pigment Int [serial online]

2015 [cited 2022 Aug 7];2:60-1.

2. https://www.vitiligodeeper.com

Jennifer M. Conner, MPAS, PA-C has been a dermatology PA for over 16 years and practices in Indianapolis. She served in the U.S. Army for 11 years as a medic, Medical Specialist Corps officer, and battalion physician assistant. Jennifer is a past president of the Society of Dermatology PAs, founding trustee of the Dermatology PA Foundation, and is proud to be a founding member of the Elevate Derm Advisory Board.