Background

Vitiligo is a chronic, autoimmune skin disorder characterized by depigmented patches in the skin due to melanocyte loss from immune attack. Affecting approximately 1% of the global population, vitiligo imposes significant social and psychological burdens, often leading to stigma and reduced quality of life. A major challenge in vitiligo management is its perception as a cosmetic condition. Despite being an autoimmune disease, several state Medicaid programs, including those in New York, Arizona, Virginia, West Virginia, Alabama, South Dakota, and North Dakota, deny coverage for vitiligo treatments due to this designation. Commercial insurance coverage also varies widely, creating disparities in access to care. These barriers underscore the need for advocacy to reframe vitiligo as a medical condition warranting comprehensive treatment.

Latest in Clinical Evaluation

Accurate clinical evaluation is critical for tailored vitiligo treatment. Subtypes are classified primarily by distribution pattern and extent of body surface area (BSA) involvement. Classifications help guide prognostication and therapeutic decision-making.

Vitiligo Subtypes: Segmental – Unilateral, localized to one dermatome or body segment; usually has an early onset and stabilizes quickly Nonsegmental – Bilateral and often symmetrical; most common form, typically progressive over time. Acrofacial – Involves distal extremities (hand, feet) and eyes, nose, or mouth; often resistant to treatment Focal – Isolated depigmented macules/patches without clear segmental pattern. Generalized – Widespread depigmentation across multiple body regions; often rapidly progressive Lip-tip – Involvement of lips and tips of fingers/toes

Key elements in clinical evaluation: Age of onset, progression rate, triggers, lesion distribution mapping (i.e., pattern, symmetry, BSA involvement), photography for progression monitoring, assessment of disease activity (i.e., Koebnerization, trichome lesions)

Recognizing Disease Activity

The first step in clinical evaluation is determining whether vitiligo is active or stable, as this influences prognosis and urgency of treatment. Disease activity can be assessed using patient history, physical examination, and the below scoring system. General epidemiology and risk factors include: Age between 10-30 years old, family history of vitiligo, thyroid disease, history of skin trauma (Koebner phenomenon).

Vitiligo Signs of Activity Score (VSAS)

VSAS is a valuable tool for predicting disease progression. A 2024 study showed that chance of progression within 6–12 months in patients with one sign of activity is 76.9%, 92.3% with two signs of activity, and 87.1% if there are two affected locations.1 Conversely, the absence of activity signs correlates with a 60% chance of disease stability. This scoring system aids clinicians in identifying patients at risk of rapid progression, enabling timely intervention.

Clinical Signs of Activity

Up to 61% of patients present with one or more of the following signs of activity. These findings are not tied to a specific subtype (e.g., segmental, nonsegmental), but rather reflect the disease’s current behavior and likelihood of progression:

• Koebner Phenomenon: Development of new lesions at sites of skin injury. Observed in 34.1% of patients, and is associated with earlier onset (3–5 years younger than average), greater treatment resistance (23.9% vs. 11.6%), and larger BSA involvement (10.1% vs. 2.4%).2
• Trichrome Vitiligo: Three distinct skin tones (normal, hypopigmented, depigmented). This pattern reflects transitional activity between normal and fully depigmented skin, often with perilesional inflammation.3
• Confetti-like Depigmentation: Small (1–5 mm) depigmented macules, often precede broader depigmentation. May coalesce into larger patches; often an early sign of rapid spread. First reported in 2015.4
• Inflammatory Changes: Erythematous, raised borders surrounding depigmented patches, with histologic evidence of interface dermatitis and focal spongiosis; rare but strongly suggests active inflammation.5

Systemic and Emerging Therapies

The goal of emerging therapies is to halt disease progression and promote repigmentation by targeting the autoimmune and inflammatory pathways implicated in vitiligo.

Systemic Corticosteroids and Pulse Therapy

Systemic corticosteroids, particularly pulse therapy, remain a cornerstone for halting vitiligo progression. A 1993 case series of 40 patients with extensive or rapidly spreading vitiligo, 89% of patients taking corticosteroids (5mg dexamethasone or betamethasone) for two consecutive days per week reported a halt in progression.6 In 2013, a retrospective analysis of 444 patients showed that 91.8% of patients taking dexamethasone for two consecutive days each week(2.5 mg daily) achieved disease stabilization within an average of 13.22 weeks.7

In contrast, repigmentation outcomes with systemic corticosteroids are modest. In the 1993 series, only 3 of 40 patients achieved 90–95% repigmentation, while 8 had no repigmentation. The 2013 study reported that only 1.4% (6/444) of patients achieved over 75% repigmentation.

Adverse events included weight gain (12.5%), lethargy, acne (9.2%), glaucoma, zoster, amenorrhea, headaches, weakness, and bad taste, highlighting the need for vigilant clinician monitoring.

Antimetabolites and Other Agents

Antimetabolites such as methotrexate, mycophenolate mofetil, azathioprine, and cyclosporine are used off-label to manage active vitiligo.

Minocycline is a tetracycline antibiotic known to have potent antioxidant effects. It has shown promise in reducing oxidative stress-induced apoptosis and promoting melanogenesis in vitro.8 A 2014 study compared minocycline (100 mg daily) to dexamethasone minipulse (2.5 mg daily) in 50 patients with recent disease activity. Minocycline reduced the Vitiligo Area Scoring Index (VASI) by 11% (1.71 to 1.52), with 24% of patients developing new lesions, while dexamethasone achieved a 16% VASI reduction, with 12% developing new lesions.9 These findings suggest minocycline as a potential alternative for patients intolerant to corticosteroids.

Janus Kinase (JAK) Inhibitors and Emerging Therapies

JAK inhibitors represent a transformative advancement in vitiligo treatment. Dr. Huang highlighted three JAK inhibitors currently in Phase III trials: ritlecitinib (JAK3 and TEC kinase inhibitor), upadacitinib (JAK1 inhibitor), and povorcitinib (JAK1 inhibitor). Additionally, deucravacitinib (TYK2 inhibitor) and afamelanotide (MSH analogue) currently in clinical trials, with some also approved for other conditions and being explored off-label, alongside Phase II trials for anifrolumab (IFN-alpha receptor inhibitor), MK-6194 (IL-2 analogue), and AMG-714 (IL-15 inhibitor). Clinical trial data for JAK inhibitors demonstrate significant improvements in facial and total VASI scores (F-VASI and T-VASI).