The latest consensus statement released in JAMA Dermatology on March 13, 2024, sets a new standard in the USA for vitiligo treatment among children, teenagers, and young adults. This pioneering guideline, led by Drs. Yael Renert-Yuval and Nanette Silverberg of the Icahn School of Medicine at Mt Sinai in New York, synthesizes research and expert insights to address vitiligo's distinct challenges in younger patients.

Through a thorough review of English-language studies providing primary data on pediatric vitiligo, the team established 42 key recommendations, focusing on diagnosis and the effective use of topical treatments, with 33 of these recommendations receiving strong consensus. 

Key findings highlighted the importance of topical corticosteroids (TCSs), calcineurin inhibitors (TCIs), and Janus kinase (JAK) inhibitors as essential elements of initial treatment, underscored by substantial evidence and expert agreement. The statement provides specific guidance on dosages, treatment durations, and considerations for different age groups. For instance, it backs the twice-daily application of topical calcineurin inhibitors and circumspect use of topical corticosteroids to mitigate the risk of skin atrophy. It also supports the off-label application of 1.5% ruxolitinib cream as a first-line treatment for children under 12 with nonsegmental vitiligo.

TAKEAWAY

• TCIs, TCSs, JAK inhibitors, and phototherapy, specifically narrowband ultraviolet (UV)-B light therapy, are mainstay treatments; the combination of UV-B light and topical therapy may enhance initial repigmentation.
• Long-term monitoring for skin cancers is advised, and short outdoor UV exposure is suggested for pediatric patients.
• TCIs, such as tacrolimus and pimecrolimus, are recommended as first-line therapy, particularly on the face, applied twice daily for ≥ 3 months; continued use for 6-12 additional months is recommended if repigmentation is observed.
• The choice of TCS class depends on the site and planned usage duration. Short-term use or overlap with TCIs is recommended because of the risk for atrophy with long-term TCS use. Class 5-6 agents are another option.
• For areas with thin skin, TCSs can be considered second-line treatments.
• Topical JAK inhibitors, specifically topical 1.5% ruxolitinib cream, are recommended for patients aged ≥ 12 years, as first- or second-line therapy. Limitation to 10% body surface area is recommended to minimize systemic absorption. Limited evidence exists for children aged < 12 years.

"Suggested next steps include development of a long-term vitiligo registry and head-to-head short- and long-term comparisons of all three major classes of topical therapy," the authors write. "Future studies of vitiligo should aim to identify the role of early intervention as a means of controlling long-term disease activity and preventing T-memory cell accumulation."

SUMMARY

Section 1. General Definition and Diagnosis

1)  Vitiligo is an acquired and often progressive chronic, relapsing, pigmentation disorder characterized by depigmented patches corresponding to a substantial loss of functioning melanocytes. It can be segmental, non-segmental/ or mixed and has high impact on quality of life (Expert consensus).
2)  Wood’s lamp is considered a useful in office tool for confirmation of diagnosis and extent of disease (Expert consensus).
3)  Biopsy at the edge of a lesion can also be used for confirmation of diagnosis, when diagnosis cannot be ascertained clinically (Expert consensus).
4)  In the setting of concerning prognostic signs, closer observation for progression and more aggressive therapy is needed including: Leukotrichia, halo nevi, trichrome, confetti depigmentation, Koebner phenomenon, nonhair bearing anatomical site, young age with diffuse nonsegmenal disease (Expert consensus).

Section 2. Therapeutics with Sort Grading

i. General Recommendations

1)  Topical steroids (C3), topical calcineurin inhibitors and UVB light therapy in the form of light box or excimer laser (A1) are standard of care in young patients, however emerging data on the usage of JAK inhibitors topically is promising (C3).
2)  The combination of ultraviolet B light sources including 308-nm laser or Narrowband UVB to topical therapies, including topical calcineurin inhibitors (A1) or
topical corticosteroids, may enhance initial repigmentation response (C3).

Section 3. 

1)  Consideration for risk of carcinogenesis includes counseling and long-term monitoring of patients with prior phototherapy for skin cancers (Expert consensus).
2)  For pediatric patients, Short Outdoor UV Exposure (10-15 minutes) May Enhance Response to Topical Therapy (Expert consensus).

i. Topical Calcineurin Inhibitor Recommendations

1)  Topical tacrolimus can be used as first-line therapy for vitiligo in children, adolescents (ages 2-18 years), and young adults (A1).
2)  Topical pimecrolimus can be used as first-line therapy for vitiligo in children, adolescents (ages 2-18 years), and young adults (C2).
3)  TCI can be used as first-line therapy for vitiligo in children, adolescents (ages 2-18 years), and young adults (A1).
4)  TCI can be used first line for vitiligo on the face and body, without causing atrophy (A1).
5)  Due to risk of thinning with long-term usage of topical corticosteroids, short-term usage or overlap with calcineurin inhibitors is needed (Expert consensus).
6)  The standard protocol of usage of TCIs for pediatric vitiligo is twice-daily application for a minimum of three-months (Expert consensus).
7)  If no evidence of repigmentation at 3 months, alternative agents should be considered (Expert consensus).
8)  Usage trials support continued usage for 6-12 months when evidence of repigmentation is noted (A1).
9)  Counseling on risk of burning, stinging or itching in the first month of application is recommended (A1).
10)  Patients should be advised to discontinue for visible signs of irritation or inflammation (Expert consensus).
11)  Although current databases do not show statistically significant increases in lymphoma and skin cancer in children receiving TCI therapy, counseling about theoretical risk based on the label is recommended (Expert consensus).
12)  Usage of topical calcineurin inhibitors for children under the age of 2 years with vitiligo has some limited supporting evidence (C2).
13)  Topical calcineurin inhibitors appear effective in all pediatric Fitzpatrick skin types, but may be more effective in darker phototypes (C3).
14)  TCI are effective in most body areas, but are most effective on head and neck, with intermediate response on the trunk and extremities, and the most limited response on the hands and feet (A1).
15)  TCI can be Used to Maintain Color BIW for Locations with Concern for Relapse (C3).

iii. Topical Corticosteroid recommendations:

1) Topical corticosteroids may be used as first line therapy (A1).
2) Choice of corticosteroid class depends on the site and the length of time for planned usage (Expert consensus).
3) For areas with thin skin (e.g. face, groin, intertriginous), topical corticosteroids may be considered as second-line therapeutic agents (Expert consensus).
4) Daily Class 2 topical corticosteroids and intermittent or short-term continuous Class 1 Corticosteroids can be effective in repigmentation.
5)  Counseling regarding risk of atrophy and monitoring for atrophy are recommended in the setting of Class I and II topical corticosteroid usage (A1).
6)  While high-potency corticosteroids are effective for eyelid vitiligo, risk of glaucoma and thinning of the eyelid skin precludes prolonged usage
(Consensus opinion).
7) There is a limited body of data supporting the addition of topical calcipotriene to a corticosteroid regimen to enhance repigmentation (C3).
8) As with all topical agents, facial response is best, followed by response on the torso, the arms and legs and finally the hands and feet (A1).

Section 4. 

iv. Topical JAK Inhibitor Recommendations

1)  Topical JAK inhibitors are beneficial for usage in childhood vitiligo, with best grade of data for topical ruxolitinib 1.5% cream for age 12 years and over (A1) and case reports and consensus experience for children under the age of 12 years (C3).
2)  Topical JAK inhibitors should be considered as first-line therapy or second-line therapy at 12 years of age and up, and below that age with lesser evidence (Expert consensus).
3)  Topical JAKi have been well-studied in adolescents and young adults (A1).
4)  Topical JAKi may be used off label in younger children but has limited evidence and should be used with limited BSA until absorption data is better-understood (C3).
5)  Patients may need more than 3 months to see initial repigmentation with use of topical JAKi (A1). Patients may need to be treated with topical JAKi beyond 1 year before maximal repigmentation is achieved (Expert consensus).
6)  Counseling patients treated with topical JAK inhibitors includes mention of the label adverse events which are derived from trials of systemic JAK inhibitors, with focus on common adverse events including acne and application site reactions (Expert consensus).
7)  Combination of JAKi and phototherapy (natural sunlight or NBUVB) may be synergistic based on evidence in adults but needs to be confirmed in pediatric patients (C3).

Section 5. Other

1) There is not enough evidence to recommend pseudocatalase due to extreme variability between formulations. The usage of microdermabrasion as an adjunctive therapy is expected to promote absorption and caution should be exerted.

FUNDING 

This research was funded by the PeDRA Consensus Grant, Vitiligo Research Foundation, and Incyte Pharmaceuticals