Autoimmune markers in vitiligo

Vitiligo is traditionally classified as an autoimmune skin disorder, with melanocyte destruction leading to depigmented patches. For clinicians, the challenge is not only choosing treatment, but also interpreting “autoimmune markers” that may appear on lab tests. One of the most common—and also one of the most ambiguous—markers is antinuclear antibodies (ANA). ANA can be detected in people with vitiligo, but they are also found in a subset of healthy individuals, which is why its clinical meaning in day-to-day management remains debated.

This raises a practical question: if a patient is ANA-positive, should we expect a poorer response to phototherapy, or a higher risk of adverse events?

Study aims and design

This was the focus of a prospective, single-center cohort study from China evaluating whether ANA status influences the effectiveness and safety of 308-nm excimer light therapy in patients with vitiligo [1]. The goal was straightforward: to determine whether ANA should be taken into account when planning a 308-nm excimer light course—specifically, whether seropositivity affects the degree of repigmentation, the cumulative dose required, or the frequency of adverse reactions. The authors also note a broader concern discussed in the literature: repeated UV exposure may theoretically stimulate B-cell activity and autoantibody production. Still, the clinical relevance of this in the context of vitiligo care remains unclear.

The study included 86 patients with vitiligo aged 10–65 years; all had Fitzpatrick skin types III or IV. ANA was measured by indirect immunofluorescence. ANA positivity was defined as a titer ≥1:100, and ANA negativity as <1:100.

Patients were followed for 6 months while receiving 308-nm excimer light therapy 1–2 times weekly in combination with topical agents: topical calcineurin inhibitors for face/neck lesions and potent topical corticosteroids for other body areas. In highly active disease (VIDA ≥4), oral prednisone acetate could be added as a mini-pulse regimen (15 mg twice weekly). Excimer dosing was tailored to the anatomic site and increased by 10–20% to achieve “transient pink erythema.” If “bright red erythema” developed, treatment was paused until it improved and then resumed at the last tolerated dose.

Outcomes were assessed using the Vitiligo Area Scoring Index (VASI) and standardized photography. Repigmentation was categorized as poor (<25%), moderate (25–49%), good (50–74%), or excellent (≥75%).

Characteristics of ANA-positive patients

ANA positivity was found in 26.7% of patients (23 of 86). Women were more common in the ANA-positive group (73.9% vs 47.6% in the ANA-negative group; p=0.030), and the median age was higher (38 vs 31 years; p=0.029). ANA titers were generally low: 82.6% had a 1:100 titer and 17.4% had a 1:320 titer; a speckled nuclear staining pattern was most frequent.

Importantly, extractable nuclear antigen (ENA) screening was positive in 7.0% (6 patients), but during follow-up, no one was diagnosed with connective tissue disease, including systemic lupus erythematosus.

The authors also reported laboratory differences suggesting a “thyroid–autoimmunity” context in part of the ANA-positive group: compared with ANA-negative patients, ANA-positive individuals had higher TSH and TPOAb levels and lower FT3 and FT4 levels (all statistically significant).

Results: effectiveness and dose burden

The key question was whether ANA status changes in response to 308-nm excimer light therapy. The authors evaluated 134 lesions across 86 patients and analyzed results by location: face/neck, hands/feet, and trunk/limbs.

Overall, ANA positivity did not translate into a clearly “failed” clinical response and did not worsen tolerability. However, for face and neck lesions, the distribution of outcomes differed: ANA-positive lesions more often achieved good repigmentation of 50–74% (41.7% vs 14.5%; p=0.006), but were less likely to reach excellent repigmentation ≥75% (16.7% vs 43.5%; p=0.020). For other locations, no statistically significant differences in repigmentation categories were reported. According to the authors, multivariable analysis supported an independent association between ANA status and repigmentation outcomes specifically for face/neck lesions after adjustment for sex, age, disease phase, and several thyroid-related variables.

From the standpoint of dose burden and safety, differences between groups were minimal. Cumulative phototherapy doses (J/cm²) and doses at the time erythema appeared did not differ significantly between ANA-positive and ANA-negative lesions in the analyzed subgroups (p>0.05).

Adverse events related to phototherapy were documented in 9 of 86 patients (10.5%). The authors found no ANA-related difference in frequency or clinical pattern (p>0.05). Reactions occurred after episodes of bright red erythema; erythema was the most common, and some patients had erythema with blisters. All adverse events resolved with dose reduction or temporary treatment pauses, and patients were able to continue therapy.

The authors also assessed whether prednisone mini-pulse therapy could confound outcomes; adding prednisone acetate did not lead to statistically significant differences in treatment response (p>0.05).

Limitations and interpretation

The study’s limitations were explicitly stated: a single-center design, a relatively small sample size, a short follow-up, and a predominance of low-titer ANA. The authors emphasize that the findings apply specifically to 308-nm excimer light therapy and should not be automatically extrapolated to other phototherapy modalities (for example, broadband or narrowband UVB), given differences in treatment field and potential systemic effects.

Practical takeaways

What does this mean for physicians?

First, ANA positivity by itself—at the titers most common in this study (1:100–1:320)—does not appear to warrant lowering expectations for 308-nm excimer light therapy or changing the protocol due to safety concerns.

Second, if an ANA-positive patient has lesions predominantly on the face/neck, it may be useful to keep in mind the pattern reported here: a higher chance of reaching 50–74% repigmentation, but a lower likelihood of achieving ≥75% compared with ANA-negative patients.

Third, erythema-guided dose management (targeting mild pink erythema and pausing for bright red erythema) functioned as a practical safety control regardless of ANA status.

Finally, because thyroid-related markers (including TSH and TPOAb) were more often discordant in the ANA-positive group, clinicians may want to keep thyroid assessment and the broader autoimmune context in mind as part of the standard evaluation of patients with vitiligo—consistent with their local practice and guidelines.

Reference

1. Han N., Jia D., Chen C. et al. Does ANA positivity affect treatment outcomes in vitiligo? A clinical evaluation of 308-nm excimer light therapy. J Dermatolog Treat 2026; 37(1): 2612433. https://doi.org/10.1080/09546634.2025.2612433