European Journal of Cardiovascular Medicine

Vitiligo is a chronic, acquired pigmentary disorder characterized by well-demarcated depigmented macules and patches that may expand centrifugally over time. While it does not impair general physical health or communicability, vitiligo exerts a disproportionate psychosocial impact due to visibility, body-image concerns, stigma, and anxiety. Prevalence estimates vary widely depending on geography and study methodology: population-based U.S. data suggest an adult prevalence near 0.8%, while Indian cohorts report 0.25–4%, reflecting regional and ascertainment differences. Women present more often in outpatient cohorts, although true sex predilection may vary. Young adulthood is the most common age of presentation in clinics, whereas community-based surveys from India have described peaks in childhood or early adolescence, underscoring epidemiologic heterogeneity. (1–4)

Pathobiology

Vitiligo is increasingly viewed as the result of converging mechanisms. Autoimmune injury—mediated by autoreactive T cells and anti-melanocyte antibodies—is the central driver of melanocyte destruction. Genetic susceptibility, oxidative stress, and environmental triggers (Koebnerization, infections, psychological stress) further modulate disease onset and course. This “multihit” model explains the diverse clinical phenotypes (segmental vs. non-segmental; acral vs. facial) and variable therapeutic responsiveness. (5–7)

Therapeutic Landscape

Management is multimodal. For localized disease, topical therapies remain first-line, often combined with phototherapy (narrowband UVB), while surgical interventions (e.g., melanocyte–keratinocyte transplantation) are reserved for stable, extensive disease. Topical corticosteroids (TCS), such as clobetasol propionate 0.05%, are widely used due to potent anti-inflammatory and immunosuppressive properties but are constrained by cutaneous side effects—atrophy, telangiectasia, and striae—particularly on the face, flexures, and genitalia when used long-term.

Topical calcineurin inhibitors (TCIs), especially tacrolimus 0.1%, are steroid-sparing immunomodulators that inhibit T-cell activation and cytokine transcription with minimal risk of skin atrophy. They are especially valuable on cosmetically sensitive sites (face, neck, flexures, genitalia).

Safety Considerations

Safety is a pivotal factor in treatment selection.

• Clobetasol (TCS): Long-term use is limited by steroid-related adverse effects such as cutaneous atrophy, telangiectasia, and striae, particularly on the face, flexures, and genitalia. Tachyphylaxis with chronic use is another concern.
• Tacrolimus (TCI): Tacrolimus inhibits T-cell activation without causing atrophy, making it a safer option for prolonged use and for sensitive areas. Indian multicentric phase III data confirmed significant clinical improvement with transient burning as the main side effect, without systemic toxicity (Saple et al., 2003)【17】. Large real-world series (Park et al., 2019) 【18】further showed that vitiligo patients experience the lowest incidence of tacrolimus-related adverse events compared to other dermatoses, reinforcing its favorable safety profile for long-term maintenance.

Evidence from Comparative Studies

Head-to-head trials and reviews suggest broadly similar efficacy of tacrolimus and clobetasol, with differences often small or site-specific: clobetasol tends to yield faster or numerically greater early repigmentation at non-facial sites, while tacrolimus performs equally well on the face and offers superior cutaneous safety. For example, Lepe et al. (2003)【13】 and Ho et al. (2011)【14】 demonstrated this pattern in pediatric RCTs, while systematic reviews (Arora et al., 2020)【10】 confirm tacrolimus as an effective and safe steroid-sparing alternative. Consensus recommendations (Sarkar et al., 2024)【12】 further emphasize: tacrolimus 0.1% BID is the most common regimen; repigmentation is best on the face and least on acral sites; >50% repigmentation typically requires 3–6 months; and combination with NBUVB significantly increases high-grade response rates.

Rationale

Given the widespread use of both agents and the need for practical, comparative, real-world data in localized vitiligo, we conducted a 12-week, prospective, head-to-head study of tacrolimus 0.1% ointment vs clobetasol propionate 0.05% cream. Our study provides early-phase outcomes on efficacy, safety, compliance, and clinical phenotypes, complementing the longer-duration and combination-based strategies that remain standard in practice.

Aim

To compare the clinical efficacy and safety of tacrolimus 0.1% ointment and clobetasol propionate 0.05% cream in patients with localized vitiligo over 12 weeks, and to generate practical, evidence-informed guidance for drug selection in outpatient dermatology.

Objectives

Primary (Efficacy):

• To compare repigmentation at 12 weeks between tacrolimus and clobetasol, stratified into categories (1–25%, 26–50%, 51–75%, >75%).

Secondary (Safety/Tolerability & Use):

• To assess adverse effects (frequency and type) with each drug.
• To evaluate treatment compliance (missed applications, discontinuations, loss to follow-up).

Design & Setting:

• Prospective, comparative, parallel-group clinical study.
• Conducted in the OPD of Department of Dermatology, Venereology & Leprosy, Sri Balaji Medical College, Tirupati.
• Study period: November 2023 – October 2024.

Sample Size:

• 80 consecutive, eligible patients with clinically diagnosed localized vitiligo.
• Randomized into two equal groups (n=40 each).

Eligibility:

• Inclusion: Localized vitiligo subtypes (focal, segmental, lip-tip, acrofacial), stable or active disease.
• Exclusion: Generalized/universal vitiligo; recent use of vitiligo therapy (<2 months); hypersensitivity to study drugs; uncontrolled comorbidities; systemic conditions requiring immunosuppressants.

Intervention:

• Tacrolimus group: 0.1% ointment, applied twice daily.
• Clobetasol group: 0.05% cream, applied once daily (at night).
• Monotherapy only; no phototherapy.

Follow-up & Outcomes:

• Monthly reviews (Weeks 4, 8, 12).
• Primary outcome:Repigmentation categories and responder rates at Week 12.
• Secondary outcomes: Monthly progression, adverse effects, compliance, lost to follow-up.

Assessment:

• Repigmentation visually estimated from standardized digital photographs and lesion charts by the same investigator (with second opinion if needed).
• Patients monitored for local/systemic adverse events.

Data & Analysis:

• Data recorded in pretested forms with photographic documentation.
• Per-protocol and intention-to-treat (with LTFU imputed as non-responders) analyses performed.
• Statistical tests: χ²/Fisher’s exact for categorical data; t-test/Mann–Whitney for continuous data. Trend tests used for dose–response evaluation. Significance set at p<0.05.

Ethics:

• Institutional Ethics Committee approval obtained.
• Written informed consent/assent taken.
• Study conducted in accordance with the Declaration of Helsinki.

A total of 80 clinically diagnosed vitiligo patients were included and divided into two equal groups:

• Group A: Tacrolimus ointment 0.1% (n = 40)
• Group B: Clobetasol propionate cream 0.05% (n = 40)
  Treatment duration was 3 months.

Demographic Profile

Table 1. Age and Gender Distribution of Vitiligo Patients (n = 80)

• Peak incidence: 21–30 years (40%).
• Gender: Female predominance (57.5%) vs males (42.5%); ratio ≈ 1:1.35.
•  

Figure 1: Age and Gender Distribution

Clinical Distribution of Vitiligo

Table 2. Distribution of Vitiligo Types (n = 80)

Focal vitiligo was the most common type (36.3%), followed by acrofacial (26.3%) and segmental (23.7%). Lip-tip vitiligo was the least common (13.7%).

Figure 2: Clinical Distribution of Vitiligo Types

Response to Treatment

Table 3. Response to Tacrolimus Ointment (0.1%) (n = 40)

Total responders (excluding lost to follow-up): 25/32 = 78%.

Figure 3: Response Distribution: Tacrolimus vs Clobetasol

Table 4. Response to Clobetasol Propionate Cream (0.05%) (n = 40)

Total responders (excluding lost to follow-up): 31/37 = 84%.

Figure 4. Response to Clobetasol Propionate (0.05%)

Comparative Distribution & Response

Table 5. Clinical Distribution of Vitiligo (n = 80)

Focal vitiligo was the most common clinical type (43.8%), followed by segmental (27.5%).

Acrofacial vitiligo was least frequent (12.5%).

Figure 5.  Clinical Distribution of Vitiligo

Table 6. Comparative Response: Tacrolimus vs Clobetasol

• Clobetasol showed a slightly higher efficacy (84% vs. 78%).
• More high-grade responders (>50%) were seen with clobetasol.
• Tacrolimus, however, retained efficacy with a better safety profile.

Figure 6. Comparative Response: Tacrolimus vs Clobetasol

Adverse Effects, Cost & Compliance

Table 7. Adverse Effects

• Tacrolimus: Mild burning sensation (resolved spontaneously).
• Clobetasol: Folliculitis (5 cases), burning sensation (2), erythema (2), others (2).
• Side effects were ~5 times more frequent with clobetasol.
•  

Figure 7. Adverse Effects (%)

Table 8. Cost and Compliance

• Clobetasol: More affordable, better compliance, but higher adverse events.
• Tacrolimus: Costlier, moderate compliance, but superior safety profile for long-term use.

Figure 8. Radar Chart -Cost, Compliance, and Safety

SUMMARY OF RESULTS

• Demographics: Vitiligo peaked in young adults (21–30 years) with a slight female predominance, consistent with known epidemiology.
• Clinical types: Focal vitiligo was the most common subtype, while lip-tip and acrofacial forms were less frequent.
• Efficacy: Both tacrolimus and clobetasol were effective in inducing repigmentation, with clobetasol showing a higher overall response (84% vs 78%).
• Safety: Tacrolimus had markedly fewer side effects (5% vs 27.5%), highlighting its role as a safer long-term option.
• Cost/compliance: Clobetasol was cheaper and thus associated with better compliance, while tacrolimus posed cost limitations despite better safety.
• Overall: Clobetasol may be preferred for short-term efficacy and affordability, while tacrolimus is better suited for long-term management where safety and sustained tolerability are priorities.

FIGURE 9 : Before And After Treatment.Vitiligo Treatment Images Illustrating Repigmentation On Various Body Areas. Facial patch with Repigmentation Occurred Within 2 Months of Tacrolimus therapy.

FIGURE 10: Before And After Treatment- Vitiligo Treatment Images

Wuth Clobetasol Propionate cream

This prospective, comparative study evaluated tacrolimus 0.1% ointment and clobetasol propionate 0.05% cream in 80 patients with localized vitiligo over a period of 12 weeks. Both drugs were found to be effective in inducing repigmentation, with clobetasol showing a slightly higher overall response (84% vs 78%) among patients completing follow-up, but with a significantly higher adverse event rate (27.5% vs 5%). Tacrolimus, while marginally less efficacious in short-term repigmentation, demonstrated a markedly superior safety profile.

Demographic Profile

The peak age group in our cohort was 21–30 years (40%), with a female preponderance (M:F ≈ 1:1.35). These findings are in line with Koranne & Sachdeva (1988)【3】 who reported higher prevalence of vitiligo in patients under 30 years in clinic-based studies. In contrast, community surveys such as Mehta et al. (1973)【4】 identified peak incidence in the 6–15 year age group without sex predilection, highlighting the role of study setting and health-seeking behavior in shaping epidemiological trends.

Clinical Phenotype

Our patients most commonly presented with focal vitiligo (43.8%), followed by segmental (27.5%), lip-tip (16.3%), and acrofacial (12.5%) types. This distribution is consistent with localized, non-segmental forms that generally present to outpatient clinics, as noted in the Pigmentary Disorders Society (PDS) Consensus (2024)【12】. Exclusion of generalized/universal vitiligo was methodologically important, since these variants require different therapeutic approaches and carry different prognostic implications.

Treatment Response

Tacrolimus vs Clobetasol

Our study showed slightly superior short-term efficacy of clobetasol over tacrolimus, consistent with previous RCTs and comparative studies:

• Lepe et al. (2003): Pediatric RCT reported mean repigmentation of 49.3% with clobetasol vs 41.3% with tacrolimus at 2 months, with steroid-induced atrophy noted in the clobetasol arm【13】.
• Ho et al. (2011): Comparable efficacy on the face (≈58% achieving ≥50% repigmentation); non-facial sites responded better to clobetasol (39% vs 23%)【14】.
• Mumtaz et al. (2020): Pragmatic RCT (n=162) found efficacy in 58% clobetasol vs 52% tacrolimus (NS)【15】.
• Suseela & Srinivas (2019): Comparative RCT (n=70) showed a numerical advantage for clobetasol at all time-points, but without statistical significance【16】.

Our observed rates (84% clobetasol vs 78% tacrolimus responders) reinforce this pattern: clobetasol tends to provide faster or higher early repigmentation, especially on non-facial sites, while tacrolimus yields comparable outcomes in facial and sensitive areas.

Time Course and Site Specificity

The PDS Consensus (2024) emphasizes that repigmentation usually peaks at 3–6 months, with the face responding best and acral sites poorly【12】. Since our follow-up was limited to 3 months, we likely captured early response; extending treatment may have yielded higher proportions of moderate-to-high responders. Tacrolimus 0.1% ointment applied twice daily remains the most effective dosing regimen, while occlusion is not recommended【12】.

Monotherapy vs Combination

While both tacrolimus and clobetasol are effective as monotherapy, consensus and trial data increasingly support combination therapy—particularly tacrolimus + NBUVB—to maximize repigmentation. Sarkar et al. (2024)【12】 and Arora et al. (2020)【10】 highlight that such regimens achieve >75% repigmentation more frequently than monotherapy. Our findings, restricted to single-agent use, may therefore underestimate the true potential of these drugs in combined protocols.

Safety

Safety emerged as the key differentiator. In our cohort, adverse effects occurred in 27.5% of clobetasol-treated patients (folliculitis, erythema, burning) compared to only 5% of tacrolimus-treated patients (transient burning). These observations are strongly corroborated by prior studies:

• Lepe et al. (2003): Atrophy (15%) and telangiectasia (10%) with clobetasol; transient burning (10%) with tacrolimus【13】.
• Suseela & Srinivas (2019): Higher atrophy with clobetasol (14%, p=0.02); higher burning with tacrolimus (23%, p=0.03), no major SAEs【16】.
• Saple et al. (2003): Large Indian multicenter study in atopic dermatitis confirmed significant improvement with tacrolimus and an excellent tolerability profile, with only mild, transient burning/erythema【17】.
• Park et al. (2019): Korean real-world chart review (n=734) showed severe adverse events in only 4.1% overall, with discontinuation in 1.36%. Notably, vitiligo patients had the lowest incidence of tacrolimus-related AEs among chronic dermatoses【18】.

Taken together, these data establish tacrolimus as markedly safer for long-term use, especially on the face, flexures, and genitalia, where steroid-induced atrophy and telangiectasia are of greater concern.

Compliance and Cost

Clobetasol had better compliance in our cohort (dropout 7.5% vs 20% with tacrolimus), primarily because of cost. The PDS Consensus (2024) explicitly acknowledges cost as a limitation for widespread tacrolimus use【12】. Thus, while clobetasol is often favored initially for affordability and rapid response, tacrolimus should be prioritized for maintenance, steroid-sensitive sites, and long-term safety.

Clinical Implications

• First-line options: Both agents are reasonable choices for localized vitiligo.
• Short-term: Clobetasol is more affordable and yields quicker repigmentation, especially on non-facial sites.
• Long-term: Tacrolimus is safer, steroid-sparing, and better suited to maintenance, children, and sensitive sites.
• Combination therapy: TAC + NBUVB is recommended where feasible for higher-grade repigmentation.
• Patient counseling: Treatment decisions should balance efficacy, safety, cost, disease site, and patient preference, with clear explanation that maximal repigmentation may require 3–6 months and/or combination therapy.

Both tacrolimus 0.1% and clobetasol 0.05%, are effective medications for treatment of Vitiligo with Tacrolimus being safer for long term use and on sensitive areas with minimal side effects while Clobetasol can be used on patches avoiding Face and other sensitive areas for short term for initial prompt response before shifting to other medications.

Strengths

• Direct head-to-head comparison of tacrolimus 0.1% and clobetasol 0.05%, two commonly used agents for localized vitiligo.
• Real-world clinical relevance with outpatient cases, reflecting practical therapeutic outcomes.
• Safety profiling highlighted tacrolimus’ superior long-term tolerability.
• Clinically meaningful grading of repigmentation response.

Limitations

• Single-center design with modest sample size (n=80), limiting generalizability.
• Short follow-up (12 weeks) captured only early repigmentation, not long-term durability or relapse.
• Non-randomized, open-label design raises potential observer bias.
• Repigmentation assessed by visual estimation rather than validated indices (e.g., VASI).
• Exclusion of combination therapy arms (e.g., tacrolimus + NBUVB) may underestimate optimal outcomes.
• No formal cost-effectiveness analysis, though compliance and affordability were noted.

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