Abstract
Background
Topical corticosteroids are acknowledged as the first-line treatment for pediatric alopecia areata. There are cases that are recalcitrant to topical corticosteroid application.
Objective
The objective was to evaluate the efficacy of calcipotriol/betamethasone ointment in pediatric alopecia areata.
Methods
In a 12-week retrospective study, 40 patients under 10 years old with alopecia areata were included. The patients were treated with a topical ointment combining 0.005% calcipotriol and betamethasone dipropionate once daily. The efficacy was monitored through changes in Severity of Alopecia Tool (SALT) scores.
Results
The 40 patients, with a mean age of 4.1±2.1 years, were categorized by their SALT scores into two groups: those above and below 50. Patients with SALT scores over 50 showed hair regrowth in 7.44±4.44 weeks, while those with SALT scores under 50 showed regrowth in 5.71±2.58 weeks. After 12 weeks, 80.0% of the patients showed hair regrowth and 20.0% of patients showed no response or worsening. Only minor adverse events were documented during follow-up.
Conclusion
Calcipotriol/betamethasone ointment may represent a useful topical option for pediatric alopecia areata.
Keywords: Alopecia, Alopecia areata, Betamethasone, Calcipotriol, Child
INTRODUCTION
Alopecia areata (AA) is a chronic, relapsing nonscarring alopecia posing a significant impact on patients’ quality of life1. Standard treatment mainly focuses on immune modulation, such as topical or intralesional corticosteroids or contact immunotherapy2,3. However, a subset of patients is refractory to conventional therapies, demanding the exploration of alternative treatment modalities.
Recent studies have suggested the potential role of calcipotriol, a synthetic vitamin D analog, in AA treatment4. The rationale for employing calcipotriol in AA treatment is its immunomodulatory properties in hair follicle cycling. Active form of vitamin D binds to vitamin D receptors (VDRs) in the nuclei of target cells including keratinocytes and maintains the normal hair cycle5. VDR expression is reduced in the hair follicles of AA patients which provides a strong rationale for the utilization of calcipotriol for AA treatment6. The use of topical calcipotriol in AA has been reported in several studies showing various degrees of success in hair regrowth with minimal side effects7,8,9. However, the literature also suggests the complexity of treatment response to calcipotriol treatment.
Focusing on pediatric AA patients, it is imperative to acknowledge the unique characteristics of this patient group. Although pediatric AA shares many clinical features with adult AA, this specific group of patients poses additional challenges including the psychological impact and the limited treatment choices1. Visible hair loss imposes profound emotional and social stress on children, affecting their self-esteem, social interactions, and overall quality of life10. Treatment choices are limited by their distinct physiological and developmental traits, which necessitates the tailored approach for treatment selection in pediatric patients. Topical corticosteroids are a recognized first-line treatment for pediatric AA. However, careful consideration of potential long-term effects on children’s growth and development should be taken into account since children’s more permeable skin raises the risk of systemic absorption of topical corticosteroids11,12,13.
A topical combination regimen of calcipotriol and corticosteroid recently emerged as an attractive treatment option for the pediatric AA patient group. We focused on evaluating its efficacy and safety in pediatric AA, proposing it as a viable treatment option for this specific demographic.
MATERIALS AND METHODS
Patients
Our study conducted a retrospective analysis of medical records and clinical photographs from patients under the age of 10 years diagnosed with AA at the outpatient clinic of the Department of Dermatology, Pusan National University Hospital, Republic of Korea. The inclusion period spanned from January 2017 to December 2023. The criteria for inclusion required participants to have received treatment with a commercially available fixed-dose combination ointment containing calcipotriol monohydrate 52.2 μg/g (equivalent to calcipotriol 50 μg/g) and betamethasone dipropionate 0.643 mg/g, administered once daily for at least 12 weeks. The study protocol was reviewed and approved by the Pusan National University Hospital Institutional Review Board (IRB No. 2404-011-138).
Severity assessment
Therapeutic response was documented through a series of clinical photographs. High-resolution imaging was taken by a Canon EOS 800D digital camera, outfitted with an EFS 18–55 mm lens (Canon, Tokyo, Japan). The Severity of Alopecia Tool (SALT) scores, as the primary measure, were utilized to assess the severity of AA. Assessments were conducted at the baseline and then at 4, 8, and 12 weeks after the treatment began. Additionally, the alopecia grading score (AGS) was used for the baseline evaluation to enhance the granularity of severity assessment. The AGS employs a 6-point scale, categorizing alopecia severity as follows: S0 indicating no alopecia, S1 for hair loss less than 10%, S2 for hair loss ranging from 11% to 25%, S3 for hair loss between 26% and 50%, S4 for hair loss from 51% to 75%, and S5 for hair loss exceeding 75%.
Treatment efficacy
The efficacy of the treatment was quantitatively assessed by a 5-point semiquantitative regrowth score (RGS) at week 12. The regrowth categories were defined as follows: a score of 0 indicating poor regrowth (less than 10%), 1 denoting minimal regrowth (11%–25%), 2 representing moderate regrowth (26%–50%), 3 indicating significant regrowth (51%–75%), and 4 representing excellent regrowth (more than 75%). For the binary treatment response analysis, hair regrowth was defined as any visible regrowth documented by clinical photographs with a decrease in SALT score from baseline by week 12; patients with unchanged or increased SALT scores were classified as having non-regrowth, including no response and worsening.
Safety assessment
Safety evaluation was based on medical record review and clinically documented adverse events during follow-up. Considering the children are usually anxious about needle puncture and only local treatment was performed, no routine laboratory tests were performed to assess overall condition or systemic adverse effects.
Statistical analysis
Statistical analyses were performed using IBM SPSS Statistics for Windows, version 28.0 (IBM Corp., Armonk, NY, USA). Continuous variables were summarized as mean ± standard deviation, median, and range, as appropriate, and categorical variables as number (%). Baseline characteristics were compared between the baseline SALT <50 and baseline SALT ≥50 groups using Fisher’s exact test for categorical variables and the Mann-Whitney U test for continuous variables. Baseline AGS distribution was not statistically compared because it was inherently related to the SALT-based severity grouping. Fisher’s exact test was used to compare the proportion of patients with hair regrowth according to baseline severity group (baseline SALT <50 vs. baseline SALT ≥50). The onset of hair regrowth was compared between the two groups using the Mann-Whitney U test. In responders, temporal changes in SALT scores from baseline to weeks 4, 8, and 12 were analyzed using the Friedman test, and changes between baseline and week 12 were additionally assessed using the Wilcoxon signed-rank test. All tests were two-tailed, and p-values <0.05 were considered statistically significant.
RESULTS
The demographic and baseline characteristics of the patients were summarized in Table 1. The cohort of 40 patients, comprised 18 patients with baseline SALT scores less than 50 and 22 patients with baseline SALT scores of 50 or greater. The average age of participants was 4.1±2.1 years, with those in the SALT <50 group being older (4.6±1.7 years) compared to the SALT ≥50 group (3.6±2.4 years). The study cohort consisted of 15 male patients (37.5%) and 25 female patients (62.5%). Males comprised 38.9% and 36.4% of the patients in the SALT <50 and SALT ≥50 groups, respectively. The mean duration of illness prior to the study was 5.2±7.2 months, with a shorter duration observed in the SALT <50 group (3.5±4.5 months) compared to the SALT ≥50 group (6.6±8.7 months). A family history of AA was reported in 3 patients (3/40, 7.5%), all from the SALT ≥50 group. The presence of co-morbid conditions was similar across both groups, with 26 patients (26/40, 65.0%) having no co-morbidities. The most common co-morbid conditions were atopic dermatitis (7/40, 17.5%) and allergic rhinitis (5/40, 12.5%). Notably, nail changes were observed only in the SALT ≥50 group (4/40, 10.0%). The distribution of patients across different AGS was as follows: 6 patients (6/40, 15.0%) in S1, 12 patients (12/40, 30.0%) in S2, 7 patients (7/40, 17.5%) in S3, 8 patients (8/40, 20.0%) in S4, and 7 patients (7/40, 17.5%) in S5. Baseline demographic and clinical characteristics did not differ significantly between the baseline SALT <50 and baseline SALT ≥50 groups, except for AGS distribution, which was not statistically tested because it was inherently related to the SALT-based severity classification.
Table 1. Baseline characteristics.
| Variable | Total | Baseline SALT <50 | Baseline SALT ≥50 | p-value | |
|---|---|---|---|---|---|
| Number of patients | 40 | 18 | 22 | ||
| Sex | 1.000 | ||||
| Male | 15 (37.5) | 7 (38.9) | 8 (36.4) | ||
| Female | 25 (62.5) | 11 (61.1) | 14 (63.6) | ||
| Age (yr) | 4.1±2.1 | 4.6±1.7 | 3.6±2.4 | 0.081 | |
| Duration of illness (mo) | 5.2±7.2 | 3.5±4.5 | 6.6±8.7 | 0.244 | |
| Family history of AA | 3 (7.5) | 0 (0) | 3 (13.6) | 0.238 | |
| Co-morbidity | |||||
| None | 26 (65.0) | 12 (66.7) | 14 (63.6) | 1.000 | |
| Atopic dermatitis | 7 (17.5) | 3 (16.7) | 4 (18.2) | 1.000 | |
| Allergic rhinitis | 5 (12.5) | 3 (16.7) | 2 (9.1) | 0.642 | |
| Nail changes | 4 (10.0) | 0 (0) | 4 (18.2) | 0.114 | |
| AGS at baseline | |||||
| S1 | 6 (15.0) | 6 (33.3) | 0 (0) | N/T | |
| S2 | 12 (30.0) | 12 (66.6) | 0 (0) | N/T | |
| S3 | 7 (17.5) | 0 (0) | 7 (31.8) | N/T | |
| S4 | 8 (20.0) | 0 (0) | 8 (36.4) | N/T | |
| S5 | 7 (17.5) | 0 (0) | 7 (31.8) | N/T | |
Data are presented as number (%) or mean ± standard deviation, as appropriate. The p-values were calculated using Fisher’s exact test for categorical variables and the Mann-Whitney U test for continuous variables. Baseline AGS distribution was not statistically tested because it was intrinsically related to the SALT-based severity grouping.
SALT: Severity of Alopecia Tool, AA: alopecia areata, AGS: alopecia grading score, N/T: not tested.
The primary outcome measure was the treatment response at week 12 and the change in SALT score over time. Overall, 80.0% of patients (32/40) showed hair regrowth after treatment with calcipotriol/betamethasone ointment. Hair regrowth was observed in 77.8% (14/18) of patients in the baseline SALT <50 group and 81.8% (18/22) of those in the baseline SALT ≥50 group, with no significant difference between the two groups (p=1.000) (Table 2). Non-regrowth, which included no response to treatment and worsening, was noted in 22.2% (4/18) of the baseline SALT <50 group and 18.2% (4/22) of the baseline SALT ≥50 group. Specifically, no response to treatment was observed in 11.1% (2/18) and 4.5% (1/22) of patients in the baseline SALT <50 and baseline SALT ≥50 groups, respectively, whereas worsening was observed in 11.1% (2/18) and 13.6% (3/22), respectively. The mean onset of hair regrowth was 6.69±3.79 weeks in the overall cohort, occurring at 5.71±2.58 weeks in the baseline SALT <50 group and 7.44±4.44 weeks in the baseline SALT ≥50 group, without a statistically significant difference between the groups (p=0.282).
Table 2. Treatment response at week 12.
| Variable | Total | Baseline SALT <50 | Baseline SALT ≥50 | p-value | ||
|---|---|---|---|---|---|---|
| Number of patients | 40 | 18 | 22 | |||
| Treatment response | ||||||
| Hair regrowth | 32 (80.0) | 14 (77.8) | 18 (81.8) | 1.000 | ||
| Non-regrowth | 8 (20.0) | 4 (22.2) | 4 (18.2) | |||
| No response to treatment | 3 (7.5) | 2 (11.1) | 1 (4.5) | |||
| Worsening | 5 (12.5) | 2 (11.1) | 3 (13.6) | |||
| Onset of hair regrowth (wk) | 6.69±3.79 | 5.71±2.58 | 7.44±4.44 | 0.282 | ||
Data are presented as number (%) or mean ± standard deviation, as appropriate. The p-value for hair regrowth versus non-regrowth was calculated using Fisher’s exact test, and p-value for onset of hair regrowth was calculated using the Mann-Whitney U test. Non-regrowth includes no response to treatment and worsening.
SALT: Severity of Alopecia Tool.
To further characterize treatment response, temporal changes in SALT scores were analyzed among the 32 responders, including 14 patients in the baseline SALT <50 group and 18 in the baseline SALT ≥50 group (Table 3, Fig. 1). In the overall responder group, the mean SALT score decreased from 43.8±32.9 at baseline to 40.5±32.6 at week 4, 35.3±30.6 at week 8, and 28.0±27.9 at week 12. In the baseline SALT <50 group, the mean SALT score decreased from 10.2±6.41 at baseline to 8.07±6.79 at week 4, 5.5±4.45 at week 8, and 2.71±1.82 at week 12. In the baseline SALT ≥50 group, the mean SALT score decreased from 69.9±17.0 at baseline to 65.7±19.2 at week 4, 58.4±20.0 at week 8, and 47.6±21.9 at week 12. These temporal changes were statistically significant in both severity subgroups and in the overall responder group (all p<0.001, Friedman test). In addition, the reduction in SALT score from baseline to week 12 was significant in the baseline SALT <50 group (p=0.001), the baseline SALT ≥50 group (p<0.001), and the overall responder group (p<0.001) by Wilcoxon signed-rank test.
Table 3. Temporal changes in SALT scores among responders with hair regrowth.
| Variable | Baseline SALT <50 | Baseline SALT ≥50 | Total | |
|---|---|---|---|---|
| Number of patients | 14 | 18 | 32 | |
| Baseline SALT | ||||
| Mean | 10.2±6.4 | 69.9±17.0 | 43.8±32.9 | |
| Median | 8 | 67.5 | 50 | |
| Range | 2–22 | 50–100 | 2–100 | |
| Week 4 SALT | ||||
| Mean | 8.1±6.8 | 65.7±19.2 | 40.5±32.6 | |
| Median | 6.5 | 65 | 43.5 | |
| Range | 1–27 | 40–95 | 1–95 | |
| Week 8 SALT | ||||
| Mean | 5.5±4.5 | 58.4±20.0 | 35.3±30.6 | |
| Median | 4.5 | 54 | 36.5 | |
| Range | 0–16 | 25–90 | 0–95 | |
| Week 12 SALT | ||||
| Mean | 2.7±1.8 | 47.6±21.9 | 28.0±27.9 | |
| Median | 2.5 | 40 | 27.5 | |
| Range | 0–5 | 15–90 | 0–90 | |
| p for trend* | <0.001 | <0.001 | <0.001 | |
| p for baseline vs. week 12† | 0.001 | <0.001 | <0.001 | |
Data are presented as mean ± standard deviation, median, and range.
SALT: Severity of Alopecia Tool.
*p-values for temporal changes across baseline, week 4, week 8, and week 12 were calculated using the Friedman test.
†p-values for comparisons between baseline and week 12 were calculated using the Wilcoxon signed-rank test.
Fig. 1. Clinical progression of pediatric alopecia areata patients before and after application of calcipotriol/betamethasone ointment. (A) Representative cases showing patients with a baseline SALT score of less than 50. (B) Representative cases showing patients with a baseline SALT score of 50 or greater.
SALT: Severity of Alopecia Tool.
During the extended 24-week follow-up, 19 patients were available for evaluation, including 3 patients in the baseline SALT <50 group and 16 in the baseline SALT ≥50 group. Among them, all 3 patients of the SALT <50 group and 14 of 16 patients in the SALT ≥50 group had shown hair regrowth at week 12. At week 24, the mean SALT score was 3.0±1.1 in the baseline SALT <50 group and 27.8±17.8 in the baseline SALT ≥50 group, with an overall mean of 24.7±17.0. The long-term outcomes of patients who were not available for the 24-week follow-up could not be determined.
Table 4 summarizes the week-12 distribution of RGSs among responders according to baseline AGS. Poor regrowth (RGS 0) and minimal regrowth (RGS 1) were observed only in patients with moderate-to-severe baseline alopecia (S3–S5), and were absent in those with milder disease (S1–S2). Those with more severe initial conditions exhibited poor regrowth (33.3% [2/6] in S5) or minimal regrowth (20% [1/5] in S3, 28.6% [2/7] in S4, and 33.3% [2/6] in S5). Moderate regrowth (RGS 2) was observed across several AGS categories: S2 (3/9, 33.3%), S3 (3/5, 60%), S4 (3/7, 42.9%), and S5 (1/6, 16.7%). Significant regrowth (RGS 3) was more prominent in patients with milder baseline alopecia (60% [3/5] in S1, 33.3% [3/9] in S2, 20% [1/5] in S3, 28.6% [2/7] in S4, and 16.7% [1/6] in S5). Excellent regrowth (RGS 4) was observed exclusively in patients with milder baseline disease (S1 [2/5, 40%] and S2 [3/9, 33.3%]). Patients with a baseline severity of S3 or higher did not attain RGS 4 at week 12.
Table 4. Distribution of RGSs at week 12 according to baseline AGS among patients with hair regrowth.
| Variable | Baseline SALT <50 | Baseline SALT ≥50 | ||||
|---|---|---|---|---|---|---|
| AGS at baseline | S1 | S2 | S3 | S4 | S5 | |
| RGS | ||||||
| RGS 0 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 2 (33.3) | |
| RGS 1 | 0 (0.0) | 0 (0.0) | 1 (20.0) | 2 (28.6) | 2 (33.3) | |
| RGS 2 | 0 (0.0) | 3 (33.3) | 3 (60.0) | 3 (42.9) | 1 (16.7) | |
| RGS 3 | 3 (60.0) | 3 (33.3) | 1 (20.0) | 2 (28.6) | 1 (16.7) | |
| RGS 4 | 2 (40.0) | 3 (33.3) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |
Data are presented as number (%).
RGS: regrowth score, AGS: alopecia grading score, SALT: Severity of Alopecia Tool.
The treatment was generally well tolerated, with only minor adverse effects reported, including greasiness in most patients and scalp folliculitis in six patients. No severe adverse events requiring treatment discontinuation were observed during the study. Because safety assessment was based on routine clinical follow-up and medical record review, only clinically documented adverse events could be evaluated, and no clinically evident systemic adverse effects were recorded.
DISCUSSION
A range of topical therapies, including anthralin, contact immunotherapy, minoxidil, calcineurin inhibitors, and corticosteroids, has been used in pediatric AA, with inconsistent efficacy and tolerability12,13. Topical corticosteroids remain a first-line option for pediatric AA; however, prolonged use is a concern in children because the disease is often chronic or relapsing and treatment may need to be repeated11,12,13. For this reason, calcipotriol-containing regimens have emerged as potential topical options, although the available evidence remains limited7,8,9.
Most previous studies of calcipotriol-containing regimens in AA have involved older patients with mild-to-moderate disease7,8,9,14,15,16,17,18,19. Reported outcomes with calcipotriol monotherapy have been variable, and comparative studies have not consistently shown clear superiority over topical corticosteroids (Table 5)14,15. For example, Molinelli et al.15 reported greater and faster response rates with calcipotriol than with clobetasol in mild-to-moderate patchy AA, although the between-group differences were not statistically significant and adverse effects were limited and reversible. Comparative studies of combination therapy have also yielded mixed results16,17,18,19. Alam et al.16 and Gupta et al.17 reported greater SALT improvement with calcipotriol-containing combination therapy than with topical corticosteroid monotherapy. In contrast, El-Ghareeb18 and Nassar et al.19 found efficacy comparable to topical corticosteroid monotherapy, while suggesting fewer adverse effects or a more favorable tolerability profile with calcipotriol-containing regimens. Taken together, these studies suggest that calcipotriol-containing combination therapy may be a practical topical option with acceptable tolerability, although its comparative efficacy over topical corticosteroid monotherapy remains uncertain15,16,17,18,19.
Table 5. Previous reports of topical calcipotriol-containing regimens for AA.
| Reference | Subject | Age (yr) | Administration | Baseline SALT | 12 weeks f/u | 24 weeks f/u | Response rate/main outcome |
|---|---|---|---|---|---|---|---|
| Nassar et al.19 | SALT <25 (n=20) | 33.05±12.91 | Calcipotriol 0.005%/betamethasone, 12 weeks | 4.85±1.46 | 2.45±1.47 | N/A | Comparable efficacy to clobetasol monotherapy |
| Gupta et al.17 | SALT <50 (n=30) | 27.35±3.56 | Calcipotriol 0.005%/clobetasol, 24 weeks | 9.85±4.95 | 5.32±3.22 | 3.66±3.53 | Statistically significant greater SALT reduction than clobetasol monotherapy |
| El-Ghareeb18 | Mild-to-moderate AA (n=20) | Range 10–54 | Calcipotriol 0.005%/betamethasone, 12 weeks | 10.0±7.9 | 6.4±5.6 | N/A | Comparable efficacy to betamethasone monotherapy |
| El Taieb et al.14 | Scalp AA (n=15) | 22.9±3.2 | Calcipotriol 0.005%, 12 weeks | 4.0±1.1 | 2.8±1.0 | N/A | Superiority over NB-UVB not established |
| Alam et al.16 | SALT<50 (n=50) | 22.38 (range 13–64) | Calcipotriol 0.005%/mometasone, 24 weeks | 7.22±4.27 | 4.30±3.78 | 2.98±3.35 | Statistically significant greater SALT reduction than mometasone monotherapy |
| Narang et al.8 | SALT <40 (n=22) | 30.4±10.8 | Calcipotriol 0.005% lotion, 12 weeks | 14.6 | ΔSALT 0%: 9 (40.9%) | N/A | 59.1%/Superiority not assessed in this single-arm study |
| ΔSALT <25%: 4 (30.8%) | |||||||
| ΔSALT 26~50%: 3 (23.1%) | |||||||
| ΔSALT >50%: 6 (46.2%) | |||||||
| Cerman et al.7 | SALT <50 (n=48) | 33.0±11.1 | Calcipotriol cream, 12 weeks | 11.06±7.25 | 3.76±5.29 | N/A | RGS ≥4: 62.5% |
| RGS 1-3: 37.5%/superiority not assessed in this single-arm study | |||||||
| Present study | Scalp AA (n=40) | 4.0±2.2 (range 1–10) | Calcipotriol 0.005%/betamethasone, 12 weeks (up to 24 weeks) | 42.3±32.3 | 28.0±27.9 | 24.7±17.0 | 80.0%/no significant difference between baseline SALT <50 and SALT ≥50 groups |
Data are presented as mean ± standard deviation, unless otherwise indicated. Because efficacy outcomes were reported heterogeneously across studies, either the response rate or the main efficacy outcome reported by the authors is presented.
AA: alopecia areata, SALT: Severity of Alopecia Tool, f/u: follow-up, N/A: not applicable, NB-UVB: narrowband ultraviolet B.
In this regard, our study is clinically meaningful because it specifically focused on children younger than 10 years and included a broad spectrum of disease severity, including severe cases. Hair regrowth was observed in 80.0% of patients overall, and there was no significant difference in hair regrowth rates between the baseline SALT <50 and baseline SALT ≥50 groups. These findings indicate that calcipotriol/betamethasone ointment may be relevant across a broad range of pediatric AA severity, including more extensive disease. At the same time, RGS analysis showed that excellent regrowth (RGS 4) occurred only in patients with milder baseline disease, whereas poorer regrowth categories were confined to patients with moderate-to-severe baseline alopecia, suggesting that the degree of regrowth may still vary according to initial severity.
The clinical relevance of this regimen in pediatric AA may lie less in demonstrating superiority over topical corticosteroid monotherapy than in providing a practical and well-tolerated topical option for young children11,12,13,15,18,19. Given the concerns regarding prolonged topical corticosteroid use in children, this combination may serve as a reasonable alternative topical approach11,12,13,20. However, because our study did not directly compare calcipotriol/betamethasone ointment with topical corticosteroid monotherapy, its comparative advantage should be interpreted cautiously and requires confirmation in controlled studies.
The therapeutic effect of calcipotriol/betamethasone may be supported by complementary mechanisms. Calcipotriol has been implicated in immunomodulation and hair follicle cycling through VDR-related pathways, whereas betamethasone provides anti-inflammatory effects5,6. In addition, previous work in psoriasis has shown that calcipotriol can reduce the frequency of CD8+ IL-17+ T cells, supporting the biological plausibility of an immunomodulatory effect21. Nevertheless, the direct relevance of these findings to AA remains to be established6,21.
Several limitations should be considered when interpreting our findings. First, spontaneous remission is common in AA, particularly in patchy forms, and some of the observed improvement in our cohort may not have been solely attributable to treatment3. Second, the study was retrospective and did not include a control group, which limits causal interpretation of treatment efficacy. In addition, the longitudinal SALT analysis was restricted to patients who demonstrated hair regrowth; therefore, the observed SALT reduction may overestimate the treatment effect and should be interpreted as a responder-only, best-case scenario rather than the average response of the entire cohort. Third, follow-up beyond 12 weeks was incomplete and unevenly distributed between severity groups. Therefore, long-term outcomes should be interpreted with caution, and the outcomes of patients who were not evaluated at week 24 remain unknown. Finally, because safety assessment was based on medical record review in routine clinical practice, no routine laboratory monitoring for systemic adverse effects was performed; therefore, our safety findings are limited to clinically documented adverse events.
Despite these limitations, this study expands the available evidence by evaluating calcipotriol/betamethasone ointment in children younger than 10 years across a broad severity range, including severe AA cases that have been underrepresented in earlier reports. In conclusion, calcipotriol/betamethasone ointment may be a useful topical option for pediatric AA, including more severe disease. Further prospective, controlled studies are needed to clarify its comparative efficacy, long-term outcomes, and safety in pediatric patients.
Footnotes
FUNDING SOURCE: None.
CONFLICTS OF INTEREST: The authors have nothing to disclose.
DATA SHARING STATEMENT: The data that support the findings of this study are available from the corresponding author upon reasonable request.
References
- 1.Toussi A, Barton VR, Le ST, Agbai ON, Kiuru M. Psychosocial and psychiatric comorbidities and health-related quality of life in alopecia areata: a systematic review. J Am Acad Dermatol. 2021;85:162–175. doi: 10.1016/j.jaad.2020.06.047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Strazzulla LC, Wang EHC, Avila L, Lo Sicco K, Brinster N, Christiano AM, et al. Alopecia areata: an appraisal of new treatment approaches and overview of current therapies. J Am Acad Dermatol. 2018;78:15–24. doi: 10.1016/j.jaad.2017.04.1142. [DOI] [PubMed] [Google Scholar]
- 3.Sibbald C. Alopecia areata: an updated review for 2023. J Cutan Med Surg. 2023;27:241–259. doi: 10.1177/12034754231168839. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Lin X, Meng X, Song Z. Vitamin D and alopecia areata: possible roles in pathogenesis and potential implications for therapy. Am J Transl Res. 2019;11:5285–5300. [PMC free article] [PubMed] [Google Scholar]
- 5.Bikle DD. Vitamin D metabolism and function in the skin. Mol Cell Endocrinol. 2011;347:80–89. doi: 10.1016/j.mce.2011.05.017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Daroach M, Narang T, Saikia UN, Sachdeva N, Sendhil Kumaran M. Correlation of vitamin D and vitamin D receptor expression in patients with alopecia areata: a clinical paradigm. Int J Dermatol. 2018;57:217–222. doi: 10.1111/ijd.13851. [DOI] [PubMed] [Google Scholar]
- 7.Çerman AA, Solak SS, Altunay İ, Küçükünal NA. Topical calcipotriol therapy for mild-to-moderate alopecia areata: a retrospective study. J Drugs Dermatol. 2015;14:616–620. [PubMed] [Google Scholar]
- 8.Narang T, Daroach M, Kumaran MS. Efficacy and safety of topical calcipotriol in management of alopecia areata: a pilot study. Dermatol Ther. 2017;30:e12464. doi: 10.1111/dth.12464. [DOI] [PubMed] [Google Scholar]
- 9.Arifin EM, Tabri F, Djawad K, Wahab S, Suswardana, Achmad H, et al. Successful treatment of alopecia totalis with topical calcipotriol: serial case report and review of the literature. Syst Rev Pharm. 2020;11:506–510. [Google Scholar]
- 10.Altunisik N, Ucuz I, Turkmen D. Psychiatric basics of alopecia areata in pediatric patients: evaluation of emotion dysregulation, somatization, depression, and anxiety levels. J Cosmet Dermatol. 2022;21:770–775. doi: 10.1111/jocd.14122. [DOI] [PubMed] [Google Scholar]
- 11.Afford R, Leung AKC, Lam JM. Pediatric alopecia areata. Curr Pediatr Rev. 2021;17:45–54. doi: 10.2174/1573396316666200430084825. [DOI] [PubMed] [Google Scholar]
- 12.Waśkiel-Burnat A, Kołodziejak M, Sikora M, Stochmal A, Rakowska A, Olszewska M, et al. Therapeutic management in paediatric alopecia areata: a systematic review. J Eur Acad Dermatol Venereol. 2021;35:1299–1308. doi: 10.1111/jdv.17187. [DOI] [PubMed] [Google Scholar]
- 13.Barton VR, Toussi A, Awasthi S, Kiuru M. Treatment of pediatric alopecia areata: a systematic review. J Am Acad Dermatol. 2022;86:1318–1334. doi: 10.1016/j.jaad.2021.04.077. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.El Taieb MA, Hegazy EM, Ibrahim HM, Osman AB, Abualhamd M. Topical calcipotriol vs narrowband ultraviolet B in treatment of alopecia areata: a randomized-controlled trial. Arch Dermatol Res. 2019;311:629–636. doi: 10.1007/s00403-019-01943-8. [DOI] [PubMed] [Google Scholar]
- 15.Molinelli E, Campanati A, Brisigotti V, Sapigni C, Paolinelli M, Offidani A. Efficacy and safety of topical calcipotriol 0.005% versus topical clobetasol 0.05% in the management of alopecia areata: an intrasubject pilot study. Dermatol Ther (Heidelb) 2020;10:515–521. doi: 10.1007/s13555-020-00379-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Alam M, Amin SS, Adil M, Arif T, Zahra FT, Varshney I. Comparative study of efficacy of topical mometasone with calcipotriol versus mometasone alone in the treatment of alopecia areata. Int J Trichology. 2019;11:123–127. doi: 10.4103/ijt.ijt_18_19. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Gupta ML, Singh S, Khan BH. Comparative evaluation of efficacy between topical calcipotriol used along with topical clobetasol and topical clobetasol monotherapy in treatment of alopecia areata: a randomised clinical trial. J Clin Diagn Res. 2021;15:5–8. [Google Scholar]
- 18.El-Ghareeb MI. Topical calcipotriol mixed with topical steroid versus topical steroid alone in treatment of alopecia areata. Egypt J Dermatol Venereol. 2019;39:78–82. [Google Scholar]
- 19.Nassar A, Elradi M, Radwan M, Albalat W. Comparative evaluation of the efficacy of topical tacrolimus 0.03% and topical calcipotriol 0.005% mixed with betamethasone dipropionate versus topical clobetasol 0.05% in treatment of alopecia areata: a clinical and trichoscopic study. J Cosmet Dermatol. 2023;22:1297–1303. doi: 10.1111/jocd.15558. [DOI] [PubMed] [Google Scholar]
- 20.Lamba S, Lebwohl M. Combination therapy with vitamin D analogues. Br J Dermatol. 2001;144(Suppl 58):27–32. doi: 10.1046/j.1365-2133.2001.144s58027.x. [DOI] [PubMed] [Google Scholar]
- 21.Dyring-Andersen B, Bonefeld CM, Bzorek M, Løvendorf MB, Lauritsen JP, Skov L, et al. The vitamin D analogue calcipotriol reduces the frequency of CD8+ IL-17+ T cells in psoriasis lesions. Scand J Immunol. 2015;82:84–91. doi: 10.1111/sji.12304. [DOI] [PubMed] [Google Scholar]