10.5826/dpc.1304a306
Introduction: The diagnosis of vitiligo is mainly based on clinical findings. However, dermoscopy or reflectance confocal microscopy (RCM) could be useful for assessing its progression (stability, pigmentation, or depigmentation).
Objective: To evaluate the correlation of dermatological findings by dermoscopy and RCM in pediatric vitiligo.
Methods: We conducted a cross-sectional, descriptive, and analytical clinical study. Pediatric patients with vitiligo of both sexes, aged &gt;1 year and &lt;18 years, with all spectrums of the disease were included. Vitiligo lesions were evaluated clinically, by dermoscopy, and microscopy.
Results: A total of 40 patients with vitiligo were included. Eight dermoscopic patterns were found: reduced/absent pigment network, perifollicular pigmentation, trichromic, tapioca sago, perifollicular depigmentation, starburst, leukotrichia, and erythema. Skin with a normal pigment network showed complete dermal papillary rings and half-rings. Skin with reduced/absent pigment network had an absence of papillary rings or only showed half-rings and was more common in unstable vitiligo. The trichrome pattern only showed half-rings. The tapioca sago pattern showed complete papillary rings and appeared in younger patients. Perifollicular pigmentation showed half-rings and complete rings and did not show associations. The diffuse borders did not present complete papillary structures. We found that vitiligo duration time of &lt;24 months (OR 4.56 CI 1.09-18.99) and absent papillary rings (OR 2.75 CI 1.01-7.51) are associated with an unstable prognosis.
Conclusions: The dermoscopic and microscopic findings, such as the reduction/absence of the pigment network, tapioca sago pattern, and absence of papillary rings, can be used to support the evaluation of the clinical prognosis of vitiligo.
text/xml
2160-9381
3659
en
Claudia Camelia Calzada-Mendoza 
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
reflectance confocal microscopy
Dermatoscopic Patterns in Childhood Vitiligo and Their Association With Reflectance Confocal Microscopy Findings
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Original Article
2023-10-31
2023-07-05
2023-10-31
2024-01-16
e2023306
Dermatol Pract Concept
Introduction: The diagnosis of vitiligo is mainly based on clinical findings. However, dermoscopy or reflectance confocal microscopy (RCM) could be useful for assessing its progression (stability, pigmentation, or depigmentation).
Objective: To evaluate the correlation of dermatological findings by dermoscopy and RCM in pediatric vitiligo.
Methods: We conducted a cross-sectional, descriptive, and analytical clinical study. Pediatric patients with vitiligo of both sexes, aged &gt;1 year and &lt;18 years, with all spectrums of the disease were included. Vitiligo lesions were evaluated clinically, by dermoscopy, and microscopy.
Results: A total of 40 patients with vitiligo were included. Eight dermoscopic patterns were found: reduced/absent pigment network, perifollicular pigmentation, trichromic, tapioca sago, perifollicular depigmentation, starburst, leukotrichia, and erythema. Skin with a normal pigment network showed complete dermal papillary rings and half-rings. Skin with reduced/absent pigment network had an absence of papillary rings or only showed half-rings and was more common in unstable vitiligo. The trichrome pattern only showed half-rings. The tapioca sago pattern showed complete papillary rings and appeared in younger patients. Perifollicular pigmentation showed half-rings and complete rings and did not show associations. The diffuse borders did not present complete papillary structures. We found that vitiligo duration time of &lt;24 months (OR 4.56 CI 1.09-18.99) and absent papillary rings (OR 2.75 CI 1.01-7.51) are associated with an unstable prognosis.
Conclusions: The dermoscopic and microscopic findings, such as the reduction/absence of the pigment network, tapioca sago pattern, and absence of papillary rings, can be used to support the evaluation of the clinical prognosis of vitiligo.
Claudia Camelia Calzada-Mendoza 
2023/10/31
10.5826/dpc.1304a306
e2023306
Graduate Studies and Research Section, School of Medicine, National Polytechnic Institute, Mexico City, Mexico 
2160-9381
reflectance confocal microscopy
en
e2023306
Nirmal B, Antonisamy B, Peter CVD, George L, George AA, Dinesh GM. Cross-Sectional Study of Dermatoscopic Findings in Relation to Activity in Vitiligo: BPLeFoSK Criteria for Stability. J Cutan Aesthet Surg. 2019;12(1):36-41. DOI: 10.4103/JCAS.JCAS_75_18. PMID: 31057267.
Dermatoscopic Patterns in Childhood Vitiligo and Their Association With Reflectance Confocal Microscopy Findings
https://dpcj.org/index.php/dpc/article/download/3659/2338
      Dermatoscopic Patterns in Childhood Vitiligo
     and Their Association With Reflectance Confocal
                   Microscopy Findings
        Juan Alberto Godínez-Chaparro1,2, Rodrigo Roldán-Marín3, Adrián Soto-Mota4,5,
                             Claudia Camelia Calzada-Mendoza2


1 Paediatric Dermatology Service, High Specialty Medical Unit of Dr. Gaudencio González Garza General Hospital, La Raza National
  Medical Centre, Mexican Institute of Social Security, Mexico City, Mexico
2 Graduate Studies and Research Section, School of Medicine, National Polytechnic Institute, Mexico City, Mexico
3 Dermato-Oncology Clinic at the Experimental Medicine Unit of the Faculty of Medicine, National Autonomous University of Mexico,
  Mexico City, Mexico
4 Metabolic Diseases Research Unit, Salvador Zubirán National Institute of Medical Sciences and Nutrition, Ministry of Health, Mexico City,
  Mexico
5 Tecnologico de Monterrey, School of Medicine, Mexico City, Mexico



Key words: vitiligo, pediatric vitiligo, dermoscopic patterns, reflectance confocal microscopy
Citation: Godínez-Chaparro JA, Roldán-Marín R, Soto-Mota A, Calzada-Mendoza CC. Dermatoscopic Patterns In Childhood Vitiligo
And Their Association With Reflectance Confocal Microscopy Findings. Dermatol Pract Concept. 2023;13(4):e2023306.
DOI: https://doi.org/10.5826/dpc.1304a306
Accepted: September 1, 2023; Published: October 2023
Copyright: ©2023 Godínez-Chaparro et al. This is an open-access article distributed under the terms of the Creative Commons
Attribution-NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted
noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: None.
Authorship: All authors have contributed significantly to this publication.
Corresponding Author: Juan Alberto Godínez-Chaparro, Tuxpan 28, 202-A Roma Sur, Cuauhtémoc, CP:06760 Mexico City, Mexico
Phone: 55 52 65 28 00 ext.1541, 1503 Email: alberto.godinezch@gmail.com




  ABSTRACT             Introduction: The diagnosis of vitiligo is mainly based on clinical findings. However, dermoscopy or
                       reflectance confocal microscopy (RCM) could be useful for assessing its progression (stability, pigmen-
                       tation, or depigmentation).
                       Objectives: To evaluate the correlation of dermatological findings by dermoscopy and RCM in pedi-
                       atric vitiligo.
                       Methods: We conducted a cross-sectional, descriptive, and analytical clinical study. Pediatric patients
                       with vitiligo of both sexes, aged > 1 year and < 18 years, with all spectrums of the disease were includ-
                       ed. Vitiligo lesions were evaluated clinically, by dermoscopy, and microscopy.
                       Results: A total of 40 patients with vitiligo were included. Eight dermoscopic patterns were found:
                       reduced/absent pigment network, perifollicular pigmentation, trichromic, tapioca sago, perifollicular




Original Article | Dermatol Pract Concept. 2023;13(4):e2023306                                                                           1
                      depigmentation, starburst, leukotrichia, and erythema. Skin with a normal pigment network showed
                      complete dermal papillary rings and half-rings. Skin with reduced/absent pigment network also had an
                      absence of papillary rings or only showed half-rings and was more common in unstable vitiligo. The
                      trichrome pattern only showed half-rings. The Tapioca sago pattern showed complete papillary rings
                      and appeared in younger patients. Perifollicular pigmentation showed half-rings and complete rings
                      and did not show associations. The diffuse borders did not present complete papillary structures. It
                      was found that vitiligo duration time of fewer than 24 months (Odds Ratio 4.56, CI 1.09-18.99) and
                      absent papillary rings (OR 2.75, CI 1.01-7.51) are associated with unstable prognosis.
                      Conclusions: Certain dermatoscopic and microscopic findings, such as the reduction/absence of the
                      pigment network, tapioca sago pattern, and absence of papillary rings, can be used to assess the stabil-
                      ity of the disease and provide insight into the clinical behaviour of vitiligo.




Introduction                                                        that allows visualizing sub-macroscopic morphological
                                                                    structures that are invisible to the naked eye and correspond
Vitiligo is a chronic and acquired disorder of pigmentation.        to specific histological structures [8]. Initially, dermoscopy
It is characterized by the loss of function and/or destruction      was used for the study and screening of pigmented lesions,
of epidermal melanocytes and, occasionally, of the hair folli-      but nowadays, it has different applications, including disor-
cle, causing achromatic macules or spots that increase in size      ders of pigmentation such as vitiligo. This diagnostic tool
over the years [1]. It is the most frequent disorder of pigmen-     detects subtle changes in the pigmentary pattern that help
tation and has a worldwide incidence of 0.38% to 1% [2].            in the non-invasive confirmation of vitiligo, evaluates its
Vitiligo affects both sexes equally and in 37% of cases it ap-      activity, and differentiates it from other hypo-pigmentary
pears during infancy [2,3]. Since children have thinner skin,       disorders in the early stages of the disease (eg, piebaldism,
greater regenerative capacity, and a lower frequency of vitil-      tuberous sclerosis, hypomelanosis of Ito, Waardenburg syn-
igo associated with other autoimmune diseases, vitiligo has a       drome, achromic nevus, post-inflammatory hypomelanosis,
distinct clinical prognosis and expression compared with the        etc) [9]. The application of this technique to hypopigmented
adult population [4-6].                                             lesions is recent; therefore, there have been only a few stud-
    Under its evolution, vitiligo can change and exhibit            ies conducted on vitiligo. The majority of these studies has
three distinct behaviours: stability, progression, or regres-       been conducted in adults and is limited to describing derma-
sion. Vitiligo is considered stable or inactive when no new         toscopic patterns. So far, there has been no successful cor-
lesions have developed in the last 12 months and existing           relation between the microscopic structures beneath these
lesions show no signs of progression. On the other hand, it         dermatoscopic images.
is referred to as progressive or unstable vitiligo when there          RCM is a non-invasive study that allows for the instant
is formation and/or development of new lesions within 12            capture of black- and -white images of the skin, ranging
months, or when pre-existing lesions grow larger. Finally,          from the epidermis to the upper reticular dermis, with an
regressive or pigmentary vitiligo occurs when spontaneous           imaging depth of up to 250-300 μm. This provides a resolu-
­re-pigmentation of existing lesions takes place [3,4].             tion similar to that of skin histology and is particularly well-
    The diagnosis of vitiligo is clinical and usually does not      suited for pigmentary disorders due to the contrast provided
require laboratory tests or extension studies. Skin biopsy is       by melanin. In vitiligo lesions, RCM reveals the absence of
reserved for cases of diagnostic doubt or when other pigmen-        dermal papillary rings (non-edged papillae), and bright ke-
tary disorders need to be excluded [7]. Clinical evaluation         ratinocytes are not detected in the epidermis [10]. Currently,
of the different evolutionary stages of this disease (stability,    there are no studies that establish a connection between der-
pigmentation, or depigmentation) remains inconclusive. To           matoscopic patterns, and the microscopic findings observed
date, there is no standardized method for determining the           through RCM.
stability of vitiligo. The lack of standardization is due to the
high variability in vitiligo assessment. Because of these issues,   Objectives
objective and non-invasive methods are needed to assess the
behaviour and extent of depigmented skin in comparison to           The objective of this study was to evaluate the association
the surrounding normal skin.                                        of different dermatoscopic patterns with findings observed
    Dermoscopy (also known as epiluminescence micros-               with RCM as a diagnostic alternative to help evaluate the
copy or dermatoscopy) is an in vivo diagnostic technique            evolution of vitiligo in children.


2                                                                       Original Article | Dermatol Pract Concept. 2023;13(4):e2023306
Methods                                                          type of vitiligo and its prognosis. The SPSS program version
                                                                 26 IBM was used, and a bilateral P value of <0.05 was as-
Study Type and Location                                          sumed to be statistically significant.
We conducted a cross-sectional, descriptive, analytical, pro-
spective, and observational study at the Dermato-Oncology
                                                                 Results
Clinic, Experimental Medicine Unit, Faculty of Medicine,
National Autonomous University of Mexico from March              Forty patients with vitiligo were enrolled, including 27 men
27th to November 30th, 2022. This study adhered to the           (67.5%) and 13 women (32.5%). All participants underwent
guidelines outlined in the Helsinki Declaration, Belmont Re-     clinical, dermatoscopic, and reflectance confocal microscopy
port, and the General Health Law regarding health research,      evaluations. Table 1 shows the characteristics of the popu-
including information regarding internal ethics committees       lation. Only 13 patients had any associated comorbidity: 4
in health institutions (Articles 100, 103, and 105) and the      had atopic dermatitis, 3 had diabetes mellitus, 2 had hypo-
Mexican Official Standard NOM012-SSA3-2012, the inter-           thyroidism, 2 had epilepsy, and there was one case each of
nal registration number is ODFM/059/22 [11,12].                  psoriasis and cyclic neutropenia.
                                                                    Tables 2 and 3 summarize the characteristics of patients
Study Protocol                                                   with vitiligo stratified by type of vitiligo (segmental, non-
Pediatric patients with vitiligo who spontaneously attended      segmental, and indeterminate) and by behavior (unstable,
the Clinic, of both sexes, >1 year and <18 years old, with all   stable, and pigmented).
spectra of the disease and regardless of associated diseases        Regarding dermatoscopy, 8 different dermatoscopic pat-
were included. Those who withdrew informed consent were          terns were found in vitiligo lesions: 1) reduced/absent pig-
eliminated.                                                      ment network, 2) perifollicular pigmentation, 3) trichromy,
    A vitiligo patch was evaluated clinically, dermoscopi-       4) tapioca sago, 5) perifollicular depigmentation, 6) starburst,
cally, and with RCM. The most recent lesion was evaluated.       7) leukotrichia, and 8) erythema (Figure 1). The most
The extent of vitiligo was calculated using the online appli-    common pattern was reduced or absent pigment network,
cation Vitiligo Extend Score (VES). A panoramic image of         ­followed by leukotrichia, tapioca sago, and trichromy. When
the dermatosis was taken with the Fotofinder ATBM MAS-           comparing dermatoscopic patterns with clinical characteris-
TER equipment, and then polarized dermoscopic evaluation         tics, we found that reduced/absent pigment network pattern
of the healthy skin (10 cm away from the lesion), center,        was associated with unstable vitiligo (P = 0.05). A tapioca
and edge of the lesion was performed with 20x magnifi-           sago pattern appeared in younger patients (6.5 ± 5.1 versus
cation. The same areas were evaluated with the Vivascope         10.8 ± 3.9 years, P = 0.05) and leukotrichia was more com-
3000 RCM (Caliber I.D.) to assess microscopic findings,          mon in segmental vitiligo (100% of cases, P < 0.05). The rest
and photographs of both techniques were taken. All three         of the dermatoscopic patterns showed no association with
evaluations were performed on the same day. The selection        the other study variables.
of participants and clinical, dermoscopic, and microscopic          In Table 4 and Figure 2, the results of dermatoscopic pat-
results were evaluated by 1 pediatric dermatologist and 1        terns contrasted with the microscopic findings seen on the re-
dermatologist specialized in dermoscopy and RCM .                flectance confocal microscope are summarized; normal skin,
                                                                 the center, and the edge of the lesion were analyzed (see Ta-
Statistical Analysis                                             ble 4). Table 5 summarizes the unadjusted logistic regression
The sample size was calculated using the statistical program     model to predict vitiligo instability with the main variables
Open Epi version 3 based on a population proportion with a       of interest; only evolution time less than 24 months, reduced/
hypothetical disease frequency of 2.8%, the prevalence was       absent pigment network, and RCM of the lesion edge were
derived from information described in other populations.         risk factors associated with vitiligo instability. Finally, in Ta-
Kolmogorov-Smirnov hypothesis tests were conducted to            ble 6, an adjusted logistic regression model is presented with
assess normality. Variables meeting this criterion were sum-     the variables of time of evolution and absent papillary rings.
marized as means and standard deviation as a measure of
dispersion. Variables with non-normal distributions were         Conclusions
summarized as means and interquartile range (IQR). Nomi-
nal variables such as dermoscopic patterns were summarized       In our study, the most relevant epidemiological characteristics
with frequencies and percentages. A comparison of dermo-         were a) vitiligo was more common in men (67.5%), this result
scopic findings between the center and edge of the lesion was    differs from what has been reported in the literature but did
                                  2
made using a Chi-Square (Xi ) test. Multivariate analysis        not show a statistically significant, b) the onset age of vitiligo
logistic regression analyses were stratified according to the    occurred in middle childhood (7.3 years +3.8) and was similar


Original Article | Dermatol Pract Concept. 2023;13(4):e2023306                                                                   3
      Table 1. Characteristics of the pediatric                     with a frequency similar to other populations [13-16],
             population with vitiligo.                              d) Segmental vitiligo appeared in younger patients, and early
                                                                    onset has been reported in other pediatric populations [15].
                   Variable                             N = 40
                                                                    Additionally, it usually does not have a re-pigmentation
 Male gender, No. (%)                                 27 (67.5)
                                                                    treatment (P < 0.05); this situation may occur because, at
 Age, mean (SD), years.                               10.4 (4.2)
 Onset of dermatosis                                   7.3 (3.8)    the beginning, the lesion is single, small, and non-specific,
                                                                    therefore, it does not receive management and continues the
 Skin phototypes, No. (%)
    - III                                             27 (67.5)     natural history of the disease. e) The Vitiligo Extent Score
    - IV                                              13 (32.5)     (VES), which measures the extent of dermatosis, showed
 Type of vitiligo, No. (%)                                          that the condition in children is less than 10% [17]. On the
    - Segmental                                       10 (25.0)     other hand, the non-segmental type had the highest extent
    - Non-segmental                                   23 (57.5)     (0.78) followed by the segmental (0.49) and the indetermi-
    - Indeterminate                                    7 (17.5)     nate (0.16). The differences were statistically significant and
 Non-segmental subtype, No. (%) N = 23                              can be explained because indeterminate vitiligo precedes any
   1. Acrofacial                                       4 (10.0)
                                                                    of the other types by months or years, thus, its extent stops
   2. Generalized                                     16 (40.0)
                                                                    and/or occurs slowly, making its final classification difficult.
   3. Universal                                            -
   4. Mucosal                                              -           There are different ways to diagnose vitiligo without
   5. Mixed                                             2 (5.0)     the need for invasive procedures. These methods serve to
   6. Rare variants (Follicular/Menor                   1 (2.5)     assess size, stability, severity, and treatment response. These
      vitiligo/Punctate)                                            methods can be divided into subjective, semi-objective, and
 Segmental subtype, No. (%) N = 10                                  objective categories. Subjective methods include clinical
    1. Unsegmented                                     8 (20.0)     evaluation by a dermatologist, as well as visual comparisons
    2. Bisegmental                                      2 (5.0)
                                                                    of the skin before and after treatment using photos that can
    3. Multisegmental                                      -
                                                                    be digital or non-digital, taken under visible or ultraviolet
 Indeterminate subtype, No. (%) N = 7
                                                                    light, and the Vitiligo Disease Activity Score to assess vitiligo
    1. Focal                                           7 (17.5)
    2. Mucosal                                            0         stability over time. This last method relies on information
 Asymmetric distribution No. (%)                      20 (50.0)     provided by the patient about the activity of their disease.

 Duration time, median (IQR), months                   24 (12.0,    Semi-objective methods include the Vitiligo Area Scoring In-
                                                        57.0)       dex (VASI) and point counting. Objective methods include
 Evolution, N° (%)                                                  image analysis using software, tristimulus colorimetry, spec-
   1. Pigmentary                                      11 (27.5)     trophotometry, reflectance confocal microscopy, and more
   2. Stable                                           7 (17.5)     recently, dermatoscopy [10].
   3. Unstable                                        22 (55.0)        This study described the dermatoscopy of vitiligo in chil-
 VES (Vitiligo Extent Score), median                     0.59       dren. Eight different patterns were found: reduced/absent
 (IQR)                                                (0.16,1.36)   pigment network, perifollicular pigmentation, trichrome,
 Patients with treatment, No. (%)                     31 (77.5)     tapioca sago, perifollicular depigmentation, starburst, leu-
 Type of treatment, No. (%)                                         kotrichia, and erythema. The border of the lesion showed
   1. None                                             9 (22.5)     more dermatoscopic findings. Analyzing the patterns indi-
   2. Topical steroid                                   3 (7.5)
                                                                    vidually, we found that the reduced/absent pigment network
   3. Topical calcineurin inhibitor                   10 (25.0)
   4. Topical steroid + Topical                       12 (30.0)     was more common in unstable vitiligo. The tapioca sago
      calcineurin inhibitor                             2 (5.0)     appeared in younger patients, and some authors associate it
   5. Psoralens                                        4 (10.0)     with instability and early stages of the disease [18,19]. The
   6. Phototherapy                                                  perifollicular depigmentation showed no associations; how-
 Comorbidity, No. (%)                                               ever, in two publications by Kumar Jha et al, it was related
   1. No                                              27 (67.5)     to stable vitiligo [18,19]. Leukotrichia appeared in segmental
   2. Yes                                             13 (32.5)
                                                                    and asymmetric vitiligo (P = 0.05), and this pattern has also
IQR = intequartile ranges; SD = standard deviation.                 been associated with stable or pigmentary vitiligo [18,19].
                                                                    Perifollicular pigmentation had no association in our study;
to the French and Brazilian pediatric populations, c) Skin          however, some studies link it to pigmentary vitiligo [20-22].
phototype III was the most common and did not show any              The starburst and erythema patterns showed no associations
epidemiological association, d) Non-segmental vitiligo was          in our study, but the number of cases collected is limited to as-
the most common, followed by segmental and indeterminate,           sert the presence or absence of possible clinical associations.



4                                                                       Original Article | Dermatol Pract Concept. 2023;13(4):e2023306
                                                                                                               Table 2. Characteristics of pediatric patients with vitiligo stratified by type of vitiligo.
                                                                                                                                                                       Type of vitiligo
                                                                                                                               Other types             Non-segmental      Other types               Indeterminate       Other types
                                                                                                          Segmental (SV)      (NSV and IV)                 (NSV)          (SV and IV)                    (IV)           (SV y NSV)
                                                                                 Variable                       N = 10           N = 30      P-value       N = 23            N = 17       P-value        N=7              N = 33      P-value
                                                                     Sex
                                                                       Male N = 27                             5 (18.5)        22 (81.5)      0.24a        7 (63.0)        10 (37.0)       0.49a        5 (18.5)         22 (81.5)     0.99a
                                                                       Female, No. (%) N = 13                  5 (38.5)        8 (61.5)                    6 (46.2)         7 (53.8)                    2 (15.4)         11 (84.6)
                                                                     Age, mead (SD), years                    8.3 (±4.1)       11.1 (±4.0)    0.05b      11.0 (±4.4)       9.6 (±3.9)      0.03b      11.5 (±2.8)       10.1 (±4.4)    0.43b
                                                                     Skin phototypes, No. (%)
                                                                       - III N = 27                            6 (22.2)        21 (77.8)      0.70a       15 (55.6)        12 (44.4)       0.99a        6 (22.2)         21 (77.8)     0.39a




Original Article | Dermatol Pract Concept. 2023;13(4):e2023306
                                                                       - IV N = 13                             4 (30.8)        9 (62.9)                    8 (61.5)         5 (38.5)                    1 (7.7)          12 (92.3)
                                                                     Distribution
                                                                       - Symmetrical, No. (%) N = 20            1 (5.0)        19 (95.0)      0.01a       17 (85.5)         3 (15.0)       0.01a        2 (10.0)         18 (90.0)     0.40a
                                                                       - Asymmetrical No. (%)N = 20            9 (45.0)        11 (55.0)                   6 (30.0)        14 (70.0)                    5 (25.0)         15 (75.0)
                                                                     Duration time, median (IQR),          24.0 (5.0, 45.0)    27.0 (16.5,    0.34c      30.0 (22.0,       24.0 (6.5,      0.21c    24.0 (7.0, 48.0)    24.0 (15.0,    0.60c
                                                                     months                                                      60.0)                     60.0)             42.0)                                        60.0)
                                                                     VES (Vitiligo Extent Score),         0.49 (0.20, 1.63)    0.60 (0.14,   0.98***     0.78 (0.19,       0.22 (0.13,     0.04c    0.16 (0.08, 0.24)   0.70 (0.20,    0.01c
                                                                     median (IQR)                                                 1.40)                     1.51)             0.63)                                        1.46)
                                                                     Evolution, No. (%)
                                                                       - Pigmentary N = 11                     2 (18.2)        9 (81.8)       0.89a        7 (63.6)         4 (36.4)       0.29a        2 (18.2)          9 (81.8)     0.08a
                                                                       - Stable N = 7                          2 (28.6)        5 (71.4)                    2 (28.6)         5 /71.4)                    3 (42.9)          4 (57.1)
                                                                       - Unstable N = 22                       6 (28.3)        16 (72.7)                  14 (63.6)         8 (36.4)                    2 (9.1)          20 (90.9)
                                                                     Patients with treatment, No. (%)
                                                                       - No N = 9                              5 (55.6)        4 (44.4)       0.02a        3 (33.3)         6 (66.7)       0.13a        1 (11.1)          8 (88.9)     0.99a
                                                                       - Yes N = 31                            5 (16.1)        26 (86.9)                  20 (63.5)        11 (35.5)                    6 (19.4)         25 (80.6)
                                                                 a
                                                                 Fisher exact test, bStudent t-test, cMann-Whitney U test.




5
6
                                                                                                                     Table 3. Characteristics of pediatric patients with vitiligo by clinical stability.
                                                                                                                                                                                       Vitiligo stability
                                                                                                                                Others: stable                                          Others: unstable                                           Others: stable
                                                                                                              Unstable         and pigmentary                             Stable        and pigmentary                           Pigmentary        and unstable
                                                                                  Variable                      N = 22             N = 18                P-value           N=7                N = 33              P-value            N =11              N = 29            P-value
                                                                     Sex
                                                                       Male, No. (%) N = 27                    14 (51.9)           13 (48.1)              0.73a          4 (14.8)            23 (85.2)              0.66a           9 (33.3)           18 (66.7)           0.28a
                                                                       Female, No. (%) N = 13                   8 (61.5)            5 (38.5)                             3 (23.1)            10 (76.9)                              2 (15.4)           11 (84.6)
                                                                     Age, mead (SD), years                    9.6 (±4.0)          11.3 (±4.4)             0.19 b       11.8 (±3.1)          10.1 (±4.4)             0.33a         11.0 (±5.1)         10.1 (±3.9)          0.54b
                                                                     Skin phototypes, No. (%)
                                                                       - III N = 27                            17 (63.0)           10 (37.0)              0.18a          5 (18.5)            22 (81.5)              0.99a           5 (18.5)           22 (81.5)           0.12a
                                                                       - IV N = 13                              5 (38.5)            8 (61.5)                             2 (15.4)            11 (84.6)                              6 (46.2)           7 (53.8)
                                                                     Distribution
                                                                       - Symmetrical, No. (%) N = 20           10 (50.0)           10 (50.0)              0.75a          2 (10.0)            18 (90.0)              0.40a           8 (40.0)           12 (60.0)           0.15a
                                                                       - Asymmetrical No. (%) N = 20           12 (60.0)            8 (40.0)                             5 (25.0)            15 (75.0)                              3 (15.0)           17 (85.0)
                                                                     Duration time, median (IQR),              24 (7.5,         48 (24.0, 72.0)           0.01c          72 (48.0,        24 (8.5, 36.0)           <0.01c       24 (22.0, 72.0)     24 (8.5, 48.0)         0.45 c
                                                                     months                                     31.5)                                                     84.0)
                                                                     VES (Vitiligo Extent Score),             0.63 (0.10,      0.45 (0.18, 2.30)          0.63a         0.25 (0.11,      0.63 (0.17, 1.41)         0.42 c         0.70 (0.19,         0.35 (0.11,          0.22 c
                                                                     median (IQR)                                1.10)                                                     0.78)                                                     3.38)               1.05)
                                                                     Type of vitiligo, No. (%)
                                                                       - Segmental N = 10                       6 (60.0)            4 (40.0)              0.37a          2 (20.0)             8 (80.0)              0.11a           2 (20.0)           8 (80.0)            0.89a
                                                                       - Non-segmental N = 23                  14 (60.9)            9 (39.1)                              2 (8.7)            21 (91.3)                              7 (30.4)           16 (69.6)
                                                                       - Indeterminate N = 7                    2 (28.6)            5 (71.4)                             3 (42.9)             4 (57.1)                              2 (28.6)           5 (71.4)
                                                                     Comorbidity, No. (%)
                                                                       - No N = 27                             18 (66.7)            9 (33.3)              0.04a           2 (7.4)            25 (92.6)              0.02a           7 (25.9)           20 (74.1)           0.99a
                                                                       - Si N = 13                              4 (30.8)            9 (69.2)                             5 (38.5)             8 (61.5)                              4 (30.8)           9 (69.2)
                                                                     Patients with treatment, No. (%)
                                                                       - No N = 9                               6 (66.7)            3 (33.3)              0.47a          2 (22.2)             7 (77.8)              0.64a          1 (11.1)            8 (88.9)            0.39a
                                                                       - Yes N = 31                            16 (51.6)           15 (48.4)                             5 (16.1)            26 (83.9)                             10 (32.3)           21 (67.7)
                                                                 a
                                                                 Fisher exact test, bStudent t-test, cMann-Whitney U test.

                                                                 This study showed that instability is associated with a shorter duration of dermatosis and usually does not have associated comorbidities. On the other hand, stable vitiligo had a longer duration, 6 years after the
                                                                 onset of the dermatosis. Additionally, stability was more associated with the presence of comorbidities.




Original Article | Dermatol Pract Concept. 2023;13(4):e2023306
Figure 1. Dermoscopic patterns of vitiligo. (A) Normal pigment network; (B) Absent pigment network; (C) Perifollicular pigmentation (blue
arrow); (D) Trichrome (blue arrow); (E) Tapioca-like pattern; (F) Perifollicular depigmentation (blue arrow); (G) Satellite lesion (blue arrow);
(H) Leukotrichia; (I) Erythema (blue arrow).




Figure 2. (A) Normal pigment network and complete ringed pattern. (B) Trichrome pattern and half rings. (C) Absent pigment network and
lack of rings.



Original Article | Dermatol Pract Concept. 2023;13(4):e2023306                                                                                7
         Table 4. Dermoscopic patterns contrasted with findings in reflectance confocal microscopy.
                           Dermatoscopy                                              Reflectance confocal microscopy
                      Dermatoscopic patterns                                                    Papillary rings
                                                                       Absence of
             Normal skin adjacent to the lesion                          rings              Half rings      Complete rings         P-value
    Normal pigment network No. (%) N = 40                                     -              7 (17.5)           33 (82.5)              -
    Center of the lesion                                             Absence of rings       Half rings       Complete rings         P-value
                                                                          N =1               N =28              N =11
    Reduced/absent pigment network, No. (%) N = 31                       21 (67.7)           10(32.7)                -               0.69a
    Others (Leukotrichia/Perifollicular depigmentation/                  7 (77.8)            2 (22.2)                -
    Erythema) N =9
    Border of the lesion                                             Absence of rings       Half rings       Complete rings
                                                                         N =18               N =15              N =7
    Pattern 1, No. (%)
      - Reduced/absent pigment network N = 17                            11 (64.7)            5 (29.4)            1 (5.9)            0.08a
      - All other patterns N = 23                                        7 (30.4)            10 (43.5)           6 (26.1)
    Pattern 2, No. (%)
      - Perifollicular pigmentation N = 3                                    0               1 (33.3)            2 (66.7)            0.03a
      - All other patterns N = 37                                        18 (48.6)           14 (37.0)           3 (13.5)
    Pattern 3, No. (%)
      - Trichromic´ N = 4                                                    0                4 (100)               0                0.02a
      - All other patterns N = 36                                        18 (50.0)           11 (30.6)           7 (19.4)
    Pattern 4, No. (%)
      - Tapioca sago N = 4                                                   0               1 (25.0)            3 (75.0)           <0.01a
      - All other patterns N = 36                                        18 (50.0)           14 (38.9)           4 (11.1)
    Pattern 5, No. (%)
      - Perifollicular depigmentation N = 3                              1 (33.3)             2 (66.7)              0                0.76a
      - All other patterns N = 37                                        17 (45.9)           13 (35.1)           7 (18.9)
    Pattern 6, No. (%)
      - Starburst N = 1                                                   1 (100)                0                  0                0.99a
      - All other patterns N = 39                                        17 (43.6)           15 (38.5)           7 (17.9)
    Pattern 7, No. (%)
      - Leukotrichia N = 7                                               4 (57.1)            2 (28.6)            1 (14.3)            0.86a
      - All other patterns N = 33                                        14 (42.4)           13 (39.4)           6 (18.2)
    Pattern 8, No. (%)
      - Erythema N = 1                                                    1 (100)                0                  0                0.99a
      - All other patterns N = 39                                        17 (43.6)           15 (38.5)           7 (17.9)
    Types of borders                                                 Absence of rings       Half rings       Complete rings
                                                                          n=18               n=15                n=7
    1. Defined
      - Well-defined border N = 20                                        9 (45.0)            4 (20.0)           7 (35.0)           <0.01a
      - All the others N = 20                                             9 (45.0)           11 (55.0)              0
    2. Trichromic
      - Trichromic border N = 5                                          1 (20.0)             4 (80.0)              0                0.17 a
      - All the others N = 35                                            17 (48.6)           11 (31.4)           7 (20.0)
    3. Diffuse
      - Diffuse border N = 15                                            8 (53.3)            7 (46.7)               0                0.06a
      - All the others N = 25                                            10 (40.0)           8 (32.0)            7 (28.0)
a
 Fisher exact test.

The results reveal that skin with a normal pigment network displayed complete dermal papillary rings, although in certain cases only half
rings were observed. Within the center of the lesion, all four dermatoscopic patterns exhibited a lack of dermal papillary rings or only half
rings. At the border, the perifollicular pigmentation demonstrated half-rings as well as complete rings. The trichrome and tapioca sago pattern
showcased complete papillary rings. Lastly, some complete papillary rings appeared in well-defined borders.




8                                                                             Original Article | Dermatol Pract Concept. 2023;13(4):e2023306
 Table 5. Unadjusted model of clinical factors and dermatological findings associated with unstable
                                         childhood vitiligo.
                 Variable                       OR         CI 95% inferior         CI 95% superior         P-value        R squared
 Male                                          1.486              0.386                  5.722              0.565           0.011
 Age < 6 years                                 3.000              0.525                 17.159              0.217           0.055
 Skin phototypes (III)                         2.720              0.696                 10.633              0.150           0.069
 Type of vitiligo
   - Non-segmental                             1.750              0.492                  6.230              0.387           0.025
 Duration time
  - < of 24 months                             4.286              1.135                 16.182              0.032           0.155
 Vitiligo extent score (VES)
   - > 1.5                                     2.436              0.494                 12.014              0.274           0.041
 Treatment, yes                                1.875              0.396                  8.875              0.428           0.022
 Dermatoscopy of the center
   - Reduced/absent pigment network            3.167              0.663                 15.115              0.148           0.072
 Dermatoscopy Border
   - Reduced/absent pigment network            5.056              1.248                 20.480              0.023            0.178
   - Tapioca sago                              0.238              0.023                  2.517              0.233            0.054
   - Leukotrichia                              0.533              0.106                  2.873              0.481            0.017
   - Trichromic                                2.684              0.254                 28.311              0.411           0.0253
   - Diffuse border                            1.385              0.378                  5.066              0.623            0.008
 Reflectance Confocal Microscopy               2.635              1.038                  5.687              0.041           0.146
 border- absence rings
CI = Confidence Interval; OR = Odds Ratio.

In the unadjusted model of logistic regression, it was found that vitiligo duration time <24 months, a reduced or absent pigment network,
and the absence of papillary rings are factors associated with vitiligo instability.




             Table 6. Adjusted model of clinical factors and dermatological findings associated
                                           with unstable vitiligo.
            Variable                   OR            CI 95% inferior          CI 95% superior            P-value         R squared
 Absent papillary rings               2.757               1.011                      7.513                0.047
 Duration time                        4.561               1.095                     18.998                0.037             0.278
 < de 24 months
CI = Confidence Interval; OR = Odds Ratio.




    Regarding RCM, in two separate studies conducted by                the presence of incomplete melanocytic cells, resulting in
Ardigo et al and Lai et al, the skin of adolescent and adult pa-       an image of partial rings or similar to a "scaly" border-like
tients with vitiligo was evaluated, as well as that of patients        pattern [23,24]. The results of our study revealed the same
without the condition. In both studies, at the dermo-epidermal         microscopic findings in both healthy and affected skin.
junction of the control group, the presence of bright refrac-             Lai et al. also compared the findings observed through
tive keratinocytes and melanocytes forming crowns or rings             RCM with other pigmentation conditions such as nevus
around the dermal papillae (edged papillae) was observed.              depigmentosus and anemic nevus and noted that the der-
In the case of vitiligo lesions, the absence of these dermal           mal papillary rings in both affected skin and adjacent skin
papillary ring structures was noted, or only remnants of               maintained their integrity and brightness. Additionally, they
them remained. Additionally, a decrease in brightness, the             described that in areas of re-pigmentation, vitiligo exhib-
presence of inflammatory cells (lymphocyte exocytosis), and            ited three distinct patterns: 1) Marginal re-pigmentation
the absence of melanocytes were observed in the affected ar-           with highly refractive melanocytes moving from normal
eas. In the skin adjacent to vitiligo, complete dermal papil-          skin to the affected area, 2) Perifollicular re-pigmentation
lary rings with the same brightness were found, or there was           with melanocytes surrounding hair follicles, and 3) Diffuse



Original Article | Dermatol Pract Concept. 2023;13(4):e2023306                                                                         9
re-pigmentation with melanocytes distributed in the affected       microscopic findings, c) it is a cross-sectional study that did
skin [24]. In our study, being a cross-sectional study, a second   not have follow-up of the patients, d) due to the number of
measurement of the lesions was not conducted, therefore, it        participants, only 2 predictor variables could be entered into
was not possible to compare their microscopic behavior in          the multivariate model.
lesions with re-pigmentation.                                         This study opens up the possibility for future studies to
     The strength of our study was to associate the derma-         expand the sample size to improve the generalization and
toscopic and microscopic reflectance confocal findings             validation of the results, to conduct cohort studies to deter-
of childhood vitiligo. This detailed association provides a        mine the dermatoscopic and microscopic changes influenced
unique and valuable perspective to understand the nature           by the disease prognosis or therapeutic regimen, to consider
and evolution of vitiligo within a specific age group. The         replicating the study in populations with different skin types
study revealed that the skin with a normal pigment network         or in adult populations, and to explore new methodological
showed complete dermal papillary rings, but in some cases          approaches in data analysis.
(17.5%), only half rings or festooned borders were present.           The dermatoscopic patterns associated with cutaneous
This may be a normal characteristic of infantile skin or there     microscopic findings can be used to support the evaluation
may already be a reduction in melanocytic structures that          of the clinical behaviour of vitiligo. The reduced/absent
predisposes to the spread of dermatoses. In the center of          pigment network located in the center of the lesion did not
the lesion, all 4 dermatoscopic patterns showed the absence        present complete dermal papillary structures or only had
of dermal papillary rings or only half rings. The absence of       partial rings and was associated with instability. The borders
dermal papillary rings was a predictor of the instability of       of the lesion showed more dermatoscopic and microscopic
the dermatosis. On the other hand, the border of the le-           changes. The tapioca sago presented complete papillary
sion showed different characteristics according to the type        rings and appeared in younger patients. The trichrome pat-
of dermatoscopic pattern. For example, the trichrome pat-          tern only had partial rings, the perifollicular pigmentation
tern only had half rings. This pattern has been associated by      showed partial and complete rings, and the diffuse borders
other authors with unstable and stable vitiligo [20,25]. The       did not show papillary structures. However, none of the
tapioca sago pattern showed complete papillary rings, and          three patterns showed clinical associations. Further studies
this pattern has been associated with unstable behavior and        with a larger sample size and evaluating concordance are re-
could be found at the beginning of the disease due to having       quired to determine possible associations and validate the
complete papillary structures [19,21]. Perifollicular pigmen-      reported results.
tation showed half rings and complete rings, and this pat-
tern has been described in re-pigmentation but other authors
                                                                   Acknowledgment: To all the staff at the Oncodermatology
such as Pumirna and Wang have associated it with instability
                                                                   Clinic of the UNAM for facilitating the completion of this
of the disease [20-22,26]. Perifollicular areas are key pieces
                                                                   project.
for depigmentation or repigmentation because melanocytic
stem cells are at the hair bulb [27]; through various mecha-
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Original Article | Dermatol Pract Concept. 2023;13(4):e2023306                                                                                11
