Dermatoscopic and histopathological correlation in stable and unstable vitiligo

INTRODUCTION

Vitiligo is a common autoimmune disorder that results in progressive melanocyte destruction, leading to depigmented macules of varying shapes and sizes. It affects an estimated 0.06–2.28% of the global population, with higher prevalence rates reported in India (1–8%).^[1] Despite being non-life-threatening, vitiligo has a profound psychosocial impact, often leading to depression, anxiety, and diminished quality of life.^[2]

From a pathophysiological perspective, vitiligo is an immune-mediated disease wherein the T-cell-driven destruction of melanocytes is a key mechanism.^[3] The disease is classified as stable or unstable, with stability being defined by the absence of new or enlarging lesions for at least 1 year.^[4] Stable vitiligo is a prerequisite for surgical treatment options such as melanocyte transplantation and punch grafting, whereas unstable vitiligo requires immunomodulatory therapies such as corticosteroids, calcineurin inhibitors, and phototherapy. However, clinical history alone is often insufficient to determine disease stability, making objective diagnostic methods essential.

Dermoscopy and histopathology serve as important adjuncts in vitiligo assessment. While histopathology is invasive and time-consuming, dermoscopy, a non-invasive imaging technique, has gained prominence as it allows real-time visualization of pigmentary changes, particularly in early and ambiguous cases.^[5] The present study aims to correlate dermoscopic findings with histopathological features to determine their clinical relevance in assessing vitiligo stability.

MATERIALS AND METHODS

This was a hospital-based, cross-sectional study conducted in a tertiary care hospital in Northeast India over a 1-year period. The study population comprised 40 clinically diagnosed vitiligo patients, classified as stable or unstable vitiligo. The inclusion criteria were willing patients with clinically confirmed stable or unstable vitiligo aged between 10 and 60 years, while cases of drug-induced vitiligo, patients with other concurrent dermatological disorders, and pregnant or lactating women were excluded from the study.

After taking informed written consent, each study participant underwent a detailed history-taking, including disease duration, family history, lesion stability, and progression followed by dermoscopic examination using a “Dermlite Dino Video Dermoscope” to assess the following features: (1) Border definition (sharp vs. ill-defined), (2) pigment network (absent, reduced, and reversed), (3) presence of perilesional and perifollicular hyperpigmentation, and (4) specific markers of unstable disease (starburst appearance, comet tail sign, and tapioca sago lesions). Skin biopsies were taken from both stable and unstable vitiligo lesions and stained with hematoxylin and eosin and Human Melanoma Black 45 (HMB-45) to analyze (1) basal cell vacuolization, (2) lymphocytic infiltration, and (3) epidermal spongiosis.

RESULTS

This study included a total of 40 patients diagnosed with vitiligo, of whom 21 (52.5%) had stable vitiligo, while 19 (47.5%) had unstable vitiligo. The age distribution revealed that the highest number of patients fell within the “21–40” years age group (55%), followed by 25% in the “41–60” years age group and 20% in the “1–20” years category. There was a slight male predominance, with 52.5% of patients being male and 47.5% female. Occupational analysis showed that 47.5% of patients were working professionals, 32.5% were students, and 20% were housewives.

Among the 40 patients, 32.5% had mucosal involvement, with the oral mucosa (61.5%) being the most commonly affected, followed by genital mucosa (31.5%). The distribution of vitiligo types showed that 80% of cases were non-segmental vitiligo, while 20% were segmental vitiligo. Within the non-segmental vitiligo group, generalized vitiligo was most frequent (40%), followed by acrofacial vitiligo (25%), and focal vitiligo (15%). The distribution of segmental vitiligo cases was relatively uniform across anatomical regions as seen in Figure 1.

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Figure 1:

Clinical spectrum of vitiligo in our study: (a) Nonsegmental vitiligo, (b) acral vitiligo, (c) generalized vitiligo, (d) mucosal vitiligo.

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Dermoscopy provided significant differences between stable and unstable vitiligo. Sharp borders were observed in 95.24% of stable vitiligo cases, whereas 57.89% of unstable cases exhibited ill-defined borders. The trichrome pattern, often indicative of disease activity, was found exclusively in unstable vitiligo (42.11%). The absence of a pigment network was recorded in 61.9% of stable cases, compared to only 15.79% of unstable cases, while a reversed pigment network was noted in 31.58% of unstable cases.

Perilesional hyperpigmentation, often linked to disease stability, was significantly more frequent in stable vitiligo (80.95%) than in unstable vitiligo (26.32%) (P < 0.05). Perifollicular hyperpigmentation, another potential marker of repigmentation, was present in 80.95% of stable cases, while only 36.84% of unstable cases showed this feature (P < 0.05) [Figures 2 and 3].

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Figure 2:

Dermoscopic findings in stable vitiligo in our study: (e) Depigmented macule with absent pigment network, (f) Depigmented macule with sharp border, (g) Perifollicular hyperpigmentation, (h) Sharp, well-defined border in stable vitiligo lesions.

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Figure 3:

Dermoscopic findings in unstable vitiligo in our study: (i) Satellite lesions, (j) Trichrome pattern, (k) Micro-Koebner phenomenon, (l) Irregular borders.

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Markers of disease instability, such as starburst appearance (73.68%) and comet tailing (63.16%), were highly prevalent in unstable cases, compared to 4.76% in stable vitiligo cases. Tapioca sago lesions were identified in 68.42% of unstable cases but only 4.76% of stable cases (P < 0.05).

Histopathology revealed distinct features differentiating between stable and unstable vitiligo [Figure 4]. Basal cell vacuolization was present in 68.42% of unstable cases, whereas it was virtually absent in stable cases. Dense lymphocytic infiltration was seen in 47.37% of unstable cases, compared to none in stable cases (P < 0.01). Epidermal spongiosis, suggestive of active immune-mediated melanocyte destruction, was observed in 68.42% of unstable cases (P = 0.01).

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Figure 4:

Histopathological findings in our study: (m) Hematoxylin and eosin (H&E) photomicrograph showing mild epidermal hyperplasia, spongiosis, and markedly decreased basal melanin and mild chronic inflammatory cell infiltration in the upper dermis (×40), (n) H&E photomicrograph showing marked chronic inflammatory cell infiltration in the periadnexal and perivascular regions and the upper dermis (×40), (o) Immunohistochemistry photomicrograph showing loss of staining of human melanoma black 45 (HMB-45) in the basal layer (×40), (p) Immunohistochemistryphotomicrograph showing normal staining pattern of HMB-45 in the basal layer (×40).

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HMB-45 staining showed focal positivity in 52.38% of stable cases, whereas 63.16% of unstable cases demonstrated partial positivity. However, complete HMB-45 negativity was recorded in 47.62% of stable cases and 36.84% of unstable cases, indicating greater melanocyte depletion in unstable lesions.

Further stratification of the data based on the duration of disease revealed that patients with stable vitiligo had an average disease duration of 5.2 years, whereas patients with unstable vitiligo had an average duration of 2.8 years. Upon evaluating the pattern of lesion spread, progressive vitiligo was more common in individuals with extensive body surface involvement, affecting more than 25% of the body surface area in 57.89% of unstable cases, whereas only 9.52% of stable cases showed similar extensive involvement.

Regional variations in lesion distribution were also analyzed, showing that facial lesions were more frequently associated with unstable vitiligo (42.1%), compared to stable vitiligo cases (19.04%). In contrast, limb lesions were more prevalent in stable vitiligo cases (61.90%) compared to unstable vitiligo cases (26.32%). Another important finding was that the Koebner phenomenon, a well-known marker of vitiligo activity, was noted in 68.42% of unstable vitiligo cases, whereas it was completely absent in stable vitiligo cases (P < 0.01).

To further explore dermoscopic patterns, the presence of perifollicular pigmentation was categorized by vitiligo subtype. Among generalized vitiligo cases, perifollicular hyperpigmentation was observed in 84.6% of stable cases, compared to only 38.5% of unstable cases. However, among segmental vitiligo cases, perifollicular pigmentation was seen in 66.7% of stable cases and only 16.7% of unstable cases.

Interestingly, the presence of residual perifollicular pigment was more frequently observed in younger patients (1–20 years age group), where it was noted in 92.3% of cases, compared to only 63.6% of patients aged above 40 years.

DISCUSSION

The findings of this study are consistent with prior research demonstrating that dermoscopy is a valuable tool in distinguishing stable and unstable vitiligo. The presence of sharp borders in 95.24% of stable vitiligo cases with a P < 0.05% aligns with studies by Elkazzaz et al., who reported a similar prevalence of sharply demarcated lesions in stable disease.^[6] Conversely, ill-defined borders were predominantly seen in unstable vitiligo (57.89%) (P < 0.05), which has been corroborated by studies from Yuan et al., indicating that blurred and irregular borders are markers of active disease progression.^[7]

The absence of a pigment network in 61.9% (P < 0.05) of stable vitiligo cases supports findings from Nirmal et al., who identified an absent pigment network as a specific indicator of stable disease.^[8] In addition, the reversed pigment network, which was seen in 31.58% (P < 0.01) of unstable cases in this study, has been recognized in prior research as an early dermoscopic sign of unstable vitiligo, confirming its utility as a diagnostic marker.^[8]

Perilesional hyperpigmentation was significantly associated with stable vitiligo (80.95%) (P < 0.05%), consistent with the findings of Jha et al. and Kamath et al., who reported similar prevalence rates.^[9,10] This feature is thought to reflect melanocyte activity and repigmentation potential. Similarly, perifollicular hyperpigmentation was observed in 80.95% (P < 0.05%) of stable vitiligo cases, aligning with findings by Varma et al., which suggested that perifollicular pigmentation is a hallmark of stable and repigmenting vitiligo.^[11]

Dermoscopic markers of unstable vitiligo, including starburst appearance and comet tailing, were present in 73.68% and 63.16% of unstable cases (P-values of both <0.05), respectively, findings that align with those of Elkazzaz et al. and Thatte et al., who found a high prevalence of these features in actively spreading vitiligo.^[6,12] The presence of tapioca sago lesions in 68.42% (P < 0.05) of unstable cases further confirms the role of dermoscopy in assessing disease activity, as previously noted by Nirmal et al.^[8]

Histopathological findings support the dermoscopic distinctions between stable and unstable vitiligo. The presence of dense lymphocytic infiltration in 47.37% (P < 0.0001%) of unstable cases corresponds with the observations of Benzekri et al., who found that inflammatory cell infiltration is significantly associated with progressive disease.^[13] The detection of basal cell vacuolization in 68.42% (P < 0.05%) of unstable cases suggests ongoing immune-mediated melanocyte destruction, consistent with the findings of Yadav et al.^[14]

Epidermal spongiosis was observed in 68.42% of unstable cases, a significantly higher prevalence than in stable vitiligo (28.57%) (P = 0.01). This finding aligns with the study by Kim et al., which demonstrated that spongiosis is a marker of inflammatory activity in vitiligo lesions.^[15] The increased presence of melanophages in unstable vitiligo (62.16%), though statistically not significant with a P = 0.11, supports the hypothesis that immune-mediated phagocytosis of melanocytes is a key mechanism in vitiligo progression.

We conducted Fisher’s exact test to assess the correlation between dermatoscopic and histopathological features of stable and unstable vitiligo. A statistically significant (P < 0.05) correlation was found. However, we could not find any similar study during the literature search. This highlights the uniqueness of our study.

These findings reinforce the role of dermoscopy as a reliable, non-invasive diagnostic tool in vitiligo assessment. While histopathology remains the gold standard, its invasive nature limits its widespread use. The strong correlation between dermoscopic and histopathological findings in this study suggests that dermoscopy can serve as an effective alternative for evaluating vitiligo stability. Future research with larger sample sizes and prospective follow-up is needed to refine dermoscopic criteria and standardize their application in clinical practice.

Despite the strong findings, this study has certain limitations, including a small sample size and a lack of long-term follow-up. In addition, advancements in AI-assisted dermoscopy could enhance accuracy and standardization in vitiligo evaluation.

CONCLUSION

This study confirms the utility of dermoscopy in distinguishing stable from unstable vitiligo, with strong correlations between clinical, dermoscopic, and histopathological features. Future multicenter studies will be crucial in establishing standardized diagnostic criteria for clinical decision-making and treatment planning.