Evaluating Interferon γ to Interleukin 10 Ratio as a Biomarker for Stability and Severity in Vitiligo: A Clinical and Histopathologic Correlation
Context.—
Vitiligo is a chronic autoimmune depigmenting disorder characterized by the selective destruction of epidermal melanocytes. Proinflammatory and anti-inflammatory cytokines, such as interferon γ (IFN-γ) and interleukin 10 (IL-10), play a pivotal role in its pathogenesis. Quantifying these cytokines and assessing their ratio may aid in disease prognosis and therapeutic monitoring.
Objective.—
To evaluate the association between the IFN-γ:IL-10 ratio and the clinical as well as histopathologic characteristics of stable and unstable vitiligo.
Design.—
A hospital-based prospective case-control study was conducted during 1 year (2023–2024) on 70 patients with active vitiligo and 30 healthy controls. Serum levels of IFN-γ and IL-10 were quantified, and their correlations with clinical severity, disease stability, and histopathologic grading were analyzed.
Results.—
Unstable vitiligo cases demonstrated significantly higher histopathologic scores (≥3 in 39.62% versus 0% in stable cases, P = .002). IFN-γ levels were markedly elevated in unstable vitiligo (11.9 ± 2.56 versus 10.58 ± 1.04 pg/mL, P = .003) and in patients with a histopathologic score of 3 or higher (13.35 ± 3.21 versus 10.84 ± 1.34 pg/mL, P = .002). The IFN-γ:IL-10 ratio was also significantly higher in these groups.
Conclusions.—
Differentiating stable from unstable vitiligo is essential for optimal disease management. Cytokine profiling, particularly IFN-γ and IL-10 levels, offers a minimally invasive biomarker for assessing disease activity and monitoring therapeutic response.
Vitiligo is a chronic autoimmune depigmenting disorder characterized by the selective destruction of epidermal melanocytes, resulting in well-demarcated, hypopigmented patches.1 The condition exhibits a global prevalence ranging from approximately 0.5% to 1% and affects individuals irrespective of age, sex, skin type, or ethnic background.2
The destruction of melanocytes and the formation of depigmented patches in vitiligo have been attributed to multiple interrelated mechanisms, including neural, genetic, autoimmune, and oxidative stress pathways, as well as the production of inflammatory mediators.3,4 Dysregulation of the immune system leads to an imbalance between effector T cells (Teffs) and regulatory T cells (Tregs), characterized by the upregulation of Teffs and the downregulation of Tregs. This immune imbalance results in excessive activation of CD8+ and CD4+ T cells, which play a key role in melanocyte destruction.4
Altered levels of various proinflammatory and anti-inflammatory cytokines, including interleukin (IL) 2, IL-6, IL-8, IL-10, tumor necrosis factor α, and interferon γ (IFN-γ), have been implicated in vitiligo and other autoimmune disorders.5 IL-10, a potent anti-inflammatory cytokine, functions as a key regulator by suppressing cytokine production from type 1 T helper (Th1) cells and macrophages.5,6 Conversely, increased levels of IFN-γ have been shown to induce apoptosis, and melanocyte death in vitiligo is thought to be mediated through apoptotic pathways in the context of autoimmunity.7
Vitiligo is clinically classified into stable and unstable forms. Stable vitiligo is characterized by the absence of new lesions, no increase in the size of existing lesions, and no occurrence of Koebner phenomenon (KP) for at least 1 year.8,9 Stability is a crucial factor in disease prognostication and treatment selection. In contrast, unstable vitiligo is associated with a poorer prognosis, an increased risk of graft failure, and a heightened likelihood of disease progression following photochemotherapy.10
This study aimed to evaluate the histopathologic characteristics of patients with stable and unstable vitiligo and to correlate these findings with their clinical grade. Additionally, we sought to assess the balance between proinflammatory marker IFN-γ and anti-inflammatory marker IL-10 cytokine serum levels in these cases and their association with histopathologic features. The findings of this study are expected to enhance treatment outcomes, as histopathologic examination may provide a more accurate prognosis for vitiligo patients. Furthermore, the IFN-γ:IL-10 ratio has the potential to serve as a valuable biomarker for assessing disease prognosis and treatment response. To the best of our knowledge, this is the first study to investigate the association between the IFN-γ:IL-10 ratio and the clinical as well as histologic characteristics of stable and unstable vitiligo.
MATERIALS AND METHODS
This hospital-based, prospective, case-control study was conducted on 70 patients with active vitiligo and 30 healthy controls during a 1-year period from 2023 to 2024. The research was carried out in the Departments of Pathology and Dermatology, as well as the Multidisciplinary Research Unit, Jorhat Medical College and Hospital, Jorhat, Assam, India. Ethical approval for the study was obtained from the institutional ethics committee prior to its initiation (IEC[H] Reg No. EC/NEW/INST/2020/1221).
Inclusion and Exclusion Criteria
Patients with newly diagnosed cases of vitiligo, as well as patients who had discontinued treatment for at least 3 months, were included in the study. However, individuals currently undergoing treatment or those who had received any form of vitiligo treatment within the past 3 months were excluded.
Patients with inflammatory or autoimmune disorders known to alter cytokine levels, such as asthma, cancer, cardiovascular diseases, Hashimoto thyroiditis, Graves disease, type 1 insulin-dependent diabetes mellitus, Addison disease, psoriasis, rheumatoid arthritis, and thyroid dysfunction, were also excluded from the study.
The control group comprised healthy patient attendants and community members, matched for age, sex, and ethnicity, who voluntarily participated in the study. Control participants had no personal or family history of vitiligo or any inflammatory or autoimmune diseases.
Biopsy Sample Collection Histopathologic Evaluation
A 3-mm punch biopsy was obtained from the perilesional region (within 5 cm of the lesion) for histopathologic examination.11 The sample was preserved in 10% neutral buffered formalin and sent to the Department of Pathology for further processing and evaluation. Hematoxylin-eosin staining was performed on all samples and independently assessed by 2 histopathologists.
A total of 5 histopathologic variables were selected for evaluation using a light microscope at ×10 and ×40 magnification, and dermal lymphocyte counts were assessed at ×100 and ×400 magnification. These variables included 3 epidermal changes—spongiosis, epidermal lymphocytic infiltration, and basal vacuolization—and 2 dermal changes—dermal lymphocytic infiltration and melanophages.11,12
Each histopathologic feature was assigned a score of 1 (present) or 0 (absent). Based on the cumulative scores, cases were classified into 4 categories: stable vitiligo, favors stable, favors unstable, and unstable vitiligo (Table 1).11,12
Determination of IFN-γ and IL-10
Blood serum analysis was performed using the quantitative sandwich enzyme-linked immunosorbent assay method (ABclonal Technology Co Ltd). Serum samples were collected in sterile vials and either processed immediately or stored at −80°C for later use. A venous blood sample was also collected from 30 healthy control subjects for the estimation of IFN-γ and IL-10 levels.
For the enzyme-linked immunosorbent assay procedure, a 96-well plate was coated with 100 μL of capture antibody per well and incubated overnight at 4°C. The wells were then blocked with 200 μL/well of diluent and incubated for 1 hour at room temperature (RT). Following blocking, 100 μL/well of serum samples and standards was added and incubated for 2 hours at RT. After incubation, 100 μL/well of detection antibody was added and left to incubate for 1 hour at RT. This was followed by the addition of 100 μL/well of avidin–horseradish peroxidase, which was incubated for 30 minutes at RT. The plate was then treated with 100 μL/well of substrate solution and incubated for 15 minutes at RT, followed by the addition of 50 μL/well of stop solution. Each step was interspersed with 5 to 7 wash cycles to ensure no carryover. Absorbance was measured at 450 and 540 nm, and IFN-γ and IL-10 levels were calculated in picograms per milliliter for each sample. A ratio of IFN-γ:IL-10 was then derived for further analysis.
Clinical Evaluation
Cases were clinically evaluated and classified into stable and unstable vitiligo. Stable vitiligo was defined as the absence of lesion progression or the development of new lesions, along with no occurrence of KP (the appearance of new lesions on previously unaffected skin due to trauma), for the past 1 year. In contrast, unstable vitiligo was characterized by a history and clinical evidence of lesion progression or the appearance of new lesions, as well as the presence of newly developed KP.13,14 Demographic and clinical data, including age, sex, socioeconomic status, family history, and history of similar illnesses, were recorded for all patients.
Statistical Analysis
Data entry was performed using Microsoft Excel (Microsoft), and the final statistical analysis was conducted using SPSS software (version 25, IBM). Categorical variables were summarized as frequencies and percentages. Quantitative variables following a normal distribution were expressed as mean ± SD, whereas nonnormally distributed data were reported as the median with interquartile range (IQR; 25th–75th percentile).
The normality of data distribution was assessed using the Shapiro-Wilk test. For variables that did not conform to a normal distribution, nonparametric statistical tests were applied. The Mann-Whitney U test and the Kruskal-Wallis test were used for comparisons of nonnormally distributed quantitative variables. In contrast, normally distributed quantitative variables were analyzed using the independent t test and analysis of variance.
Associations between categorical variables were evaluated using the χ2 test. In cases where any value had an expected frequency of less than 5, the Fisher exact test was used. Correlations between IFN-γ and IL-10, as well as between age and the final histologic score with IFN-γ, IL-10, and the IFN-γ:IL-10 ratio, were assessed using the Spearman rank correlation coefficient. For statistical significance, a P value of less than .05 was considered statistically significant.
RESULTS
Demographic and Clinical Characteristics
The present study encompassed a total of 70 patients diagnosed with vitiligo, with a mean age of 34.94 ± 14.1 years. The median age was 35 years (IQR, 24.25–45 years). Of the total cohort, 38 patients (54.29%) were female, and 32 (45.71%) were male. Regarding the pattern of disease involvement, nondermatomal distribution was observed in 46 cases (65.71%), segmental vitiligo in 8 cases (11.43%), acrofacial involvement in 6 cases (8.57%), mucosal vitiligo in 6 cases (8.57%), and focal vitiligo in 4 cases (5.71%). Disease stability assessment revealed that 53 patients (75.71%) had unstable vitiligo, whereas 17 patients (24.29%) had stable disease. Among other demographic and clinical parameters, 56 patients (80.00%) presented with newly developed lesions, 26 (37.14%) exhibited KP, and a family history of vitiligo was noted in 12 cases (17.14%) (Table 2).
Histopathologic Analysis and Comparison With Various Clinical Parameters
In the present study, we evaluated the presence of 5 key histopathologic parameters in vitiligo. Among the 70 cases analyzed, melanophages were the most frequently observed feature, detected in 44 cases (62.86%). This was followed by the presence of dermal lymphocytes in 30 cases (42.86%), basal vacuolization in 25 cases (35.71%), spongiosis in 24 cases (34.29%), and epithelial lymphocytic infiltration in 19 cases (27.14%) (Figures 1 through 3).
Citation: Archives of Pathology & Laboratory Medicine 149, 12; 10.5858/arpa.2025-0099-OA
For the histopathologic scoring, an overall score of 3 or higher was considered indicative of a higher likelihood of unstable vitiligo. In our study, 49 cases (70%) had a final histologic score lower than 3, whereas 21 cases (30%) had a score of 3 or higher. The mean histologic score was 2.03 ± 1.48, with a median value of 2 (IQR, 1–3) (Supplemental Table 1; see supplemental digital content containing 6 tables at https://meridian.allenpress.com/aplm in the December 2025 table of contents).
In comparison with the stable vitiligo group, the unstable group exhibited a significantly higher prevalence of spongiosis (41.51% versus 11.76%, P = .04), epithelial lymphocytic infiltration (33.96% versus 5.88%, P = .03), basal vacuolization (43.40% versus 11.76%, P = .02), and dermal lymphocytic infiltration (50.94% versus 17.65%, P = .02). The proportion of melanophages was comparable between the 2 groups (64.15% in the unstable group versus 58.82% in the stable group, P = .69).
The final histopathologic score was significantly higher in the unstable vitiligo group, with a score of 3 or higher observed in 39.62% of cases compared with 0% in the stable group (P = .01). Conversely, a score lower than 3 was significantly lower in the unstable group (60.38% versus 100%, P = .01). The median histologic score was also significantly elevated in the unstable group (2 [IQR, 1–3] versus 1 [IQR, 0–2], P = .002) (Supplemental Table 2).
Furthermore, among the 56 patients presenting with new lesions, 15 (26.79%) had a histologic score of 3 or higher. A histopathologic score of 3 or higher was also significantly more frequent in patients exhibiting KP (P = .01).
Comparison of Serum Concentration of IFN-γ, IL-10, and IFN-γ:IL-10 Ratio with Various Clinical Parameters
In patients with vitiligo, serum levels of IFN-γ were significantly elevated compared with healthy controls (11.59 ± 2.36 versus 10.68 ± 1.03 pg/mL, P = .01). In contrast, IL-10 levels were significantly lower in vitiligo patients compared with normal controls (8.34 ± 2.57 versus 13.11 ± 4.53 pg/mL, P < .002) (Supplemental Table 3; Figure 4).
Citation: Archives of Pathology & Laboratory Medicine 149, 12; 10.5858/arpa.2025-0099-OA
Additionally, the IFN-γ:IL-10 ratio was markedly higher in vitiligo patients, with a median value of 1.3 (IQR, 1.066–1.687) compared with 0.83 (IQR, 0.628–1.051) in the control group (P < .005).
A significant variation in the IFN-γ:IL-10 ratio was observed across different disease distribution patterns (P = .03). The highest ratio was recorded in mucosal vitiligo (2.48 [IQR, 1.627–6.582]), followed by acrofacial (1.61 [IQR, 1.232–1.894]), nondermatomal (1.27 [IQR, 0.995–1.579]), segmental (1.26 [IQR, 1.112–1.491]), and focal vitiligo (1.22 [IQR, 1.157–1.273]). However, no significant differences were observed in absolute IFN-γ and IL-10 levels across different disease distribution patterns.
When comparing the 2 clinical groups, patients in the unstable vitiligo group exhibited significantly higher levels of IFN-γ (11.9 ± 2.56 versus 10.58 ± 1.04 pg/mL, P = .003) and a significantly elevated IFN-γ:IL-10 ratio (1.45 [IQR, 1.019–1.886] versus 1.15 [IQR, 1.12–1.188], P = .02). Conversely, IL-10 levels were significantly lower in the unstable group compared with the stable group (8.08 ± 2.8 versus 9.23 ± 1.29 pg/mL, P = .03).
No significant associations were observed between IFN-γ, IL-10, or the IFN-γ:IL-10 ratio and the presence of KP, sex, or history of new lesions. However, IFN-γ levels were significantly lower in individuals from the lower socioeconomic group (10.99 ± 1.71 pg/mL) compared with those in the middle socioeconomic group (12.31 ± 2.82 pg/mL, P = .03).
Patients with a positive family history of vitiligo exhibited significantly lower IFN-γ levels compared with those without a family history (10.67 ± 1.22 versus 11.79 ± 2.5 pg/mL, P = .03). However, no significant differences were observed in IL-10 levels (8.32 ± 3.67 versus 8.34 ± 2.32 pg/mL, P = .98) or in the IFN-γ/IL-10 ratio (1.13 [IQR, 1.009–1.303] versus 1.41 [IQR, 1.143–1.712], P = .26) between the 2 groups (Supplemental Table 4).
Relationship of Serum Concentration of IFN-γ, IL-10, and IFN-γ:IL-10 Ratio With Various Histopathologic Parameters
IFN-γ levels were significantly elevated in patients exhibiting specific histopathologic features, including spongiosis (12.93 ± 2.91 versus 10.9 ± 1.66 pg/mL, P = .003), epithelial lymphocytic infiltration (13.43 ± 3.39 versus 10.91 ± 1.34 pg/mL, P = .005), basal vacuolization (12.86 ± 3.12 versus 10.89 ± 1.42 pg/mL, P = .006), and dermal lymphocytic infiltration (12.51 ± 2.94 versus 10.91 ± 1.52 pg/mL, P = .01). However, no statistically significant difference in IFN-γ levels was observed in relation to the presence of dermal melanophages (11.94 ± 2.8 versus 11.01 ± 1.16 pg/mL, P = .06) (Figure 5).
Citation: Archives of Pathology & Laboratory Medicine 149, 12; 10.5858/arpa.2025-0099-OA
IL-10 levels did not exhibit any significant association with the presence of spongiosis, epithelial lymphocytic infiltration, or basal vacuolization. However, IL-10 levels were significantly lower in cases with melanophages (7.68 ± 2.53 versus 9.46 ± 2.27 pg/mL, P = .004) and dermal lymphocytic infiltration (7.31 ± 2.61 versus 9.12 ± 2.27 pg/mL, P = .003). Additionally, the IFN-γ:IL-10 ratio was significantly elevated across all histopathologic parameters analyzed (Figures 6 and 7).
Citation: Archives of Pathology & Laboratory Medicine 149, 12; 10.5858/arpa.2025-0099-OA
Citation: Archives of Pathology & Laboratory Medicine 149, 12; 10.5858/arpa.2025-0099-OA
When correlated with the final histologic score, IFN-γ levels were significantly elevated in patients with a score of 3 or higher compared with those with a score lower than 3 (13.35 ± 3.21 versus 10.84 ± 1.34 pg/mL, P = .002). Similarly, the IFN-γ:IL-10 ratio was significantly higher in patients with a final histologic score of 3 or higher (1.9 [IQR, 1.149–2.789] versus 1.27 [IQR, 1.009–1.514], P = .01). Conversely, IL-10 levels were significantly lower in patients with a histologic score of 3 or higher compared with those with a score lower than 3 (7.17 ± 3.42 versus 8.84 ± 1.93 pg/mL, P = .045) (Supplemental Table 4).
In the present study, a significant moderate positive correlation was observed between the final histologic score and both IFN-γ levels (r = 0.443) and the IFN-γ:IL-10 ratio (r = 0.434). Additionally, a significant weak negative correlation was noted between the final histologic score and IL-10 levels (r = −0.242). However, a nonsignificant very weak negative correlation was found between IFN-γ and IL-10 levels (r = −0.134) (Supplemental Tables 5 and 6; Figure 8).
Citation: Archives of Pathology & Laboratory Medicine 149, 12; 10.5858/arpa.2025-0099-OA
DISCUSSION
Vitiligo is a multifactorial disorder characterized by the progressive loss of melanocytes in the epidermis, driven by a complex interplay of genetic predisposition, immune dysregulation, oxidative stress, and environmental factors.15 During disease pathogenesis, an imbalance between Teffs and Tregs results in excessive proliferation and activation of CD8+ and CD4+ T cells, ultimately leading to melanocyte destruction. The stressed or damaged melanocytes release damage-associated molecular patterns, which function as endogenous damage signals.4,16 These damage-associated molecular patterns are recognized by pattern recognition receptors, expressed on various innate immune cells, including dendritic cells.15,16 Pattern recognition receptors are categorized into toll-like receptors, located on the cell membrane, and NOD-like receptors (NLRs), present in the cytoplasm. Among the NLR family, NLR family pyrin domain containing 1 (NLRP1) and NLR family pyrin domain containing 3 (NLRP3) play a pivotal role in vitiligo pathogenesis by forming inflammasome complexes upon activation. This leads to the activation of caspase-1, which subsequently triggers the maturation and secretion of proinflammatory cytokines, including IL-1β and IL-18, further exacerbating immune-mediated melanocyte destruction.17
IFN-γ is a critical proinflammatory cytokine involved in immune modulation, melanocyte apoptosis, and inhibition of melanogenesis.18 Elevated IFN-γ levels have been consistently observed in vitiligo, contributing to melanocyte dysfunction and destruction through multiple mechanisms, including suppression of melanogenesis, increased reactive oxygen species production, and CD8+ T cell–mediated cytotoxicity.19–21 IFN-γ exerts its pathologic effects primarily through the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling cascade. The upregulation of JAK1 and JAK3 in vitiligo lesions amplifies IFN-γ signaling, leading to increased immune responses. Additionally, IFN-γ activates STAT1, which plays a pivotal role in promoting melanocyte apoptosis and inhibiting Tregs, thereby exacerbating the autoimmune response and sustaining disease progression.22–24
In the current study, 5 key histopathologic parameters were used to differentiate between stable and unstable vitiligo cases. These included 3 epidermal changes—spongiosis, epidermal lymphocytic infiltration, and basal vacuolization—as well as 2 dermal changes—dermal lymphocytic infiltration and the presence of melanophages. The presence of these histopathologic features indicates CD4+ and CD8+ T cell–mediated melanocyte-specific cytotoxicity, which is characteristic of unstable vitiligo. Although vitiligo is primarily a clinical diagnosis and skin biopsy is not routinely performed, evidence from previous studies has highlighted the role of histopathologic evaluation in disease classification and prognostication.11,12
In the present study, vitiligo cases were clinically classified into stable and unstable forms, and the corresponding histopathologic features were analyzed. Spongiosis, epidermal lymphocytic infiltration, basal vacuolization, and dermal lymphocytic infiltration were observed at significantly higher frequencies in unstable vitiligo. However, the presence of dermal melanophages was comparable between the 2 groups. A composite histopathologic scoring system was developed based on these parameters, with a score of 3 or higher indicating unstable disease. In this study, the final histopathologic score was significantly elevated in the unstable vitiligo group, with a score of 3 or higher observed in 39.62% of cases. These findings are consistent with those reported by Yadav et al,11 who also documented higher histopathologic scores in unstable vitiligo.
Furthermore, a histopathologic score of 3 or higher was significantly more prevalent in patients exhibiting KP. In vitiligo, external trauma plays a critical role in the development of KP through multiple mechanisms, including immune dysregulation, enhanced oxidative stress response, impaired melanocyte adhesion, and deficiency of growth factors. Similarly, previous studies have established a strong association between KP and disease activity, indicating its relevance as a marker of disease instability.25,26
In the present study, levels of the proinflammatory cytokine IFN-γ were significantly elevated in vitiligo patients compared with the healthy control group. Experimental studies in murine models have demonstrated that depigmentation is dependent on IFN-γ, which facilitates the local accumulation of melanocyte-specific CD8+ T cells within the skin, underscoring the pivotal role of IFN-γ in vitiligo pathogenesis.27 Conversely, levels of the anti-inflammatory cytokine IL-10 were markedly reduced in patients compared with controls, suggesting a diminished type 2 T helper (Th2) cells cytokine response, which may contribute to the dysregulated immune environment characteristic of vitiligo.28
When comparing the 2 clinical groups, patients with unstable vitiligo exhibited significantly higher levels of IFN-γ and lower levels of IL-10. Similar findings were reported by Ala et al,29 who observed elevated IFN-γ levels in nonsegmental vitiligo, suggesting a more severe disease phenotype in these patients. The role of IFN-γ in vitiligo has been extensively studied, with elevated levels detected not only in lesional skin but also in perilesional skin and serum when compared with healthy controls.30,31
The findings of this study indicate that IFN-γ levels were significantly elevated in patients exhibiting specific histopathologic features, including spongiosis, epidermal lymphocytic infiltration, basal vacuolization, and dermal lymphocytic infiltration. Moreover, when correlated with the final histopathologic score, IFN-γ levels were markedly increased in patients with a score of 3 or higher, indicating disease instability. These findings further substantiate the consistent association between elevated IFN-γ levels and unstable vitiligo, providing critical insights into the underlying T-cell–mediated cytotoxicity of melanocytes and the ongoing disease activity.19,29
The IFN-γ:IL-10 ratio, which reflects the balance between proinflammatory and anti-inflammatory immune responses, has been proposed as a potential diagnostic and prognostic biomarker in various diseases.29,32 In a study by Espíndola et al,32 an elevated IFN-γ:IL-10 relative expression ratio was found to aid in the identification of asymptomatic carriers in HTLV-1–associated myelopathy/tropical spastic paraparesis. Additionally, other studies have suggested that the IFN-γ:IL-10 ratio may serve as a predictive biomarker for treatment response in patients with advanced melanoma undergoing programmed death receptor-1 (PD-1) checkpoint inhibitor therapy.33 Furthermore, its role as a theranostic marker has been explored in the context of hydrocortisone therapy for patients with septic shock.34
In our analysis, the IFN-γ:IL-10 ratio was significantly elevated in the vitiligo cohort compared with healthy controls. Furthermore, this ratio was markedly higher in patients with unstable vitiligo. Our findings align with the observations of Ala et al,29 who also reported an increased IFN-γ:IL-10 ratio in patients with more severe disease. Additionally, the IFN-γ:IL-10 ratio was significantly elevated across all histopathologic parameters, including patients with a histopathologic score of 3 or higher. These findings suggest that the IFN-γ:IL-10 ratio may serve as a valuable biomarker for assessing disease severity and classifying vitiligo subtypes.
This study is a single-center, hospital-based study with a relatively small sample size. As a result, the findings may not fully represent the broader population. Furthermore, additional studies with larger sample sizes, conducted across diverse ethnic groups, are needed to evaluate various other inflammatory cytokine levels and their ratios before and after treatment. Such research could help validate our findings and potentially lead to new therapeutic possibilities. We also acknowledge that, although blood cytokine levels are widely used as markers in various inflammatory diseases, they are subject to fluctuation. Therefore, clinical and histopathologic correlation may be necessary for accurate interpretation.
CONCLUSIONS
Distinguishing between stable and unstable vitiligo is crucial for effective disease management. Although the role of histopathology in this context is not yet fully established, specific histologic features, when correlated with clinical findings, can aid in diagnosis in most cases. Additionally, the evaluation of proinflammatory and anti-inflammatory cytokines, along with their ratios, offers a minimally invasive approach for assessing disease stability and monitoring treatment response.
Presence of many lymphocytes along with a few melanophages in upper dermis in a patient with unstable vitiligo (hematoxylin-eosin, original magnification ×10).
Figure 2. A case of unstable vitiligo showing basal vacuolization, dermal lymphocytes, epidermal lymphocytes, and spongiosis in the epithelium (hematoxylin-eosin, original magnification ×4).
Figure 3. Presence of dermal spongiosis and focal basal vacuolization in unstable vitiligo (hematoxylin-eosin, original magnification ×4).
Comparison of interferon γ (IFN-g) to interleukin 10 (IL-10) ratio between patients with vitiligo and normal controls (nonparametric variable, box-whisker plot).
Correlation of final histologic score with interferon γ (IFN-g).
Correlation of final histologic score with interleukin 10 (IL-10).
Correlation of final histologic score with interferon γ (IFN-g) to interleukin 10 (IL-10) ratio.
Correlation of interferon γ (IFN-g) with interleukin 10 (IL-10).
Contributor Notes
Supplemental digital content is available for this article at https://meridian.allenpress.com/aplm in the December 2025 table of contents.
Funded by the Multidisciplinary Research Unit (MRU), Jorhat Medical College and Hospital, Jorhat, Assam, India.
The authors have no relevant financial interest in the products or companies described in this article.