Background: Cutaneous Lupus Erythematosus (CLE) represents a spectrum of autoimmune skin disorders with varying clinical and histological manifestations. Early and accurate diagnosis is essential to prevent progression to systemic lupus erythematosus. While histopathological examination remains a cornerstone in diagnosis, the adjunct use of immunohistochemical (IHC) markers may enhance diagnostic precision by identifying early immune-mediated alterations. Materials and Methods: This cross-sectional study was conducted on 40 skin biopsy samples clinically suspected of CLE and collected over a period of one year. Histopathological evaluation included hematoxylin and eosin (H&E) staining for epidermal atrophy, basal cell degeneration, follicular plugging, and dermal inflammation. IHC analysis was performed using markers such as CD123, MXA, and CD3 to assess plasmacytoid dendritic cell infiltration and T-cell distribution. The results were analyzed for correlation between histopathological findings and IHC marker expression. Results: Histopathological analysis revealed epidermal atrophy in 85% of cases, basal cell degeneration in 75%, and perivascular lymphocytic infiltration in 90%. Follicular plugging was noted in 60% of biopsies. IHC showed strong CD123 positivity in 78% of CLE samples, indicating significant plasmacytoid dendritic cell presence. MXA positivity, reflective of type I interferon activity, was seen in 70% of cases. CD3 demonstrated a diffuse T-cell infiltration pattern in 88% of the CLE specimens. Statistical correlation revealed that CD123 and MXA had significant association with early histological changes (p < 0.05). Conclusion: The combination of histopathological features and immunohistochemical markers, particularly CD123 and MXA, enhances the early detection of CLE. Incorporating IHC into routine diagnostic workflows may improve diagnostic accuracy in ambiguous or early-stage cases, allowing for timely therapeutic intervention.
Cutaneous Lupus Erythematosus (CLE) is an autoimmune dermatosis representing a localized manifestation of lupus erythematosus confined primarily to the skin. It encompasses a variety of clinical subtypes, including acute, subacute, and chronic forms, each exhibiting distinct morphological and histopathological features. CLE can precede or coexist with systemic lupus erythematosus (SLE), making its early detection crucial for timely management and prevention of systemic involvement (1).
Histopathological evaluation remains the cornerstone in diagnosing CLE, typically revealing features such as interface dermatitis, basal cell vacuolization, follicular plugging, and a perivascular lymphocytic infiltrate (2). However, these histological patterns may overlap with other inflammatory dermatoses, especially in early or ambiguous cases, complicating the diagnosis. Therefore, adjunctive diagnostic tools such as immunohistochemistry (IHC) are being increasingly explored to enhance diagnostic precision in CLE (3).
Immunohistochemical markers, particularly those reflecting immune activation and interferon pathways, have shown promise in identifying early pathological changes in lupus-related skin lesions. CD123, a marker for plasmacytoid dendritic cells (pDCs), and MXA, an interferon-induced protein, have emerged as reliable indicators of CLE due to their overexpression in lupus-affected skin (4). Additionally, CD3 serves as a pan-T cell marker, helping to delineate the lymphocytic component of the inflammatory infiltrate (5).
This study aims to evaluate the diagnostic utility of combining histopathological analysis with IHC markers—CD123, MXA, and CD3—in the early identification of CLE, thereby improving diagnostic accuracy and guiding early therapeutic intervention.
A total of 40 skin biopsy specimens were collected from patients presenting with clinical features suggestive of Cutaneous Lupus Erythematosus (CLE), including erythematous plaques, photosensitivity, and discoid lesions.
Histopathological Examination:
All biopsy specimens were fixed in 10% buffered formalin, processed routinely, and embedded in paraffin. Sections of 4–5 µm thickness were stained with hematoxylin and eosin (H&E). Histological features evaluated included epidermal atrophy, basal cell degeneration, follicular plugging, hyperkeratosis, dermal edema, and perivascular or periadnexal lymphocytic infiltrates.
Immunohistochemistry (IHC):
Paraffin-embedded tissue sections were subjected to IHC staining using antibodies against CD123 (marker for plasmacytoid dendritic cells), MXA (a type I interferon-induced protein), and CD3 (pan-T cell marker). Antigen retrieval was performed using a citrate buffer in a pressure cooker. Following blocking of endogenous peroxidase activity, sections were incubated with primary antibodies at room temperature. Detection was carried out using a polymer-based HRP detection system and visualized with diaminobenzidine (DAB) chromogen. Counterstaining was done using Mayer’s hematoxylin.
Scoring and Statistical Analysis:
IHC staining was assessed semi-quantitatively based on the percentage of positively stained cells and staining intensity. Expression levels were categorized as negative, weak, moderate, or strong. The correlation between histopathological changes and IHC marker expression was analyzed using the chi-square test and Fisher’s exact test where applicable. A p-value of <0.05 was considered statistically significant. All statistical analyses were performed using SPSS version 26.
The study included 40 clinically suspected cases of Cutaneous Lupus Erythematosus (CLE), comprising 26 females and 14 males with a mean age of 34.2 ± 9.6 years. Histopathological evaluation and immunohistochemical (IHC) profiling were performed on all biopsy samples.
Histopathological Findings
Among the histological parameters observed, epidermal atrophy was present in 34 cases (85%), basal cell degeneration in 30 cases (75%), and follicular plugging in 24 cases (60%). Perivascular lymphocytic infiltration was noted in 36 cases (90%), while dermal edema was seen in 18 cases (45%).
Table 1: Frequency of Histopathological Features in CLE (n = 40)
|
Histopathological Feature |
Number of Cases (n) |
Percentage (%) |
|
Epidermal Atrophy |
34 |
85% |
|
Basal Cell Degeneration |
30 |
75% |
|
Follicular Plugging |
24 |
60% |
|
Perivascular Lymphocytic Infiltrate |
36 |
90% |
|
Dermal Edema |
18 |
45% |
Immunohistochemical Analysis
CD123 showed positive expression in 31 out of 40 cases (77.5%), with strong staining in 22 cases. MXA positivity was noted in 28 cases (70%), with moderate to strong intensity in 18 cases. CD3 expression, indicative of T-lymphocyte infiltration, was observed in 35 cases (87.5%).
Table 2: Immunohistochemical Marker Expression in CLE Samples (n = 40)
|
IHC Marker |
Positive Cases (n) |
Moderate to Strong Staining |
Percentage (%) |
|
CD123 |
31 |
22 |
77.5% |
|
MXA |
28 |
18 |
70% |
|
CD3 |
35 |
29 |
87.5% |
Correlation Analysis
Statistical analysis showed a significant correlation between CD123 expression and basal cell degeneration (p = 0.04), as well as between MXA positivity and the presence of epidermal atrophy (p = 0.03). CD3 expression was significantly associated with perivascular lymphocytic infiltrates (p = 0.02).
These findings suggest that CD123 and MXA are potential markers for early immune-mediated changes in CLE and may complement routine histopathological diagnosis.
Cutaneous Lupus Erythematosus (CLE) presents diagnostic challenges due to its varied clinical and histopathological manifestations. Early diagnosis is crucial in preventing disease progression and systemic involvement. In our study, histopathological and immunohistochemical (IHC) evaluation played complementary roles in identifying early features of CLE.
Histopathologically, epidermal atrophy, basal cell degeneration, and perivascular lymphocytic infiltration were the most frequently observed features, consistent with previous reports that highlight interface dermatitis and adnexal involvement as diagnostic hallmarks of CLE (1,2). The high prevalence of follicular plugging in our cohort also aligns with findings from studies on discoid lupus erythematosus, suggesting chronicity and folliculotropism as common patterns in CLE (3,4).
IHC analysis provided additional diagnostic value, especially in early lesions where histological findings were subtle. CD123, a marker for plasmacytoid dendritic cells (pDCs), was significantly expressed in the majority of our cases. pDCs are known to accumulate in lupus lesions and play a key role in initiating immune responses by producing type I interferons (5,6). Previous studies have reported CD123 as a sensitive marker for pDCs in cutaneous lupus and have supported its utility in distinguishing CLE from other inflammatory dermatoses such as dermatomyositis and lichen planus (7,8).
MXA, a surrogate marker of type I interferon activity, was also frequently expressed in our samples. Type I interferons are central to the pathogenesis of CLE, contributing to keratinocyte apoptosis and inflammatory signaling (9,10). MXA has been identified as a reliable indicator of interferon-mediated immune activation in CLE, and our findings further support its relevance, particularly in identifying subacute and early lesions (11,12).
CD3, a pan-T cell marker, revealed robust lymphocytic infiltration in most cases. This reinforces previous observations that CLE lesions are dominated by T-cell–mediated interface dermatitis, predominantly CD4+ and CD8+ subsets (13,14). The strong association between CD3 positivity and perivascular lymphocytic infiltration in our study is indicative of ongoing immune activity and tissue damage.
Our data also highlighted significant correlations between histopathological changes and IHC marker expression. For example, CD123 positivity was strongly associated with basal cell degeneration, suggesting that pDC infiltration may precede or coincide with epidermal injury. Similarly, MXA expression correlated with epidermal atrophy, supporting the hypothesis that type I interferons mediate early keratinocyte damage in CLE (15).
The combined evaluation of histopathological features and immunohistochemical markers significantly enhances the early diagnosis of Cutaneous Lupus Erythematosus. Markers such as CD123 and MXA provide valuable insights into the underlying immune mechanisms and can support histological findings, particularly in early or atypical presentations. Integrating IHC into routine diagnostic protocols may lead to more accurate and timely management of CLE, potentially preventing progression to systemic disease.
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