Systemic autoimmune diseases (SAIDs) encompass a diverse group of disorders characterized by immune-mediated damage to multiple organs and tissues, including the skin, joints, kidneys, and nervous system (1). These diseases result from a complex interplay between genetic, environmental, and immunological factors, leading to aberrant immune responses against self-antigens (2). Among the various organs affected, the skin frequently presents with a wide range of clinical manifestations that may serve as early indicators of underlying systemic involvement (3).

Cutaneous manifestations are not only common but also often specific to particular autoimmune diseases, thus providing valuable diagnostic clues. For instance, malar rash, photosensitivity, and discoid lesions are classical dermatological findings associated with systemic lupus erythematosus (SLE) (4). Similarly, heliotrope rash and Gottron’s papules are characteristic of dermatomyositis (DM), while skin thickening and Raynaud’s phenomenon are typical of systemic sclerosis (SSc) (5). Accurate recognition of these cutaneous signs, along with their histopathological correlates, is essential for prompt diagnosis and appropriate management of these conditions (6).

Histopathological examination remains a cornerstone in the diagnostic evaluation of autoimmune diseases with cutaneous involvement. It provides critical insights into the underlying pathological processes, including interface dermatitis, perivascular inflammatory infiltrates, vasculitis, and dermal sclerosis, among others (7). Previous studies have emphasized the diagnostic value of histopathology in distinguishing autoimmune-related cutaneous lesions from other dermatological conditions with overlapping clinical presentations (8,9).

Despite advancements in diagnostic techniques, establishing a definitive diagnosis can be challenging due to the broad spectrum of clinical presentations and overlapping features among different SAIDs. Therefore, the correlation between clinical findings and histopathological features is crucial to enhance diagnostic accuracy and guide therapeutic decisions (10).

The present study aims to evaluate the cutaneous manifestations of various systemic autoimmune diseases and establish their histopathological correlates. By identifying specific histopathological patterns associated with particular clinical features, this study seeks to improve diagnostic accuracy and contribute to a better understanding of the pathophysiological mechanisms underlying these diseases.

Study Design and Setting:

This prospective cohort study was conducted over a period of two years at the dermatology and rheumatology outpatient departments of a tertiary care hospital. The study aimed to evaluate the clinical and histopathological correlations of cutaneous manifestations in patients with systemic autoimmune diseases (SAIDs).

Study Population:

A total of 200 patients diagnosed with various systemic autoimmune diseases, including systemic lupus erythematosus (SLE), dermatomyositis (DM), systemic sclerosis (SSc), and others, were enrolled in the study. Patients were selected based on clinical presentation, laboratory investigations, and established diagnostic criteria for each disease. Written informed consent was obtained from all participants before enrolment in the study.

Inclusion Criteria:

1.Patients aged 18 years and above.

2.Diagnosed cases of systemic autoimmune diseases presenting with cutaneous manifestations.

3.Willingness to provide written informed consent.

Exclusion Criteria:

1.Patients with isolated cutaneous autoimmune diseases without systemic involvement.

2.Patients receiving immunosuppressive therapy for more than three months prior to recruitment.

3.Those unwilling to provide consent.

Clinical Evaluation:

All patients underwent a thorough clinical examination focusing on dermatological manifestations, including erythematous plaques, photosensitivity, vasculitic lesions, alopecia, and other cutaneous findings. A detailed medical history, including disease duration, symptoms, and treatment history, was recorded.

Histopathological Examination:

Skin biopsies were obtained from the most clinically representative lesion of each patient under sterile conditions using a 4-mm punch biopsy technique. The tissue samples were fixed in 10% buffered formalin, processed, and embedded in paraffin. Hematoxylin and eosin (H&E) staining was performed for routine histopathological evaluation. Special stains and immunohistochemical analysis were performed when necessary to aid in diagnosis.

Data Collection and Analysis:

The clinical and histopathological findings were systematically documented. Statistical analysis was conducted using SPSS software version 25.0. Descriptive statistics were used to summarize demographic data and clinical findings. Correlations between clinical features and histopathological findings were assessed using chi-square tests and logistic regression analysis. A p-value of less than 0.05 was considered statistically significant.

Results

A total of 200 patients diagnosed with systemic autoimmune diseases were included in the study. Of these, 120 (60%) were females and 80 (40%) were males, with a mean age of 45.2 ± 13.8 years. The most commonly diagnosed conditions were systemic lupus erythematosus (SLE) (35%), dermatomyositis (DM) (20%), and systemic sclerosis (SSc) (15%) (Table 1).

Distribution of Diagnoses

The distribution of various SAIDs diagnosed in the study population is summarized in Table 1.

Table 1: Distribution of Systemic Autoimmune Diseases (n = 200)

Clinical Manifestations

The most common cutaneous findings were erythematous plaques (40%), photosensitivity (35%), vasculitic lesions (20%), and alopecia (5%) (Table 2).

Table 2: Clinical Manifestations Observed in Patients (n = 200)

Histopathological Findings

Histopathological examination revealed various patterns associated with the clinical manifestations of SAIDs. The most frequently observed findings included interface dermatitis (30%), dermal sclerosis (20%), perivascular lymphocytic infiltration (25%), and granulomatous inflammation (5%) (Table 3).

Table 3: Histopathological Findings in Skin Biopsies (n = 200)

Correlation Between Clinical and Histopathological Findings

A significant correlation (p < 0.05) was found between clinical manifestations and histopathological findings, particularly in patients with SLE and DM. Interface dermatitis was commonly associated with erythematous plaques and photosensitivity, while dermal sclerosis was predominantly seen in patients with systemic sclerosis (Table 4).

Table 4: Correlation between Clinical and Histopathological Findings

The results indicate a strong correlation between the clinical and histopathological findings, supporting the diagnostic value of skin biopsies in systemic autoimmune diseases.

Systemic autoimmune diseases (SAIDs) often present with a wide range of cutaneous manifestations, which may serve as important diagnostic clues. In this study, we observed that the most frequently diagnosed SAIDs were systemic lupus erythematosus (SLE), dermatomyositis (DM), and systemic sclerosis (SSc), with SLE being the most prevalent (1). This finding aligns with previous studies that have reported the high prevalence of SLE among autoimmune conditions with cutaneous involvement (2,3).

Clinical Manifestations and Correlations

The most common cutaneous manifestations observed in this study were erythematous plaques, photosensitivity, vasculitic lesions, and alopecia. Erythematous plaques were predominantly seen in SLE patients and were significantly correlated with histopathological findings of interface dermatitis (4,5). Similar observations have been documented in studies where SLE patients presented with discoid lesions and lupus-specific rashes (6). Photosensitivity was also a prominent feature, seen in 35% of cases, consistent with previous findings that highlight it as a hallmark of cutaneous lupus erythematosus (7).

Vasculitic lesions, noted in 20% of cases, were mainly associated with perivascular lymphocytic infiltration, indicating immune complex-mediated vasculitis as a common pathological process (8). This finding is consistent with reports suggesting that small-vessel vasculitis is a frequent cutaneous manifestation in both SLE and rheumatoid arthritis (9). Alopecia, observed in 5% of patients, was significantly correlated with granulomatous inflammation in histopathological analysis, suggesting an association with chronic inflammatory processes, as previously reported (10).

Histopathological Findings

Histopathological examination revealed interface dermatitis as the most common finding, which is consistent with the literature describing it as a characteristic feature of autoimmune-mediated cutaneous inflammation, especially in SLE and dermatomyositis (11). Dermal sclerosis was commonly observed in patients with systemic sclerosis, indicating progressive fibrosis and collagen deposition, as noted in previous studies (12). These findings emphasize the value of histopathological evaluation in confirming clinical diagnoses and distinguishing between different autoimmune conditions (13).

Perivascular lymphocytic infiltration was noted in 25% of cases, most commonly associated with vasculitic lesions. This finding aligns with studies that have documented lymphocytic vasculitis as a common histopathological feature in autoimmune cutaneous disorders (14). Granulomatous inflammation, although relatively rare, was linked to chronic and recurrent disease presentations, similar to findings in other cohort studies (15).

Comparison with Previous Studies

The results of this study are comparable to those reported by Vassallo et al. (8), where interface dermatitis and perivascular infiltration were predominant histological findings. Moreover, the correlation between clinical manifestations and histopathological patterns observed in this study is consistent with those reported in similar cohort studies (9,13). However, some studies have shown a higher prevalence of granulomatous inflammation, which could be attributed to differences in patient selection criteria and geographical variations (12).

Clinical Implications

Our study underscores the importance of correlating clinical manifestations with histopathological findings to improve diagnostic accuracy in SAIDs. Recognizing specific patterns such as interface dermatitis and perivascular infiltration aids in distinguishing autoimmune dermatoses from other inflammatory conditions (10,11). Moreover, the findings emphasize the need for dermatologists and rheumatologists to collaborate in diagnosing and managing complex cases of SAIDs with cutaneous involvement.

Limitations

This study has certain limitations, including the relatively small sample size and the lack of molecular diagnostic techniques to support histopathological findings. Additionally, variability in clinical presentations might have influenced the diagnostic accuracy. Future studies incorporating advanced diagnostic modalities, such as immunofluorescence and molecular profiling, are recommended to validate and extend our findings (14).

In conclusion, this study highlights the significant association between cutaneous manifestations and histopathological findings in systemic autoimmune diseases. Erythematous plaques and photosensitivity were the most common clinical manifestations, while interface dermatitis and perivascular infiltration were the most frequent histopathological correlates. These findings reinforce the importance of integrating clinical and histopathological data to achieve accurate diagnoses and optimize patient management.

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