Erythema nodosum (EN) represents the most prevalent type of panniculitis, presenting as symmetrical, red, painful, and warm nodules or plaques, often found on the front of the legs. It affects one to five individuals per 100,000 people, with a male-to-female ratio of 1:1 in children and 1:5 in adults [1]. While EN can occur at any age, it predominantly affects those in their 20s to 40s [2]. EN is believed to result from a hypersensitivity reaction triggered by various antigens, including those associated with infections, inflammatory diseases, cancers, and certain medications [3]. Early lesions show signs of circulating immune complexes, suggesting that antigen-antibody interactions and complement activation are key in the disease’s development and tissue damage. However, some studies report no immunological complexes in uncomplicated EN, hinting at a potential type IV hypersensitivity [1].

EN is classified as either primary (idiopathic) or secondary, based on whether a specific cause is identified [4]. Additionally, histologically, EN can be categorized into acute or chronic forms, depending on the timing of the lesions [5,6]. Studies suggest that 32-72% of EN cases are idiopathic, while 28-68% are secondary. The factors contributing to secondary EN remain unclear and may differ due to ethnic, racial, and geographic variations in various studies [7,8]. Clinically, both idiopathic and secondary EN typically resolve on their own within 3-6 weeks, usually without leaving scars [4,5]. However, some evidence suggests that idiopathic EN may have a higher tendency to recur than the secondary form [4,7]. Understanding the clinical and histopathological features and their links to the causes of EN is vital for predicting recurrence, enabling better diagnosis and management. Despite this, there is a scarcity of research on EN and its related conditions [9-11].

This study underscores the importance of correctly diagnosing panniculitis and its subtypes for effective patient management. Its goals are to examine the clinicopathological range of erythema nodosum, identify the type of panniculitis, and investigate potential causes.

The present study was conducted at the Department of Pathology, Subharti Medical College, to evaluate the clinicopathological spectrum of EN. A total of 25 consecutive cases with a clinical diagnosis of EN were included in the study. These cases were identified and selected based on clinical presentations consistent with EN, which is characterized by painful, erythematous nodules or plaques primarily located on the anterior aspects of the lower extremities. The selected patients underwent a comprehensive evaluation, including a detailed clinical history, physical examination, and relevant laboratory investigations to rule out underlying systemic conditions commonly associated with EN, such as infections, autoimmune diseases, and malignancies.

Histopathological examination of biopsy samples from affected skin lesions was performed to confirm the diagnosis of EN and to assess the underlying pathological changes. Special attention was given to the nature of inflammatory infiltrates, granulomatous formation, and the presence of any other histological features that could suggest associated systemic conditions. The findings were subsequently correlated with clinical data, allowing for a better understanding of the disease's varied presentation and associated etiological factors. Data were analyzed systematically using SPSS (v.22) to identify patterns in the clinicopathological characteristics of EN and to explore any potential associations with comorbid conditions or environmental factors.

The results of study on Erythema Nodosum, including figures and tables that illustrate age and gender distributions, the sites of erythema, histological diagnoses, types of panniculitis, and the presence of inflammatory cells and vasculitis among the cases studied.

Figure 1: Age distributions

The age distribution shows the number of cases across different age groups, with the highest frequency observed in the 21-30 years group [Figure 1].

Figure 2: Gender distribution

This figure displays the gender distribution of the cases, indicating a higher number of cases in females compared to males [Figure 2].

Figure 3: Site of Erythema Nodosum

The majority of cases of erythema nodosum were located on the lower leg, followed by the left thigh, highlighting the common sites affected [Figure 3].

Figure 4: Histopathological diagnosis of Erythema Nodosum Cases

The histological diagnoses reveal that the most common diagnosis was Erythema Nodosum, followed by Erythema Induratum, with fewer cases of Erythema Nodosum Leprosum and inadequate septolobular diagnoses [Figure 4].

Figure 4 (a): Histopathological examination [Image A to Image E]

Figure 5: type of Panniculitis

The types of panniculitis shown indicate that the majority of cases were of the septal type, with fewer cases of lobular and mixed types [Figure 5].

Table 1: Inflammatory Cells

This table lists the types of inflammatory cells identified in the cases. Lymphocytes were the most prevalent (18 cases), followed by macrophage histiocytes (14 cases) and granulomatous cells (5 cases) [Table 1]. These results are not significant

Table 2: Presence of Vasculitis

The presence of vasculitis was noted in 3 of the 25 cases, while the majority (22 cases) did not exhibit vasculitis [Table 2]. These results are not significant

EN is a common type of panniculitis that typically presents as tender, red nodules, most often appearing on the front of the lower legs, especially over the shins. The findings from this study confirm earlier research showing that EN occurs most frequently in people aged 21–30 years, with women being more commonly affected [12,13]. This gender difference has been widely noted and may be linked to hormonal factors and differences in immune system activity [14].

In this study, the lower legs were the most commonly affected sites, followed by the thighs. This pattern aligns with the well-documented tendency for EN lesions to appear symmetrically on the lower limbs [15]. Histopathological analysis identified septal panniculitis lacking vasculitis as the predominant feature, consistent with the classic histological characteristics of EN. The inflammatory cells mainly consisted of lymphocytes and histiocytes, with occasional multinucleated giant cells, as described in prior studies [16,17].

EN can be triggered by various factors, including infections, autoimmune disorders, malignancies, and certain medications. Among infectious causes, streptococcal infections are the most common, particularly in younger individuals, while tuberculosis and other pathogens are significant causes in regions where these infections are endemic [18,19]. Sarcoidosis is another important systemic cause of EN, often appearing as part of Löfgren syndrome, which also involves bilateral hilar lymphadenopathy as well as arthritis [20].

Drug-related EN has been reported with the use of oral contraceptives, antibiotics, and nonsteroidal anti-inflammatory drugs. Although no drug-related cases were identified in this study, taking a detailed medication history remains essential in clinical evaluation [21].

EN usually resolves on its own within 3–6 weeks without leaving scars, and recurrences are uncommon in idiopathic cases. Treatment mainly involves identifying and addressing the underlying cause. For symptomatic relief, nonsteroidal anti-inflammatory drugs and supportive care are commonly used. In severe or persistent cases, corticosteroids and immunosuppressive therapies may be considered [22].

This study highlights the value of histopathological confirmation in accurately diagnosing EN. A thorough investigation to determine potential underlying causes is critical for ensuring effective treatment and better outcomes for patients.

The most prevalent type of panniculitis observed was septal panniculitis (Erythema Nodosum), which primarily affects females in their second to fourth decades of life. Painful nodules often appear in clusters on the legs, particularly on the shin and thigh. A proper biopsy is essential for establishing a definitive diagnosis. The investigation of underlying causes should be guided by the clinical context of the patient

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