Clinical and immunological predictors of chronicity in erythema nodosum

Background Erythema nodosum (EN) is a painful inflammatory disorder of the subcutaneous fat and the most common type of septal panniculitis. It often presents as erythematous, tender subcutaneous nodules, typically affecting the shins. EN is frequently a hypersensitivity reaction that can serve as a warning sign for an underlying systemic disorder, making it crucial to identify the cause. Though self-limiting in many cases, EN can sometimes become chronic, leading to significant discomfort. The pathogenesis of EN and the predictors of chronicity remain unclear, necessitating further investigation. Aims This study aimed to evaluate the various etiologies of EN and determine the clinical, laboratory, and immunohistochemical predictors of chronicity. Methods We conducted a prospective hospital-based study between July 2022 and June 2024 at a tertiary care centre in Eastern India. Clinical and histopathologically confirmed cases of EN presenting within 2-3 days of onset, without prior treatment, were enrolled. A detailed clinical examination and laboratory investigations were performed during the initial visit, including immunohistochemical analysis of skin biopsies. The total number of T cells (CD3+), helper T cells (CD4+), cytotoxic T cells (CD8+), CD4:CD8 ratio, and NK (natural killer) cells (CD56+) were quantified per skin biopsy specimen using a standardised technique. Patients were treated at the discretion of the treating physician. Patients were monitored monthly for three months and categorised as either having "Classic EN" (lesions resolving within three months) or "Chronic EN" (lesions persisting beyond three months). Data collected at the initial visit were correlated between the two groups to identify potential predictors of chronicity. Results Out of 63 suspected cases, EN was confirmed in 41 patients, who were predominantly females (65.85%), with a median age of 49 years (Q1 - Q3: 32 - 57). Pulmonary tuberculosis was the most frequent underlying condition (n = 15, 36.59%), followed by sarcoidosis (n = 8, 19.51%) and rheumatoid arthritis (n = 6, 14.63%). Chronic EN was observed in 36.59% of cases, with significantly elevated baseline C-reactive protein (CRP) levels (p = 0.003) and Mantoux test readings (p = 0.002). Immunohistochemistry revealed higher CD3, CD4, CD8, and CD56 levels in chronic EN cases (p < 0.05). Limitations The study's limitations include a small sample size and short follow-up duration. Multivariable analysis could not be performed due to the small sample size. Conclusion This study identified clinical and immunohistochemical markers associated with the chronicity of EN and highlighted pulmonary tuberculosis as the most common underlying cause. Elevated CRP levels, positive Mantoux test results, and increased expression of CD3, CD4, CD8, and CD56 observed at baseline were linked to chronicity. The findings suggest the predominant role of T helper 1 (Th1) cell response and innate immunity in the pathogenesis of chronic EN lesions. Understanding these predictors and underlying aetiologies can help clinicians identify high-risk patients and tailor management accordingly.