Around half of those with the inflammatory skin disorder erythema nodosum (EN) report chronic or recurrent disease, according to a recent analysis, and 26% of this half of EN patients showed incomplete response to treatment.¹

EN is an inflammatory skin disorder that is often painful and known for being the most common panniculitis. The disease is characterized, typically, with erythematous nodules seen in the bilateral pretibial regions of the body.

A new study, led by Jill T. Shah, BA, from the Ronald O. Perelman Department of Dermatology at New York University Langone Health, expanded upon the limited data available on EN. Shah and colleagues acknowledged that the smaller cohorts of EN patients often do not cover chronicity and exist outside of the US.²

“In this retrospective cohort study, we characterize the presentation, causes, treatment, and disease course of EN, and identify associations with chronicity/recurrence,” Shah and colleagues wrote.

Background and Findings

The investigators, after receiving institutional review board approval exemption, conducted their research in the form of a retrospective review of available medical records found at New York University’s Langone Health.

The research team worked to find data related to EN cases, working to ensure diagnostic precision of those they found. Their criteria for inclusion covered individuals in the age range of 18 - 89 years.

Additional criteria for inclusion included presenting with the disease in the period between January 2000 - November 2021 and follow-up that exceeded 12 total weeks. Their exclusion criteria encompassed individuals diagnosed with other types of panniculitides.

The investigators looked into data related to disease presentation, demographic information, workup,comorbidities, EN triggers, treatments, and patient responses. They classified ‘classic EN’ as symptom resolution within 12 weeks and ‘chronic/recurrent EN’ as EN with symptoms continuing or recurring for 12 weeks or more.

In their analyses of the statistics, the research team utilized a Pearson χ2 test, unpaired t test, Fisher exact test, or Wilcoxon rank sum test through the use of R. They set significance at P < .05.

The team found that 340 of the 740 records of subjects had clinically or histopathologically confirmed EN and were identified in their research. They reported that 53% of these individuals reported having classic EN, with a mean follow-up of 3.6 (2.6) years, and 47% had chronic/recurrent EN and a mean follow-up of 4.4 (2.7) years.

Among the 120 subjects in the chronic/recurrent EN group who reported having multiple episodes, the median number of episodes was shown to be 3. The investigators also noted that, in this group, median time between the initial and final episode of EN was shown to be 3.4 years.

An interesting element of the team’s findings was that individuals with chronic/recurrent EN, as opposed to classic EN, were shown to be more likely to be of younger age at the point of symptom onset (median age, 39 years vs 42 years; P = .02). They also were found to be more likely to be of younger age with onset of rheumatoid arthritis (RA; 5% vs 1%; P = .05), truncal nodules (8% vs 3%; P = .04), and/or preceding tumor necrosis factor (TNF) inhibitor implementation (5% vs 1%; P = .05).

Those in the chronic/recurrent EN were shown by the investigators to, compared to those with classic, have more frequently needed several different treatments to reach clinical response (42% compared to 25%; P < .001).

Chronic/recurrent EN was also noted by the team to have required intralesional or topical corticosteroids, nonsteroidal immunomodulatory treatments, and potassium iodide. Systemic therapy was necessary in 64% of patients with chronic/recurrent EN, compared to 48% in patients with classic EN (P = .003), and incomplete response to treatment was found to have occurred in 26% and 1%, respectively (P < .001).

A more comprehensive examination of subjects with chronic/recurrent cases of EN for underlying causes was also shown to be more likely, including for autoantibodies (71% compared to 55%; P = .003) and colonoscopy/endoscopy (14% compared to 5%; P = .003). Seventy-five percent of the patients were shown to have disease associations or triggers and there were not any major distinctions between both cohorts.

“Although this study has a large cohort, it may be insufficiently powered to identify subtle differences, such as racial differences, in those with chronic/recurrent EN,” they wrote. “Further studies are warranted to identify risk factors leading to chronicity/recurrence of EN, results of autoantibody testing, and ideal management strategies.”

References

1. ^{Shah JT, Richardson WM, Caplan AS, Mazori DR, Femia AN. Clinical Characteristics of Erythema Nodosum and Associations With Chronicity and Recurrence. JAMA Dermatol. Published online January 03, 2024. doi:10.1001/jamadermatol.2023.5306.}
2. ^{García-Porrúa C, González-Gay MA, Vázquez-Caruncho M, et al. Erythema nodosum: etiologic and predictive factors in a defined population. Arthritis Rheum. 2000;43(3):584-592. doi:10.1002/1529-0131(200003)43:3<584::AID-ANR15>3.0.CO;2-6.}