Thalidomide effective in chronic erythema multiforme

Erythema multiforme (EM) is an uncommon dermatological disorder characterized by typical target lesions and mucosal erosions. Common triggers are infections, including herpes simplex virus and Mycoplasma pneumoniae. Erythema multiforme (EM) may become chronic in 30% of cases or may become long term, with a recurrent or persistent course having a negative impact on quality of life. Many treatments including dapsone, azathioprine, intravenous immunoglobulin have been used off-label with partial to complete remission of chronic disease.

This was a retrospective national multicenter cohort study conducted with an aim to assess the effectiveness of treatment with thalidomide for patients with chronic EM. A total of 68 French hospital dermatology departments were contacted by e-mail of which only 10 reported to have eligible cases. All adults aged 18 years or older under dermatology care for chronic EM (including recurrent and persistent forms) diagnosed clinically, who had received thalidomide between 2010 and 2018 were included. Analyses were conducted from June 24, 2019, to December 31, 2019. Recurrent EM was defined as having at least 1 flare per year. Persistent EM was defined as having continuous disease or flares separated by fewer than 15 days.

The primary outcome was the proportion of patients achieving complete remission (CR) within 6 months of initiating treatment with thalidomide (ie, complete absence of relapse during the 6 months for recurrent EM and complete regression without relapse for persistent EM).

Secondary outcomes were the proportion of patients achieving CR at 3 and 12months, number of relapses during the period covered by thalidomide prescription, corticosteroid consumption, factors associated with lack of relapse, doses, treatment duration, adverse events, and withdrawals.

The authors calculated the proportion of patients without EM relapse at 3, 6, and 12 months with 95% CIs. The authors used intention to- treat analyses for primary and secondary outcomes: patients who stopped treatment before the end point analysis, for whatever reason, were considered to have experienced treatment failure. Clinical factors associated with lack of relapse were investigated by univariate analyses with χ2 or Fisher exact test.

Results

Overall, 35 patients with chronic EM, 22 with recurrent EM and 13 with persistent EM (median [range] age, 33 [15-65] years were included. After 6months of thalidomide, 23 of 35 patients (66%;95% CI, 50%-81%) achieved CR, and 7 of 35 (20%) experienced at least 1 flare. At 3 and 12 months, 29 of 35 (83%; 95% CI, 70%- 95%) and 14 of 35 (40%; 95% CI, 24%-56%) achieved CR.

Eight of 13 patients (62%) with persistent EM achieved CR at 6 months. For patients with recurrent EM who did not achieve CR after 12 months of thalidomide (n = 7), the median number of relapses decreased by 67%, from 6 per year (IQR, 5-8) before initiation vs 2 per year (IQR, 1.5-2) under treatment. Four of the 7 patients previously dependent taking corticosteroids were able to stop systemic corticosteroids therapy, and 3 of the 9 patients still on valaciclovir discontinued it after thalidomide initiation (2 continued,4missingdata).

After 6 months of continuous thalidomide treatment, 23 (66%) were in complete remission, 5 (14%) had stopped the treatment, and 7 (20%) experienced at least 1 flare. The median (IQR) initial dose followed by remission was 50 (50-100)mg/d.

Main adverse effects were asthenia (16 [46%]) and neuropathy (14 [40%]). Twenty-five (71%) of patients stopped thalidomide treatment after a median (IQR) of 12 (8-20) months owing to lack of effect (7/25 [28%]), neuropathy or another adverse effect (14/25 [56%]), or long-term complete remission (4/25 [16%]). Low-dose thalidomide, less than 50mg every other day was sufficient in 9 of 23 (39%) of responders and was associated with less neuropathy and longer treatment duration.

Conclusion

This study widens the horizon for dermatologists about the efficacy of thalidomide in chronic erythema multiforme. It causes complete remission of disease and in cases where complete remission is not achievable it decreases the frequency of relapses. Only concern is about its side effects so dose reduction whenever possible may allow for continuation by improving tolerance.

Source- Roux C, Sbidian E, Bouaziz JD, Kottler D, Joly P, Descamps V, Prost C, Samimi M, Seneschal J, Dupin N, Girard C, Paul M, Le Cleach L, Ingen-Housz-Oro S. Evaluation of Thalidomide Treatment of Patients With Chronic Erythema Multiforme: A Multicenter Retrospective Cohort Study. JAMA Dermatol. 2021 Dec 1;157(12):1472-1476. doi: 10.1001/jamadermatol.2021.4083. PMID: 34757396; PMCID: PMC8581790.