Cutaneous lupus erythematosus (CLE) may cause extensive skin damage leading to aesthetic prejudice and poor quality of life. Antimalarial agents are recommended as first-line systemic therapy for CLE patients with moderate-to-severe skin lesions. In case of failure of antimalarial agents, a European expert consensus for CLE treatment and EULAR recommendation for systemic lupus erythematosus (SLE) recommend adding quinacrine, methotrexate, retinoids, dapsone or mycophenolate mofetil.¹ However, the overall efficacy of these second-line treatments is approximately 50% depending on CLE subtypes and may be associated with potential toxicity. Thalidomide (a-N-phthalimidoglutarimide) is currently recommended as a ‘rescue’ therapy in patients with severe and refractory CLE treatment. However, in France, a ‘Temporary Recommendations for Use’ has been granted for thalidomide in CLE after failure of antimalarials as second-line agent.^{1 2} Moreover, in a systematic literature review including 21 observational studies and 548 patients the pooled rate of response to thalidomide 50–100mg/day was 90% (95% CI, 85–94), with similar response rates between CLE subtypes.³ The clinical benefits need to be balanced against potential adverse events with a pooled rate of thalidomide withdrawal related to adverse events of 24% (95% CI 14–35) including high teratogenicity, peripheral neuropathy 16% (95% CI 9–25), thromboembolic events in 2% (95% CI 1–3). Moreover, the efficacy of thalidomide is only suppressive with a rate of relapse of 71% (95% CI 65–77) after thalidomide withdrawal which supports the use of a minimal maintenance dose.³ In case of failure of thalidomide, lenalidomide 5 mg/day a 4-amino-glutamyl analogue of thalidomide has shown promising results with partial response of 88% in a retrospective study of 40 patients.⁴ Importantly, no cases of new or worsening peripheral thalidomide-induced neuropathy was reported with lenalidomide.⁴ A case of progression to SLE with renal involvement was reported in a patient with isolated CLE after starting lenalidomide.⁵ Recent data did not confirm this finding but suggested that lenalidomide has little or no effect on global SLE activity.

Learning Objectives

• Describe the therapeutic strategy in CLE

• Explain when to prescribe thalidomide and lenalidomide

• Discuss the safety profile of thalidomide and lenalidomide

References

1. Fanouriakis A, Kostopoulou M, Alunno A, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736–45.

2. Kuhn A, Aberer E, Bata-Csörgő Z, et al. S2k guideline for treatment of cutaneous lupus erythematosus - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV). J Eur Acad Dermatol Venereol. 2017;31(3):389–404.

3. Chasset F, Tounsi T, Cesbron E, et al. Efficacy and tolerance profile of thalidomide in cutaneous lupus erythematosus: A systematic review and meta-analysis. J Am Acad Dermatol. 2018;78(2):342–50.e4.

4. Aitmehdi R, Arnaud L, Francès C, et al. Long-term efficacy and safety outcomes of lenalidomide for cutaneous lupus erythematosus: a multicenter retrospective observational study of 40 patients. J Am Acad Dermatol. 2020.

5. Braunstein I, Goodman NG, Rosenbach M, et al. Lenalidomide therapy in treatment-refractory cutaneous lupus erythematosus: histologic and circulating leukocyte profile and potential risk of a systemic lupus flare. J Am Acad Dermatol. 2012;66(4):571–82.