Successful treatment of discoid lupus erythematosus with fumaric acid esters
Authors: Athanasios Tsianakas, Sabine Herzog, Aysche Landmann, Nikolaos Patsinakidis, Ana María Perusquía Ortiz, Gisela Bonsmann, Thomas A. Luger, Annegret Kuhn
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: Fumaric acid esters (FAEs) have proven their therapeutic efficacy in moderate to severe psoriasis and have been licensed in Germany since 1994. The most pharmacologically effective molecule among the FAEs is dimethyl fumarate.1Mrowietz U. Asadullah K. Dimethylfumarate for psoriasis: more than a dietary curiosity.Trends Mol Med. 2005; 11: 43-48Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar It has previously been shown that this lipophilic molecule inhibits the activity of the transcription factor NF-κB and the secretion of proinflammatory cytokines by T cells.2Meissner M. Valesky E.M. Kippenberger S. Kaufmann R. Dimethyl fumarate – only an anti-psoriatic medication?.J Dtsch Dermatol Ges. 2012; 10: 793-801PubMed Google Scholar Several further antipsoriatic effects of FAEs have been suggested, including the induction of pro-apoptotic pathways, the suppression of adhesion molecules, and the inhibition of keratinocyte proliferation. The efficacy of FAEs in psoriasis may therefore be mediated by immunomodulatory mechanisms, which might also play a role in the treatment of other inflammatory diseases, such as cutaneous lupus erythematosus. Here we report systemic treatment with FAEs in a 52-year-old woman with discoid lupus erythematosus presenting with severe erythematous, scarring lesions on the face (Table I; Fig 1, A and B). Previous therapies included topical glucocorticoids, tacrolimus ointment, hydroxychloroquine, chloroquine, and alitretinoin with only short-term improvement. The patient was included in a pilot study, and Fumaderm initial (Biogen Idec, Cambridge, MA) (30 mg dimethyl fumarate and 75 mg monoethyl fumarate salts) was administered orally – 1 tablet up to 3 tablets per day. The Revised Cutaneous Lupus Disease Area and Severity Index (RCLASI), a validated disease activity and damage scoring system, was used to evaluate the patient's skin lesions during the treatment period.3Kuhn A. Meuth A.M. Bein D. Amler S. Beissert S. Bohm M. et al.Revised Cutaneous Lupus Erythematosus Disease Area and Severity Index (RCLASI): a modified outcome instrument for cutaneous lupus erythematosus.Br J Dermatol. 2010; 163: 83-92PubMed Google Scholar The patient did not receive any additive therapeutic agent other than Fumaderm initial. The activity of the discoid lesions decreased from 17 points to 8 points, and the damage from 5 points to 3 points, which was a clear improvement after 6 months of treatment (Fig 1, C and D). Severe adverse events were not recorded during treatment with FAEs; however, the patient only tolerated the starting dose of 1 tablet of Fumaderm initial. A higher dose resulted in nausea, diarrhea, headache, flush, and abdominal cramps. Consequently, it was not possible to switch from Fumaderm initial to Fumaderm (Biogen Idec, Cambridge, MA) (120 mg dimethyl fumarate and 95 mg monoethyl fumarate salts). After 6 months of treatment, Fumaderm initial was discontinued according to the study protocol, and the skin lesions became severely aggravated. The treatment with Fumaderm initial was started again and the patient reported significant improvement after some weeks. Moreover, the patient then had fewer side effects from therapy and even tolerated 1 tablet of Fumaderm per day.Table IDemographic and clinical data of patients treated with fumaric acid estersReferenceSexAgeSubtypeClinical manifestationsPrevious therapy: ineffectiveFumaderm agentTherapeutic regimenClinical responseAdverse effectsBalak et al, 20114Balak D.M. Thio H.B. Treatment of lupus erythematosus with fumaric acid esters: two case-reports.J Transl Med. 2011; 9: 15Crossref PubMed Google ScholarF35LETErythematous, indurated swelling of the nose, present for 1 yearHydroxychloroquine, intralesional steroid injectionsFumaderm initialDosage was gradually increased up to 6 tablets per dayLesions resolved completely within 3 months of treatmentNausea, diarrhea, mild leukopenia and proteinuriaBalak et al, 20114Balak D.M. Thio H.B. Treatment of lupus erythematosus with fumaric acid esters: two case-reports.J Transl Med. 2011; 9: 15Crossref PubMed Google ScholarF24SLEErythematous, scaly plaques, Raynaud phenomenon, alopecia, and oral ulcersPrednisone, hydroxychloroquine, cyclosporineFumaderm initialDosage was gradually increased up to 6 tablets per day in combination with 10 mg prednisoneGood effects within 3 months of treatmentTiredness, pruritus, abdominal cramps, transient proteinuriaKlein et al, 20125Klein A. Coras B. Landthaler M. Babilas P. Off-label use of fumarate therapy for granulomatous and inflammatory skin diseases other than psoriasis vulgaris: a retrospective study.J Eur Acad Dermatol Venereol. 2012; 26: 1400-1406Crossref PubMed Scopus (16) Google ScholarM42DLEErythematous, scarring discoid lesions on both cheeks and the chinHydroxychloroquine, topical steroids, tacrolimus ointmentFumaderm initial, FumadermDosage was gradually increased up to 6 tablets of Fumaderm per day in combination with hydroxychloroquineComplete resolution of erythematous lesions (stable disease), 73 months of treatmentNot availablePresent case reportF52DLESevere, erythematous, scarring discoid lesions on the faceHydroxychloroquine, chloroquine, alitretinoin, topical steroids, tacrolimus ointmentFumaderm initial (Fumaderm was not tolerated during the study)Dosage was gradually increased up to 3 tablets per dayRCLASI activity of discoid lesions decreased from 17 to 8 points and RCLASI damage from 5 to 3 points after 6 months of treatmentNausea, diarrhea, headache, flush, abdominal crampsDLE, Discoid lupus erythematosus; LET, lupus erythematosus tumidus; RCLASI, Revised Cutaneous Lupus Disease Area and Severity Index; SLE, systemic lupus erythematosus. Open table in a new tab DLE, Discoid lupus erythematosus; LET, lupus erythematosus tumidus; RCLASI, Revised Cutaneous Lupus Disease Area and Severity Index; SLE, systemic lupus erythematosus. To our knowledge, to date, only 1 case of discoid lupus erythematosus treated with FAEs in combination with hydroxychloroquine has been published. Furthermore, a poster presentation has described the effective treatment with FAEs of a patient with lupus erythematosus tumidus and a patient with systemic lupus erythematosus (Table I).4Balak D.M. Thio H.B. Treatment of lupus erythematosus with fumaric acid esters: two case-reports.J Transl Med. 2011; 9: 15Crossref PubMed Google Scholar, 5Klein A. Coras B. Landthaler M. Babilas P. Off-label use of fumarate therapy for granulomatous and inflammatory skin diseases other than psoriasis vulgaris: a retrospective study.J Eur Acad Dermatol Venereol. 2012; 26: 1400-1406Crossref PubMed Scopus (16) Google Scholar In summary, these case reports suggest that FAEs could be an effective alternative treatment of cutaneous lupus erythematosus; however, randomized controlled trials are warranted to evaluate the efficacy and safety of FAEs in this disease. We thank Dr N. Núnez Gómez and Dr M. Neureither of Biogen Idec GmbH, Ismaning, Germany, for supporting this study. The figures were kindly provided by the Photographic Laboratory (with thanks to J. Bueckmann and P. Wissel), Department of Dermatology, University of Muenster, Germany.