Efficacy of topical tacrolimus in the treatment of various cutaneous manifestations of lupus erythematosus

Cutaneous lesions of patients with lupus erythematosus (LE) are usually treated with topical corticosteroids. The side-effects of corticosteroids in the case of prolonged application limit their long-term use. Topical tacrolimus appears to provide comparable therapeutic potency without significant adverse effects. It has been successfully applied in the treatment of atopic dermatitis,1, 2 and is registered for this indication. Further successful topical applications of tacrolimus have been demonstrated for contact dermatitis,3 facial lesions of psoriasis,4 and erosive lichen planus.5 Kanekura et al.6 recently demonstrated the efficacy of topical tacrolimus for the treatment of skin lesions of systemic lupus erythematosus (SLE). They treated three patients (female : male = 2 : 1) with 0.1% tacrolimus ointment twice daily for 3 weeks. Variable results in the treatment of the facial lesions of cutaneous LE and dermatomyositis were observed by Yoshimasu et al.7 Topical tacrolimus therapy was applied to facial skin lesions in 11 cases. Six of the 11 patients [three with SLE, one with disseminated discord lupus erythematosus (DLE), and two with dermatomyositis] responded well to topical therapy with tacrolimus; however, four of the patients treated (three with DLE and one with dermatomyositis) were resistant to this therapy. We report four patients suffering from different forms of LE, whose skin lesions were treated with tacrolimus 0.1% ointment twice daily, to explore whether this agent is effective for the treatment of cutaneous LE manifestations. Patient 1. A 39-year-old woman presented to our department with a 4-year history of SLE with lupus nephritis. Skin lesions had re-occurred on her face, as well as on the upper and lower extremities, for a few months. They presented as finely scaled, sharply defined erythema, measuring 1.5–2.5 cm in diameter. Abnormal laboratory findings included leukocytosis with a white blood cell count of 16.79/nL, elevated α2-globulins at 13.6%, positive antinuclear antibodies (ANA) (1 : 1600), and positive antibodies to double-stranded deoxyribonucleic acid (dsDNA), single-stranded (ss)DNA and Ro/SSA. Urine analysis showed proteinuria and urobilinogen excretion. The patient received azathioprine 100 mg/day and hydroxychloroquine 200 mg/day as basic treatment. In the past, she had received different topical corticosteroids, including betamethasone valerate 0.1% ointment, clobetasol 0.05% ointment, and mometasone furoate 0.1% cream for local treatment without sufficient effect. We stopped this treatment and started therapy with 0.1% tacrolimus ointment twice daily. The basic therapy was continued as described above. After 1 week of treatment, no changes in the skin lesions were observed. After a further 2 months, the treatment was still not effective. Therefore, therapy with tacrolimus was stopped. The patient reported no burning sensations, irritation, or pruritus during treatment with tacrolimus. Patient 2. A 51-year-old woman with SLE since 1979 and renal involvement since 1983 presented with lesions (measuring up to 5 cm in diameter) of sharply defined erythema with fine scaling on the cheeks, central atrophy, and follicular hyperkeratosis. Laboratory findings were as follows: positive ANA (1 : 800), anti-dsDNA antibodies, anti-ssDNA antibodies, and anti-Ro antibodies. Other laboratory findings were within normal limits. She received mycophenolate mofetil 2 g/day and prednisolone 20 mg/day as basic therapy. The lesions on her cheeks were also treated with tacrolimus 0.1% ointment twice and then once daily. The infiltrations and erythema decreased in 3 weeks with burning sensations at the start of therapy. Daily treatment with tacrolimus has continued with good response to date (Fig. 1). Before (a) and 3 weeks after (b) the beginning of local treatment with tacrolimus 0.1% ointment in a patient with systemic lupus erythematosus (SLE) Patient 3. A 36-year-old woman suffering from DLE since 1996 presented with sharply defined erythematous plaques, measuring 2–4 cm in diameter, with slight hyperkeratosis and central atrophy on the cheeks. As basic therapy, she received prednisolone 10 mg/day and hydroxychloroquine 300 mg/day. Abnormal laboratory findings included leukopenia with a white blood cell count of 4.15/nL, reduced hemoglobin of 11.2 g/dL, reduced mean cell hemoglobin (MCH) of 24.1 pg, and mean cell volume (MCV) of 72 fL. ANAs were positive (anti-U1RNP antibodies) and circulating immune complexes were elevated (61 µg/mL; reference value, < 55 µg/mL). Topical therapy with tacrolimus 0.1% ointment twice daily was initiated. After 4 weeks of treatment, the skin lesions had improved slightly and therapy was continued. Eight weeks after the beginning of treatment with tacrolimus, the skin lesions had worsened again and the local therapy was stopped. No side-effects occurred during treatment with tacrolimus. Patient 4. A 53-year-old woman with cutaneous DLE since 1990 presented with multiple, hyperkeratotic, sharply defined plaques on her face and back, measuring between 2 and 5 cm in diameter. Abnormal laboratory findings included circulating immune complexes (133 µg/mL; reference value, < 55 µg/mL). ANAs were negative and the blood cell count was normal. Therapy with hydroxychloroquine 300 mg/day and low-dose prednisolone (5–10 mg/day) was initiated in combination with prednisolone pulse therapy (up to 60 mg for 5 days every month). She had been prescribed triamcinolone acetonide 0.1% cream for local treatment without effect. Treatment of the skin lesions on her face was initiated with 0.1% tacrolimus ointment twice daily for 4 months. The basic therapy was continued. Three weeks after the beginning of local therapy with tacrolimus, the lesions on her cheeks started to become smoother without complete remission. No burning sensations, irritation, or pruritus at the sites of application occurred. Local therapy with tacrolimus has continued to date. As reported above, we observed variable responses of facial lesions of patients suffering from SLE and DLE when treated with topical tacrolimus 0.1% ointment for up to 2 months. The application of highly potent corticosteroids did not lead to sufficient remission of the skin lesions. Two patients (one with SLE and one with DLE) showed marked regression of their skin lesions after 3 weeks of treatment with tacrolimus 0.1% ointment, whereas the others showed no response. Topical application of tacrolimus 0.1% ointment was well tolerated, and side-effects such as burning or pruritus did not occur. These results clearly demonstrate that topical tacrolimus is well tolerated when it is applied to cutaneous LE lesions. Its effectiveness, however, needs to be determined in prospective clinical trials with a larger number of cases and defined protocols.