Discoid lupus erythematosus (DLE) is one of the three types of lupus erythematosus (LE)-specific skin diseases, localized on the face and scalp in 80% of patients1. In the absence of systemic disease, the goals of therapy in a patient with DLE are improvement of the patient's appearance and prevention of deforming scars, atrophy or dyspigmentation2. Potent topical steroids are frequently prescribed, although their long-term use is often limited by adverse effects such as skin atrophy and telangiectasia3.

The compound macrolides, tacrolimus (FK506) and pimecrolimus (SDZ ASM 981), are members of a triad of calcineurin inhibitors that include cyclosporine A. They inhibit T-cell activation and the release of numerous inflammatory cytokines4. They are anti-inflammatory medications that might replace steroids for the topical treatment of many inflammatory skin diseases, including atopic dermatitis, contact dermatitis, pyoderma gangrenosum, psoriasis, alopecia areata, Behcet's disease, vitiligo, and lichen sclerosus, without having atrophogenic potential or risking other steroid-specific side effects4-10.

We herein report 4 cases of facial DLE successfully treated with therapeutic adjuvants, topical tacrolimus or pimecrolimus.

There are several case reports suggesting that tacrolimus and pimecrolimus provide good therapeutic efficacy for the cutaneous lesions of LE. Kanekura et al.11 assessed the efficacy of 0.1% tacrolimus ointment for a malar rash in 3 patients with systemic LE. After 3 weeks of twice-daily tacrolimus usage, all the lesions were gone. Druke et al.12 reported a case of subacute cutaneous LE, in which erythematous lesions were treated successfully with twice daily 0.1% topical tacrolimus application during an 8-week period. For patients with DLE, however, results thus far on the therapeutic efficacy of topical tacrolimus and pimecrolimus seem to be controversial. Yoshimasu et al.13 reported on the efficacy of 0.1% topical tacrolimus in 9 patients with LE. A good response was obtained for systemic LE, whereas the lesions of DLE did not improve. The lack of response in DLE cases was explained by the low absorption due to the hyperkeratotic and acanthotic changes present in chronic, scaly DLE lesions. However, recent studies have reported that DLE can be controlled by application of tacrolimus or pimecrolimus alone. For example, Walker et al.14 reported that a formulation of 0.3% tacrolimus in 0.05% clobetasol propionate ointment was effective in 2 patients with severe recalcitrant chronic DLE. Moreover, de la Rosa Carrillo and Christensen15 noticed both the improvement of facial lesions as well as the regrowth of terminal hair in most of the scalp lesions of DLE with tacrolimus monotherapy. Since then, a few studies have used severity scoring systems for clinical assessment. In Hefferman's open-label pilot study, 3 subjects applied 0.1% tacrolimus to 2 target lesions twice a day for 12 weeks16. The target lesions were assessed using 4 criteria: diameter size, erythema, scarring, and thickness. These 4 criteria were graded using a 5-point scale. The mean percentage improvement in scores for the 4 criteria was 32%, 53%, 56%, and 33%, respectively. In our case, the mean percentage improvements in scores for 3 criteria, which were erythema, scale/thickness, and scarring/atrophy, were 82%, 67%, and 33%, respectively. Similarly, Kreuter et al.17 performed a twice daily regimen for 3 weeks with 1% pimecrolimus cream in 11 subjects, including 4 DLE patients, and assessed the skin involvement with a clinical score using a 3-grade and 4-point scale before and after treatment. For all patients of the study, the overall percentage improvement in scores was 58%, but for the 4 patients with DLE it was 48%. Recently, Tlacuilo-Parra et al.18 used a severity score as well as the Skindex-29 for evaluation of the quality of life; their results showed a mean improvement of 46% in the quality of life of DLE patients after the use of tacrolimus.

Based on the good results reported in previous reports, we provided a twice-daily regimen of topical tacrolimus or pimecrolimus for 8 weeks and semiquantitatively assessed the skin involvement before and after therapy using a clinical severity score. After 8 weeks of therapy, both tacrolimus and pimecrolimus showed good responses in all patients (mean percentage improvement of all patients was 66.5%). The effects of treatment were more pronounced in our study, but this appears to be due to the fact that the majority of patients had lesions that showed erythema and scaling, as opposed to scarring and atrophy, which are seen in lesions that are more resistant to therapy. With regard to the efficacy of topical tacrolimus vs. pimecrolimus, no significant difference was found in the efficacy or side effects. Moreover, the improvement in skin condition was sustained in all patients for 4 weeks during the follow-up period. Since completion of the study, these 4 patients have been intermittently applying topical tacrolimus or pimecrolimus in combination with topical steroids; this treatment has provided adequate control of their lesions. However, the role of tacrolimus and pimecrolimus in the treatment of cutaneous LE will depend on its efficacy when compared to established topical treatments such as steroids. Therefore, double blind, placebo-controlled studies are needed in order to confirm our findings.

In conclusion, our reports suggest that tacrolimus 0.1% ointment and pimecrolimus 1% cream for patients with DLE seem to be safe and clinically effective options, especially for resistant DLE on a sensitive site, such as the face, where use of potent topical steroids carries a high risk for thinning of the skin and telangiectasia.