Topical tacrolimus for recalcitrant vulvar lichen sclerosus

ARTICLE

Auteur(s) : Eleni Sotiriou, Zoi Apalla, Aikaterini Patsatsi, Despina Panagiotidou

First dermatologic department, Medical school, Aristotle university Thessaloniki, 8, Papakyriazi str, 54645 Thessaloniki, Greece

Vulvar lichen sclerosus (VLS) is a chronic inflammatory skin disorder of uncertain origin predominantly affecting postmenopausal women. As immunological alterations seem to be important in the aetiopathogenesis of VLS, tacrolimus – an immunomodulating topical agent – could be an alternative therapeutic approach [1-6].

Recent data introducing beneficial effects of calcineurin inhibitors in patients with LS [2-6], led us to use tacrolimus in our patients. Our purpose was to present the clinical results of topical tacrolimus in 10 postmenopausal women with biopsy-proven recalcitrant VLS. Exclusion criteria were infections of the anogenital area within 2 weeks of treatment initiation and any treatment administered within 4 weeks of tacrolimus initiation. Written informed consent was provided by all patients. Patients’ mean age was 53.4 years and mean disease duration 2.9 years. Previous treatments consisted of intermittent topical potent and ultra-potent corticosteroids with only temporary improvement. All patients were treated with tacrolimus ointment 0.1% twice daily for 8 weeks. Biopsy specimens were obtained at the end of treatment only from patients no 1 and no 8 as these cases were the most representative ones for early and late stage VLS accordingly. Clinical assessments were performed at baseline, at 8 weeks and 8 weeks after treatment discontinuation. Four objective parameters (hyperkeratosis, atrophy, sclerosis and depigmentation) were graded on the following scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe. Total score was calculated by adding the scores obtained for each separate parameter. At the same visits, subjective evaluation of pruritus, burning and pain was obtained by using a horizontal visual analogue (0 = no symptoms, 1 = slight pruritus, burning and pain 2 = moderate pruritus, burning and pain, 3 = strong pruritus, burning and pain). Before initiation and 2 months after discontinuation of treatment, patients were asked to complete a DLQI (Dermatology Life Quality Index) questionnaire.

Drug-related side effects described as a burning sensation at the point of application occurred in 4 patients, within the first week of treatment. Reactions were mild and transient. Treatment discontinuation was not necessary in any case. Analysis of subjective scores shows a positive result of the drug on pruritus, burning and pain. Reduction of symptoms occurred within the first 2 weeks of treatment in all patients. Mean values in the visual analogue scale decreased from 2.55 at baseline to 0.95 at 8 weeks and only rose to 1.5 at the last follow-up visit. DLQI questionnaires showed a mean reduction of 53% (range 40-70%). Analysis of objective scores shows a minor influence on the parameters evaluated. Nine out of 10 patients achieved a minor improvement in clinical signs, while there was no improvement in one patient. There was no alteration in the objective scores evaluated at the last follow-up visit. Patient characteristics and results are shown in table 1. Histology, performed in 2 cases, revealed no resolution of typical LS.
Table 1 Patient characteristics and results

Although subjective symptom relief should not be underestimated, minor clinical improvement points to the possibility of a tacrolimus placebo effect. In a recent multicenter study [6], symptomatic relief occurred rapidly with therapy, which is in accordance with our results. However, the clinical response, either partial or complete, was achieved after 16, 20 or even 24 weeks of treatment. Treatment duration in our study was only 8 weeks, which could explain the poor clinical response achieved. In the same study [6], no malignancy was observed during an 18-month follow-up period, which seems to minimize the concern for predisposition to malignancies due to local immunosuppression.

In this small series, tacrolimus appeared to be well tolerated, producing relief of symptoms and improving quality of life. Further randomized, controlled studies are needed to determine the best modalities and lengths of treatment with tacrolimus in VLS.

Acknowledgements

References

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