Methotrexate for the treatment of generalized lichen planus

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To the Editor: Topical treatment is impractical and patient compliance is usually poor for patients with generalized lichen planus (LP). We investigated the efficacy and safety of oral methotrexate (MTX) therapy for generalized LP. The Ethics Committee of the Uludag University Medical Faculty approved this retrospective study.

Eleven patients (8 women and 3 men) with clinical and histologically proven generalized LP who had been referred to our department between 2001 and 2005 and received oral MTX therapy were included (Fig 1, A). Clinical data were collected from the medical reports. Previously recorded clinical photographs were also collected. The age of patients ranged from 27 to 55 years (mean, 44.2 yrs). The mean duration of the disease was 6.3 months (range, 2-24 mos). Two patients had typical oral mucosal involvement. There was no scalp, genital, or nail involvement. All patients had a history of topical or systemic corticosteroid therapy that failed to control the disease. Demographic characteristics of the patients are shown in Table I. The patients were screened for hepatitis serology and the other hepatic diseases before initiation of MTX. A “complete response” was considered as the complete resolution of pruritus and the disappearance of cutaneous lesions. A “partial response” was considered as more than 50% improvement, and “no response” was defined as less than 50% clearance of cutaneous lesions and relief of pruritus.

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• Fig 1. 

  Clinical appearance before (A) and after (B) methotrexate therapy.

Table I. Demographic characteristics and follow-up data of patients with generalized lichen planus treated with methotrexate

CS, Corticosteroid; F, female; M, male.

MTX was initiated at a single oral dose of 15 mg/week in four patients and 20 mg/week in seven patients. Improvement of mucocutaneous lesions and pruritus was noted within the first month in all patients. Complete response was achieved in 10 patients at the end of the first month, and the dosage of MTX was then decreased gradually (Fig 1, B). One patient discontinued MTX because of intolerable adverse effects (nausea and fatigue) at the fourth week. The therapy was well tolerated without any adverse effects or laboratory abnormalities in 10 patients.

Patients received MTX therapy for 5 to 15 weeks (median, 9.6 wks) with a cumulative dose between 65 and 260 mg. During the follow-up period of 6 months, one patient had a recurrence after 2.5 months (Table I).

There are no large controlled studies assessing the efficacy and safety of systemic treatment alternatives for generalized LP. Only systemic corticosteroids have been widely used and are usually found to be effective, but prolonged use often results in serious side effects.¹

The efficacy of MTX is mainly related to its effect on epidermal cell proliferation. However, in vitro studies demonstrate that MTX has a more significant effect on lymphoid cells.² Nylander Lundqvist et al³ treated four patients with erosive LP with MTX (10-15 mg/wk) in combination of topical corticosteroids for 17 months and concluded that MTX was a well tolerated and effective treatment for severe erosive LP. To our knowledge, no clinical trials for MTX in generalized LP have been reported previously. The results of this small retrospective case series suggest that use of weekly oral MTX can be a highly effective and tolerable treatment alternative to systemic corticosteroids. Larger prospective controlled trials are needed to establish the optimal dosage and duration of MTX therapy for generalized LP.

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References 

1. Gallant C, Kenny P. Oral glucocorticoids and their complications. A review. J Am Acad Dermatol. 1986;14(2 pt 1):161–177
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2. Jeffes EW, McCullough JL, Pittelkow MR, McCormick A, Almanzor J, Liu G, et al. Methotrexate therapy of psoriasis: differential sensitivity of proliferating lymphoid and epithelial cells to cytotoxic and growth inhibitory effects of methotrexate. J Invest Dermatol. 1995;104:183–188
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3. Nylander Lundqvist E, Wahlin YB, Hofer PA. Methotrexate supplemented with steroid ointments for the treatment of severe erosive lichen ruber. Acta Derm Venereol. 2002;82:63–64
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