Low-dose Methotrexate for Vitiligo

July 2017 | Volume 16 | Issue 7 | Case Reports | 705 | Copyright © July 2017

Anna Cristina Garza-Mayers BA PhDa,b and Daniela Kroshinsky MD MPHa,b

aDepartment of Dermatology, Massachusetts General Hospital, Boston, MA bHarvard Medical School, Boston, MA


BACKGROUND: Treatment of vitiligo is aimed at repigmentation and often consists of multiple modalities, none of which are universally or rapidly successful. Extensive cases are most often treated with ultraviolet light therapy, which can be both costly and time-consuming. Though vitiligo is an autoimmune disease, there is no current data to support systemic immunosuppressive monotherapy.

CASE SUMMARY: Here we present a case series of 3 patients with vitiligo treated for 11-16 months with low-dose methotrexate (12.5-25 mg per week) with folic acid supplementation with clinically significant skin repigmentation, with response within 6 months in one case. There were no severe adverse effects reported.

CONCLUSION: These cases demonstrate an unexplored effective and steroid-sparing therapeutic alternative in patients with vitiligo for whom topical therapy has failed and phototherapy is cost-prohibitive or ineffective.

J Drugs Dermatol. 2017;16(7):705-706.


Vitiligo is an autoimmune leukodermic disorder of acquired skin depigmentation due to the destruction of melanocytes. Pigment loss can be stigmatizing and cause significant psychological stress, requiring early treatment with monitoring at regular intervals for improvement. Topical corticosteroids are usually first-line therapy followed by topical calcineurin inhibitors, particularly in cases with limited involvement. Narrowband ultraviolet B (NBUVB) radiation or other types of phototherapy are used in more extensive cases. Systemic corticosteroids are used rarely in rapidly progressive disease but cannot be used long-term due to well known side effects including weight gain and mood changes. Targeted immunotherapy is under development.1 The use of other immunosuppressive or immunomodulatory agents is largely empiric, with limited data to support the use of azathioprine in combination with phototherapy.  Here we describe 3 cases of vitiligo with significant clinical improvement with low-dose methotrexate therapy.Case SeriesCase 1A 33-year-old otherwise healthy woman presented for dermatologic consultation with concern for rapidly progressive generalized vitiligo. Depigmentation was first noted in adolescence with significantly accelerated progression in the few months preceding presentation. At first presentation, she was initiated on a short course of prednisone due to rapid progression, with good response but lesion progression when taper was attempted. She then initiated ultraviolet B (UVB) radiation phototherapy three times per week in conjunction with topical 0.1% tacrolimus ointment. When there was no improvement after 6 weeks, she transitioned to narrowband UVB (NBUVB) phototherapy. With this treatment, she showed slow signs of perifollicular and patchy repigmentation with decreased body surface area (BSA) of disease for approximately 2 years. Throughout this time, she expressed concern for her ability to work given the time commitment needed for NBUVB therapy with moderate difficulty obtaining a home phototherapy unit. She then presented with concern for rapidly progressive flare while on treatment and expressed an interest in monobenzyl ether of hydroquinone depigmentation therapy.On physical exam, the patient had Fitzpatrick skin type 4 with diffuse patches of depigmentation totaling more than 40% BSA, which was particularly troubling to the patient on the dorsal hands (Figure 1A and 1C). Given the patient’s frustration with the long course of her disease and with concern for long-term steroid use, the decision was made to trial a systemic immunosuppressive agent. She was started on methotrexate 10 mg once a week with 1 mg folic acid supplementation daily and titrated up over 6 weeks to 17.5 mg methotrexate once a week. Extensive repigmentation was seen within 6 weeks of initiating treatment (Figure 1B and 1D). Of note, she experienced near resolution of digital involvement. Her liver function and blood cell counts are regularly monitored with no adverse side effects noted. She continues to improve to date with only 10% BSA remaining after 11 months of therapy and with no adverse events.Case 2A 46-year-old man with Fitzpatrick skin type 4 and an approximate 10-year history of vitiligo predominantly of the back and hands presented to a rheumatologist for treatment of psoriatic arthritis. He was initiated on methotrexate for his arthritis, titrated up to 25 mg per week with folic acid supplementation.