Importance]
Observations]
Conclusions and Relevance]
INTRODUCTION
Vitiligo is a condition that often causes significant psychological distress for patients. Treatment options are limited and often inadequate. Recent progress in the scientific understanding of vitiligo suggests that Janus kinase (JAK) inhibitors may be an effective therapy. We report a case of vitiligo treated with the JAK 1/3 inhibitor tofacitinib citrate.
REPORT OF A CASE
A woman in her 50s presented for evaluation and management of vitiligo, which had been widespread and progressive for approximately the past 1 year. Increasing involvement of the face and hands was causing the patient significant concern. She had used triamcinolone ointment, 0.1% (owing to the need for a large amount of topical medication in the setting of generalized involvement), and tacrolimus ointment, 0.1%, without effect. Treatment with narrowband UV-B phototherapy had recently been initiated; however, after 3 treatments, the patient continued to note progression of the vitiligo and therefore sought a second opinion regarding treatment. She was otherwise healthy and denied a family history of vitiligo or other autoimmune conditions. Complete review of systems was negative. Physical examination revealed innumerable white macules and patches involving the forehead (Figure 1A), trunk, and extremities (Figure 2A) involving approximately 10% of body surface area, which highlighted with Wood’s lamp.
The possibility of continuing phototherapy was discussed, including the typically months-long duration of treatment that is required to achieve repigmentation, which is usually incomplete.1 Given the progressive, generalized nature of the vitiligo, the limited and often inadequate treatment options, and the patient’s associated concern, we decided to pursue a therapeutic trial of an agent that, based on recent advances in the understanding of vitiligo,2 might yield faster and more complete repigmentation.
Treatment with oral tofacitinib citrate (Xeljanz) was initiated at a dosage of 5 mg every other day. After 3 weeks, the dosage was increased to 5 mg/d (half the approved dosage for rheumatoid arthritis, which is 5 mg twice daily). After 2 months of therapy, partial repigmentation of the face and upper extremities was evident. After 5 months, repigmentation of the forehead (Figure 1B) and hands (Figure 2B) was nearly complete, and the remaining involved areas demonstrated partial repigmentation. Approximately 5% of the total body surface area remained depigmented. The patient tolerated tofacitinib without adverse effects, and results of laboratory monitoring revealed no abnormalities in complete blood cell count, serum creatinine, hepatic function, or lipids during the course of treatment.
DISCUSSION
Tofacitinib is a JAK 1/3 inhibitor that was approved by the US Food and Drug Administration in 2012 for the treatment of moderate to severe rheumatoid arthritis. Within dermatology, oral and topical formulations of tofacitinib have been demonstrated to be safe and effective for the treatment of plaque psoriasis,3- 7 and we have recently described the success of oral tofacitinib in treating alopecia universalis.8 Clinical trials evaluating tofacitinib treatment of several disorders are presently under way.
Alopecia areata and vitiligo share genetic risk factors and can co-occur within families and individual patients, suggesting a common pathogenesis.9 As such, it is not surprising that a medication that has been shown to be effective in treating alopecia areata8 may also be effective in treating vitiligo. Moreover, recent advances in the scientific understanding of vitiligo support the use of JAK inhibitors for this condition. Interferon-gamma–induced expression of C-X-C motif chemokine 10 (CXCL10) in keratinocytes is an important mediator of depigmentation in vitiligo.2 Antibody neutralization of interferon gamma or CXCL10 reverses depigmentation.10 We propose that because interferon gamma signal transduction occurs through JAK 1/2,11 the use of the JAK 1/3 inhibitor tofacitinib effectively leads to blockade of interferon gamma signaling and downstream CXCL10 expression, thus giving rise to repigmentation in vitiligo.
To our knowledge, this report is the first to demonstrate effective pathogenesis-based therapy for a patient with vitiligo. The fairly rapid response and the repigmentation of the hands, which are often resistant to therapy, are noteworthy. Further investigation of the efficacy and safety of tofacitinib in the treatment of patients with vitiligo, including those for whom the condition has been more long-standing, will be important. Although uncommon, serious adverse effects, including malignant disease, have been reported in patients taking tofacitinib; therefore, investigation of the efficacy of a topical formulation for the treatment of localized vitiligo would be useful.
This case exemplifies the ways by which advances in basic science can guide treatment decisions and ultimately benefit patients. As we better understand the pathomechanisms of different diseases, targeted therapy becomes possible, and existing medications can be repurposed and/or new medications created for diseases with limited, if any, treatment options.
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That's some extremely promissing stuff, if you ask me.
Re: new Vitiligo treatment, that actually works (repigmentation)
I read about these a while back. There was another woman who regained all her hair within two weeks of taking a similar kinase inhibitor,( alopecia areata is what she had)I looked up whether this could be used as a vitiligo treatment even before this study was released and its possible. The way they put it though was that the inhibitors are suppressing far too much for it too be considered worthwhile. Dropping a nuke on a city to kill one man effectively speaking. Theyre trying to find the "switch" further down the autoimmune pathway to "turn off" these specific autoimmune diseases but it doesn't seem they're all to close. Still interesting though definitely
This was a very interesting article. I am glad I had the opportunity to read it. I am going to be keeping an eye out for this. I have a lot of psychological stress and am having difficulty in finding anything that will relieve it. I am wanting to have something that is more natural than Prozac. I do not think this is the best medicine for anyone, especially long term.
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Thanks for posting this article, vitiligo really fascinates me since I feel like I've noticed it on a lot more people? My ex had it, as did a roommate, and a coworker, and it just seems not as uncommon as people say. I've always been mystified that there doesn't seem to be a cure for it, but that article definitely shows that progress has been made. Pretty exciting.
Thanks for the article. It is a really interesting read and I never knew how effective vitiligo was. I think the side effects might defer some people though.
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