Vitiligo in a Patient with Rheumatoid Arthritis under Methotrexate

One of our patients with rheumatoid arthritis is suffering from concomitant vitiligo. Vitiligo is a condition of sectional depigmentation of the skin. As melanocytes might only have a functional problem, medications might have an effect. As caspases and interleukin-1ß are overexpressed in patients with vitiligo, medications that inhibit this overexpression might work. There has been a letter to the editor in the Indian Journal of Dermatology in 1998 (Sandra A, Pai S, Shenoi SD. Unstable vitiligo responding to methotrexate. Indian J Dermatol Venereol Leprol 1998;64:309 – Link: http://www.ijdvl.com/article.asp?issn=0378-6323;year=1998;volume=64;issue=6;spage=309;epage=309;aulast=Sandra), which addressed the question of methotrexate and vitiligo. I have searched the PubMed data base, which only yielded references to some German articles during the 1970ies.

The patient is 48 years old, RF just positive, ACPA 78 IU/ml, low 25-OH Vitamin D. X-ray charts didn’t show any erosions. Start of 15 mg methotrexate s.c. in March 2012, 5 mg folate 48 hours after methotrexate. Follow-ups showed low disease activity; DAS28 2.81 in June 2012 and 3.15 in October 2012, 2.80 in October 2013, and X.XX now.

Both patient and I think that areas of vitiligo have been diminished during therapy with methotrexate. So methotrexate might help in patients with intact melanocytes that ceased to work under influence of overexpressed interleukin-1ß.
Thanks for allowing the pictures to be published.

Vitiligo in October 2012

Vitiligo in January 2013

PS. please tell me if you have made the same observation.

24.07.2013
Yesterday the patient showed up for a routine check. She's still taking 15 mg MTX s.c.
And here's the picture of her hands:

Definitely a larger area with pigmentation. The new pigmentation is more intense than the pigmentation of the non vitiligo area.

16.10.2013
Today the patient showed up for a routine check. She's still taking 15 mg MTX s.c.
And here's the picture of her hands:

Even more and larger repigmented areas! The left hand has gained quite a lot.

04.02.2014:
Another routine check. The rheumatoid arthritis is still good under methotrexate. We have just looked at the photographs here. The hands have gained more in repigmentation, but as there is no exposure to sunlight right now, we didn't take a new photograph, but we'll do so in three months.

13.05.2014:
This routine check didn't show any big differences. Some areas seem a little larger others smaller. All in all there still is vitiligo to be seen. Medication didn't change.

20.06.2014:
There has been an article on alopecia universalis, in which the process has been reversed under tofacitinib. 

"Hairless Man Grows Full Head Of Hair In Yale Arthritis Drug Trial" http://boston.cbslocal.com/2014/06/19/hairless-man-grows-full-head-of-hair-in-yale-arthritis-drug-trial/. Maybe this (unknown) mechanism of tofacitinibis is also working in vitiligo. 

There  has been an interesting study at the EULAR 2014 Meeting in Paris by L. Mery-Bossard and colleagues [THU0165]: "NEW ONSET VITILIGO UNDER BIOLOGICAL AGENTS: A CASE SERIES", which I'll discuss later in detail.

24.06.2014:

I’ve found this interesting poster on vitiligo at the EULAR 2014 Meeting in Paris. It is related to the findings in our patient as the patients described were also receiving DMARDs, not methotrexate but biologics. The patients in the study were developing non-segmental vitiligo. TNF-alpha plays a role in the pathogenesis, so that patients have been treated with TNF-alpha-inhibitors. Maybe methotrexate works in our patient in the same. But the case series showed the development of vitiligo as a paradox side effect of biologics. I see a parallel to the development of psoriasis under TNFi, as these are also successfully used to treat psoriasis.

[THU0165]

NEW ONSET VITILIGO UNDER BIOLOGICAL AGENTS: A CASE SERIES

L. Mery-Bossard 1, G. Chaby 2, F. Maccari 3, N. Quiles 4, Z. Reguiai 5, A. Khemis 6, A. Grasland 7, D. Jullien 8, J. Sibilia 9, E. Toussirot 10.

1Dermatology, Centre Hospitalier, Mantes la Jolie; 2Dermatology, University Hospital, Amiens; 3Dermatology, HIA Begin, St Mande; 4Dermatology, Hopital St Joseph, Marseille; 5Dermatology, University Hospital, Reims; 6Dermatology, University Hospital, Nice; 7Internal Medicine, University Hospital, Colombe; 8Dermatology, University Hospital, Lyon; 9Federation de Medecine Translationnelle, INSERM UMR1110 University hospital, Strasbourg; 10Clinical Investigation Center Biotherapy, University Hospital, Besancon, France

Conclusions: experimental evidences have shown that TNF-α may play a role in the pathogenesis of non segmental vitiligo, and successful cases of vitiligo treated with TNFα inhibitors have been reported. However, a vitiligo may occur during a biological treatment. In this series, anti TNFα was the main (but not exclusive) biologic class associated with this event. Only non segmental vitiligo was observed allowing the maintenance of the treatment. Concomitant occurrence of vitiligo and inflammatory disease such as RA, AS or CD, although rare, has been described. On the other hand, the depigmentation may be related to the biological agent and could represent a new paradoxical side effect.

DOI: 10.1136/annrheumdis-2014-eular.2560

I'd like to thank the authors for allowing to use the picture of the poster here.

17.10.2014:
Today I saw the patient again for a routine visit. The rheumatoid arthritis is still in remission under MTX. The vitiligo hasn't changed since the last photograph. But she developed teleangiectasia (spider angioma / nevus araneus). We'll pause methotrexate as she is in remission concerning RA.

14.09.2015:
Again the patient showed up for a routine visit. MTX has been stopped nearly a year ago. The rheumatoid arthritis shows low activity. The vitiligo has worsened since the last photograph; please see below:

10.11.2016:
In the meantime, I've seen another patient with vitiligo. She is suffering from ankylosing spondylitis and we treat her with infliximab since 2010. The vitiligo had developed in the wake of another (unknown) skin disease. She observed an on/off mode of depigmentation and pigmentation. Interestingsly during the winter half year there's more pigmentation than in the summer half year. No fluctuations occuring with infliximab.
Thanks very much for allowing the pictures to be published.

Vitiligo at the 3rd of June 2015

Vitiligo at the 9th of November 2016