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Indian J Dermatol
Indian J Dermatol
IJD
Indian J Dermatol
Indian Journal of Dermatology
0019-5154
1998-3611
Wolters Kluwer - Medknow India

IJD-69-366b
10.4103/ijd.ijd_515_23
E–IJD®: Correspondence
Use of Oral Tofacitinib in the Treatment of Pediatric Vitiligo: A Case Series
Biswal Anisha
Agrawal Ishan 1
Panda Maitreyee
From the Department of Skin and VD, IMS and SUM Hospital, Bhubaneswar, Odisha, India E-mail: pandamaitreyee@gmail.com
1 Department of Skin and VD, Maulana Azad Medical College, New Delhi, India
Jul-Aug 2024
19 8 2024
69 4 366366
8 2023
4 2024
Copyright: © 2024 Indian Journal of Dermatology
2024
https://creativecommons.org/licenses/by-nc-sa/4.0/ This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.
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pmcDear Editor,

Vitiligo causes depigmentation by progressive autoimmune melanocyte destruction. Paediatric patients account for 26% of cases, and peak onset is between 4 and 8 years. Available treatment modalities include corticosteroids, calcineurin inhibitors and narrow-band ultraviolet B (NB-UVB) phototherapy.[1] Recently, Janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibitors have been effective in treating vitiligo. However, its use in children is limited. Recent findings indicate JAK-STAT pathway involvement in vitiligo pathogenesis, driven by CD8+ T cells producing IFN-γ via the JAK1/2 pathway. This leads to the expression of CXCL9 and CXCL10 in keratinocytes, further damaging the melanocytes. Tofacitinib, a JAK 1/3 inhibitor, effectively blocks these pathways, showing promise in vitiligo treatment. Originally approved for rheumatoid arthritis, tofacitinib is now used in various dermatological conditions. Few case reports have been published showing repigmentation with oral tofacitinib and sun exposure.[2] We enrolled 13 patients of progressive vitiligo with inclusion criteria being, failure to topical treatment >3 months, oral steroids and cyclosporine >6 weeks, no significant improvement in vitiligo extent score (VES), progressive, non-segmental resistance to treatment cases and excluded patients with a history of any recent live vaccination, active infection or malignancy. Relevant baseline investigations like complete blood count, liver function test, renal function test, lipid profile, Mantoux test, TB QuantiFERON Gold, chest X-ray and Triple H. Patients were started with oral tofacitinib 5 mg twice daily along with sun exposure for 5 to 10 minutes at 8 am. There was gradual dose tapering in 3 to 6 months. Follow-up was done for another 6 months. The response evaluation was assessed by VES at baseline and 6 months. The dermoscopy finding at baseline showed a decreased pigment network and no perilesional pigmentation, and after 6 months of therapy, there was a significant increase in the perilesional and perifollicular pigmentation along with background erythema. The details of all the patients enrolled with their efficacy and safety profiles are depicted in Table 1. The literature regarding the use of tofacitinib in paediatric vitiligo is limited. There is a single case report in paediatric age, where segmental vitiligo was treated successfully with a combination of topical 2% tofacitinib and phototherapy for 3 months.[3] Phan et al. explained the synergistic action of JAK inhibitors with phototherapy.[4] JAK inhibitors suppress the CD8+ T cells and IFN-γ.[5] Joshipura et al. reported rapid improvement in facial vitiligo when treated with a combination of systemic tofacitinib and low-dose NB-UVB phototherapy. Additionally, they reported a comparatively better response over photo-exposed areas.[5] Common systemic side effects include upper respiratory tract infections, nasopharyngitis, transient cytopenias and dearranged lipid profiles. Cutaneous side effects like acne, acneiform eruptions, eczema herpeticum and herpes zoster have been reported recently with JAK inhibitors. In our case series, at the end of 6 months out of 13 patients, TWO Patients showed near complete pigmentation, six patients showed 70–80% repigmentation, one patient was lost to follow-up, and four patients were unresponsive to therapy. Sun-exposed areas responded better than covered areas. Overall the VES score showed significant improvement. After 6 months of treatment with tofacitinib 5 mg twice daily, the dose was tapered to 5 mg once daily for 3 months and then it was stopped. Patients were followed up for 6 months for any side effects or reappearance of lesions. One patient showed the reappearance of vitiligo lesions in the follow-up period and one patient reported grade 2 acne post-3 months of tofacitinib indicating the role of JAK signalling in the expression of acne. We did not encounter any other major side effects. Although serious side effects including lymphoproliferative disorders are uncommon, they need to be addressed and the patient needs to be counselled regarding the same.[5] Our case series suggests tofacitinib monotherapy is a safe and effective treatment modality for paediatric vitiligo. In cases where the immune response in vitiligo patients is significantly suppressed, the need for standard UV radiation therapy two or three times a week may be reduced. Lower UV fluences can still stimulate repigmentation. Larger prospective studies with longer follow-ups are required to confirm the efficacy, long-term safety and durability of treatment response.

Table 1 Case description

Case	Age/Sex	Duration	Part involved.	Family history	Previous Treatment	Treatment response	VES score.	Side effects reported.	
1.	6/F	2 years	vulvam	No history of Autoimmune disorder or any family member affection.	Topical steroids and calcineurin inhibitors.	Near-complete repigmentation with 6 months of therapy of tofacitinib 5 mg BID [Figure 1]	Baseline: 0.822 Post-treatment: 0.057	No side effects with 6 months of therapy. No change in CBC, Lipid profile and LFT.	
2.	16/M	8 months	Lateral side of bilateral feet, neck and posterior trunk.	Mother	Topical steroids, PUVA.	response with tofacitinib 5 mg BID	Baseline: 0.485 Post-treatment: 0.05	No side effects with 3 months of therapy. No alteration in CBC, lipid profile and LFT from baseline.	
3.	12/M	6 months	Trunk and bilateral limbs.	None	Topical steroids, calcineurin inhibitors	Complete response with 5 months of therapy.	Baseline: 1.955 Post-treatment: 0.74	No reported side effects with 3 months of therapy. No significant change in the CBC, lipid profile and LFT from baseline.	
4.	15 yr/F	9 months	face and chest	None	Topical corticosteroids	Complete pigmentation within 6 months of therapy with tofacitinib 5 mg BID [Figure 3]	Baseline: 1.08 Post-treatment: 0.2	Grade 2 acne post-3 months of tofacitinib Treated with oral doxycycline 100 BID. No other side effects seen.	
5.	14 year/F	4 months	face and bilateral lower leg	mother	Topical steroids	Complete response within 5 months of therapy	Baseline: 1.04 Post-treatment: 0.2	No side effects reported, no change in CBC, lipid profile and LFT	
6.	7 year/F	1 year	Forehead with poliosis	No family history	Topical steroids, PUVA	Complete Response within 7 months with tofacitinib 5 mg BID Persistence of white hairs	Baseline: 0.9 Post-treatment: 0.1	No side effects within 7 months of therapy No change in haematological parameters from baseline	
7.	6 year/F	8 months	upper eyelid and bilateral lower leg	No family history	Topical steroids, calcineurin inhibitors	Near complete pigmentation within 6 months of therapy with tofacitinib 5 mg BID	Baseline: 1.4 Post-treatment: 0.2	No side effects within 6 months of therapy. No change in haematological parameters from baseline	
8.	13 yr/M	7 months	Bilateral lower leg	No family history	Topical steroids	Complete pigmentation within 6 months of therapy with tofacitinib 5 mg BID [Figure 2]	Baseline: 1.03 Post-treatment: 0.2	No side effects within 6 months of therapy No change in haematological parameters	
9.	9 years/f	1 year	Bilateral upper eyelid and left inner thigh	No family history	Topical corticosteroids	Lost to follow-up after 2 months of therapy with tofacitinib 5 mg BID	Baseline: 1.04 Post-treatment: lost to follow-up	No side effects till 2 months of therapy	
10.	10 yr/M	1 year	Bilateral upper eyelid	No family history	Topical steroids	No response after 6 months of therapy with tofacitinib 5 mg BID	Baseline: 1.02 Post-treatment: 0.8	No side effects within 6 months of therapy. No change in Cbc, lft, Lipid profile from baseline	
11.	13 year/F	8 months	Behind neck (nape), chest near clavicle	No family history	Topical steroids and calcineurin inhibitors	No response after 4 months of therapy with tofacitinib 5 mg BID	Baseline: 1.06 Post-treatment 4 months: 0.9	Mildly dearranged lipid profile so patient was asked to stop tofacitinib. And was not included in the study.	
12.	12 year/F	1 ½ year	Sternum area (chest)	No family history	Topical steroids and calcineurin inhibitors	No response after 6 months of therapy with tofacitinib 5 mg BID	Baseline: 1.0 Post-treatment 6 months: 0.8	No side effects within 6 months of therapy, Non hematological parameters change from baseline	
13.	11 year/F	3 years	Bilateral feet	No family history	No treatment was taken except ayurvedic medications	No response after 6 months of therapy with tofacitinib 5 mg BID	Baseline: 0.9 Post-treatment: 0.5	No side effects within 6 months of therapy, Noheamatological parameters change from baseline	

Figure 1 Case 1 images. (a) A single depigmented patch over vulva (Baseline). (b) Complete repigmentation of the patch after 6 months of tofacitinib 5 mg BID

Figure 2 Case 8 images. (a) Depigmented patches over bilateral legs and knee (Baseline). (b) Complete repigmentation of the patches after 6 months of tofacitinib 5 mg BID

Figure 3 Case 4 images. (a) Multiple ill-defined depigmented patches over face and chest (Baseline). (b) Near complete repigmentation of the patches after 6 months of tofacitinib 5 mg BID

Declaration of patient consent

Informed consent was taken from the patient for using the clinical data and publication of photographs after ensuring anonymity.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.
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1 Vu M Heyes C Robertson SJ Varigos GA Ross G Oral tofacitinib: A promising treatment in atopic dermatitis, alopecia areata and vitiligo Clin Exp Dermatol 2017 42 942 4 29034491
2 Liu LY Strassner JP Refat MA Harris JE King BA Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require concomitant light exposure J Am Acad Dermatol 2017 77 675 82 28823882
3 Olamiju B Craiglow BG Tofacitinib cream plus narrowband ultraviolet B phototherapy for segmental vitiligo in a child Pediatr Dermatol 2020 37 754 5 32255214
4 Phan K Phan S Shumack S Gupta M Repigmentation in vitiligo using januskinase (JAK) inhibitors with phototherapy: Systematic review and meta-analysis J Dermatolog Treat 2022 33 173 7 32096671
5 Joshipura D Plotnikova N Goldminz A Deverapalli S Turkowski Y Gottlieb A Importance of light in the treatment of vitiligo with JAK-inhibitors J Dermatolog Treat 2018 29 98 9 28581823
