INTRODUCTION
Tofacitinib is a Janus kinase (JAK) 1-3 inhibitor first U.S. Food and Drug Administration (FDA) approved in 2012 for rheumatoid arthritis, with subsequent approval for psoriatic arthritis, ulcerative colitis, polyarticular course juvenile idiopathic arthritis, and ankylosing spondylitis in 2017, 2018, 2020, and 2021, respectively.1,2 In the last several years, oral tofacitinib has become an increasingly utilized treatment option for immune-mediated skin conditions such as alopecia areata (AA), vitiligo, plaque psoriasis, and atopic dermatitis; however, it is not FDA approved for these diseases.3,4 These conditions’ pathophysiology involves an interplay of cytokines and interleukins in which the JAK-signal transducer and activation of transcription (STAT) signaling pathway has a role.5
AA and vitiligo are largely TH1 and interferon-gamma driven diseases.6 In AA, CD8+ T cells produce interferon-gamma which leads to collapse of immune privilege and increased production of IL-15, propagating autoimmune destruction of the hair follicle.6 In vitiligo, an autoimmune disease in which melanocytes are destroyed resulting in de-pigmentation, interferon-gamma induces expression of the C-X-C motif in chemokine-10 (CXCL10) in immune cells, leading to melanocyte destruction and depigmentation.7 Notably, interferon-gamma mediates its effects through the JAK-STAT pathway.5,8 Due to the relationship between AA and vitiligo with interferon gamma and the JAK-STAT pathway, JAK inhibitors, such as tofacitinib, are an appropriate choice for targeted therapy of these conditions. In this case report, we present a patient with concomitant AA and non-segmental vitiligo who was treated with oral tofacitinib. The autoimmune components of both diseases and similar pathophysiology cause AA and vitiligo to occur together more often than one would expect by chance; with approximately 3-8% of patients with AA having concomitant vitiligo.9 The patient in this report attempted multiple different treatment regimens with minimal improvement, however, upon initiation with tofacitinib, had moderate to significant improvement in both her AA and vitiligo, with no reported side effects.
CASE REPORT
DISCUSSION
Only two case reports exist in the literature of patients with concomitant alopecia areata and vitiligo who were treated with tofacitinib.1,3 Of those cases, one patient additionally had inverse plaque psoriasis, while the other patient additionally had atopic dermatitis. In both of these cases, tofacitinib was effective; however, it was utilized as adjunctive therapy rather than monotherapy. In our case report, we present a patient treated with low-dose tofacitinib monotherapy. Our patient’s response to tofacitinib monotherapy is similar to that of other patients on multiple treatments, where clinical response was observed as quickly as 2 months with significant improvement reached around 6-8 months of treatment.1
Tofacitinib is well studied in AA with improvement rates of >50% in 30-60% of patients on tofacitinib 5 mg BID.10-12 In vitiligo, the use of tofacitinib is less studied with some patients reporting marginal improvement and others reporting near complete repigmentation.1,7,13-16 In these reports, tofacitinib is commonly used concordantly with ultraviolet B phototherapy. In general, patients have greater improvement in areas of sun exposure or those additionally treated with phototherapy. Nonetheless, our patient had good improvement in her hand vitiligo, with minimal reported sun exposure and no additional phototherapy.
The use of JAK inhibitors off-label has become increasingly utilized and is effective for the treatment of AA, vitiligo, and other immune-mediated diseases. While JAK inhibitors are associated with several Black Box warnings and require careful monitoring, they may be a suitable alternative for patients refractory to previous treatments. In particular, in the few patients in the literature who have concomitant AA and vitiligo, tofacitinib appears to be an effective treatment option.
DISCLOSURES
REFERENCES
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SOURCE
Content and images used with permission from the Journal of Drugs in Dermatology.
Adapted from original article for length and style.