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April 2016

Tofacitinib Citrate for the Treatment of Nail Dystrophy Associated With Alopecia Universalis

Author Affiliations
  • 1Albany Medical College, Albany, New York
  • 2Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut
JAMA Dermatol. 2016;152(4):492-493. doi:10.1001/jamadermatol.2015.3772

Nail dystrophy associated with alopecia areata (AA) and variants alopecia totalis and alopecia universalis (AU) may cause discomfort or pain and limitation of function. Currently, no reliably effective treatment options are available.1 The successful treatment of AA and variants with the oral Janus kinase (JAK) inhibitors tofacitinib, ruxolitinib, and baricitinib2-4 suggests the possibility that this class of agents may be a therapeutic option for nail dystrophy associated with AA.

Report of Cases

We describe 3 patients with AU with severe nail dystrophy who experienced normalization of nail growth during treatment with tofacitinib, a JAK-1/3 inhibitor.

Case 1

Patient 1 was a man in his 20s who presented with AU and trachyonychia causing substantial discomfort (Figure, A). He was treated with tofacitinib, 5 mg, twice daily for 2 months and then, because he was not experiencing hair growth, 10 mg in the morning and 5 mg at night for the next 4 months.

Figure.  Clinical Images of Alopecia Universalis–Associated Trachyonychia Before and After Treatment With Tofacitinib Citrate
Clinical Images of Alopecia Universalis–Associated Trachyonychia Before and After Treatment With Tofacitinib Citrate

A, Brittle, thin nails with longitudinal ridging involving the fingers (thumbs shown) of patient 1 prior to treatment. B, Near resolution of nail abnormalities is visible after 5 months of treatment with tofacitinib.

Case 2

Patient 2 was a woman in her 40s who presented with AU and frequent episodes of onycholysis for which she needed to keep 1 or 2 fingertips wrapped with tape daily. She was treated with tofacitinib, 5 mg, twice daily.

Case 3

Patient 3 was a man in his 20s who presented with AU and severe nail pitting and nail fragility that was the cause of frequent painful injury. He was treated with tofacitinib, 5 mg, twice daily.

The results of baseline laboratory evaluation, including complete blood cell count, comprehensive metabolic panel, lipid panel, QuantiFERON-TB Gold (Quest Diagnostics), and human immunodeficiency virus, hepatitis B, and hepatitis C blood tests, were normal in all 3 patients.

All 3 patients experienced remission of nail changes and associated discomfort or pain during treatment with tofacitinib over a period of 5 to 6 months (Figure, B). Interestingly, patients 2 and 3 also experienced hair growth, but patient 1 (Figure) did not. Ten weeks after discontinuation of tofacitinib treatment, patient 1 did not exhibit recurrence of nail dystrophy. Patients 2 and 3 continued to take tofacitinib. Tofacitinib was well tolerated in all cases, and infections, cytopenias, transaminitis, decreased renal function, or increased lipid levels were not observed.


Nail dystrophy in AA and variants is common, affecting 7% to 66% of patients, and includes nail pitting, trachyonychia, onychorrhexis, red spotting of the lunulae, onycholysis, onychomadesis, and Beau lines.5 Little is known about the pathogenesis of these changes.1,5 Recently, it has been shown that hair follicle gene expression of interleukin-15, NKG2D ligands, and major histocompatibility complex molecules leads to recruitment and activation of interferon γ–producing, NKG2D-expressing CD8 T cells that target the hair follicle for attack. Because JAK family protein kinases are downstream effectors of the interferon γ receptor in keratinocytes, JAK signaling mediates interleukin 15 activation of T cells, explaining the effectiveness of JAK inhibitors for the treatment of AA.2-4 The nail matrix, like the hair follicle, is an epithelial keratin-producing structure, and it may be that nail matrix keratinocytes exhibit gene expression similar to hair follicle keratinocytes in AA. In this case, JAK inhibitors would be expected to reverse nail dystrophy associated with AA.

The outcomes in the 3 patients described here suggest that tofacitinib and other JAK inhibitors may be effective in the treatment of severe nail dystrophy associated with AA and variants. Additional studies will be needed to confirm their efficacy and further explore their safety.

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Article Information

Corresponding Author: Brett A. King, MD, PhD, Department of Dermatology, Yale University School of Medicine, PO Box 208059, New Haven, CT 06520 (brett.king@yale.edu).

Published Online: December 2, 2015. doi:10.1001/jamadermatol.2015.3772.

Conflict of Interest Disclosures: Dr King has served on an advisory board for Pfizer. No other conflicts are reported.

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