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Observation
April 2016

Topical Ruxolitinib for the Treatment of Alopecia Universalis

Author Affiliations
  • 1Department of Dermatology, Yale University School of Medicine, New Haven, Connecticut
  • 2Quality Care Drug, Centerbrook, Connecticut
JAMA Dermatol. 2016;152(4):490-491. doi:10.1001/jamadermatol.2015.4445

Alopecia areata and variants alopecia totalis and alopecia universalis are common conditions for which treatment options are limited. Oral Janus kinase (JAK) inhibitors have recently been shown to be effective for the treatment of these disorders. There are, however, risks for serious adverse effects with systemic therapy that may be avoided if topical therapy were an option.

Report of a Case

A patient in her late teens presented for evaluation and management of alopecia universalis. Treatment with prednisone, intralesional triamcinolone, sulfasalazine, topical squaric acid dibutylester, and topical anthralin had been ineffective. The patient had not had any treatment in the previous 2 years. She was otherwise healthy and took no medications. There was no family history of alopecia areata or other autoimmune disease. Findings from a complete review of systems were negative. On examination, there was complete absence of scalp and arm hair and only sparse hair growth of the right lateral eyebrow (Figure, A).

Figure.
Eyebrows Before and After Treatment With Topical Ruxolitinib, 0.6%, Cream
Eyebrows Before and After Treatment With Topical Ruxolitinib, 0.6%, Cream

A, At baseline, there is sparse hair growth of the right lateral eyebrow only (eyebrows are drawn in with makeup). B, After 12 weeks of treatment, the right eyebrow is normal, and there has been significant regrowth of the left eyebrow.

In light of the recent successful treatment of alopecia areata and variants with the JAK inhibitors tofacitinib1 and ruxolitinib,2 these were discussed as therapeutic options. Apprehensive of the potential risks of these medications, the patient and her parents decided to pursue a trial of a topical JAK inhibitor. Topical formulations of both tofacitinib and ruxolitinib have been demonstrated to be effective in reversing disease in a murine model of alopecia areata,2 and topical tofacitinib ointment has been demonstrated to be well tolerated and effective for the treatment of plaque psoriasis.3 To our knowledge, the use of topical JAK inhibitors has not yet been explored for the treatment of alopecia areata and variants in humans.

Results of baseline laboratory tests, including QuantiFERON-TB Gold (Quest Diagnostics), human immunodeficiency virus, and hepatitis B and C blood tests were negative, and a complete blood cell count and comprehensive metabolic panel were within normal limits, though the white blood cell (WBC) count was borderline low at 4500/μL (normal, 4500/μL-13 000/μL) (to convert WBC to ×109/L, multiply by 0.001).

The patient began treatment with topical ruxolitinib, 0.6%, cream twice daily to the scalp and eyebrow regions. After 12 weeks of treatment, the eyebrows were nearly normal (Figure, B), and there was growth of about 10% of scalp hair with numerous 5- to 10-mm darkly pigmented hairs in arcuate and annular patches distributed over the entire scalp. The patient tolerated the medication without adverse effects. Laboratory monitoring at weeks 4, 8, and 12 demonstrated a small, stable decrease in WBC count at 3800/μL , 4100/μL , and 3800/μL, respectively. Otherwise, there were no abnormalities in complete blood cell count or renal or liver function.

Discussion

To our knowledge, this is the first report of successful treatment of alopecia universalis with a topical JAK inhibitor. While additional studies will be needed to confirm the efficacy, further explore the safety and tolerability, and determine optimal concentrations of topical ruxolitinib and other topical JAK inhibitors for alopecia areata and variants, the results in this case are promising. Although uncommon, serious adverse effects including cancer have been reported in patients taking oral JAK inhibitors. In the case of the present patient, the small decrease in WBC count after starting topical ruxolitinib treatment is suggestive of systemic absorption; however, the patient’s baseline WBC count was borderline low, and so causality is difficult to assess.

Topical JAK inhibitors represent an exciting new treatment opportunity for an often psychologically devastating condition. Given the likely more favorable safety profile associated with topical administration, their use may be considered in patients for whom the potential for serious adverse effects makes oral administration unattractive, most notably the pediatric population.

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Article Information

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

Published Online: December 9, 2015. doi:10.1001/jamadermatol.2015.4445.

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

Additional Contributions: We thank the patient for granting permission to publish this information.

References
1.
Craiglow  BG, King  BA.  Killing two birds with one stone: oral tofacitinib reverses alopecia universalis in a patient with plaque psoriasis.  J Invest Dermatol. 2014;134(12):2988-2990.PubMedGoogle ScholarCrossref
2.
Xing  L, Dai  Z, Jabbari  A,  et al.  Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition.  Nat Med. 2014;20(9):1043-1049.PubMedGoogle ScholarCrossref
3.
Ports  WC, Khan  S, Lan  S,  et al.  A randomized phase 2a efficacy and safety trial of the topical Janus kinase inhibitor tofacitinib in the treatment of chronic plaque psoriasis.  Br J Dermatol. 2013;169(1):137-145.PubMedGoogle ScholarCrossref
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