Letters
RESEARCH LETTER
Treatment of Alopecia Areata
With Tofacitinib
Tofacitinib citrate is a Janus kinase 1/3 inhibitor approved for
the treatment of rheumatoid arthritis, but it has recently been
used to treat alopecia areata (AA).1-3 In this study, investiga-
tors searched the medical records of the Cleveland Clinic for
any patients with confirmed AA who were treated with oral
tofacitinib (Xeljanz; Pfizer) using a standardized, systematic
treatment regimen.
Methods | A standard departmental treatment protocol was de-
veloped prior to this review. Treatment with tofacitinib ci-
trate was initiated at 5 mg twice daily, and all other AA thera-
pies were ceased. The daily dosage was increased, as allowable
by insurance coverage, by 5 mg per month until the treating
physician noted first signs of hair regrowth and then held the
medication at that dose. The Cleveland Clinic Foundation In-
stitutional Review Board approved this retrospective medi-
cal record review and waived the patient informed consent
requirement. The review took place from May 1, 2016, to June
1, 2016.
Scalp hair loss was calculated from visit to visit by the
same treating physician (M.P. or W.B.) using the validated
Severity of Alopecia Tool (SALT)4 score, which can range
from 0% to 100%; the higher the score, the greater the
amount of scalp hair loss. In all, patients were treated by 2
different physicians (M.P. and W.B.) from January 10, 2015,
to April 30, 2016.
Figure. Case of Alopecia Totalis Responsive to Oral Tofacitinib Citrate
A Before treatment B After 3 mo of treatment with tofacitinib
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Results | We identified 13 patients with AA who were or are being
treated with tofacitinib. The mean (SD) pretreatment scalp hair
loss was 93% (11.5), with 2 patients having alopecia totalis
(Figure, A) and 7 patients having alopecia universalis. Re-
growth rate—(final SALT score − initial SALT score)/(initial SALT
score) × 100—ranged from 2% to 90%, with a mean (SD) of
44.3% (31.9) and a median (range) of 50.5% (90 [0-90]) (Table).
Seven patients (53.8%) achieved a regrowth of at least 50%
(Figure, B). Response time—time from initiation of treatment
to any sign of hair regrowth—ranged from 1 to 9 months, with
a mean (SD) of 4.2 (2.6) months.
One patient developed a morbilliform eruption and
peripheral edema that led to medication withdrawal. Two
patients stopped therapy after 3 months because of loss of
insurance and within 2 weeks experienced a shed that led
back to baseline levels. The remaining 11 patients continued
treatment. Of note, 2 patients demonstrated lipid and liver
abnormalities that were resolved when the dose was
reduced (Table).
Discussion | Janus kinase inhibitors have been shown to attenu-
ate the inflammatory cascade associated with AA.1 Our results
indicate that tofacitinib is efficacious in the treatment of AA.
Although small, our cohort achieved greater median improve-
ment in SALT scores than reported in previously published stud-
ies (50.5% vs 21%).3 This outcome may be related to our higher
doses, longer duration of therapy, and patients’ shorter dura-
tion of current disease episode. In addition, our results dem-
onstrate lack of durability of effect after the discontinuation of
therapy, a finding similar to that in other studies.3
Patient 7 presented with alopecia
totalis (A) and attained 90%
regrowth (B) after 3 months of
treatment with oral tofacitinib.
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Table. Treatment Record of Patients With Alopecia Areata Taking Oral Tofacitinib Citrate
Scalp
Scalp Involvement at
Duration Holding Involvement at Final
Patient of Disease Duration of Duration Dosage Baseline, Follow-up,
No./ Failed (Since AA AT or AU of Therapy, (Split Twice SALT SALT Regrowth, Adverse
Sex/Age Therapies Diagnosis), y Episode, y mo Daily), mg/d Score, % Score, % % Events
1/F/20s TC, ILC, MTX, 16 4 7 20 100 (AU) 90 10 None
DPCP
2/M/20s TC, ILC 5 1.5 4 10 100 (AU) 100 0 None
3/F/30s MTX, Infx, TC, 8 3 12 15 100 (AU) 98 2 Liver enzyme
DPCP abnormalitiesa
4/F/30s ILC, TC, DPCP, 13 1 0.5 NA 100 (AT) NA NA Morbilliform
minoxidil eruption,
peripheral
edemab
5/F/40s ILC, TC, 35 NA 3 10 79.30 40.00 50 None
minoxidil,
DPCP,
anthralin
6/F/50s ILC, TC, 18 NA 6 10 78.30 39.60 49 None
minoxidil,
DPCP,
anthralin
7/F/50s ILC, TC, 30 1 3 10 100 (AU) 10 90 None
minoxidil,
DPCP, excimer
laser
8/F/50s ILC, TC, 54 7 10 20 100 (AU) 40.10 60 Lipid
minoxidil, abnormalitiesc
DPCP
9/F/50sd ILC, TC, 11 NA 4 25 71.60 35 51 None
minoxidil,
DPCP
10/F/50s ILC, TC, 15 2 5 10 100 (AT) 30.80 69 None
minoxidil,
DPCP
11/F/50s ILC, TC, 15 NA 9 20 76 15.00 80 None
minoxidil,
DPCP, MTX
12/F/50s SC, TC, Cys, 8 7 13 20 100 (AU) 35.40 65 None
Infx, squaric
acid
dibutylester
13/F/60s ILC, TC, 6 3 7 20 100 (AU) 95 5 None
minoxidil,
DPCP,
anthralin
Mean (SD) 18 (14) 3.3 (2.3) 6.4 (3.7) 15.8 (5.6) 92.70 (11.5) 52.40 (33.4) 44.30 (31.9)
Median 77.2 39.8 50.5
(range) (71.6-100) (10-100) (0-90)
b
Abbreviations: AA, alopecia areata; ALT, alanine transaminase; AST, aspartate Within 2 weeks of therapy, patient developed morbilliform eruption and
transaminase; AT, alopecia totalis; AU, alopecia universalis; Cys, cyclosporine; peripheral edema, which resolved completely 2 weeks after medication
DPCP, diphenylcyclopropenone; ILC, intralesional corticosteroids; Infx, withdrawal.
infliximab; LDL, low-density lipoprotein; MTX, methotrexate; NA, not available; c
Abnormalities were noted at 30 mg total daily dose. Total cholesterol
SALT, Severity of Alopecia Tool; SC, systemic corticosteroids; TC, topical increased to 270 mg/dL (normal range, 150-200 mg/dL), and LDL increased to
corticosteroids. 175 mg/dL (normal range, <130 mg/dL). Abnormalities resolved at 20 mg total
a
Abnormalities were noted at 25 mg total daily dose. Aspartate transaminase daily dose. (To convert total cholesterol and LDL levels to millimoles per liter,
increased to 43 U/L (normal range, 10-38 U/L) and ALT to 48 U/L (normal multiply by 0.0259.)
range, 7-56 U/L). Abnormality resolved and regrowth began at 15 mg total d
Patient 9 was the exception to the standard protocol because treatment was
daily dose. (To convert AST and ALT to microkatals per liter, multiply by initiated with 10 mg twice daily (20 mg total).
0.0167.)

Limitations of this study included the absence of a con-
trol group, which prevented the comparison of tofacitinib with
a placebo, and the small sample size, which precluded sub-
group analyses. In retrospect, the daily doses could have been
lower and increased more gradually yet still achieved similar
results given that patient response seemed to be both dose and
time dependent.3 Dosages higher than 10 mg twice a day may
be associated with higher risk for serious infections and ma-
lignant neoplasms, which have been reported at baseline dos-
ages of 5 mg twice daily.5
Conclusions | Oral tofacitinib is a successful treatment for AA,
but its efficacy varies widely. To truly assess efficacy, thera-
peutic trials should continue in the clinical setting for a

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minimum of 4 months and potentially up to 1 year. Patients
should be informed of the lack of durability of effects after
the treatment is discontinued. Future studies, including
those6 using other Janus kinase inhibitors, such as ruxoli-
tinib phosphate, are needed and should continue to eluci-
date these medications’ efficacy, safety, and durability in
the treatment of AA.
Omer Ibrahim, MD
Cheryl B. Bayart, MD, MPH
Sara Hogan, MD
Melissa Piliang, MD
Wilma F. Bergfeld, MD
Author Affiliations: Department of Dermatology, Cleveland Clinic Foundation,
Cleveland, Ohio.
Accepted for Publication: December 29, 2016.
Corresponding Author: Omer Ibrahim, MD, Department of Dermatology,
Cleveland Clinic Foundation, 9500 Euclid Ave, A61, Cleveland, OH 44195
(khobel608@hotmail.com).
Published Online: March 29, 2017. doi:10.1001/jamadermatol.2017.0001
Author Contributions: Drs Ibrahim and Bergfeld had full access to all the data
in the study and take responsibility for the integrity of the data and the accuracy
of the data analysis.
Study concept and design: Ibrahim, Piliang, Bergfeld.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Ibrahim, Bergfeld.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Ibrahim, Bayart.
Administrative, technical, or material support: Bayart, Hogan, Piliang, Bergfeld.
Study supervision: Piliang, Bergfeld.
Conflict of Interest Disclosures: None reported.
Additional Contributions: We thank the patient depicted in the Figure for
granting permission to publish this information.
1. 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.
2. Jabbari A, Nguyen N, Cerise JE, et al. Treatment of an alopecia areata patient
with tofacitinib results in regrowth of hair and changes in serum and skin
biomarkers. Exp Dermatol. 2016;25(8):642-643.
3. Kennedy Crispin M, Ko JM, Craiglow BG, et al. Safety and efficacy of the JAK
inhibitor tofacitinib citrate in patients with alopecia areata. JCI Insight. 2016;1
(15):e89776.
4. Olsen EA, Hordinsky MK, Price VH, et al; National Alopecia Areata
Foundation. Alopecia areata investigational assessment guidelines—part II. J Am
Acad Dermatol. 2004;51(3):440-447.
5. Xeljanz [package insert]. New York, NY: Pfizer; 2016.
6. Mackay-Wiggan J, Jabbari A, Nguyen N, et al. Oral ruxolitinib induces hair
regrowth in patients with moderate-to-severe alopecia areata. JCI Insight. 2016;
1(15):e89790.
Rates of Dermoscopy Use for Melanoma Diagnosis
in the Miami VA Medical Center
In the past 25 years, dermoscopy has had a major impact on
the diagnosis of cutaneous lesions. Adequate dermoscopy
training can be cost-effective and reduce melanoma-
associated morbidity and mortality.1 Since 2006, dermato-
scopes have been provided to incoming dermatology resi-
dents at the University of Miami as a part of the training
curriculum in addition to didactic dermoscopy training by a
pigmented lesion expert.
Methods | We sought to determine the rates of dermoscopy
use in melanoma detection at the Miami Veterans Affairs
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(VA) Medical Center whereby dermatology residents are the
frontline clinicians. With approval from the Miami Veterans
Affairs institutional review board, we searched by Interna-
tional Classification of Diseases, Ninth Revision diagnosis
codes (172.0-172.9) for cutaneous melanoma cases with his-
topathological confirmation between January 2000 and
December 2015 (n = 519). Medical record review captured
patient demographics, Breslow depth, and dermoscopy use.
Cases were considered to have dermoscopy use if dermo-
scopic features (eg, general patterns or features of a pig-
mented lesion) were documented and used to prompt
biopsy of the lesion found to be a melanoma. Patient
informed consent was not required due to the nature of the
study.
Results | We found that dermoscopy usage increased from 8
of 127 cases [6%] between 2000 and 2005 to 63 of 168 cases
[37%] between 2006 and 2010 to 157 of 224 cases [70%]
between 2011 and 2015. The data demonstrates a significant
trend over time (Figure). There was an inverse correlation
between dermoscopy use and Breslow depth with signifi-
cantly thinner melanomas associated with dermoscopy-use
cases compared to nondermoscopy use cases (median Bres-
low depth 0 mm vs 0.26 mm; Wilcoxon rank-sum test,
P < .001).
Discussion | Similar to the trend seen at our training institu-
tion, the rates of dermoscopy use have increased over the past
2 decades. In a 2002 survey,2 only 38% of US dermatology resi-
dents reported dermoscopy training during their residency, and
more than one-third had never used a dermatoscope. The same
group updated their survey in 2010 and noted a 40% in-
crease in the proportion of residency programs that used der-
moscopy and 52% increase in those residents receiving
training.3 This same temporal trend has been reported in the
United Kingdom: 54% of respondents reported regular der-
moscopy use in 2003, compared with 98.5% in 2012. In the
United States, dermoscopy users are more likely to be younger,
Figure. Dermoscopy Use in VA Melanoma Cases Between 2000
and 2015
90
80
70
60
50
Cases, %
40
30
20
10
0
2000 2002 2004 2006 2008 2010 2012 2014 2016
Year
The increasing rates of dermoscopy use demonstrate a significant trend over
time (P < .001).
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