CASE REPORT
Treatment of granuloma annulare with
tofacitinib 2% ointment
William Damsky, MD, PhD, and Brett A. King, MD, PhD
New Haven, Connecticut
Key words: granuloma annulare; JAK; Janus kinase; tofacitinib.
G ranuloma annulare (GA) is an autoimmune
cutaneous disorder characterized by clus-
ters of macrophages and T cells giving rise
to pink papules and annular plaques. GA can be
Abbreviations used:
GA:
IFN:
JAK:
Granuloma annulare
interferon
Janus kinase
challenging to treat, and even localized disease is JAK-STAT: Janus kinase signal transducer and
often unresponsive to topical corticosteroids and activator of transcription
calcineurin inhibitors; intralesional triamcinolone
can be effective in some cases. Better therapies are
needed for GA and other cutaneous granulomatous
disorders. recalcitrant sarcoidosis and GA with an oral JAK
In GA, CD41 helper T cells with a Th1 phenotype inhibitor, tofacitinib, induced dramatic disease
tend to predominate among the lymphocytic portion remission in these patients.3,4
of the infiltrate.1 These T cells produce interferon In most patients with localized GA, treatment with
(IFN)-g, a cytokine that has a well-characterized role an oral JAK inhibitor would be inappropriate.
in macrophage activation and granuloma forma- Despite the apparent efficacy of oral tofacitinib in
tion.2 In GA, IFN-g is likely a key driver of macro- cutaneous granulomatous disorders, it remains un-
phage recruitment, activation, and retention in known whether a topical JAK inhibitor might show
lesional skin. IFN-g (and other cytokines) signals similar efficacy. Here we evaluate the efficacy of
through the Janus kinase-signal transducer and tofacitinib 2% ointment in a patient with localized
activator of transcription (JAK-STAT) pathway inside GA.
target cells. Thus, drugs that inhibit the activity of A 69-year-old man with a 1-year history of GA
IFN-g (and other cytokines) via blocking JAK-STAT presented for evaluation and treatment. The lesions
signaling, may offer a pathogenesis-directed treat- were asymptomatic. He also had type 2 diabetes and
ment approach for GA and other granulomatous hypertension. Cutaneous examination revealed pink
disorders. papules and annular plaques without scale on the
Along these lines, we recently showed that JAK- neck, forehead, arms and hands (Fig 1). A skin
STAT signaling is constitutively activated in GA biopsy from the forearm showed a perivascular
(and sarcoidosis) in a pattern consistent with lymphocytic infiltrate associated with a perivascular
IFN-gedependent activation of macrophages.3,4 and interstitial histocytic infiltrate in the dermis, with
We showed that treatment of patients with focal areas of degenerated collagen palisaded by
From the Department of Dermatology, Yale School of Medicine. Correspondence to: Brett A. King, MD, PhD, Department of
Funding sources: Supported by a gift (to Dr King) from the Ranjini Dermatology, Yale School of Medicine, 333 Cedar St, LCI 501,
and Ajay Poddar Resource Fund for Dermatologic Diseases PO Box 208059, New Haven, CT 06520. E-mail: brett.king@yale.
Research. Dr Damsky is supported by the Dermatology edu.
Foundation. JAAD Case Reports 2020;6:69-71.
Conflicts of interest: Dr Damsky has research funding from Pfizer, 2352-5126
but Pfizer did not support this work. Dr Damsky is a consultant Ó 2019 by the American Academy of Dermatology, Inc. Published
for Eli Lilly. Dr King is an investigator for Concert Pharmaceu- by Elsevier, Inc. This is an open access article under the CC BY-
ticals Inc, Eli Lilly and Company, and Pfizer Inc. Dr King is a NC-ND license (http://creativecommons.org/licenses/by-nc-nd/
consultant to and/or has served on advisory boards for Aclaris 4.0/).
Therapeutics, Arena Pharmaceuticals, Concert Pharmaceuticals https://doi.org/10.1016/j.jdcr.2019.10.016
Inc, Dermavant Sciences, Eli Lilly and Company, and Pfizer Inc;
he is on speakers bureau for Pfizer Inc, Regeneron, and Sanofi
Genzyme.
69
70 Damsky and King JAAD CASE REPORTS
JANUARY 2020
Fig 1. Effect of tofacitinib 2% ointment in GA. Upper panels, Clinical images before tofacitinib
(left panels) and after 15 weeks of tofacitinib 2% ointment twice daily (right panels). Lower
panels, a single lesion was left untreated to control for spontaneous resolution of GA. Clinical
image of the untreated lesion before and after treatment of the other lesions.
JAAD CASE REPORTS Damsky and King 71
VOLUME 6, NUMBER 1
with oral ruxolitinib (another JAK inhibitor), admin-
istered for concomitant myeloproliferative neo-
plasms.5,6 Clinical trials are underway to better
characterize the role of oral JAK inhibitors in the
treatment of severe cutaneous sarcoidosis and GA
(NCT03910543, NCT03793439).
We show that tofacitinib 2% ointment was effec-
tive in a patient with localized GA. Tofacitinib 2%
ointment was chosen because this concentration of
tofacitinib has been used in clinical trials. A specific
effect of tofacitinib is supported by the observation
that a single untreated lesion did not also improve
during tofacitinib treatment of the other lesions.
Biopsy after clinical improvement of the GA was
not pursued; however, in patients treated with oral
Fig 2. Skin biopsy shows GA. Histocytes and lymphocytes tofacitinib, histologic clearance of granulomas has
in the dermis, with focal areas of degenerated collagen
been observed.3,4
palisaded by histiocytes, consistent with GA. (Original
These data suggest that topical JAK inhibitors may
magnification: 3200.)
be beneficial in patients with cutaneous granuloma-
tous disorders with limited involvement. Larger
histiocytes, consistent with GA (Fig 2). Solar elastosis studies are warranted to better characterize the role
was minimal, and elastophagocytosis was not of topical JAK inhibitors in treating GA and related
observed. disorders.
The patient was previously treated with triamcin-
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