Tofacitinib Treatment and Molecular Analysis of Cutaneous Sarcoidosis

Damsky, William M.D., Ph.D.
Thakral, Durga M.Phil., M.S.
Emeagwali, Nkiruka M.D., Ph.D.
Galan, Anjela M.D.
King, Brett M.D., Ph.D.

From the Departments of Dermatology (W.D., D.T., A.G., B.K.), Immunobiology (W.D.), and Pathology (A.G.) and the Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine (N.E.), Yale School of Medicine, New Haven, CT.

Address reprint requests to Dr. King at the Department of Dermatology, Yale School of Medicine, 333 Cedar St., LCI 501, P.O. Box 208059, New Haven, CT 06520, or at [email protected].

Supported by a grant (to Dr. King) from the Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research, a training grant (T32AR007016, to Dr. Damsky) from the National Institutes of Health (NIH), a Research Fellowship and Career Development Award (to Dr. Damsky) from the Dermatology Foundation, and a Medical Science Training Program grant (T32GM007205, to Ms. Thakral) from the NIH.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

We thank V. Klump and M. Napoletano and the staff of the Yale dermatopathology laboratory; M. Zhong and E. Cheng for RNA sequencing performed at the Yale Stem Cell Center Genomics Core Facility, which was supported by the Connecticut Regenerative Medicine Research Fund and the Li Ka Shing Foundation; M. Gulati and N. Kaminski of the Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine at the Yale School of Medicine; and the staff of the Yale Center for Research Computing for guidance and use of the research computing infrastructure.

New England Journal of Medicine 379(26):p 2540-2546, December 27, 2018. | DOI: 10.1056/NEJMoa1805958

SUMMARY

There is evidence that Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signaling plays a role in the pathogenesis of sarcoidosis. We treated a patient with cutaneous sarcoidosis with the JAK inhibitor tofacitinib; the patient had not previously had a response to medications and had not received systemic glucocorticoids. This treatment resulted in clinical and histologic remission of her skin disease. Sequencing of RNA and immunohistochemical examination of skin-lesion samples obtained from the patient before and during therapy and immunohistochemical testing of lesion samples obtained from other patients with cutaneous sarcoidosis support a role for JAK-STAT signaling in cutaneous sarcoidosis. (Funded by the Ranjini and Ajay Poddar Resource Fund for Dermatologic Diseases Research and others.)