Tofacitinib Treatment and Molecular Analysis of Cutaneous Sarcoidosis

N Engl J Med. 2018 Dec 27;379(26):2540-2546. doi: 10.1056/NEJMoa1805958.

Abstract

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.).

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Female
  • Humans
  • Immunohistochemistry
  • Janus Kinases / antagonists & inhibitors*
  • Janus Kinases / metabolism
  • Middle Aged
  • Piperidines / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Pyrroles / therapeutic use*
  • Remission Induction
  • STAT Transcription Factors / metabolism
  • Sarcoidosis / drug therapy*
  • Sarcoidosis / genetics
  • Sarcoidosis / pathology
  • Sarcoidosis, Pulmonary / drug therapy
  • Sequence Analysis, RNA
  • Signal Transduction
  • Skin / metabolism
  • Skin / pathology*
  • Skin Diseases / drug therapy*
  • Skin Diseases / genetics
  • Skin Diseases / pathology

Substances

  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • STAT Transcription Factors
  • tofacitinib
  • Janus Kinases