Bilateral, sequential orbital inflammatory syndrome associated with ruxolitinib

Ruxolitinib is an oral Janus associated kinase (JAK) inhibitor commonly used in the treatment of primary myelofibrosis. We describe a case of an 86-year-old woman on ruxolitinib for primary myelofibrosis who presented with a three-day history of worsening left eyelid swelling, pain, and decreased vision. Her exam was notable for left upper lid ptosis, periorbital edema, and nearly complete external ophthalmoplegia along with diffuse conjunctival injection and microcystic corneal edema. An orbital computed tomography demonstrated left proptosis accompanied by extensive inflammatory changes of the preseptal and orbital soft tissues. She was diagnosed with acute left orbital inflammatory syndrome (OIS) and treated with intravenous methylprednisolone, one gram over 48 hours followed by an oral steroid taper as well as discontinuation of her ruxolitinib. Complete recovery was noted at her one-week follow-up visit and ruxolitinib was restarted. However, 3 weeks later, she presented with new right periorbital swelling and pain and was found to have a sequential right OIS for which she was again treated with methylprednisolone and discontinuation of ruxolitinib with the goal of transitioning to an alternative biologic agent. Although there are no previous documented cases of ruxolitinib associated orbital inflammatory syndrome, a similar JAK inhibitor medication, Fedratinib, has been reported to cause a similar side effect. We propose that her ruxolitinib paradoxically lead to a pro-inflammatory state leading to bilateral, sequential orbital inflammatory syndrome.