A case report: corneal melting after patch graft in a rheumatoid arthritis patient taking Upadacitinib: paradoxical manifestation or uncontrolled disease activity?

Abstract

Background: Peripheral ulcerative keratitis (PUK) is a serious and uncommon ocular manifestation associated with poorly controlled rheumatoid arthritis (RA). Upadacitinib (UPA), a selective Janus kinase 1 inhibitor, is an effective therapy for patients with moderate-to-severe disease activity RA who do not respond to or are intolerant to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). However, episodes of paradoxical ocular inflammation associated with its use have not been reported before. We summarized a case report of corneal erosion following DALK in a UPA-treated RA patient with ophthalmological manifestations and discussed the potential etiological mechanisms.

Case description: A 64-year-old female patient with a 36-year history of erosive RA was added on iguratimod, a new DMARD and followed by one month of UPA treatment, which was discontinued due to the development of pulmonary nodules. After three months of pharmacotherapy, PUK showed no signs of improvement and progressed to descemetocele in the right eye at admission. The patient underwent DALK and recovered well within 3 months after the surgery. However, corneal graft rejection occurred 9 months after surgery coinciding with a one-month course of UPA treatment. Over the subsequent six months, a recurrent tendency of corneal erosion was observed in the reexaminations despite treatment with topical and systemic immunosuppressive agents, in addition to systemic corticosteroids. Her Disease Activity Score-28 (DAS-28) was recorded at 5.7, and anti-cyclic citrullinated protein antibody levels remained strongly positive throughout this period. It's worth noting that ocular symptoms manifested in the right eye approximately one month after the discontinuation of UPA therapy.

Conclusion: Paradoxical ocular inflammation has been documented in several case reports and series following a switch to other targeted synthetic DMARDs (tsDMARDs) or biologic DMARDs (bDMARDs). This case suggests that PUK may occur either as a potential adverse effect of UPA or due to uncontrolled disease activity. These findings emphasize the urgent need to focus on the UPA-associated ocular adverse events.