PCR-confirmed severe geographic HSV-1 keratitis associated with systemic JAK inhibitor therapy

BACKGROUND: Janus kinase inhibitors (JAKi) are successfully used for the treatment of refractory systemic autoimmune diseases. However, JAK-inhibition is known to increase the risk of infection. Herpes Zoster reactivation is the most recognised infectious complication of JAKi. Events involving herpes simplex are reported less frequently than zoster and have generally received less attention. Our goal is to raise awareness of JAKi-associated herpes simplex keratitis. METHODS: This paper describes four cases of severe herpes simplex keratitis in patients treated with oral JAK inhibitors. RESULTS: All patients presented with a geographic epithelial keratitis. One patient presented with bilateral involvement. Viral PCR of corneal swabs demonstrated the presence of HSV-1 and absence of VZV in all patients, confirming the diagnosis of herpes simplex keratitis. The patients were treated with various oral JAK inhibitors (baricitinib, upadacitinib, ruxolitinib and abrocitinib), which demonstrated an underlying class effect. Finally, the time lapse also supports an association between the use of oral JAKi and herpetic keratitis, as evidenced by the development of HSV1-related keratitis shortly after the start of oral JAKi in 3 of the 4 patients. CONCLUSIONS: Clinicians should be aware of the association between the use of oral JAKi and herpes simplex keratitis. Not only can HSV1-related keratitis manifest itself in this patient group as a severe geographic keratitis, it can also occur bilaterally. An urgent ophthalmological evaluation is recommended for patients taking oral JAKi who present with unilateral or bilateral red, painful eye(s), even in the absence of periocular signs of Herpes Zoster infection.