Successful management of refractory pediatric dupilumab-associated ocular surface disease with topical tacrolimus

Dear Editor, Dupilumab, a monoclonal antibody targeting the interleukin (IL)-4 receptor alpha subunit, has become a cornerstone in the management of moderate-to-severe atopic dermatitis (AD). While its safety profile is generally favorable, dupilumab-associated ocular surface disease (DAOSD) has emerged as a frequent comorbidity, with incidence rates in pediatric populations reported between 7.4% and 34.6%.[1,2] Although mild cases often respond to lubricants, severe DAOSD in children remains a therapeutic challenge with undefined optimal management strategies.[3] We report a severe case of pediatric DAOSD refractory to conventional corticosteroid therapy that resolved successfully with topical 0.03% tacrolimus ointment. A 10-year-old girl with severe AD (Eczema Area and Severity Index [EASI] score 12.2) refractory to systemic corticosteroids was initiated on dupilumab 300 mg every 4 weeks. Baseline laboratory investigations revealed significant risk factors for DAOSD, including a markedly elevated serum immunoglobulin E (IgE) level (5820 kU/L) and peripheral eosinophilia (1122.4/μL). Following the third injection, while her dermatological symptoms improved (EASI 7.4), she developed bilateral redness, photophobia, and discharge. Ophthalmic examination revealed eczematoid changes of the eyelids, marked conjunctival injection, a papillary reaction of the conjunctiva, and diffuse superficial punctate keratitis (SPK) [Figure 1]. Best-corrected visual acuity (BCVA) was 20/25 in the right eye and 20/30 in the left eye. Despite discontinuing dupilumab and initiating an intensive regimen of 0.1% betamethasone drops, tobramycin/dexamethasone ophthalmic ointment, and frequent preservative-free artificial tears, the condition deteriorated over 4 weeks. This clinical worsening likely reflects the prolonged systemic half-life of dupilumab and a persistent, self-sustaining inflammatory response on the ocular surface that was unresponsive to a topical steroid regimen alone. BCVA declined to 20/30 in the right eye and 20/40 in the left eye. Conjunctival cultures were negative for infection.Figure 1: External photograph and slit lamp photograph at presentation. (a) External photograph at presentation. (b) Slit lamp photograph of the right eye at presentation. (c) Slit lamp photograph of the left eye at presentation. (d) Slit lamp examination with fluorescein dye of the right eye at presentation. (e) Slit lamp examination with fluorescein dye of the right eye at presentationGiven the refractory nature of the inflammation and the risks associated with prolonged topical steroid use in a child (e.g., cataract formation, intraocular pressure elevation), the treatment regimen was substituted with topical 0.03% tacrolimus ointment applied to the eyelid margins and periocular skin twice daily. All topical steroids were gradually tapered and discontinued, while preservative-free artificial tears were maintained four times daily for ocular surface support. Two months later, substantial regression of conjunctival hyperemia and SPK was observed [Figure 2], and BCVA improved to 20/25 in both eyes. Following the resolution of DAOSD, dupilumab was permanently discontinued. The patient’s systemic AD was subsequently managed with non-biologic immunosuppressants, including oral cyclosporine and methotrexate, during which the ocular surface remained stable without recurrence.Figure 2: External photograph and slit lamp photograph after treatment. (a) External photograph after treatment. (b) Slit lamp photograph of the right eye after treatment. (c) Slit lamp photograph of the left eye after treatment. (d) Slit lamp examination with fluorescein dye of the right eye after treatment. (e) Slit lamp examination with fluorescein dye of the right eye after treatmentThe pathogenesis of DAOSD is distinct from classic allergic conjunctivitis and is thought to involve a dupilumab-induced blockade of IL-4/IL-13 signaling, leading to goblet cell depletion and mucin deficiency, thereby compromising ocular surface homeostasis.[4] While mild cases often respond to lubricants or short courses of corticosteroids, severe cases in children pose a therapeutic challenge. This case underscores two critical clinical considerations. First, high baseline IgE and eosinophilia should heighten suspicion for DAOSD in pediatric patients. Second, topical calcineurin inhibitors, such as tacrolimus, offer a potent, steroid-sparing alternative for refractory surface inflammation. Tacrolimus inhibits T-cell activation and cytokine production, effectively modulating the Th1/Th2-mediated inflammation without the intraocular pressure or cataractogenic risks associated with corticosteroids.[5] While the 2-month resolution likely coincided with the systemic “washout” of dupilumab, the failure of initial intensive steroid therapy suggests that tacrolimus played a primary role in arresting the refractory inflammation. Specifically, the application of tacrolimus ointment to the eyelid margins addressed the associated blepharitis and meibomian gland dysfunction, stabilizing the tear film and facilitating corneal surface recovery. While dupilumab is a transformative therapy for pediatric AD, clinicians must remain vigilant for severe DAOSD. This case demonstrates that DAOSD can be refractory to aggressive steroid therapy. In such instances, topical 0.03% tacrolimus ointment serves as a safe, effective, and steroid-sparing alternative that should be considered early in the treatment algorithm to prevent ocular morbidity and steroid-related complications. Ethics approval The study was approved by the Institutional Review Board (IRB) of Chang Gung Memorial Hospital, Taoyuan, Taiwan (IRB No. 202500958B0) and followed the Declaration of Helsinki. Declaration of patient consent The authors certify that they have obtained appropriate consent forms from the legal guardians of the patient. In the form, the guardians have given the consent for the images and other clinical information of the patient to be reported in the journal. The guardians understand that the name and initials of the patient will not be published and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed. Data availability statement Data sharing not applicable to this article as no datasets were generated or analyzed during the current study. Financial support and sponsorship Nil. Conflicts of interest Dr. David Hui-Kang Ma, an editorial board member at Taiwan Journal of Ophthalmology, had no role in the peer review process of or decision to publish this article. All authors declared no conflicts of interest in writing this paper.