Sinthiya Sivarajah
Introduction
Dupilumab is a biologic agent licensed in the treatment of multiple atopic conditions such as atopic dermatitis, asthma and rhinosinusitis with nasal polyps. However, with continued use, reports of ocular side-effects associated with dupilumab use seem to be increasing (1).
Ocular side effects range from mild eye disease such as conjunctivitis and blepharitis, to more severe ocular manifestations such as ulcerative keratitis (2).
Epidemiology and Prevalence
Patients with a history of atopy have a greater risk of developing allergic conjunctivitis and ocular surface disease (3). Dupilumab related ocular side-effects have been reported in patients of all ages and ethnicities. Interestingly, patients treated with dupilumab for atopic dermatitis had greater incidence of developing conjunctivitis (8.6-22.1%) than patients that were treated with dupilumab for asthma (0–1·7%) (4).
Pathophysiology
Dupilumab is a monoclonal antibody that works by inhibiting interleukin-4 (IL-4) and interleukin-13 (IL-13) (1). This prevents the release of proinflammatory signals and chemokines. It also downregulates type 2 helper T-cells (Th2) thus reducing inflammation in atopic conditions (2). The mechanism by which dupilumab exacerbates, or increases the occurrence of, ocular disease is poorly understood. It is thought inhibition of IL-13 may affect regulation of conjunctival goblet cells and ocular mucus production thereby affecting quality of tears (4). Another suggestion is, downregulation of IL-4 and IL-13 ocular cytokines allows for an environment where demodex mites can thrive, leading to IL-17 mediated inflammation leading to presentation similar to ocular rosacea (5, 6).
Diagnosis
On average, symptoms start to occur six weeks after treatment with dupilumab (2). Diagnosis is primarily clinical made by thorough history and examination, including slit-lamp examination to evaluate for keratitis (3).
Management
The main goal of treatment is to limit the inflammatory process. First line therapy options include topical corticosteroid eye drops, topical tacrolimus eye ointment, artificial tears or ciclosporin eye drops, all of which have been successful in managing dupilumab related ocular side effects (1). One study found starting artificial tears one week prior to starting dupilumab may reduce incidence of ocular side effects (6).
Conclusion
It is clear patients on dupilumab have a greater risk of developing ocular side effects. Therefore, close collaboration is needed with ophthalmologists to ensure early diagnosis and management of ocular side effects.
References
1. Wollenberg A, Ariens L, Thurau S, van Luijk C, Seegräber M, de Bruin-Weller M. Conjunctivitis occurring in atopic dermatitis patients treated with dupilumab–clinical characteristics and treatment. The Journal of Allergy and Clinical Immunology: In Practice. 2018 Sep 1;6(5):1778-80.
2. Chu CY. Keeping an eye on the ocular problems in dupilumab clinical trials. British Journal of Dermatology. 2019 Sep 1;181(3):436-7.
3. de Bruin-Weller M, Graham NM, Pirozzi G, Shumel B. Could conjunctivitis in patients with atopic dermatitis treated with dupilumab be caused by colonization with Demodex and increased interleukin-17 levels?: reply from the authors. The British journal of dermatology. 2018 Mar 2;178(5):1220-1.
4. Akinlade B, Guttman‐Yassky E, de Bruin‐Weller M, Simpson EL, Blauvelt A, Cork MJ, Prens E, Asbell P, Akpek E, Corren J, Bachert C. Conjunctivitis in dupilumab clinical trials. British Journal of Dermatology. 2019 Sep 1;181(3):459-73.
5. Treister AD, Kraff-Cooper C, Lio PA. Risk factors for dupilumab-associated conjunctivitis in patients with atopic dermatitis. JAMA dermatology. 2018 Oct 1;154(10):1208-11.
6. Ivert LU, Wahlgren CF, Ivert L et al. Eye complications during dupilumab treatment for severe atopic dermatitis. Acta Derm Venereol 2019; 99:375–8.