Recognition of Atopic Keratoconjunctivitis During Treatment With Dupilumab for Atopic Dermatitis

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• Dupilumab use may result in ophthalmic complications—commonly, simple reactive conjunctivitis and, rarely, atopic keratoconjunctivitis (AKC). In this papaer, 3 cases of AKC, a severe form of allergic ocular disease that can cause blindness, are reported, along with an ophthalmology-developed algorithm for screening patients before and after beginning dupilumab (Figure 2 in the article). Prior to starting dupilumab, screen patients by asking about a prior diagnosis of allergic conjunctivitis or whether prior use of steroid eye drops was required. Severe symptoms after starting dupilumab, such as new photophobia or decreased vision, should prompt urgent referral to ophthalmology and discontinuation of dupilumab until evaluation.

• Although most ocular side effects of dupilumab may be managed conservatively with lubricating eye drops, AKC is a severe inflammation of the entire ocular surface, which can lead to blindness, and it may be caused by dupilumab. Screening prior to starting dupilumab and recognizing danger signs afterward are critical for dermatologists.

– Margaret Hammond, MD

Written by

 

 

Jane Grant-Kels MD

Atopic dermatitis (AD) is extremely common as it is seen in approximately 7% of adults and 25% of children. Prior to the new targeted therapies, recalcitrant AD was extremely challenging to treat. Dupilumab has been found to not only be efficacious (as it is a monoclonal antibody that specifically targets IL-4 receptor alpha, resulting in the blocking of IL-4 and IL-13, the two key mediators of the TH2 pathway) but also shown to be relatively safe.1 Unfortunately, conjunctivitis, which is commonly seen in patients with AD, is a commonly reported adverse event in patients treated with dupilumab as well. Patients treated with this medication have a higher incidence of developing conjunctivitis (9%–22%) than those receiving placebo (2%–11%). What are the risk factors for patients developing this side effect?—severe atopic dermatitis and a self-reported history of conjunctivitis.2

This excellent collaborative research letter from the departments of dermatology and ophthalmology at the University of Iowa discusses the risk of developing severe atopic keratoconjunctivitis (AKC) with dupilumab versus "simple conjunctivitis." Severe AKC can result in significant inflammation of the cornea and conjunctiva, which can lead to blindness via "corneal neovascularization, infection, perforation, destruction of epithelial stem cells, and cicatricial malposition of the eyelids." Although their recommendations are based upon their experience with only a few patients, the authors' advice is entirely appropriate and should be followed so that we do not inadvertently improve a patient's AD but cause him severe ocular morbidity!

These authors recommend:

• Screening patients for a history of preexisting severe allergic conjunctivitis. Those with such a history should be evaluated by an ophthalmologist. If the patient has only a history of milder conjunctivitis, we should educate her to use preventive antihistamine and mast cell–stabilizer eye drop combinations, which are available over the counter.
• Once the patient is on dupilumab, she should be screened for ocular symptoms. Mild symptoms can be managed with artificial tears and antihistamine and mast cell–stabilizer eye drops. Patients with severe symptoms (including photophobia or decreased vision) should be immediately referred to ophthalmology, and their dupilumab should be held until this consultation.

References

1. Brunner PM, Guttman-Yassky E, Leung DYM. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017;139(4):S65-S76. https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(17)30205-1
2. Agnihotri G, Shi K, Lio PA. A clinician's guide to the recognition and management of dupilumab-associated conjunctivitis. Drug RD. 2019;19(4):311-318. https://link.springer.com/article/10.1007/s40268-019-00288-x

Abstract

Dupilumab, a monoclonal antibody that blocks Th2 cytokines,[1-4] is approved for the 3 treatment of cutaneous manifestations of atopic dermatitis (AD). Unfortunately, dupilumab use 4 can result in ophthalmic complications. In the inaugural phase III clinical trials, 14-19% of 5 patients reported dupilumab associated conjunctivitis but were not examined by an 6 ophthalmologist.[1, 4] Thus, it is possible that some of these patients could have experienced a 7 more severe form of ocular surface disease than simple reactive conjunctivitis. In this report, we 8 describe 3 patients who developed atopic keratoconjunctivitis (AKC), a severe inflammatory 9 condition affecting the cornea and conjunctiva, that results in more ocular morbidity than simple 10 conjunctivitis.[5] We also propose an algorithm that dermatologists may use to screen patients 11 for concerning ocular symptoms.

Journal of the American Academy of Dermatology

Recognition of Atopic Keratoconjunctivitis During Treatment With Dupilumab for Atopic Dermatitis

J Am Acad Dermatol 2020 Sep 18;[EPub Ahead of Print], J Cheng, L Jiang, NC Morrow, A Avdic, JA Fairley, JJ Ling, MA Greiner 

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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