Ocular surface disease in moderate‐to‐severe atopic dermatitis patients and the effect of biological therapy

Author:

Achten Roselie1ORCID,Thijs Judith1ORCID,van der Wal Marlot2ORCID,van Luijk Chantal3ORCID,Bakker Daphne1ORCID,Knol Edward12ORCID,van Luin Matthijs4,El Amrani Mohsin4ORCID,Delemarre Eveline2,Elfiky Ahmed M I2,de Boer Joke3,van Wijk Femke2,de Graaf Marlies1ORCID,de Bruin‐Weller Marjolein1ORCID

Affiliation:

1. Department of Dermatology and Allergology, National Expertise Center for Atopic Dermatitis University Medical Center Utrecht Utrecht The Netherlands

2. Center for Translational Immunology University Medical Center Utrecht, Utrecht University Utrecht The Netherlands

3. Department of Ophthalmology University Medical Center Utrecht Utrecht The Netherlands

4. Division Laboratories, Pharmacy and Biomedical Genetics, Department of Clinical Pharmacy University Medical Center Utrecht Utrecht The Netherlands

Abstract

AbstractAtopic dermatitis (AD) is a chronic inflammatory skin disease for which new targeted therapies are currently available. Due to the increased rates of ocular surface disease (OSD) reported during treatment with these new targeted treatments, more insight into the occurrence and pathomechanism of OSD in moderate‐to‐severe AD patients is needed. Therefore, this review's first part highlights that most patients with moderate‐to‐severe AD already have characteristics of OSD before starting targeted treatment. Remarkably, not all AD patients with OSD report ocular symptoms. OSD in AD is associated with less conjunctival goblet cells (GC) compared to healthy controls. In addition, OSD severity in AD patients is associated with high AD activity, the presence of eyelid and/or facial eczema, and high levels of AD‐related severity biomarkers in tear fluid. The second part of this review highlights that pre‐existing ocular pathology (e.g. in combination with the use of ophthalmic medication or eyelid eczema) may be associated with the development of dupilumab‐associated ocular surface disease (DAOSD). During dupilumab treatment, DAOSD (which can be new‐onset OSD or worsening of pre‐existing OSD) is observed in approximately one‐third of the dupilumab‐treated AD patients. Anti‐inflammatory ophthalmic treatment improves DAOSD, and dose reduction of dupilumab may also be an effective treatment option. The pathomechanism of DAOSD is still not fully elucidated. In a prospective study low, but stable conjunctival GC numbers were observed in moderate‐to‐severe AD patients, before and during dupilumab treatment. However, the Mucin 5 AC (MUC5AC) expression of GCs decreased during dupilumab treatment, suggesting an impairment of the GC function by dupilumab treatment. In addition, higher dupilumab tear fluid levels were found in dupilumab‐treated AD patients with moderate‐to‐severe OSD compared to patients with no or mild OSD, whereas the dupilumab serum levels are similar. Clinicians should be aware of the frequent occurrence of OSD in moderate‐to‐severe AD patients, and a low‐threshold referral to an ophthalmologist is recommended.

Publisher

Wiley

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