BPG is committed to discovery and dissemination of knowledge
Minireviews
Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Virol. Mar 25, 2026; 15(1): 117124
Published online Mar 25, 2026. doi: 10.5501/wjv.v15.i1.117124
Phlyctenular keratoconjunctivitis with viral triggers
Matteo Capobianco, Francesco Cappellani, Federico Visalli, Alessandro Avitabile, Giuseppe Gagliano, Simonetta Gaia Nicolosi, Marieme Khouyyi, Fabiana D’Esposito, Caterina Gagliano, Marco Zeppieri
Matteo Capobianco, Giuseppe Gagliano, Eye Clinic, Policlinico G. Rodolico, University of Catania, Catania 95121, Italy
Matteo Capobianco, Alessandro Avitabile, Giuseppe Gagliano, Simonetta Gaia Nicolosi, Faculty of Medicine, University of Catania, Catania 95123, Italy
Francesco Cappellani, Fabiana D’Esposito, Caterina Gagliano, Department of Medicine and Surgery, University of Enna “Kore”, Enna 94100, Italy
Francesco Cappellani, Caterina Gagliano, Mediterranean Foundation, “G.B. Morgagni”, Catania 95125, Italy
Federico Visalli, Department of Ophthalmology, University of Catania, Catania 95123, Italy
Marieme Khouyyi, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina 98121, Italy
Fabiana D’Esposito, Imperial College Ophthalmic Research Group Unit, Imperial College, London NW1 5QH, United Kingdom
Marco Zeppieri, Department of Ophthalmology, University Hospital of Udine, Udine 33100, Italy
Marco Zeppieri, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste 34129, Italy
Co-corresponding authors: Caterina Gagliano and Marco Zeppieri.
Author contributions: Zeppieri M, Nicolosi SG, D’Esposito F, Gagliano G, and Capobianco M did the research and writing of the manuscript; Zeppieri M, Nicolosi SG, D’Esposito F, Cappellani F, Khouyyi M, Visalli F, Gagliano C, and Capobianco M assisted in the writing of the draft and final paper; Zeppieri D’Esposito F, Cappellani F, Khouyyi M, Gagliano C, and Capobianco M were responsible for the conception and design of the study; Zeppieri M, Nicolosi SG, Avitabile A, D’Esposito F, Cappellani F, D’Esposito F, Gagliano C, Gagliano G, and Capobianco M assisted in the writing and editing of the manuscript; Zeppieri M and Gagliano C have played important and indispensable roles in the manuscript preparation as the co-corresponding authors; all authors provided the final approval of the article.
Conflict-of-interest statement: All authors declare no conflict of interest.
Corresponding author: Marco Zeppieri, MD, PhD, Consultant, Department of Ophthalmology, University Hospital of Udine, p. le S. Maria della Misericordia 15, Udine 33100, Italy. mark.zeppieri@asufc.sanita.fvg.it
Received: December 1, 2025
Revised: December 30, 2025
Accepted: February 5, 2026
Published online: March 25, 2026
Processing time: 104 Days and 22.1 Hours
Abstract

Phlyctenular keratoconjunctivitis (PKC) goes beyond limbal nodules. This pediatric ocular surface condition caused by delayed-type hypersensitivity to microbial antigens. The trigger is context-dependent: Mycobacterial antigens in tuberculosis-endemic areas; staphylococcal eyelid disease and rosacea in high-income areas. Although classically bacterial-driven, virus-associated presentations like herpes simplex virus (HSV)-linked phlyctenular disease, pediatric PKC during acute coronavirus disease 2019 (COVID-19) infection, and molluscum contagiosum-driven keratoconjunctivitis suggest the same antigen-mediated pathway. Photophobia and discomfort are prevalent, and corneal involvement can cause neovascularization, scarring, amblyopia, and perforation. This minireview combines epidemiologic, clinical, and immunopathologic data to identify causes and update care. Practical takeaways: (1) Treat the antigen source (blepharitis/rosacea, chlamydia, parasites) and screen for tuberculosis when risk factors exist. Consider viral triggers when history or exam suggest HSV, recent COVID-19, or eyelid molluscum; (2) Suppress inflammation promptly with a short, carefully tapered course of topical corticosteroids; (3) Use topical cyclosporine as a steroid-sparing agent in recurrent or steroid-dependent disease; and (4) Reduce antigen load with lid hygiene and targeted antimicrobials. Start antitubercular treatment for tuberculosis. If a viral cause is anticipated, add antiviral medication or molluscum lesion eradication to the steroid-sparing regimen. Trigger-focused, steroid-sparing treatment reduces recurrences, vision-threatening consequences, and steroid exposure.

Keywords: Phlyctenular keratoconjunctivitis; Pediatric ophthalmology; Delayed-type hypersensitivity; Staphylococcus aureus; Tuberculosis; Ocular rosacea; Viral infection; Herpes simplex virus; COVID; Molluscum contagiosum

Core Tip: Phlyctenular keratoconjunctivitis is a delayed-type hypersensitivity disorder that often affects children. Triggers vary by setting: Mycobacterial antigens in tuberculosis-endemic areas; staphylococcal lid disease and ocular rosacea elsewhere. A minority of cases have viral associations [herpes simplex virus (HSV), coronavirus disease, molluscum contagiosum, etc.] that mirror the same antigen-driven mechanism and should be managed by addressing the viral source-antivirals when HSV is plausible and excision/ablation for eyelid molluscum-alongside brief steroids, lid hygiene, targeted antibiotics, and topical cyclosporine to reduce recurrences and steroid burden.