Skip to content
How It Works
Explore
Resources Ask a Question
Who It's For
Patients Caregivers Providers
Log In Ask a Question
PubMed This is a summary of 20 peer-reviewed journal articles Updated
Ophthalmology

The Biology of AKC and How It Differs from Other Eye Allergies

At a Glance

Atopic keratoconjunctivitis (AKC) is a chronic, year-round immune condition that is far more severe than typical seasonal eye allergies. It is driven by an overactive Th2 immune response and can sometimes be unexpectedly worsened by eczema medications like dupilumab.

Understanding the biology of atopic keratoconjunctivitis (AKC) helps explain why it is more aggressive than typical “eye allergies.” While most allergies are a temporary reaction to pollen or pet dander, AKC is a profound, year-round malfunction of the immune system that specifically targets the eye [1][2].

The Th2 Response: An Immune System “Short Circuit”

In a healthy body, the immune system uses various “pathways” to fight different threats. AKC is driven by an overactive Type 2 (Th2) response [3][4]. You can think of this as a specific “short circuit” in your immune wiring that involves several key players:

  • IL-4 and IL-13: These are signaling proteins called cytokines. In AKC, your body overproduces them, sending constant “danger” signals to your eye surface, even when no allergen is present [3][5].
  • Eosinophils: These are white blood cells that normally fight parasites. In AKC, they flood the eye surface, releasing toxic proteins that cause tissue damage and intense itching [6][7].
  • Periostin: This is a protein that serves as a “glue” for inflammation. High levels of periostin in your tears are often a direct indicator of how severe the disease has become [8][9].

AKC vs. Other Eye Allergies

It is common to confuse AKC with other conditions, but they have distinct biological differences:

Condition Primary Biological Driver Typical Patient
Standard Allergies Acute IgE-mediated (temporary) Anyone; usually seasonal [10].
Vernal (VKC) Seasonal Th2 response Mostly children; often improves after puberty [11][12].
Atopic (AKC) Chronic Th2 and Th1/Th3 Adults with atopic dermatitis; perennial (year-round) [11][5].

Unlike other allergies, AKC can involve lymphoid neogenesis, where the immune system actually builds new “mini-factories” of inflammatory cells directly in your eye tissue, making the inflammation much harder to turn off [13][14].

The Dupilumab Paradox

If you are taking dupilumab (Dupixent) for your eczema, you may encounter a confusing phenomenon. While this medication is designed to block IL-4 and IL-13—the very same proteins involved in AKC—it can sometimes cause or worsen eye inflammation [15][16].

This is known as dupilumab-associated ocular surface disease (DAOSD) [15]. Scientists believe this happens because blocking certain pathways for the skin might “unbalance” the immune system in the eye, sometimes leading to a different type of inflammation involving neutrophils (another type of white blood cell) rather than just eosinophils [17][18].

If your eyes begin to itch or turn red shortly after starting a biologic for your skin, it doesn’t necessarily mean the medication is “failing.” Instead, it means your care team (dermatologist and ophthalmologist) may need to add targeted eye treatments to manage this specific side effect while your skin continues to heal [19][20].

Common questions in this guide

How is atopic keratoconjunctivitis (AKC) different from normal eye allergies?
Unlike seasonal eye allergies that happen temporarily in response to triggers like pollen, AKC is a chronic, year-round malfunction of the immune system. It involves long-term inflammation and changes to the eye tissue, making it much more aggressive and harder to control than standard allergies.
Why does my eczema medication (dupilumab) make my eyes red and itchy?
Dupilumab treats eczema by blocking certain immune signals, but this can sometimes unbalance the immune system in the eye. This condition is known as dupilumab-associated ocular surface disease (DAOSD), and it can cause new or worsening eye inflammation even as your skin improves.
Do I have to stop taking my skin biologic if it causes eye flares?
Not necessarily. In many cases, your dermatologist and ophthalmologist can work together to add targeted eye drops or therapies to manage the eye inflammation. This approach allows you to continue your skin treatment without losing its benefits.
What are IL-4 and IL-13, and why do they matter for AKC?
IL-4 and IL-13 are signaling proteins in the immune system that normally help fight off threats. In AKC, your body overproduces these proteins, sending constant danger signals to your eyes and causing continuous, damaging inflammation.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Am I currently showing signs of dupilumab-associated ocular surface disease (DAOSD) versus my baseline AKC?
  2. 2.Are there specific cytokines, like IL-4 or IL-13, that we should be targeting with my medication?
  3. 3.How do the inflammatory markers in my tears compare to the severity of my skin eczema?
  4. 4.Is there evidence of a secondary Staph infection or 'lymphoid neogenesis' (new immune structures) in my eye tissue?
  5. 5.If my biologic treatment for eczema is causing eye flares, can we manage them without stopping the skin treatment?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (20)
  1. 1

    Atopic Keratoconjunctivitis: Pharmacotherapy for the Elderly.

    Ridolo E, Kihlgren P, Pellicelli I, et al.

    Drugs & aging 2019; (36(7)):581-588 doi:10.1007/s40266-019-00676-7.

    PMID: 31055787
  2. 2

    Allergic conjunctivitis: current concepts on pathogenesis and management.

    Sacchetti M, Abicca I, Bruscolini A, et al.

    Journal of biological regulators and homeostatic agents 2018; (32(1 Suppl. 1)):49-60.

    PMID: 29552874
  3. 3

    IL-1α antibody inhibits dose-dependent exacerbation of eosinophilic inflammation by crude house-dust-mite antigen in the conjunctiva of an atopic keratoconjunctivitis mouse model.

    Shiraki Y, Shoji J, Inada N, et al.

    Current eye research 2021; (46(8)):1115-1124 doi:10.1080/02713683.2021.1874022.

    PMID: 33428487
  4. 4

    Dupilumab-associated ocular surface disease or atopic keratoconjunctivitis not improved by dupilumab? Upadacitinib may clarify the dilemma: A case report.

    Galluzzo M, Tofani L, Spelta S, et al.

    Skin health and disease 2024; (4(3)):e354 doi:10.1002/ski2.354.

    PMID: 38846697
  5. 5

    Cytokine Levels and Clinical Characteristics in the Tear Fluid of Patients with Atopic Dermatitis and Atopic Keratoconjunctivitis.

    Hansen PM, Utheim TP, Aass HCD, et al.

    The ocular surface 2026; doi:10.1016/j.jtos.2026.02.010.

    PMID: 41759910
  6. 6

    Histamine H1 and H4 receptor expression on the ocular surface of patients with chronic allergic conjunctival diseases.

    Inada N, Shoji J, Shiraki Y, et al.

    Allergology international : official journal of the Japanese Society of Allergology 2017; (66(4)):586-593 doi:10.1016/j.alit.2017.03.004.

    PMID: 28391980
  7. 7

    Clinical Usefulness of Monitoring Expression Levels of CCL24 (Eotaxin-2) mRNA on the Ocular Surface in Patients with Vernal Keratoconjunctivitis and Atopic Keratoconjunctivitis.

    Shiraki Y, Shoji J, Inada N

    Journal of ophthalmology 2016; (2016()):3573142 doi:10.1155/2016/3573142.

    PMID: 27721987
  8. 8

    The usefulness of measuring tear periostin for the diagnosis and management of ocular allergic diseases.

    Fujishima H, Okada N, Matsumoto K, et al.

    The Journal of allergy and clinical immunology 2016; (138(2)):459-467.e2.

    PMID: 26964692
  9. 9

    Periostin promotes inflammation and neovascularization in atopic keratoconjunctivitis.

    Nunomura S, Nanri Y, Honda Y, et al.

    The Journal of allergy and clinical immunology 2026; (157(2)):387-397 doi:10.1016/j.jaci.2025.10.004.

    PMID: 41110673
  10. 10

    Current Knowledge in Allergic Conjunctivitis.

    Villegas BV, Benitez-Del-Castillo JM

    Turkish journal of ophthalmology 2021; (51(1)):45-54 doi:10.4274/tjo.galenos.2020.11456.

    PMID: 33631915
  11. 11

    Recalcitrant Atopic Keratoconjunctivitis in Children: A Case Report and Literature Review.

    Li J, Luo X, Ke H, Liang L

    Pediatrics 2018; (141(Suppl 5)):S470-S474 doi:10.1542/peds.2016-2069.

    PMID: 29610174
  12. 12

    Severe allergic eye disease: What to do and when?

    Dahlmann-Noor A, Muthusamy K, Hingorani M

    Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 2021; (51(8)):989-991 doi:10.1111/cea.13985.

    PMID: 34337807
  13. 13

    Transcriptome profiling of refractory atopic keratoconjunctivitis by RNA sequencing.

    Matsuda A, Asada Y, Suita N, et al.

    The Journal of allergy and clinical immunology 2019; (143(4)):1610-1614.e6 doi:10.1016/j.jaci.2018.11.007.

    PMID: 30471305
  14. 14

    Where eye meets body part 2: uniting allergy pathways in ocular and atopic disease - T cells take the lead.

    Borges S, Pereira VA, Chang C, Galor A

    Current opinion in allergy and clinical immunology 2025; (25(5)):364-373 doi:10.1097/ACI.0000000000001097.

    PMID: 40747966
  15. 15

    Dupilumab-associated ocular surface disease: An interdisciplinary decision framework for prescribers in the Australian setting.

    Foley P, Kerdraon YA, Hogden JP, et al.

    The Australasian journal of dermatology 2022; (63(4)):421-436 doi:10.1111/ajd.13924.

    PMID: 36125089
  16. 16

    Conjunctivitis in atopic dermatitis patients with and without dupilumab therapy - international eczema council survey and opinion.

    Thyssen JP, de Bruin-Weller MS, Paller AS, et al.

    Journal of the European Academy of Dermatology and Venereology : JEADV 2019; (33(7)):1224-1231 doi:10.1111/jdv.15608.

    PMID: 31056788
  17. 17

    Persistent Neutrophil Infiltration and Unique Ocular Surface Microbiome Typify Dupilumab-Associated Conjunctivitis in Patients with Atopic Dermatitis.

    Patra V, Woltsche N, Cerpes U, et al.

    Ophthalmology science 2024; (4(1)):100340 doi:10.1016/j.xops.2023.100340.

    PMID: 37869024
  18. 18

    Two cases of dupilumab-associated conjunctivitis with high expression of IL-8 mRNA on the ocular surface: a case report.

    Adachi R, Shoji J, Hirota A, et al.

    Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 2022; (18(1)):89 doi:10.1186/s13223-022-00727-6.

    PMID: 36184619
  19. 19

    Clinical characteristics and management of dupilumab-associated ocular surface disease in Japan.

    Shoji J, Ebihara N

    Japanese journal of ophthalmology 2026; (70(1)):1-17 doi:10.1007/s10384-025-01299-9.

    PMID: 41269446
  20. 20

    Ocular Surface Diseases Induced by Dupilumab in Severe Atopic Dermatitis.

    Maudinet A, Law-Koune S, Duretz C, et al.

    Ophthalmology and therapy 2019; (8(3)):485-490 doi:10.1007/s40123-019-0191-9.

    PMID: 31230264

This page explains the biology of atopic keratoconjunctivitis (AKC) for educational purposes. Always consult your ophthalmologist or dermatologist for an accurate diagnosis and treatment plan.

Get notified when new evidence is published on Atopic keratoconjunctivitis.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.