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Allergic conjunctivitis

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Allergic conjunctivitis
Other names: Ocular allergy (OA);[1] allergic eye disease; allergic rhinoconjunctivitis
Drawing of allergic conjunctivitis
SpecialtyOphthalmology, allergy and immunology
SymptomsBoth eyes itchy and red[2]
TypesAcute: Seasonal, perennial[1]
Chronic: Vernal, atopic, giant papillary[1]
CausesExposure to an allergen, such as house dust, pollen, or pet hair[1]
Diagnostic methodOften based on symptoms, examination[1]
Differential diagnosisOther types of conjunctivitis, trachoma, SJS/TEN[3]
TreatmentAvoiding the allergen, cold cloths, artificial tears[2][1]
MedicationAntihistamines, mast cell stabilizers, NSAIDs, steroids, immunotherapy, cyclosporine[2][1]
PrognosisGenerally good[3]
Frequency40%[1]

Allergic conjunctivitis (AC) is inflammation of the surface of the eye due to an allergic reaction.[1] Symptoms generally include itchy, redness, and swelling around the eyes with white discharge.[2][1] Generally both eyes are involved.[2] Often inflammation of the nose is also present.[4]

It occurs due to exposure to an allergen, such as house dust, pollen, or pet hair.[1] Air pollution is also implicated.[4] The underlying mechanism involves IgE with release of mediators by mast cells.[1] Diagnosis is often based on symptoms and examination.[1] It may be divided into acute, including seasonal and perennial; and chronic, including vernal, atopic, and giant papillary conjunctivitis.[1]

Treatment include avoiding the allergen, cold cloths, and artificial tears.[2][1] Medications may include antihistamines, mast cell stabilizers, and NSAIDs eye drops.[2] More severe cases may be treated with steroids, immunotherapy, or cyclosporine.[2][1] Outcomes are genenrally good.[3]

Allergic conjunctivitis affects up to 40% of people.[1] It has become more common in the 2000s.[3] Onset if often before the age of 20 and it becomes less common with age.[3] The condition was first described by John Bostock in 1819.[5]

Signs and symptoms

The conjunctiva is a thin membrane that covers the eye. When an allergen irritates the conjunctiva, common symptoms include: eye itching, eyelid swelling, tearing, sensitivity to light, watery discharge, and foreign body sensation (with pain).[6][7]

Itching is the most typical symptom of ocular allergy, and more than 75% of patients report this symptom when seeking treatment.[7] Symptoms are usually worse for patients when the weather is warm and dry, whereas cooler weather with lower temperatures and rain tend to assuage symptoms.[6] Signs in phlyctenular keratoconjunctivitis include small yellow nodules that develop over the cornea, which ulcerate after a few days.[8]

In addition to the physical discomfort allergic conjunctivitis causes, it also alters patients' routines, with patients limiting certain activities such as going outdoors, reading, sleeping, and driving.[7]

  • Seasonal and perennial allergic conjunctivitis: mild conjunctival injection and moderate chemosis.
    Seasonal and perennial allergic conjunctivitis: mild conjunctival injection and moderate chemosis.
  • Eye with mild allergic conjunctivitis
    Eye with mild allergic conjunctivitis

Causes

The cause of allergic conjunctivitis is an allergic reaction of the body's immune system to an allergen. Allergic conjunctivitis is common in people who have other signs of allergic disease such as hay fever, asthma and eczema.

Among the most common allergens are:[9]

  • Pollen from trees, grass and ragweed
  • Animal skin and secretions such as saliva
  • Perfumes
  • Cosmetics
  • Skin medicines
  • Air pollution
  • Smoke
  • Dust mites
  • Balsam of Peru (used in food and drink for flavoring, in perfumes and toiletries for fragrance, and in medicine and pharmaceutical items for healing properties)
  • Eye drops (A reaction to preservatives in eye drops can cause toxic conjunctivitis)
  • Contact lens solution (some preservatives can irritate the eye over time resulting in conjunctivitis)
  • Contact lens (conjunctivitis is also caused by repeated mechanical irritation of the conjunctiva by contact lens wearers)

Most cases of seasonal conjunctivitis are due to pollen and occur in the hay fever season, grass pollens in early summer and various other pollens and moulds may cause symptoms later in the summer.[10]

Pathophysiology

Binding IL-33 to receptor prompts the MyD88/IRAK1/IRAK4/TRAF6/NFκκB- dependent signaling pathway(and TRAF6/MAPK/AP-1-dependent pathway). Pathophysiological changes seen in allergic conjunctivitis happen after the transcription of IL-33-responsive genes[11]

The ocular allergic response is a cascade of events that is coordinated by mast cells.[12]

Beta chemokines such as eotaxin and MIP-1 alpha have been implicated in the priming and activation of mast cells in the ocular surface. When a particular allergen is present, sensitization takes place and prepares the system to launch an antigen specific response. TH2 differentiated T cells release cytokines, which promote the production of antigen specific immunoglobulin E (IgE). IgE then binds to IgE receptors on the surface of mast cells. Then, mast cells release histamine, which then leads to the release of cytokines, prostaglandins, and platelet-activating factor. Mast cell intermediaries cause an allergic inflammation and symptoms through the activation of inflammatory cells.[7]

When histamine is released from mast cells, it binds to H1 receptors on nerve endings and causes the ocular symptom of itching. Histamine also binds to H1 and H2 receptors of the conjunctival vasculature and causes vasodilatation. Mast cell-derived cytokines such as chemokine interleukin IL-8 are involved in recruitment of neutrophils. TH2 cytokines such as IL-5 recruit eosinophils and IL-4, IL-6, and IL-13, which promote increased sensitivity. Immediate symptoms are due to the molecular cascade. Encountering the allergen a patient is sensitive to leads to increased sensitization of the system and more powerful reactions. Advanced cases can progress to a state of chronic allergic inflammation.[7]

Diagnosis

In terms of the diagnosis we find the following:[13]

  • Physical exam
  • Clinical evaluation
  • Medical history

Diagnostic tests such as conjunctival scrapings to look for eosinophils are helpful in determining the cause of the allergic response.[14] If rhinitis is present, the condition is termed "allergic rhinoconjunctivitis" (ARC).

Classification

SAC and PAC

Both seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) are two acute allergic conjunctival disorders.[14] SAC is the most common ocular allergy.[6][15] Symptoms of the aforementioned ocular diseases include itching and pink to reddish eye(s).[14] These two eye conditions are mediated by mast cells.[14][15] Nonspecific measures to ameliorate symptoms include cold compresses, eyewashes with tear substitutes, and avoidance of allergens.[14] Treatment consists of antihistamine, mast cell stabilizers, dual mechanism anti-allergen agents, or topical antihistamines.[14] Corticosteroids are another option, but, considering the side-effects of cataracts and increased intraocular pressure, corticosteroids are reserved for more severe forms of allergic conjunctivitis such as vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC).[14]

VKC and AKC

Both vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis (AKC) are chronic allergic diseases wherein eosinophils, conjunctival fibroblasts, epithelial cells, mast cells, and TH2 lymphocytes aggravate the biochemistry and histology of the conjunctiva.[14] VKC is a disease of childhood and is prevalent in males living in warm climates.[14] AKC is frequently observed in males between the ages of 30 and 50.[14] VKC and AKC can be treated by medications used to combat allergic conjunctivitis or the use of steroids.[14] Maxwell-Lyons sign, shield ulcer, cobblestones papillae, gelatinous thickening at the limbus, and Horner-Trantas dots are specific features of vernal type.[citation needed]

Giant papillary conjunctivitis

Giant papillary conjunctivitis is not a true ocular allergic reaction and is caused by repeated mechanical irritation of the conjunctiva.[14] Repeated contact with the conjunctival surface caused by the use of contact lenses is associated with GPC.[15]

PKC

Main article: Phlyctenular keratoconjunctivitis

Phlyctenular keratoconjunctiviti (PKC) results from a delayed hypersensitivity/inflammatory reaction to antigens expressed by various pathogens. Common agents include Staph. aureus, Mycobacterium tuberculosis, Chlamydia and Candida.[16]

Management

(Potential) future therapeutic targets for allergic conjunctivitis[17]

Antihistamines, mast cell stabilizers or dual activity drugs are safe and usually effective.[14] Corticosteroids are reserved for more severe cases of inflammation, and their use should be monitored by an optometrist due to possible side-effects.[14] When an allergen is identified, the person should avoid the allergen as much as possible.[15]

If the allergen is encountered and the symptoms are mild, a cold compress or artificial tears can be used to provide relief.

Mast cell stabilizers

Mast cell stabilizers can help people with allergic conjunctivitis. They tend to have delayed results, but they have fewer side-effects than the other treatments and last much longer than those of antihistamines. Some people are given an antihistamine at the same time so that there is some relief of symptoms before the mast cell stabilizers becomes effective. Doctors commonly prescribe lodoxamide and nedocromil as mast cell stabilizers, which come as eye drops.[citation needed]

A mast cell stabilizer is a class of non-steroid controller medicine that reduces the release of inflammation-causing chemicals from mast cells. They block a calcium channel essential for mast cell degranulation, stabilizing the cell, thus preventing the release of histamine. Decongestants may also be prescribed. Another common mast cell stabilizer that is used for treating allergic conjunctivitis is sodium cromoglicate.

Antihistamines

Antihistamines such as diphenhydramine and chlorpheniramine are commonly used as treatment. People treated with H1 antihistamines exhibit reduced production of histamine and leukotrienes as well as downregulation of adhesion molecule expression on the vasculature which in turn attenuates allergic symptoms by 40–50%.[18]

Dual activity agents

Dual-action medications are both mast cell stabilizers and antihistamines. They are the most common prescribed class of topical anti allergy agent. Olopatadine[19] and ketotifen fumarate[20] are both commonly prescribed. Ketotifen is available without a prescription in some countries.

Corticosteroids

Ester based "soft" steroids such as loteprednol (Alrex) are typically sufficient to calm inflammation due to allergies, and carry a much lower risk of adverse reactions than amide based steroids.

A systematic review of 30 trials, with 17 different treatment comparisons found that all topical antihistamines and mast cell stabilizers included for comparison were effective in reducing symptoms of seasonal allergic conjunctivitis.[21] There was not enough evidence to determine differences in long-term efficacy among the treatments.[21]

Many of the eye drops can cause burning and stinging, and have side-effects. Proper eye hygiene can improve symptoms, especially with contact lenses. Avoiding precipitants, such as pollen or mold can be preventative.[citation needed]

Immunotherapy

Allergen immunotherapy (AIT) treatment involves administering doses of allergens to accustom the body to substances that are generally harmless (pollen, house dust mites), thereby inducing specific long-term tolerance.[22] Allergy immunotherapy can be administered orally (as sublingual tablets or sublingual drops), or by injections under the skin (subcutaneous). Discovered by Leonard Noon and John Freeman in 1911, allergy immunotherapy represents the only causative treatment for respiratory allergies.

Experimental research has targeted adhesion molecules known as selectins on epithelial cells. These molecules initiate the early capturing and margination of leukocytes from circulation. Selectin antagonists have been examined in preclinical studies, including cutaneous inflammation, allergy and ischemia-reperfusion injury. There are four classes of selectin blocking agents: (i) carbohydrate based inhibitors targeting all P-, E-, and L-selectins, (ii) antihuman selectin antibodies, (iii) a recombinant truncated form of PSGL-1 immunoglobulin fusion protein, and (iv) small-molecule inhibitors of selectins. Most selectin blockers have failed phase II/III clinical trials, or the studies were ceased due to their unfavorable pharmacokinetics or prohibitive cost.[18] Sphingolipids, present in yeast like Saccharomyces cerevisiae and plants, have also shown mitigative effects in animal models of gene knockout mice.[18]

Epidemiology

Allergic conjunctivitis occurs more frequently among those with allergic conditions, with the symptoms having a seasonal correlation.

Allergic conjunctivitis is a frequent condition as it is estimated to affect 20 percent of the population on an annual basis and approximately one-half of these people have a personal or family history of atopy.[citation needed]

Giant papillary conjunctivitis accounts for 0.5–1.0% of eye disease in most countries.[citation needed]

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 Bielory, L; Delgado, L; Katelaris, CH; Leonardi, A; Rosario, N; Vichyanoud, P (February 2020). "ICON: Diagnosis and management of allergic conjunctivitis". Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 124 (2): 118–134. doi:10.1016/j.anai.2019.11.014. PMID 31759180.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Alfonso, SA; Fawley, JD; Alexa Lu, X (September 2015). "Conjunctivitis". Primary care. 42 (3): 325–45. doi:10.1016/j.pop.2015.05.001. PMID 26319341.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 Baab, S; Le, PH; Gurnani, B; Kinzer, EE (January 2025). "Allergic Conjunctivitis". StatPearls. PMID 28846256.
  4. ↑ 4.0 4.1 Miyazaki, D; Fukagawa, K; Okamoto, S; Fukushima, A; Uchio, E; Ebihara, N; Shoji, J; Namba, K; Shimizu, Y (October 2020). "Epidemiological aspects of allergic conjunctivitis". Allergology international : official journal of the Japanese Society of Allergology. 69 (4): 487–495. doi:10.1016/j.alit.2020.06.004. PMID 32654975.
  5. ↑ Rodrigues, J; Kuruvilla, ME; Vanijcharoenkarn, K; Patel, N; Hom, MM; Wallace, DV (March 2021). "The spectrum of allergic ocular diseases". Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 126 (3): 240–254. doi:10.1016/j.anai.2020.11.016. PMID 33276116.
  6. ↑ 6.0 6.1 6.2 Bielory L, Friedlaender MH (February 2008). "Allergic conjunctivitis". Immunol Allergy Clin North Am. 28 (1): 43–58, vi. doi:10.1016/j.iac.2007.12.005. PMID 18282545.
  7. ↑ 7.0 7.1 7.2 7.3 7.4 Whitcup SM (2006). Cunningham ET Jr; Ng EWM (eds.). "Recent advances in ocular therapeutics". Int Ophthalmol Clin. 46 (4): 1–6. doi:10.1097/01.iio.0000212140.70051.33. PMID 17060786. S2CID 32853661.
  8. ↑ Onofrey, Bruce E.; Skorin, Leonid; Holdeman, Nicky R. (2005-01-01). Ocular Therapeutics Handbook: A Clinical Manual. Lippincott Williams & Wilkins. ISBN 9780781748926. Archived from the original on 2021-07-10. Retrieved 2022-07-19. ... including virus, fungus, chlamydia, and nematodes.
  9. ↑ Karakus, S. "Allergic Conjunctivitis". Johns Hopkins Medicine. Archived from the original on 10 July 2021. Retrieved 10 July 2021. Archived 10 July 2021 at the Wayback Machine
  10. ↑ "What is conjunctivitis?". patient.info. Archived from the original on 30 April 2010. Retrieved 2010-04-06. Archived 2010-04-30 at the Wayback Machine
  11. ↑ Chigbu, DeGaulle I.; Karbach, Nicholas J.; Abu, Sampson L.; Hehar, Navpreet K. (7 March 2024). "Cytokines in Allergic Conjunctivitis: Unraveling Their Pathophysiological Roles". Life (Basel, Switzerland). 14 (3): 350. doi:10.3390/life14030350. ISSN 2075-1729.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  12. ↑ Liu G, Keane-Myers A, Miyazaki D, Tai A, Ono SJ (1999). "Molecular and cellular aspects of allergic conjunctivitis". Immune Response and the Eye. Chemical Immunology and Allergy. Vol. 73. pp. 39–58. doi:10.1159/000058748. ISBN 978-3-8055-6893-7. PMID 10590573. {{cite book}}: |journal= ignored (help)
  13. ↑ Baab, Shad; Le, Patrick H.; Gurnani, Bharat; Kinzer, Eilene E. (2024). "Allergic Conjunctivitis". StatPearls. StatPearls Publishing. Archived from the original on 2024-08-04. Retrieved 2024-08-01. Archived 2024-08-04 at the Wayback Machine
  14. ↑ 14.00 14.01 14.02 14.03 14.04 14.05 14.06 14.07 14.08 14.09 14.10 14.11 14.12 14.13 Ono SJ, Abelson MB (January 2005). "Allergic conjunctivitis: update on pathophysiology and prospects for future treatment". J. Allergy Clin. Immunol. 115 (1): 118–22. doi:10.1016/j.jaci.2004.10.042. PMID 15637556.
  15. ↑ 15.0 15.1 15.2 15.3 Buckley RJ (December 1998). "Allergic eye disease—a clinical challenge". Clin. Exp. Allergy. 28 (Suppl 6): 39–43. doi:10.1046/j.1365-2222.1998.0280s6039.x. PMID 9988434. S2CID 23496108.
  16. ↑ Allansmith M.R.; Ross R.N. (1991). "Phlyctenular keratoconjunctivitis". In Tasman W.; Jaeger E.A. (eds.). Duane's Clinical Ophthalmology. Vol. 1 (revised ed.). Philadelphia: Harper & Row. pp. 1–5.
  17. ↑ Labib, Bisant A.; Chigbu, DeGaulle I. (28 April 2022). "Therapeutic Targets in Allergic Conjunctivitis". Pharmaceuticals (Basel, Switzerland). 15 (5): 547. doi:10.3390/ph15050547. ISSN 1424-8247. Archived from the original on 18 April 2024. Retrieved 26 July 2024.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  18. ↑ 18.0 18.1 18.2 Sun, W. Y.; Bonder, C. S. (2012). "Sphingolipids: A Potential Molecular Approach to Treat Allergic Inflammation". Journal of Allergy. 2012: 1–14. doi:10.1155/2012/154174. PMC 3536436. PMID 23316248.
  19. ↑ Rosenwasser LJ, O'Brien T, Weyne J (September 2005). "Mast cell stabilization and anti-histamine effects of olopatadine ophthalmic solution: a review of pre-clinical and clinical research". Curr Med Res Opin. 21 (9): 1377–87. doi:10.1185/030079905X56547. PMID 16197656. S2CID 8954933.
  20. ↑ Avunduk AM, Tekelioglu Y, Turk A, Akyol N (September 2005). "Comparison of the effects of ketotifen fumarate 0.025% and olopatadine HCl 0.1% ophthalmic solutions in seasonal allergic conjunctivities: a 30-day, randomized, double-masked, artificial tear substitute-controlled trial". Clin Ther. 27 (9): 1392–402. doi:10.1016/j.clinthera.2005.09.013. PMID 16291412.
  21. ↑ 21.0 21.1 Castillo M, Scott NW, Mustafa MZ, Mustafa MS, Azuara-Blanco A (2015). "Topical antihistamines and mast cell stabilisers for treating seasonal and perennial allergic conjunctivitis". Cochrane Database Syst Rev. 6 (6): CD009566. doi:10.1002/14651858.CD009566.pub2. hdl:2164/6048. PMID 26028608.
  22. ↑ Van Overtvelt L. et al. Immune mechanisms of allergen-specific sublingual immunotherapy. Revue française d'allergologie et d'immunologie clinique. 2006; 46: 713–720.

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