Allergic conjunctivitis

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Allergic eye disease
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Illustration of allergic conjunctivitis
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Allergic conjunctivitis (AC) is inflammation of the conjunctiva (the membrane covering the white part of the eye) due to allergy. [1] Although allergens differ among patients, the most common cause is hay fever. Symptoms consist of redness (mainly due to vasodilation of the peripheral small blood vessels), edema (swelling) of the conjunctiva, itching, and increased lacrimation (production of tears). If this is combined with rhinitis, the condition is termed allergic rhinoconjunctivitis (ARC).

Contents

The symptoms are due to release of histamine and other active substances by mast cells, which stimulate dilation of blood vessels, irritate nerve endings, and increase secretion of tears.

Treatment of allergic conjunctivitis is by avoiding the allergen (e.g., avoiding grass in bloom during "hay fever season") and treatment with antihistamines, either topical (in the form of eye drops), or systemic (in the form of tablets). Antihistamines, medications that stabilize mast cells, and nonsteroidal anti-inflammatory drugs (NSAIDs) are generally safe and usually effective. [2]

Signs and symptoms

The conjunctiva is a thin membrane that covers the eye. When an allergen irritates the conjunctiva, common symptoms that occur in the eye include: ocular itching, eyelid swelling, tearing, photophobia, watery discharge, and foreign body sensation (with pain). [1] [3]

Itching is the most typical symptom of ocular allergy, and more than 75% of patients report this symptom when seeking treatment. [3] 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. [1] Signs in phlyctenular keratoconjunctivitis include small yellow nodules that develop over the cornea, which ulcerate after a few days. [4]

A study by Klein et al. showed that 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. [3] Therefore, treating patients with allergic conjunctivitis may improve their everyday quality of life.[ citation needed ]

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. [ citation needed ]

Among the most common allergens that cause conjunctivitis are: [5]

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. [6]

Pathophysiology

Eye with mild allergic conjunctivitis 01-09-11 0222.jpg
Eye with mild allergic conjunctivitis

The ocular allergic response is a cascade of events that is coordinated by mast cells. [7] 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. [3]

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. [3]

Diagnosis

Classification

SAC and PAC

Both seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) are two acute allergic conjunctival disorders. [2] SAC is the most common ocular allergy. [1] [8] Symptoms of the aforementioned ocular diseases include itching and pink to reddish eye(s). [2] These two eye conditions are mediated by mast cells. [2] [8] Nonspecific measures to ameliorate symptoms include cold compresses, eyewashes with tear substitutes, and avoidance of allergens. [2] Treatment consists of antihistamine, mast cell stabilizers, dual mechanism anti-allergen agents, or topical antihistamines. [2] 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). [2]

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. [2] VKC is a disease of childhood and is prevalent in males living in warm climates. [2] AKC is frequently observed in males between the ages of 30 and 50. [2] VKC and AKC can be treated by medications used to combat allergic conjunctivitis or the use of steroids. [2] 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. [2] Repeated contact with the conjunctival surface caused by the use of contact lenses is associated with GPC. [8]

PKC

Phlyctenular keratoconjunctivitis (PKC) results from a delayed hypersensitivity/inflammatory reaction to antigens expressed by various pathogens. Common agents include Staph. aureus, Mycobacterium tuberculosis, Chlamydia and Candida. [9]

Management

A detailed history allows doctors to determine whether the presenting symptoms are due to an allergen or another source. Diagnostic tests such as conjunctival scrapings to look for eosinophils are helpful in determining the cause of the allergic response. [2] Antihistamines, mast cell stabilizers or dual activity drugs are safe and usually effective. [2] Corticosteroids are reserved for more severe cases of inflammation, and their use should be monitored by an optometrist due to possible side-effects. [2] When an allergen is identified, the person should avoid the allergen as much as possible. [8]

Non-pharmacological methods

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

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%. [10]

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 (Patanol, Pazeo) [11] and ketotifen fumarate (Alaway or Zaditor) [12] are both commonly prescribed. Ketotifen is available without a prescription in some countries.[ citation needed ] However, studies demonstrates that olopatadine is more effective than ketotifen in reducing the itching associated with allergic conjunctivitis in the antigen challenge model. [13]

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. [14] There was not enough evidence to determine differences in long-term efficacy among the treatments. [14]

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. [15] 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. [10] Sphingolipids, present in yeast like Saccharomyces cerevisiae and plants, have also shown mitigative effects in animal models of gene knockout mice. [10]

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 ]

Related Research Articles

<span class="mw-page-title-main">Conjunctivitis</span> Inflammation of the eye

Conjunctivitis, also known as pink eye, is inflammation of the outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. Pain, burning, scratchiness, or itchiness may occur. The affected eye may have increased tears or be "stuck shut" in the morning. Swelling of the white part of the eye may also occur. Itching is more common in cases due to allergies. Conjunctivitis can affect one or both eyes.

An allergen is a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body. Such reactions are called allergies.

H1 antagonists, also called H1 blockers, are a class of medications that block the action of histamine at the H1 receptor, helping to relieve allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines; other agents may have antihistaminergic action but are not true antihistamines.

<span class="mw-page-title-main">Allergic rhinitis</span> Nasal inflammation due to allergens in the air

Allergic rhinitis, of which the seasonal type is called hay fever, is a type of inflammation in the nose that occurs when the immune system overreacts to allergens in the air. Signs and symptoms include a runny or stuffy nose, sneezing, red, itchy, and watery eyes, and swelling around the eyes. The fluid from the nose is usually clear. Symptom onset is often within minutes following allergen exposure, and can affect sleep and the ability to work or study. Some people may develop symptoms only during specific times of the year, often as a result of pollen exposure. Many people with allergic rhinitis also have asthma, allergic conjunctivitis, or atopic dermatitis.

<span class="mw-page-title-main">Rhinitis</span> Irritation and inflammation of the mucous membrane inside the nose

Rhinitis, also known as coryza, is irritation and inflammation of the mucous membrane inside the nose. Common symptoms are a stuffy nose, runny nose, sneezing, and post-nasal drip.

<span class="mw-page-title-main">Hives</span> Skin disease characterized by red, raised, and itchy bumps

Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasting skin change. Fewer than 5% of cases last for more than six weeks. The condition frequently recurs.

<span class="mw-page-title-main">Type I hypersensitivity</span> Type of allergic reaction

Type I hypersensitivity, in the Gell and Coombs classification of allergic reactions, is an allergic reaction provoked by re-exposure to a specific type of antigen referred to as an allergen. Type I is distinct from type II, type III and type IV hypersensitivities. The relevance of the Gell and Coombs classification of allergic reactions has been questioned in the modern-day understanding of allergy, and it has limited utility in clinical practice.

<span class="mw-page-title-main">Olopatadine</span> Chemical compound

Olopatadine, sold under the brand name Patanol among others, is an antihistamine medication used to decrease the symptoms of allergic conjunctivitis and allergic rhinitis. It is used as eye drops or as a nasal spray. The eye drops generally result in an improvement within half an hour.

<span class="mw-page-title-main">Ketotifen</span> Antihistamine medication

Ketotifen is an antihistamine medication and a mast cell stabilizer used to treat allergic conditions such as conjunctivitis, asthma, and urticaria (hives). Ketotifen is available in ophthalmic and oral forms: the ophthalmic form relieves eye itchiness and irritation associated with seasonal allergies, while the oral form helps prevent systemic conditions such as asthma attacks and allergic reactions. In addition to treating allergies, ketotifen has shown efficacy in managing systemic mast cell diseases such as mastocytosis and mast cell activation syndrome (MCAS), which involve abnormal accumulation or activation of mast cells throughout the body. Ketotifen is also used for other allergic-type conditions like atopic dermatitis (eczema) and food allergies.

<span class="mw-page-title-main">Allergic contact dermatitis</span> Medical condition

Allergic contact dermatitis (ACD) is a form of contact dermatitis that is the manifestation of an allergic response caused by contact with a substance; the other type being irritant contact dermatitis (ICD).

<span class="mw-page-title-main">Vernal keratoconjunctivitis</span> Medical condition

Vernal keratoconjunctivitis is a recurrent, bilateral, and self-limiting type of conjunctivitis having a periodic seasonal incidence.

<span class="mw-page-title-main">Nedocromil</span> Chemical compound

Nedocromil sodium is a medication considered as mast cell stabilizer which acts to prevent wheezing, shortness of breath, and other breathing problems caused by asthma. It is administered by an inhaler under the brand name Tilade, and as an eye drop under the brand name Alocril. The effects of nedocromil versus asthma are gradual rather than fast-acting and it is not indicated for acute respiratory distress compared to fast acting bronchodilators like albuterol or other well-known inhaler medications. Liquid preparations of nedocromil are available in the UK under the name Rapitil for use for allergic eye reactions. Nedocromil sodium has been shown to be effective in alleviating symptoms of allergic conjunctivitis.

<span class="mw-page-title-main">Emedastine</span> Chemical compound

Emedastine (trade name Emadine) is a second generation antihistamine used in eye drops to alleviate the symptoms of allergic conjunctivitis. It acts as a H1 receptor antagonist. It works by blocking the action of histamine that causes allergic symptoms. It is used in form of the difumarate. The emedastine difumarate is a white, crystalline, water-soluble fine powder. Emedastine eye drops is usually applied twice a day to the affected eye. When the patients with allergic conjunctivitis were treated with 0.05% emedastine difumarate ophthalmic solution for six weeks, the signs and symptoms such as redness, itching and swelling of the eyes were relieved. Emedastine appears to be devoid of effects on adrenergic, dopaminergic and serotonin receptors. This drug was developed by Alcon, which is global medical company specializing in eye care products.

<span class="mw-page-title-main">Allergic inflammation</span>

Allergic inflammation is an important pathophysiological feature of several disabilities or medical conditions including allergic asthma, atopic dermatitis, allergic rhinitis and several ocular allergic diseases. Allergic reactions may generally be divided into two components; the early phase reaction, and the late phase reaction. While the contribution to the development of symptoms from each of the phases varies greatly between diseases, both are usually present and provide us a framework for understanding allergic disease.

<span class="mw-page-title-main">Mast cell stabilizer</span> Category of pharmaceutical drugs

Mast cell stabilizers are medications used to prevent or treat certain allergic disorders. They block mast cell degranulation, stabilizing the cell and thereby preventing the release of histamine and related mediators. One suspected pharmacodynamic mechanism is the blocking of IgE-regulated calcium channels. Without intracellular calcium, the histamine vesicles cannot fuse to the cell membrane and degranulate.

A drug allergy is an allergy to a drug, most commonly a medication, and is a form of adverse drug reaction. Medical attention should be sought immediately if an allergic reaction is suspected.

<span class="mw-page-title-main">Allergic response</span>

An allergic response is a hypersensitive immune reaction to a substance that normally is harmless or would not cause an immune response in everyone. An allergic response may cause harmful symptoms such as itching or inflammation or tissue injury.

<span class="mw-page-title-main">Alcaftadine</span> Chemical compound

Alcaftadine, sold under the brand name Lastacaft, is an antihistamine used to help prevent itching of the eyes. It is an H1 histamine receptor antagonist. It is given as an drops in the eye.

Mast cell activation syndrome (MCAS) is a term referring to one of two types of mast cell activation disorder (MCAD); the other type is idiopathic MCAD. MCAS is an immunological condition in which mast cells inappropriately and excessively release chemical mediators, resulting in a range of chronic symptoms, sometimes including anaphylaxis or near-anaphylaxis attacks. Primary symptoms include cardiovascular, dermatological, gastrointestinal, neurological and respiratory problems.

Anti-allergic agents are medications used to treat allergic reactions. Anti-allergic agents have existed since 3000 B.C in countries such as China and Egypt. It was not until 1933 when antihistamines, the first type of anti-allergic agents, were developed. Common allergic diseases include allergic rhinitis, allergic asthma and atopic dermatitis with varying symptoms, including runny nose, watery eyes, itchiness, coughing, and shortness of breath. More than one-third of the world's population is currently being affected by one or more allergic conditions.

References

  1. 1 2 3 4 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. S2CID   34371872.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 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.
  3. 1 2 3 4 5 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.
  4. ↑ Onofrey, Bruce E.; Skorin, Leonid; Holdeman, Nicky R. (2005-01-01). Ocular Therapeutics Handbook: A Clinical Manual. Lippincott Williams & Wilkins. ISBN   9780781748926. ... including virus, fungus, chlamydia, and nematodes.
  5. ↑ Karakus, S. "Allergic Conjunctivitis". Johns Hopkins Medicine. Retrieved 10 July 2021.
  6. ↑ "What is conjunctivitis?". patient.info. Archived from the original on 30 April 2010. Retrieved 2010-04-06.
  7. ↑ 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)
  8. 1 2 3 4 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.
  9. ↑ 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.
  10. 1 2 3 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ Berdy, Gregg J.; Spangler, Dennis L.; Bensch, George; Berdy, Susan S.; Brusatti, Robert C. (May 17, 2000). "Comparison of the analgesic efficacy of concurrent ibuprofen and paracetamol with ibuprofen or paracetamol alone in the management of moderate to severe acute postoperative dental pain in adolescents and adults: A randomized, double-blind, placebo-controlled, parallel-group, single-dose, two-center, modified factorial study". Clinical Therapeutics. 22 (7): 826–833. doi:10.1016/S0149-2918(00)80055-7. PMID   10945509.
  14. 1 2 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. 2015 (6): CD009566. doi:10.1002/14651858.CD009566.pub2. hdl: 2164/6048 . PMC   10616535 . PMID   26028608.
  15. ↑ 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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