Editing Allergic conjunctivitis

{{Infobox medical condition (new)
| name            = Allergic eye disease
| synonyms        =
| image           = Blausen 0013 AllergicConjunctivitis.png
| caption         = Illustration of allergic conjunctivitis
| pronounce       =
| field           =
| symptoms        =
| complications   =
| onset           =
| duration        =
| types           =
| causes          =
| risks           =
| diagnosis       =
| differential    =
| prevention      =
| treatment       =
| medication      =
| prognosis       =
| frequency       =
| deaths          =
}}

'''Allergic conjunctivitis''' ('''AC''') is [[Allergic Inflammation|inflammation]] of the [[conjunctiva]] (the [[membrane]] covering the white part of the eye) due to [[allergy]].<ref name="Bielory">{{cite journal |vauthors=Bielory L, Friedlaender MH | title = Allergic conjunctivitis | journal = Immunol Allergy Clin North Am | volume = 28 | issue = 1 | pages = 43–58, vi |date=February 2008 | pmid = 18282545 | doi = 10.1016/j.iac.2007.12.005 | s2cid = 34371872 }}</ref> Although [[allergen]]s differ among patients, the most common cause is [[hay fever]]. Symptoms consist of redness (mainly due to [[vasodilation]] of the peripheral small [[blood vessel]]s), [[edema]] (swelling) of the conjunctiva, [[itch]]ing, and increased [[lacrimation]] (production of [[tears]]). If this is combined with [[rhinitis]], the condition is termed '''allergic rhinoconjunctivitis''' ('''ARC''').

The symptoms are due to release of [[histamine]] and other active substances by [[mast cell]]s, which stimulate dilation of blood vessels, irritate [[nerve ending]]s, 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 [[antihistamine]]s, either topical (in the form of [[eye drop]]s), or systemic (in the form of tablets). Antihistamines, medications that stabilize mast cells, and [[nonsteroidal anti-inflammatory drug]]s (NSAIDs) are generally safe and usually effective.<ref name="Ono"/>

==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]] [[itch]]ing, eyelid swelling, tearing, [[photophobia]], watery discharge, and foreign body sensation (with pain).<ref name="Bielory"/><ref name="Cunningham">{{cite journal | author = Whitcup SM | title = Recent advances in ocular therapeutics | journal = Int Ophthalmol Clin |editor1=Cunningham ET Jr |editor2=Ng EWM | volume = 46 | issue = 4 | pages = 1–6 | year = 2006 | pmid = 17060786 | doi = 10.1097/01.iio.0000212140.70051.33 | s2cid = 32853661 }}</ref>

Itching is the most typical symptom of ocular allergy, and more than 75% of patients report this symptom when seeking treatment.<ref name="Cunningham"/> 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.<ref name="Bielory"/> Signs in [[phlyctenular keratoconjunctivitis]] include small yellow nodules that develop over the cornea, which ulcerate after a few days.<ref>{{Cite book|url=https://books.google.com/books?id=LOuL8W1UJKgC&q=phlyctenule&pg=PA176|title=Ocular Therapeutics Handbook: A Clinical Manual|last1=Onofrey|first1=Bruce E.|last2=Skorin|first2=Leonid|last3=Holdeman|first3=Nicky R.|date=2005-01-01|publisher=Lippincott Williams & Wilkins|isbn=9780781748926|language=en|quote=... including virus, fungus, chlamydia, and nematodes.}}</ref>

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.<ref name="Cunningham"/> Therefore, treating patients with allergic conjunctivitis may improve their everyday [[quality of life]].{{cn|date=February 2023}}

==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|date=April 2014}}

Among the most common allergens that cause conjunctivitis are:<ref>{{cite web |last=Karakus |first=S |url=https://www.hopkinsmedicine.org/health/conditions-and-diseases/allergic-conjunctivitis| title=Allergic Conjunctivitis
|website=Johns Hopkins Medicine |access-date= 10 July 2021}}</ref>
* [[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 [[Mold (fungus)|moulds]] may cause symptoms later in the summer.<ref name="PatUK">{{cite web|url = http://patient.info/health/allergic-conjunctivitis-leaflet|title = What is conjunctivitis?|publisher = patient.info|access-date = 2010-04-06|archive-url = https://web.archive.org/web/20100430232351/http://www.patient.co.uk/health/Allergic-Conjunctivitis.htm|archive-date = 30 April 2010 |url-status = live}}</ref>

==Pathophysiology==
[[File:01-09-11 0222.jpg|thumb|250px|right|Eye with mild allergic conjunctivitis]]
The ocular allergic response is a cascade of events that is coordinated by [[mast cells]].<ref>{{cite book |vauthors=Liu G, Keane-Myers A, Miyazaki D, Tai A, Ono SJ | title = Immune Response and the Eye | chapter = Molecular and cellular aspects of allergic conjunctivitis | journal = Chem. Immunol. | volume = 73 | pages = 39–58 | year = 1999 | pmid = 10590573 | doi = 10.1159/000058748 | series = Chemical Immunology and Allergy | isbn = 978-3-8055-6893-7 }}</ref> Beta [[chemokine]]s such as [[eotaxin]] and [[CCL3|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. [[T helper cell|TH2 differentiated]] [[T cell]]s 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, [[prostaglandin]]s, and [[platelet-activating factor]]. Mast cell intermediaries cause an allergic inflammation and symptoms through the activation of inflammatory cells.<ref name="Cunningham"/>

When [[histamine]] is released from mast cells, it binds to [[histamine H1 receptor|H1 receptors]] on nerve endings and causes the ocular symptom of itching. Histamine also binds to H1 and [[histamine H2 receptor|H2 receptors]] of the conjunctival vasculature and causes [[vasodilatation]]. Mast cell-derived cytokines such as chemokine interleukin [[Interleukin 8|IL-8]] are involved in recruitment of [[neutrophil]]s. TH2 cytokines such as [[Interleukin 5|IL-5]] recruit eosinophils and [[Interleukin 4|IL-4]], [[Interleukin 6|IL-6]], and [[Interleukin 13|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.<ref name="Cunningham"/>

==Diagnosis==
===Classification===

====SAC and PAC====
Both seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) are two acute allergic conjunctival disorders.<ref name="Ono">{{cite journal |vauthors=Ono SJ, Abelson MB | title = Allergic conjunctivitis: update on pathophysiology and prospects for future treatment | journal = J. Allergy Clin. Immunol. | volume = 115 | issue = 1 | pages = 118–22 |date=January 2005 | pmid = 15637556 | doi = 10.1016/j.jaci.2004.10.042 }}</ref> SAC is the most common ocular allergy.<ref name="Bielory"/><ref name="Buckley">{{cite journal | author = Buckley RJ | title = Allergic eye disease—a clinical challenge | journal = Clin. Exp. Allergy | volume = 28 | issue =Suppl 6 | pages = 39–43 |date=December 1998 | pmid = 9988434 | doi = 10.1046/j.1365-2222.1998.0280s6039.x | s2cid = 23496108 }}</ref> Symptoms of the aforementioned ocular diseases include itching and pink to reddish eye(s).<ref name="Ono"/> These two eye conditions are mediated by mast cells.<ref name="Ono"/><ref name="Buckley"/> Nonspecific measures to ameliorate symptoms include cold compresses, eyewashes with tear substitutes, and avoidance of allergens.<ref name="Ono"/> Treatment consists of [[antihistamine]], [[mast cell stabilizer]]s, dual mechanism anti-allergen agents, or topical antihistamines.<ref name="Ono"/> [[Corticosteroid]]s 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).<ref name="Ono"/>

====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]].<ref name="Ono"/> VKC is a disease of childhood and is prevalent in males living in warm climates.<ref name="Ono"/> AKC is frequently observed in males between the ages of 30 and 50.<ref name="Ono"/> VKC and AKC can be treated by medications used to combat allergic conjunctivitis or the use of steroids.<ref name="Ono"/> Maxwell-Lyons sign, shield ulcer, cobblestones papillae, gelatinous thickening at the limbus, and Horner-Trantas dots are specific features of vernal type.{{citation needed|date=February 2014}}

====Giant papillary conjunctivitis====
Giant papillary conjunctivitis is not a true ocular allergic reaction and is caused by repeated mechanical irritation of the conjunctiva.<ref name="Ono"/> Repeated contact with the conjunctival surface caused by the use of contact lenses is associated with GPC.<ref name="Buckley"/>

====PKC====
{{main article|Phlyctenular keratoconjunctivitis}}
Phlyctenular keratoconjunctivitis (PKC) results from a delayed hypersensitivity/inflammatory reaction to antigens expressed by various pathogens. Common agents include [[Staph. aureus]], [[Mycobacterium tuberculosis]], [[Chlamydia (bacterium)|Chlamydia]] and [[Candida (genus)|Candida]].<ref name="ReferenceA">{{cite book |author1=Allansmith M.R. |author2=Ross R.N. |chapter=Phlyctenular keratoconjunctivitis |editor1=Tasman W. |editor2=Jaeger E.A. |title=Duane's Clinical Ophthalmology |publisher=Harper & Row |location=Philadelphia |year=1991 |pages=1–5 |edition=revised |volume=1}}</ref>

==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.<ref name="Ono"/> Antihistamines, mast cell stabilizers or dual activity drugs are safe and usually effective.<ref name="Ono"/> Corticosteroids are reserved for more severe cases of inflammation, and their use should be monitored by an optometrist due to possible side-effects.<ref name="Ono"/> When an allergen is identified, the person should avoid the allergen as much as possible.<ref name="Buckley"/>

===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.{{cn|date=July 2022}}

===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.{{cn|date=July 2022}}

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%.<ref name="sphingo">{{Cite journal | last1 = Sun | first1 = W. Y. | last2 = Bonder | first2 = C. S. | doi = 10.1155/2012/154174 | title = Sphingolipids: A Potential Molecular Approach to Treat Allergic Inflammation | journal = Journal of Allergy | volume = 2012 | pages = 1–14 | year = 2012 | pmid = 23316248 | pmc =3536436 | doi-access = free }}</ref>

===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)<ref>{{cite journal |vauthors=Rosenwasser LJ, O'Brien T, Weyne J |title=Mast cell stabilization and anti-histamine effects of olopatadine ophthalmic solution: a review of pre-clinical and clinical research |journal=Curr Med Res Opin |volume=21 |issue=9 |pages=1377–87 |date=September 2005 |pmid=16197656 |doi=10.1185/030079905X56547 |s2cid=8954933 }}</ref> and [[ketotifen fumarate]] (Alaway or Zaditor)<ref>{{cite journal |vauthors=Avunduk AM, Tekelioglu Y, Turk A, Akyol N |title=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 |journal=Clin Ther |volume=27 |issue=9 |pages=1392–402 |date=September 2005 |pmid=16291412 |doi=10.1016/j.clinthera.2005.09.013 }}</ref> are both commonly prescribed. Ketotifen is available without a prescription in some countries.{{citation needed|date=October 2022|reason=where?}} However, studies demonstrates that olopatadine is more effective than ketotifen in reducing the itching associated with allergic conjunctivitis in the antigen challenge model.<ref>{{cite journal |last1=Berdy |first1=Gregg J. |last2=Spangler |first2=Dennis L. |last3=Bensch |first3=George |last4=Berdy |first4=Susan S. |last5=Brusatti |first5=Robert C. |title=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 |journal=Clinical Therapeutics |date=May 17, 2000 |volume=22 |issue=7 |pages=826–833 |doi=10.1016/S0149-2918(00)80055-7 |url=https://www.clinicaltherapeutics.com/article/S0149-2918(00)80055-7/ |pmid=10945509|url-access=subscription }}</ref>

===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.<ref name="Castillo">{{cite journal |vauthors=Castillo M, Scott NW, Mustafa MZ, Mustafa MS, Azuara-Blanco A |title= Topical antihistamines and mast cell stabilisers for treating seasonal and perennial allergic conjunctivitis |journal=Cochrane Database Syst Rev|volume=2015 |issue= 6 |pages= CD009566 |date=2015 |pmid= 26028608 |doi= 10.1002/14651858.CD009566.pub2|pmc= 10616535 |hdl= 2164/6048 |hdl-access= free }}</ref> There was not enough evidence to determine differences in long-term efficacy among the treatments.<ref name="Castillo"/>

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|date=January 2013}}

===Immunotherapy===
[[Allergy 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.<ref>Van Overtvelt L. et al. Immune mechanisms of allergen-specific sublingual immunotherapy. Revue française d'allergologie et d'immunologie clinique. 2006; 46: 713–720.</ref> 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.<ref name="sphingo"/> Sphingolipids, present in yeast like ''[[Saccharomyces cerevisiae]]'' and plants, have also shown mitigative effects in animal models of gene knockout mice.<ref name="sphingo"/>

==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]].{{cn|date=July 2022}}

Giant papillary conjunctivitis accounts for 0.5–1.0% of [[eye disease]] in most countries.{{citation needed|date=April 2014}}

==References==
{{Reflist}}

== External links ==
{{Medical resources
| DiseasesDB      = 30842
| ICD10           = {{ICD10|H|10|1|h|10}}
| ICD9            = {{ICD9|372.14}}
| ICDO            =
| OMIM            =
| MedlinePlus     = 001031
| eMedicineSubj   =
| eMedicineTopic  =
| MeshID          = D003233
| SNOMED CT       = 473460002
}}
* {{MeshName|Conjunctivitis,+Allergic|3= Allergic Conjunctivitis}}

{{Allergic conditions}}
{{Eye pathology}}
{{Hypersensitivity and autoimmune diseases}}

{{DEFAULTSORT:Allergic Conjunctivitis}}
[[Category:Disorders of conjunctiva]]
[[Category:Allergology]]

[[de:Konjunktivitis#Conjunktivitis allergica]]