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Pseudoallergy

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Pseudoallergy, sometimes known as nonallergic hypersensitivity, is a type of hypersensitivity reaction mostly described in the context of drug allergy. The mechanism is somewhat similar to the type 1 hypersensitivity in the Gell and Coombs classification in that the effector cell is also mast cell. In pseudoallergic reaction, the mast cell is directly activated, rather than through the mediation of Immunoglobulin E (IgE). Therefore, it is also known as direct mast cell activation.[1][2]

Pseudoallergy
Other namesNonallergic hypersensitivity
SpecialtyDermatology, Rheumatology, Internal medicine
CausesDirect mast cell activation through non-IgE receptors

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), along with certain food ingredients and additives like tartrazine, benzoates, and salicylates, are the most common causes of pseudoallergic reactions. Since these reactions don't require IgE sensitization, they may manifest themselves after only one exposure. Doses-dependent, pseudoallergic reactions typically involve substances that are chemically unrelated to each other.[3]

The lack of information in skin tests and serology makes the diagnosis challenging. Nonallergic hypersensitivity is diagnosed on the basis of symptoms. Oral challenge tests can be used to confirm pseudoallergy in the proper clinical context, i.e. a person consumes progressively larger quantities of a suspected allergen under medical supervision.[4][5]

Signs and symptoms

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Clinically, pseudoallergy and anaphylaxis are identical.[6] Pseudoallergy symptoms include gastrointestinal symptoms, urticaria, bronchospasm, and angioedema,[7] along with headache, edema, skin flushing, hypotension, and shock.[8]

Causes

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Although they are commonly used to treat pain related to fractures, opioid medications have well-known side effects.[9] Almost all opioids have the ability to directly induce mast cell degranulation, which in turn can result in pseudoallergy.[10] Opioid medications, including morphine, codeine, and meperidine, have been known to cause pseudoallergy.[11] By directly activating mast cells, opioids cause histamine release, which results in flushing or pruritus that is almost always mistaken for allergy symptoms.[12] Compared to other opioids, codeine and morphine have been shown to be more likely to cause mast cell degranulation. By using a non-immunologic mechanism that is not dependent on IgE or the high-affinity IgE receptor FcεRI, codeine causes pseudoallergy.[13] This suggests that codeine may activate mast cell degranulation by acting on the opioid receptor.[14]

Mechanism

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One recognized mechanism is through the activation of mast cell receptor Mas-Related G Protein-Coupled Receptor-X2 (MRGPRX2).[15] MRGPRX2 is a G protein-coupled receptor capable of recognizing both endogenous and exogenous stimuli, therefore activating the degranulation of mast cell, results in pseudoallergic reaction. MRGPRX2 is expressed in mast cells (particularly connective tissue mast cells [MCTC] found in the skin), sensory neurons, and keratinocytes. Comparing to type 1 hypersensitivity, MRGPRX2-mediated response is more rapid and transient. It is proposed that single nucleotide polymorphism of this receptor may results in different reaction among individuals, although clinical significance is undertermined.[2]

Other mechanisms results in direct mast cell activation are suggested, including complement receptors (CR3, CR4, CR3a, CR5a) activated by the respective complement factors; toll-like receptors activated by bacterial lipopolysaccharide or peptidoglycan; surface IgE receptors (FcεRI, FcεRII) activated by autoantibodies or parasites; IgG receptors (FcγRII) activated by pathogen-specific IgG; Cysteinyl leukotriene receptors (CysLT1R/2R) activated by cysteinyl leukotrienes; Protease-activated receptors (PAR2) activated by other mast-cell proteases.[2]

While pseudoallergy and IgE-mediated allergy share some similarities in their clinical manifestations,[16] pseudoallergy is not the same as common allergy or type 1 reactions.[17] Pseudoallergy can be caused by a variety of medications through various pathways. For example, taxol can cause pseudoallergy by stimulating the complement system. The reaction occurs for the first time without any prior sensitization.[18]

See also

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References

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  1. ^ Zuberbier, Torsten (2001). "The Role of Allergens and Pseudoallergens in Urticaria". Journal of Investigative Dermatology Symposium Proceedings. 6 (2). Elsevier BV: 132–134. doi:10.1046/j.0022-202x.2001.00024.x. ISSN 1087-0024. PMID 11764298.
  2. ^ a b c Rich, Robert R.; Fleisher, Thomas A.; Schroeder, Harry W.; Weyand, Cornelia M.; Corry, David B.; Puck, Jennifer, eds. (2023). Clinical immunology: principles and practice (6th ed.). Amsterdam, The Netherlands: Elsevier. ISBN 978-0-7020-8165-1. OCLC 1295106160.
  3. ^ Grattan, Clive E.H.; Borzova, Elena (2019). "Urticaria, Angioedema, and Anaphylaxis". Clinical Immunology. Elsevier. pp. 585–600.e1. doi:10.1016/b978-0-7020-6896-6.00042-9. ISBN 978-0-7020-6896-6.
  4. ^ Reese, Imke; Zuberbier, Torsten; Bunselmeyer, Britta; Erdmann, Stephan; Henzgen, Margot; Fuchs, Thomas; Jäger, Lothar; Kleine‐Tebbe, Jörg; Lepp, Ute; Niggemann, Bodo; Raithel, Martin; Saloga, Joachim; Vieths, Stephan; Werfel, Thomas (2009). "Diagnostic approach for suspected pseudoallergic reaction to food ingredients". JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 7 (1): 70–77. doi:10.1111/j.1610-0387.2008.06894.x. ISSN 1610-0379. PMID 19054425. S2CID 23773448.
  5. ^ Cleveland Clinic medical professional (2017-09-12). "Food Challenge Tests". Cleveland Clinic. Retrieved 2024-06-21.
  6. ^ He, Shao-heng; Zhang, Hui-yun; Zeng, Xiao-ning; Chen, Dong; Yang, Ping-chang (August 26, 2013). "Mast cells and basophils are essential for allergies: mechanisms of allergic inflammation and a proposed procedure for diagnosis". Acta Pharmacologica Sinica. 34 (10). Springer Science and Business Media LLC: 1270–1283. doi:10.1038/aps.2013.88. ISSN 1671-4083. PMC 4002163. PMID 23974516.
  7. ^ Toncić, Ruzica Jurakić; Marinović, Branka; Lipozencić, Jasna (2009). "Nonallergic hypersensitivity to nonsteroidal antiinflammatory drugs, angiotensin-converting enzyme inhibitors, radiocontrast media, local anesthetics, volume substitutes and medications used in general anesthesia". Acta Dermatovenerologica Croatica. 17 (1): 54–69. PMID 19386216.
  8. ^ Wang, Zhiguo; Wang, Danqiao; Sui, Yu; Cui, Haifeng; Yu, Youhua (2012). "Experimental study on anaphylaxis of Qingkailing injection and its components on Beagle dogs". Journal of Traditional Chinese Medicine. 32 (4). Elsevier BV: 641–645. doi:10.1016/s0254-6272(13)60085-0. ISSN 0254-6272. PMID 23427403.
  9. ^ Baker, Mark D.; Gullett, John P. (2015). "Ultrasound-Guided Femoral Nerve Blocks". Pediatric Emergency Care. 31 (12). Ovid Technologies (Wolters Kluwer Health): 864–868. doi:10.1097/pec.0000000000000634. ISSN 0749-5161. PMID 26626896. S2CID 5150857.
  10. ^ Becker, Daniel E. (December 1, 2013). "Drug Allergies and Implications for Dental Practice". Anesthesia Progress. 60 (4). American Dental Society of Anesthesiology (ADSA): 188–197. doi:10.2344/0003-3006-60.4.188. ISSN 0003-3006. PMC 3891459. PMID 24423421.
  11. ^ Wang, Hong (2011). "Agents that induce pseudo-allergic reaction". Drug Discoveries & Therapeutics. 5 (5). International Research and Cooperation Association for Bio & Socio-Sciences Advancement (IRCA-BSSA): 211–219. doi:10.5582/ddt.2011.v5.5.211. ISSN 1881-7831. PMID 22466368.
  12. ^ "1868-2020: Supporting general practitioners for more than 150 years". The Practitioner. September 24, 2015. Retrieved December 20, 2023.
  13. ^ Yoo, Hye-Soo; Yang, Eun-Mi; Kim, Mi-Ae; Hwang, Sun-Hyuk; Shin, Yoo-Seob; Ye, Young-Min; Nahm, Dong-Ho; Park, Hae-Sim (2014). "A Case of Codeine Induced Anaphylaxis via Oral Route". Allergy, Asthma & Immunology Research. 6 (1). The Korean Academy of Asthma, Allergy and Clinical Immunology and The Korean Academy of Pediatric Al: 95. doi:10.4168/aair.2014.6.1.95. ISSN 2092-7355. PMC 3881408.
  14. ^ Sheen, C. H.; Schleimer, R. P.; Kulka, M. (April 12, 2007). "Codeine induces human mast cell chemokine and cytokine production: involvement of G‐protein activation". Allergy. 62 (5). Wiley: 532–538. doi:10.1111/j.1398-9995.2007.01345.x. ISSN 0105-4538. PMC 2199376. PMID 17441793.
  15. ^ McNeil, Benjamin D.; Pundir, Priyanka; Meeker, Sonya; Han, Liang; Undem, Bradley J.; Kulka, Marianna; Dong, Xinzhong (March 2015). "Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions". Nature. 519 (7542): 237–241. doi:10.1038/nature14022. ISSN 0028-0836. PMC 4359082. PMID 25517090.
  16. ^ Ring, J; Messmer, K (1977). "Incidence and Severity of Anaphylactoid Reactions to Colloid Volume Substitutes". The Lancet. 309 (8009). Elsevier BV: 466–469. doi:10.1016/s0140-6736(77)91953-5. ISSN 0140-6736. S2CID 37201704.
  17. ^ Zhang, Bo; Li, Qin; Shi, Chenyang; Zhang, Xinyue (November 15, 2017). "Drug-Induced Pseudoallergy: A Review of the Causes and Mechanisms". Pharmacology. 101 (1–2). S. Karger AG: 104–110. doi:10.1159/000479878. ISSN 0031-7012. PMID 29136631.
  18. ^ Szebeni, Janos; Alving, Carl R.; Savay, Sandor; Barenholz, Yechezkel; Priev, Aba; Danino, Dganit; Talmon, Yeshayahu (2001). "Formation of complement-activating particles in aqueous solutions of Taxol: possible role in hypersensitivity reactions". International Immunopharmacology. 1 (4). Elsevier BV: 721–735. doi:10.1016/s1567-5769(01)00006-6. ISSN 1567-5769. PMID 11357884.

Further reading

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