pseudoallergy

Clinically, pseudoallergy and anaphylaxis are identical.{{cite journal | last1=He | first1=Shao-heng | last2=Zhang | first2=Hui-yun | last3=Zeng | first3=Xiao-ning | last4=Chen | first4=Dong | last5=Yang | first5=Ping-chang | title=Mast cells and basophils are essential for allergies: mechanisms of allergic inflammation and a proposed procedure for diagnosis | journal=Acta Pharmacologica Sinica | publisher=Springer Science and Business Media LLC | volume=34 | issue=10 | date=August 26, 2013 | issn=1671-4083 | doi=10.1038/aps.2013.88 | pages=1270–1283| pmid=23974516 | pmc=4002163 }} Pseudoallergy symptoms include gastrointestinal symptoms, urticaria, bronchospasm, and angioedema,{{cite journal |last1=Toncić |first1=Ruzica Jurakić |last2=Marinović |first2=Branka |last3=Lipozencić |first3=Jasna |title=Nonallergic hypersensitivity to nonsteroidal antiinflammatory drugs, angiotensin-converting enzyme inhibitors, radiocontrast media, local anesthetics, volume substitutes and medications used in general anesthesia |journal=Acta Dermatovenerologica Croatica |date=2009 |volume=17 |issue=1 |pages=54–69 |pmid=19386216}} along with headache, edema, skin flushing, hypotension, and shock.{{cite journal | last1=Wang | first1=Zhiguo | last2=Wang | first2=Danqiao | last3=Sui | first3=Yu | last4=Cui | first4=Haifeng | last5=Yu | first5=Youhua | title=Experimental study on anaphylaxis of Qingkailing injection and its components on Beagle dogs | journal=Journal of Traditional Chinese Medicine | publisher=Elsevier BV | volume=32 | issue=4 | year=2012 | issn=0254-6272 | doi=10.1016/s0254-6272(13)60085-0 | pages=641–645 | pmid=23427403 |doi-access=free}}

Although they are commonly used to treat pain related to fractures, opioid medications have well-known side effects.{{cite journal | last1=Baker | first1=Mark D. | last2=Gullett | first2=John P. | title=Ultrasound-Guided Femoral Nerve Blocks | journal=Pediatric Emergency Care | publisher=Ovid Technologies (Wolters Kluwer Health) | volume=31 | issue=12 | year=2015 | issn=0749-5161 | doi=10.1097/pec.0000000000000634 | pages=864–868| pmid=26626896 | s2cid=5150857 }} Almost all opioids have the ability to directly induce mast cell degranulation, which in turn can result in pseudoallergy.{{cite journal | last=Becker | first=Daniel E. | title=Drug Allergies and Implications for Dental Practice | journal=Anesthesia Progress | publisher=American Dental Society of Anesthesiology (ADSA) | volume=60 | issue=4 | date=December 1, 2013 | issn=0003-3006 | doi=10.2344/0003-3006-60.4.188 | pages=188–197| pmid=24423421 | pmc=3891459 }} Opioid medications, including morphine, codeine, and meperidine, have been known to cause pseudoallergy.{{cite journal | last=Wang | first=Hong | title=Agents that induce pseudo-allergic reaction | journal=Drug Discoveries & Therapeutics | publisher=International Research and Cooperation Association for Bio & Socio-Sciences Advancement (IRCA-BSSA) | volume=5 | issue=5 | year=2011 | pages=211–219 | issn=1881-7831 | doi=10.5582/ddt.2011.v5.5.211 | pmid=22466368 | doi-access=free }} By directly activating mast cells, opioids cause histamine release, which results in flushing or pruritus that is almost always mistaken for allergy symptoms.{{cite web | title=1868-2020: Supporting general practitioners for more than 150 years | website=The Practitioner | date=September 24, 2015 |url=https://www.thepractitioner.co.uk/Photoguide/7693-/Allergic-reactions | access-date=December 20, 2023}} 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.{{cite journal | last1=Yoo | first1=Hye-Soo | last2=Yang | first2=Eun-Mi | last3=Kim | first3=Mi-Ae | last4=Hwang | first4=Sun-Hyuk | last5=Shin | first5=Yoo-Seob | last6=Ye | first6=Young-Min | last7=Nahm | first7=Dong-Ho | last8=Park | first8=Hae-Sim | title=A Case of Codeine Induced Anaphylaxis via Oral Route | journal=Allergy, Asthma & Immunology Research | publisher=The Korean Academy of Asthma, Allergy and Clinical Immunology and The Korean Academy of Pediatric Al | volume=6 | issue=1 | year=2014 | pages=95–97 | issn=2092-7355 | doi=10.4168/aair.2014.6.1.95 | pmid=24404400 | pmc=3881408 }} This suggests that codeine may activate mast cell degranulation by acting on the opioid receptor.{{cite journal | last1=Sheen | first1=C. H. | last2=Schleimer | first2=R. P. | last3=Kulka | first3=M. | title=Codeine induces human mast cell chemokine and cytokine production: involvement of G-protein activation | journal=Allergy | publisher=Wiley | volume=62 | issue=5 | date=April 12, 2007 | issn=0105-4538 | doi=10.1111/j.1398-9995.2007.01345.x | pages=532–538| pmid=17441793 | pmc=2199376 }}

One recognized mechanism is through the activation of mast cell receptor Mas-Related G Protein-Coupled Receptor-X2 (MRGPRX2).{{Cite journal |last1=McNeil |first1=Benjamin D. |last2=Pundir |first2=Priyanka |last3=Meeker |first3=Sonya |last4=Han |first4=Liang |last5=Undem |first5=Bradley J. |last6=Kulka |first6=Marianna |last7=Dong |first7=Xinzhong |date=March 2015 |title=Identification of a mast-cell-specific receptor crucial for pseudo-allergic drug reactions |journal=Nature |volume=519 |issue=7542 |pages=237–241 |doi=10.1038/nature14022 |issn=0028-0836 |pmc=4359082 |pmid=25517090}} 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 [MC_TC] 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.

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.

While pseudoallergy and IgE-mediated allergy share some similarities in their clinical manifestations,{{cite journal | last1=Ring | first1=J | last2=Messmer | first2=K | title=Incidence and Severity of Anaphylactoid Reactions to Colloid Volume Substitutes | journal=The Lancet | publisher=Elsevier BV | volume=309 | issue=8009 | year=1977 | issn=0140-6736 | doi=10.1016/s0140-6736(77)91953-5 | pages=466–469| s2cid=37201704 }} pseudoallergy is not the same as common allergy or type 1 reactions.{{cite journal | last1=Zhang | first1=Bo | last2=Li | first2=Qin | last3=Shi | first3=Chenyang | last4=Zhang | first4=Xinyue | title=Drug-Induced Pseudoallergy: A Review of the Causes and Mechanisms | journal=Pharmacology | publisher=S. Karger AG | volume=101 | issue=1–2 | date=November 15, 2017 | issn=0031-7012 | doi=10.1159/000479878 | pages=104–110| pmid=29136631 | doi-access=free }} 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.{{cite journal | last1=Szebeni | first1=Janos | last2=Alving | first2=Carl R. | last3=Savay | first3=Sandor | last4=Barenholz | first4=Yechezkel | last5=Priev | first5=Aba | last6=Danino | first6=Dganit | last7=Talmon | first7=Yeshayahu | title=Formation of complement-activating particles in aqueous solutions of Taxol: possible role in hypersensitivity reactions | journal=International Immunopharmacology | publisher=Elsevier BV | volume=1 | issue=4 | year=2001 | issn=1567-5769 | doi=10.1016/s1567-5769(01)00006-6 | pages=721–735| pmid=11357884 }}

• Anaphylaxis
• Type I hypersensitivity

{{reflist}}

• {{cite journal | last=Zuberbier | first=T | title=Pseudoallergy or nonallergic hypersensitivity | journal=Allergy | volume=54 | issue=4 | date=1999 | issn=0105-4538 | doi=10.1034/j.1398-9995.1999.00155.x | pages=397–400 | pmid=10371101 | s2cid=29977457 | ref=none}}
• {{cite journal | last=Waller | first=Derek G. | title=Allergy, pseudo-allergy and non-allergy | journal=British Journal of Clinical Pharmacology | publisher=Wiley | volume=71 | issue=5 | date=April 11, 2011 | issn=0306-5251 | doi=10.1111/j.1365-2125.2011.03976.x | pages=637–638 | pmid=21480945 | pmc=3093068 | ref=none}}

• [https://medical-dictionary.thefreedictionary.com/pseudoallergy The Free Dictionary]
• UpToDate - [https://www.uptodate.com/contents/nsaids-including-aspirin-allergic-and-pseudoallergic-reactions NSAIDs (including aspirin): Allergic and pseudoallergic reactions]

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{{Hypersensitivity and autoimmune diseases}}

Category:Allergology