Epidemiology: has also been described with lamb and some cuts of pork
Physiology
Tick Acquires the Oligosaccharide, Alpha-Gal, After Feasting on a Mammal, Retaining it in its Gastrointestinal Tract Until it Bites a Human: the bite provokes an IgE response in the human
Alpha-Gal is Found in Red Meats
Alpha-Gal is Also Found in Cetuximab (Erbitux) (see Cetuximab, [[Cetuximab]])
Alpha-Gal May Also Be Found in Porcine Products, Such as Heart Valves and Heparin
Clinical
Alpha-Gal Related Meat Allergy is Unusual in that it has a Delayed Onset, Occurring 4-6 hrs After Meat Ingestion
Alpha-Gal Associated Cetuximab (Erbitux) Allergy (see Cetuximab, [[Cetuximab]]): may occur on first exposure and may be severe, resulting in anaphylaxis
Allergy May Recede Over Months-Years if Red Meat is Avoided
Phylum Arthropoda -> Class Insecta -> Order Lepidoptera
Pine Processionary Caterpillar Envenomation
Puss Caterpillar Envenomation (see Puss Caterpillar Envenomation, [[Puss Caterpillar Envenomation]]): may induce an anaphylaxis-like reaction (unknown if IgE-mediated)
Gemcitabine (Gemzar) (see Gemcitabine, [[Gemcitabine]]): cases of laryngeal edema have been reported
Heparin (see Heparin, [[Heparin]]): anaphylaxis is a manifestation of heparin-induced thrombocytopenia (HIT) (see Heparin-Induced Thrombocytopenia, [[Heparin-Induced Thrombocytopenia]])
Procaine (Novocaine, Novocain) (see Procaine, [[Procaine]])
Monoclonal Antibodies/Biologics
Cetuximab (Erbitux) (see Cetuximab, [[Cetuximab]])
Physiology: tick bite-associated alpha-galactosidase sensitization has been found to be a mechanism of allergic sensitization to cetuximab and read meats (J Allergy Clin Immunol, 2015) [MEDLINE]
Epidemiology: although contrast-associated IgE-mediated anaphylaxis was once considered rare, contrast-specific IgE antibodies have been demonstrated in some cases (Am J Roentgenol, 2008) [MEDLINE] (Allerg Immunol, 1993; Paris) [MEDLINE]
Physiology
IgE-Mediated: some cases
Non-IgE-Mediated: most cases
Activation of Coagulation/Kinin/Complement Cascades
Direct Mast Cell Activation
Inhibition of Cholinesterase
Inhibition of Platelet Aggregation with Increased Serotonin Release
Sorafenib (Nexavar) (see Sorafenib, [[Sorafenib]])
Epidemiology: rare cases of patients with very low levels of IgA and anti-IgA Ab’s, may develop anaphylaxis upon receiving blood with IgA present (these patients need IgA-deficient blood products)
Non-Immunologic Direct Mast Cell/Basophil Activation
Ethanol (see Ethanol, [[Ethanol]]): rarely induces anaphylaxis by itself, but may augment mast cell activation
Foods: these “pseudoallergens” may cause urticaria (or contact urticaria) via IgE-mediated or via non-immunologic mechanisms, especially in children
Relative Incidence (in Australian Study from 2002-2011): Rocuronium (56% of cases) > Succinylcholine (21% of cases) > Vecuronium (11% of cases) (Br J Anaesth, 2013) [MEDLINE])
Cisatracurium Had the Lowest Prevalence of Cross-Reactivity in Patients with Known Anaphylaxis to Either Rocuronium or Vecuronium
Epidemiology: although contrast-associated IgE-mediated anaphylaxis was once considered rare, contrast-specific IgE antibodies have been demonstrated in some cases (Am J Roentgenol, 2008) [MEDLINE] (Allerg Immunol, 1993; Paris) [MEDLINE]
Physiology
IgE-Mediated: some cases
Non-IgE-Mediated: most cases
Activation of Coagulation/Kinin/Complement Cascades
Direct Mast Cell Activation
Inhibition of Cholinesterase
Inhibition of Platelet Aggregation with Increased Serotonin Release
Stinging Nettle (Urtica Dioica) (see Stinging Nettle, [[Stinging Nettle]]): urticaria was named after this weed (which is commonly found in North America, South Americam Europe, and parts of Africa
Physiology: histamine (and pain-causing mediators) contained in the plant
Mast Cell/Basophil Activation with Release of Multiple Mediators
Histamine
IL-4
IL-13
Leukotrienes
Platelet Activating Factor
Prostaglandin D2 (PGD2)
TNFα
Tryptase
Distributive Shock (Similar to Sepsis) (see Hypotension, [[Hypotension]])
Variable Cardiac Output (CO)
Early (Before Volume Resuscitation): hypovolemia predominates -> decreased preload -> normal or decreased CO
Later (After Volume Resuscitation): high CO with low SVR state
Myocardial depression (decreased ejection fraction observed on echocardiogram) is frequent, despite increased CO
Venous and Arterial Vasodilation
Capillary Leak: due to endothelial cell dysfunction
Interstitial edema
Tachycardia: due to hypotension-induced reflexive increase in heart rate
Hypovolemia (early in course): due to capillary leak and venous/arterial vasodilation
Diagnosis
Mast Cell Serum Tryptase Level (see Serum Tryptase, [[Serum Tryptase]])
Draw within hours of event to diagnose anaphylaxis
May not be elevated in some cases
RAST Testing
Useful for Allergy Testing: detects allergen-specific IgE
Chest X-Ray (CXR) (see Chest X-Ray, [[Chest X-Ray]])
Normal CXR: most common pattern
Hyperinflation: may indicate the presence of bronchospasm
Pulmonary Edema: may occur in severe cases
Diagnostic Criteria (One of Three Following Criteria) [MEDLINE]
Acute Onset of Illness (Within Min-Several Hours) with Skin/Mucosal Tissue Involvement (Flushing/Generalized Erythema, Hives, Pruritus, Swollen Lips/Tongue/Uvula) and At Least One of the Following
Hypotension After Exposure to a Known Allergen for a Specific Patient Within Min-Several Hours (see Hypotension, [[Hypotension]])
Adult: systolic blood pressure 90 mm Hg or >30% in systolic blood pressure from patient’s baseline
Infant/Children: age-specific hypotension or >30% decrease in systolic blood pressure
Clinical Manifestations
General Comments
Onset: within min-4 hrs
Biphasic Reaction: symptoms can recur 10 hrs later -> due to this clinical characteristic, prolonged observation may be required (and corticosteroids are often useful to blunt the development of the second phase)
Cardiovascular Manifestations
General Comments
Cardiovascular Manifestations Occur in 45% of Cases
Sinus Bradycardia (see Sinus Bradycardia, [[Sinus Bradycardia]]): may occur in some cases
Hypotension/Cardiovascular Collapse (see Hypotension, [[Hypotension]]): common
Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome, [[Acute Respiratory Distress Syndrome]]): may occur in severe cases
Acute Respiratory Failure (see Respiratory Failure, [[Respiratory Failure]])
Physiology: high-grade upper airway obstruction or bronchospasm with excessive work of breathing
Non-Code Blue Situation: IM into thigh is preferred over SQ route
Code Blue Situation: IV route (with 1:10,000 solution) is preferred
Preloaded Epinephrine Injectable Devices
Advantages
Patient Can Keep Nearby at Home for Emergency Use: do not store in warm/hot places (such as a car), due to drug stability
Shelf-Life: 1 year (when stored properly)
Adult Dose: 0.3 mg IM (1:1000) for adults
Brands
Epipen
Hold like a pen, not like a knife (to avoid inadvertent injection into the thumb)
Remove blue safety cap -> firmly push orange tip against lateral thigh (don’t need to remove clothes to use), until it clicks -> hold in place for 5-10 sec
Case report: recurrent anaphylactic shock to radiographic contrast media. Evidence supporting an exceptional IgE-mediated reaction. Allerg Immunol (Paris). 1993;25(10):425 [MEDLINE]
Anaphylaxis induced by horsefly bites: identification of a 69 kd IgE-binding salivary gland protein from Chrysops spp. (Diptera, Tabanidae) by western blot analysis. J Allergy Clin Immunol. 1998;101(1 Pt 1):134. [MEDLINE]
Second symposium on the definition and management of anaphylaxis: summary report–Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 2006 Feb;117(2):391-7 [MEDLINE]
Anaphylaxis to iodinated contrast material: nonallergic hypersensitivity or IgE-mediated allergy? AJR Am J Roentgenol. 2008;190(3):666 [MEDLINE]
World allergy organization guidelines for the assessment and management of anaphylaxis. World Allergy Organ J. 2011 Feb;4(2):13-37. doi: 10.1097/WOX.0b013e318211496c [MEDLINE]
The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose. J Allergy Clin Immunol. 2011;127(5):1286. Epub 2011 Mar 31 [MEDLINE]
Anaphylaxis to neuromuscular blocking drugs: incidence and cross-reactivity in Western Australia from 2002 to 2011. Br J Anaesth. 2013 Jun;110(6):981-7. doi: 10.1093/bja/aes506. Epub 2013 Jan 18 [MEDLINE]
Tick bites and red meat allergy. Curr Opin Allergy Clin Immunol. 2013 Aug;13(4):354-9. doi: 10.1097/ACI.0b013e3283624560 [MEDLINE]
International consensus on (ICON) anaphylaxis. World Allergy Organ J. 2014; 7(1): 9 [MEDLINE]
The alpha-gal story: lessons learned from connecting the dots. J Allergy Clin Immunol. 2015;135(3):58 [MEDLINE]
Comparative Risk of Anaphylactic Reactions Associated With Intravenous Iron Products. JAMA. 2015 Nov 17;314(19):2062-2068. doi: 10.1001/jama.2015.15572 [MEDLINE]
Red meat allergy induced by tick bites: A Norwegian case report. Eur Ann Allergy Clin Immunol. 2017 Jul;49(4):186-188 [MEDLINE]
