A Case of Recurrent Urticaria
CASE
A 50-year-old male with no significant past medical history presents to the Emergency Department with a chief complaint of facial swelling. The patient had been in his usual state of health when he awoke suddenly in the middle of the night just prior to presentation with lip swelling and an urticarial rash on his back and neck. He denies dyspnea, wheezing, trouble swallowing, nausea, vomiting, or diarrhea. He has no known personal or family history of angioedema or anaphylaxis. He has not started any new medications. He has no history of ACE inhibitor or ARB use and denies new food consumption, detergents, or soaps. Last night, he reportedly consumed a dinner consisting of shrimp, steak, and broccoli and reports all are foods he has previously consumed. He is visiting the Rhode Island area on business but typically resides in North Carolina. He reveals he has had multiple similar episodes with unknown trigger over the last 6 months. He sought care previously at an urgent care and was administered diphenhydramine with mild relief.
PMH: None
PSH: None
Medications: None
Allergies: NKDA
Social Hx: Lives in North Carolina with family. Works in business, travels frequently for work. No tobacco use, drug use, or alcohol. Hobbies include watching football, traveling, and gardening.
VS: T 99.1, HR 90 BPM, BP 118/80, RR 16, SpO2 98% on RA
Physical Exam:
General: Awake, alert, NAD
HEENT: Extensive perioral edema, mild periorbital edema, no tongue or uvular edema, tolerating secretions without difficulty
Resp: Clear to auscultation bilaterally, no appreciable wheezing
CV: Regular rate, rhythm, no murmurs, rubs, gallops
Abd: Soft, nontender, non-distended
Skin: Urticarial, blanchable rash to nape of neck
Neuro: AOX3
Laboratory testing reveals:
Albumin 5, tBili: 0.9, Alk Phos: 119, ALT: 34, AST: 28
PT/INR: 11/1.1
WBC: 9, HGB: 14.2, HCT: 40, PLT 152
Glu: 114, BUN 10, Cr 0.9, Na 140, K 4.2, CL 102, HCO3 24
A send out laboratory test reveals the diagnosis. What was the test?
Alpha-Gal Panel
· Galactose-alpha-1,3-galactose IgE:4 kU/L, Ref<01.10
· Beef IgE: 0, Ref <0.10
· Lamb/Mutton IgE: 0, Ref <0.10
· Pork IgE: 0, Ref <0.10
DIAGNOSIS
Alpha-Gal
DISCUSSION
Background
Alpha-gal is an IgE-mediated allergic reaction to the carbohydrate moiety galactose-alpha-1,3-galactose (alpha-gal). It is known as a red meat allergy, as the carbohydrate moiety alpha-gal is expressed on the cells and tissues of all mammalian species with the exception of primates. Alpha-gal is the only known tick-borne allergy. While most allergens are proteins, alpha-gal is one of only two described carbohydrate allergens.
Antibodies to alpha-gal were first described in regard to the administration of the monoclonal antibody cetuximab. When first introduced, a percentage of patients had anaphylactic reactions to cetuximab. It was found that 30 % of the structure of cetuximab consisted of an oligosaccharide epitope, alpha-gal. The patients who were having allergic reactions tested positive for IgE to alpha-gal. Interestingly, the case reports of allergic reactions to cetuximab tended to occur in regions with the greatest incidence of Rocky Mountain Spotted Fever, a tick-born bacterial illness. Eventually the connection was made that lone star tick carried the alpha-gal antigen. The tick feeds on a mammalian vector such as a deer and inoculates itself with alpha-gal. When humans are subsequently bitten by the tick, it secretes saliva contained the carbohydrate moiety, alpha-gal, leading to IgE-mediated activation against alpha-gal.
Upon sensitization to alpha-gal, patients experience delayed allergic reaction to consumption of mammalian meat (particularly beef, lamb, and pork) as well as milk, gelatin, cetuximab, and bovine or porcine heart valves.
Image 1. Sensitization to alpha-gal
Signs and Symptoms
Symptoms of alpha-gal are typical of IgE-mediated allergic reactions and include pruritis, urticaria, angioedema, or anaphylaxis. Some individuals may experience gastrointestinal symptoms alone, making it particularly difficult to diagnosis as an allergic reaction. Symptoms may be highly variable even within the same patient. In comparison to typical Ig-E-mediated allergic reactions, the symptoms of alpha-gal are typically delayed, often presenting 3-6 hours after time of ingestion. The theory behind the delayed onset of symptoms is that unlike proteins, alpha-gal is lipid-bound, resulting in slower absorption.
Diagnosis
-Clinical history and exam
-Alpha-Gal Panel: Test Code 91380
· Galactose-alpha-1,3-galactose (Alpha-Gal) IgE
· Beef (Bos spp) IgE
· Pork (Sus spp) IgE
· Lamb/Mutton (Ovis spp) IgE
Treatment
-Standard allergic reaction treatment
· H1 and H2 blockers
· Epinephrine IM
· Glucocorticoids
-Referral to Allergist
-Mammalian meat avoidance, may also need to avoid mammalian products such as daily
-Resolves in time in the majority of individuals over time
· Important to follow with an allergist to monitor IgE levels
· Allergist may perform a monitored oral meat challenge prior to reintroducing meat
Tick Bite Prevention:
Beware of grassy, brushy or wooded areas. If you are going for a hike, consider wearing EPA registered insect repellents. Treat clothing with 0.5% permethrin. While hiking, walk in the center of the trail. After spending time outdoors, perform an extensive self-exam and shower immediately.
Image 2. How To Prevent Tick Bites [https://blog.nols.edu/2015/07/24/how-to-prevent-and-manage-tick-bites-infographic]
CASE RESOLUTION
The patient was administered Benadryl and steroids and monitored for a period of hours. He was discharged home with a prescription for a steroid taper, H2 blocker prn, EpiPen prn, and referral to an allergist.
AUTHOR: Caroline Meehan, MD is a fourth year emergency medicine resident at Brown University/Rhode Island Hospital.
FACULTY REVIEWER: Melanie Lippmann, MD is an attending emergency medicine physician at Brown University/Rhode Island Hospital.
REFERENCES
1. Zhang B, Hauk M, Clyne J. Alpha-gal antibody due to Lone Star tick bite, a unique case of allergic reaction. IDCases. 2020. doi:10.1016/j.idcr.2020.e00908
2. Stoltz LP, Cristiano LM, Dowling APG, Wilson JM, Platts-Mills TAE, Traister RS. Could chiggers be contributing to the prevalence of galactose-alpha-1,3-galactose sensitization and mammalian meat allergy? J Allergy Clin Immunol Pract. 2019. doi:10.1016/j.jaip.2018.07.014
3. Pattanaik D, Lieberman P, Lieberman J, Pongdee T, Keene AT. The changing face of anaphylaxis in adults and adolescents. Ann Allergy, Asthma Immunol. 2018. doi:10.1016/j.anai.2018.07.017
4. Hilger C, Fischer J, Wölbing F, Biedermann T. Role and Mechanism of Galactose-Alpha-1,3-Galactose in the Elicitation of Delayed Anaphylactic Reactions to Red Meat. Curr Allergy Asthma Rep. 2019. doi:10.1007/s11882-019-0835-9
5. Flaherty MG, Kaplan SJ, Jerath MR. Diagnosis of life-threatening alpha-gal food allergy appears to be patient driven. J Prim Care Community Heal. 2017. doi:10.1177/2150131917705714
6. Crispell G, Commins SP, Archer-Hartman SA, Choudhary S, Dharmarajan G, Azadi P, et al. Discovery of alpha-gal-containing antigens in North American tick species believed to induce red meat allergy. Front Immunol. 2019. doi:10.3389/fimmu.2019.01056
7. Commins SP, Satinover SM, Hosen J, Mozena J, Borish L, Lewis BD, et al. Delayed anaphylaxis, angioedema, or urticaria after consumption of red meat in patients with IgE antibodies specific for galactose-α-1,3-galactose. J Allergy Clin Immunol. 2009. doi:10.1016/j.jaci.2008.10.052
8. Commins SP, Platts-Mills TAE. Allergenicity of carbohydrates and their role in anaphylactic events. Curr Allergy Asthma Rep. 2010. doi:10.1007/s11882-009-0079-1
9. Commins SP. Allergy to Meats. In: UpToDate [Internet]. 2020 [cited 9 Jan 2020]. Available: https://www.uptodate.com/contents/allergy-to-meats
10. Preventing tick bites. 2020 [cited 9 Apr 2020]. Available: https://www.cdc.gov/ticks/avoid/on_people.html
11. What Is Alpha-gal Syndrome (AGS)? 2019 [cited 4 Sep 2020]. Available: https://alphagalinformation.org/what-is-ags/