Perioperative Management of Alpha-Gal Syndrome

Perioperative
Management of Alpha-
Gal Syndrome

LAURA L. WIGGINS, DNP, CRNA

Alpha-Gal

Commonly
recognized by a
red meat allergy







Alpha-Gal Symptoms

 Hives, itching, or itchy, scaly skin (eczema)
 Swelling of the lips, face, tongue and throat, or other body parts
 Wheezing or shortness of breath
 A runny nose
 Stomach pain, diarrhea, nausea or vomiting
 Sneezing
 Headaches
 A severe, potentially deadly allergic reaction that restricts

breathing(anaphylaxis)



Causes

Tick bites

Ticks that cause alpha-gal syndrome are believed to carry alpha-gal molecules from the blood of
the animals they commonly bite, such as cows and sheep. When a carrier tick bites a human, the
tick injects alpha-gal into the person's body.
For unknown reasons, some people have such a strong immune response to these molecules that
they can no longer eat red meat or products made from mammals without a mild to severe allergic
reaction. People who are exposed to many tick bites over time may develop more-severe
symptoms.

The cancer drug cetuximab

People with antibodies related to alpha-gal syndrome can have allergic reactions to the cancer drug
cetuximab (Erbitux). Cetuximab-induced cases of this condition are most common in regions with a
high population of Lone Star ticks, suggesting a possible link between Lone Star tick bites and an
increased vulnerability to alpha-gal syndrome. More research is needed to understand the
connection between ticks that carry alpha-gal in certain regions and cases of alpha-gal syndrome
that don't seem directly linked to tick bites.

Risk Factors

•Spend a lot of time outdoors
•Have received multiple Lone Star tick bites
•Have a mast cell abnormality such as indolent systemic mastocytosis



Complications

•Constriction of airways
•Swelling of the throat that makes it difficult to breathe
•A severe drop in blood pressure (shock)
•Rapid pulse
•Dizziness, lightheadedness or loss of consciousness





Diagnosis

•Blood test. A blood test can confirm and measure the amount of alpha-gal
antibodies in your bloodstream. This is the key test for diagnosis of alpha-gal
syndrome.

•Skin test. Doctors prick your skin and expose it to small amounts of substances
extracted from commercial or fresh red meat. If you're allergic, you develop a
raised bump (hive) at the test site on your skin. Your doctor or allergist may also
test your skin for an allergic reaction to individual types of red meat because there
are different kinds of allergies to meat.

See an Allergist!

Anesthesia Concerns

 Be vigilant
 Identify potential reactions to drugs and devices
 Identification of patients
 Pre-anesthesia consult
 Continued research on drugs and devices
 Involve Pharmacy early
 Identify triggering agents
 Education to all providers on this relatively new syndrome
 Avoid allergy list fatigue



Reactions to drugs and devices

 Alpha-gal epitope

 Many reactions result from inactive substances that are part of the manufacturing
or preparation process, such as gelatin or stearic acid.

 Magnesium stearate (a form of stearic acid) is used to facilitate the
manufacturing of many drugs.

 Patients with alpha-gal syndrome may also react to recombinant human proteins
produced in non-primate mammals.

 Bio-prosthetic heart valves are often constructed with bovine or porcine
pericardium. Consider de-cellularized valves for patients with alpha-gal.

Inactive Compounds Containing
Animal Derivative and Alpha-Gal
Carbohydrate

 Gelatin * (contains bovine and /or porcine). There may be
exceptions such as gelatin containing plant-based products

 Stearate or Steric acid is derived from bovine or plant sources
 Glycerin
 Lactic Acid
 Magnesium Stearate

Inactive Compounds Common Perioperative drugs and materials containing inactive
Compounds

Gelatin * Acetaminophen tablet, celecoxib tablet, pregabalin tablet,
Glycerin gabapentin tablet, lidocaine patch, surgifoam
Lactic Acid
Acetaminophen and codeine elixir, acetaminophen liquid, ibuprofen
suspension, morphine solution

Hydromorphone injection by Hospira

Magnesium Stearate Acetaminophen tablet, oxycontin tablet, diphenhydramine tablet,
Steric Acid Lisinopril tablet

Ocycodone tablet by Hospira, Mallinckrodt

Case Study #1

Demographics Anesthetic Surgical and
Evaluation Perioperative Tx
74- year old male, retired
professional health care Patient reported > 30 General Anesthesia for elective
worker anaphylactic reactions major cervical spine surgery.
between 2015-2018. Anterior cervical 4-7
Reactions included decompression, corpectomy,
medications with hidden instrumented fusion with cages
ingredients containing and allograft; plate and screws.
mammalian byproducts; Outsourcing food and meals from
cross-contaminated foods. home.

Case Study #2

Demographics Anesthetic Surgical and
Evaluation Perioperative Tx
59 year old female
Reported immediate General anesthesia for
anaphylaxis to the cancer elective gynecologic surgery:
drug cetuximab. Delayed hysteroscopy, polypectomy.
allergy to beef and porcine
containing products;
medications containing
maltose. Hydroxychloroquine
induced Steven-Johnson
syndrome.

Case Study #3

Demographics Anesthetic Surgical and
Evaluation Perioperative Tx
84 year old female
Reported positive formal Neuraxial anesthesia for elective
allergy testing for alpha-gal total knee arthroplasty and
syndrome. Reactions received perioperative triggering
included pruritis and urticarial agents inadvertently via ERAS
after consuming beef on protocol.
several occasions.

Case Study #4

Demographics Anesthetic Surgical and
Evaluation
37 year old female Perioperative TX
Cushing’s Disease, diabetes
insipidus, Alpha-gal allergy General anesthesia for elective
was known by patient, but total laparoscopic
was not updated in the EMR. hysterectomy and cystoscopy.
Patient inadvertently The pharmacy packaging for
received celecoxib and the drugs did not have an NDC
gabapentin as part of an number. The drug lot number
ERAS protocol before her proved to be insufficient for
Alpha-gal allergy was providers to determine the
realized. manufacturer in a timely
fashion. Subsequently, pre-
emptive steroids and
antihistamines were
administered perioperatively.

Case Study #5

Demographics Anesthesia Surgical and
Evaluation Perioperative Tx
80 year old female
Patient reported an allergy to General anesthesia for elective
beef and pork in the PACU. colpopexy, extraperitoneal sling for stress
incontinence, repair of rectocele,
The allergy was unclassified as cystoscopy. Pt. did not qualify for ERAS
Alpha-gal allergy prior to protocol, therefore common triggering
surgery. Other allergies agents were not introduced.
including anaphylaxis, hives
or swelling included: Intraoperative management included
dextromethorphan, dexamethasone. In PACU, the patient
hydrocodone, oxycodone, developed anaphylaxis including
amoxicillin, Levaquin. bronchospasm, diffuse rash over the
chest and neck, and perioral swelling
immediately after receiving IV Albumin
for fluid management and correction of
hypotension. EBL=125mls.

Symptoms improved with
diphenhydramine IV.

Challenges in Anesthesia

 Patient Awareness
 Healthcare Provider Awareness
 Data Collection and limitations of EMR
 Pharmacy Information and Updates
 Access to Pharmaceutical or Surgical Product Manufacturer

Specifications
 Demographic Changes
 Blood Supply (Pooled products such as platelets and Albumin)

Pharmacology Considerations

 This is an area of extreme challenge. The same drug may be safe or unsafe
depending on manufacturer.

 Offenders: drugs with gelatin, magnesium stearate, stearic acid, lactic acid.
 In acute situations with unknowns, risks and benefits must be weighed with

considerations that reactions might not be immediate.
 Unsafe: Heparin, Lactated Ringers
 Safe: Albumin (derived from human plasma)
 Propofol is safe if the glycerol used is plant based. Dilaudid may contain lactic

acid that is animal derived and be unsafe.
 Intrathecal and epidural medications are preservative free which decreases

risks, but still need to confirm their safety with pharmacy.

Treatment of Reactions

 Reactions should be treated as with other allergic reactions
 Consider: antihistamines, albuterol, epinephrine as indicated
 Prolonged monitoring is essential considering that this syndrome has a

propensity towards reactions being delayed.
 Blood levels of IgE to alpha gal often drop in patients who avoid repeat

tick bites.

Personal Prevention and Protection

• Cover up.
• Use insect repellents.
• Do your best to tick-proof your yard.
• Check yourself, your children and your pets for ticks.
• It's helpful to shower as soon as you come indoors.
• Remove a tick as soon as possible with tweezers





References

 A tick-acquired red meat allergy. Khoury JK, Khoury NC, Schaefer D, Chitnis A, Hassen GW.Khoury JK, et al.
Am J Emerg Med. 2018 Feb;36(2):341.e1-341.e3. doi: 10.1016/j.ajem.2017.10.044. Epub 2017 Oct 16.Am J
Emerg Med. 2018. PMID: 29074067

 Alpha gal specific IgE positivity due to tick bites and red meat allergy: the first case report in Turkey. Keleş
Ş, Gündüz M.Keleş Ş, et al. Turk J Pediatr. 2019;61(4):615-617. doi: 10.24953/turkjped.2019.04.023.Turk J
Pediatr. 2019. PMID: 31990484

 Galactose-α-1,3-galactose syndrome: an Italian survey. VillaltaD, Cecchi L, Farsi A, Chiarini F, Minale P,
Voltolini S, Scala E, Quercia O, Muratore L, Pravettoni V, Calamari AM, Cortellini G, Asero R.Villalta D, et al.
Eur Ann Allergy Clin Immunol. 2017 Nov;49(6):263-269. doi: 10.23822/EurAnnACI.1764-1489.35.Eur Ann
Allergy Clin Immunol. 2017. PMID: 29249134

 Food allergy to the carbohydrate galactose-alpha-1,3-galactose (alpha-gal): four case reports and a
review. Bircher AJ, Hofmeier KS, Link S, Heijnen I.Bircher AJ, et al. Eur J Dermatol. 2017 Feb 1;27(1):3-9. doi:
10.1684/ejd.2016.2908.Eur J Dermatol. 2017. PMID: 27873733 Review.

 Environmental and Molecular Drivers of the α-Gal Syndrome. Cabezas-Cruz A, Hodžić A, Román-Carrasco
P, Mateos-Hernández L, Duscher GG, Sinha DK, Hemmer W, Swoboda I, Estrada-Peña A, de la Fuente
J.Cabezas-Cruz A, et al. Front Immunol. 2019 May 31;10:1210. doi: 10.3389/fimmu.2019.01210. eCollection
2019.Front Immunol. 2019. PMID: 31214181 Free PMC article. Review.

References

 Commins SP, Platts-Mills TA (2013) Delayed anaphylaxis to red meat in patients with IgE specific for galactose-α-
1,3-galactose (alpha gal). Curr Allergy Asthma Report 13: 72-77.

 Commins SP, Platts-Mills TA (2009) Anaphylaxis syndromes related to a new mammalian cross-reactive
carbohydrate determinant. J Allergy Clin Immunol 124: 652-657.

 (2019) National Institute of Allergy and Infectious Diseases.
 Oneil BH, Allen R, Spigel DR, et al. (2007) High incidence of cetuximab-related infusion reactions in Tennesse and

North Carolina; association with atopic history. J Clin Oncol 25: 3644-3648.
 Chung CH, Mirakhur B, Chan E, et al. (2008) Cetuximab-induced anaphylaxis and IgE specific for galactose-α-1,3-

galactose. New Engl J Med 358: 1109-1117.
 Commins SP, James HR, Kelly LA, et al. (2011) The relevance of tick bites to the production of IgE antibodies to the

mammaliam oligosaccharide galactose-α-1,3-galactose. J Allergy Clin Immunol 127: 1286-1293.
 Centers for Disease Control and Prevention (2017) Tickborne Diseases of the United States: A Reference Manual

for Health Care Providers, (4th edn).
 (2019) Centers for Disease Control and Prevention. Geographic distribution of ticks that bite humans

References

 (2019) Centers for Disease Control and Prevention. Geographic distribution of ticks that bite humans.
 Hamsten C, Starkhammer M, Tran TA, et al. (2013) Identification of galactose-α-1,3-galactose in the gastrointestinal tract of the tick

Ixodes ricisnus: Possible relationship with red meat allergy. Allergy 68: 549-552.
 Nuñez R, Carballada F, Gonzazlez-Quintel A, et al. (2011) Delayed mammalian meat-induced anaphylaxis due togalactose-α-1,3-

galactose in 5 European patients. J Allergy Clin Immunol 128: 1122.e1-1124.e1.
 Bircher AJ, Hofmeier HS, Link S, et al. (2017) Food allergy to the carbohydrate galactose-alpha-1,3-galactose (alpha-gal): Four case

reports and a review. European Journal of Dermatology 27: 3-9.
 Kennedy JL, Stallings AP, Platts-Mills TA, et al. (2013) Galactose-α-1,3-galactose and Delayed Anaphylaxis, Angioedema, Urticaria in

Children. Pediatrics 131: 1545-1552.
 Berg EA, Platts-Mills TA, Commins SP (2014) Drug allergens and food: The cetuximab and galactose-α-1,3-galactose story. Ann Allergy

Asthma Immunol 112: 97-101.
 Stewart PH, McMiullan, KL, LeBlanc SB (2015) Delayed red meat allergy: Clinical ramifications of galactose-α-1,3-galactose

sensitization. Ann Allergy Asthma Immunol 115: 260-264.
 Steinke JW, Platts-Mills TA, Comins SP (2015) The alpha-gal story: Lessons learned from connecting the dots. J Allergy Clin Immunol 135:

589

 https://www.ncbi.nlm.nih.gov/pubmed/23390540

Anesthesia Specific References

 D'Ercole FJ, Dhandha VH, Levi ML, et al. (2019) Perioperative Challenges in
Patients with Alpha-Gal Allergy. J Clin Anesth Pain Manag 3(1):70-78.

 Dunkman WJ, Rycek W, Manning MW. What Does a Red Meat Allergy
Have to Do With Anesthesia? Perioperative Management of Alpha-Gal
Syndrome. Anesth Analg. 2019 Nov;129(5):1242-1248. doi:
10.1213/ANE.0000000000003460. PMID: 29847378.

Questions?