Answer:
I can certainly appreciate the issue you are reporting, however some of this is beyond the scope of Ask the Expert. I did research your questions, though like you, I was unable to find any specific policies or protocols addressing this. In my opinion, this would be an excellent topic for a task force or work group report.
There were some references that I felt may be helpful. A good review by Scott P. Commins, MD, PhD, at UNC, who is an alpha-gal expert, reviews medical alpha-gal glycosylation and human IgE binding to commercial drugs and implants. (1) There are several non-peer reviewed lists of potential medications containing gelatin, glycerin, lactose, microcrystalline cellulose, and magnesium stearate, etc. I found one website that offered the most complete list of potentially impacted medications, Inpharmd (2), though I cannot speak to its validity. The CDC has a link that also addresses potential exposures to alpha-gal within the medical arena. (3) Perioperative concerns with alpha-gal was addressed in a previous Ask the Expert question. (4)
1) Commins SP. Diagnosis & management of alpha-gal syndrome: lessons from 2,500 patients. Expert Rev Clin Immunol. 2020 Jul;16(7):667-677. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344025/
2) Last accessed 1/27/23: https://inpharmd.com/inquiries/7b59a192d887a7bce18eb339b9cbc82289c04016bae4cfb8656cbb41a53ce033
3) CDC: Products that may contain alpha-gal: https://www.cdc.gov/ticks/alpha-gal/products.html
4) Alpha-gal Syndrome a Perioperative Concerns
https://www.aaaai.org/Allergist-Resources/Ask-the-Expert/Answers/2021/periop
I reached out to Dr. Matt Greenhawt, an expert in this area. He provided some very thorough and insightful comments as follows.
These are very interesting questions.
In general, excipient cross-reactivity is difficult to assess, and likely rife with more theoretical than actual concern, but at the same time not entirely absent of actual concern (such as cases described with cetuximab). As is highlighted in a review by Dr. Scott Commins from 2020, the degree to which this may manifest in patients is selective, and patients who tolerate dairy may not have to avoid items containing gelatin necessarily. (Commins et al Exp Rev Clin Immnol 2020) It is difficult to provide blanket recommendations at a healthcare system level for alpha-gal and bovine/porcine products (including gelatin), given there is not much published experience per se, and no standardized approach.
The most literature regarding this issue has described alpha-gal allergic persons receiving heparin, which is porcine derived. Nwamara et al (Ticks Tick Borne Dis 2022) noted that 56/57 alpha-gal allergic patients tolerated heparin products, but Hawkins et al (Ann Thorac Surg 2021) noted that 4/17 patients with alpha-gal reacted to heparin. Some groups have published limited success with skin testing to heparin for risk assessment of this scenario, but this is not a validated skin testing reagent. Overall, the heparin scenario is considered low risk, but not absent risk and there are cases of reported anaphylaxis in such patients, along with cases of tolerance (both scenarios in patients who were pre-medicated for the exposure). With both case series, the persons who reacted had very high alpha-gal sIgE levels compared to those who tolerated heparin.
Taking this one step further, to gelatin containing medications, reviews will caution that gelatin containing vaccines and medications are best avoided, though gelatin capsules and items like lactulose are often tolerated. There is description of reactions to gelatin administered in IV form contained in plasma expanders (Uyttebroek et al J Clin Anesth. 2014), and to gelatin-containing vaccines in alpha-gal allergic patients (Stone et al J Allergy Clin Immunol Pract 2019), though a case series has shown that only 12/40 red meat allergic patients testing positive to gelatin actually reacted upon gelatin provocation challenge (Mullins et al J Allergy Clin Immunol 2012). With the data suggesting some (to most) tolerate but not all do, one has to wonder about threshold issues with the quantity of the gelatin exposure, if there is an issue with the quantity of alpha-gal sensitization (as suggested with the heparin cases), or something related to the route of exposure. This is the difficulty in that the issue has not been robustly studied.
The rest of the question deals with how to hedge such risk at a system-level. By description it sounds like your service is already involved with assisting in such cases, and your pharmacy/anesthesia are proactive in identifying potential issues with such cross-reactivity. This is a good sign that the issue is being taken seriously. However, it is beyond the scope of what Ask the Expert can advise in terms of the question about a screening form or the legality of the situation, or who would be the most appropriate clinician to counsel regarding the risk and then obtain such consent. The only thing I can offer as a potential parallel is that before drug or food challenges, drug desensitization, and any form of immunotherapy, it is strongly recommended that the patient be explained the risks and benefits of the procedure and provide written consent. Of course, the situation you describe is very different than the allergist office specific context of where, when, why and by whom consent is obtained for the aforementioned procedures.
References:
Commins SP. Diagnosis & management of alpha-gal syndrome: lessons from 2,500 patients. Expert Rev Clin Immunol. 2020 Jul;16(7):667-677.
Mullins RJ, James H, Platts-Mills TA, et al. Relationship between red meat allergy and sensitization to gelatin and galactose-alpha-1,3-galactose. J Allergy Clin Immunol. 2012. May;129(5):1334–1342 e1
Uyttebroek A, Sabato V, Bridts CH, et al. Anaphylaxis to succinylated gelatin in a patient with a meat allergy: galactose-alpha(1, 3)-galactose (alpha-gal) as antigenic determinant. J Clin Anesth. 2014. November;26(7):574–6.
Stone CA Jr., Commins SP, Choudhary S, et al. Anaphylaxis after vaccination in a pediatric patient: further implicating alpha-gal allergy. J Allergy Clin Immunol Pract. 2019. January;7(1):322–324 e2.
Nwamara U, Kaplan MC, Mason N, Ingemi AI. A retrospective evaluation of heparin product reactions in patients with alpha-gal allergies. Ticks Tick Borne Dis. 2022;13 (1):101869.
Hawkins RB, Wilson JM, Mehaffey JH, Platts-Mills TAE, Ailawadi G. Safety of intrave- nous heparin for cardiac surgery in patients with alpha-gal syndrome. Ann Thorac Surg. 2021;111(6):1991–1997.
Mawhirt SL, Banta E. Successful intravenous heparin administration during coro- nary revascularization surgery in a patient with alpha-gal anaphylaxis history. Ann Allergy Asthma Immunol. 2019;123(4):399–401.
Koo G, Plager J, Fahrenholz JM, Phillips E, Stone C Jr. Reactivity to heparin in patients with alpha-gal allergy: A potential role for skin testing? Ann Allergy Asthma Immunol. 2022 Oct;129(4):515-517.
Your questions are very insightful and unfortunately have not been well addressed in the literature. I hope you found this helpful. Very special thanks to Dr. Matt Greenhawt.
Jeffrey G. Demain, MD, FAAAAI