Climate Change, Vector Range, and Alpha-Gal in Psychiatric Practice

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Alpha-gal syndrome (AGS) arises via delayed allergic (IgE) reaction to galactose-alpha-1,3–galactose (alpha-gal), which is an oligosaccharide molecule found in mammalian products such as meat, milk, and mammalian byproducts, including medications and medical devices.¹ Bites from the lone star tick are the most common cause of AGS, sensitizing individuals to the alpha-gal molecule on subsequent exposure to mammalian products; however, globally there may be other explanatory vectors. Symptoms present hours to days after exposure and include urticaria, gastrointestinal distress, angioedema, and possibly anaphylaxis, with significant variability among individuals. The psychological impacts of AGS are broad, and this vector-borne disease may cause patients to seek or be referred to psychiatric care.

Case Example

“Ben” is an 11-year-old boy referred to the psychiatric clinic by his pediatrician after experiencing years of gastrointestinal symptoms, including nausea, diarrhea, and episodic stomach pains. Workup including upper gastrointestinal endoscopy and colonoscopy was unrevealing and conservative management has failed. He has been missing school due to his symptoms and the school district is concerned about truancy. He lives in rural Missouri with his family who manages a tight budget, saving money by purchasing half of a steer or a whole hog at a time to feed the family. Ben is a picky eater, preferring meat with most meals.

Psychiatric Concerns

AGS lies at the intersection of physical and mental health. This case emphasizes some of the principal psychiatric concerns originating from AGS. This syndrome, which can arrive unannounced, may be triggered by foods and medications the patient has consumed their entire life. Suddenly, individuals with AGS may be limited in the types of food they eat, which can ostracize them from their family and culture, as well as place undue financial and administrative stressors on the individual and family. Of the top 20 pharmaceutical companies, only 60% were able to accurately provide information on whether there were animal products in their formulation. Of those respondents, many required repeated calls and prompting to coax out this information.² Climate change applies additional pressure onto mental health concerns, from increased AGS range to changes in food choice/availability, and even potential disruptions to supply chains for medication.

The prevalence of AGS is greatest in the United States, where the link between tick bites and AGS was initially identified by an Australian group in 2009. Subsequently, an American group discovered that cetuximab reactions overlapped with Rocky Mountain Spotted fever, a Rickettsial infection transmitted by the lone star tick (Amblyomma americanum).¹ Recent data showed 18,885 positive tests in the United States in 2021, rising from 13,371 in 2017 with geographic preference for the Midwest, Southern, and Mid-Atlantic regions, which not so coincidentally mirrors the distribution of the lone star tick.³ Without established surveillance for AGS, its exact prevalence is largely unknown. A survey from the same Centers for Disease Control and Prevention (CDC) weekly morbidity and mortality report highlights the lack of provider knowledge on AGS and its underdiagnosis.⁴

Changing climates alter regions suitable for ticks, and the range of AGS will likely follow such migrations.1 The northward expansion of lone star ticks and AGS is amplified by the acceleration of the tick life cycle from climate impacts. One study identified that milder northeastern winters facilitated increased survival of the lone star tick, where patients with AGS may appear in the clinic of unsuspecting clinicians.5

Diagnosis

This condition poses a challenge for many physicians. There is no consensus diagnostic threshold of IgE to alpha-gal molecules, as testing itself is relatively new. Likewise, there are no curative treatments for this condition, which can be life-threatening.^1,4 A 28-person survey from 2016 found an average time to diagnosis of 7 years, requiring repeat visits, workups, and independent research, with roughly 3 out of 4 patients self-diagnosing their unique presentation of this presently rare condition.⁶ This increased time to diagnosis for a chronic condition with a risk of repeated symptom flares can have an immense psychological impact. Core aspects of people’s lives now have the potential to induce a reaction, making you think twice about pets, eating out, apparel choices (leather), and personal care products. Unlabeled food and drug products pose a hazard to patients seeking to manage their condition chronically. Products containing alpha-gal moieties are ubiquitous—even when excluding red meat. Currently, the US Food and Drug Administration does not require labeling products this way, which is an added daily stressor for patients, seeding doubt, anxiety, and isolation even after a drawn-out diagnosis. The costs for health care, prescriptions including EpiPens, social impacts, and ambiguity when seeking information about the syndrome compound. The distress felt by patients and families navigating AGS can be immense. Supportive communities and resources with appropriate therapy can help manage this condition.

For the practicing psychiatrist, there are obstacles to medical management for many psychiatric conditions. Gelatin capsules and animal-derived stabilizers, including lactose and other mammalian products, frequently occupy selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, 1st and 2nd generation antipsychotics, mood stabilizers (lithium, anticonvulsants), and anxiolytic (benzodiazepine and nonbenzodiazepine) medications. These were found just from a cursory glance online, because not even the CDC has a comprehensive list, deferring to the patient’s provider.^7-10 A column from the American Academy of Allergy, Asthma, and Immunology takes a similar stance to the CDC, where a blanket response defers patient risk, treatment consent, and care decisions to the institution, as there is no standardized reporting of product ingredients.¹¹ This significantly impinges on the therapeutic latitude available for patients with AGS and psychiatric concerns, with elevated risks in acute management. Pharmacies themselves may only receive information from the manufacturer, who may be rather lax in their reporting. A case report on initiating psychotropic treatment in the setting of AGS emphasized the necessity of interdisciplinary care for initiating appropriate treatment, and that generic manufacturers may use different ingredients, so generalizing alpha-gal content from one formulation to another is not possible.⁷ For some patients, multiple trials of medication may be needed for effective treatment. Chronic illness is related to psychiatric comorbidities such as depression and anxiety.¹² Addressing mental health alongside organic disease should be pursued in patients with AGS if applicable, as this diagnosis can be life-altering.

Challenges in managing patients with AGS have been documented across many specialties. In the emergency department, AGS should be on the differential for anaphylaxis of unknown origin, as well as an adverse drug reaction in an unknown patient.¹³ In the operative setting, porcine valves, certain types of sutures, and common drugs including heparin and oxycodone are off-limits.¹⁴ Once outpatient, compounding pharmacies with custom medication formulations can provide an answer to the uncertainty of living with AGS, but these are often more expensive than traditional pharmacies. Rural patients may not have access to this, or other options if there are no pharmacies in their area with the available prescriptions to turn to when first-line meds contain the alpha-gal epitope. Prescription medications are something individuals living with AGS become hyperaware of, as common entities can cause flares in symptoms. In a recent survey, half of patients with AGS have had an anaphylactic reaction to a health product.⁸ 

Treatment of AGS involves avoiding allergens and having rescue medications available if a reaction occurs.¹⁵ On first presentation, if suspicious for AGS physicians should encourage mammalian meat and product avoidance, provide an EpiPen and antihistamine prescription, and refer the patient to an allergist.¹³ Once diagnosed, significant patient education surrounding lifestyle changes is needed to help avoid reactions, though complete avoidance is next to impossible. After reviewing the broad swath of everyday products where we encounter alpha-gal, education on label reading can help mitigate encountering the antigen. Advocating for more information about medical treatments like vaccines and prescriptions is key to reducing iatrogenic risks, and tick avoidance remains essential in preventing disease onset or worsening. Psychiatrists have an important role in the interdisciplinary treatment of patients with AGS to address psychological sequelae. Collaboration with pharmacists and registered dietitians helps in providing comprehensive care to people with AGS, too.¹⁵ As with many of the rarer chronic diseases receiving insufficient attention from research, there seems to be a robust, supportive online community for those living with AGS. With accelerating climate change, the reality of AGS becoming more prevalent and significant for practicing physicians including psychiatrists, provides another incentive to allocate more energy towards the diagnosis and management of AGS. Through gene editing, an alpha-gal free porcine products are on the horizon, but increasing awareness on the part of physicians to identify and adequately treat people with AGS would yield substantial benefit to those unfortunate enough to be sensitized to the oligosaccharide.

Concluding Thoughts

AGS is a chronic disease affecting an increasing number of Americans and is difficult for physicians to identify. Its physical and psychological impact on patients is significant, and providers should have a plan in place in their practice for addressing the needs of these patients. Mandated reporting of all drug ingredients would go a long way in managing their care and alleviating stress for both patients and their providers. Future efforts to evaluate the burden of this disease, clear guidelines for AGS diagnosis, and improved labeling would have substantial benefits to those learning to live with alpha-gal.

List of Resources for Patients and Providers

• https://alphagalinformation.org/
• https://www.aaaai.org/allergist-resources/ask-the-expert/answers/2023/alpha-gal
• https://www.twoalphagals.com/blog/psychological-impacts
• https://tickedoffmastcells.org/?p=181

Mr Babineau is a medical student at Virginia Commonwealth University School of Medicine. Dr Daily is adjunct faculty at the Oklahoma State University School of Osteopathic Medicine at The Cherokee Nation.

References

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16. Technologies. Revivicor. Accessed October 4, 2024. https://www.revivicor.com/technologies