lone star ticks: alpha-gal anaphylaxis from eating red meat

 

The spread of the lone star tick as a result of climate change/warmer weather has led to the northward spread of some tick-borne illnesses. A prior blog highlighted the spread of the potentially fatal Heartland virus, associated with the lone star tick (http://gmodestmedblogs.blogspot.com/2023/03/climate-change-tick-disease-spreads.html); this blog includes a picture of the tick as well as more general observations of the effects of climate change on the spread of infectious diseases. And, now the alpha-gal syndrome (AGS)

 

Details:

-- the lone star tick bites have been associated with the alpha-gal syndrome, AGS (also called the red meat allergy or tick bite meat allergy), a potentially life-threatening allergic condition

    -- it seems that AGS is primarily associated with lone star tick bites, though other ticks may also be involved (one suspect is Ixodes spp: the culprit also in anaplasmosis, Lyme disease, babesiosis, Borrelia miyamotoi disease, Powassan virus disease, and ehrlichiosis).

        -- AGS has been found in areas where lone star ticks have not been found, further suggesting a role for other tick species

-- AGS occurs because the oligosaccharide galactose-α- 1,3 galactose (aka, alpha-gal) is not found in humans, or in fish, reptiles, or birds. And sensitization to this sugar in humans can lead to subsequent severe hypersensitivity reactions

    -- but alpha-gal is found in meat (beef, pork, rabbit, lamb, venison) as well as products from these animals (cow's milk or any milk products). of note, certain medications can also have alpha-gal, including gelatin derived from pork or beef and used in meds (eg some gelcaps, such as acetaminophen; gelatin-containing vaccines, heparin and antivenoms)

-- it appears that lone star tick bites can initiate this allergic response if one subsequently eats one of the foods above. 

    -- the current accepted model per the CDC is that AGS is an IgE-mediated hypersensitivity reaction to ingesting alpha-gal, though symptoms are often delayed by 2-6 hours or more after eating a food with alpha-gal, and this can happen after years of eating these foods without prior hypersensitivity symptoms

        -- there are lots of unanswered questions, including:

            -- what is the exact role of ticks: how do they initiate this IgE response to subsequent ingestion of foods with galactose-α- 1,3 galactose, yet just eating those foods seems okay.

                -- alpha-gal moieties have been found in black tick saliva (Ixodes scapularis, a black-legged "deer tick" found in eastern US, related to Ixodes pacificus in the west), as well as in the lone star tick: all of this suggesting a link between the tick bites and subsequent AGS. 

            -- why do some people get AGS but others do not (what is the specific immunologic mechanism that leads to these rather different responses to those foods)

                -- epidemiologic information is spotty: 

                    -- https://www.cdc.gov/ticks/alpha-gal/index.html : the CDC estimates that between 2010 and 2022 there have been >110,000 suspected cases of AGS after people are exposed to red meat or other products containing alpha-gal (some estimates are between 96,000 and 450,000 getting AGS in the US since 2010)

                    -- unfortunately,  AGS is not a notifiable condition to the CDC, so prevalence data are not likely very accurate.

                    --  And, many health care providers are unaware of this syndrome, further decreasing accuracy of reporting: the CDC has found that 42% of health care providers were not aware of AGS and another 35% were not confident on their ability to diagnose or manage AGS patients (https://pubmed.ncbi.nlm.nih.gov/37498792/ )

                    -- one commercial lab tested 105,674 people between 2010 and 2018 and found 32% were positive for galactose-α- 1,3 galactose IgE

                    -- based on the limited data available, one estimate suggests that 20%-78% of AGS cases are undiagnosed

                    -- for the CDC reporting form for AGS cases: https://www.cdc.gov/ticks/alpha-gal/pdfs/328065-A_NCEZID_FRM_Alpha_gal_CRF_508_2.pdf

 

--- typical symptoms of AGS include abdominal cramping, urticaria and anaphylaxis, though the full list includes nausea, diarrhea, vomiting, heartburn, itching, swelling of lips/tongue/throat/face/eyelids, shortness of breath, cough, wheezing, acute episodes of hypotension. Attributing these symptoms to AGS also requires the absence of a clear alternative diagnosis (though the absence of a clear cause for urticaria is really common in clinical practice, especially an issue since about 20% of people have hives at some point in their lives. i have a patient with chronic recurrent hives who was found to have H Pylori stool antigen on routine testing, this was treated, and, unexpectedly, the hives have not recurred now for several years)

    -- though AGS symptoms may be as mild as a rash or GI upset

 

-- case definitions of AGS (see https://cdn.ymaws.com/www.cste.org/resource/resmgr/ps/ps2021/21-ID-07_Alpha_Gal_Syndrome.pdf )

-- laboratory confirmation: IgE specific to alpha-gal > 0.1 IU/mL or >= 0.1 kU/L

    -- presumptive lab evidence: allergy skin test being positive to one or more of pork, beef, lamb, or other mammalian-derived products

-- confirmed care: meets clinical criteria and confirmatory lab test

-- probable case: meets clinical criteria and presumptive lab test

-- suspected case: meets confirmatory lab test but no clinical information available

 

-- treatment: antihistamines, epinephrine and the elimination of products with galactose-α- 1,3 galactose. Other meds used include omalizumab

    --  an epi-pen should also be prescribed, given the ubiquity of foods/products that might (unknowingly) include alpha-gal and the potentially lethal effects of the hypersensitivity reaction

 

Commentary:

-- The Boston Globe had an article on the AGS, "Here’s some red meat for all the tick haters": https://edition.pagesuite.com/popovers/dynamic_article_popover.aspx?artguid=92bf6a80-ac85-4392-ac42-05972c99caca , making several of the points above, and highlighting several cases:

    -- a woman who developed hives and difficulty breathing after a tick bite, then a few weeks later had a bowl of beef chili but attributed this to "panicking"

    -- another woman who had an intense allergic reaction after taking "Tylenol gelcaps and candy corn", both of which could lead to AGS after a sensitizing tick bite

    -- there has been wide-spread invasion of the lone star tick locally: "in Rhode Island and probably the Cape and Islands, (researchers) saw a 300% increase between 2019-2022 when compared to 2014-2018"

    -- this alpha-gal allergy seems to disappear after 3-5 years if no subsequent tick bite [this is not so surprising: data on severe penicillin allergy also show dramatic decreases on allergy testing years later: http://gmodestmedblogs.blogspot.com/2017/03/penicillin-allergy.html]

    -- as a personal anecdote, we have a small house in very rural Vermont. Over the past 3 years, there has been a huge increase in ticks (mostly the blacklegged ones, though lone star ticks have occasionally been found in southern Vermont), such that for a couple of months in the summer, just walking outside to the car led to 4-6 ticks crawling up one's body; and more prolonged exposure to 10-20 ticks....  eg see https://www.healthvermont.gov/disease-control/tickborne-diseases/information-ticks-vermont

 

-- here is the current spread of the lone star tick in the US, from its meager beginnings in the South:

 

 

so, what does this all mean:

-- health care workers need to be familiar with AGS as a potential source of severe allergic reactions

-- many people may be unaware of having had a tick bite, especially with some of the smaller ticks or ticks in hard to see locations

-- if no source of the allergic reaction can be identified, we should consider getting specific IgE testing (best test) or allergy testing to see if likely to be AGS

-- patients should have epi-pens

-- patients with AGS should avoid potential foods that might lead to the allergic reaction (seems like vegans are doing it right....)

-- and, and, and: this is yet another of the very many reasons that there needs to be a global concerted effort to decrease the use of fossil fuels and try to bend the curve against continued climate change

 

geoff

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