AGS In-Depth by Darcie Clements
These original articles are reprinted with permission to edit by Darcie Clements at alphagalsyndrome.blogspot.com.
What Is Alpha-gal Syndrome?
by Darcie Clements
January 25, 2018
Alpha-gal syndrome (AGS), often described as “red meat allergy”, is a food allergy characterized by a delayed – and potentially life threatening – reaction that can strike a person at any age. It saw a surge in popularity and discussion somewhat recently, but just like many subjects that go viral in a short amount of time, misconceptions and story-driven slants are bound to crop up along the way.
Alpha-gal Syndrome isn’t new
When the condition was first described in 2009, the offending molecule, galactose-alpha-1,3-galactose (alpha-gal for short, hence the name), was only known to be found in the flesh of mammals (excluding some primates like humans) and a new intravenous cancer treatment (reactions to which led to the discovery). It was also assumed that it took intravenous or large dietary exposures to trigger reactions. Since then it has been found that people with the condition may also react to other mammal products, such as gelatin, dairy, lanolin and derivatives, and that small trace amounts of cross contamination are enough to cause illness in sensitive patients. To make matters worse, carrageenan, a vegan additive frequently used in non-dairy substitutes, also contains the alpha-gal epitope.
The diversity of products containing alpha-gal, combined with label laws that don’t yet require derived products to indicate what they were made from, make alpha-gal syndrome one of the most challenging allergies to live with. Unfortunately, while alpha-gal syndrome (AGS) likely existed in some form long before its discovery, it seems that it may also be increasing in frequency and severity in westernized countries in recent years. The exact reasons for this are unclear, but the prevalence of mammal products in processed foods, the addition of carrageenan to the diet, and an increase in tick activity have all been speculated to play a role. That’s right, alpha-gal syndrome is yet another tick induced ailment on what seems like an endlessly expanding list.
What Causes Alpha-gal Syndrome?
Many, but not all, people who develop the alpha-gal allergy report experiencing tick bites a few months prior to onset, yet AGS does not appear to be caused by an infectious agent like other tick-borne ailments. Instead, it is thought to be an immune response to the saliva of the tick. Humans naturally have strong immune reactions to alpha-gal; this is why animal organ transplants can not safely be done on humans. Normally, the human body suppresses the reaction and keeps it firmly limited to IgG antibodies, but when a tick bites a human, the immune system suddenly starts producing igE antibodies. These IgE responses are what cause allergic reactions.
Until recently, only three species of ticks had been verified as causing the condition worldwide, but no species had been ruled out. New species are now being found, thanks to success with inducing alpha-gal syndrome in mouse models using tick saliva, but there are hundreds out there to be tested. That, of course, means that the most aggressive types are the ones first on the list to be checked. There may also be other triggers and risk factors that haven’t been discovered yet. Scientists just don’t know enough about how the condition starts yet to be entirely sure. What is known is that once AGS has begun, the more bites a person gets, the more severe the condition gets. In the worst cases, even cooking fumes can cause reactions when inhaled, much like the infamous peanut allergy.
Symptoms of Alpha-gal Syndrome
by Darcie Clements
January 25, 2018
Alpha-gal syndrome (AGS), characterized by the sudden onset of an often atypical allergic reaction to mammal products and sometimes carrageenan, was not described until 2009. As awareness of alpha-gal syndrome and the ticks that are known to trigger it spread, so too do the number of confirmed cases.
Many of those unknowingly affected face an uphill battle, as detailed descriptions of the various symptoms of alpha-gal syndrome are under-published. Diagnosis is often preceded by misdiagnosis, since alpha-gal syndrome is not yet listed as a differential diagnosis for a number of look-alike conditions in medical texts and databases. The story of misdiagnosis is especially common for those who do not recall previous tick bites, or who live outside the most affected regions. Those who have gone through misdiagnosis and are now diagnosed frequently lament “I wish I had known what to look for sooner,”, “I didn’t know trace sources were behind my other symptoms,”, and most of all “I hope no one else has to suffer as long as I did,” when they uncover the full extent and cause of their personal symptoms.
Here we discuss a variety of anecdotal symptoms of alpha-gal syndrome, commonly reported by people with alpha-gal syndrome, that they have traced back to the condition and corrected with dietary changes. Many of the differential diagnoses confused with alpha-gal syndrome lack effective treatment, so knowing the culprit is alpha-gal syndrome and having a way to recover is invaluable. If you suspect you may have undiagnosed alpha-gal syndrome, consider talking with your doctor about seeing a specialist and being formally tested or diagnosed.
Part of what makes AGS so difficult to recognize is the complexity and variability of the reaction pattern. As more variants and factors are documented, diagnosis and recognition continue to improve. The fingerprint of AGS is becoming clearer, and a detailed food and symptom journal can now easily unmask cases with clear reactions. Unfortunately, milder cases and less clear reactions remain difficult to distinguish from other common conditions. Only recently have these murky symptom sets come to light as more and more patients report having old chronic conditions vanish like magic when they finally develop clear reactions to alpha-gal, and are forced to change their diet.
Reaction Patterns and Influencing Factors
Beef, the meat of cattle, is usually the first mammal product to start causing clear reactions, and a delay of two-to-ten hours is common for clear reactions from it. Reactions in less than two hours, or even within minutes, have been documented in people with AGS that have consumed organ meat such as pork kidneys, which have especially high concentrations of alpha-gal. Some documented cases from Europe do not present with a clear reaction unless the affected individual specifically eats kidney, suggesting that mild sub-clinical forms of the allergy that do not produce a clear reaction with meat may be more common than realized in populations that do not consume organ meat.
Exercise and alcohol consumption can also make the difference between a clear and obscure reaction taking place, as well as reduce the amount of time before a clear reaction begins. It is thought that alcohol increases absorption of alpha-gal and thus causes faster, stronger reactions. Exercise seems to play a role in worsening all food allergies and AGS is not an exception.
People who are reacting to a trace exposure from dairy, gelatin, or carrageenan may experience either a shorter or much longer delay before a clear reaction, and/or only experience the less obvious low-level reaction symptoms. Further complicating matters are biphasic reactions, which may result in two reactions as much as 72 hours apart without re-exposure, either of which may be stronger than the other. Biphasic reactions expand the timeline even further for a major reaction, but a long-term detailed symptom and food journal can help clarify that this is what is occurring.
Those experiencing the symptoms of classic anaphylaxis, including rash, hives, itching, swelling, blood pressure drops, etc., for unknown reasons, are usually diagnosed with idiopathic anaphylaxis or a mast cell condition, unless a specific allergen can be found. Because alpha-gal allergic reactions can be delayed by many hours, and not every red meat exposure may result in a full anaphylactic reaction, it is easily overlooked that the source is, in fact, mammal meat. Additionally, standard allergy panels do not yet include alpha-gal specific detection. All of these factors complicate diagnosis, but many doctors are now aware of these facts, and most people suffering from classic anaphylaxis symptoms will be diagnosed through a specially ordered blood test and/or case history. However, the same cannot be said for the less classic allergic presentations that often precede these reactions, until another tick bite suddenly sends the patient over the edge.
For whatever the reason, many people with alpha-gal syndrome experience anaphylaxis symptoms as a combination of digestive distress, fatigue, and blood pressure drops without any sort of clearly visible external change. Again, these symptoms usually begin hours after the consumption of alpha-gal containing products like mammal meat, milk, and/or carrageenan. Blood pressure drops may lead to cardiac arrest in severe reactions, and are no less dangerous than classic food allergy reactions that impact breathing. Indeed, they may be more dangerous, as warning signs may be few to none. While not as clearly allergic in nature as classic anaphylaxis, these reactions are very obvious when looked for, and can be used just as easily in recognizing the characteristic delayed reaction pattern described earlier.
Digestive ailments can also occur in isolation or as part of anaphylaxis, and follow the same delays as other symptom sets caused by alpha-gal syndrome. This can lead to misdiagnoses ranging from irritable bowel syndrome to acid reflux disease to gallbladder problems. Any idiopathic digestive condition is suspect. Digestive distress usually begins two-to-ten hours after eating red meat, and by those sensitive enough to react to dairy or carrageenan, longer. The symptoms of digestive distress include any of the following: upset stomach, constipation lasting for several days (may be chronic in those who eat red meat frequently), diarrhea, gas, cramping, bloating, pain around the gallbladder, nausea and dizziness, vasovagal response, and heartburn.
When alpha-gal related, removal of mammal meats will usually end gastrointestinal symptoms, but some may also need to avoid cross-contamination, dairy, and/or carrageenan before recovering. Digestive distress may be the most common and least recognized presentation (outside of allergy specialist offices) of alpha-gal syndrome, but the timing of onset after eating mammal meat can be used as a clear indicator of a reaction when looking for the alpha-gal pattern.
Low Blood Pressure and Heartrate
Occasionally, someone may experience mild blood pressure drops without a large digestive reaction nor external signs. Symptoms of low blood pressure include dizziness upon standing, generalized dizziness, nausea, seeing stars, tunnel vision, syncope, anxiety attack or feelings of impending doom, momentary blackout without losing consciousness, loss of consciousness, and/or cardiac arrest.
Patients have reported being misdiagnosed with generalized hypotension or orthostatic hypotension prior to their alpha-gal syndrome diagnosis. Anxiety disorders may also be confused with frequent blood pressure drops. Tachycardia may also be experienced in some cases.
When alpha-gal is responsible for these conditions, they will clear quickly once dietary changes have been made, but may persist while trace sources remain according to those who have experienced this symptom set. It is much harder to pair blood pressure changes with the diagnostic pattern describe earlier, as blood pressure may continue to be erratic in the days following an initial reaction.
Although breathing difficulties are uncommon when a person reacts to ingesting alpha-gal contaminated products, for the unlucky, airborne alpha-gal is a problem. When mammal products are cooked, especially when fried or smoked, small amounts enter the air. When a person with a severely sensitive case of AGS breathes in these droplets, they are at risk for major uncontrollable coughing fits and immediate responses typical of airborne allergies. Additionally, some people report experiencing mild digestive problems or joint pain the next day. Burning eyes, runny nose, and areas with open cuts turning red and swollen are also frequently reported in those sensitive to fumes. Washing after an airborne exposure may help reduce further reactions if any of the vapors redeposited on the skin.
Surprisingly, few people with alpha-gal syndrome experience notable allergic reactions to pet dander. This is assumed to be because most household pets such as cats and dogs do not have a strong alpha-gal expression in their skin cells. However, reactions to pet saliva and even farts are frequently reported. According to alpha-gal patients with pets, changing your pet’s diet to one that uses non-mammal meat can help tremendously, and HEPA air filters are not a bad idea.
Reports of airborne reactions to skunk smell, or when near cattle and livestock are not uncommon. Candles, air fresheners, cleaning products, and personal scents are other sources of fumes to which reactions have been reported.
Those experiencing mild reactions with low tolerance are the most obscure group of alpha-gal sufferers. Often such individuals have had some of the other presentations in the past (and may have even been diagnosed via blood test) but have since recovered. Or they may still have reactions to large exposures, but experience additional symptoms compared to other patients when even small trace sources enter their diet. These symptoms include fatigue, headache, body aches, uterine cramps, wet itchy ears, hair loss and joint pain. These types of presentations have differential diagnoses of rheumatoid arthritis, fibromyalgia, and other idiopathic or autoimmune conditions.
Further complicating the matter, evidence is building to suggest that other immune changes and conditions may be more common in those who have alpha-gal syndrome. It remains unclear what this relationship may be.
Preliminary work has yet to reveal any significant genetic risk factors for developing alpha-gal syndrome, though when scientists looked closer at patients with B and AB blood types, they found them to have several different antibody presentations beyond the classic IgE that causes allergic reactions. Such complexities may account for some of these symptoms not normally seen with allergies. According to patients previously diagnosed with autoimmune and/or idiopathic conditions, when alpha-gal syndrome is a factor, highly vigilant avoidance of trace sources brings relief/remission. This is reported anecdotally most frequently by those who were experiencing joint pain and/or fatigue, but the specifics and prevalence have not yet been formally studied.
Diagnosing Alpha-gal Syndrome
by Darcie Clements
January 25, 2018
How is Alpha-Gal Syndrome Diagnosed?
Alpha-gal Syndrome (AGS) is relatively new to medicine in the grand scheme of things, diagnosing the ailment can be tricky, to say the least.1 From symptoms that are easily confused with other more famous or common issues, to a general lack of common knowledge on the subject, doctors are put to the test when called on to recognize this condition. It’s no wonder the majority of currently known cases came about after an average of more than seven years of symptoms, with patients often self diagnosing and teaching their doctors, rather than the other way around.11 Thankfully, this is starting to change, with more and more people being diagnosed correctly within a year of symptom onset, and we have written this article to help with that process.
Multiple factors are taken into account when a specialist diagnoses alpha-gal syndrome, some of which we describe below. If you are concerned you may have alpha-gal syndrome, talk to your doctor about finding and seeing a specialist experienced with the condition for definitive answers. Should someone wish to investigate if their symptom set may be alpha-gal related, several tools are available to help your doctor make the diagnosis.
History of Delayed Reactions
The most distinctive feature of alpha-gal syndrome is the delay experienced between consumption of mammal meat (and other mammal products in sensitive individuals), and the onset of an acute allergic reaction. This delay is usually around two-to-ten hours after mammal meat has been consumed, and may be either shorter or longer for other mammal products. Additionally, these acute symptoms are somewhat more diverse than what is classically associated with an allergic reaction or anaphylaxis.
Acute digestive distress involving cramping, nausea, diarrhea, and constipation is a very common presentation. Urticaria (aka hives), rash, flushing, swelling, and/or itching is the other common clear acute response. Blood pressure drops resulting in an inability to stand, tunnel vision, blacking out, and/or headache, or even cardiac arrest are also very common. Slightly less common are asthmatic reactions and throat closings, though in people with a history of this type of reaction from other allergies or a predisposition, throat closings and asthma from eating mammal can still occur. When any of these symptom groups occur together, it is known as anaphylaxis.
While alpha-gal syndrome has a variety of additional more chronic symptoms that result from constant low-level exposure to alpha-gal, it is the dramatic acute reactions with their distinctive time delay that sets alpha-gal syndrome apart from other similar conditions. Additionally, it is important to note that alpha-gal syndrome reactions do not always happen after every exposure to meat, so a single instance of eating a hamburger and being fine does not eliminate AGS (but does eliminate a traditional beef protein allergy).
Indications of Delayed Reactions
In people who do not eat mammal meat regularly, it is fairly easy to see the pattern of eating mammal meat and then a reaction occurring two-to-ten hours later, but in people who consume a lot of mammal products, it can be much harder to notice, especially if they don’t react on every exposure as mentioned above. In those who consume mammal meat primarily for dinner, reactions in the middle of the night or first thing in the morning are frequently reported. Very few conditions share this tendency to occur in the middle of the night, so this strongly suggests a delayed food consumption reaction. If a person is experiencing what is thought to be random allergic reactions, or seems to be allergic to everything, alpha-gal syndrome should be considered as the time delay and inconsistency of reactions can appear as either of these scenarios on the surface.
A past diagnosis of irritable bowel syndrome, idiopathic hypotension, chronic urticaria, or any kind of mast cell activation condition in which alpha-gal syndrome was not already eliminated as a possible cause should be re-examined as a probable case of alpha-gal syndrome, as these diagnoses are based on the inability to find a reason for reactions. If AGS was never checked for, it could have been missed.
Many cases of alpha-gal syndrome have been found by re-examining idiopathic chronic conditions. The single most important component of an alpha-gal syndrome diagnosis is this delayed reaction. Additional evidence and testing are simply to help rule out other conditions that may present similarly.
Mild cases of alpha-gal syndrome may lack dramatic reactions, which will make diagnosis significantly more challenging. In such cases, additional evidence gathering is vital, though a diet change can also be used to confirm or eliminate AGS as a diagnosis, provided the person in question is up for it.
Some people with alpha-gal syndrome react to airborne mammal meat droplets produced during cooking or found in laundry products etc. These reactions are not usually delayed more than 30 minutes, so if the affected person is also the cook, they may seem to present with immediate reactions to mammal meat consumption. Airborne reactions are also more likely to cause asthma or throat closing reactions, and often involve uncontrollable coughing fits in addition to the other acute presentations seen in consumption reactions. Alpha-gal syndrome involves more immune changes than the mammal meat allergy seen on the surface, and it is entirely possible that some people develop the other immune changes without the allergy, but for now it is the allergy element that is used in diagnosis.
History of Tick Bites
Those who have symptoms that could indicate alpha-gal syndrome should consider asking themselves “Have I been in an environment that could have ticks, such as a forest or field with tall grass?” rather than “Do I remember being bitten by a tick?” as a tick need not fully attach to inflict the condition. Minute hatchling ticks barely visible to the naked eye can also bite and cause alpha-gal syndrome.2 While the absence of a tick bite does not eliminate alpha-gal syndrome as the cause, the presence of such a bite lends strong evidence to support the diagnosis. Why tick bites lead to the condition remains unclear, but it is well documented that they frequently play a role.3 In most of the world, the Ixodes genus of ticks are thought to be responsible, but in the United States Amblyomma americanum, the Lone Star Tick, is the main offender.7
It seems it may not matter so much what tick inflicts the bite, as all identified culprits to date have simply been the most aggressive species in their given geographic area. While people predisposed to severe allergic reactions do get AGS, they seem to still get it from tick bites. People who are resistant to allergies also get AGS from tick bites. If a person knows they have been bitten by a tick, it is very strong evidence that their symptoms are indeed from alpha-gal syndrome, but lack of a known tick bite does not exclude AGS. For those who are concerned about recent tick bites, it is worth noting that alpha-gal allergy symptoms usually take around two weeks to appear. Just because someone has been bitten does not mean that they will develop alpha-gal syndrome, and just because someone was bitten in the past and did not develop it does not mean that they won’t develop alpha-gal syndrome after the next tick bite. If a tick bite is suspected but not confirmed, a blood test can help clarify if the event was recent.4
Galactose-Alpha-1,3-Galactose sIgE Blood Test
Immunoassay blood tests have been developed to look for alpha-gal specific immunoglobulin E (sIgE) antibodies by several labs, and such a test is a good choice for recently acquired cases in which tick bite history is unclear.4 However, the results of this test alone are not enough for diagnosis, as additional circumstances alter the accuracy of the test dramatically, including time since onset, medications, current diet, and even blood type. Instead it is best used in combination with additional information, and in some cases may not be worth pursuing. Specifically, it has recently become apparent that this blood test is only effective in establishing if a person has recently been bitten by a tick4 rather than if they have alpha-gal syndrome, because in people who have recently been bitten, mature B cells appear to undergo class switching to suddenly produce sIgE in place of the normal sIgG found in healthy humans.5 It is this sIgE that the test measures, but it is actually a change induced in basophil cells and their kin that determine reactivity.8
People who were bitten a long time ago may test negative despite having alpha-gal syndrome because all of the altered B cells may have died off with little or no replacements made. This is especially true of people with B+ blood (and to a lesser extent B-, AB+ and AB-) which have self-tolerance systems that attempt to halt the production of new alpha-gal sIgE producing B cells.6 Initially, it was thought this made people with B+ blood resistant, but it is now known that it simply disrupts the test, with only minor changes to the condition’s presentation. Having a B blood type does not prevent someone from developing alpha-gal syndrome, though the full extent of immune changes may be slightly different.6 Additionally, B cells only produce sIgE if the antigen of concern is detected, which means people who have strict avoidance of alpha-gal containing products can also test negative while still being reactive. This problem is not unique to alpha-gal allergy, and is found in all food allergy tests of this kind. The best time to test is within a few days of a major reaction, after all drugs used to treat the reaction are out of the system and any antigens in the system that may eat up the antibodies have dissipated, leaving the still active B cells to flood the blood with the antibodies the test is looking for.
Meanwhile, nearly all people who do not have alpha-gal syndrome, but have been bitten by a tick recently will also test positive, despite being entirely asymptomatic; this is a false positive.4 These findings come from a study evaluating Australian individuals in high risk regions between 2013 and 2016. The longer it has been since such people have been bitten, the less likely they are to show as positive, and it is likely that their numbers drop more quickly than true positive cases (excluding B+ blood type).
Most labs do not report which form of alpha-gal molecules are used as the antigen in their test, which is problematic given recent collective findings that show vastly different performance between different antigen sources in different studies in which this factor was published. It appears that the more commonly used biotin based alpha-gal is significantly less reliable than bovine thyroglobulin (bTG), which is a molecule heavily adorned with alpha-gal.12 If you get this test done, it may be worthwhile to contact the lab ahead and verify that they are using bTG and not biotin as these findings are new in 2017. It is now known that basophil activation is the best predictor of alpha-gal syndrome and that the alpha-gal sIgE is somewhat incidental,8 but the sIgE blood test can still be used to monitor a known case.
Some people do recover from alpha-gal syndrome once their sIgE levels have dropped to zero, so for those hoping to recover, sIgE can be monitored to see if there is a possibility that recovery has occurred. Unfortunately, though, a negative test is not a guarantee, so make sure you work with your doctor to safely investigate if alpha-gal foods can again be tolerated. It is also important to note that for the same reasons mentioned above, the actual amount of sIgE detected has no correlation with reaction severity from one person to the next.
What does the result number mean?
Some labs still quote the generic IgE test standard of a value less than 0.1 (undetectable) as negative, a value of 0.1-0.34 as equivocal(unsure), and a value greater than or equal to 0.35 as positive, but most have taken recent findings to heart and changed their ranges to simply detectable vs undetectable, with a value of less than 0.1 as negative, and any other value as positive. This change came about after it was found that alpha-gal sIgE is incidental to reaction strength, to reduce confusion in interpreting results. If someone has symptoms of AGS and tests positive, then they are more likely to have AGS than any of the other conditions it can be confused with.
Alpha-gal syndrome is not as rare as some seem to believe. Two-to-five percent of people treated with an intravenous drug containing alpha-gal (cetuximab) react to it,10 and this two-to-five percent is concentrated in tick endemic areas, suggesting an even higher percentage of people bitten by ticks go on to develop AGS. With tick populations skyrocketing and ranges expanding, it is very likely to become increasingly common, even in areas not known to contain ticks, as they can easily be spread through shipping routes.
A positive test in someone without symptoms is not predictive of future development of symptoms. In other words, it has no more meaning than finding a tick on someone.4 If someone with recent symptom onset who does not have B+ blood type tests negative in this blood test, then they likely do NOT have alpha-gal syndrome. In such cases, alternative diagnoses should be fully explored before returning to AGS as a possibility. If no other diagnosis pans out, a diet change can be tried to see if it helps. A negative test in people who had symptom onset years ago, or are of the B+ blood type, should be taken with a grain of salt.6 There is little value in testing someone who already has confirmed tick bites within a few months of symptom onset.4
Alpha-gal Basophil Reaction Test
This is a new test being developed that is expected to be more definitive8 than any of the current diagnostic methods. It is still under development, but will work by maintaining live basophil cells filtered from a blood sample,9 and then exposing them to alpha-gal containing molecules to see if they react. Basophil reactions are thought to be at the core of the histamine response to mammal products in people with alpha-gal syndrome.
Alpha-gal Blood Panel
This is a four-part test developed to collect as much data as possible to help in diagnosing alpha-gal syndrome. It consists of an alpha-gal sIgE test as discussed above, plus three additional sIgE tests looking for antibodies against proteins in the meat of cattle (beef), swine (pork) and sheep (lamb). These proteins may or may not have alpha-gal incorporated in them, and alone these tests do not indicate alpha-gal syndrome or a lack of alpha-gal syndrome. Instead this test provides more evidence that when taken together can help lead to a diagnosis. In those who have reaction delays between 30 minutes and two hours, the grey area, this panel can help weed out protein allergies vs alpha-gal allergy. If only one meat has been reacted to and the only positive test in the panel is to that meat, then there is a good chance the person is allergic only to that meat protein, and does not have alpha-gal syndrome. If the person is positive for 2 or more of any of the tests, then they most likely have AGS, though if the pair happens to be pork and beef, pork-cat syndrome should also be considered a possibility.
In people who have had only one sudden reaction, especially those who had this reaction after eating pork kidney, a positive on the alpha-gal test indicates AGS is more likely than pork-cat syndrome. A positive on the pork test but a negative on the alpha-gal test suggests pork-cat syndrome or a pork allergy may be more likely. This is also true if beef and pork are positive while alpha-gal is negative (but only in this scenario).
In people with clearly delayed reactions, a positive on the alpha-gal, beef, or pork test is a good indicator that the person has alpha-gal syndrome. Lamb is a very poor predictor of alpha-gal syndrome,12 so if it is the only positive, it is less likely the person has AGS. The more of these tests that come back positive, the more likely it is that the person has alpha-gal syndrome, but these tests have the same limitations described in the solo alpha-gal sIgE test.
While not recommended, a more definitive single test known as an oral challenge13 can be done. This red meat challenge, under the supervision of medical professionals, can verify alpha-gal syndrome in patients who experience clear reactions, but is considered extremely risky and to be avoided unless necessary due to the inconsistent time delay in the reaction.
It’s a common myth that alpha-gal reactions are just like those of any other food allergy, and some of the symptoms can be quite dangerous; it is extremely important to note that this test should only be done under the supervision of medical professionals who can intervene and prevent the reaction from becoming lethal if necessary.
When positive, such a test results in the patient experiencing a large clear-cut reaction roughly two-to-eight hours after eating the meat, so be prepared to spend the whole day at your allergist’s, and to have a massive reaction if going this route.
Oral challenges are the gold standard for food allergy testing, but alpha-gal syndrome offers up some additional challenges since reactions are delayed. Individuals with mild AGS may not react to meat consistently, leading to a false negative if this test is only done once.
It may be of interest to know that reactions actually begin much sooner than outward symptoms suggest. The body begins acting metabolically atypically during the digestive process, seemingly holding back absorption of the offending molecules until finally accepting them in a sudden flood. Research into this matter has only just begun, but it may someday offer a means of less risky oral challenge, or a test that can pick up milder cases of alpha-gal syndrome. Alternatively, this research could lead to understanding risk factors for developing AGS, or even unique ways in which to treat it.
Skin Prick Tests
Traditional skin prick tests against meat extracts are very poor predictors of alpha-gal syndrome2 and cannot be used to help diagnose or exclude it when taken alone. However, a skin prick test against the drug Cetuximab (which cross reacts with AGS) is slightly more reliable, but false negatives can still occur. Scratch tests using raw meat rather than commercially prepared testing solutions are also more accurate in producing a response.
In general, skin prick tests are not used due to the frequency of false negatives encountered, but when positive for numerous alpha-gal sources they can lend a little more evidence for revealing the bigger picture, just like the blood panel tests. It is important to note that skin prick tests may be positive even when other type of allergies are at play, so several positive skin prick tests to different mammals is not enough evidence on its own.
Another somewhat safer option is to keep a detailed food and symptom journal to get a clearer case history. Experienced allergists may be able to diagnose the condition with just case history, and may choose to skip any formal testing if the pattern is clear enough from the beginning. Often, they will propose an elimination diet to see if symptoms are alleviated at the same time the journal is begun. An additional benefit of food journals and elimination diets is that they can detect the causal relationship between the consumption of alpha-gal containing products and less clear reaction symptoms over a longer period of time.
Creating a food journal is pretty easy, but requires dedication to be effective. It’s important that each meal, and even snacks, are recorded thoroughly to make sure that everything is fully noted and able to be tracked down the road. Symptoms, even those thought to be unrelated or trivial, must also be diligently recorded. Since alpha-gal reactions are typically delayed, pairing a specific reaction to a food entry can be tricky, but an experienced allergist can make short work of finding the characteristic alpha-gal reaction pattern from a well written journal.
- Additive Method
A patient may begin with a diet that’s very restrictive in nature, but slowly add in foods to test for tolerance and reactions as they go. If reactions persist despite the minimalistic diet, a different minimalistic diet should be tried. Once symptoms end, new foods can be slowly added. This offers the opportunity to start with what you’re sure of and build upon it from there.
- Subtractive Method
The subtractive method works in the exact opposite way the additive method does. Proponents of this method start by removing a single food at a time (for instance first mammal meat, then dairy, then gelatin, and so on) until symptoms end.
Those experiencing high sensitivity symptoms such as joint pain or extreme fatigue may need to eliminate all trace sources to find relief, and usually benefit most from the additive method. An additional benefit of the additive method is that it may also uncover other food allergies and intolerances.
Those suffering from extreme reactions only may be of lower sensitivity and will find the subtractive method easier to implement. Most doctors will recommend starting with the subtractive method for this reason.
In the end, some people have very low tolerance, while others can tolerate all sources of alpha-gal contaminated food, with the exception of fatty meats and organs like beef steak and pork kidney. Some people are highly sensitive and will experience milder symptoms with smaller exposures. Others have low sensitivity and only have large clear reactions or none at all, with no in-betweens.
About half of patients are high tolerance, low sensitivity, reacting only to one or more red meats and not to cross contamination, carrageenan, gelatin, dairy, or other trace sources. Someone who was once only reactive to beef may later become reactive to all sources, and someone who was once reactive to all sources may later become less reactive or even fully recover.
AGS is highly inconsistent in how it presents over time. The only consistent factor is that there is a delay between eating and a reaction (excluding pork kidney reactions).
Original articles reprinted with permission to edit by Darcie Clements at alphagalsyndrome.blogspot.com.
by Darcie Clements
January 25, 2018
It is worth noting that an additional condition very similar to alpha-gal syndrome was described back in the 90s. Pork-cat syndrome should be suspected if reactions seem limited to pork (and rarely beef) products, and the alpha-gal blood test comes back negative, or if reactions to red meat happen in less than an hour. Oddly, people with pork-cat syndrome will test positive for allergies to cats, but sometimes do not have clear allergic reactions to pet cats.15 Instead, they have massive allergic reactions to pork. This is how it got its name. Unlike alpha-gal syndrome, pork-cat syndrome is caused by a protein (like most food allergies), and reactions occur in less than an hour. At this time, it is thought that pork-cat syndrome is more like a classic allergy with an unusual cross reaction, rather than something as unique as the alpha-gal allergy. It was originally assumed that keeping cats caused the condition, but the allergy is rare outside of Europe, lending evidence to the theory that keeping cats is not directly related beyond the fact that doing so may make it worse.
It is not unheard of for someone to have both alpha-gal syndrome and pork-cat syndrome at the same time, and early studies frequently confused the two, leading to muddled data. Now that both conditions have blood tests, newer data sets are able to avoid this problem, by only including patients who test blood positive to the condition of interest. While diagnosing alpha-gal syndrome still has a long way to go as far as consistency and assurance of results is concerned, progress is being made on a regular and consistent basis. For now, dealing with the symptoms and reactions that result continues to be one of the most difficult aspects of the condition.
Original articles reprinted with permission to edit by Darcie Clements at alphagalsyndrome.blogspot.com.
5 Big Myths About Alpha-Gal Syndrome
by Darcie Clements
January 25, 2018
Red meat allergy, also known as alpha-gal syndrome would seem like a pretty straightforward condition, but as it turns out, it’s anything but. It’s no surprise that the internet caught wind of an allergy to red meat and ran with it; as tends to happen, a concept popped up with viral potential, and in the process of creating snappy headlines and attention-grabbing copy, facts have been distorted along the way. We’re here to clear up, in particular, five myths about alpha-gal syndrome that you’ve probably seen floating around in one form or another.
Myth 1: Alpha-gal syndrome is like any other food allergy.
Reality: When alpha gal syndrome was discovered, it shook the scientific and medical communities to their core. For the first time ever, a carbohydrate rather than a protein was found to cause life-threatening allergic reactions, but the weirdness didn’t end there. Unlike other food allergies, after a contaminated food item has been eaten, alpha-gal reactions take an average of two-to-ten hours to start, as opposed to your standard immediate sort of reaction. This delay is generally credited with why it took so long for the condition to be recognized by science. To this day it misleads people about why they are chronically and “randomly” ill on and off. What may seem like a cluster of strange symptoms, often misdiagnosed, is actually alpha-gal syndrome at work. Add into the mix that it appears to be triggered by tick bites that cause a major immune system disruption, and you have one seriously strange syndrome.
Myth 2: Red meat allergy is a vegetarian/vegan plot.
Reality: While offered up in good humor, this common response to first learning of alpha-gal syndrome ignores the full scope of the condition. Were it actually a vegetarian/vegan plot, we’d certainly recommend a trip back to the drawing board to avoid the self-sabotage. Vegetarians may be surprised to find they have developed the syndrome when milk products such as ice cream or whey powder supplements suddenly cause reactions (sometimes including anaphylaxis). This is because the alpha-gal molecule can be found in any product derived from mammals, not just meat. What about vegans then, surely they’d be safe? Not quite. Recent research has revealed that carrageenan, an additive made from red algae – used heavily in dairy substitutes and baked goods – can cause reactions in patients suffering from the so-called “red meat allergy.”
On the bright side, if you do fall victim to alpha-gal syndrome, poultry, fish, and other non-mammalian meats remain on the table as perfectly viable alternatives. Many people say that ostrich and emu taste just like beef; while we’ve certainly cleared up the myth that AGS is any sort of vegetarian/vegan plot in particular, we’re not taking the ostrich/emu farmer plot concept off of the table quite yet. Eat more Ostrich!
Myth 3: Alpha-gal syndrome only happens to people bitten by Lone Star Ticks.
Reality: While the Lone Star Tick is frequently given flack for causing alpha-gal syndrome (AGS), it may be unfairly singled out (yes, we’ve just defended a tick) simply by being the first tick species proven to trigger AGS in North America. Like many initial culprits, the first one proven isn’t by any means the only one to blame. In Australia, an unrelated species of tick called the paralysis tick is the main culprit cited, while in Europe a third species has been identified that’s called the castor bean tick. Recently, a 4th species has been found in South America.
All of these ticks have one particular thing in common: they’re all aggressive hunters of human hosts. More aggression towards humans tends to mean more bites overall, and more bites mean more potential for inducing AGS. With an estimated 899 different types of tick species in the world, it’s quite probable that there are plenty of other species that can also induce the syndrome – we just haven’t found them yet. Unfortunately, many people with alpha-gal syndrome are unable to recall having ever been bitten by a tick to begin with. It seems the full extent of what can cause alpha gal syndrome remains largely a mystery, but one thing is clear: new tick bites make the condition worse, regardless of how it begins. The takeaway here is that yes, you should be mindful of yourself and surroundings when in an area that has a high prevalence of Lone Star Ticks – but you should be just as mindful of ticks everywhere else too.
Myth 4: Alpha-gal reactions are obvious.
Reality: While some people with alpha-gal syndrome do experience the classic combo of rash, hives, itching, swelling, throat closing, and blood pressure loss associated with anaphylaxis, others do not. Oddly enough, throat closing is especially rare as a reaction in AGS. In fact, where many other anaphylactic reactions have symptoms and tells that can be easily recognized and acted upon, AGS’s life-threatening reactions sometimes consist almost exclusively of a drop in blood pressure that can then lead to cardiac arrest. Considering a drop in blood pressure isn’t as easy to spot as swelling or the blossoming of hives and rashes across the skin, alpha-gal syndrome anaphylactic reactions are especially dangerous when outward symptoms may be next to non-existent for some people.
Less dangerous reactions are just as strange, with the most common symptoms manifesting as various forms of digestive distress, with or without rash/hives/itching. What may seem like discomfort to something that simply didn’t sit well from last night’s dinner, or a stomach bug, may actually be an allergic reaction; this is one of the many reasons why alpha-gal syndrome tends to get misdiagnosed.
The biggest danger of misdiagnoses when reactions are minor is that symptoms can suddenly take a turn for the worse after years of being little more than digestive upsets. Incorrect treatments also mean people continue to suffer needlessly. To make things even more confusing and difficult to pin down, other rare reactions reported by patients include wet itching ears, joint pain, fatigue, chills or tremors, menstrual cramping (including post-menopausal), and sleep disruptions. While we’re not trying to create a readership of hypochondriacs, it goes without saying that it’s quite likely that you may not see people jumping into action when they see an early AGS reaction, the way they might with other allergic reactions – simply because they likely won’t even know one has begun.
Myth 5: Alpha gal syndrome will go away with time.
Reality: Unfortunately, this is not always the case. While there have been reports of patients recovering, some do not. Those who have recovered usually do so by avoiding further tick bites and exposure to alpha-gal containing products, but this is by no means a guarantee that the condition will go into remission. Those who do experience remission may find themselves suddenly reactive again in the future, either after a fresh tick bite, or seemingly at random, and there is no long-term data available yet to predict the outcome decades down the road.
Due to the unique nature of this allergy, conventional allergy shots are not yet considered an option, and no real treatment beyond avoidance has been found to date. With the absence of a treatment, the only way to minimize reactions is to work on the formation of habits that’ll help avoid putting yourself into situations where a reaction may be likely. From avoidance of mammal products to a heightened awareness of tick-populated areas and how best to minimize the risk of exposure, the condition can ultimately be managed, but it’s not by any means something easy to accomplish.
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- What is Alpha-Gal Syndrome? (2017) https://alphagalsyndrome.blogspot.com/2018/01/what-is-alpha-gal-syndrome.html
- Symptoms of Alpha-Gal Syndrome (2017) https://alphagalsyndrome.blogspot.com/2018/01/symptoms-of-alpha-gal-syndrome.html
- 5 Big Myths About Alpha-Gal Syndrome (2017) https://alphagalsyndrome.blogspot.com/2018/01/5-big-myths-about-alpha-gal-syndrome.html