Alpha Gal Syndrome

0:05 hello this is Eric strong from strong medicine and in this installment of my series on underappreciated diseases I'll be discussing the alpha gal syndrome to get us started what is alphal syndrome in extreme brief it is a constellation of systemic skin and GI manifestations triggered by an allergic reaction to red meat consumption in which the ini development of the allergy was in response to a tick bite if you haven't heard of it before it may sound like a bizarre phenomenon but it's quite real and not all that rare let's discuss the clinical features the first thing to note is that unlike most allergies the onset of alpha

0:51 gal syndrome typically happens in adulthood after having eaten meat without problems for years the classic presentation resembled a typical type 1 hypers sensitivity reaction composed of purtis that is itching ticaria which are large raised bumps on the skin known by late persons as hives angio edema which is swelling of the mucous membranes most commonly those of the lips and oral cavity abdominal pain and nausea and in severe episodes anaphylaxis which can be fatal what is unlike a typical type 1 hypers sensitivity reaction is a 2 to 6h hour delay between consumption of meat and the development of symptoms as a consequence patients commonly describe symptoms waking them from sleep after

1:38 having had consumed meat for dinner several hours previously this delay between exposure and reaction can result in a delayed recognition of the association the concurrent ingestion of alcohol and non-steroidal anti-inflammatory drugs like ibuprofen as well as physical exertion have been reported to increase the probability of a reaction there are also non-classic presentations which are even harder to recognize these include abdominal pain and nausea only without classic allergic symptoms joint pains weight loss and the development of a condition called chronic spontaneous ticaria so what kind of food triggers these reactions well in almost all

2:25 patients the consumption of beef pork including lard and lamb triggers SYM symptoms in some parts of the US it would also be relevant to avoid bison venison or deer rabbit and bare meat as well the reason the number here is 99 plus% and not 100% is that there are some patients who only get symptoms in response to organ meat such as pork kidney liver or a dish called sweet bread which if you're not familiar is definitely not bread but rather calf or lamb thymus or pancreas a minority of patients will also get a reaction to dairy in addition to Conventional meat what animal-based foods are safe for these patients any kind of poultry

3:11 such as chicken duck goose turkey or pheasant and any kind of seafood also while not pictured reptiles and amphibians are safe as well however beware of foods that often contain M million meat products despite not looking like mammals that includes things like turkey and chicken sausages which can use pork or beef in their casings reffed beans and baked beans which are often flavored with beef or pork various baked items which can be made with lard and even mashed potatoes can occasionally contain lard particularly in the American South any food that contains even a tiny amount of mammal should be considered potentially unsafe for patients with Alpha gal

3:56 syndrome in addition to reactions to eating m patients may experience other related life-threatening allergies these include the monoclonal antibod sumab which we'll come back to in a minute and heprin one difference between reactions to these medications and that of food is that the medication induced reactions tend to be more rapid as the antigen is injected directly into the bloodstream gelatin is also a potential problem although serious reactions to gelatin and Alpha gal syndrome are relatively uncomon common gelatin is in so many different things that it can be challenging to totally avoid for those people even medication capsules often include gelatin as a so-called inactive

4:42 ingredient notably though most gelatin allergies are not related to alphal so anyone watching this who knows they have an allergy to gelatin but who has no problems eating red meat it is very very unlikely you have Alpha G syndrome okay so how does this work how do you de develop an allergy to so many different foods in adulthood and what do ticks have to do with it it's a fascinating story which represents a novel pathophysiologic mechanism alpaga was first discovered in 2006 when a disproportionately high number of patients in the American Southeast were observed to have an allergic reaction to the newly approved cancer drug

5:28 sumab it was determined that the allergic reaction was due to pre-existing IG antibody against a specific portion of the drug containing the oligosaccharide galactose Alpha 13 galactose an oligosaccharide is the name of a compound composed of multiple connected simple sugars in this case there are two both of which are galactose the alpha 13 denotes the specific way in which they are connected and this particular oligosaccharide is commonly known as Alpha gal a nickname which predates the discovery of this syndrome after patients were identified with this unexpected form of allergy to sumab it was found that they also displayed an unusual delayed allergic reaction to red meat the connection here

6:16 is that red meat is full of alpha gal furthermore it was observed that individuals who carried this unusual anti-alpha gal IG lived in the general Geographic range of the lone star tick bats from which have subsequently been shown to trigger an increase in alag gal IG precisely why this happens is not yet known as a demonstration of how our understanding of this condition is incomplete here's a map from the CDC showing the incidence of alpha gal syndrome in various counties throughout the United States and here is the natural range of the lone star tick there is strong over laap between areas of the highest incidence and the tick but that overlap

7:03 is not perfect in addition alphal Syndrome has been reported in other parts of the world where it appears to be triggered by other tick species but not all tick species for example alphal syndrome is rare in California despite California being home to multiple species of tick regarding the pathogenic connection between tix and the allergy it was initially speculated that tick triggered the allergy by introducing animal blood from a prior meal directly into the human bloodstream however scientific studies suggest that the mechanism may be more complicated than this after all if it was just a matter of introducing animal blood into human blood why do only some tick species have the ability to trigger

7:50 alphal and even more surprising there is evidence that unfed ticks that is ticks which have not fed on the animals containing the AL alal protein can still trigger the relevant immune response suggesting either that the ticks themselves are the origin of the alpha gal epitope that they convert an oligosaccharide in human blood to Alpha gal or that they release a structurally similar oligosaccharide that our immune system can't tell apart from alphal as you might imagine it's challenging to study a disease that requires simultaneous expertise in human immunology and invertebrate biochemistry some of you might have wondered if people with alphal can't

8:35 consume Mamon meat because they carry antibodies to trigger an immune response to it why don't these antibodies get triggered by their own bod's tissues it might seem like Alpha gal should look more like an autoimmune disease because you know after all humans are mammals well it's because of all mammals on Earth humans apes and oldw World monkeys do not express Alpha gal Although our genetic code carries the gene for the enzyme that would create Alpha Gal A mutation inactivated it approximately 20 to 30 million years ago why this happened is a fascinating question that is outside the scope of this particular video but it's been speculated that a pandemic among the ancestors of modern

9:21 primates created evolutionary pressure to get rid of endogenous Alpha gal in order to create antibodies against Alpha gal Express by the contagion I'll put some links into this video's description about this hypothesis when it comes to the diagnosis of alphal syndrome it requires two things a consistent history and elevated serum alphal IG elevated Alpha gal IG by itself is not sufficient for diagnosis if there is not also a consistent history of reactions to the consumption of Maman meat products unfortunately there is no consensus on the specific threshold for the elevation of alpha gal IG diagnosis is then confirmed by a

10:09 resolution of symptoms on a diet free of meleon products regarding the differential diagnosis of alpha gal syndrome that is the diseases that can present similarly they include other food related allergies such as conventional food allergies but also other red meat allergies in addition to alphal the other classically described red meat allergies include primary beef allergy which is an allergy to bovine albumin and something called pork cat syndrome in which cat allergic people develop an allergy to Pork only other diseases on the differential are chronic spontaneous ticaria which can be confusing because as mentioned near the beginning it's thought that alphal syndrome can rarely trigger the

10:55 development of chronic spontaneous ticaria also Mass cell disorders a rare disease called hereditary angioedema and in patients who present with only GI symptoms the presentation can mimic irritable bowel syndrome treatment of alpha gal syndrome is straightforward avoid Mamon food products most patients also avoid dairy products but this may not be necessary for everyone avoid future tick bites repeated tick bites will maintain and may even increase Alpha gal G levels while avoiding them may result in lower levels over time last General severe allergy treatment including an EpiPen for most

11:41 or all patients for obvious reasons allergists are typically the best Specialists to help patients manage the disease I'll end with prognosis while there is no conventional cure with complete avoidance of tick bites the Alpha gal IG levels of some patients normalize in which case consideration can be given to very cautiously reintroducing red meat to their diet